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<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="255" xmlns="https://uniprot.org/uniprot">
    <accession>P31946</accession>
    <accession>A8K9K2</accession>
    <accession>E1P616</accession>
    <name>1433B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>14-3-3 protein beta/alpha</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Protein 1054</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein kinase C inhibitor protein 1</fullName>
            <shortName>KCIP-1</shortName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>14-3-3 protein beta/alpha, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">YWHAB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway.</title>
            <authorList>
                <person name="Leffers H."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
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            <authorList>
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                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
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                <person name="Saito K."/>
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                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
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                <person name="Sudo H."/>
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                <person name="Kondo H."/>
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                <person name="Kanda K."/>
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                <person name="Furuya T."/>
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                <person name="Tanai H."/>
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                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
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                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Shiohata N."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
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                <person name="Wakebe H."/>
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                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
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                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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                <person name="Itoh T."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
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                <person name="Takahashi Y."/>
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                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
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                <person name="Nakai K."/>
                <person name="Yada T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG)</scope>
        <source>
            <tissue>Thymus</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="11780052"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
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        <scope>PROTEIN SEQUENCE OF 1-11; 30-51; 63-73 AND 130-159</scope>
        <scope>INTERACTION WITH PI4KB; TBC1D22A AND TBC1D22B</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PROTEIN SEQUENCE OF 1-11; 14-57; 63-70; 106-117; 130-169 AND 215-246</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT MET-1 AND THR-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PROTEIN SEQUENCE OF 3-20</scope>
        <source>
            <tissue>Platelet</tissue>
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        <scope>INTERACTION WITH TESK1</scope>
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        <scope>INTERACTION WITH CHLAMYDIA INCG</scope>
        <scope>SUBUNIT (MICROBIAL INFECTION)</scope>
        <scope>SUBCELLULAR LOCATION (MICROBIAL INFECTION)</scope>
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        <scope>INTERACTION WITH AANAT</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Lymphoblast</tissue>
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        <scope>INTERACTION WITH CRTC2</scope>
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            </authorList>
            <dbReference type="PubMed" id="27030597"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.aaf1471"/>
        </citation>
        <scope>INTERACTION WITH MEFV</scope>
    </reference>
    <reference key="41">
        <citation type="journal article" date="2021" name="HGG Adv." volume="2" first="100015" last="100015">
            <title>Missense substitutions at a conserved 14-3-3 binding site in HDAC4 cause a novel intellectual disability syndrome.</title>
            <authorList>
                <consortium name="DDD Study"/>
                <person name="Wakeling E."/>
                <person name="McEntagart M."/>
                <person name="Bruccoleri M."/>
                <person name="Shaw-Smith C."/>
                <person name="Stals K.L."/>
                <person name="Wakeling M."/>
                <person name="Barnicoat A."/>
                <person name="Beesley C."/>
                <person name="Hanson-Kahn A.K."/>
                <person name="Kukolich M."/>
                <person name="Stevenson D.A."/>
                <person name="Campeau P.M."/>
                <person name="Ellard S."/>
                <person name="Elsea S.H."/>
                <person name="Yang X.J."/>
                <person name="Caswell R.C."/>
            </authorList>
            <dbReference type="PubMed" id="33537682"/>
            <dbReference type="DOI" id="10.1016/j.xhgg.2020.100015"/>
        </citation>
        <scope>INTERACTION WITH HDAC4</scope>
    </reference>
    <reference key="42">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="17237" last="17242">
            <title>Structural basis for protein-protein interactions in the 14-3-3 protein family.</title>
            <authorList>
                <person name="Yang X."/>
                <person name="Lee W.H."/>
                <person name="Sobott F."/>
                <person name="Papagrigoriou E."/>
                <person name="Robinson C.V."/>
                <person name="Grossmann J.G."/>
                <person name="Sundstroem M."/>
                <person name="Doyle D.A."/>
                <person name="Elkins J.M."/>
            </authorList>
            <dbReference type="PubMed" id="17085597"/>
            <dbReference type="DOI" id="10.1073/pnas.0605779103"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-239</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH PHOSPHOSERINE MOTIFS</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="43">
        <citation type="journal article" date="2011" name="Nature" volume="469" first="539" last="542">
            <title>Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.</title>
            <authorList>
                <person name="Varela I."/>
                <person name="Tarpey P."/>
                <person name="Raine K."/>
                <person name="Huang D."/>
                <person name="Ong C.K."/>
                <person name="Stephens P."/>
                <person name="Davies H."/>
                <person name="Jones D."/>
                <person name="Lin M.L."/>
                <person name="Teague J."/>
                <person name="Bignell G."/>
                <person name="Butler A."/>
                <person name="Cho J."/>
                <person name="Dalgliesh G.L."/>
                <person name="Galappaththige D."/>
                <person name="Greenman C."/>
                <person name="Hardy C."/>
                <person name="Jia M."/>
                <person name="Latimer C."/>
                <person name="Lau K.W."/>
                <person name="Marshall J."/>
                <person name="McLaren S."/>
                <person name="Menzies A."/>
                <person name="Mudie L."/>
                <person name="Stebbings L."/>
                <person name="Largaespada D.A."/>
                <person name="Wessels L.F.A."/>
                <person name="Richard S."/>
                <person name="Kahnoski R.J."/>
                <person name="Anema J."/>
                <person name="Tuveson D.A."/>
                <person name="Perez-Mancera P.A."/>
                <person name="Mustonen V."/>
                <person name="Fischer A."/>
                <person name="Adams D.J."/>
                <person name="Rust A."/>
                <person name="Chan-On W."/>
                <person name="Subimerb C."/>
                <person name="Dykema K."/>
                <person name="Furge K."/>
                <person name="Campbell P.J."/>
                <person name="Teh B.T."/>
                <person name="Stratton M.R."/>
                <person name="Futreal P.A."/>
            </authorList>
            <dbReference type="PubMed" id="21248752"/>
            <dbReference type="DOI" id="10.1038/nature09639"/>
        </citation>
        <scope>VARIANT ILE-99</scope>
    </reference>
    <comment type="function">
        <text evidence="16 20 22">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 6 7 8 9 10 11 12 13 15 16 17 18 19 20 21 22 24 25 27 29 30 31 32">Homodimer (PubMed:17717073). Interacts with SAMSN1 and PRKCE (By similarity). Interacts with AKAP13 (PubMed:21224381). Interacts with SSH1 and TORC2/CRTC2 (PubMed:15159416, PubMed:15454081). Interacts with ABL1; the interaction results in cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis (PubMed:15696159). Interacts with ROR2 (dimer); the interaction results in phosphorylation of YWHAB on tyrosine residues (PubMed:17717073). Interacts with GAB2 (PubMed:19172738). Interacts with YAP1 (phosphorylated form) (PubMed:17974916). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with MYO1C (PubMed:24636949). Interacts with SIRT2 (PubMed:18249187). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (PubMed:22827337). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (PubMed:15538381). Interacts with SLITRK1 (PubMed:19640509). Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 for interaction with SYNPO2 (By similarity). Interacts with RIPOR2 (via phosphorylated form) isoform 2; this interaction occurs in a chemokine-dependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity (PubMed:25588844). Interacts with MARK2 and MARK3 (PubMed:16959763). Interacts with TESK1; the interaction is dependent on the phosphorylation of TESK1 'Ser-437' and inhibits TESK1 kinase activity (PubMed:11555644). Interacts with MEFV (PubMed:27030597). Interacts with HDAC4 (PubMed:33537682). Interacts with ADAM22 (via C-terminus) (PubMed:15882968).</text>
    </comment>
    <comment type="subunit">
        <text evidence="26">(Microbial infection) Interacts with herpes simplex virus 1 protein UL46.</text>
    </comment>
    <comment type="subunit">
        <text evidence="35">(Microbial infection) Probably interacts with Chlamydia trachomatis protein IncG.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
            <label>ACIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
            <label>ADAM22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-365875">
            <id>P55196</id>
            <label>AFDN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1373806">
            <id>Q12802</id>
            <label>AKAP13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-720593">
            <id>Q96B36</id>
            <label>AKT1S1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-25928834">
            <id>A0A0S2Z5Q7</id>
            <label>ALS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1044902">
            <id>Q96Q42</id>
            <label>ALS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-700771">
            <id>Q92934</id>
            <label>BAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-519672">
            <id>P55957</id>
            <label>BID</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>14</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-518228">
            <id>P22681</id>
            <label>CBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-722425">
            <id>O00257</id>
            <label>CBX4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-747671">
            <id>P30304</id>
            <label>CDC25A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1051746">
            <id>P30305</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-7202104">
            <id>P30305-2</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-974439">
            <id>P30307</id>
            <label>CDC25C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1043945">
            <id>O94921</id>
            <label>CDK14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-79537">
            <id>Q9P2M7</id>
            <label>CGN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-974488">
            <id>O14757</id>
            <label>CHEK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1181987">
            <id>Q53ET0</id>
            <label>CRTC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-347804">
            <id>P68400</id>
            <label>CSNK2A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-3951744">
            <id>Q9NYF0</id>
            <label>DACT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1046479">
            <id>Q7Z401</id>
            <label>DENND4A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1053596">
            <id>Q13627</id>
            <label>DYRK1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1053621">
            <id>Q13627-2</id>
            <label>DYRK1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-997311">
            <id>Q96F86</id>
            <label>EDC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1052044">
            <id>O43491</id>
            <label>EPB41L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-310986">
            <id>Q9Y2J2</id>
            <label>EPB41L3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-741729">
            <id>Q96NE9</id>
            <label>FRMD6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1104821">
            <id>O94915</id>
            <label>FRYL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-975200">
            <id>Q9UQC2</id>
            <label>GAB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1049788">
            <id>Q14C86</id>
            <label>GAPVD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-359050">
            <id>Q92538</id>
            <label>GBF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-744104">
            <id>P55040</id>
            <label>GEM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-308629">
            <id>P56524</id>
            <label>HDAC4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-310559">
            <id>Q9ULT8</id>
            <label>HECTD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-475981">
            <id>P08069</id>
            <label>IGF1R</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1049582">
            <id>Q9Y4H2</id>
            <label>IRS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1047335">
            <id>Q9H1K1</id>
            <label>ISCU</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-8559445">
            <id>O14649</id>
            <label>KCNK3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-1053969">
            <id>Q6ICG6</id>
            <label>KIAA0930</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
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        <interactant intactId="EBI-306852">
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        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-6930266">
            <id>P61588</id>
            <label>Rnd3</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-7623057">
            <id>Q91YE8</id>
            <label>Synpo2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-2504426">
            <id>B7UM99</id>
            <label>tir</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-647803">
            <id>P22893</id>
            <label>Zfp36</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359815">
            <id>P31946</id>
        </interactant>
        <interactant intactId="EBI-6248077">
            <id>Q76353</id>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="14">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="14">Melanosome</location>
        </subcellularLocation>
        <text>Identified by mass spectrometry in melanosome fractions from stage I to stage IV.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Vacuole membrane</location>
        </subcellularLocation>
        <text evidence="5">(Microbial infection) Upon infection with Chlamydia trachomatis, this protein is associated with the pathogen-containing vacuole membrane where it colocalizes with IncG.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>P31946-1</id>
            <name>Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P31946-2</id>
            <name>Short</name>
            <sequence type="described" ref="VSP_018632"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="1">The alpha, brain-specific form differs from the beta form in being phosphorylated. Phosphorylated on Ser-60 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion.</text>
    </comment>
    <comment type="similarity">
        <text evidence="34">Belongs to the 14-3-3 family.</text>
    </comment>
    <dbReference type="EMBL" id="X57346">
        <property type="protein sequence ID" value="CAA40621.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAF85406.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW75893.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW75894.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW75896.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001359">
        <property type="protein sequence ID" value="AAH01359.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="P31946-1"/>
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    <dbReference type="PIR" id="S34755">
        <property type="entry name" value="S34755"/>
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    <dbReference type="RefSeq" id="NP_003395.1">
        <molecule id="P31946-1"/>
        <property type="nucleotide sequence ID" value="NM_003404.5"/>
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    <dbReference type="RefSeq" id="NP_647539.1">
        <molecule id="P31946-1"/>
        <property type="nucleotide sequence ID" value="NM_139323.4"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=2-239"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.65 A"/>
        <property type="chains" value="A=2-239"/>
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        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=1-246"/>
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        <property type="resolution" value="1.60 A"/>
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        <property type="resolution" value="2.34 A"/>
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        <property type="resolution" value="3.79 A"/>
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        <property type="resolution" value="1.86 A"/>
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        <property type="method" value="EM"/>
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        <property type="chains" value="A/B=1-239"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B=1-239"/>
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    <dbReference type="PDBsum" id="2BQ0"/>
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        <property type="interactions" value="1136"/>
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    <dbReference type="CORUM" id="P31946"/>
    <dbReference type="DIP" id="DIP-743N"/>
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    <dbReference type="FunCoup" id="P31946">
        <property type="interactions" value="3698"/>
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        <property type="interactions" value="888"/>
    </dbReference>
    <dbReference type="MINT" id="P31946"/>
    <dbReference type="STRING" id="9606.ENSP00000361930"/>
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    <dbReference type="ChEMBL" id="CHEMBL3710403"/>
    <dbReference type="DrugBank" id="DB09130">
        <property type="generic name" value="Copper"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12695">
        <property type="generic name" value="Phenethyl Isothiocyanate"/>
    </dbReference>
    <dbReference type="GlyGen" id="P31946">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P31946"/>
    <dbReference type="MetOSite" id="P31946"/>
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    <dbReference type="SwissPalm" id="P31946"/>
    <dbReference type="BioMuta" id="YWHAB"/>
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    <dbReference type="OGP" id="P31946"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00216318"/>
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    <dbReference type="MassIVE" id="P31946"/>
    <dbReference type="PaxDb" id="9606-ENSP00000361930"/>
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    <dbReference type="PRIDE" id="P31946"/>
    <dbReference type="ProteomicsDB" id="54816"/>
    <dbReference type="ProteomicsDB" id="54817">
        <molecule id="P31946-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P31946"/>
    <dbReference type="TopDownProteomics" id="P31946-1">
        <molecule id="P31946-1"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="P31946-2">
        <molecule id="P31946-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="1906">
        <property type="antibodies" value="698 antibodies from 49 providers"/>
    </dbReference>
    <dbReference type="CPTC" id="P31946">
        <property type="antibodies" value="3 antibodies"/>
    </dbReference>
    <dbReference type="DNASU" id="7529"/>
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        <molecule id="P31946-1"/>
        <property type="protein sequence ID" value="ENSP00000300161.4"/>
        <property type="gene ID" value="ENSG00000166913.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000372839.7">
        <molecule id="P31946-1"/>
        <property type="protein sequence ID" value="ENSP00000361930.3"/>
        <property type="gene ID" value="ENSG00000166913.14"/>
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    <dbReference type="MANE-Select" id="ENST00000353703.9">
        <property type="protein sequence ID" value="ENSP00000300161.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_139323.4"/>
        <property type="RefSeq protein sequence ID" value="NP_647539.1"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:12849"/>
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    <dbReference type="GeneCards" id="YWHAB"/>
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        <property type="gene designation" value="YWHAB"/>
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    <dbReference type="HPA" id="ENSG00000166913">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="601289">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166913"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01090000260040"/>
    <dbReference type="HOGENOM" id="CLU_058290_1_0_1"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P31946"/>
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    <dbReference type="Reactome" id="R-HSA-111447">
        <property type="pathway name" value="Activation of BAD and translocation to mitochondria"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-1445148">
        <property type="pathway name" value="Translocation of SLC2A4 (GLUT4) to the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-165159">
        <property type="pathway name" value="MTOR signalling"/>
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    <dbReference type="Reactome" id="R-HSA-166208">
        <property type="pathway name" value="mTORC1-mediated signalling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170968">
        <property type="pathway name" value="Frs2-mediated activation"/>
    </dbReference>
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        <property type="pathway name" value="ARMS-mediated activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2028269">
        <property type="pathway name" value="Signaling by Hippo"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-392517">
        <property type="pathway name" value="Rap1 signalling"/>
    </dbReference>
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        <property type="pathway name" value="Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-450513">
        <property type="pathway name" value="Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA"/>
    </dbReference>
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        <property type="pathway name" value="RHO GTPases activate PKNs"/>
    </dbReference>
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        <property type="pathway name" value="TP53 Regulates Metabolic Genes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5673000">
        <property type="pathway name" value="RAF activation"/>
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        <property type="pathway name" value="MAP2K and MAPK activation"/>
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        <property type="pathway name" value="Negative regulation of MAPK pathway"/>
    </dbReference>
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        <property type="pathway name" value="Signaling by moderate kinase activity BRAF mutants"/>
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        <property type="pathway name" value="Signaling by high-kinase activity BRAF mutants"/>
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        <property type="pathway name" value="Signaling by BRAF and RAF1 fusions"/>
    </dbReference>
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        <property type="pathway name" value="Paradoxical activation of RAF signaling by kinase inactive BRAF"/>
    </dbReference>
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        <property type="pathway name" value="Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex"/>
    </dbReference>
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        <property type="pathway name" value="Regulation of localization of FOXO transcription factors"/>
    </dbReference>
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        <property type="pathway name" value="Signaling downstream of RAS mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9656223">
        <property type="pathway name" value="Signaling by RAF1 mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9726840">
        <property type="pathway name" value="SHOC2 M1731 mutant abolishes MRAS complex function"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9726842">
        <property type="pathway name" value="Gain-of-function MRAS complexes activate RAF signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9735871">
        <property type="pathway name" value="SARS-CoV-1 targets host intracellular signalling and regulatory pathways"/>
    </dbReference>
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        <property type="pathway name" value="SARS-CoV-2 targets host intracellular signalling and regulatory pathways"/>
    </dbReference>
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        <property type="pathway name" value="Transcriptional and post-translational regulation of MITF-M expression and activity"/>
    </dbReference>
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    </dbReference>
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    </dbReference>
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        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 20"/>
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        <property type="molecule type" value="protein"/>
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    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="C:focal adhesion"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="IntAct"/>
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        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="F:phosphoserine residue binding"/>
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        <property type="project" value="BHF-UCL"/>
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    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
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            <position position="58"/>
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    <sequence length="246" mass="28082" checksum="6BE1A9BF97468017" modified="2007-01-23" version="3">MTMDKSELVQKAKLAEQAERYDDMAAAMKAVTEQGHELSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTERNEKKQQMGKEYREKIEAELQDICNDVLELLDKYLIPNATQPESKVFYLKMKGDYFRYLSEVASGDNKQTTVSNSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLNEESYKDSTLIMQLLRDNLTLWTSENQGDEGDAGEGEN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-08-01" modified="2026-01-28" version="245" xmlns="https://uniprot.org/uniprot">
    <accession>P27348</accession>
    <accession>D6W4Z5</accession>
    <accession>Q567U5</accession>
    <accession>Q5TZU8</accession>
    <accession>Q9UP48</accession>
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            <fullName>14-3-3 protein theta</fullName>
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        <alternativeName>
            <fullName>14-3-3 protein T-cell</fullName>
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        <alternativeName>
            <fullName>14-3-3 protein tau</fullName>
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        <alternativeName>
            <fullName>Protein HS1</fullName>
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        <name type="primary">YWHAQ</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Biochim. Biophys. Acta" volume="1088" first="425" last="428">
            <title>Primary structure of a human protein kinase regulator protein.</title>
            <authorList>
                <person name="Nielsen P.J."/>
            </authorList>
            <dbReference type="PubMed" id="2015305"/>
            <dbReference type="DOI" id="10.1016/0167-4781(91)90136-a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>T-cell</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="J. Mol. Biol." volume="231" first="982" last="998">
            <title>Molecular cloning and expression of the transformation sensitive epithelial marker stratifin. A member of a protein family that has been involved in the protein kinase C signalling pathway.</title>
            <authorList>
                <person name="Leffers H."/>
                <person name="Madsen P."/>
                <person name="Rasmussen H.H."/>
                <person name="Honore B."/>
                <person name="Andersen A.H."/>
                <person name="Walbum E."/>
                <person name="Vandekerckhove J."/>
                <person name="Celis J.E."/>
            </authorList>
            <dbReference type="PubMed" id="8515476"/>
            <dbReference type="DOI" id="10.1006/jmbi.1993.1346"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2004-10" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
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                <person name="Cochet E."/>
                <person name="Medlej-Hashim M."/>
                <person name="Megarbane A."/>
                <person name="Schroder K."/>
                <person name="Savic S."/>
                <person name="Goris A."/>
                <person name="Amselem S."/>
                <person name="Wouters C."/>
                <person name="Liston A."/>
            </authorList>
            <dbReference type="PubMed" id="27030597"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.aaf1471"/>
        </citation>
        <scope>INTERACTION WITH MEFV</scope>
    </reference>
    <reference key="33">
        <citation type="journal article" date="2017" name="J. Clin. Invest." volume="127" first="2192" last="2205">
            <title>An inflammatory bowel disease-risk variant in INAVA decreases pattern recognition receptor-induced outcomes.</title>
            <authorList>
                <person name="Yan J."/>
                <person name="Hedl M."/>
                <person name="Abraham C."/>
            </authorList>
            <dbReference type="PubMed" id="28436939"/>
            <dbReference type="DOI" id="10.1172/jci86282"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH INAVA</scope>
    </reference>
    <reference key="34">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-49</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="35">
        <citation type="journal article" date="1995" name="Nature" volume="376" first="188" last="191">
            <title>Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways.</title>
            <authorList>
                <person name="Xiao B."/>
                <person name="Smerdon S.J."/>
                <person name="Jones D.H."/>
                <person name="Dodson G.G."/>
                <person name="Soneji Y."/>
                <person name="Aitken A."/>
                <person name="Gamblin S.J."/>
            </authorList>
            <dbReference type="PubMed" id="7603573"/>
            <dbReference type="DOI" id="10.1038/376188a0"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)</scope>
    </reference>
    <reference key="36">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="17237" last="17242">
            <title>Structural basis for protein-protein interactions in the 14-3-3 protein family.</title>
            <authorList>
                <person name="Yang X."/>
                <person name="Lee W.H."/>
                <person name="Sobott F."/>
                <person name="Papagrigoriou E."/>
                <person name="Robinson C.V."/>
                <person name="Grossmann J.G."/>
                <person name="Sundstroem M."/>
                <person name="Doyle D.A."/>
                <person name="Elkins J.M."/>
            </authorList>
            <dbReference type="PubMed" id="17085597"/>
            <dbReference type="DOI" id="10.1073/pnas.0605779103"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-234</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH PHOSPHOSERINE MOTIFS</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 5 6 7 8 9 10 11 12 13 14 15 16">Homodimer. Interacts with CDK16 (By similarity). Interacts with RGS7 (phosphorylated form) (PubMed:10862767). Interacts with SSH1. Interacts with CDKN1B ('Thr-198' phosphorylated form); the interaction translocates CDKN1B to the cytoplasm. Interacts with GAB2. Interacts with the 'Ser-241' phosphorylated form of PDPK1. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509). Interacts with RIPOR2 isoform 2 (PubMed:25588844). Interacts with INAVA; the interaction increases upon PRR (pattern recognition receptor) stimulation and is required for cellular signaling pathway activation and cytokine secretion (PubMed:28436939). Interacts with MARK2, MARK3 and MARK4 (PubMed:16959763). Interacts with MEFV (PubMed:27030597).</text>
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            <id>P27348</id>
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        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
            <label>ADAM22</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-743313">
            <id>P49407</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        </interactant>
        <interactant intactId="EBI-714559">
            <id>P32121</id>
            <label>ARRB2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-930964">
            <id>P54253</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-700771">
            <id>Q92934</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-365980">
            <id>P15056</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-518228">
            <id>P22681</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-11977221">
            <id>Q86Z20</id>
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    <comment type="interaction">
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        </interactant>
        <interactant intactId="EBI-747671">
            <id>P30304</id>
            <label>CDC25A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1043945">
            <id>O94921</id>
            <label>CDK14</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-519280">
            <id>P46527</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1046479">
            <id>Q7Z401</id>
            <label>DENND4A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-997311">
            <id>Q96F86</id>
            <label>EDC3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-297353">
            <id>P00533</id>
            <label>EGFR</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
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        </interactant>
        <interactant intactId="EBI-1046713">
            <id>Q32P44</id>
            <label>EML3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
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        </interactant>
        <interactant intactId="EBI-1052044">
            <id>O43491</id>
            <label>EPB41L2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-310986">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1047240">
            <id>A6ND36</id>
            <label>FAM83G</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-348571">
            <id>P02671</id>
            <label>FGA</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        <interactant intactId="EBI-848239">
            <id>P23945</id>
            <label>FSHR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-308629">
            <id>P56524</id>
            <label>HDAC4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1049582">
            <id>Q9Y4H2</id>
            <label>IRS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-722905">
            <id>P28290</id>
            <label>ITPRID2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        </interactant>
        <interactant intactId="EBI-2556221">
            <id>Q14678</id>
            <label>KANK1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        </interactant>
        <interactant intactId="EBI-6173812">
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    <comment type="interaction">
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        <interactant intactId="EBI-1053969">
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            <label>KIAA0930</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-1644048">
            <id>O43896</id>
            <label>KIF1C</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        <interactant intactId="EBI-306852">
            <id>Q02241</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        <interactant intactId="EBI-355878">
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            <label>KIF5B</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        </interactant>
        <interactant intactId="EBI-717170">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
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        <interactant intactId="EBI-726994">
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            <label>KLC2</label>
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        <interactant intactId="EBI-949319">
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        <interactant intactId="EBI-1052114">
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        <interactant intactId="EBI-5323863">
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        <interactant intactId="EBI-299134">
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        <interactant intactId="EBI-307281">
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        <interactant intactId="EBI-707595">
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        <organismsDiffer>false</organismsDiffer>
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        <interactant intactId="EBI-1022605">
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        <interactant intactId="EBI-713738">
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        <organismsDiffer>false</organismsDiffer>
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        <interactant intactId="EBI-1053685">
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        <interactant intactId="EBI-1058434">
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        <interactant intactId="EBI-717097">
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        <interactant intactId="EBI-2609540">
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        <interactant intactId="EBI-1045582">
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        <interactant intactId="EBI-447043">
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        <interactant intactId="EBI-1023749">
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        <interactant intactId="EBI-1047489">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-2822128">
            <id>Q96JI7</id>
            <label>SPG11</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1055655">
            <id>Q08AE8</id>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q8WYL5</id>
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        <interactant intactId="EBI-1042602">
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            <id>P27348</id>
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        <interactant intactId="EBI-5235829">
            <id>Q8IWZ5</id>
            <label>TRIM42</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-396587">
            <id>P49815</id>
            <label>TSC2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-1050865">
            <id>P40818</id>
            <label>USP8</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        <interactant intactId="EBI-1044059">
            <id>P46937</id>
            <label>YAP1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-359815">
            <id>P31946</id>
            <label>YWHAB</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>14</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
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    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
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            <label>YWHAQ</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-7540603">
            <id>P67828</id>
            <label>CSNK1A1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-1030357">
            <id>Q51451</id>
            <label>exoS</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359854">
            <id>P27348</id>
        </interactant>
        <interactant intactId="EBI-6930266">
            <id>P61588</id>
            <label>Rnd3</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-2504426">
            <id>B7UM99</id>
            <label>tir</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <text>In neurons, axonally transported to the nerve terminals.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Abundantly expressed in brain, heart and pancreas, and at lower levels in kidney and placenta. Up-regulated in the lumbar spinal cord from patients with sporadic amyotrophic lateral sclerosis (ALS) compared with controls, with highest levels of expression in individuals with predominant lower motor neuron involvement.</text>
    </comment>
    <comment type="PTM">
        <text evidence="17">Ser-232 is probably phosphorylated by CK1.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the 14-3-3 family.</text>
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        <property type="protein sequence ID" value="CAA39840.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAA40622.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAV38817.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="EAX00977.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAX00979.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC050601">
        <property type="protein sequence ID" value="AAH50601.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC056867">
        <property type="protein sequence ID" value="AAH56867.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH93019.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF070556">
        <property type="protein sequence ID" value="AAC28640.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="S15076"/>
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        <property type="nucleotide sequence ID" value="NM_006826.4"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=1-234"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B=1-245"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.99 A"/>
        <property type="chains" value="A/B/E/F=1-245"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.65 A"/>
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        <property type="glycosylation" value="6 sites, 1 O-linked glycan (6 sites)"/>
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        <property type="gene designation" value="YWHAQ"/>
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        <property type="type" value="gene"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
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        <property type="pathway name" value="Activation of BAD and translocation to mitochondria"/>
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        <property type="pathway name" value="Translocation of SLC2A4 (GLUT4) to the plasma membrane"/>
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        <property type="pathway name" value="RHO GTPases activate PKNs"/>
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        <property type="pathway name" value="TP53 Regulates Metabolic Genes"/>
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        <property type="pathway name" value="SARS-CoV-2 targets host intracellular signalling and regulatory pathways"/>
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        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00244">
        <property type="entry name" value="14-3-3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF000868">
        <property type="entry name" value="14-3-3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00305">
        <property type="entry name" value="1433ZETA"/>
    </dbReference>
    <dbReference type="SMART" id="SM00101">
        <property type="entry name" value="14_3_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48445">
        <property type="entry name" value="14-3-3 protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00796">
        <property type="entry name" value="1433_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00797">
        <property type="entry name" value="1433_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0944">Nitration</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000058636" description="14-3-3 protein theta">
        <location>
            <begin position="1"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="127"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="18 22 23">
        <location>
            <position position="1"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="21">
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            <position position="3"/>
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    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="21">
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    <feature type="modified residue" description="N6-acetyllysine" evidence="21">
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            <position position="68"/>
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    <feature type="modified residue" description="3'-nitrotyrosine" evidence="2">
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            <position position="82"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="92"/>
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    <feature type="modified residue" description="3'-nitrotyrosine" evidence="2">
        <location>
            <position position="104"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="21">
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            <position position="115"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="17 20">
        <location>
            <position position="232"/>
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    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate" evidence="24">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAV38817." evidence="19" ref="3">
        <original>D</original>
        <variation>N</variation>
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            <position position="136"/>
        </location>
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            <begin position="3"/>
            <end position="16"/>
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    <feature type="helix" evidence="25">
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    <feature type="helix" evidence="25">
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    <evidence type="ECO:0000250" key="1">
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            <dbReference type="UniProtKB" id="P68254"/>
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    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9CQV8"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
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    <evidence type="ECO:0000269" key="6">
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15159416"/>
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            <dbReference type="PubMed" id="23572552"/>
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        <source>
            <dbReference type="PubMed" id="25588844"/>
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    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="26047703"/>
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            <dbReference type="PubMed" id="27030597"/>
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        <source>
            <dbReference type="PubMed" id="28436939"/>
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    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="9360956"/>
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    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000305" key="19"/>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="19608861"/>
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    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="22814378"/>
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    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="25944712"/>
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    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="6BCR"/>
        </source>
    </evidence>
    <sequence length="245" mass="27764" checksum="175534325E9E37C4" modified="1992-08-01" version="1">MEKTELIQKAKLAEQAERYDDMATCMKAVTEQGAELSNEERNLLSVAYKNVVGGRRSAWRVISSIEQKTDTSDKKLQLIKDYREKVESELRSICTTVLELLDKYLIANATNPESKVFYLKMKGDYFRYLAEVACGDDRKQTIDNSQGAYQEAFDISKKEMQPTHPIRLGLALNFSVFYYEILNNPELACTLAKTAFDEAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDSAGEECDAAEGAEN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-10-01" modified="2026-01-28" version="245" xmlns="https://uniprot.org/uniprot">
    <accession>Q04917</accession>
    <name>1433F_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>14-3-3 protein eta</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Protein AS1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">YWHAH</name>
        <name type="synonym">YWHA1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>The human and bovine 14-3-3 eta protein mRNAs are highly conserved in both their translated and untranslated regions.</title>
            <authorList>
                <person name="Swanson K.D."/>
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            </authorList>
            <dbReference type="PubMed" id="8218406"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
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            <title>cDNA cloning and chromosome assignment of the gene for human brain 14-3-3 protein eta chain.</title>
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                <person name="Ichimura-Ohshima Y."/>
                <person name="Morii K."/>
                <person name="Ichimura T."/>
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            <dbReference type="DOI" id="10.1002/jnr.490310403"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="1994-03" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Leffers H."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
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            <title>The effect on methamphetamine on the mRNA level for 14.3.3 eta chain in the human cultured cells.</title>
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                <person name="Muratake T."/>
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            <dbReference type="PubMed" id="8561965"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <title>Structural organization and chromosomal assignment of the human 14-3-3 eta chain gene (YWHAH).</title>
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                <person name="Muratake T."/>
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            </authorList>
            <dbReference type="PubMed" id="8812417"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="15461802"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            </authorList>
            <dbReference type="PubMed" id="10591208"/>
            <dbReference type="DOI" id="10.1038/990031"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lymph</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="8515476"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 27-225</scope>
        <source>
            <tissue>Keratinocyte</tissue>
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            <dbReference type="PubMed" id="12665801"/>
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        </citation>
        <scope>PROTEIN SEQUENCE OF 2-10</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
    <reference key="11">
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        <scope>PROTEIN SEQUENCE OF 2-10; 29-50; 62-69; 126-132; 144-155; 163-172 AND 218-227</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT GLY-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="23572552"/>
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        </citation>
        <scope>PROTEIN SEQUENCE OF 1-10; 13-50; 62-78; 111-120 AND 133-162</scope>
        <scope>INTERACTION WITH PI4KB; TBC1D22A AND TBC1D22B</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="13">
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                <person name="Zilliacus J."/>
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            </authorList>
            <dbReference type="PubMed" id="11266503"/>
            <dbReference type="DOI" id="10.1210/mend.15.4.0624"/>
        </citation>
        <scope>INTERACTION WITH AR; ESR1; ESR2; MC2R; NRIP1; NR3C1; PPARBP AND THRA</scope>
    </reference>
    <reference key="14">
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            </authorList>
            <dbReference type="PubMed" id="12177059"/>
            <dbReference type="DOI" id="10.1074/jbc.m205141200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PDPK1</scope>
    </reference>
    <reference key="15">
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            <title>Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization.</title>
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                <person name="Fujita N."/>
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            <dbReference type="PubMed" id="14504289"/>
            <dbReference type="DOI" id="10.1074/jbc.m306614200"/>
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        <scope>INTERACTION WITH CDKN1B</scope>
    </reference>
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            <title>JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage.</title>
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                <person name="Yoshida K."/>
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                <person name="Miki Y."/>
            </authorList>
            <dbReference type="PubMed" id="15696159"/>
            <dbReference type="DOI" id="10.1038/ncb1228"/>
        </citation>
        <scope>INTERACTION WITH ABL1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2008" name="EMBO J." volume="27" first="2305" last="2316">
            <title>Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein.</title>
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                <person name="Brummer T."/>
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            </authorList>
            <dbReference type="PubMed" id="19172738"/>
            <dbReference type="DOI" id="10.1038/emboj.2008.159"/>
        </citation>
        <scope>INTERACTION WITH GAB2</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2009" name="Biol. Psychiatry" volume="66" first="918" last="925">
            <title>SLITRK1 binds 14-3-3 and regulates neurite outgrowth in a phosphorylation-dependent manner.</title>
            <authorList>
                <person name="Kajiwara Y."/>
                <person name="Buxbaum J.D."/>
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            </authorList>
            <dbReference type="PubMed" id="19640509"/>
            <dbReference type="DOI" id="10.1016/j.biopsych.2009.05.033"/>
        </citation>
        <scope>INTERACTION WITH SLITRK1</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
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            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="20">
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            <title>Initial characterization of the human central proteome.</title>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="22">
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                <person name="Yuasa K."/>
                <person name="Ota R."/>
                <person name="Matsuda S."/>
                <person name="Isshiki K."/>
                <person name="Inoue M."/>
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            </authorList>
            <dbReference type="PubMed" id="26047703"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2015.05.105"/>
        </citation>
        <scope>INTERACTION WITH DAPK2</scope>
    </reference>
    <reference key="23">
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            <title>N-terminome analysis of the human mitochondrial proteome.</title>
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                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
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                <person name="Rompais M."/>
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                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="24">
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            <title>Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.</title>
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                <person name="Masters S.L."/>
                <person name="Lagou V."/>
                <person name="Jeru I."/>
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            </authorList>
            <dbReference type="PubMed" id="27030597"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.aaf1471"/>
        </citation>
        <scope>INTERACTION WITH MEFV</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="17237" last="17242">
            <title>Structural basis for protein-protein interactions in the 14-3-3 protein family.</title>
            <authorList>
                <person name="Yang X."/>
                <person name="Lee W.H."/>
                <person name="Sobott F."/>
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                <person name="Robinson C.V."/>
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            </authorList>
            <dbReference type="PubMed" id="17085597"/>
            <dbReference type="DOI" id="10.1073/pnas.0605779103"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS)</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH PHOSPHOSERINE MOTIFS</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 4 6 7 8 9 10 11 12 13">Homodimer (By similarity). Interacts with many nuclear hormone receptors and cofactors including AR, ESR1, ESR2, MC2R, NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with ARHGEF28 and CDK16 (By similarity). Weakly interacts with CDKN1B. Interacts with GAB2. Interacts with KCNK18 in a phosphorylation-dependent manner. Interacts with SAMSN1 (By similarity). Interacts with the 'Ser-241' phosphorylated form of PDPK1. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509). Interacts with MEFV (PubMed:27030597).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-720593">
            <id>Q96B36</id>
            <label>AKT1S1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-700771">
            <id>Q92934</id>
            <label>BAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-6424030">
            <id>Q8N5S9</id>
            <label>CAMKK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-518228">
            <id>P22681</id>
            <label>CBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-11977221">
            <id>Q86Z20</id>
            <label>CCDC125</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-1049189">
            <id>Q8ND76</id>
            <label>CCNY</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-1051746">
            <id>P30305</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-1043945">
            <id>O94921</id>
            <label>CDK14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-749343">
            <id>P49674</id>
            <label>CSNK1E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-3959469">
            <id>Q6ZV73</id>
            <label>FGD6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-944395">
            <id>O60565</id>
            <label>GREM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-308629">
            <id>P56524</id>
            <label>HDAC4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-11900149">
            <id>Q9NRR6</id>
            <label>INPP5E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-6173812">
            <id>Q14678-2</id>
            <label>KANK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-5323863">
            <id>Q5S007</id>
            <label>LRRK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-307281">
            <id>Q99759</id>
            <label>MAP3K3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-306940">
            <id>Q04917</id>
        </interactant>
        <interactant intactId="EBI-476263">
            <id>Q99683</id>
            <label>MAP3K5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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        <text>Expressed mainly in the brain and present in other tissues albeit at lower levels.</text>
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        <text evidence="1">Phosphorylated on Ser-59 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion.</text>
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        <text evidence="15">Belongs to the 14-3-3 family.</text>
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        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035259">
        <property type="term" value="F:nuclear glucocorticoid receptor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019904">
        <property type="term" value="F:protein domain specific binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046982">
        <property type="term" value="F:protein heterodimerization activity"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017080">
        <property type="term" value="F:sodium channel regulator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044325">
        <property type="term" value="F:transmembrane transporter binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006713">
        <property type="term" value="P:glucocorticoid catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008104">
        <property type="term" value="P:intracellular protein localization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0006886">
        <property type="term" value="P:intracellular protein transport"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0086010">
        <property type="term" value="P:membrane depolarization during action potential"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0050774">
        <property type="term" value="P:negative regulation of dendrite morphogenesis"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0042921">
        <property type="term" value="P:nuclear receptor-mediated glucocorticoid signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0045893">
        <property type="term" value="P:positive regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0099171">
        <property type="term" value="P:presynaptic modulation of chemical synaptic transmission"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:regulation of neuron differentiation"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:regulation of sodium ion transport"/>
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        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="P:regulation of synaptic plasticity"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0021762">
        <property type="term" value="P:substantia nigra development"/>
        <property type="evidence" value="ECO:0007007"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="CDD" id="cd10025">
        <property type="entry name" value="14-3-3_eta"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.20.190.20:FF:000001">
        <property type="entry name" value="14-3-3 gamma 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.190.20">
        <property type="entry name" value="14-3-3 domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR000308">
        <property type="entry name" value="14-3-3"/>
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    <dbReference type="InterPro" id="IPR023409">
        <property type="entry name" value="14-3-3_CS"/>
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    <dbReference type="InterPro" id="IPR036815">
        <property type="entry name" value="14-3-3_dom_sf"/>
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    <dbReference type="InterPro" id="IPR023410">
        <property type="entry name" value="14-3-3_domain"/>
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    <dbReference type="PANTHER" id="PTHR18860">
        <property type="entry name" value="14-3-3 PROTEIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00244">
        <property type="entry name" value="14-3-3"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="14-3-3"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00305">
        <property type="entry name" value="1433ZETA"/>
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    <dbReference type="SMART" id="SM00101">
        <property type="entry name" value="14_3_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48445">
        <property type="entry name" value="14-3-3 protein"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00796">
        <property type="entry name" value="1433_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00797">
        <property type="entry name" value="1433_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="5 14">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000058623" description="14-3-3 protein eta">
        <location>
            <begin position="2"/>
            <end position="246"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylglycine" evidence="14">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="16">
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; CAA40620." evidence="15" ref="9">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA35483." evidence="15" ref="1">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="157"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA35483." evidence="15" ref="1">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="4"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="20"/>
            <end position="31"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="39"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="76"/>
            <end position="106"/>
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    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="107"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="117"/>
            <end position="137"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="140"/>
            <end position="164"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="170"/>
            <end position="185"/>
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    <feature type="helix" evidence="17">
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            <begin position="190"/>
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    <feature type="helix" evidence="17">
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            <begin position="207"/>
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            <begin position="216"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="P68510"/>
        </source>
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        <source>
            <dbReference type="PubMed" id="11266503"/>
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            <dbReference type="PubMed" id="26047703"/>
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            <dbReference type="PubMed" id="27030597"/>
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        <source ref="11"/>
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    <evidence type="ECO:0000305" key="15"/>
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            <dbReference type="PubMed" id="19690332"/>
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    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="2C63"/>
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    </evidence>
    <sequence length="246" mass="28219" checksum="D70FBC100C45D6E5" modified="2007-01-23" version="4">MGDREQLLQRARLAEQAERYDDMASAMKAVTELNEPLSNEDRNLLSVAYKNVVGARRSSWRVISSIEQKTMADGNEKKLEKVKAYREKIEKELETVCNDVLSLLDKFLIKNCNDFQYESKVFYLKMKGDYYRYLAEVASGEKKNSVVEASEAAYKEAFEISKEQMQPTHPIRLGLALNFSVFYYEIQNAPEQACLLAKQAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDEEAGEGN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="134" xmlns="https://uniprot.org/uniprot">
    <accession>Q4AC99</accession>
    <name>1A1L2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Probable inactive 1-aminocyclopropane-1-carboxylate synthase-like protein 2</fullName>
            <shortName>ACC synthase-like protein 2</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACCSL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2005-08" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of novel human genes predicted by combining multiple gene-finders.</title>
            <authorList>
                <person name="Totoki Y."/>
                <person name="Yada T."/>
                <person name="Sakaki Y."/>
                <person name="Takeda T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ARG-529</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
                <person name="Bruford E."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Eichler E."/>
                <person name="FitzGerald M.G."/>
                <person name="Jaffe D.B."/>
                <person name="LaButti K."/>
                <person name="Nicol R."/>
                <person name="Park H.-S."/>
                <person name="Seaman C."/>
                <person name="Sougnez C."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Zody M.C."/>
                <person name="Birren B.W."/>
                <person name="Nusbaum C."/>
                <person name="Fujiyama A."/>
                <person name="Hattori M."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="similarity">
        <text evidence="4">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">While belonging to the class-I pyridoxal-phosphate-dependent aminotransferase family, it lacks a number of residues which are necessary for activity thus suggesting that it lacks enzymatic activity.</text>
    </comment>
    <dbReference type="EMBL" id="AB231734">
        <property type="protein sequence ID" value="BAE17132.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC134775">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS41636.1"/>
    <dbReference type="RefSeq" id="NP_001027025.2">
        <property type="nucleotide sequence ID" value="NM_001031854.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q4AC99"/>
    <dbReference type="SMR" id="Q4AC99"/>
    <dbReference type="BioGRID" id="133403">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q4AC99">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000368109"/>
    <dbReference type="iPTMnet" id="Q4AC99"/>
    <dbReference type="PhosphoSitePlus" id="Q4AC99"/>
    <dbReference type="SwissPalm" id="Q4AC99"/>
    <dbReference type="BioMuta" id="ACCSL"/>
    <dbReference type="DMDM" id="296439453"/>
    <dbReference type="jPOST" id="Q4AC99"/>
    <dbReference type="MassIVE" id="Q4AC99"/>
    <dbReference type="PaxDb" id="9606-ENSP00000368109"/>
    <dbReference type="PeptideAtlas" id="Q4AC99"/>
    <dbReference type="Antibodypedia" id="26088">
        <property type="antibodies" value="44 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="390110"/>
    <dbReference type="Ensembl" id="ENST00000378832.1">
        <property type="protein sequence ID" value="ENSP00000368109.1"/>
        <property type="gene ID" value="ENSG00000205126.2"/>
    </dbReference>
    <dbReference type="GeneID" id="390110"/>
    <dbReference type="KEGG" id="hsa:390110"/>
    <dbReference type="MANE-Select" id="ENST00000378832.1">
        <property type="protein sequence ID" value="ENSP00000368109.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001031854.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001027025.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001mxw.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:34391"/>
    <dbReference type="ClinPGx" id="PA164714805"/>
    <dbReference type="CTD" id="390110"/>
    <dbReference type="DisGeNET" id="390110"/>
    <dbReference type="GeneCards" id="ACCSL"/>
    <dbReference type="HGNC" id="HGNC:34391">
        <property type="gene designation" value="ACCSL"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000205126">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000205126"/>
    <dbReference type="eggNOG" id="KOG0256">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162841"/>
    <dbReference type="HOGENOM" id="CLU_017584_1_3_1"/>
    <dbReference type="InParanoid" id="Q4AC99"/>
    <dbReference type="OMA" id="HIAQKCL"/>
    <dbReference type="OrthoDB" id="691673at2759"/>
    <dbReference type="PAN-GO" id="Q4AC99">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q4AC99"/>
    <dbReference type="PathwayCommons" id="Q4AC99"/>
    <dbReference type="SignaLink" id="Q4AC99"/>
    <dbReference type="Agora" id="ENSG00000205126"/>
    <dbReference type="BioGRID-ORCS" id="390110">
        <property type="hits" value="9 hits in 1135 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACCSL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="390110"/>
    <dbReference type="Pharos" id="Q4AC99">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q4AC99"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q4AC99">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000205126">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 12 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q4AC99">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030170">
        <property type="term" value="F:pyridoxal phosphate binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008483">
        <property type="term" value="F:transaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006520">
        <property type="term" value="P:amino acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd00609">
        <property type="entry name" value="AAT_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.1150.10">
        <property type="entry name" value="Aspartate Aminotransferase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.640.10">
        <property type="entry name" value="Type I PLP-dependent aspartate aminotransferase-like (Major domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004839">
        <property type="entry name" value="Aminotransferase_I/II_large"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050478">
        <property type="entry name" value="Ethylene_sulfur-biosynth"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015424">
        <property type="entry name" value="PyrdxlP-dep_Trfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015421">
        <property type="entry name" value="PyrdxlP-dep_Trfase_major"/>
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    <dbReference type="InterPro" id="IPR015422">
        <property type="entry name" value="PyrdxlP-dep_Trfase_small"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43795">
        <property type="entry name" value="BIFUNCTIONAL ASPARTATE AMINOTRANSFERASE AND GLUTAMATE/ASPARTATE-PREPHENATE AMINOTRANSFERASE-RELATED"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR43795:SF1">
        <property type="entry name" value="INACTIVE 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE-LIKE PROTEIN 2-RELATED"/>
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    <dbReference type="Pfam" id="PF00155">
        <property type="entry name" value="Aminotran_1_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ACCSYNTHASE"/>
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    <dbReference type="SUPFAM" id="SSF53383">
        <property type="entry name" value="PLP-dependent transferases"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0663">Pyridoxal phosphate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000337057" description="Probable inactive 1-aminocyclopropane-1-carboxylate synthase-like protein 2">
        <location>
            <begin position="1"/>
            <end position="568"/>
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    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="21"/>
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    </feature>
    <feature type="modified residue" description="N6-(pyridoxal phosphate)lysine" evidence="1">
        <location>
            <position position="395"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060626" description="In dbSNP:rs2074051." evidence="3">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="311"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="434"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAE17132." evidence="4" ref="1">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="454"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="568" mass="65249" checksum="233FC638E76AC393" modified="2010-05-18" version="3"> </sequence>
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    <accession>P62258</accession>
    <accession>B3KY71</accession>
    <accession>D3DTH5</accession>
    <accession>P29360</accession>
    <accession>P42655</accession>
    <accession>Q4VJB6</accession>
    <accession>Q53XZ5</accession>
    <accession>Q63631</accession>
    <accession>Q7M4R4</accession>
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        <recommendedName>
            <fullName>14-3-3 protein epsilon</fullName>
            <shortName>14-3-3E</shortName>
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    <gene>
        <name type="primary">YWHAE</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>14-3-3 proteins associate with cdc25 phosphatases.</title>
            <authorList>
                <person name="Conklin D.S."/>
                <person name="Galaktionov K."/>
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            <dbReference type="PubMed" id="7644510"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
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                <person name="Chong S.S."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1996" name="Nature" volume="382" first="308" last="308">
            <title>Function of 14-3-3 proteins.</title>
            <authorList>
                <person name="Jin D.-Y."/>
                <person name="Lyu M.S."/>
                <person name="Kozak C.A."/>
                <person name="Jeang K.-T."/>
            </authorList>
            <dbReference type="PubMed" id="8684458"/>
            <dbReference type="DOI" id="10.1038/382308a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
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            <authorList>
                <person name="Han D."/>
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            <dbReference type="PubMed" id="20417184"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2010.04.104"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SV)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Sequence determination of human epsilon 14-3-3 protein.</title>
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                <person name="Luk S.C.W."/>
                <person name="Lee C.Y."/>
                <person name="Waye M.M.Y."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Heart</tissue>
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    </reference>
    <reference key="6">
        <citation type="submission" date="1998-08" db="EMBL/GenBank/DDBJ databases">
            <title>14-3-3 epsilon genomic sequence.</title>
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                <person name="Tanigami A."/>
                <person name="Chong S.S."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND SV)</scope>
        <source>
            <tissue>Caudate nucleus</tissue>
            <tissue>Heart</tissue>
            <tissue>Subthalamic nucleus</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
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            <dbReference type="PubMed" id="12665801"/>
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        <scope>PROTEIN SEQUENCE OF 1-19</scope>
        <source>
            <tissue>Platelet</tissue>
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        <scope>PROTEIN SEQUENCE OF 1-56; 62-73; 95-118; 131-193 AND 197-255</scope>
        <scope>INTERACTION WITH PI4KB; TBC1D22A AND TBC1D22B</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PROTEIN SEQUENCE OF 1-19; 30-50 AND 131-170</scope>
        <scope>ACETYLATION AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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            <tissue>B-cell lymphoma</tissue>
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        <scope>PROTEIN SEQUENCE OF 50-60</scope>
        <scope>INTERACTION WITH KSR1</scope>
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        <scope>PROTEIN SEQUENCE OF 103-108; 120-123; 131-141 AND 143-153</scope>
        <source>
            <tissue>Histiocytic lymphoma</tissue>
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        <scope>PROTEIN SEQUENCE OF 131-141 AND 154-190</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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            <tissue>Brain</tissue>
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                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-50</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="46">
        <citation type="journal article" date="2018" name="IScience" volume="11" first="134" last="145">
            <title>Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A Recruitment.</title>
            <authorList>
                <person name="Sonntag T."/>
                <person name="Ostojic J."/>
                <person name="Vaughan J.M."/>
                <person name="Moresco J.J."/>
                <person name="Yoon Y.S."/>
                <person name="Yates J.R. III"/>
                <person name="Montminy M."/>
            </authorList>
            <dbReference type="PubMed" id="30611118"/>
            <dbReference type="DOI" id="10.1016/j.isci.2018.12.012"/>
        </citation>
        <scope>INTERACTION WITH CRTC1; CRTC2 AND CRTC3</scope>
    </reference>
    <reference key="47">
        <citation type="journal article" date="2018" name="Nature" volume="557" first="585" last="589">
            <title>KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.</title>
            <authorList>
                <person name="Chen J."/>
                <person name="Ou Y."/>
                <person name="Yang Y."/>
                <person name="Li W."/>
                <person name="Xu Y."/>
                <person name="Xie Y."/>
                <person name="Liu Y."/>
            </authorList>
            <dbReference type="PubMed" id="29769719"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0128-9"/>
        </citation>
        <scope>INTERACTION WITH KLHL22</scope>
    </reference>
    <reference key="48">
        <citation type="journal article" date="2022" name="Adv. Sci." volume="9" first="0" last="0">
            <title>RNF115 Inhibits the Post-ER Trafficking of TLRs and TLRs-Mediated Immune Responses by Catalyzing K11-Linked Ubiquitination of RAB1A and RAB13.</title>
            <authorList>
                <person name="Zhang Z.D."/>
                <person name="Li H.X."/>
                <person name="Gan H."/>
                <person name="Tang Z."/>
                <person name="Guo Y.Y."/>
                <person name="Yao S.Q."/>
                <person name="Liuyu T."/>
                <person name="Zhong B."/>
                <person name="Lin D."/>
            </authorList>
            <dbReference type="PubMed" id="35343654"/>
            <dbReference type="DOI" id="10.1002/advs.202105391"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RNF115</scope>
    </reference>
    <reference key="49">
        <citation type="journal article" date="2023" name="J. Virol." volume="0" first="0" last="0">
            <title>Cleavage of 14-3-3epsilon by the enteroviral 3C protease dampens RIG-I-mediated antiviral signaling.</title>
            <authorList>
                <person name="Andrews D.D.T."/>
                <person name="Vlok M."/>
                <person name="Akbari Bani D."/>
                <person name="Hay B.N."/>
                <person name="Mohamud Y."/>
                <person name="Foster L.J."/>
                <person name="Luo H."/>
                <person name="Overall C.M."/>
                <person name="Jan E."/>
            </authorList>
            <dbReference type="PubMed" id="37555661"/>
            <dbReference type="DOI" id="10.1128/jvi.00604-23"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CLEAVAGE BY POLIOVIRUS PROTEASE 3C (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH RIGI</scope>
        <scope>MUTAGENESIS OF GLN-236</scope>
    </reference>
    <reference key="50">
        <citation type="journal article" date="2023" name="Cancer Biol. Ther." volume="24" first="2246203" last="2246203">
            <title>Nucleo-cytoplasmic shuttling of 14-3-3 epsilon carrying hnRNP C promotes autophagy.</title>
            <authorList>
                <person name="Guo M."/>
                <person name="He M."/>
                <person name="Zhang Y."/>
                <person name="Liu W."/>
                <person name="Qi M."/>
                <person name="Liu Z."/>
                <person name="Yi G."/>
                <person name="Deng S."/>
                <person name="Li Y."/>
                <person name="Sun X."/>
                <person name="Zhao L."/>
                <person name="Chen T."/>
                <person name="Liu Y."/>
            </authorList>
            <dbReference type="PubMed" id="37599448"/>
            <dbReference type="DOI" id="10.1080/15384047.2023.2246203"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH HNRNPC</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="51">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="17237" last="17242">
            <title>Structural basis for protein-protein interactions in the 14-3-3 protein family.</title>
            <authorList>
                <person name="Yang X."/>
                <person name="Lee W.H."/>
                <person name="Sobott F."/>
                <person name="Papagrigoriou E."/>
                <person name="Robinson C.V."/>
                <person name="Grossmann J.G."/>
                <person name="Sundstroem M."/>
                <person name="Doyle D.A."/>
                <person name="Elkins J.M."/>
            </authorList>
            <dbReference type="PubMed" id="17085597"/>
            <dbReference type="DOI" id="10.1073/pnas.0605779103"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-233</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH PHOSPHOSERINE MOTIFS</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="3 9 19 20 28 29 30">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 5 7 8 9 10 11 12 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30">Homodimer (PubMed:17085597). Heterodimerizes with YWHAZ (PubMed:16376338). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (PubMed:15696159). Interacts with ARHGEF28 (By similarity). Interacts with BEX3 (By similarity). Weakly interacts with CDKN1B (PubMed:12042314). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A (PubMed:26055712). Interacts with GAB2 (PubMed:19172738). Interacts with phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 (PubMed:10409742). Interacts with NDEL1 (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with TIAM2. Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via phosphorylated form) (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner (PubMed:12917326). Interacts with RIPOR2 isoform 2 (PubMed:25588844). Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation (PubMed:29769719). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (probably when phosphorylated at 'Ser-171') (PubMed:30611118). Interacts with CRTC3 (probably when phosphorylated at 'Ser-162' and/or 'Ser-273') (PubMed:30611118). Interacts with ATP2B1 and ATP2B3; this interaction inhibits calcium-transporting ATPase activity (PubMed:18029012). Interacts with MEFV (PubMed:27030597). Interacts with RIGI (PubMed:22607805, PubMed:37555661). Interacts with TRIM25 (PubMed:22607805). Interacts with HNRNPC (PubMed:37599448). Interacts with RNF115 (PubMed:35343654). Interacts with GPR15; this interaction promotes ER-to-Golgi transport of GPR15 (PubMed:21189250).</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">(Microbial infection) Interacts with HCV core protein.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-487024">
            <id>O14639</id>
            <label>ABLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-11603395">
            <id>Q8N961</id>
            <label>ABTB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
            <label>ACD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-6423957">
            <id>Q96QP1</id>
            <label>ALPK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-446492">
            <id>O14727</id>
            <label>APAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-365961">
            <id>P10398</id>
            <label>ARAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1057448">
            <id>Q5VV41</id>
            <label>ARHGEF16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-302405">
            <id>Q92974</id>
            <label>ARHGEF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-6658043">
            <id>Q5SQI0</id>
            <label>ATAT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-700771">
            <id>Q92934</id>
            <label>BAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-525456">
            <id>Q9UQB8</id>
            <label>BAIAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-527196">
            <id>Q13873</id>
            <label>BMPR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-696657">
            <id>P51813</id>
            <label>BMX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-3232062">
            <id>Q8IWQ3</id>
            <label>BRSK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1001438">
            <id>O60566</id>
            <label>BUB1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1383687">
            <id>Q9UQM7</id>
            <label>CAMK2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-351018">
            <id>Q13557</id>
            <label>CAMK2D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-6424030">
            <id>Q8N5S9</id>
            <label>CAMKK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-518228">
            <id>P22681</id>
            <label>CBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-4392727">
            <id>O00257-3</id>
            <label>CBX4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-947308">
            <id>Q9Y3M2</id>
            <label>CBY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-11977221">
            <id>Q86Z20</id>
            <label>CCDC125</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-747671">
            <id>P30304</id>
            <label>CDC25A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1051746">
            <id>P30305</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-7202104">
            <id>P30305-2</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-974439">
            <id>P30307</id>
            <label>CDC25C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1043945">
            <id>O94921</id>
            <label>CDK14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-726261">
            <id>Q00536</id>
            <label>CDK16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-624648">
            <id>Q00537</id>
            <label>CDK17</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-746238">
            <id>Q07002</id>
            <label>CDK18</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1245761">
            <id>Q00526</id>
            <label>CDK3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-2836899">
            <id>Q8N8E3</id>
            <label>CEP112</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1104799">
            <id>Q5SW79</id>
            <label>CEP170</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-372775">
            <id>Q96GE4</id>
            <label>CEP95</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-3388952">
            <id>Q0VF96</id>
            <label>CGNL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1020839">
            <id>Q13111</id>
            <label>CHAF1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-913476">
            <id>Q7Z460</id>
            <label>CLASP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-724292">
            <id>Q8TBC3</id>
            <label>SHKBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-1181640">
            <id>P57059</id>
            <label>SIK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
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            <id>P62258</id>
        </interactant>
        <interactant intactId="EBI-311323">
            <id>O94875</id>
            <label>SORBS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-13618641">
            <id>Q96N96</id>
            <label>SPATA13</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2822128">
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            <label>SPG11</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-6381269">
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-353655">
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    </comment>
    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2814208">
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            <label>TFEB</label>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-527670">
            <id>P21580</id>
            <label>TNFAIP3</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356498">
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        <interactant intactId="EBI-1383444">
            <id>Q13470</id>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2130449">
            <id>Q6AZZ1</id>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-720828">
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-396587">
            <id>P49815</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-6423734">
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    <comment type="interaction">
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        <interactant intactId="EBI-1050865">
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    <comment type="interaction">
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        <interactant intactId="EBI-359815">
            <id>P31946</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-356498">
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    <comment type="interaction">
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    <comment type="interaction">
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            <id>Q08981</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-55031236">
            <id>C6K4R4</id>
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 30">Nucleus</location>
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            <location evidence="9">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8 13">Melanosome</location>
        </subcellularLocation>
        <text evidence="8 13">Identified by mass spectrometry in melanosome fractions from stage I to stage IV.</text>
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    <comment type="alternative products">
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        <isoform>
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    <comment type="miscellaneous">
        <molecule>Isoform SV</molecule>
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        <text evidence="34">Belongs to the 14-3-3 family.</text>
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    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000058618" description="14-3-3 protein epsilon">
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            <begin position="1"/>
            <end position="255"/>
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            <begin position="234"/>
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    <feature type="site" description="Interaction with phosphoserine on interacting protein">
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            <position position="57"/>
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    <feature type="site" description="Interaction with phosphoserine on interacting protein">
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            <position position="130"/>
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            <begin position="236"/>
            <end position="237"/>
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            <position position="1"/>
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            <end position="22"/>
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    <feature type="mutagenesis site" description="Complete loss of cleavage by poliovirus protease 3C." evidence="29">
        <original>Q</original>
        <variation>A</variation>
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            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 15; AA sequence." evidence="34" ref="15">
        <original>KH</original>
        <variation>NY</variation>
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    <feature type="sequence conflict" description="In Ref. 15; AA sequence." evidence="34" ref="15">
        <original>E</original>
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        <original>S</original>
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    <sequence length="255" mass="29174" checksum="07817CCBD1F75B26" modified="2004-07-05" version="1">MDDREDLVYQAKLAEQAERYDEMVESMKKVAGMDVELTVEERNLLSVAYKNVIGARRASWRIISSIEQKEENKGGEDKLKMIREYRQMVETELKLICCDILDVLDKHLIPAANTGESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAASDIAMTELPPTHPIRLGLALNFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDMQGDGEEQNKEALQDVEDENQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-05" modified="2026-01-28" version="162" xmlns="https://uniprot.org/uniprot">
    <accession>Q96QU6</accession>
    <accession>B4E219</accession>
    <accession>Q8WUL4</accession>
    <accession>Q96LX5</accession>
    <name>1A1L1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>1-aminocyclopropane-1-carboxylate synthase-like protein 1</fullName>
            <shortName>ACC synthase-like protein 1</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACCS</name>
        <name type="synonym">PHACS</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="8 10" key="1">
        <citation type="journal article" date="2001" name="Gene" volume="272" first="75" last="84">
            <title>The human cDNA for a homologue of the plant enzyme 1-aminocyclopropane-1-carboxylate synthase encodes a protein lacking that activity.</title>
            <authorList>
                <person name="Koch K.A."/>
                <person name="Capitani G."/>
                <person name="Gruetter M.G."/>
                <person name="Kirsch J.F."/>
            </authorList>
            <dbReference type="PubMed" id="11470512"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(01)00533-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="11" key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue evidence="11">Trachea</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
                <person name="Bruford E."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Eichler E."/>
                <person name="FitzGerald M.G."/>
                <person name="Jaffe D.B."/>
                <person name="LaButti K."/>
                <person name="Nicol R."/>
                <person name="Park H.-S."/>
                <person name="Seaman C."/>
                <person name="Sougnez C."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Zody M.C."/>
                <person name="Birren B.W."/>
                <person name="Nusbaum C."/>
                <person name="Fujiyama A."/>
                <person name="Hattori M."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="12" key="4">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="8 9" key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT LEU-421</scope>
        <source>
            <tissue evidence="9">Uterus</tissue>
        </source>
    </reference>
    <reference evidence="8" key="6">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] GLU-221 AND LEU-393</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Does not catalyze the synthesis of 1-aminocyclopropane-1-carboxylate but is capable of catalyzing the deamination of L-vinylglycine.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743387">
            <id>Q96QU6</id>
        </interactant>
        <interactant intactId="EBI-743387">
            <id>Q96QU6</id>
            <label>ACCS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743387">
            <id>Q96QU6</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
            <label>CFTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743387">
            <id>Q96QU6</id>
        </interactant>
        <interactant intactId="EBI-743128">
            <id>P14927</id>
            <label>UQCRB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96QU6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96QU6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055800 VSP_055801"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">Similar to plant 1-aminocyclopropane-1-carboxylate synthases but lacks a number of residues which are necessary for activity.</text>
    </comment>
    <dbReference type="EMBL" id="AY026508">
        <property type="protein sequence ID" value="AAK11482.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK057649">
        <property type="protein sequence ID" value="BAB71541.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK304074">
        <property type="protein sequence ID" value="BAG64981.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC134775">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471064">
        <property type="protein sequence ID" value="EAW68072.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020197">
        <property type="protein sequence ID" value="AAH20197.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7907.1">
        <molecule id="Q96QU6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001120691.1">
        <molecule id="Q96QU6-1"/>
        <property type="nucleotide sequence ID" value="NM_001127219.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_115981.1">
        <molecule id="Q96QU6-1"/>
        <property type="nucleotide sequence ID" value="NM_032592.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96QU6"/>
    <dbReference type="SMR" id="Q96QU6"/>
    <dbReference type="BioGRID" id="124199">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96QU6">
        <property type="interactions" value="36"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96QU6">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="MINT" id="Q96QU6"/>
    <dbReference type="STRING" id="9606.ENSP00000263776"/>
    <dbReference type="DrugBank" id="DB03214">
        <property type="generic name" value="Vinylglycine"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96QU6"/>
    <dbReference type="PhosphoSitePlus" id="Q96QU6"/>
    <dbReference type="BioMuta" id="ACCS"/>
    <dbReference type="DMDM" id="74717198"/>
    <dbReference type="jPOST" id="Q96QU6"/>
    <dbReference type="MassIVE" id="Q96QU6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000263776"/>
    <dbReference type="PeptideAtlas" id="Q96QU6"/>
    <dbReference type="ProteomicsDB" id="5797"/>
    <dbReference type="ProteomicsDB" id="77907"/>
    <dbReference type="Antibodypedia" id="13193">
        <property type="antibodies" value="204 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84680"/>
    <dbReference type="Ensembl" id="ENST00000263776.9">
        <molecule id="Q96QU6-1"/>
        <property type="protein sequence ID" value="ENSP00000263776.8"/>
        <property type="gene ID" value="ENSG00000110455.15"/>
    </dbReference>
    <dbReference type="GeneID" id="84680"/>
    <dbReference type="KEGG" id="hsa:84680"/>
    <dbReference type="MANE-Select" id="ENST00000263776.9">
        <property type="protein sequence ID" value="ENSP00000263776.8"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032592.4"/>
        <property type="RefSeq protein sequence ID" value="NP_115981.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001mxx.3">
        <molecule id="Q96QU6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23989"/>
    <dbReference type="ClinPGx" id="PA162375284"/>
    <dbReference type="CTD" id="84680"/>
    <dbReference type="DisGeNET" id="84680"/>
    <dbReference type="GeneCards" id="ACCS"/>
    <dbReference type="HGNC" id="HGNC:23989">
        <property type="gene designation" value="ACCS"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000110455">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="608405">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000110455"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000110455"/>
    <dbReference type="eggNOG" id="KOG0256">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161101"/>
    <dbReference type="HOGENOM" id="CLU_017584_1_3_1"/>
    <dbReference type="InParanoid" id="Q96QU6"/>
    <dbReference type="OMA" id="PYYGTFV"/>
    <dbReference type="OrthoDB" id="7042322at2759"/>
    <dbReference type="PAN-GO" id="Q96QU6">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96QU6"/>
    <dbReference type="PathwayCommons" id="Q96QU6"/>
    <dbReference type="SignaLink" id="Q96QU6"/>
    <dbReference type="Agora" id="ENSG00000110455"/>
    <dbReference type="BioGRID-ORCS" id="84680">
        <property type="hits" value="8 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACCS">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84680"/>
    <dbReference type="Pharos" id="Q96QU6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96QU6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96QU6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000110455">
        <property type="expression patterns" value="Expressed in right uterine tube and 120 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96QU6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030170">
        <property type="term" value="F:pyridoxal phosphate binding"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008483">
        <property type="term" value="F:transaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006520">
        <property type="term" value="P:amino acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd00609">
        <property type="entry name" value="AAT_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.640.10:FF:000102">
        <property type="entry name" value="1-aminocyclopropane-1-carboxylate synthase homolog (inactive)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.1150.10">
        <property type="entry name" value="Aspartate Aminotransferase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.640.10">
        <property type="entry name" value="Type I PLP-dependent aspartate aminotransferase-like (Major domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004839">
        <property type="entry name" value="Aminotransferase_I/II_large"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050478">
        <property type="entry name" value="Ethylene_sulfur-biosynth"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015424">
        <property type="entry name" value="PyrdxlP-dep_Trfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015421">
        <property type="entry name" value="PyrdxlP-dep_Trfase_major"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015422">
        <property type="entry name" value="PyrdxlP-dep_Trfase_small"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43795:SF17">
        <property type="entry name" value="1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE-LIKE PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43795">
        <property type="entry name" value="BIFUNCTIONAL ASPARTATE AMINOTRANSFERASE AND GLUTAMATE/ASPARTATE-PREPHENATE AMINOTRANSFERASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00155">
        <property type="entry name" value="Aminotran_1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00753">
        <property type="entry name" value="ACCSYNTHASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53383">
        <property type="entry name" value="PLP-dependent transferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0663">Pyridoxal phosphate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000318071" description="1-aminocyclopropane-1-carboxylate synthase-like protein 1">
        <location>
            <begin position="1"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="480"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="490"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="105"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-(pyridoxal phosphate)lysine" evidence="1">
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055800" description="In isoform 2." evidence="7">
        <original>LSQRDMQRVEPSLLQYADWRGHLFLREEVAKFLSFYCKSPVP</original>
        <variation>PPGGSGQVPVFLLQEPSTPQTRECGCPEWWCLALLCSGHGAV</variation>
        <location>
            <begin position="117"/>
            <end position="158"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055801" description="In isoform 2." evidence="7">
        <location>
            <begin position="159"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048227" description="In dbSNP:rs33952257.">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048228" description="In dbSNP:rs2018795.">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038685" description="In a breast cancer sample; somatic mutation; dbSNP:rs35514614." evidence="6">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="221"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038686" description="In a breast cancer sample; somatic mutation." evidence="6">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="393"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038687" description="In dbSNP:rs3107275." evidence="5">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="421"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB71541." evidence="8" ref="2">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB71541." evidence="8" ref="2">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="410"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11470512"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="EMBL" id="AAH20197.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="EMBL" id="AAK11482.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="EMBL" id="BAB71541.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="EMBL" id="EAW68072.1"/>
        </source>
    </evidence>
    <sequence length="501" mass="57324" checksum="62C99045F0BF8D5E" modified="2001-12-01" version="1">MFTLPQKDFRAPTTCLGPTCMQDLGSSHGEDLEGECSRKLDQKLPELRGVGDPAMISSDTSYLSSRGRMIKWFWDSAEEGYRTYHMDEYDEDKNPSGIINLGTSENKLCFDLLSWRLSQRDMQRVEPSLLQYADWRGHLFLREEVAKFLSFYCKSPVPLRPENVVVLNGGASLFSALATVLCEAGEAFLIPTPYYGAITQHVCLYGNIRLAYVYLDSEVTGLDTRPFQLTVEKLEMALREAHSEGVKVKGLILISPQNPLGDVYSPEELQEYLVFAKRHRLHVIVDEVYMLSVFEKSVGYRSVLSLERLPDPQRTHVMWATSKDFGMSGLRFGTLYTENQDVATAVASLCRYHGLSGLVQYQMAQLLRDRDWINQVYLPENHARLKAAHTYVSEELRALGIPFLSRGAGFFIWVDLRKYLPKGTFEEEMLLWRRFLDNKVLLSFGKAFECKEPGWFRFVFSDQVHRLCLGMQRVQQVLAGKSQVAEDPRPSQSQEPSDQRR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="215" xmlns="https://uniprot.org/uniprot">
    <accession>Q15172</accession>
    <accession>B2R6D2</accession>
    <accession>B7Z7L2</accession>
    <accession>D3DT99</accession>
    <accession>Q2NL72</accession>
    <accession>Q5VVB2</accession>
    <accession>Q8TBI9</accession>
    <name>2A5A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B'-alpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B56-alpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform PR61-alpha</fullName>
            <shortName>PR61alpha</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform R5-alpha</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R5A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Testis</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            <tissue>Testis</tissue>
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        <scope>PHOSPHORYLATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-42</scope>
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        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-42</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
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            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-42 AND SER-49</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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    <comment type="function">
        <text>The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-4400025">
            <id>Q9Y2T1</id>
            <label>AXIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-10305393">
            <id>Q9H246</id>
            <label>C1orf21</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-998108">
            <id>Q86YF9</id>
            <label>DZIP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-18398448">
            <id>A6NGS2</id>
            <label>ERICH4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-641642">
            <id>Q9BVP2</id>
            <label>GNL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-1757866">
            <id>P00540</id>
            <label>MOS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-745426">
            <id>Q13136</id>
            <label>PPFIA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-712311">
            <id>P67775</id>
            <label>PPP2CA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-357094">
            <id>P30154</id>
            <label>PPP2R1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-989069">
            <id>Q5FBB7</id>
            <label>SGO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
        </interactant>
        <interactant intactId="EBI-989213">
            <id>Q562F6</id>
            <label>SGO2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-11955083">
            <id>Q9NUL5-4</id>
            <label>SHFL</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q15172</id>
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            <id>Q7Z699</id>
            <label>SPRED1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q15172</id>
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            <id>P45379-11</id>
            <label>TNNT2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
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        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Chromosome</location>
            <location evidence="2">Centromere</location>
        </subcellularLocation>
        <text evidence="2">From mitotic prophase to metaphase, localizes at the inner centromere between a pair of sister kinetochores. Decreased expression at the onset of anaphase.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q15172-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15172-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_042889"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed with the highest expression in heart and skeletal muscle.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Phosphorylated on serine residues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the phosphatase 2A regulatory subunit B56 family.</text>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAH13648.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW93392.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW93393.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH22474.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI10884.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="Reactome" id="R-HSA-6811558">
        <property type="pathway name" value="PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-68877">
        <property type="pathway name" value="Mitotic Prometaphase"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9648025">
        <property type="pathway name" value="EML4 and NUDC in mitotic spindle formation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9833482">
        <property type="pathway name" value="PKR-mediated signaling"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q15172"/>
    <dbReference type="SIGNOR" id="Q15172"/>
    <dbReference type="Agora" id="ENSG00000066027"/>
    <dbReference type="BioGRID-ORCS" id="5525">
        <property type="hits" value="20 hits in 1167 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="8C2F96ED">
        <property type="entry name" value="Centrosome"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R5A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="PPP2R5A"/>
    <dbReference type="GenomeRNAi" id="5525"/>
    <dbReference type="Pharos" id="Q15172">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q15172"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q15172">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000066027">
        <property type="expression patterns" value="Expressed in monocyte and 205 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005813">
        <property type="term" value="C:centrosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000775">
        <property type="term" value="C:chromosome, centromeric region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0031430">
        <property type="term" value="C:M band"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0030018">
        <property type="term" value="C:Z disc"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0019900">
        <property type="term" value="F:kinase binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:1903077">
        <property type="term" value="P:negative regulation of protein localization to plasma membrane"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.10.10:FF:000010">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.10.10">
        <property type="entry name" value="Leucine-rich Repeat Variant"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011989">
        <property type="entry name" value="ARM-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016024">
        <property type="entry name" value="ARM-type_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002554">
        <property type="entry name" value="PP2A_B56"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10257">
        <property type="entry name" value="SERINE/THREONINE PROTEIN PHOSPHATASE 2A PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10257:SF6">
        <property type="entry name" value="SERINE_THREONINE-PROTEIN PHOSPHATASE 2A 56 KDA REGULATORY SUBUNIT ALPHA ISOFORM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01603">
        <property type="entry name" value="B56"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF028043">
        <property type="entry name" value="PP2A_B56"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48371">
        <property type="entry name" value="ARM repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0137">Centromere</keyword>
    <keyword id="KW-0158">Chromosome</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="9">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000071448" description="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform">
        <location>
            <begin position="2"/>
            <end position="486"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="1">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="1">
        <location>
            <begin position="27"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="1">
        <location>
            <begin position="38"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylserine" evidence="9">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="6 7 8 10">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="6 7 8 10">
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_042889" description="In isoform 2." evidence="4">
        <original>MSSSSPPAGAASAAISASEKVDGFTRKSVRKAQRQKRSQGSSQFRSQGSQAELHPLPQLKD</original>
        <variation>MIMN</variation>
        <location>
            <begin position="1"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AA sequence." evidence="5" ref="6">
        <original>E</original>
        <variation>F</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AA sequence." evidence="5" ref="6">
        <original>H</original>
        <variation>S</variation>
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH22474." evidence="5" ref="5">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="176"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH22474." evidence="5" ref="5">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AA sequence." evidence="5" ref="6">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="451"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16541025"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="8703017"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="486" mass="56194" checksum="D31407F7032A6D44" modified="1996-11-01" version="1">MSSSSPPAGAASAAISASEKVDGFTRKSVRKAQRQKRSQGSSQFRSQGSQAELHPLPQLKDATSNEQQELFCQKLQQCCILFDFMDSVSDLKSKEIKRATLNELVEYVSTNRGVIVESAYSDIVKMISANIFRTLPPSDNPDFDPEEDEPTLEASWPHIQLVYEFFLRFLESPDFQPSIAKRYIDQKFVQQLLELFDSEDPRERDFLKTVLHRIYGKFLGLRAFIRKQINNIFLRFIYETEHFNGVAELLEILGSIINGFALPLKAEHKQFLMKVLIPMHTAKGLALFHAQLAYCVVQFLEKDTTLTEPVIRGLLKFWPKTCSQKEVMFLGEIEEILDVIEPTQFKKIEEPLFKQISKCVSSSHFQVAERALYFWNNEYILSLIEENIDKILPIMFASLYKISKEHWNPTIVALVYNVLKTLMEMNGKLFDDLTSSYKAERQREKKKELEREELWKKLEELKLKKALEKQNSAYNMHSILSNTSAE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="197" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y2T4</accession>
    <accession>A8MSY7</accession>
    <accession>B7Z3Y1</accession>
    <accession>Q7Z4V7</accession>
    <accession>Q8NEC4</accession>
    <accession>Q9H3G7</accession>
    <name>2ABG_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>IMYPNO1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform B55-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform PR55-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform R2-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform gamma</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R2C</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="DNA Res." volume="6" first="323" last="327">
            <title>Genomic structure and localization of the human phosphatase 2A BR gamma regulatory subunit.</title>
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                <person name="Torres R."/>
                <person name="Ide S.E."/>
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            </authorList>
            <dbReference type="PubMed" id="10574460"/>
            <dbReference type="DOI" id="10.1093/dnares/6.5.323"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Genomics" volume="67" first="83" last="86">
            <title>Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16.</title>
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            <dbReference type="PubMed" id="10945473"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1999-04" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of a new human cDNA homologous to Oryctolagus cuniculus protein phosphatase 2A1 B gamma subunit.</title>
            <authorList>
                <person name="Yu L."/>
                <person name="Zhao S.Y."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
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                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
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                <person name="Nomura N."/>
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                <person name="Nakai K."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Testis</tissue>
            <tissue>Thalamus</tissue>
        </source>
    </reference>
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                <person name="Fewell G.A."/>
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                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
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                <person name="Grewal N."/>
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                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Shah N."/>
                <person name="Swearengen-Shahid S."/>
                <person name="Snider J."/>
                <person name="Strong J.T."/>
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                <person name="Yoakum M."/>
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                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
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                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
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                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
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                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
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                <person name="Mardis E.R."/>
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                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2015" name="FEBS Lett." volume="589" first="1150" last="1155">
            <title>HSF1 transcriptional activity is modulated by IER5 and PP2A/B55.</title>
            <authorList>
                <person name="Ishikawa Y."/>
                <person name="Kawabata S."/>
                <person name="Sakurai H."/>
            </authorList>
            <dbReference type="PubMed" id="25816751"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2015.03.019"/>
        </citation>
        <scope>INTERACTION WITH IER5</scope>
    </reference>
    <comment type="function">
        <text>The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with IER5 (PubMed:25816751).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Y2T4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y2T4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_036457"/>
        </isoform>
        <isoform>
            <id>Q9Y2T4-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_036458"/>
        </isoform>
        <isoform>
            <id>Q9Y2T4-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_043380"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the phosphatase 2A regulatory subunit B family.</text>
    </comment>
    <comment type="caution">
        <text evidence="5">The EMBL entry for PubMed:10574460 is not complete, the paper shows the rest of the sequence (residues 1 to 23).</text>
    </comment>
    <dbReference type="EMBL" id="AH007514">
        <property type="protein sequence ID" value="AAD20987.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF086924">
        <property type="protein sequence ID" value="AAG39636.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF145027">
        <property type="protein sequence ID" value="AAP97279.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093115">
        <property type="protein sequence ID" value="BAG52658.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296474">
        <property type="protein sequence ID" value="BAH12367.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK316003">
        <property type="protein sequence ID" value="BAH14374.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC093323">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC114815">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC116317">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC122939">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82393.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82394.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82395.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC032954">
        <property type="protein sequence ID" value="AAH32954.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS3387.1">
        <molecule id="Q9Y2T4-1"/>
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    <dbReference type="CCDS" id="CCDS3388.1">
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    <dbReference type="CCDS" id="CCDS56304.1">
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    <dbReference type="PIR" id="JC7153">
        <property type="entry name" value="JC7153"/>
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    <dbReference type="RefSeq" id="NP_001193923.1">
        <molecule id="Q9Y2T4-4"/>
        <property type="nucleotide sequence ID" value="NM_001206994.2"/>
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    <dbReference type="RefSeq" id="NP_001193924.1">
        <molecule id="Q9Y2T4-4"/>
        <property type="nucleotide sequence ID" value="NM_001206995.2"/>
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    <dbReference type="RefSeq" id="NP_001193925.1">
        <molecule id="Q9Y2T4-3"/>
        <property type="nucleotide sequence ID" value="NM_001206996.2"/>
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    <dbReference type="RefSeq" id="NP_065149.2">
        <molecule id="Q9Y2T4-1"/>
        <property type="nucleotide sequence ID" value="NM_020416.3"/>
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    <dbReference type="RefSeq" id="NP_870991.1">
        <molecule id="Q9Y2T4-2"/>
        <property type="nucleotide sequence ID" value="NM_181876.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9Y2T4"/>
    <dbReference type="SMR" id="Q9Y2T4"/>
    <dbReference type="BioGRID" id="111514">
        <property type="interactions" value="69"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26587">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B55 gamma variant"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y2T4">
        <property type="interactions" value="1492"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y2T4"/>
    <dbReference type="STRING" id="9606.ENSP00000372042"/>
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    <dbReference type="PhosphoSitePlus" id="Q9Y2T4"/>
    <dbReference type="BioMuta" id="PPP2R2C"/>
    <dbReference type="DMDM" id="145559437"/>
    <dbReference type="jPOST" id="Q9Y2T4"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000335083"/>
    <dbReference type="PeptideAtlas" id="Q9Y2T4"/>
    <dbReference type="ProteomicsDB" id="85893"/>
    <dbReference type="ProteomicsDB" id="85894">
        <molecule id="Q9Y2T4-2"/>
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    <dbReference type="ProteomicsDB" id="85895">
        <molecule id="Q9Y2T4-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="85896">
        <molecule id="Q9Y2T4-4"/>
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    <dbReference type="Antibodypedia" id="22656">
        <property type="antibodies" value="103 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5522"/>
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        <molecule id="Q9Y2T4-2"/>
        <property type="protein sequence ID" value="ENSP00000335083.5"/>
        <property type="gene ID" value="ENSG00000074211.14"/>
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    <dbReference type="Ensembl" id="ENST00000382599.9">
        <molecule id="Q9Y2T4-1"/>
        <property type="protein sequence ID" value="ENSP00000372042.4"/>
        <property type="gene ID" value="ENSG00000074211.14"/>
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    <dbReference type="Ensembl" id="ENST00000506140.5">
        <molecule id="Q9Y2T4-4"/>
        <property type="protein sequence ID" value="ENSP00000423649.1"/>
        <property type="gene ID" value="ENSG00000074211.14"/>
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    <dbReference type="Ensembl" id="ENST00000507294.1">
        <molecule id="Q9Y2T4-4"/>
        <property type="protein sequence ID" value="ENSP00000425247.1"/>
        <property type="gene ID" value="ENSG00000074211.14"/>
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    <dbReference type="Ensembl" id="ENST00000515571.5">
        <molecule id="Q9Y2T4-3"/>
        <property type="protein sequence ID" value="ENSP00000422374.1"/>
        <property type="gene ID" value="ENSG00000074211.14"/>
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    <dbReference type="GeneID" id="5522"/>
    <dbReference type="KEGG" id="hsa:5522"/>
    <dbReference type="MANE-Select" id="ENST00000382599.9">
        <property type="protein sequence ID" value="ENSP00000372042.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_020416.4"/>
        <property type="RefSeq protein sequence ID" value="NP_065149.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003gja.3">
        <molecule id="Q9Y2T4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9306"/>
    <dbReference type="ClinPGx" id="PA33670"/>
    <dbReference type="CTD" id="5522"/>
    <dbReference type="DisGeNET" id="5522"/>
    <dbReference type="GeneCards" id="PPP2R2C"/>
    <dbReference type="HGNC" id="HGNC:9306">
        <property type="gene designation" value="PPP2R2C"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000074211">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R2C"/>
    <dbReference type="MIM" id="605997">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000074211"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000074211"/>
    <dbReference type="eggNOG" id="KOG1354">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182864"/>
    <dbReference type="HOGENOM" id="CLU_021713_3_3_1"/>
    <dbReference type="InParanoid" id="Q9Y2T4"/>
    <dbReference type="OMA" id="LVPMELI"/>
    <dbReference type="OrthoDB" id="6274823at2759"/>
    <dbReference type="PAN-GO" id="Q9Y2T4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y2T4"/>
    <dbReference type="PathwayCommons" id="Q9Y2T4"/>
    <dbReference type="SignaLink" id="Q9Y2T4"/>
    <dbReference type="SIGNOR" id="Q9Y2T4"/>
    <dbReference type="Agora" id="ENSG00000074211"/>
    <dbReference type="BioGRID-ORCS" id="5522">
        <property type="hits" value="11 hits in 1144 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R2C">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="PPP2R2C"/>
    <dbReference type="GenomeRNAi" id="5522"/>
    <dbReference type="Pharos" id="Q9Y2T4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y2T4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y2T4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000074211">
        <property type="expression patterns" value="Expressed in middle temporal gyrus and 162 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y2T4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="2.130.10.10:FF:000002">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000009">
        <property type="entry name" value="PP2A_PR55"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018067">
        <property type="entry name" value="PP2A_PR55_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11871">
        <property type="entry name" value="PROTEIN PHOSPHATASE PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037309">
        <property type="entry name" value="PP2A_PR55"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00600">
        <property type="entry name" value="PP2APR55"/>
    </dbReference>
    <dbReference type="SMART" id="SM00320">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01024">
        <property type="entry name" value="PR55_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01025">
        <property type="entry name" value="PR55_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000071428" description="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform">
        <location>
            <begin position="1"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1">
        <location>
            <begin position="22"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2">
        <location>
            <begin position="87"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3">
        <location>
            <begin position="171"/>
            <end position="209"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4">
        <location>
            <begin position="220"/>
            <end position="260"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5">
        <location>
            <begin position="279"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6">
        <location>
            <begin position="334"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7">
        <location>
            <begin position="410"/>
            <end position="446"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_036457" description="In isoform 2." evidence="3">
        <original>MGEDTDTRKINHSFLRDHSYVTE</original>
        <variation>MGLSFFSKHLPIQEGQPWALKTP</variation>
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_036458" description="In isoform 3." evidence="4">
        <original>MGEDTDTRKINHSFLRDHSYVTE</original>
        <variation>MGKRDT</variation>
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043380" description="In isoform 4." evidence="3">
        <original>MGEDTDTRKINHSFLRDHSYVTE</original>
        <variation>MREADTLRPPQLMEVS</variation>
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAG39636." evidence="5" ref="2">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAG39636." evidence="5" ref="2">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAG39636 and 3; AAP97279." evidence="5" ref="2 3">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="293"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="25816751"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="447" mass="51515" checksum="DB002C2384686BBD" modified="2007-04-17" version="4">MGEDTDTRKINHSFLRDHSYVTEADIISTVEFNHTGELLATGDKGGRVVIFQREPESKNAPHSQGEYDVYSTFQSHEPEFDYLKSLEIEEKINKIKWLPQQNAAHSLLSTNDKTIKLWKITERDKRPEGYNLKDEEGKLKDLSTVTSLQVPVLKPMDLMVEVSPRRIFANGHTYHINSISVNSDCETYMSADDLRINLWHLAITDRSFNIVDIKPANMEDLTEVITASEFHPHHCNLFVYSSSKGSLRLCDMRAAALCDKHSKLFEEPEDPSNRSFFSEIISSVSDVKFSHSGRYMLTRDYLTVKVWDLNMEARPIETYQVHDYLRSKLCSLYENDCIFDKFECAWNGSDSVIMTGAYNNFFRMFDRNTKRDVTLEASRESSKPRAVLKPRRVCVGGKRRRDDISVDSLDFTKKILHTAWHPAENIIAIAATNNLYIFQDKVNSDMH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-09-13" modified="2026-01-28" version="220" xmlns="https://uniprot.org/uniprot">
    <accession>P63104</accession>
    <accession>A8K1N0</accession>
    <accession>B7Z465</accession>
    <accession>P29213</accession>
    <accession>P29312</accession>
    <accession>Q32P43</accession>
    <accession>Q5XJ08</accession>
    <accession>Q6GPI2</accession>
    <accession>Q6IN74</accession>
    <accession>Q6NUR9</accession>
    <accession>Q6P3U9</accession>
    <accession>Q86V33</accession>
    <name>1433Z_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>14-3-3 protein zeta/delta</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Protein kinase C inhibitor protein 1</fullName>
            <shortName>KCIP-1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">YWHAZ</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1992" name="J. Biol. Chem." volume="267" first="8707" last="8710">
            <title>Cloning and expression of a human 14-3-3 protein mediating phospholipolysis. Identification of an arachidonoyl-enzyme intermediate during catalysis.</title>
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                <person name="Zupan L.A."/>
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            <dbReference type="PubMed" id="1577711"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)50334-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
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                <person name="Seluja G.A."/>
                <person name="Pietromonaco S.F."/>
                <person name="Elias L."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="3">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Irie R."/>
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                <person name="Hayashi K."/>
                <person name="Sato H."/>
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                <person name="Sekine M."/>
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                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
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                <person name="Ono Y."/>
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                <person name="Hotuta T."/>
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                <person name="Hara H."/>
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                <person name="Nomura Y."/>
                <person name="Togiya S."/>
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                <person name="Imose N."/>
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                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
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                <person name="Matsunawa H."/>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
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                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Hippocampus</tissue>
            <tissue>Tongue</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
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                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
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                <person name="Flanigan M.J."/>
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                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
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                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Colon</tissue>
            <tissue>Eye</tissue>
            <tissue>Melanoma</tissue>
            <tissue>PNS</tissue>
            <tissue>Skin</tissue>
            <tissue>Testis</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
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            <title>Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.</title>
            <authorList>
                <person name="Gevaert K."/>
                <person name="Goethals M."/>
                <person name="Martens L."/>
                <person name="Van Damme J."/>
                <person name="Staes A."/>
                <person name="Thomas G.R."/>
                <person name="Vandekerckhove J."/>
            </authorList>
            <dbReference type="PubMed" id="12665801"/>
            <dbReference type="DOI" id="10.1038/nbt810"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 1-18</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
    <reference key="7">
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            <title>ACBD3 interaction with TBC1 domain 22 protein is differentially affected by enteroviral and kobuviral 3A protein binding.</title>
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                <person name="Greninger A.L."/>
                <person name="Knudsen G.M."/>
                <person name="Betegon M."/>
                <person name="Burlingame A.L."/>
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            <dbReference type="PubMed" id="23572552"/>
            <dbReference type="DOI" id="10.1128/mbio.00098-13"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 1-9; 12-49; 57-74; 84-103; 128-158 AND 194-222</scope>
        <scope>INTERACTION WITH PI4KB; TBC1D22A AND TBC1D22B</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="8">
        <citation type="submission" date="2005-11" db="UniProtKB">
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Potts A."/>
                <person name="Barblan J."/>
                <person name="Claeys D."/>
                <person name="Quadroni M."/>
            </authorList>
        </citation>
        <scope>PROTEIN SEQUENCE OF 1-9; 12-18; 28-49; 61-68; 86-91; 128-158 AND 213-222</scope>
        <scope>ACETYLATION AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>B-cell lymphoma</tissue>
            <tissue>Platelet</tissue>
        </source>
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            <authorList>
                <person name="Lubec G."/>
                <person name="Afjehi-Sadat L."/>
                <person name="Chen W.-Q."/>
                <person name="Sun Y."/>
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        </citation>
        <scope>PROTEIN SEQUENCE OF 92-103; 140-157; 194-212 AND 223-245</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Cajal-Retzius cell</tissue>
            <tissue>Fetal brain cortex</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1997" name="J. Biol. Chem." volume="272" first="28882" last="28888">
            <title>14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction.</title>
            <authorList>
                <person name="Dubois T."/>
                <person name="Rommel C."/>
                <person name="Howell S."/>
                <person name="Steinhussen U."/>
                <person name="Soneji Y."/>
                <person name="Morrice N."/>
                <person name="Moelling K."/>
                <person name="Aitken A."/>
            </authorList>
            <dbReference type="PubMed" id="9360956"/>
            <dbReference type="DOI" id="10.1074/jbc.272.46.28882"/>
        </citation>
        <scope>PHOSPHORYLATION AT THR-232</scope>
        <scope>INTERACTION WITH RAF1</scope>
        <scope>FUNCTION</scope>
    </reference>
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                <person name="Zhang S."/>
                <person name="Xing H."/>
                <person name="Muslin A.J."/>
            </authorList>
            <dbReference type="PubMed" id="10455159"/>
            <dbReference type="DOI" id="10.1074/jbc.274.35.24865"/>
        </citation>
        <scope>INTERACTION WITH TLK2</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2001" name="Proc. Natl. Acad. Sci. U.S.A." volume="98" first="8083" last="8088">
            <title>Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis.</title>
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                <person name="Ganguly S."/>
                <person name="Gastel J.A."/>
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                <person name="Beauverger P."/>
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                <person name="Klein D.C."/>
            </authorList>
            <dbReference type="PubMed" id="11427721"/>
            <dbReference type="DOI" id="10.1073/pnas.141118798"/>
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        <scope>INTERACTION WITH AANAT</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="21639" last="21642">
            <title>Identification of 14-3-3zeta as a protein kinase B/Akt substrate.</title>
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                <person name="Powell D.W."/>
                <person name="Rane M.J."/>
                <person name="Chen Q."/>
                <person name="Singh S."/>
                <person name="McLeish K.R."/>
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            <dbReference type="PubMed" id="11956222"/>
            <dbReference type="DOI" id="10.1074/jbc.m203167200"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-58</scope>
        <scope>INTERACTION WITH AKT1</scope>
    </reference>
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        <citation type="journal article" date="2003" name="Biochem. Biophys. Res. Commun." volume="301" first="991" last="999">
            <title>The interaction between ADAM 22 and 14-3-3zeta: regulation of cell adhesion and spreading.</title>
            <authorList>
                <person name="Zhu P."/>
                <person name="Sun Y."/>
                <person name="Xu R."/>
                <person name="Sang Y."/>
                <person name="Zhao J."/>
                <person name="Liu G."/>
                <person name="Cai L."/>
                <person name="Li C."/>
                <person name="Zhao S."/>
            </authorList>
            <dbReference type="PubMed" id="12589811"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(03)00056-1"/>
        </citation>
        <scope>INTERACTION WITH ADAM22</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="36323" last="36327">
            <title>The dimeric versus monomeric status of 14-3-3zeta is controlled by phosphorylation of Ser58 at the dimer interface.</title>
            <authorList>
                <person name="Woodcock J.M."/>
                <person name="Murphy J."/>
                <person name="Stomski F.C."/>
                <person name="Berndt M.C."/>
                <person name="Lopez A.F."/>
            </authorList>
            <dbReference type="PubMed" id="12865427"/>
            <dbReference type="DOI" id="10.1074/jbc.m304689200"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-58</scope>
        <scope>DIMERIZATION</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>MUTAGENESIS OF LYS-49</scope>
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        <scope>INTERACTION WITH GAB2</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3 AND LYS-68</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-207 AND THR-232</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="44">
        <citation type="journal article" date="2015" name="Biochem. Biophys. Res. Commun." volume="464" first="70" last="75">
            <title>Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins.</title>
            <authorList>
                <person name="Yuasa K."/>
                <person name="Ota R."/>
                <person name="Matsuda S."/>
                <person name="Isshiki K."/>
                <person name="Inoue M."/>
                <person name="Tsuji A."/>
            </authorList>
            <dbReference type="PubMed" id="26047703"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2015.05.105"/>
        </citation>
        <scope>INTERACTION WITH DAPK2</scope>
    </reference>
    <reference key="45">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
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                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="46">
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            <title>Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.</title>
            <authorList>
                <person name="Masters S.L."/>
                <person name="Lagou V."/>
                <person name="Jeru I."/>
                <person name="Baker P.J."/>
                <person name="Van Eyck L."/>
                <person name="Parry D.A."/>
                <person name="Lawless D."/>
                <person name="De Nardo D."/>
                <person name="Garcia-Perez J.E."/>
                <person name="Dagley L.F."/>
                <person name="Holley C.L."/>
                <person name="Dooley J."/>
                <person name="Moghaddas F."/>
                <person name="Pasciuto E."/>
                <person name="Jeandel P.Y."/>
                <person name="Sciot R."/>
                <person name="Lyras D."/>
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                <person name="De Somer L."/>
                <person name="van Nieuwenhove E."/>
                <person name="Ruuth-Praz J."/>
                <person name="Copin B."/>
                <person name="Cochet E."/>
                <person name="Medlej-Hashim M."/>
                <person name="Megarbane A."/>
                <person name="Schroder K."/>
                <person name="Savic S."/>
                <person name="Goris A."/>
                <person name="Amselem S."/>
                <person name="Wouters C."/>
                <person name="Liston A."/>
            </authorList>
            <dbReference type="PubMed" id="27030597"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.aaf1471"/>
        </citation>
        <scope>INTERACTION WITH MEFV</scope>
    </reference>
    <reference key="47">
        <citation type="journal article" date="2018" name="PLoS Pathog." volume="14" first="e1006852" last="e1006852">
            <title>Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25 autoubiquitination and functional inactivation of the RIG-I signalosome.</title>
            <authorList>
                <person name="Gupta S."/>
                <person name="Ylae-Anttila P."/>
                <person name="Callegari S."/>
                <person name="Tsai M.H."/>
                <person name="Delecluse H.J."/>
                <person name="Masucci M.G."/>
            </authorList>
            <dbReference type="PubMed" id="29357390"/>
            <dbReference type="DOI" id="10.1371/journal.ppat.1006852"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TRIM25 AND EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="48">
        <citation type="journal article" date="2019" name="PLoS Pathog." volume="15" first="e1008146" last="e1008146">
            <title>14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition of the type I interferon response by herpesvirus deconjugases.</title>
            <authorList>
                <person name="Gupta S."/>
                <person name="Ylae-Anttila P."/>
                <person name="Sandalova T."/>
                <person name="Sun R."/>
                <person name="Achour A."/>
                <person name="Masucci M.G."/>
            </authorList>
            <dbReference type="PubMed" id="31710640"/>
            <dbReference type="DOI" id="10.1371/journal.ppat.1008146"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TRIM25 AND EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="49">
        <citation type="journal article" date="2022" name="Mol. Cell" volume="0" first="0" last="0">
            <title>Itaconate is a lysosomal inducer that promotes antibacterial innate immunity.</title>
            <authorList>
                <person name="Zhang Z."/>
                <person name="Chen C."/>
                <person name="Yang F."/>
                <person name="Zeng Y.X."/>
                <person name="Sun P."/>
                <person name="Liu P."/>
                <person name="Li X."/>
            </authorList>
            <dbReference type="PubMed" id="35662396"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2022.05.009"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="50">
        <citation type="journal article" date="1999" name="Mol. Cell" volume="4" first="153" last="166">
            <title>Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding.</title>
            <authorList>
                <person name="Rittinger K."/>
                <person name="Budman J."/>
                <person name="Xu J."/>
                <person name="Volinia S."/>
                <person name="Cantley L.C."/>
                <person name="Smerdon S.J."/>
                <person name="Gamblin S.J."/>
                <person name="Yaffe M.B."/>
            </authorList>
            <dbReference type="PubMed" id="10488331"/>
            <dbReference type="DOI" id="10.1016/s1097-2765(00)80363-9"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)</scope>
    </reference>
    <reference key="51">
        <citation type="journal article" date="2001" name="Cell" volume="105" first="257" last="267">
            <title>Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation.</title>
            <authorList>
                <person name="Obsil T."/>
                <person name="Ghirlando R."/>
                <person name="Klein D.C."/>
                <person name="Ganguly S."/>
                <person name="Dyda F."/>
            </authorList>
            <dbReference type="PubMed" id="11336675"/>
            <dbReference type="DOI" id="10.1016/s0092-8674(01)00316-6"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH AANAT</scope>
    </reference>
    <reference key="52">
        <citation type="journal article" date="2005" name="Mol. Cell" volume="20" first="199" last="211">
            <title>Molecular basis for the recognition of phosphorylated and phosphoacetylated histone h3 by 14-3-3.</title>
            <authorList>
                <person name="Macdonald N."/>
                <person name="Welburn J.P.I."/>
                <person name="Noble M.E.M."/>
                <person name="Nguyen A."/>
                <person name="Yaffe M.B."/>
                <person name="Clynes D."/>
                <person name="Moggs J.G."/>
                <person name="Orphanides G."/>
                <person name="Thomson S."/>
                <person name="Edmunds J.W."/>
                <person name="Clayton A.L."/>
                <person name="Endicott J.A."/>
                <person name="Mahadevan L.C."/>
            </authorList>
            <dbReference type="PubMed" id="16246723"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2005.08.032"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH HISTONE H3 PHOSPHOPEPTIDE</scope>
    </reference>
    <reference key="53">
        <citation type="journal article" date="2007" name="EMBO J." volume="26" first="902" last="913">
            <title>Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis.</title>
            <authorList>
                <person name="Ottmann C."/>
                <person name="Yasmin L."/>
                <person name="Weyand M."/>
                <person name="Veesenmeyer J.L."/>
                <person name="Diaz M.H."/>
                <person name="Palmer R.H."/>
                <person name="Francis M.S."/>
                <person name="Hauser A.R."/>
                <person name="Wittinghofer A."/>
                <person name="Hallberg B."/>
            </authorList>
            <dbReference type="PubMed" id="17235285"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7601530"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-230 IN COMPLEX WITH PSEUDOMONAS AERUGINOSA EXOS</scope>
    </reference>
    <reference key="54">
        <citation type="journal article" date="2019" name="Front. Physiol." volume="10" first="388" last="388">
            <title>A YWHAZ variant associated with cardiofaciocutaneous syndrome activates the RAF-ERK pathway.</title>
            <authorList>
                <person name="Popov I.K."/>
                <person name="Hiatt S.M."/>
                <person name="Whalen S."/>
                <person name="Keren B."/>
                <person name="Ruivenkamp C."/>
                <person name="van Haeringen A."/>
                <person name="Chen M.J."/>
                <person name="Cooper G.M."/>
                <person name="Korf B.R."/>
                <person name="Chang C."/>
            </authorList>
            <dbReference type="PubMed" id="31024343"/>
            <dbReference type="DOI" id="10.3389/fphys.2019.00388"/>
        </citation>
        <scope>VARIANTS POPCHAS 14-GLU--ASN-245 DEL; ARG-53; LEU-145 AND TRP-230</scope>
        <scope>CHARACTERIZATION OF VARIANT POPCHAS TRP-230</scope>
        <scope>INVOLVEMENT IN POPCHAS</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH BRAF AND RAF1</scope>
        <scope>PHOSPHORYLATION AT THR-232 BY CK1</scope>
        <scope>MUTAGENESIS OF THR-232</scope>
    </reference>
    <reference key="55">
        <citation type="journal article" date="2023" name="Hum. Mol. Genet." volume="32" first="462" last="472">
            <title>YWHAZ variation causes intellectual disability and global developmental delay with brain malformation.</title>
            <authorList>
                <person name="Wan R.P."/>
                <person name="Liu Z.G."/>
                <person name="Huang X.F."/>
                <person name="Kwan P."/>
                <person name="Li Y.P."/>
                <person name="Qu X.C."/>
                <person name="Ye X.G."/>
                <person name="Chen F.Y."/>
                <person name="Zhang D.W."/>
                <person name="He M.F."/>
                <person name="Wang J."/>
                <person name="Mao Y.L."/>
                <person name="Qiao J.D."/>
            </authorList>
            <dbReference type="PubMed" id="36001342"/>
            <dbReference type="DOI" id="10.1093/hmg/ddac210"/>
        </citation>
        <scope>VARIANT POPCHAS ASN-49</scope>
        <scope>CHARACTERIZATION OF VARIANT POPCHAS ASN-49</scope>
        <scope>INVOLVEMENT IN POPCHAS</scope>
    </reference>
    <comment type="function">
        <text evidence="1 12 14 16 22 23 33 35 37">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 5 6 7 8 9 10 11 12 13 14 15 16 17 18 20 21 22 23 25 26 27 28 29 30 31 33 37">Interacts with CDK16 and BSPRY (By similarity). Interacts with WEE1 (C-terminal). Interacts with SAMSN1 (By similarity). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with Thr-phosphorylated ITGB2 (By similarity). Interacts with BCL2L11 (By similarity). Homodimer (PubMed:12865427, PubMed:16376338). Heterodimerizes with YWHAE (PubMed:16376338). Homo- and heterodimerization is inhibited by phosphorylation on Ser-58 (PubMed:16376338). Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232 (PubMed:31024343). Interacts with BRAF (PubMed:31024343). Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation. Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization. Interacts with GAB2 and TLK2. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with ZFP36L1 (via phosphorylated form); this interaction occurs in a p38 MAPK- and AKT-signaling pathways (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with AK5, LDB1, MADD, MARK3, PDE1A and SMARCB1 (PubMed:16959763). Interacts with MEFV (PubMed:27030597). Interacts with ADAM22 (via C-terminus) (PubMed:12589811).</text>
    </comment>
    <comment type="subunit">
        <text evidence="32 34">(Microbial infection) Interacts with Epstein-Barr virus protein BPLF1 and TRIM25; leading to inhibition of the type-I IFN response.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-487024">
            <id>O14639</id>
            <label>ABLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-353944">
            <id>P60709</id>
            <label>ACTB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
            <label>ADAM22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
            <label>ADAM22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1373806">
            <id>Q12802</id>
            <label>AKAP13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-720593">
            <id>Q96B36</id>
            <label>AKT1S1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-727707">
            <id>P25054</id>
            <label>APC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-365961">
            <id>P10398</id>
            <label>ARAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1642518">
            <id>Q5T5U3</id>
            <label>ARHGAP21</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1057448">
            <id>Q5VV41</id>
            <label>ARHGEF16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-302405">
            <id>Q92974</id>
            <label>ARHGEF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-2410430">
            <id>Q8NHH9</id>
            <label>ATL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-351437">
            <id>P25705</id>
            <label>ATP5F1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-356231">
            <id>P06576</id>
            <label>ATP5F1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-700771">
            <id>Q92934</id>
            <label>BAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-525456">
            <id>Q9UQB8</id>
            <label>BAIAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-355504">
            <id>P27708</id>
            <label>CAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-397435">
            <id>P62158</id>
            <label>CALM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-518228">
            <id>P22681</id>
            <label>CBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-4392727">
            <id>O00257-3</id>
            <label>CBX4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-947308">
            <id>Q9Y3M2</id>
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        <interactant intactId="EBI-355164">
            <id>P55072</id>
            <label>VCP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-353844">
            <id>P08670</id>
            <label>VIM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-2819293">
            <id>Q69YN4</id>
            <label>VIRMA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-914695">
            <id>P30291</id>
            <label>WEE1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-457907">
            <id>Q9H4A3</id>
            <label>WNK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-751647">
            <id>Q15007</id>
            <label>WTAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1055121">
            <id>Q6AWC2</id>
            <label>WWC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-355867">
            <id>O14980</id>
            <label>XPO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1044059">
            <id>P46937</id>
            <label>YAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>17</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
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        <interactant intactId="EBI-446413">
            <id>Q29495</id>
            <label>AANAT</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
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        <interactant intactId="EBI-400328">
            <id>Q61337</id>
            <label>Bad</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-8615392">
            <id>Q6P6S3</id>
            <label>Bspry</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-7540603">
            <id>P67828</id>
            <label>CSNK1A1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-1030357">
            <id>Q51451</id>
            <label>exoS</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-994554">
            <id>P54256-2</id>
            <label>Hap1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-7291149">
            <id>P29172</id>
            <label>MAPT</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-6930266">
            <id>P61588</id>
            <label>Rnd3</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-347088">
            <id>P63104</id>
        </interactant>
        <interactant intactId="EBI-457639">
            <id>P84198</id>
            <label>VIM</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="24">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="24">Melanosome</location>
        </subcellularLocation>
        <text evidence="24">Located to stage I to stage IV melanosomes.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P63104-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P63104-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_047505"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="9 11 14 18 19 22 37 40">The delta, brain-specific form differs from the zeta form in being phosphorylated (Probable). Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria (PubMed:15071501, PubMed:15696159). Phosphorylation on Thr-232; inhibits binding of RAF1 (PubMed:9360956). Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion (PubMed:11956222, PubMed:12865427, PubMed:15883165, PubMed:16376338). Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53 (PubMed:11956222, PubMed:12865427, PubMed:15883165, PubMed:16376338).</text>
    </comment>
    <comment type="disease" evidence="33 36">
        <disease id="DI-05565">
            <name>Popov-Chang syndrome</name>
            <acronym>POPCHAS</acronym>
            <description>An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, facial dysmorphism, and behavioral manifestations including autistic-like behavior, self-injurious behavior, fear of social interaction, and poor concentration. Additional features are highly variable and can include seizures, short stature, feeding difficulties, and skin abnormalities.</description>
            <dbReference type="MIM" id="618428"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="40">Belongs to the 14-3-3 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="41">Was originally thought to have phospholipase A2 activity.</text>
    </comment>
    <comment type="sequence caution" evidence="40">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH51814" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="40">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH73141" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAF82634.1"/>
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        <property type="protein sequence ID" value="BAH12451.1"/>
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        <property type="protein sequence ID" value="EAW91823.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH03623.3"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="term" value="P:synaptic target recognition"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0035148">
        <property type="term" value="P:tube formation"/>
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        <property type="project" value="Ensembl"/>
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        <property type="entry name" value="14-3-3_beta_zeta"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="14-3-3 gamma 1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="14-3-3 domain"/>
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        <property type="entry name" value="14-3-3"/>
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        <property type="entry name" value="14-3-3_CS"/>
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        <property type="entry name" value="14-3-3_dom_sf"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="14-3-3 protein"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="1433_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000058627" description="14-3-3 protein zeta/delta">
        <location>
            <begin position="1"/>
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    <feature type="site" description="Interaction with phosphoserine on interacting protein" evidence="4">
        <location>
            <position position="56"/>
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    <feature type="site" description="Interaction with phosphoserine on interacting protein" evidence="4">
        <location>
            <position position="127"/>
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    <feature type="modified residue" description="N-acetylmethionine" evidence="38 45 46 47">
        <location>
            <position position="1"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="42">
        <location>
            <position position="3"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA and PKB/AKT1" evidence="9 11 19 22">
        <location>
            <position position="58"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="42">
        <location>
            <position position="68"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine; by MAPK8" evidence="14 18">
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="43 44">
        <location>
            <position position="207"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="210"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by CK1" evidence="33 37 44">
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_047505" description="In isoform 2." evidence="39">
        <original>MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVL</original>
        <variation>MSQPCRKLWRHNYETSSCIEFLK</variation>
        <location>
            <begin position="1"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082640" description="In POPCHAS; likely pathogenic; dbSNP:rs775309705." evidence="33">
        <location>
            <begin position="14"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_091045" description="In POPCHAS; likely pathogenic; variant knockin in Drosophila results in significant memory defects and abnormal brain structures indicating impaired YWHAZ protein function." evidence="36">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082641" description="In POPCHAS; uncertain significance; dbSNP:rs1563691700." evidence="33">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082642" description="In POPCHAS; uncertain significance; dbSNP:rs754522887." evidence="33">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="145"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082643" description="In POPCHAS; likely pathogenic; gain-of-function mutation in signal transduction; changed regulation of ERK1 and ERK2 cascade; increased interaction with BRAF; increased interaction with RAF1; loss of phosphorylation by CK1 at Thr-232; dbSNP:rs1554612377." evidence="33">
        <original>S</original>
        <variation>W</variation>
        <location>
            <position position="230"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with NOXA1." evidence="26">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes lamellipodia formation and induces filopodia formation." evidence="23">
        <original>RSSWR</original>
        <variation>ASSWA</variation>
        <location>
            <begin position="56"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of sphingosine-activated PKA phosphorylation. Promotes homodimerization and heterodimerization with YWHAE. Enhanced transcriptional activity of P53." evidence="19 22">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of homodimerization. Reduced dimerization with YWHAE. Significantly reduced interaction with P53. No enhancement of P53 transcriptional activity." evidence="19 22">
        <original>S</original>
        <variation>E</variation>
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="On DNA damage, loss of MAPK8-mediated phosphorylation. Loss of binding ABL1. Attenuates ABL1-mediated apoptosis. No loss of interaction with BAX under stress conditions. Inhibits translocation of BAX to mitochondria." evidence="14 18">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of phosphorylation by CK1." evidence="33">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH68456." evidence="40" ref="5">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAH12451." evidence="40" ref="3">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="136"/>
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    <feature type="helix" evidence="48">
        <location>
            <begin position="3"/>
            <end position="15"/>
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    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="19"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="38"/>
            <end position="67"/>
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    </feature>
    <feature type="turn" evidence="48">
        <location>
            <begin position="69"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="76"/>
            <end position="103"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="105"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="112"/>
            <end position="131"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="135"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="165"/>
            <end position="180"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="185"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="201"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="turn" evidence="48">
        <location>
            <begin position="208"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="helix" evidence="48">
        <location>
            <begin position="211"/>
            <end position="228"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O55043"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P63101"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P63102"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P63103"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="Q9ES28"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10455159"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11336675"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="11427721"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="11956222"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12589811"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="12865427"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="14578935"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="14970201"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="15071501"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="15159416"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="15644438"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="15660133"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="15696159"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="15883165"/>
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    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="16114898"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="16246723"/>
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    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="16376338"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="16959763"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="24">
        <source>
            <dbReference type="PubMed" id="17081065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="25">
        <source>
            <dbReference type="PubMed" id="17235285"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="26">
        <source>
            <dbReference type="PubMed" id="17913709"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="27">
        <source>
            <dbReference type="PubMed" id="19172738"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="28">
        <source>
            <dbReference type="PubMed" id="19640509"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="29">
        <source>
            <dbReference type="PubMed" id="23572552"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="30">
        <source>
            <dbReference type="PubMed" id="26047703"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="31">
        <source>
            <dbReference type="PubMed" id="27030597"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="32">
        <source>
            <dbReference type="PubMed" id="29357390"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="33">
        <source>
            <dbReference type="PubMed" id="31024343"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="34">
        <source>
            <dbReference type="PubMed" id="31710640"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="35">
        <source>
            <dbReference type="PubMed" id="35662396"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="36">
        <source>
            <dbReference type="PubMed" id="36001342"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="37">
        <source>
            <dbReference type="PubMed" id="9360956"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="38">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000303" key="39">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="40"/>
    <evidence type="ECO:0000305" key="41">
        <source>
            <dbReference type="PubMed" id="1577711"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="42">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="43">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="44">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="45">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="46">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="47">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="48">
        <source>
            <dbReference type="PDB" id="2O02"/>
        </source>
    </evidence>
    <sequence length="245" mass="27745" checksum="D464DF2286BBFE60" modified="2004-09-13" version="1">MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="207" xmlns="https://uniprot.org/uniprot">
    <accession>Q15173</accession>
    <accession>Q13853</accession>
    <name>2A5B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B'-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B56-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform PR61-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform R5-beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R5B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="J. Biol. Chem." volume="270" first="26123" last="26128">
            <title>Identification of a new family of protein phosphatase 2A regulatory subunits.</title>
            <authorList>
                <person name="McCright B."/>
                <person name="Virshup D.M."/>
            </authorList>
            <dbReference type="PubMed" id="7592815"/>
            <dbReference type="DOI" id="10.1074/jbc.270.44.26123"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="Biochem. J." volume="317" first="187" last="194">
            <title>The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits.</title>
            <authorList>
                <person name="Zolnierowicz S."/>
                <person name="van Hoof C."/>
                <person name="Andjelkovic N."/>
                <person name="Cron P."/>
                <person name="Stevens I."/>
                <person name="Merlevede W."/>
                <person name="Goris J."/>
                <person name="Hemmings B.A."/>
            </authorList>
            <dbReference type="PubMed" id="8694763"/>
            <dbReference type="DOI" id="10.1042/bj3170187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-2)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1996" name="J. Biol. Chem." volume="271" first="22081" last="22089">
            <title>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</title>
            <authorList>
                <person name="McCright B."/>
                <person name="Rivers A.M."/>
                <person name="Audlin S."/>
                <person name="Virshup D.M."/>
            </authorList>
            <dbReference type="PubMed" id="8703017"/>
            <dbReference type="DOI" id="10.1074/jbc.271.36.22081"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="46" last="52">
            <title>Shugoshin collaborates with protein phosphatase 2A to protect cohesin.</title>
            <authorList>
                <person name="Kitajima T.S."/>
                <person name="Sakuno T."/>
                <person name="Ishiguro K."/>
                <person name="Iemura S."/>
                <person name="Natsume T."/>
                <person name="Kawashima S.A."/>
                <person name="Watanabe Y."/>
            </authorList>
            <dbReference type="PubMed" id="16541025"/>
            <dbReference type="DOI" id="10.1038/nature04663"/>
        </citation>
        <scope>INTERACTION WITH SGO1</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="Mol. Cell" volume="41" first="471" last="479">
            <title>Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt.</title>
            <authorList>
                <person name="Rodgers J.T."/>
                <person name="Vogel R.O."/>
                <person name="Puigserver P."/>
            </authorList>
            <dbReference type="PubMed" id="21329884"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2011.02.007"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT SER-32; SER-35; SER-44; SER-46; SER-47 AND SER-48</scope>
        <scope>INTERACTION WITH AKT1</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2012" name="J. Biol. Chem." volume="287" first="43378" last="43389">
            <title>Selective proteasomal degradation of the B'beta subunit of protein phosphatase 2A by the E3 ubiquitin ligase adaptor Kelch-like 15.</title>
            <authorList>
                <person name="Oberg E.A."/>
                <person name="Nifoussi S.K."/>
                <person name="Gingras A.C."/>
                <person name="Strack S."/>
            </authorList>
            <dbReference type="PubMed" id="23135275"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.420281"/>
        </citation>
        <scope>INTERACTION WITH CUL3 AND KLHL15</scope>
        <scope>IDENTIFICATION IN PP2A COMPLEX</scope>
        <scope>UBIQUITINATION</scope>
        <scope>MUTAGENESIS OF TYR-52; 103-LYS-ARG-104 AND 232-ARG-LYS-233</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Hum. Mol. Genet." volume="24" first="4775" last="4779">
            <title>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</title>
            <authorList>
                <consortium name="Childhood Overgrowth Collaboration"/>
                <person name="Loveday C."/>
                <person name="Tatton-Brown K."/>
                <person name="Clarke M."/>
                <person name="Westwood I."/>
                <person name="Renwick A."/>
                <person name="Ramsay E."/>
                <person name="Nemeth A."/>
                <person name="Campbell J."/>
                <person name="Joss S."/>
                <person name="Gardner M."/>
                <person name="Zachariou A."/>
                <person name="Elliott A."/>
                <person name="Ruark E."/>
                <person name="van Montfort R."/>
                <person name="Rahman N."/>
            </authorList>
            <dbReference type="PubMed" id="25972378"/>
            <dbReference type="DOI" id="10.1093/hmg/ddv182"/>
        </citation>
        <scope>VARIANT LEU-161</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2019" name="Hum. Mol. Genet." volume="28" first="1578" last="1578">
            <authorList>
                <consortium name="Childhood Overgrowth Collaboration"/>
                <person name="Loveday C."/>
                <person name="Tatton-Brown K."/>
                <person name="Clarke M."/>
                <person name="Westwood I."/>
                <person name="Renwick A."/>
                <person name="Ramsay E."/>
                <person name="Nemeth A."/>
                <person name="Campbell J."/>
                <person name="Joss S."/>
                <person name="Gardner M."/>
                <person name="Zachariou A."/>
                <person name="Elliott A."/>
                <person name="Ruark E."/>
                <person name="Montfort R.V."/>
                <person name="Rahman N."/>
            </authorList>
            <dbReference type="PubMed" id="30615140"/>
            <dbReference type="DOI" id="10.1093/hmg/ddy424"/>
        </citation>
        <scope>ERRATUM OF PUBMED:25972378</scope>
    </reference>
    <comment type="function">
        <text evidence="3">As the regulatory component of the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme, modulates substrate specificity, subcellular localization, and responsiveness to phosphorylation. The phosphorylated form mediates the interaction between PP2A and AKT1, leading to AKT1 dephosphorylation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3 4">Component of the serine/threonine-protein phosphatase 2A complex (PP2A). This complex consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant scaffold subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (PubMed:23135275). Interacts with SGO1 (PubMed:16541025). Interacts with AKT1 (PubMed:21329884). Interacts with CUL3 and KLHL15; this interaction leads to proteasomal degradation (PubMed:23135275).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1369497">
            <id>Q15173</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1369497">
            <id>Q15173</id>
        </interactant>
        <interactant intactId="EBI-1748945">
            <id>P46695</id>
            <label>IER3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1369497">
            <id>Q15173</id>
        </interactant>
        <interactant intactId="EBI-712311">
            <id>P67775</id>
            <label>PPP2CA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1369497">
            <id>Q15173</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q15173-1</id>
            <name>Beta-1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15173-2</id>
            <name>Beta-2</name>
            <sequence type="described" ref="VSP_005109"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Highest expression in brain.</text>
    </comment>
    <comment type="induction">
        <text>By retinoic acid; in neuroblastoma cell lines.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">Ubiquitinated by E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the phosphatase 2A regulatory subunit B56 family.</text>
    </comment>
    <dbReference type="EMBL" id="L42374">
        <property type="protein sequence ID" value="AAC37602.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z69028">
        <property type="protein sequence ID" value="CAA93152.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC045619">
        <property type="protein sequence ID" value="AAH45619.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8085.1">
        <molecule id="Q15173-1"/>
    </dbReference>
    <dbReference type="PIR" id="I70147">
        <property type="entry name" value="I70147"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006235.1">
        <molecule id="Q15173-1"/>
        <property type="nucleotide sequence ID" value="NM_006244.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047283155.1">
        <molecule id="Q15173-1"/>
        <property type="nucleotide sequence ID" value="XM_047427199.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054225226.1">
        <molecule id="Q15173-1"/>
        <property type="nucleotide sequence ID" value="XM_054369251.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q15173"/>
    <dbReference type="SMR" id="Q15173"/>
    <dbReference type="BioGRID" id="111518">
        <property type="interactions" value="47"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2574">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B56 beta variant"/>
    </dbReference>
    <dbReference type="ELM" id="Q15173"/>
    <dbReference type="FunCoup" id="Q15173">
        <property type="interactions" value="1407"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15173">
        <property type="interactions" value="27"/>
    </dbReference>
    <dbReference type="MINT" id="Q15173"/>
    <dbReference type="STRING" id="9606.ENSP00000164133"/>
    <dbReference type="iPTMnet" id="Q15173"/>
    <dbReference type="PhosphoSitePlus" id="Q15173"/>
    <dbReference type="BioMuta" id="PPP2R5B"/>
    <dbReference type="DMDM" id="7387497"/>
    <dbReference type="jPOST" id="Q15173"/>
    <dbReference type="MassIVE" id="Q15173"/>
    <dbReference type="PaxDb" id="9606-ENSP00000164133"/>
    <dbReference type="PeptideAtlas" id="Q15173"/>
    <dbReference type="ProteomicsDB" id="60483"/>
    <dbReference type="ProteomicsDB" id="60484">
        <molecule id="Q15173-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q15173"/>
    <dbReference type="TopDownProteomics" id="Q15173-1">
        <molecule id="Q15173-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="29566">
        <property type="antibodies" value="107 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5526"/>
    <dbReference type="Ensembl" id="ENST00000164133.7">
        <molecule id="Q15173-1"/>
        <property type="protein sequence ID" value="ENSP00000164133.2"/>
        <property type="gene ID" value="ENSG00000068971.15"/>
    </dbReference>
    <dbReference type="GeneID" id="5526"/>
    <dbReference type="KEGG" id="hsa:5526"/>
    <dbReference type="MANE-Select" id="ENST00000164133.7">
        <property type="protein sequence ID" value="ENSP00000164133.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006244.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006235.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001oby.4">
        <molecule id="Q15173-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9310"/>
    <dbReference type="ClinPGx" id="PA33673"/>
    <dbReference type="CTD" id="5526"/>
    <dbReference type="DisGeNET" id="5526"/>
    <dbReference type="GeneCards" id="PPP2R5B"/>
    <dbReference type="HGNC" id="HGNC:9310">
        <property type="gene designation" value="PPP2R5B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000068971">
        <property type="expression patterns" value="Tissue enriched (brain)"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R5B"/>
    <dbReference type="MIM" id="601644">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000068971"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000068971"/>
    <dbReference type="eggNOG" id="KOG2085">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01030000234620"/>
    <dbReference type="HOGENOM" id="CLU_012437_4_0_1"/>
    <dbReference type="InParanoid" id="Q15173"/>
    <dbReference type="OMA" id="QDRRMQM"/>
    <dbReference type="OrthoDB" id="10264446at2759"/>
    <dbReference type="PAN-GO" id="Q15173">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15173"/>
    <dbReference type="PathwayCommons" id="Q15173"/>
    <dbReference type="Reactome" id="R-HSA-141444">
        <property type="pathway name" value="Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-195253">
        <property type="pathway name" value="Degradation of beta-catenin by the destruction complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-196299">
        <property type="pathway name" value="Beta-catenin phosphorylation cascade"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2467813">
        <property type="pathway name" value="Separation of Sister Chromatids"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2500257">
        <property type="pathway name" value="Resolution of Sister Chromatid Cohesion"/>
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    <dbReference type="Reactome" id="R-HSA-381038">
        <property type="pathway name" value="XBP1(S) activates chaperone genes"/>
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        <property type="pathway name" value="Co-stimulation by CD28"/>
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        <property type="pathway name" value="Co-inhibition by CTLA4"/>
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        <property type="pathway name" value="Platelet sensitization by LDL"/>
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    <dbReference type="Reactome" id="R-HSA-4641262">
        <property type="pathway name" value="Disassembly of the destruction complex and recruitment of AXIN to the membrane"/>
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        <property type="pathway name" value="Signaling by GSK3beta mutants"/>
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        <property type="pathway name" value="CTNNB1 S33 mutants aren't phosphorylated"/>
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        <property type="pathway name" value="CTNNB1 S37 mutants aren't phosphorylated"/>
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        <property type="pathway name" value="CTNNB1 S45 mutants aren't phosphorylated"/>
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    <dbReference type="Reactome" id="R-HSA-5358752">
        <property type="pathway name" value="CTNNB1 T41 mutants aren't phosphorylated"/>
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    <dbReference type="Reactome" id="R-HSA-5467337">
        <property type="pathway name" value="APC truncation mutants have impaired AXIN binding"/>
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        <property type="pathway name" value="AXIN missense mutants destabilize the destruction complex"/>
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        <property type="pathway name" value="Truncations of AMER1 destabilize the destruction complex"/>
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        <property type="pathway name" value="RHO GTPases Activate Formins"/>
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        <property type="pathway name" value="RAF activation"/>
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        <property type="pathway name" value="Negative regulation of MAPK pathway"/>
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        <property type="pathway name" value="PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling"/>
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    <dbReference type="Reactome" id="R-HSA-68877">
        <property type="pathway name" value="Mitotic Prometaphase"/>
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    <dbReference type="Reactome" id="R-HSA-9648025">
        <property type="pathway name" value="EML4 and NUDC in mitotic spindle formation"/>
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        <property type="hits" value="30 hits in 1160 CRISPR screens"/>
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        <property type="term" value="F:protein phosphatase activator activity"/>
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        <property type="term" value="P:signal transduction"/>
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        <property type="project" value="InterPro"/>
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        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Leucine-rich Repeat Variant"/>
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        <property type="entry name" value="ARM-like"/>
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        <property type="entry name" value="ARM-type_fold"/>
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        <property type="entry name" value="PP2A_B56"/>
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        <property type="entry name" value="ARM repeat"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000071450" description="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform">
        <location>
            <begin position="1"/>
            <end position="497"/>
        </location>
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    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
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        </location>
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    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="475"/>
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    <feature type="compositionally biased region" description="Low complexity" evidence="1">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="1">
        <location>
            <begin position="34"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
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            <position position="32"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
        <location>
            <position position="35"/>
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    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
        <location>
            <position position="44"/>
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    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
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            <position position="46"/>
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    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
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            <position position="47"/>
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    <feature type="modified residue" description="Phosphoserine; by CLK2" evidence="9">
        <location>
            <position position="48"/>
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    </feature>
    <feature type="splice variant" id="VSP_005109" description="In isoform Beta-2." evidence="7">
        <original>METKLPPASTPTSPSSPGL</original>
        <variation>MITVNPPLPQDTVNLF</variation>
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            <begin position="1"/>
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    <feature type="sequence variant" id="VAR_090759" description="Found in a patient with intellectual disability and tall stature; uncertain significance." evidence="5">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of KLHL15-binding and enhanced stability." evidence="4">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired trimer formation with PP2A subunits A/C, no effect on KLHL15-binding." evidence="4">
        <original>KR</original>
        <variation>DE</variation>
        <location>
            <begin position="103"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired trimer formation with PP2A subunits A/C, no effect on KLHL15-binding." evidence="4">
        <original>RK</original>
        <variation>ED</variation>
        <location>
            <begin position="232"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AA sequence." evidence="8" ref="2">
        <original>QE</original>
        <variation>IF</variation>
        <location>
            <begin position="57"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AA sequence." evidence="8" ref="2">
        <original>ES</original>
        <variation>GA</variation>
        <location>
            <begin position="177"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AA sequence." evidence="8" ref="2">
        <original>F</original>
        <variation>M</variation>
        <location>
            <position position="181"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 2; AA sequence." evidence="8" ref="2">
        <original>S</original>
        <variation>M</variation>
        <location>
            <position position="184"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 2; AA sequence." evidence="8" ref="2">
        <original>W</original>
        <variation>E</variation>
        <location>
            <position position="461"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16541025"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="21329884"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="23135275"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="25972378"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="8703017"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="8694763"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="21329884"/>
        </source>
    </evidence>
    <sequence length="497" mass="57393" checksum="8BEF84F20A77982D" modified="1996-11-01" version="1">METKLPPASTPTSPSSPGLSPVPPPDKVDGFSRRSLRRARPRRSHSSSQFRYQSNQQELTPLPLLKDVPASELHELLSRKLAQCGVMFDFLDCVADLKGKEVKRAALNELVECVGSTRGVLIEPVYPDIIRMISVNIFRTLPPSENPEFDPEEDEPNLEPSWPHLQLVYEFFLRFLESPDFQPSVAKRYVDQKFVLMLLELFDSEDPREREYLKTILHRVYGKFLGLRAYIRKQCNHIFLRFIYEFEHFNGVAELLEILGSIINGFALPLKTEHKQFLVRVLIPLHSVKSLSVFHAQLAYCVVQFLEKDATLTEHVIRGLLKYWPKTCTQKEVMFLGEMEEILDVIEPSQFVKIQEPLFKQVARCVSSPHFQVAERALYFWNNEYILSLIEDNCHTVLPAVFGTLYQVSKEHWNQTIVSLIYNVLKTFMEMNGKLFDELTASYKLEKQQEQQKAQERQELWQGLEELRLRRLQGTQGAKEAPLQRLTPQVAASGGQS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-06-07" modified="2026-01-28" version="204" xmlns="https://uniprot.org/uniprot">
    <accession>P61981</accession>
    <accession>O70457</accession>
    <accession>P35214</accession>
    <accession>Q6FH52</accession>
    <accession>Q9UDP2</accession>
    <accession>Q9UN99</accession>
    <name>1433G_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="30">14-3-3 protein gamma</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Protein kinase C inhibitor protein 1</fullName>
            <shortName>KCIP-1</shortName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>14-3-3 protein gamma, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="31" type="primary">YWHAG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="DNA Cell Biol." volume="18" first="555" last="564">
            <title>14-3-3gamma interacts with and is phosphorylated by multiple protein kinase C isoforms in PDGF-stimulated human vascular smooth muscle cells.</title>
            <authorList>
                <person name="Autieri M.V."/>
                <person name="Carbone C.J."/>
            </authorList>
            <dbReference type="PubMed" id="10433554"/>
            <dbReference type="DOI" id="10.1089/104454999315105"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PHOSPHORYLATION</scope>
        <scope>INTERACTION WITH RAF1</scope>
        <source>
            <tissue>Vascular smooth muscle</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Genomics" volume="60" first="241" last="243">
            <title>Cloning, expression, and chromosomal mapping of the human 14-3-3gamma gene (YWHAG) to 7q11.23.</title>
            <authorList>
                <person name="Horie M."/>
                <person name="Suzuki M."/>
                <person name="Takahashi E."/>
                <person name="Tanigami A."/>
            </authorList>
            <dbReference type="PubMed" id="10486217"/>
            <dbReference type="DOI" id="10.1006/geno.1999.5887"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Graves T.A."/>
                <person name="Pepin K.H."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Maas J."/>
                <person name="Jaeger S."/>
                <person name="Walker R."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="O'Laughlin M.D."/>
                <person name="Schaller M.E."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
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                <person name="Sun H."/>
                <person name="Edwards J."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Andrews S."/>
                <person name="Isak A."/>
                <person name="Vanbrunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Lamar B."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
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                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Abbott A."/>
                <person name="Minx P."/>
                <person name="Maupin R."/>
                <person name="Strowmatt C."/>
                <person name="Latreille P."/>
                <person name="Miller N."/>
                <person name="Johnson D."/>
                <person name="Murray J."/>
                <person name="Woessner J.P."/>
                <person name="Wendl M.C."/>
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                <person name="Iadanoto S."/>
                <person name="Bubb K."/>
                <person name="Simms E."/>
                <person name="Levy R."/>
                <person name="Clendenning J."/>
                <person name="Kaul R."/>
                <person name="Kent W.J."/>
                <person name="Furey T.S."/>
                <person name="Baertsch R.A."/>
                <person name="Brent M.R."/>
                <person name="Keibler E."/>
                <person name="Flicek P."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Bailey J.A."/>
                <person name="Portnoy M.E."/>
                <person name="Torrents D."/>
                <person name="Chinwalla A.T."/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT VAL-2</scope>
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                <person name="Megarbane A."/>
                <person name="Schroder K."/>
                <person name="Savic S."/>
                <person name="Goris A."/>
                <person name="Amselem S."/>
                <person name="Wouters C."/>
                <person name="Liston A."/>
            </authorList>
            <dbReference type="PubMed" id="27030597"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.aaf1471"/>
        </citation>
        <scope>INTERACTION WITH MEFV</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="2017" name="Biochem. J." volume="474" first="1273" last="1287">
            <title>Structural interface between LRRK2 and 14-3-3 protein.</title>
            <authorList>
                <person name="Stevers L.M."/>
                <person name="de Vries R.M."/>
                <person name="Doveston R.G."/>
                <person name="Milroy L.G."/>
                <person name="Brunsveld L."/>
                <person name="Ottmann C."/>
            </authorList>
            <dbReference type="PubMed" id="28202711"/>
            <dbReference type="DOI" id="10.1042/bcj20161078"/>
        </citation>
        <scope>INTERACTION WITH LRRK2</scope>
    </reference>
    <reference key="33">
        <citation type="journal article" date="2017" name="Mol. Brain" volume="10" first="51" last="51">
            <title>Direct interaction with 14-3-3gamma promotes surface expression of Best1 channel in astrocyte.</title>
            <authorList>
                <person name="Oh S.J."/>
                <person name="Woo J."/>
                <person name="Lee Y.S."/>
                <person name="Cho M."/>
                <person name="Kim E."/>
                <person name="Cho N.C."/>
                <person name="Park J.Y."/>
                <person name="Pae A.N."/>
                <person name="Justin Lee C."/>
                <person name="Hwang E.M."/>
            </authorList>
            <dbReference type="PubMed" id="29121962"/>
            <dbReference type="DOI" id="10.1186/s13041-017-0331-x"/>
        </citation>
        <scope>INTERACTION WITH BEST1</scope>
    </reference>
    <reference key="34">
        <citation type="journal article" date="2019" name="Int. J. Mol. Sci." volume="20" first="0" last="0">
            <title>Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces.</title>
            <authorList>
                <person name="Uttagomol J."/>
                <person name="Ahmad U.S."/>
                <person name="Rehman A."/>
                <person name="Huang Y."/>
                <person name="Laly A.C."/>
                <person name="Kang A."/>
                <person name="Soetaert J."/>
                <person name="Chance R."/>
                <person name="Teh M.T."/>
                <person name="Connelly J.T."/>
                <person name="Wan H."/>
            </authorList>
            <dbReference type="PubMed" id="31835537"/>
            <dbReference type="DOI" id="10.3390/ijms20246221"/>
        </citation>
        <scope>IDENTIFICATION IN A COMPLEX DSG3; PKP1 AND YAP1</scope>
        <scope>INTERACTION WITH DSG3; PKP1 AND YAP1</scope>
    </reference>
    <reference key="35">
        <citation type="journal article" date="2018" name="J. Cell Sci." volume="131" first="0" last="0">
            <title>14-3-3 proteins regulate desmosomal adhesion via plakophilins.</title>
            <authorList>
                <person name="Rietscher K."/>
                <person name="Keil R."/>
                <person name="Jordan A."/>
                <person name="Hatzfeld M."/>
            </authorList>
            <dbReference type="PubMed" id="29678907"/>
            <dbReference type="DOI" id="10.1242/jcs.212191"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PKP1</scope>
    </reference>
    <reference key="36">
        <citation type="journal article" date="2021" name="Nat. Commun." volume="12" first="476" last="476">
            <title>Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response.</title>
            <authorList>
                <person name="Wang W."/>
                <person name="Li J."/>
                <person name="Tan J."/>
                <person name="Wang M."/>
                <person name="Yang J."/>
                <person name="Zhang Z.M."/>
                <person name="Li C."/>
                <person name="Basnakian A.G."/>
                <person name="Tang H.W."/>
                <person name="Perrimon N."/>
                <person name="Zhou Q."/>
            </authorList>
            <dbReference type="PubMed" id="33473107"/>
            <dbReference type="DOI" id="10.1038/s41467-020-20780-2"/>
        </citation>
        <scope>INTERACTION WITH ENDOG; TSC2 AND PIK3C3</scope>
    </reference>
    <reference key="37">
        <citation type="journal article" date="2023" name="Nat. Metab." volume="5" first="265" last="276">
            <title>AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation.</title>
            <authorList>
                <person name="Dai X."/>
                <person name="Jiang C."/>
                <person name="Jiang Q."/>
                <person name="Fang L."/>
                <person name="Yu H."/>
                <person name="Guo J."/>
                <person name="Yan P."/>
                <person name="Chi F."/>
                <person name="Zhang T."/>
                <person name="Inuzuka H."/>
                <person name="Asara J.M."/>
                <person name="Wang P."/>
                <person name="Guo J."/>
                <person name="Wei W."/>
            </authorList>
            <dbReference type="PubMed" id="36732624"/>
            <dbReference type="DOI" id="10.1038/s42255-022-00732-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH WDR24</scope>
    </reference>
    <reference key="38">
        <citation type="journal article" date="2017" name="Am. J. Hum. Genet." volume="101" first="300" last="310">
            <title>De novo mutations in YWHAG cause early-onset epilepsy.</title>
            <authorList>
                <consortium name="Epilepsy Genomics Study"/>
                <consortium name="Deciphering Developmental Disorders Study"/>
                <person name="Guella I."/>
                <person name="McKenzie M.B."/>
                <person name="Evans D.M."/>
                <person name="Buerki S.E."/>
                <person name="Toyota E.B."/>
                <person name="Van Allen M.I."/>
                <person name="Suri M."/>
                <person name="Elmslie F."/>
                <person name="Simon M.E.H."/>
                <person name="van Gassen K.L.I."/>
                <person name="Heron D."/>
                <person name="Keren B."/>
                <person name="Nava C."/>
                <person name="Connolly M.B."/>
                <person name="Demos M."/>
                <person name="Farrer M.J."/>
            </authorList>
            <dbReference type="PubMed" id="28777935"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2017.07.004"/>
        </citation>
        <scope>INVOLVEMENT IN DEE56</scope>
        <scope>VARIANTS DEE56 ALA-15; GLU-129 AND CYS-132</scope>
        <scope>VARIANTS GLN-50 AND SER-133</scope>
    </reference>
    <reference key="39">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="17237" last="17242">
            <title>Structural basis for protein-protein interactions in the 14-3-3 protein family.</title>
            <authorList>
                <person name="Yang X."/>
                <person name="Lee W.H."/>
                <person name="Sobott F."/>
                <person name="Papagrigoriou E."/>
                <person name="Robinson C.V."/>
                <person name="Grossmann J.G."/>
                <person name="Sundstroem M."/>
                <person name="Doyle D.A."/>
                <person name="Elkins J.M."/>
            </authorList>
            <dbReference type="PubMed" id="17085597"/>
            <dbReference type="DOI" id="10.1073/pnas.0605779103"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS)</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH PHOSPHOSERINE MOTIFS</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="10 11 17 23 24 27">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 5 8 9 10 11 12 13 14 15 16 17 18 19 20 21 23 24 25 26 27">Homodimer (PubMed:17085597). Part of a complex that contains DSG3, PKP1, YAP1 and YWHAG; the complex is required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes (PubMed:31835537). Interacts with SAMSN1 (By similarity). Interacts with RAF1, SSH1 and CRTC2/TORC2 (PubMed:10433554, PubMed:15159416, PubMed:15454081). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (PubMed:15696159). Interacts with GAB2 (PubMed:19172738). Interacts with MDM4 (phosphorylated); negatively regulates MDM4 activity toward TP53 (PubMed:16511572). Interacts with PKA-phosphorylated AANAT and SIRT2 (PubMed:11427721, PubMed:18249187). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509). Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation (PubMed:28202711). Interacts with MARK2 and MARK3 (PubMed:16959763). Interacts with MEFV (PubMed:27030597). Interacts with ENDOG, TSC2 and PIK3C3; interaction with ENDOG weakens its interaction with TSC2 and PIK3C3 (PubMed:33473107). Interacts with (phosphorylated) WDR24 (PubMed:36732624). Interacts with BEST1; this interaction promotes L-glutamate channel activity leading to the positive regulation of NMDA glutamate receptor activity through the L-glutamate secretion (PubMed:29121962). Interacts with PKP1 (when phosphorylated); the interaction results in translocation of PKP1 to the cytoplasm and loss of intercellular adhesion in keratinocytes (PubMed:29678907). Interacts with SPATA18/MIEAP (isoforms 1 and 2); a protein that also plays a role in MALM (PubMed:22532927).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
            <label>ACAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
            <label>ACIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
            <label>ACOT13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-365875">
            <id>P55196</id>
            <label>AFDN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1373806">
            <id>Q12802</id>
            <label>AKAP13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-25833200">
            <id>Q8IWZ3-3</id>
            <label>ANKHD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1048612">
            <id>Q92625</id>
            <label>ANKS1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-365961">
            <id>P10398</id>
            <label>ARAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1057448">
            <id>Q5VV41</id>
            <label>ARHGEF16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-302405">
            <id>Q92974</id>
            <label>ARHGEF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-717515">
            <id>Q14155</id>
            <label>ARHGEF7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-3447299">
            <id>O43307</id>
            <label>ARHGEF9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-5280499">
            <id>Q66PJ3-4</id>
            <label>ARL6IP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-2323092">
            <id>Q9Y576</id>
            <label>ASB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-8994378">
            <id>Q14032</id>
            <label>BAAT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-700771">
            <id>Q92934</id>
            <label>BAD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-25884811">
            <id>Q13072</id>
            <label>BAGE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-525456">
            <id>Q9UQB8</id>
            <label>BAIAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-11524452">
            <id>Q8N9N5-2</id>
            <label>BANP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-437804">
            <id>Q9NYF8</id>
            <label>BCLAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-6598617">
            <id>Q6PH81</id>
            <label>C16orf87</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1051869">
            <id>Q08AD1</id>
            <label>CAMSAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-518228">
            <id>P22681</id>
            <label>CBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-17641690">
            <id>Q96HJ3-2</id>
            <label>CCDC34</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-720151">
            <id>Q96A33</id>
            <label>CCDC47</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
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        <interactant intactId="EBI-17967022">
            <id>Q96LY2-2</id>
            <label>CCDC74B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P61981</id>
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        <interactant intactId="EBI-713148">
            <id>Q9GZT6</id>
            <label>CCDC90B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
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        <interactant intactId="EBI-1049189">
            <id>Q8ND76</id>
            <label>CCNY</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1051746">
            <id>P30305</id>
            <label>CDC25B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
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            <id>P61981</id>
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        <interactant intactId="EBI-374880">
            <id>Q99459</id>
            <label>CDC5L</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-726261">
            <id>Q00536</id>
            <label>CDK16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-624648">
            <id>Q00537</id>
            <label>CDK17</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
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        <interactant intactId="EBI-1210604">
            <id>Q7Z7K6</id>
            <label>CENPV</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
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        <interactant intactId="EBI-742887">
            <id>Q8TAP6</id>
            <label>CEP76</label>
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        <interactant intactId="EBI-2462313">
            <id>Q9UL40</id>
            <label>ZNF346</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-12010736">
            <id>Q8N0Y2-2</id>
            <label>ZNF444</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-742207">
            <id>Q14966</id>
            <label>ZNF638</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-751531">
            <id>O15535</id>
            <label>ZSCAN9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-7302296">
            <id>Q6ZR29</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-25901704">
            <id>Q9HBH6</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-7540603">
            <id>P67828</id>
            <label>CSNK1A1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-1030357">
            <id>Q51451</id>
            <label>exoS</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-10148373">
            <id>P61014</id>
            <label>Pln</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359832">
            <id>P61981</id>
        </interactant>
        <interactant intactId="EBI-6930266">
            <id>P61588</id>
            <label>Rnd3</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="17">Cytoplasm</location>
            <location evidence="17">Cytosol</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="17">Mitochondrion matrix</location>
        </subcellularLocation>
        <text evidence="17">Translocates to the mitochondrial matrix following induction of MALM (mitochondrial protein catabolic process).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Highly expressed in brain, skeletal muscle, and heart.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3 28">Phosphorylated by various PKC isozymes.</text>
    </comment>
    <comment type="disease" evidence="22">
        <disease id="DI-05090">
            <name>Developmental and epileptic encephalopathy 56</name>
            <acronym>DEE56</acronym>
            <description>A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE56 is an autosomal dominant condition.</description>
            <dbReference type="MIM" id="617665"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="30">Belongs to the 14-3-3 family.</text>
    </comment>
    <dbReference type="EMBL" id="AF142498">
        <property type="protein sequence ID" value="AAD48408.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AB024334">
        <property type="protein sequence ID" value="BAA85184.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CR541904">
        <property type="protein sequence ID" value="CAG46702.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CR541925">
        <property type="protein sequence ID" value="CAG46723.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC006388">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020963">
        <property type="protein sequence ID" value="AAH20963.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5584.1"/>
    <dbReference type="RefSeq" id="NP_036611.2">
        <property type="nucleotide sequence ID" value="NM_012479.3"/>
    </dbReference>
    <dbReference type="PDB" id="2B05">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.55 A"/>
        <property type="chains" value="A/B/C/D/E/F=2-247"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.86 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
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        <property type="method" value="X-ray"/>
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        <property type="resolution" value="2.50 A"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.96 A"/>
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    <dbReference type="AlphaFoldDB" id="P61981"/>
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    <dbReference type="BioGRID" id="113364">
        <property type="interactions" value="1283"/>
    </dbReference>
    <dbReference type="CORUM" id="P61981"/>
    <dbReference type="DIP" id="DIP-33406N"/>
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    <dbReference type="FunCoup" id="P61981">
        <property type="interactions" value="2844"/>
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    <dbReference type="IntAct" id="P61981">
        <property type="interactions" value="1751"/>
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    <dbReference type="MINT" id="P61981"/>
    <dbReference type="STRING" id="9606.ENSP00000306330"/>
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        <property type="family name" value="the 14-3-3 protein (14-3-3) family"/>
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    <dbReference type="GlyGen" id="P61981">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
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        <property type="antibodies" value="571 antibodies from 43 providers"/>
    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000306330.3"/>
        <property type="gene ID" value="ENSG00000170027.7"/>
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        <property type="protein sequence ID" value="ENSP00000306330.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_012479.4"/>
        <property type="RefSeq protein sequence ID" value="NP_036611.2"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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        <property type="gene designation" value="YWHAG"/>
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    <dbReference type="HPA" id="ENSG00000170027">
        <property type="expression patterns" value="Tissue enhanced (brain, skeletal muscle)"/>
    </dbReference>
    <dbReference type="MalaCards" id="YWHAG"/>
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        <property type="type" value="gene"/>
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    <dbReference type="MIM" id="617665">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000170027"/>
    <dbReference type="Orphanet" id="442835">
        <property type="disease" value="Non-specific early-onset epileptic encephalopathy"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000170027"/>
    <dbReference type="eggNOG" id="KOG0841">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT01140000282547"/>
    <dbReference type="HOGENOM" id="CLU_058290_0_0_1"/>
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        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P61981"/>
    <dbReference type="PathwayCommons" id="P61981"/>
    <dbReference type="Reactome" id="R-HSA-111447">
        <property type="pathway name" value="Activation of BAD and translocation to mitochondria"/>
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    <dbReference type="Reactome" id="R-HSA-1445148">
        <property type="pathway name" value="Translocation of SLC2A4 (GLUT4) to the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2565942">
        <property type="pathway name" value="Regulation of PLK1 Activity at G2/M Transition"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-380259">
        <property type="pathway name" value="Loss of Nlp from mitotic centrosomes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-380270">
        <property type="pathway name" value="Recruitment of mitotic centrosome proteins and complexes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-380284">
        <property type="pathway name" value="Loss of proteins required for interphase microtubule organization from the centrosome"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-380320">
        <property type="pathway name" value="Recruitment of NuMA to mitotic centrosomes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5620912">
        <property type="pathway name" value="Anchoring of the basal body to the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5625740">
        <property type="pathway name" value="RHO GTPases activate PKNs"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5628897">
        <property type="pathway name" value="TP53 Regulates Metabolic Genes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75035">
        <property type="pathway name" value="Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8854518">
        <property type="pathway name" value="AURKA Activation by TPX2"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9614399">
        <property type="pathway name" value="Regulation of localization of FOXO transcription factors"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9735871">
        <property type="pathway name" value="SARS-CoV-1 targets host intracellular signalling and regulatory pathways"/>
    </dbReference>
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        <property type="pathway name" value="SARS-CoV-2 targets host intracellular signalling and regulatory pathways"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9856649">
        <property type="pathway name" value="Transcriptional and post-translational regulation of MITF-M expression and activity"/>
    </dbReference>
    <dbReference type="SignaLink" id="P61981"/>
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        <property type="hits" value="29 hits in 1163 CRISPR screens"/>
    </dbReference>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tchem"/>
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        <property type="component" value="Chromosome 7"/>
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        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="evidence" value="ECO:0000314"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="C:focal adhesion"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
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        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
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        <property type="project" value="FlyBase"/>
    </dbReference>
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
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        <property type="project" value="IntAct"/>
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        <property type="term" value="F:insulin-like growth factor receptor binding"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="UniProtKB"/>
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    <keyword id="KW-0963">Cytoplasm</keyword>
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    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
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            <position position="1"/>
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            <position position="215"/>
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            <position position="234"/>
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            <position position="235"/>
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        <variation>A</variation>
        <location>
            <position position="15"/>
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        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="50"/>
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        <location>
            <position position="129"/>
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    <feature type="sequence variant" id="VAR_080227" description="In DEE56; dbSNP:rs1554616628." evidence="22">
        <original>R</original>
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        <location>
            <position position="132"/>
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    </feature>
    <feature type="sequence variant" id="VAR_080228" description="Found in an individual with neurodevelopmental disorder; likely pathogenic; dbSNP:rs1554616627." evidence="22">
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        <variation>S</variation>
        <location>
            <position position="133"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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        <location>
            <position position="4"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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        <location>
            <position position="19"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
        <location>
            <position position="78"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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            <position position="89"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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            <position position="104"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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            <position position="109"/>
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        <variation>RKDL</variation>
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            <begin position="119"/>
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            <begin position="144"/>
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            <begin position="200"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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    <feature type="sequence conflict" description="In Ref. 1; AAD48408." evidence="30" ref="1">
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            <position position="240"/>
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    <sequence length="247" mass="28303" checksum="B0D16C6DE1F4455D" modified="2007-01-23" version="2">MVDREQLVQKARLAEQAERYDDMAAAMKNVTELNEPLSNEERNLLSVAYKNVVGARRSSWRVISSIEQKTSADGNEKKIEMVRAYREKIEKELEAVCQDVLSLLDNYLIKNCSETQYESKVFYLKMKGDYYRYLAEVATGEKRATVVESSEKAYSEAHEISKEHMQPTHPIRLGLALNYSVFYYEIQNAPEQACHLAKTAFDDAIAELDTLNEDSYKDSTLIMQLLRDNLTLWTSDQQDDDGGEGNN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-09-27" modified="2026-01-28" version="193" xmlns="https://uniprot.org/uniprot">
    <accession>P63151</accession>
    <accession>B2RBU8</accession>
    <accession>B4E1T7</accession>
    <accession>P50409</accession>
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            <fullName>Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform</fullName>
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            <fullName>PP2A subunit B isoform B55-alpha</fullName>
            <shortName evidence="11">B55</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform PR55-alpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform R2-alpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform alpha</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R2A</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
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        <text evidence="1 3 8">Substrate-recognition subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit (PubMed:1849734, PubMed:33108758). Involved in chromosome clustering during late mitosis by mediating dephosphorylation of MKI67 (By similarity). Essential for serine/threonine-protein phosphatase 2A-mediated dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 4 5 6 7 8 9">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits (PubMed:38123684). Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (PubMed:38123684). Interacts with the PP2A C catalytic subunit PPP2CA (PubMed:38123684). Interacts with the PP2A A subunit PPP2R1A (PubMed:38123684). Interacts with TP53 (PubMed:17245430). Interacts with IER5 (PubMed:25816751). Interacts with MFHAS1; the interaction is direct (PubMed:28609714). Interacts with PABIR1/FAM122A (via its N-terminus); the interaction is direct and inhibits PP2A activity (PubMed:27588481, PubMed:33108758, PubMed:38123684). Interacts with ARPP19; the interaction is direct and inhibits PP2A activity (PubMed:27588481, PubMed:33108758, PubMed:38123684). Interacts with CRTC3 (PubMed:30611118).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-25836642">
            <id>Q8NE08</id>
            <label>COL25A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-358616">
            <id>P53355</id>
            <label>DAPK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-8835647">
            <id>Q96IG2</id>
            <label>FBXL20</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-3956892">
            <id>Q99958</id>
            <label>FOXC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-1642131">
            <id>Q9NZR2</id>
            <label>LRP1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-5323863">
            <id>Q5S007</id>
            <label>LRRK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-716247">
            <id>Q15843</id>
            <label>NEDD8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>21</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
        </interactant>
        <interactant intactId="EBI-357094">
            <id>P30154</id>
            <label>PPP2R1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P63151-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P63151-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043100"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Expressed in all tissues examined.</text>
    </comment>
    <comment type="domain">
        <text evidence="9">Has an extended WD 2 repeat that is important for the interaction with PPP2R1A.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the phosphatase 2A regulatory subunit B family.</text>
    </comment>
    <dbReference type="EMBL" id="M64929">
        <property type="protein sequence ID" value="AAA36490.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK303981">
        <property type="protein sequence ID" value="BAG64899.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314823">
        <property type="protein sequence ID" value="BAG37345.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC022911">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63578.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041071">
        <property type="protein sequence ID" value="AAH41071.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34867.1">
        <molecule id="P63151-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55213.1">
        <molecule id="P63151-2"/>
    </dbReference>
    <dbReference type="PIR" id="A38351">
        <property type="entry name" value="A38351"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001171062.1">
        <molecule id="P63151-2"/>
        <property type="nucleotide sequence ID" value="NM_001177591.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002708.1">
        <molecule id="P63151-1"/>
        <property type="nucleotide sequence ID" value="NM_002717.4"/>
    </dbReference>
    <dbReference type="PDB" id="3DW8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="B/E=1-447"/>
    </dbReference>
    <dbReference type="PDB" id="8SO0">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="B=2-447"/>
    </dbReference>
    <dbReference type="PDB" id="8TTB">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.77 A"/>
        <property type="chains" value="B=2-447"/>
    </dbReference>
    <dbReference type="PDB" id="8TWE">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.55 A"/>
        <property type="chains" value="B=2-447"/>
    </dbReference>
    <dbReference type="PDB" id="8UO5">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.27 A"/>
        <property type="chains" value="B=1-447"/>
    </dbReference>
    <dbReference type="PDB" id="9C6B">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="B=2-447"/>
    </dbReference>
    <dbReference type="PDB" id="9C7T">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="B=2-447"/>
    </dbReference>
    <dbReference type="PDBsum" id="3DW8"/>
    <dbReference type="PDBsum" id="8SO0"/>
    <dbReference type="PDBsum" id="8TTB"/>
    <dbReference type="PDBsum" id="8TWE"/>
    <dbReference type="PDBsum" id="8UO5"/>
    <dbReference type="PDBsum" id="9C6B"/>
    <dbReference type="PDBsum" id="9C7T"/>
    <dbReference type="AlphaFoldDB" id="P63151"/>
    <dbReference type="EMDB" id="EMD-40644"/>
    <dbReference type="EMDB" id="EMD-41604"/>
    <dbReference type="EMDB" id="EMD-41667"/>
    <dbReference type="EMDB" id="EMD-42428"/>
    <dbReference type="EMDB" id="EMD-45243"/>
    <dbReference type="EMDB" id="EMD-45292"/>
    <dbReference type="EMDB" id="EMD-48798"/>
    <dbReference type="EMDB" id="EMD-48799"/>
    <dbReference type="SMR" id="P63151"/>
    <dbReference type="BioGRID" id="111512">
        <property type="interactions" value="344"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2575">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B55 alpha variant"/>
    </dbReference>
    <dbReference type="CORUM" id="P63151"/>
    <dbReference type="DIP" id="DIP-29398N"/>
    <dbReference type="FunCoup" id="P63151">
        <property type="interactions" value="4161"/>
    </dbReference>
    <dbReference type="IntAct" id="P63151">
        <property type="interactions" value="151"/>
    </dbReference>
    <dbReference type="MINT" id="P63151"/>
    <dbReference type="STRING" id="9606.ENSP00000325074"/>
    <dbReference type="BindingDB" id="P63151"/>
    <dbReference type="ChEMBL" id="CHEMBL4284"/>
    <dbReference type="DrugBank" id="DB02506">
        <property type="generic name" value="2,6,8-Trimethyl-3-Amino-9-Benzyl-9-Methoxynonanoic Acid"/>
    </dbReference>
    <dbReference type="GlyGen" id="P63151">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P63151"/>
    <dbReference type="PhosphoSitePlus" id="P63151"/>
    <dbReference type="SwissPalm" id="P63151"/>
    <dbReference type="BioMuta" id="PPP2R2A"/>
    <dbReference type="DMDM" id="52783535"/>
    <dbReference type="jPOST" id="P63151"/>
    <dbReference type="MassIVE" id="P63151"/>
    <dbReference type="PaxDb" id="9606-ENSP00000325074"/>
    <dbReference type="PeptideAtlas" id="P63151"/>
    <dbReference type="PRIDE" id="P63151"/>
    <dbReference type="ProteomicsDB" id="57497"/>
    <dbReference type="ProteomicsDB" id="57498">
        <molecule id="P63151-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P63151"/>
    <dbReference type="Antibodypedia" id="22918">
        <property type="antibodies" value="219 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5520"/>
    <dbReference type="Ensembl" id="ENST00000315985.7">
        <molecule id="P63151-2"/>
        <property type="protein sequence ID" value="ENSP00000325074.7"/>
        <property type="gene ID" value="ENSG00000221914.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000380737.8">
        <molecule id="P63151-1"/>
        <property type="protein sequence ID" value="ENSP00000370113.3"/>
        <property type="gene ID" value="ENSG00000221914.12"/>
    </dbReference>
    <dbReference type="GeneID" id="5520"/>
    <dbReference type="KEGG" id="hsa:5520"/>
    <dbReference type="MANE-Select" id="ENST00000380737.8">
        <property type="protein sequence ID" value="ENSP00000370113.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_002717.4"/>
        <property type="RefSeq protein sequence ID" value="NP_002708.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xeu.4">
        <molecule id="P63151-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9304"/>
    <dbReference type="CIViC" id="5520">
        <property type="evidences" value="2 evidence items across 2 molecular profiles"/>
    </dbReference>
    <dbReference type="ClinPGx" id="PA33668"/>
    <dbReference type="CTD" id="5520"/>
    <dbReference type="DisGeNET" id="5520"/>
    <dbReference type="GeneCards" id="PPP2R2A"/>
    <dbReference type="HGNC" id="HGNC:9304">
        <property type="gene designation" value="PPP2R2A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000221914">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R2A"/>
    <dbReference type="MIM" id="604941">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000221914"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000221914"/>
    <dbReference type="eggNOG" id="KOG1354">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182864"/>
    <dbReference type="HOGENOM" id="CLU_021713_3_3_1"/>
    <dbReference type="InParanoid" id="P63151"/>
    <dbReference type="OMA" id="NQIKWCR"/>
    <dbReference type="OrthoDB" id="6274823at2759"/>
    <dbReference type="PAN-GO" id="P63151">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P63151"/>
    <dbReference type="PathwayCommons" id="P63151"/>
    <dbReference type="Reactome" id="R-HSA-2995383">
        <property type="pathway name" value="Initiation of Nuclear Envelope (NE) Reformation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-69231">
        <property type="pathway name" value="Cyclin D associated events in G1"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-69273">
        <property type="pathway name" value="Cyclin A/B1/B2 associated events during G2/M transition"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-975957">
        <property type="pathway name" value="Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9860927">
        <property type="pathway name" value="Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells"/>
    </dbReference>
    <dbReference type="SignaLink" id="P63151"/>
    <dbReference type="SIGNOR" id="P63151"/>
    <dbReference type="Agora" id="ENSG00000221914"/>
    <dbReference type="BioGRID-ORCS" id="5520">
        <property type="hits" value="208 hits in 1187 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R2A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P63151"/>
    <dbReference type="GeneWiki" id="PPP2R2A"/>
    <dbReference type="GenomeRNAi" id="5520"/>
    <dbReference type="Pharos" id="P63151">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P63151"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="P63151">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000221914">
        <property type="expression patterns" value="Expressed in calcaneal tendon and 206 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P63151">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140767">
        <property type="term" value="F:enzyme-substrate adaptor activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051721">
        <property type="term" value="F:protein phosphatase 2A binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044877">
        <property type="term" value="F:protein-containing complex binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048156">
        <property type="term" value="F:tau protein binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006470">
        <property type="term" value="P:protein dephosphorylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051983">
        <property type="term" value="P:regulation of chromosome segregation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043278">
        <property type="term" value="P:response to morphine"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="FunFam" id="2.130.10.10:FF:000002">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000009">
        <property type="entry name" value="PP2A_PR55"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018067">
        <property type="entry name" value="PP2A_PR55_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11871">
        <property type="entry name" value="PROTEIN PHOSPHATASE PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037309">
        <property type="entry name" value="PP2A_PR55"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00600">
        <property type="entry name" value="PP2APR55"/>
    </dbReference>
    <dbReference type="SMART" id="SM00320">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="7"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01024">
        <property type="entry name" value="PR55_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01025">
        <property type="entry name" value="PR55_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="initiator methionine" description="Removed" evidence="16 17">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000071415" description="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform">
        <location>
            <begin position="2"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1" evidence="9 13 14 15">
        <location>
            <begin position="11"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2" evidence="9 13 14 15">
        <location>
            <begin position="94"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3" evidence="9 13 14 15">
        <location>
            <begin position="175"/>
            <end position="218"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4" evidence="9 13 14 15">
        <location>
            <begin position="227"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5" evidence="9 13 14 15">
        <location>
            <begin position="288"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6" evidence="9 13 14 15">
        <location>
            <begin position="347"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7" evidence="9 13 14 15">
        <location>
            <begin position="414"/>
            <end position="446"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="16 17">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043100" description="In isoform 2." evidence="10">
        <original>MA</original>
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</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="233" xmlns="https://uniprot.org/uniprot">
    <accession>Q14738</accession>
    <accession>A8K3I9</accession>
    <accession>B5BUA6</accession>
    <accession>O00494</accession>
    <accession>O00696</accession>
    <accession>Q15171</accession>
    <accession>Q5TC39</accession>
    <name>2A5D_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform</fullName>
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            <fullName>PP2A B subunit isoform B'-delta</fullName>
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            <fullName>PP2A B subunit isoform B56-delta</fullName>
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        <alternativeName>
            <fullName>PP2A B subunit isoform PR61-delta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform R5-delta</fullName>
        </alternativeName>
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        <name type="primary">PPP2R5D</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Biol. Chem." volume="271" first="22081" last="22089">
            <title>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</title>
            <authorList>
                <person name="McCright B."/>
                <person name="Rivers A.M."/>
                <person name="Audlin S."/>
                <person name="Virshup D.M."/>
            </authorList>
            <dbReference type="PubMed" id="8703017"/>
            <dbReference type="DOI" id="10.1074/jbc.271.36.22081"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA-1)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="408" first="52" last="56">
            <title>Molecular heterogeneity of the cDNA encoding a 74-kDa regulatory subunit (B'' or delta) of human protein phosphatase 2A.</title>
            <authorList>
                <person name="Tanabe O."/>
                <person name="Gomez G.A."/>
                <person name="Nishito Y."/>
                <person name="Usui H."/>
                <person name="Takeda M."/>
            </authorList>
            <dbReference type="PubMed" id="9180267"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(97)00392-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DELTA-1 AND DELTA-3)</scope>
        <source>
            <tissue>Brain cortex</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1996" name="FEBS Lett." volume="379" first="107" last="111">
            <title>Molecular cloning of a 74-kDa regulatory subunit (B'' or delta) of human protein phosphatase 2A.</title>
            <authorList>
                <person name="Tanabe O."/>
                <person name="Nagase T."/>
                <person name="Murakami T."/>
                <person name="Nozaki H."/>
                <person name="Usui H."/>
                <person name="Nishito Y."/>
                <person name="Hayashi H."/>
                <person name="Kagamiyama H."/>
                <person name="Takeda M."/>
            </authorList>
            <dbReference type="PubMed" id="8566219"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)01500-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA-2)</scope>
        <scope>PROTEIN SEQUENCE OF 501-508; 550-559; 573-580 AND 584-601 (DELTA-1)</scope>
        <source>
            <tissue>Bone marrow</tissue>
            <tissue>Brain cortex</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
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                <person name="Kawai Y."/>
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                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
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                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA-2)</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2008" name="Nat. Methods" volume="5" first="1011" last="1017">
            <title>Human protein factory for converting the transcriptome into an in vitro-expressed proteome.</title>
            <authorList>
                <person name="Goshima N."/>
                <person name="Kawamura Y."/>
                <person name="Fukumoto A."/>
                <person name="Miura A."/>
                <person name="Honma R."/>
                <person name="Satoh R."/>
                <person name="Wakamatsu A."/>
                <person name="Yamamoto J."/>
                <person name="Kimura K."/>
                <person name="Nishikawa T."/>
                <person name="Andoh T."/>
                <person name="Iida Y."/>
                <person name="Ishikawa K."/>
                <person name="Ito E."/>
                <person name="Kagawa N."/>
                <person name="Kaminaga C."/>
                <person name="Kanehori K."/>
                <person name="Kawakami B."/>
                <person name="Kenmochi K."/>
                <person name="Kimura R."/>
                <person name="Kobayashi M."/>
                <person name="Kuroita T."/>
                <person name="Kuwayama H."/>
                <person name="Maruyama Y."/>
                <person name="Matsuo K."/>
                <person name="Minami K."/>
                <person name="Mitsubori M."/>
                <person name="Mori M."/>
                <person name="Morishita R."/>
                <person name="Murase A."/>
                <person name="Nishikawa A."/>
                <person name="Nishikawa S."/>
                <person name="Okamoto T."/>
                <person name="Sakagami N."/>
                <person name="Sakamoto Y."/>
                <person name="Sasaki Y."/>
                <person name="Seki T."/>
                <person name="Sono S."/>
                <person name="Sugiyama A."/>
                <person name="Sumiya T."/>
                <person name="Takayama T."/>
                <person name="Takayama Y."/>
                <person name="Takeda H."/>
                <person name="Togashi T."/>
                <person name="Yahata K."/>
                <person name="Yamada H."/>
                <person name="Yanagisawa Y."/>
                <person name="Endo Y."/>
                <person name="Imamoto F."/>
                <person name="Kisu Y."/>
                <person name="Tanaka S."/>
                <person name="Isogai T."/>
                <person name="Imai J."/>
                <person name="Watanabe S."/>
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    <comment type="function">
        <text>The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 8">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with the PP2A A subunit PPP2R1A (PubMed:37761890). Interacts with SGO1 (PubMed:16541025). Interacts with ADCY8 (PubMed:22976297).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-974439">
            <id>P30307</id>
            <label>CDC25C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
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    <comment type="interaction">
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    <comment type="interaction">
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            <id>Q14738</id>
        </interactant>
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            <id>Q13136</id>
            <label>PPFIA1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-357094">
            <id>P30154</id>
            <label>PPP2R1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-989069">
            <id>Q5FBB7</id>
            <label>SGO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
        </interactant>
        <interactant intactId="EBI-79859">
            <id>O08785</id>
            <label>Clock</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <text>Nuclear in interphase, nuclear during mitosis.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q14738-1</id>
            <name>Delta-1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q14738-2</id>
            <name>Delta-2</name>
            <sequence type="described" ref="VSP_005111"/>
        </isoform>
        <isoform>
            <id>Q14738-3</id>
            <name>Delta-3</name>
            <sequence type="described" ref="VSP_005110"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Isoform Delta-2 is widely expressed. Isoform Delta-1 is highly expressed in brain.</text>
    </comment>
    <comment type="induction">
        <text>By retinoic acid; in neuroblastoma cell lines.</text>
    </comment>
    <comment type="disease" evidence="5 6 7">
        <disease id="DI-04419">
            <name>Houge-Janssens syndrome 1</name>
            <acronym>HJS1</acronym>
            <description>An autosomal dominant disorder characterized by global developmental delay, hypotonia, variably impaired intellectual development, poor speech, and dysmorphic facial features. Additional more variable features may include macrocephaly and seizures.</description>
            <dbReference type="MIM" id="616355"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the phosphatase 2A regulatory subunit B56 family.</text>
    </comment>
    <dbReference type="EMBL" id="L76702">
        <property type="protein sequence ID" value="AAB69751.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB000634">
        <property type="protein sequence ID" value="BAA20381.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB000635">
        <property type="protein sequence ID" value="BAA20382.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D78360">
        <property type="protein sequence ID" value="BAA11372.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290604">
        <property type="protein sequence ID" value="BAF83293.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB451342">
        <property type="protein sequence ID" value="BAG70156.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB451357">
        <property type="protein sequence ID" value="BAG70171.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136304">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471081">
        <property type="protein sequence ID" value="EAX04133.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010692">
        <property type="protein sequence ID" value="AAH10692.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001095">
        <property type="protein sequence ID" value="AAH01095.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001175">
        <property type="protein sequence ID" value="AAH01175.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43464.1">
        <molecule id="Q14738-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4878.1">
        <molecule id="Q14738-1"/>
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    <dbReference type="CCDS" id="CCDS55002.1">
        <molecule id="Q14738-2"/>
    </dbReference>
    <dbReference type="PIR" id="S68686">
        <property type="entry name" value="S68686"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001257405.1">
        <property type="nucleotide sequence ID" value="NM_001270476.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006236.1">
        <molecule id="Q14738-1"/>
        <property type="nucleotide sequence ID" value="NM_006245.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_851307.1">
        <molecule id="Q14738-2"/>
        <property type="nucleotide sequence ID" value="NM_180976.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_851308.1">
        <molecule id="Q14738-3"/>
        <property type="nucleotide sequence ID" value="NM_180977.3"/>
    </dbReference>
    <dbReference type="PDB" id="8U1X">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="B=1-602"/>
    </dbReference>
    <dbReference type="PDB" id="8U89">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="B=1-602"/>
    </dbReference>
    <dbReference type="PDBsum" id="8U1X"/>
    <dbReference type="PDBsum" id="8U89"/>
    <dbReference type="AlphaFoldDB" id="Q14738"/>
    <dbReference type="EMDB" id="EMD-41837"/>
    <dbReference type="EMDB" id="EMD-42018"/>
    <dbReference type="SASBDB" id="Q14738"/>
    <dbReference type="SMR" id="Q14738"/>
    <dbReference type="BioGRID" id="111520">
        <property type="interactions" value="192"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26564">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B56 delta variant"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-29961N"/>
    <dbReference type="ELM" id="Q14738"/>
    <dbReference type="FunCoup" id="Q14738">
        <property type="interactions" value="4018"/>
    </dbReference>
    <dbReference type="IntAct" id="Q14738">
        <property type="interactions" value="100"/>
    </dbReference>
    <dbReference type="MINT" id="Q14738"/>
    <dbReference type="STRING" id="9606.ENSP00000417963"/>
    <dbReference type="GlyGen" id="Q14738">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q14738"/>
    <dbReference type="MetOSite" id="Q14738"/>
    <dbReference type="PhosphoSitePlus" id="Q14738"/>
    <dbReference type="BioMuta" id="PPP2R5D"/>
    <dbReference type="DMDM" id="7387495"/>
    <dbReference type="jPOST" id="Q14738"/>
    <dbReference type="MassIVE" id="Q14738"/>
    <dbReference type="PaxDb" id="9606-ENSP00000417963"/>
    <dbReference type="PeptideAtlas" id="Q14738"/>
    <dbReference type="ProteomicsDB" id="60149"/>
    <dbReference type="ProteomicsDB" id="60150">
        <molecule id="Q14738-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="60151">
        <molecule id="Q14738-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q14738"/>
    <dbReference type="Antibodypedia" id="30209">
        <property type="antibodies" value="384 antibodies from 40 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5528"/>
    <dbReference type="YCharOS" id="Q14738">
        <property type="antibodies" value="Tested 7 antibodies from 5 manufacturers"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000394110.7">
        <molecule id="Q14738-2"/>
        <property type="protein sequence ID" value="ENSP00000377669.3"/>
        <property type="gene ID" value="ENSG00000112640.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000461010.5">
        <molecule id="Q14738-3"/>
        <property type="protein sequence ID" value="ENSP00000420674.1"/>
        <property type="gene ID" value="ENSG00000112640.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000485511.6">
        <molecule id="Q14738-1"/>
        <property type="protein sequence ID" value="ENSP00000417963.1"/>
        <property type="gene ID" value="ENSG00000112640.17"/>
    </dbReference>
    <dbReference type="GeneID" id="5528"/>
    <dbReference type="KEGG" id="hsa:5528"/>
    <dbReference type="MANE-Select" id="ENST00000485511.6">
        <property type="protein sequence ID" value="ENSP00000417963.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006245.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006236.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003oth.5">
        <molecule id="Q14738-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9312"/>
    <dbReference type="ClinPGx" id="PA33676"/>
    <dbReference type="CTD" id="5528"/>
    <dbReference type="DisGeNET" id="5528"/>
    <dbReference type="GeneCards" id="PPP2R5D"/>
    <dbReference type="GeneReviews" id="PPP2R5D"/>
    <dbReference type="HGNC" id="HGNC:9312">
        <property type="gene designation" value="PPP2R5D"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000112640">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R5D"/>
    <dbReference type="MIM" id="601646">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="616355">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000112640"/>
    <dbReference type="Orphanet" id="457279">
        <property type="disease" value="Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000112640"/>
    <dbReference type="eggNOG" id="KOG2085">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01030000234620"/>
    <dbReference type="HOGENOM" id="CLU_012437_3_1_1"/>
    <dbReference type="InParanoid" id="Q14738"/>
    <dbReference type="OMA" id="ECSHEYT"/>
    <dbReference type="OrthoDB" id="10264446at2759"/>
    <dbReference type="PAN-GO" id="Q14738">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q14738"/>
    <dbReference type="PathwayCommons" id="Q14738"/>
    <dbReference type="Reactome" id="R-HSA-141444">
        <property type="pathway name" value="Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163767">
        <property type="pathway name" value="PP2A-mediated dephosphorylation of key metabolic factors"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-180024">
        <property type="pathway name" value="DARPP-32 events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-195253">
        <property type="pathway name" value="Degradation of beta-catenin by the destruction complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-196299">
        <property type="pathway name" value="Beta-catenin phosphorylation cascade"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-198753">
        <property type="pathway name" value="ERK/MAPK targets"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-202670">
        <property type="pathway name" value="ERKs are inactivated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2467813">
        <property type="pathway name" value="Separation of Sister Chromatids"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2500257">
        <property type="pathway name" value="Resolution of Sister Chromatid Cohesion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389356">
        <property type="pathway name" value="Co-stimulation by CD28"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389513">
        <property type="pathway name" value="Co-inhibition by CTLA4"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-432142">
        <property type="pathway name" value="Platelet sensitization by LDL"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-4641262">
        <property type="pathway name" value="Disassembly of the destruction complex and recruitment of AXIN to the membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5339716">
        <property type="pathway name" value="Signaling by GSK3beta mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358747">
        <property type="pathway name" value="CTNNB1 S33 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358749">
        <property type="pathway name" value="CTNNB1 S37 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358751">
        <property type="pathway name" value="CTNNB1 S45 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358752">
        <property type="pathway name" value="CTNNB1 T41 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5467337">
        <property type="pathway name" value="APC truncation mutants have impaired AXIN binding"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5467340">
        <property type="pathway name" value="AXIN missense mutants destabilize the destruction complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5467348">
        <property type="pathway name" value="Truncations of AMER1 destabilize the destruction complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5663220">
        <property type="pathway name" value="RHO GTPases Activate Formins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5673000">
        <property type="pathway name" value="RAF activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5675221">
        <property type="pathway name" value="Negative regulation of MAPK pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6811558">
        <property type="pathway name" value="PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-68877">
        <property type="pathway name" value="Mitotic Prometaphase"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9634600">
        <property type="pathway name" value="Regulation of glycolysis by fructose 2,6-bisphosphate metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9648025">
        <property type="pathway name" value="EML4 and NUDC in mitotic spindle formation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q14738"/>
    <dbReference type="SIGNOR" id="Q14738"/>
    <dbReference type="Agora" id="ENSG00000112640"/>
    <dbReference type="BioGRID-ORCS" id="5528">
        <property type="hits" value="20 hits in 1159 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R5D">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="PPP2R5D"/>
    <dbReference type="GenomeRNAi" id="5528"/>
    <dbReference type="Pharos" id="Q14738">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q14738"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q14738">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000112640">
        <property type="expression patterns" value="Expressed in ganglionic eminence and 209 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q14738">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072542">
        <property type="term" value="F:protein phosphatase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051177">
        <property type="term" value="P:meiotic sister chromatid cohesion"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007399">
        <property type="term" value="P:nervous system development"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.10.10:FF:000003">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.10.10">
        <property type="entry name" value="Leucine-rich Repeat Variant"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011989">
        <property type="entry name" value="ARM-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016024">
        <property type="entry name" value="ARM-type_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002554">
        <property type="entry name" value="PP2A_B56"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10257">
        <property type="entry name" value="SERINE/THREONINE PROTEIN PHOSPHATASE 2A PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10257:SF89">
        <property type="entry name" value="SERINE_THREONINE-PROTEIN PHOSPHATASE 2A 56 KDA REGULATORY SUBUNIT DELTA ISOFORM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01603">
        <property type="entry name" value="B56"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF028043">
        <property type="entry name" value="PP2A_B56"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48371">
        <property type="entry name" value="ARM repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000071452" description="Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform">
        <location>
            <begin position="1"/>
            <end position="602"/>
        </location>
    </feature>
    <feature type="repeat" description="1">
        <location>
            <begin position="37"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="repeat" description="2">
        <location>
            <begin position="39"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="repeat" description="3">
        <location>
            <begin position="41"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="repeat" description="4">
        <location>
            <begin position="43"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="repeat" description="5">
        <location>
            <begin position="45"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="repeat" description="6; approximate">
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<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="242" xmlns="https://uniprot.org/uniprot">
    <accession>P31947</accession>
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    <accession>Q6FH51</accession>
    <accession>Q96DH0</accession>
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            <fullName evidence="23">14-3-3 protein sigma</fullName>
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            <fullName evidence="19">Epithelial cell marker protein 1</fullName>
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            <fullName evidence="21 22">Stratifin</fullName>
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        <name type="primary">SFN</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="1992" name="Cell Growth Differ." volume="3" first="507" last="513">
            <title>Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that may be down-regulated in neoplastic mammary cells.</title>
            <authorList>
                <person name="Prasad G.L."/>
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                <person name="McDuffie E."/>
                <person name="Cooper H.L."/>
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            <dbReference type="PubMed" id="1390337"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Epithelium</tissue>
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    </reference>
    <reference key="2">
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            </authorList>
            <dbReference type="PubMed" id="8515476"/>
            <dbReference type="DOI" id="10.1006/jmbi.1993.1346"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PROTEIN SEQUENCE OF 19-25; 42-49; 118-122; 130-139; 149-159; 161-181; 196-199; 225-229 AND 231-239</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
    <reference key="3">
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                <person name="Hermeking H."/>
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            </authorList>
            <dbReference type="PubMed" id="9659898"/>
            <dbReference type="DOI" id="10.1016/s1097-2765(00)80002-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
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    <reference key="4">
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                <person name="Halleck A."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
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                <person name="Whitehead S.L."/>
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                <person name="Williams H."/>
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                <person name="Wray P.W."/>
                <person name="Wu Z."/>
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                <person name="Durbin R.M."/>
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                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
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            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Cervix</tissue>
            <tissue>Lung</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="7">
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            <title>Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.</title>
            <authorList>
                <person name="Rasmussen H.H."/>
                <person name="van Damme J."/>
                <person name="Puype M."/>
                <person name="Gesser B."/>
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            </authorList>
            <dbReference type="PubMed" id="1286667"/>
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        </citation>
        <scope>PROTEIN SEQUENCE OF 42-49 AND 118-122</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="15282546"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7600338"/>
        </citation>
        <scope>IDENTIFICATION IN A COMPLEX WITH XPO7; ARHGAP1; EIF4A1; VPS26A; VPS29 AND VPS35</scope>
    </reference>
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                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="16964243"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2.</title>
            <authorList>
                <person name="Yang W."/>
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                <person name="Chen J."/>
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            </authorList>
            <dbReference type="PubMed" id="18382127"/>
            <dbReference type="DOI" id="10.4161/cc.7.5.5701"/>
        </citation>
        <scope>FUNCTION IN MDM2 UBIQUITINATION</scope>
        <scope>UBIQUITINATION BY RFFL</scope>
    </reference>
    <reference key="11">
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            </authorList>
            <dbReference type="PubMed" id="19172738"/>
            <dbReference type="DOI" id="10.1038/emboj.2008.159"/>
        </citation>
        <scope>INTERACTION WITH GAB2</scope>
    </reference>
    <reference key="12">
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            <dbReference type="PubMed" id="18691976"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2008.07.007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-248</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            </authorList>
            <dbReference type="PubMed" id="19640509"/>
            <dbReference type="DOI" id="10.1016/j.biopsych.2009.05.033"/>
        </citation>
        <scope>INTERACTION WITH SLITRK1</scope>
    </reference>
    <reference key="15">
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            <dbReference type="PubMed" id="19592491"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.026237"/>
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        <scope>INTERACTION WITH SRPK2</scope>
    </reference>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-248</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <title>COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3sigma.</title>
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                <person name="Choi H.H."/>
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            </authorList>
            <dbReference type="PubMed" id="21625211"/>
            <dbReference type="DOI" id="10.1038/onc.2011.192"/>
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        <scope>INTERACTION WITH COPS6 AND COP1</scope>
    </reference>
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            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <authorList>
                <person name="Greninger A.L."/>
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            </authorList>
            <dbReference type="PubMed" id="23572552"/>
            <dbReference type="DOI" id="10.1128/mbio.00098-13"/>
        </citation>
        <scope>INTERACTION WITH PI4KB</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2013" name="PLoS ONE" volume="8" first="e77012" last="e77012">
            <title>Stratifin (14-3-3 sigma) limits plakophilin-3 exchange with the desmosomal plaque.</title>
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                <person name="Roberts B.J."/>
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            <dbReference type="PubMed" id="24124604"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0077012"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PKP3</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="22">
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                <person name="Yuasa K."/>
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            </authorList>
            <dbReference type="PubMed" id="26047703"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2015.05.105"/>
        </citation>
        <scope>INTERACTION WITH DAPK2</scope>
    </reference>
    <reference key="23">
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            <title>14-3-3 proteins regulate desmosomal adhesion via plakophilins.</title>
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                <person name="Rietscher K."/>
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            </authorList>
            <dbReference type="PubMed" id="29678907"/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PKP3</scope>
    </reference>
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            <authorList>
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                <person name="Artim S.C."/>
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            </authorList>
            <dbReference type="PubMed" id="15731107"/>
            <dbReference type="DOI" id="10.1074/jbc.m500982200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH PHOSPHOSERINE PEPTIDE</scope>
        <scope>FUNCTION</scope>
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            <authorList>
                <person name="Rose R."/>
                <person name="Rose M."/>
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            </authorList>
            <dbReference type="PubMed" id="22634725"/>
            <dbReference type="DOI" id="10.1016/j.jsb.2012.05.010"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-231 IN COMPLEX WITH PADI6 PHOSPHOPEPTIDES</scope>
        <scope>FUNCTION</scope>
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            <authorList>
                <person name="Stevers L.M."/>
                <person name="de Vries R.M."/>
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                <person name="Milroy L.G."/>
                <person name="Brunsveld L."/>
                <person name="Ottmann C."/>
            </authorList>
            <dbReference type="PubMed" id="28202711"/>
            <dbReference type="DOI" id="10.1042/bcj20161078"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 1-231 IN COMPLEX WITH LRRK2 PHOSPHOPEPTIDE</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
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                <person name="Soini L."/>
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            <dbReference type="PubMed" id="33159816"/>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 1-231</scope>
        <scope>INTERACTION WITH LCP2</scope>
    </reference>
    <reference evidence="29" key="28">
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            <title>PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection.</title>
            <authorList>
                <person name="Fisch D."/>
                <person name="Pfleiderer M.M."/>
                <person name="Anastasakou E."/>
                <person name="Mackie G.M."/>
                <person name="Wendt F."/>
                <person name="Liu X."/>
                <person name="Clough B."/>
                <person name="Lara-Reyna S."/>
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            </authorList>
            <dbReference type="PubMed" id="37797010"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (5.12 ANGSTROMS) OF 1-231 IN COMPLEX WITH GBP1</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 10 12 14 15 17 18">Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 4 6 7 8 9 10 11 12 13 14 15 16">Homodimer (PubMed:28202711). Interacts with KRT17 and SAMSN1 (By similarity). Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29 and VPS35 (PubMed:15282546). Interacts with GAB2 (PubMed:19172738). Interacts with SRPK2 (PubMed:19592491). Interacts with COPS6 (PubMed:21625211). Interacts with COP1; this interaction leads to proteasomal degradation (PubMed:21625211). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB (PubMed:23572552). Interacts with SLITRK1 (PubMed:19640509). Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation (PubMed:28202711). Interacts with PKP3 (via N-terminus); the interaction maintains the cytoplasmic pool of PKP3, facilitates PKP3 exchange at desmosomes and restricts PKP3 localization to existing desmosome cell junctions (PubMed:24124604, PubMed:29678907). Interacts with LCP2 (PubMed:33159816).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-487024">
            <id>O14639</id>
            <label>ABLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-949782">
            <id>Q96IF1</id>
            <label>AJUBA</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1048612">
            <id>Q92625</id>
            <label>ANKS1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-365961">
            <id>P10398</id>
            <label>ARAF</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1642518">
            <id>Q5T5U3</id>
            <label>ARHGAP21</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-308663">
            <id>A7KAX9</id>
            <label>ARHGAP32</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1057448">
            <id>Q5VV41</id>
            <label>ARHGEF16</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
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        </interactant>
        <interactant intactId="EBI-3936704">
            <id>Q16288</id>
            <label>NTRK3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1181722">
            <id>Q9H093</id>
            <label>NUAK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-713738">
            <id>O96013</id>
            <label>PAK4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-81968">
            <id>Q8TEW0</id>
            <label>PARD3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-12111000">
            <id>P55771</id>
            <label>PAX9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-2861522">
            <id>P16234</id>
            <label>PDGFRA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-641107">
            <id>O00750</id>
            <label>PIK3C2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-702235">
            <id>Q99959</id>
            <label>PKP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-2125301">
            <id>Q6IQ23</id>
            <label>PLEKHA7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-746202">
            <id>O00444</id>
            <label>PLK4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1045582">
            <id>Q86W92</id>
            <label>PPFIBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-719420">
            <id>Q86YV5</id>
            <label>PRAG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-706254">
            <id>Q02156</id>
            <label>PRKCE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-948453">
            <id>Q14671</id>
            <label>PUM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-747844">
            <id>Q96QF0</id>
            <label>RAB3IP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-365996">
            <id>P04049</id>
            <label>RAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1050841">
            <id>Q86X27</id>
            <label>RALGPS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-7545786">
            <id>Q6NUK4</id>
            <label>REEP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-7545592">
            <id>Q9H6H4</id>
            <label>REEP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-7067016">
            <id>Q8NFH8</id>
            <label>REPS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1387196">
            <id>Q6R327</id>
            <label>RICTOR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1047497">
            <id>Q9UPU9</id>
            <label>SAMD4A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1761310">
            <id>O94885</id>
            <label>SASH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-476295">
            <id>P31947</id>
            <label>SFN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-311339">
            <id>Q7Z6J0</id>
            <label>SH3RF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-310678">
            <id>O43166</id>
            <label>SIPA1L1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-2559690">
            <id>O60292</id>
            <label>SIPA1L3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-311323">
            <id>O94875</id>
            <label>SORBS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-353655">
            <id>O75494</id>
            <label>SRSF10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-522028">
            <id>O60343</id>
            <label>TBC1D4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1383444">
            <id>Q13470</id>
            <label>TNK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-366083">
            <id>P04637</id>
            <label>TP53</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-396587">
            <id>P49815</id>
            <label>TSC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
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        <interactant intactId="EBI-1050865">
            <id>P40818</id>
            <label>USP8</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P31947</id>
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        <interactant intactId="EBI-714790">
            <id>O43379</id>
            <label>WDR62</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P31947</id>
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        <interactant intactId="EBI-914695">
            <id>P30291</id>
            <label>WEE1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-457907">
            <id>Q9H4A3</id>
            <label>WNK1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-740767">
            <id>Q53FD0</id>
            <label>ZC2HC1C</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1644149">
            <id>P47974</id>
            <label>ZFP36L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
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        <interactant intactId="EBI-34019">
            <id>Q03373</id>
            <label>DIG2</label>
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        <organismsDiffer>true</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-476295">
            <id>P31947</id>
        </interactant>
        <interactant intactId="EBI-1030357">
            <id>Q51451</id>
            <label>exoS</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
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    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12 17">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="25">Secreted</location>
        </subcellularLocation>
        <text evidence="25">May be secreted by a non-classical secretory pathway.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P31947-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P31947-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_021768"/>
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    </comment>
    <comment type="tissue specificity">
        <text evidence="2">Present mainly in tissues enriched in stratified squamous keratinizing epithelium.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5">Ubiquitinated. Ubiquitination by RFFL induces proteasomal degradation and indirectly regulates p53/TP53 activation.</text>
    </comment>
    <comment type="similarity">
        <text evidence="24">Belongs to the 14-3-3 family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA59546.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAA40623.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAC52029.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC52030.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG46703.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG46724.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH02995.1"/>
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        <property type="protein sequence ID" value="AAH23552.1"/>
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    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000058643" description="14-3-3 protein sigma">
        <location>
            <begin position="1"/>
            <end position="248"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="site" description="Interaction with phosphoserine on interacting protein">
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="33">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="34">
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="30 31 32 33">
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021768" description="In isoform 2." evidence="20">
        <location>
            <begin position="85"/>
            <end position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048095" description="In dbSNP:rs11542705.">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAG46703." evidence="24" ref="4">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAA59546." evidence="24" ref="2">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAA59546." evidence="24" ref="2">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="3"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="19"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="38"/>
            <end position="69"/>
        </location>
    </feature>
    <feature type="strand" evidence="37">
        <location>
            <begin position="71"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="80"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="107"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="114"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="helix" evidence="36">
        <location>
            <begin position="137"/>
            <end position="139"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="140"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="167"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="187"/>
            <end position="204"/>
        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="205"/>
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        </location>
    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="210"/>
            <end position="230"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O70456"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
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            <dbReference type="PubMed" id="15282546"/>
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            <dbReference type="PubMed" id="15731107"/>
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            <dbReference type="PubMed" id="18382127"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
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            <dbReference type="PubMed" id="19172738"/>
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            <dbReference type="PubMed" id="24124604"/>
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    <evidence type="ECO:0000269" key="17">
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            <dbReference type="PubMed" id="37797010"/>
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    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="9659898"/>
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            <dbReference type="PubMed" id="1390337"/>
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    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="24124604"/>
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    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="8515476"/>
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    </evidence>
    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="9659898"/>
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    <evidence type="ECO:0000305" key="24"/>
    <evidence type="ECO:0000305" key="25">
        <source>
            <dbReference type="PubMed" id="8515476"/>
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    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="5MY9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PDB" id="5MYC"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PDB" id="6ZCJ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PDB" id="8Q4L"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PubMed" id="16964243"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="35">
        <source>
            <dbReference type="PDB" id="3IQU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="36">
        <source>
            <dbReference type="PDB" id="6RJL"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="37">
        <source>
            <dbReference type="PDB" id="8BX3"/>
        </source>
    </evidence>
    <sequence length="248" mass="27774" checksum="7F4B44E3AA59ECE6" modified="1993-07-01" version="1">MERASLIQKAKLAEQAERYEDMAAFMKGAVEKGEELSCEERNLLSVAYKNVVGGQRAAWRVLSSIEQKSNEEGSEEKGPEVREYREKVETELQGVCDTVLGLLDSHLIKEAGDAESRVFYLKMKGDYYRYLAEVATGDDKKRIIDSARSAYQEAMDISKKEMPPTNPIRLGLALNFSVFHYEIANSPEEAISLAKTTFDEAMADLHTLSEDSYKDSTLIMQLLRDNLTLWTADNAGEEGGEAPQEPQS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>Q16537</accession>
    <accession>A4FU37</accession>
    <accession>B7ZAW5</accession>
    <accession>B7ZKK8</accession>
    <accession>B7ZKK9</accession>
    <accession>J3KQN6</accession>
    <accession>Q52LW4</accession>
    <name>2A5E_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B'-epsilon</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B56-epsilon</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform PR61-epsilon</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform R5-epsilon</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R5E</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="Biochem. J." volume="317" first="187" last="194">
            <title>The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits.</title>
            <authorList>
                <person name="Zolnierowicz S."/>
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            </authorList>
            <dbReference type="PubMed" id="8694763"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PROTEIN SEQUENCE OF 449-455</scope>
        <source>
            <tissue>Fetal retina</tissue>
        </source>
    </reference>
    <reference key="2">
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            <authorList>
                <person name="McCright B."/>
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                <person name="Virshup D.M."/>
            </authorList>
            <dbReference type="PubMed" id="8703017"/>
            <dbReference type="DOI" id="10.1074/jbc.271.36.22081"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
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                <person name="Kumagai A."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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                <person name="Verdier J."/>
                <person name="Verdier-Discala C."/>
                <person name="Hillier L.W."/>
                <person name="Fulton L."/>
                <person name="McPherson J."/>
                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
                <person name="Waterston R."/>
                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="46" last="52">
            <title>Shugoshin collaborates with protein phosphatase 2A to protect cohesin.</title>
            <authorList>
                <person name="Kitajima T.S."/>
                <person name="Sakuno T."/>
                <person name="Ishiguro K."/>
                <person name="Iemura S."/>
                <person name="Natsume T."/>
                <person name="Kawashima S.A."/>
                <person name="Watanabe Y."/>
            </authorList>
            <dbReference type="PubMed" id="16541025"/>
            <dbReference type="DOI" id="10.1038/nature04663"/>
        </citation>
        <scope>INTERACTION WITH SGO1</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="Mol. Cell" volume="31" first="438" last="448">
            <title>Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.</title>
            <authorList>
                <person name="Daub H."/>
                <person name="Olsen J.V."/>
                <person name="Bairlein M."/>
                <person name="Gnad F."/>
                <person name="Oppermann F.S."/>
                <person name="Korner R."/>
                <person name="Greff Z."/>
                <person name="Keri G."/>
                <person name="Stemmann O."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="18691976"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2008.07.007"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30; SER-32 AND SER-34</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-7</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3">Found in a complex with at least ARL2, PPP2CB; PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-998108">
            <id>Q86YF9</id>
            <label>DZIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-7445625">
            <id>Q9HC29</id>
            <label>NOD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-357094">
            <id>P30154</id>
            <label>PPP2R1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-717233">
            <id>Q9H0H5</id>
            <label>RACGAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
        </interactant>
        <interactant intactId="EBI-524753">
            <id>Q8IUH5</id>
            <label>ZDHHC17</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q16537-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q16537-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054588"/>
        </isoform>
        <isoform>
            <id>Q16537-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_055163"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text>Phosphorylated on serine residues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the phosphatase 2A regulatory subunit B56 family.</text>
    </comment>
    <dbReference type="EMBL" id="Z69029">
        <property type="protein sequence ID" value="CAA93153.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L76703">
        <property type="protein sequence ID" value="AAB69752.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK316430">
        <property type="protein sequence ID" value="BAH14801.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL118555">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL132992">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136038">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093766">
        <property type="protein sequence ID" value="AAH93766.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101479">
        <property type="protein sequence ID" value="AAI01480.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143231">
        <property type="protein sequence ID" value="AAI43232.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143234">
        <property type="protein sequence ID" value="AAI43235.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS61467.1">
        <molecule id="Q16537-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS61468.1">
        <molecule id="Q16537-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9758.1">
        <molecule id="Q16537-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269108.1">
        <molecule id="Q16537-1"/>
        <property type="nucleotide sequence ID" value="NM_001282179.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269109.1">
        <molecule id="Q16537-2"/>
        <property type="nucleotide sequence ID" value="NM_001282180.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269110.1">
        <molecule id="Q16537-3"/>
        <property type="nucleotide sequence ID" value="NM_001282181.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269111.1">
        <molecule id="Q16537-3"/>
        <property type="nucleotide sequence ID" value="NM_001282182.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006237.1">
        <molecule id="Q16537-1"/>
        <property type="nucleotide sequence ID" value="NM_006246.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024305415.1">
        <molecule id="Q16537-1"/>
        <property type="nucleotide sequence ID" value="XM_024449647.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047287499.1">
        <molecule id="Q16537-2"/>
        <property type="nucleotide sequence ID" value="XM_047431543.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047287500.1">
        <molecule id="Q16537-3"/>
        <property type="nucleotide sequence ID" value="XM_047431544.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054232293.1">
        <molecule id="Q16537-1"/>
        <property type="nucleotide sequence ID" value="XM_054376318.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054232294.1">
        <molecule id="Q16537-2"/>
        <property type="nucleotide sequence ID" value="XM_054376319.1"/>
    </dbReference>
    <dbReference type="PDB" id="8UWB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.15 A"/>
        <property type="chains" value="B/E=1-467"/>
    </dbReference>
    <dbReference type="PDBsum" id="8UWB"/>
    <dbReference type="AlphaFoldDB" id="Q16537"/>
    <dbReference type="SMR" id="Q16537"/>
    <dbReference type="BioGRID" id="111521">
        <property type="interactions" value="165"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26565">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B56 epsilon variant"/>
    </dbReference>
    <dbReference type="ELM" id="Q16537"/>
    <dbReference type="FunCoup" id="Q16537">
        <property type="interactions" value="4984"/>
    </dbReference>
    <dbReference type="IntAct" id="Q16537">
        <property type="interactions" value="88"/>
    </dbReference>
    <dbReference type="MINT" id="Q16537"/>
    <dbReference type="STRING" id="9606.ENSP00000337641"/>
    <dbReference type="iPTMnet" id="Q16537"/>
    <dbReference type="MetOSite" id="Q16537"/>
    <dbReference type="PhosphoSitePlus" id="Q16537"/>
    <dbReference type="BioMuta" id="PPP2R5E"/>
    <dbReference type="DMDM" id="7387498"/>
    <dbReference type="jPOST" id="Q16537"/>
    <dbReference type="MassIVE" id="Q16537"/>
    <dbReference type="PaxDb" id="9606-ENSP00000337641"/>
    <dbReference type="PeptideAtlas" id="Q16537"/>
    <dbReference type="ProteomicsDB" id="60898"/>
    <dbReference type="ProteomicsDB" id="7180"/>
    <dbReference type="Pumba" id="Q16537"/>
    <dbReference type="Antibodypedia" id="50">
        <property type="antibodies" value="154 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5529"/>
    <dbReference type="Ensembl" id="ENST00000337537.8">
        <molecule id="Q16537-1"/>
        <property type="protein sequence ID" value="ENSP00000337641.3"/>
        <property type="gene ID" value="ENSG00000154001.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000422769.6">
        <molecule id="Q16537-3"/>
        <property type="protein sequence ID" value="ENSP00000404632.2"/>
        <property type="gene ID" value="ENSG00000154001.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000555899.1">
        <molecule id="Q16537-2"/>
        <property type="protein sequence ID" value="ENSP00000452396.1"/>
        <property type="gene ID" value="ENSG00000154001.15"/>
    </dbReference>
    <dbReference type="GeneID" id="5529"/>
    <dbReference type="KEGG" id="hsa:5529"/>
    <dbReference type="MANE-Select" id="ENST00000337537.8">
        <property type="protein sequence ID" value="ENSP00000337641.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006246.5"/>
        <property type="RefSeq protein sequence ID" value="NP_006237.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xgd.3">
        <molecule id="Q16537-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9313"/>
    <dbReference type="ClinPGx" id="PA33677"/>
    <dbReference type="CTD" id="5529"/>
    <dbReference type="DisGeNET" id="5529"/>
    <dbReference type="GeneCards" id="PPP2R5E"/>
    <dbReference type="HGNC" id="HGNC:9313">
        <property type="gene designation" value="PPP2R5E"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000154001">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R5E"/>
    <dbReference type="MIM" id="601647">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000154001"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000154001"/>
    <dbReference type="eggNOG" id="KOG2085">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01030000234620"/>
    <dbReference type="HOGENOM" id="CLU_012437_4_0_1"/>
    <dbReference type="InParanoid" id="Q16537"/>
    <dbReference type="OMA" id="MVPLFCR"/>
    <dbReference type="OrthoDB" id="10264446at2759"/>
    <dbReference type="PAN-GO" id="Q16537">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q16537"/>
    <dbReference type="PathwayCommons" id="Q16537"/>
    <dbReference type="Reactome" id="R-HSA-141444">
        <property type="pathway name" value="Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-195253">
        <property type="pathway name" value="Degradation of beta-catenin by the destruction complex"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-196299">
        <property type="pathway name" value="Beta-catenin phosphorylation cascade"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2467813">
        <property type="pathway name" value="Separation of Sister Chromatids"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2500257">
        <property type="pathway name" value="Resolution of Sister Chromatid Cohesion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389356">
        <property type="pathway name" value="Co-stimulation by CD28"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389513">
        <property type="pathway name" value="Co-inhibition by CTLA4"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-432142">
        <property type="pathway name" value="Platelet sensitization by LDL"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-4641262">
        <property type="pathway name" value="Disassembly of the destruction complex and recruitment of AXIN to the membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5339716">
        <property type="pathway name" value="Signaling by GSK3beta mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358747">
        <property type="pathway name" value="CTNNB1 S33 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358749">
        <property type="pathway name" value="CTNNB1 S37 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358751">
        <property type="pathway name" value="CTNNB1 S45 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5358752">
        <property type="pathway name" value="CTNNB1 T41 mutants aren't phosphorylated"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5467337">
        <property type="pathway name" value="APC truncation mutants have impaired AXIN binding"/>
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</entry>
<entry dataset="Swiss-Prot" created="1993-04-01" modified="2026-01-28" version="225" xmlns="https://uniprot.org/uniprot">
    <accession>Q00005</accession>
    <accession>A6NEJ2</accession>
    <accession>A8K102</accession>
    <accession>B3KPD0</accession>
    <accession>B7Z2F2</accession>
    <accession>B7Z304</accession>
    <accession>D3DQF7</accession>
    <accession>D3DQF8</accession>
    <accession>G3V149</accession>
    <name>2ABB_HUMAN</name>
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        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A subunit B isoform B55-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform PR55-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform R2-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R2B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Biochemistry" volume="30" first="3589" last="3597">
            <title>Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: evidence for a neuronal-specific isoform.</title>
            <authorList>
                <person name="Mayer R.E."/>
                <person name="Hendrix P."/>
                <person name="Cron P."/>
                <person name="Matthies R."/>
                <person name="Stone S.R."/>
                <person name="Goris J."/>
                <person name="Merlevede W."/>
                <person name="Hofsteenge J."/>
                <person name="Hemmings B.A."/>
            </authorList>
            <dbReference type="PubMed" id="1849734"/>
            <dbReference type="DOI" id="10.1021/bi00229a001"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-433 (ISOFORM 7)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Corpus callosum</tissue>
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            <dbReference type="PubMed" id="15372022"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-131 (ISOFORM 6)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Hypothalamus</tissue>
        </source>
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                <person name="Strausberg R.L."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-197 (ISOFORM 2)</scope>
    </reference>
    <reference key="7">
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            <title>Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12.</title>
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                <person name="Holmes S.E."/>
                <person name="O'Hearn E.E."/>
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            <dbReference type="PubMed" id="10581021"/>
            <dbReference type="DOI" id="10.1038/70493"/>
        </citation>
        <scope>INVOLVEMENT IN SCA12</scope>
    </reference>
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            <title>HSF1 transcriptional activity is modulated by IER5 and PP2A/B55.</title>
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                <person name="Ishikawa Y."/>
                <person name="Kawabata S."/>
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            </authorList>
            <dbReference type="PubMed" id="25816751"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2015.03.019"/>
        </citation>
        <scope>INTERACTION WITH IER5</scope>
    </reference>
    <reference key="9">
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            <title>Immediate-early response 5 (IER5) interacts with protein phosphatase 2A and regulates the phosphorylation of ribosomal protein S6 kinase and heat shock factor 1.</title>
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                <person name="Kawabata S."/>
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                <person name="Ishikawa Y."/>
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            </authorList>
            <dbReference type="PubMed" id="26496226"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2015.10.013"/>
        </citation>
        <scope>INTERACTION WITH IER5</scope>
    </reference>
    <reference key="10">
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            <title>De novo mutations in moderate or severe intellectual disability.</title>
            <authorList>
                <person name="Hamdan F.F."/>
                <person name="Srour M."/>
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                <person name="Daoud H."/>
                <person name="Nassif C."/>
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            </authorList>
            <dbReference type="PubMed" id="25356899"/>
            <dbReference type="DOI" id="10.1371/journal.pgen.1004772"/>
        </citation>
        <scope>VARIANT PRO-138</scope>
    </reference>
    <comment type="function">
        <text evidence="1">The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity (By similarity). Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 5 6">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with TOMM22 (By similarity). Interacts with IER5 (via N- and C-terminal regions) (PubMed:25816751, PubMed:26496226).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1052159">
            <id>Q00005</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1052159">
            <id>Q00005</id>
        </interactant>
        <interactant intactId="EBI-717097">
            <id>O15530</id>
            <label>PDPK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1052159">
            <id>Q00005</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1052159">
            <id>Q00005</id>
        </interactant>
        <interactant intactId="EBI-1775921">
            <id>P23443</id>
            <label>RPS6KB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion outer membrane</location>
        </subcellularLocation>
        <text evidence="1">Under basal conditions, localizes to both cytosolic and mitochondrial compartments. Relocalizes from the cytosolic to the mitochondrial compartment during apoptosis. Its targeting to the outer mitochondrial membrane (OMM) involves an association with import receptors of the TOM complex and is required to promote proapoptotic activity (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q00005-1</id>
            <name>1</name>
            <name>Bbeta</name>
            <name>Bbeta1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q00005-2</id>
            <name>2</name>
            <name>Bbeta2</name>
            <sequence type="described" ref="VSP_037976"/>
        </isoform>
        <isoform>
            <id>Q00005-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_037977"/>
        </isoform>
        <isoform>
            <id>Q00005-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_037978"/>
        </isoform>
        <isoform>
            <id>Q00005-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_037979"/>
        </isoform>
        <isoform>
            <id>Q00005-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_044923"/>
        </isoform>
        <isoform>
            <id>Q00005-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_045748"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Brain.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage.</text>
    </comment>
    <comment type="disease" evidence="3">
        <disease id="DI-01075">
            <name>Spinocerebellar ataxia 12</name>
            <acronym>SCA12</acronym>
            <description>Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).</description>
            <dbReference type="MIM" id="604326"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>Conserved additional ATG codons are found 5' of the putative initiator codon in transcripts supporting isoform 1. They may initiate the translation of upstream short open reading frames altering the expression of that isoform as described in PubMed:1849734.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="1">Contains a cryptic mitochondrial transit peptide at positions 1-26.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the phosphatase 2A regulatory subunit B family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH31790" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAG51642" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAG51642" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="M64930">
        <property type="protein sequence ID" value="AAA36493.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK056192">
        <property type="protein sequence ID" value="BAG51642.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK289717">
        <property type="protein sequence ID" value="BAF82406.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK294659">
        <property type="protein sequence ID" value="BAH11838.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK295347">
        <property type="protein sequence ID" value="BAH12040.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008728">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009186">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010251">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011386">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011357">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091919">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091924">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61829.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61831.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61832.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61833.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61834.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61835.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031790">
        <property type="protein sequence ID" value="AAH31790.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BI490027">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BI669304">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4283.1">
        <molecule id="Q00005-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4284.2">
        <molecule id="Q00005-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43380.1">
        <molecule id="Q00005-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64281.1">
        <molecule id="Q00005-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64282.1">
        <molecule id="Q00005-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS93800.1">
        <molecule id="Q00005-1"/>
    </dbReference>
    <dbReference type="PIR" id="B38351">
        <property type="entry name" value="B38351"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258828.1">
        <molecule id="Q00005-3"/>
        <property type="nucleotide sequence ID" value="NM_001271899.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258829.1">
        <molecule id="Q00005-4"/>
        <property type="nucleotide sequence ID" value="NM_001271900.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258877.1">
        <molecule id="Q00005-6"/>
        <property type="nucleotide sequence ID" value="NM_001271948.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001415206.1">
        <molecule id="Q00005-1"/>
        <property type="nucleotide sequence ID" value="NM_001428277.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001415208.1">
        <molecule id="Q00005-1"/>
        <property type="nucleotide sequence ID" value="NM_001428279.1"/>
    </dbReference>
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        <molecule id="Q00005-5"/>
        <property type="nucleotide sequence ID" value="NM_181674.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_858061.3">
        <molecule id="Q00005-1"/>
        <property type="nucleotide sequence ID" value="NM_181675.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_858062.1">
        <molecule id="Q00005-2"/>
        <property type="nucleotide sequence ID" value="NM_181676.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_858063.1">
        <property type="nucleotide sequence ID" value="NM_181677.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_858064.1">
        <molecule id="Q00005-6"/>
        <property type="nucleotide sequence ID" value="NM_181678.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q00005"/>
    <dbReference type="SMR" id="Q00005"/>
    <dbReference type="BioGRID" id="111513">
        <property type="interactions" value="242"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26586">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B55 beta variant"/>
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        <property type="interactions" value="2104"/>
    </dbReference>
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    </dbReference>
    <dbReference type="MINT" id="Q00005"/>
    <dbReference type="STRING" id="9606.ENSP00000377936"/>
    <dbReference type="GlyGen" id="Q00005">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q00005"/>
    <dbReference type="PhosphoSitePlus" id="Q00005"/>
    <dbReference type="SwissPalm" id="Q00005"/>
    <dbReference type="BioMuta" id="PPP2R2B"/>
    <dbReference type="DMDM" id="231446"/>
    <dbReference type="jPOST" id="Q00005"/>
    <dbReference type="MassIVE" id="Q00005"/>
    <dbReference type="PaxDb" id="9606-ENSP00000377936"/>
    <dbReference type="PeptideAtlas" id="Q00005"/>
    <dbReference type="PRIDE" id="Q00005"/>
    <dbReference type="ProteomicsDB" id="32258"/>
    <dbReference type="ProteomicsDB" id="57832"/>
    <dbReference type="ProteomicsDB" id="57833">
        <molecule id="Q00005-2"/>
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    <dbReference type="ProteomicsDB" id="57834">
        <molecule id="Q00005-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="57835">
        <molecule id="Q00005-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="57836">
        <molecule id="Q00005-5"/>
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    <dbReference type="Antibodypedia" id="27589">
        <property type="antibodies" value="231 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5521"/>
    <dbReference type="Ensembl" id="ENST00000336640.10">
        <molecule id="Q00005-2"/>
        <property type="protein sequence ID" value="ENSP00000336591.6"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000394409.7">
        <molecule id="Q00005-1"/>
        <property type="protein sequence ID" value="ENSP00000377931.4"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000394411.9">
        <molecule id="Q00005-1"/>
        <property type="protein sequence ID" value="ENSP00000377933.3"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000394413.7">
        <molecule id="Q00005-4"/>
        <property type="protein sequence ID" value="ENSP00000377935.4"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000394414.5">
        <molecule id="Q00005-5"/>
        <property type="protein sequence ID" value="ENSP00000377936.1"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000453001.5">
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        <property type="protein sequence ID" value="ENSP00000398779.2"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000504198.5">
        <molecule id="Q00005-3"/>
        <property type="protein sequence ID" value="ENSP00000421396.1"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="Ensembl" id="ENST00000508545.6">
        <molecule id="Q00005-6"/>
        <property type="protein sequence ID" value="ENSP00000431320.1"/>
        <property type="gene ID" value="ENSG00000156475.20"/>
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    <dbReference type="GeneID" id="5521"/>
    <dbReference type="KEGG" id="hsa:5521"/>
    <dbReference type="MANE-Select" id="ENST00000394411.9">
        <property type="protein sequence ID" value="ENSP00000377933.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_181675.4"/>
        <property type="RefSeq protein sequence ID" value="NP_858061.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003loe.6">
        <molecule id="Q00005-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9305"/>
    <dbReference type="ClinPGx" id="PA33669"/>
    <dbReference type="CTD" id="5521"/>
    <dbReference type="DisGeNET" id="5521"/>
    <dbReference type="GeneCards" id="PPP2R2B"/>
    <dbReference type="HGNC" id="HGNC:9305">
        <property type="gene designation" value="PPP2R2B"/>
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    <dbReference type="HPA" id="ENSG00000156475">
        <property type="expression patterns" value="Tissue enhanced (brain, retina)"/>
    </dbReference>
    <dbReference type="MalaCards" id="PPP2R2B"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000156475"/>
    <dbReference type="Orphanet" id="98762">
        <property type="disease" value="Spinocerebellar ataxia type 12"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000156475"/>
    <dbReference type="eggNOG" id="KOG1354">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182864"/>
    <dbReference type="HOGENOM" id="CLU_021713_3_3_1"/>
    <dbReference type="InParanoid" id="Q00005"/>
    <dbReference type="OMA" id="KWCRRTN"/>
    <dbReference type="OrthoDB" id="6274823at2759"/>
    <dbReference type="PAN-GO" id="Q00005">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q00005"/>
    <dbReference type="PathwayCommons" id="Q00005"/>
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    <dbReference type="SIGNOR" id="Q00005"/>
    <dbReference type="Agora" id="ENSG00000156475"/>
    <dbReference type="BioGRID-ORCS" id="5521">
        <property type="hits" value="14 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R2B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="PPP2R2B"/>
    <dbReference type="GenomeRNAi" id="5521"/>
    <dbReference type="Pharos" id="Q00005">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q00005"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="Q00005">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000156475">
        <property type="expression patterns" value="Expressed in sperm and 169 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q00005">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005856">
        <property type="term" value="C:cytoskeleton"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005741">
        <property type="term" value="C:mitochondrial outer membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006915">
        <property type="term" value="P:apoptotic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="FunFam" id="2.130.10.10:FF:000002">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000009">
        <property type="entry name" value="PP2A_PR55"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018067">
        <property type="entry name" value="PP2A_PR55_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11871">
        <property type="entry name" value="PROTEIN PHOSPHATASE PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037309">
        <property type="entry name" value="PP2A_PR55"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00600">
        <property type="entry name" value="PP2APR55"/>
    </dbReference>
    <dbReference type="SMART" id="SM00320">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01024">
        <property type="entry name" value="PR55_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01025">
        <property type="entry name" value="PR55_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00678">
        <property type="entry name" value="WD_REPEATS_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0523">Neurodegeneration</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0950">Spinocerebellar ataxia</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000071421" description="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform">
        <location>
            <begin position="1"/>
            <end position="443"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1">
        <location>
            <begin position="22"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2">
        <location>
            <begin position="87"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3">
        <location>
            <begin position="171"/>
            <end position="209"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4">
        <location>
            <begin position="220"/>
            <end position="260"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5">
        <location>
            <begin position="279"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6">
        <location>
            <begin position="334"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7">
        <location>
            <begin position="410"/>
            <end position="442"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="275"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="295"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044923" description="In isoform 6." evidence="8">
        <original>MEEDIDTRKINNSFLRDHSYATE</original>
        <variation>MNYPDENTYGNK</variation>
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037976" description="In isoform 2." evidence="9">
        <original>MEEDIDTRKINNSFLRDHSYA</original>
        <variation>MKCFSRYLPYIFRPPNTILSSSCH</variation>
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037977" description="In isoform 3." evidence="7">
        <original>MEEDIDTRKINNSFLRDHSYA</original>
        <variation>MIPGIGTLTQDTLWCFSQVKGTIEIGT</variation>
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037978" description="In isoform 4." evidence="7">
        <original>M</original>
        <variation>MVLQPSERHYRDWNHRRLGPWCSPTGSPAPLSCETGCGEGSWILVCRLLVPTQVSLLSM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037979" description="In isoform 5." evidence="8">
        <original>M</original>
        <variation>MLLSLPALHLQTSEHHPFFQLPHRRLGPWCSPTGSPAPLSCETGCGEGSWILVCRLLVPTQVSLLSM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045748" description="In isoform 7." evidence="7">
        <original>M</original>
        <variation>MHQPPPASCSSSSSSSSSSCECARVGVRVSALAPAAAPCPAPRQLPYPRLPEPPSRGTSTLIPARLGPWCSPTGSPAPLSCETGCGEGSWILVCRLLVPTQVSLLSM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051738" description="In dbSNP:rs11547494.">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078654" description="Found in a patient with moderate intellectual disability, autism and intractable epilepsy; uncertain significance." evidence="4">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAH11838." evidence="10" ref="2">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; BI669304." evidence="10" ref="5">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="62"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAH12040." evidence="10" ref="2">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; BI490027." evidence="10" ref="6">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAF82406." evidence="10" ref="2">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAH12040." evidence="10" ref="2">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="292"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P36877"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10581021"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="25356899"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="25816751"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="26496226"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source ref="6"/>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <sequence length="443" mass="51710" checksum="C383C834B2852B8F" modified="1993-04-01" version="1">MEEDIDTRKINNSFLRDHSYATEADIISTVEFNHTGELLATGDKGGRVVIFQREQESKNQVHRRGEYNVYSTFQSHEPEFDYLKSLEIEEKINKIRWLPQQNAAYFLLSTNDKTVKLWKVSERDKRPEGYNLKDEEGRLRDPATITTLRVPVLRPMDLMVEATPRRVFANAHTYHINSISVNSDYETYMSADDLRINLWNFEITNQSFNIVDIKPANMEELTEVITAAEFHPHHCNTFVYSSSKGTIRLCDMRASALCDRHTKFFEEPEDPSNRSFFSEIISSISDVKFSHSGRYIMTRDYLTVKVWDLNMENRPIETYQVHDYLRSKLCSLYENDCIFDKFECVWNGSDSVIMTGSYNNFFRMFDRNTKRDVTLEASRENSKPRAILKPRKVCVGGKRRKDEISVDSLDFSKKILHTAWHPSENIIAVAATNNLYIFQDKVN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-04-01" modified="2026-01-28" version="238" xmlns="https://uniprot.org/uniprot">
    <accession>P30153</accession>
    <accession>Q13773</accession>
    <accession>Q6ICQ3</accession>
    <accession>Q96DH3</accession>
    <name>2AAA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform</fullName>
            <shortName evidence="28">PP2Aa</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Medium tumor antigen-associated 61 kDa protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit A isoform PR65-alpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit A isoform R1-alpha</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="30" type="primary">PPP2R1A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="Proc. Natl. Acad. Sci. U.S.A." volume="86" first="8669" last="8672">
            <title>Molecular cloning and sequence of cDNA encoding polyoma medium tumor antigen-associated 61-kDa protein.</title>
            <authorList>
                <person name="Walter G."/>
                <person name="Ferre F."/>
                <person name="Espiritu O."/>
                <person name="Carbone-Wiley A."/>
            </authorList>
            <dbReference type="PubMed" id="2554323"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 242-255</scope>
        <source>
            <tissue>Placenta</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Cajal-Retzius cell</tissue>
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        <scope>PROTEIN SEQUENCE OF 204-214; 261-272 AND 521-527</scope>
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        <scope>BINDING DOMAINS</scope>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH GNA12</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH SGO1</scope>
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        <scope>INTERACTION WITH SPRY2</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>INTERACTION WITH CTTNBP2NL</scope>
        <scope>IDENTIFICATION IN STRIPAK COMPLEX</scope>
        <scope>FUNCTION</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>INTERACTION WITH JC VIRUS SMALL T ANTIGEN (MICROBIAL INFECTION)</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>IDENTIFICATION IN THE INTAC COMPLEX</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 9-589 IN COMPLEX WITH PPP2CA AND PPME1</scope>
    </reference>
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                <person name="Li J."/>
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            </authorList>
            <dbReference type="PubMed" id="33243860"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF INTAC COMPLEX</scope>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE INTAC COMPLEX</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            </authorList>
            <dbReference type="PubMed" id="33633399"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) IN THE STRIPAK COMPLEX</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="34762484"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF INTAC COMPLEX</scope>
        <scope>IDENTIFICATION IN THE INTAC COMPLEX</scope>
    </reference>
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                <person name="Jin Q."/>
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                <person name="Liu W."/>
                <person name="Ren Y."/>
                <person name="Zhao D."/>
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                <person name="Xu Y."/>
            </authorList>
            <dbReference type="PubMed" id="36869814"/>
            <dbReference type="DOI" id="10.1093/procel/pwad010"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (4.18 ANGSTROMS) OF INTAC COMPLEX</scope>
        <scope>IDENTIFICATION IN THE INTAC COMPLEX</scope>
    </reference>
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                <person name="Padi S.K.R."/>
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                <person name="Kruse T."/>
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            </authorList>
            <dbReference type="PubMed" id="38123684"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.55 ANGSTROMS) OF 9-589 IN COMPLEXES WITH PPP2CA; PPP2R2A; ARPP19 AND PABIR1/FAM122A</scope>
        <scope>INTERACTION WITH PPP2CA AND PPP2R1A</scope>
        <scope>HEAT REPEATS</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="38570683"/>
            <dbReference type="DOI" id="10.1038/s41586-024-07269-4"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) OF INTAC COMPLEX</scope>
        <scope>IDENTIFICATION IN THE INTAC COMPLEX</scope>
    </reference>
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                <person name="Houge G."/>
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        <scope>VARIANTS HJS2 LEU-179; TRP-182 AND HIS-258</scope>
        <scope>CHARACTERIZATION HJS2 OF VARIANTS LEU-179; TRP-182 AND HIS-258</scope>
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            </authorList>
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        </citation>
        <scope>INVOLVEMENT IN HJS2</scope>
        <scope>VARIANT HJS2 LEU-132</scope>
    </reference>
    <reference key="39">
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        <scope>VARIANTS HJS2 VAL-180; THR-180; ALA-470 AND LEU-498</scope>
        <scope>CHARACTERIZATION OF VARIANTS HJS2 THR-180; ALA-470 AND LEU-498</scope>
        <scope>INTERACTION WITH PPP2R5D AND PPP2CA</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 5 11 17 19 20 21 27">The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit (PubMed:15525651, PubMed:16580887, PubMed:33243860, PubMed:33633399, PubMed:34004147, PubMed:8694763). Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (PubMed:15525651). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (PubMed:16580887). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (By similarity). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes (PubMed:18782753, PubMed:33633399). STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling (PubMed:18782753, PubMed:33633399). Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753, PubMed:33633399). Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex (PubMed:33243860, PubMed:34004147). The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, acts as a scaffolding subunit for PPP2CA, which catalyzes dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, thereby preventing transcriptional elongation (PubMed:33243860, PubMed:34004147). Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 3 4 5 6 7 8 10 11 15 16 18 19 21 22 23 24 25 26">PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits (PubMed:38123684). Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (PubMed:38123684). Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with the PP2A C catalytic subunit PPP2CA (PubMed:37761890, PubMed:38123684). Interacts with the PP2A B subunit PPP2R2A (PubMed:38123684). Interacts with the PP2A B subunit PPP2R5D (PubMed:37761890). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (By similarity). Interacts with IPO9 (PubMed:12670497). Interacts with TP53 and SGO1 (PubMed:16580887, PubMed:17245430). Interacts with PLA2G16; this interaction might decrease PP2A activity (PubMed:17374643). Interacts with CTTNBP2NL (PubMed:18782753). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (PubMed:15525651). Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (By similarity). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (PubMed:17974561). Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26 (PubMed:18782753). Component of the Integrator-PP2A (INTAC) complex, composed of the Integrator core complex and protein phosphatase 2A subunits PPP2CA and PPP2R1A (PubMed:34004147, PubMed:33243860, PubMed:34762484, PubMed:36869814, PubMed:38570683).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 12">(Microbial infection) Interacts with JC virus small t antigen; this interaction inhibits PPP2R1A activity.</text>
    </comment>
    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-296087">
            <id>P31749</id>
            <label>AKT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-2512975">
            <id>Q9C0C7</id>
            <label>AMBRA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1773621">
            <id>Q86XL3</id>
            <label>ANKLE2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-717515">
            <id>Q14155</id>
            <label>ARHGEF7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-624291">
            <id>Q96GD4</id>
            <label>AURKB</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-718719">
            <id>Q9Y2V2</id>
            <label>CARHSP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-3905829">
            <id>P51959</id>
            <label>CCNG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>24</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
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        <interactant intactId="EBI-1379376">
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            <label>CIP2A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1763657">
            <id>Q9Y534</id>
            <label>CSDC2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-12053217">
            <id>Q4G163</id>
            <label>FBXO43</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-11163335">
            <id>Q9NYA3</id>
            <label>GOLGA6A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-10181260">
            <id>Q08AF8</id>
            <label>GOLGA8G</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-746318">
            <id>P53816</id>
            <label>PLAAT3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
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        <interactant intactId="EBI-712311">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>50</experiments>
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    <comment type="interaction">
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            <id>P30153</id>
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        <interactant intactId="EBI-16765970">
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            <label>PPP2CA</label>
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        <experiments>5</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-1044367">
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        <interactant intactId="EBI-357094">
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        <interactant intactId="EBI-1048931">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>21</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-1052159">
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            <label>PPP2R2B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-717262">
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        <experiments>15</experiments>
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        <interactant intactId="EBI-641666">
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        <interactant intactId="EBI-1369497">
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        <interactant intactId="EBI-1266156">
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        <interactant intactId="EBI-396563">
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        <interactant intactId="EBI-968374">
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            <id>P30153</id>
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        <interactant intactId="EBI-716663">
            <id>P53041</id>
            <label>PPP5C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-12164121">
            <id>Q15257-2</id>
            <label>PTPA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-73886">
            <id>Q04206</id>
            <label>RELA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-740175">
            <id>Q9Y6E0</id>
            <label>STK24</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1046642">
            <id>O43815</id>
            <label>STRN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1266294">
            <id>O43815-2</id>
            <label>STRN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1053876">
            <id>Q13033-2</id>
            <label>STRN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-366083">
            <id>P04637</id>
            <label>TP53</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-866453">
            <id>P03129</id>
            <label>E7</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-7005254">
            <id>P04020</id>
            <label>E7</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-309684">
            <id>P97346</id>
            <label>Nxn</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1369292">
            <id>Q60996-3</id>
            <label>Ppp2r5c</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-302388">
            <id>P30153</id>
        </interactant>
        <interactant intactId="EBI-1266256">
            <id>P03081</id>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18 19 21">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="19 21">Chromosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Chromosome</location>
            <location evidence="5">Centromere</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Lateral cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Dendrite</location>
        </subcellularLocation>
        <text evidence="5 19 21">Centromeric localization requires the presence of BUB1 (PubMed:16580887). Recruited to chromatin and transcription pause-release checkpoint via its association with the Integrator complex (PubMed:34004147, PubMed:33243860).</text>
    </comment>
    <comment type="domain">
        <text>Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.</text>
    </comment>
    <comment type="disease" evidence="13 14 24">
        <disease id="DI-04420">
            <name>Houge-Janssens syndrome 2</name>
            <acronym>HJS2</acronym>
            <description>An autosomal dominant disorder characterized by global developmental delay, hypotonia, variably impaired intellectual development, poor speech, and dysmorphic facial features. Some patients may develop seizures.</description>
            <dbReference type="MIM" id="616362"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="29">Belongs to the phosphatase 2A regulatory subunit A family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA35531.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAA36399.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG29336.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH01537.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="A34541"/>
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        <property type="nucleotide sequence ID" value="NM_014225.5"/>
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        <property type="method" value="X-ray"/>
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    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2574">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B56 beta variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2575">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B55 alpha variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2576">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A complex, B56 gamma variant"/>
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        <property type="entry name" value="Integrator-PP2A complex"/>
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    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000324804.6"/>
        <property type="gene ID" value="ENSG00000105568.20"/>
    </dbReference>
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    <dbReference type="MANE-Select" id="ENST00000322088.11">
        <property type="protein sequence ID" value="ENSP00000324804.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014225.6"/>
        <property type="RefSeq protein sequence ID" value="NP_055040.2"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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        <source>
            <dbReference type="PDB" id="7CUN"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="52">
        <source>
            <dbReference type="PDB" id="7K36"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="53">
        <source>
            <dbReference type="PDB" id="7SOY"/>
        </source>
    </evidence>
    <sequence length="589" mass="65309" checksum="5174EBE94D537836" modified="2007-04-03" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="224" xmlns="https://uniprot.org/uniprot">
    <accession>Q13362</accession>
    <accession>B4DYJ8</accession>
    <accession>B5BUA5</accession>
    <accession>F5GWP3</accession>
    <accession>Q14391</accession>
    <accession>Q15060</accession>
    <accession>Q15174</accession>
    <accession>Q6ZN33</accession>
    <name>2A5G_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B'-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform B56-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform PR61-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A B subunit isoform R5-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Renal carcinoma antigen NY-REN-29</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R5C</name>
        <name type="synonym">KIAA0044</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK.</title>
            <authorList>
                <person name="Letourneux C."/>
                <person name="Rocher G."/>
                <person name="Porteu F."/>
            </authorList>
            <dbReference type="PubMed" id="16456541"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7600980"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH IER3 AND ERK KINASES</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="46" last="52">
            <title>Shugoshin collaborates with protein phosphatase 2A to protect cohesin.</title>
            <authorList>
                <person name="Kitajima T.S."/>
                <person name="Sakuno T."/>
                <person name="Ishiguro K."/>
                <person name="Iemura S."/>
                <person name="Natsume T."/>
                <person name="Kawashima S.A."/>
                <person name="Watanabe Y."/>
            </authorList>
            <dbReference type="PubMed" id="16541025"/>
            <dbReference type="DOI" id="10.1038/nature04663"/>
        </citation>
        <scope>INTERACTION WITH SGO1</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2007" name="EMBO J." volume="26" first="402" last="411">
            <title>A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55.</title>
            <authorList>
                <person name="Li H.H."/>
                <person name="Cai X."/>
                <person name="Shouse G.P."/>
                <person name="Piluso L.G."/>
                <person name="Liu X."/>
            </authorList>
            <dbReference type="PubMed" id="17245430"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7601519"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TP53</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2008" name="Mol. Cell. Biol." volume="28" first="448" last="456">
            <title>Serine 15 phosphorylation of p53 directs its interaction with B56gamma and the tumor suppressor activity of B56gamma-specific protein phosphatase 2A.</title>
            <authorList>
                <person name="Shouse G.P."/>
                <person name="Cai X."/>
                <person name="Liu X."/>
            </authorList>
            <dbReference type="PubMed" id="17967874"/>
            <dbReference type="DOI" id="10.1128/mcb.00983-07"/>
        </citation>
        <scope>INTERACTION WITH TP53</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2017" name="EMBO Rep." volume="18" first="437" last="450">
            <title>Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56.</title>
            <authorList>
                <person name="Wang J."/>
                <person name="Okkeri J."/>
                <person name="Pavic K."/>
                <person name="Wang Z."/>
                <person name="Kauko O."/>
                <person name="Halonen T."/>
                <person name="Sarek G."/>
                <person name="Ojala P.M."/>
                <person name="Rao Z."/>
                <person name="Xu W."/>
                <person name="Westermarck J."/>
            </authorList>
            <dbReference type="PubMed" id="28174209"/>
            <dbReference type="DOI" id="10.15252/embr.201642788"/>
        </citation>
        <scope>INTERACTION WITH CIP2A</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2006" name="Cell" volume="127" first="1239" last="1251">
            <title>Structure of the protein phosphatase 2A holoenzyme.</title>
            <authorList>
                <person name="Xu Y."/>
                <person name="Xing Y."/>
                <person name="Chen Y."/>
                <person name="Chao Y."/>
                <person name="Lin Z."/>
                <person name="Fan E."/>
                <person name="Yu J.W."/>
                <person name="Strack S."/>
                <person name="Jeffrey P.D."/>
                <person name="Shi Y."/>
            </authorList>
            <dbReference type="PubMed" id="17174897"/>
            <dbReference type="DOI" id="10.1016/j.cell.2006.11.033"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 1-442 IN COMPLEX WITH PPP2CA AND PPP2R1A</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2007" name="Nature" volume="445" first="53" last="57">
            <title>Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme.</title>
            <authorList>
                <person name="Cho U.S."/>
                <person name="Xu W."/>
            </authorList>
            <dbReference type="PubMed" id="17086192"/>
            <dbReference type="DOI" id="10.1038/nature05351"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 30-436 IN COMPLEX WITH PPP2CA AND PPP2R1A</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2009" name="Mol. Cell" volume="35" first="426" last="441">
            <title>Structure and function of the PP2A-shugoshin interaction.</title>
            <authorList>
                <person name="Xu Z."/>
                <person name="Cetin B."/>
                <person name="Anger M."/>
                <person name="Cho U.S."/>
                <person name="Helmhart W."/>
                <person name="Nasmyth K."/>
                <person name="Xu W."/>
            </authorList>
            <dbReference type="PubMed" id="19716788"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2009.06.031"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 34-436 IN COMPLEX WITH PPP2CA; PPP2R1A AND SGO1</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2009" name="Proteins" volume="74" first="212" last="221">
            <title>The structure of the PP2A regulatory subunit B56 gamma: the remaining piece of the PP2A jigsaw puzzle.</title>
            <authorList>
                <person name="Magnusdottir A."/>
                <person name="Stenmark P."/>
                <person name="Flodin S."/>
                <person name="Nyman T."/>
                <person name="Kotenyova T."/>
                <person name="Graeslund S."/>
                <person name="Ogg D."/>
                <person name="Nordlund P."/>
            </authorList>
            <dbReference type="PubMed" id="18618707"/>
            <dbReference type="DOI" id="10.1002/prot.22150"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 11-380</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2015" name="Hum. Mol. Genet." volume="24" first="4775" last="4779">
            <title>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</title>
            <authorList>
                <consortium name="Childhood Overgrowth Collaboration"/>
                <person name="Loveday C."/>
                <person name="Tatton-Brown K."/>
                <person name="Clarke M."/>
                <person name="Westwood I."/>
                <person name="Renwick A."/>
                <person name="Ramsay E."/>
                <person name="Nemeth A."/>
                <person name="Campbell J."/>
                <person name="Joss S."/>
                <person name="Gardner M."/>
                <person name="Zachariou A."/>
                <person name="Elliott A."/>
                <person name="Ruark E."/>
                <person name="van Montfort R."/>
                <person name="Rahman N."/>
            </authorList>
            <dbReference type="PubMed" id="25972378"/>
            <dbReference type="DOI" id="10.1093/hmg/ddv182"/>
        </citation>
        <scope>VARIANT HJS4 THR-126 DEL</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2019" name="Hum. Mol. Genet." volume="28" first="1578" last="1578">
            <authorList>
                <consortium name="Childhood Overgrowth Collaboration"/>
                <person name="Loveday C."/>
                <person name="Tatton-Brown K."/>
                <person name="Clarke M."/>
                <person name="Westwood I."/>
                <person name="Renwick A."/>
                <person name="Ramsay E."/>
                <person name="Nemeth A."/>
                <person name="Campbell J."/>
                <person name="Joss S."/>
                <person name="Gardner M."/>
                <person name="Zachariou A."/>
                <person name="Elliott A."/>
                <person name="Ruark E."/>
                <person name="Montfort R.V."/>
                <person name="Rahman N."/>
            </authorList>
            <dbReference type="PubMed" id="30615140"/>
            <dbReference type="DOI" id="10.1093/hmg/ddy424"/>
        </citation>
        <scope>ERRATUM OF PUBMED:25972378</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2025" name="Am. J. Hum. Genet." volume="112" first="554" last="571">
            <title>Pathogenic de novo variants in PPP2R5C cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum.</title>
            <authorList>
                <consortium name="Undiagnosed Diseases Network"/>
                <person name="Verbinnen I."/>
                <person name="Douzgou Houge S."/>
                <person name="Hsieh T.C."/>
                <person name="Lesmann H."/>
                <person name="Kirchhoff A."/>
                <person name="Genevieve D."/>
                <person name="Brimble E."/>
                <person name="Lenaerts L."/>
                <person name="Haesen D."/>
                <person name="Levy R.J."/>
                <person name="Thevenon J."/>
                <person name="Faivre L."/>
                <person name="Marco E."/>
                <person name="Chong J.X."/>
                <person name="Bamshad M."/>
                <person name="Patterson K."/>
                <person name="Mirzaa G.M."/>
                <person name="Foss K."/>
                <person name="Dobyns W."/>
                <person name="White S.M."/>
                <person name="Pais L."/>
                <person name="O'Heir E."/>
                <person name="Itzikowitz R."/>
                <person name="Donald K.A."/>
                <person name="Van der Merwe C."/>
                <person name="Mussa A."/>
                <person name="Cervini R."/>
                <person name="Giorgio E."/>
                <person name="Roscioli T."/>
                <person name="Dias K.R."/>
                <person name="Evans C.A."/>
                <person name="Brown N.J."/>
                <person name="Ruiz A."/>
                <person name="Trujillo Quintero J.P."/>
                <person name="Rabin R."/>
                <person name="Pappas J."/>
                <person name="Yuan H."/>
                <person name="Lachlan K."/>
                <person name="Thomas S."/>
                <person name="Devlin A."/>
                <person name="Wright M."/>
                <person name="Martin R."/>
                <person name="Karwowska J."/>
                <person name="Posmyk R."/>
                <person name="Chatron N."/>
                <person name="Stark Z."/>
                <person name="Heath O."/>
                <person name="Delatycki M."/>
                <person name="Buchert R."/>
                <person name="Korenke G.C."/>
                <person name="Ramsey K."/>
                <person name="Narayanan V."/>
                <person name="Grange D.K."/>
                <person name="Weisenberg J.L."/>
                <person name="Haack T.B."/>
                <person name="Karch S."/>
                <person name="Kipkemoi P."/>
                <person name="Mangi M."/>
                <person name="Bindels de Heus K.G.C.B."/>
                <person name="de Wit M.Y."/>
                <person name="Barakat T.S."/>
                <person name="Lim D."/>
                <person name="Van Winckel G."/>
                <person name="Spillmann R.C."/>
                <person name="Shashi V."/>
                <person name="Jacob M."/>
                <person name="Stehr A.M."/>
                <person name="Krawitz P."/>
                <person name="Douzgos Houge G."/>
                <person name="Janssens V."/>
            </authorList>
            <dbReference type="PubMed" id="39978342"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2025.01.021"/>
        </citation>
        <scope>VARIANTS HJS4 ARG-49; 54-ASP-PHE-55 DEL; LEU-55; ARG-120; LYS-122; LYS-124; THR-126 DEL; ALA-130 DEL; ARG-131; ARG-133; PRO-133; LEU-133; PRO-134; LYS-174; VAL-175; TRP-177; LEU-177; GLU-244 AND LYS-344</scope>
        <scope>CHARACTERIZATION OF VARIANTS HJS4 ARG-49; 54-ASP-PHE-55 DEL; LEU-55; LYS-122; THR-126 DEL; ALA-130 DEL; ARG-131; ARG-133; PRO-133; LEU-133; PRO-134; LYS-174; VAL-175; TRP-177 AND GLU-244</scope>
        <scope>INVOLVEMENT IN HJS4</scope>
    </reference>
    <comment type="function">
        <text evidence="3 8">The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 5 6 7 8 9 10 12">PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with PPP2CA and PPP2R1A; the interaction is direct. Interacts with SGO1; the interaction is direct. Isoform 1 and isoform 2 interact with TP53 (phosphorylated at Ser-15 by ATM); increased upon DNA damage it drives PP2A-mediated dephosphorylation of TP53 at Thr-55. Interacts with IER3 and/or ERK kinases; regulates ERK dephosphorylation. Interacts with CIP2A; this interaction stabilizes CIP2A (PubMed:28174209).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-1748945">
            <id>P46695</id>
            <label>IER3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-389668">
            <id>Q00987</id>
            <label>MDM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-712311">
            <id>P67775</id>
            <label>PPP2CA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>14</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-357094">
            <id>P30154</id>
            <label>PPP2R1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-365996">
            <id>P04049</id>
            <label>RAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
        </interactant>
        <interactant intactId="EBI-366083">
            <id>P04637</id>
            <label>TP53</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266170">
            <id>Q13362-1</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266170">
            <id>Q13362-1</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266173">
            <id>Q13362-2</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266173">
            <id>Q13362-2</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1266176">
            <id>Q13362-3</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Chromosome</location>
            <location>Centromere</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q13362-1</id>
            <name>Gamma-3</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13362-2</id>
            <name>Gamma-1</name>
            <sequence type="described" ref="VSP_005112"/>
        </isoform>
        <isoform>
            <id>Q13362-3</id>
            <name>Gamma-2</name>
            <sequence type="described" ref="VSP_005113"/>
        </isoform>
        <isoform>
            <id>Q13362-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_043645 VSP_005113"/>
        </isoform>
        <isoform>
            <id>Q13362-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_046768"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Highest levels in heart, skeletal muscle and brain. Lower levels in pancreas, kidney, lung and placenta. Very low levels in liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="8">Up-regulated upon DNA damage.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3 14">Isoform Gamma-3 is phosphorylated on serine residues. Isoform Gamma-1 phosphorylation by ERK2 is IER3-dependent and inhibits ERK dephosphorylation by PP2A-PPP2R5C.</text>
    </comment>
    <comment type="disease" evidence="11 13">
        <disease id="DI-07030">
            <name>Houge-Janssens syndrome 4</name>
            <acronym>HJS4</acronym>
            <description>An autosomal dominant neurodevelopmental disorder characterized by stable developmental delay, intellectual disability of variable degrees, poor or absent speech, generalized hypotonia, seizures, behavioral features, and abnormal coordination. Most affected individuals have a large head circumference or macrocephaly. Disease onset is in infancy or early childhood.</description>
            <dbReference type="MIM" id="621185"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the phosphatase 2A regulatory subunit B56 family.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC50387" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAG63760" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="U37352">
        <property type="protein sequence ID" value="AAC50387.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z69030">
        <property type="protein sequence ID" value="CAA93154.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK131391">
        <property type="protein sequence ID" value="BAD18542.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK302470">
        <property type="protein sequence ID" value="BAG63760.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB451341">
        <property type="protein sequence ID" value="BAG70155.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL118558">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL137779">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471061">
        <property type="protein sequence ID" value="EAW81756.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-550</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-175; SER-262; SER-544; SER-550 AND THR-626</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ALTERNATIVE SPLICING (ISOFORMS LONG BGIN AND SHORT BGIN)</scope>
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        <scope>INTERACTION WITH PLXND1</scope>
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        <scope>DOMAIN</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-262; SER-264 AND SER-544</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7 8 9">GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form. By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration (PubMed:21658605). Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions (PubMed:22891260). Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment (PubMed:26465210). It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin-plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (PubMed:24841563).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 6 7 8">Interacts with RAC1 (By similarity). Interacts with the exocyst via EXOC4 and EXOC8; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells (PubMed:21658605). Interacts with CD2AP and CGNL1; probably part of a complex at cell junctions (PubMed:22891260). Interacts with CAPZA1; recruits CAPZA1 to forming cell junctions (PubMed:22891260). May interact with AFDN (PubMed:22891260). Interacts with PLXND1; they dissociate upon SEMA3E binding to PLXND1 allowing SH3BP1 to transduce downstream signal through RAC1 inactivation (PubMed:24841563). Interacts with ABL1, GRB2 and SRC (via SH3 domain) (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 8">Cell projection</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cell junction</location>
            <location evidence="7">Tight junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cell junction</location>
            <location evidence="7">Adherens junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Cell projection</location>
            <location evidence="9">Phagocytic cup</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
            <location evidence="7">Cytosol</location>
        </subcellularLocation>
        <text evidence="6 8 9">Localizes at the leading edge of migrating cells (PubMed:21658605, PubMed:24841563). Accumulation at forming phagocytic cups is PI3 kinase/PI3K-dependent and is specific for sites of large particles engagement and their phosphatidylinositol 3,4,5-triphosphate membrane content (PubMed:26465210).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <event type="alternative initiation"/>
        <isoform>
            <id>Q9Y3L3-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y3L3-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011373 VSP_011374"/>
        </isoform>
        <isoform>
            <id>Q6ZT62-1</id>
            <name evidence="11">Long BGIN</name>
            <sequence type="external"/>
        </isoform>
        <isoform>
            <id>Q6ZT62-2</id>
            <name evidence="11">Short BGIN</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="6 8">The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration (PubMed:21658605). It also mediates the interaction with PLXND1 (PubMed:24841563).</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH08282" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC85842" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAC85842" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="CR456576">
        <property type="protein sequence ID" value="CAG30462.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK124370">
        <property type="protein sequence ID" value="BAC85842.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z83844">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008282">
        <property type="protein sequence ID" value="AAH08282.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL157480">
        <property type="protein sequence ID" value="CAB75671.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13952.2">
        <molecule id="Q9Y3L3-1"/>
    </dbReference>
    <dbReference type="PIR" id="T46916">
        <property type="entry name" value="T46916"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_061830.3">
        <molecule id="Q9Y3L3-1"/>
        <property type="nucleotide sequence ID" value="NM_018957.3"/>
    </dbReference>
    <dbReference type="PDB" id="4J9D">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="B/D/F=616-625"/>
    </dbReference>
    <dbReference type="PDB" id="4J9F">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.09 A"/>
        <property type="chains" value="B/D/F=616-625"/>
    </dbReference>
    <dbReference type="PDBsum" id="4J9D"/>
    <dbReference type="PDBsum" id="4J9F"/>
    <dbReference type="AlphaFoldDB" id="Q9Y3L3"/>
    <dbReference type="SMR" id="Q9Y3L3"/>
    <dbReference type="BioGRID" id="117149">
        <property type="interactions" value="46"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y3L3">
        <property type="interactions" value="667"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y3L3"/>
    <dbReference type="STRING" id="9606.ENSP00000497104"/>
    <dbReference type="GlyCosmos" id="Q9Y3L3">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9Y3L3">
        <property type="glycosylation" value="4 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y3L3"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y3L3"/>
    <dbReference type="BioMuta" id="SH3BP1"/>
    <dbReference type="DMDM" id="51338841"/>
    <dbReference type="CPTAC" id="CPTAC-1004"/>
    <dbReference type="jPOST" id="Q9Y3L3"/>
    <dbReference type="MassIVE" id="Q9Y3L3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000350018"/>
    <dbReference type="PeptideAtlas" id="Q9Y3L3"/>
    <dbReference type="ProteomicsDB" id="86041">
        <molecule id="Q9Y3L3-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="86042">
        <molecule id="Q9Y3L3-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9Y3L3"/>
    <dbReference type="Antibodypedia" id="214">
        <property type="antibodies" value="229 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23616"/>
    <dbReference type="Ensembl" id="ENST00000417536.5">
        <molecule id="Q9Y3L3-2"/>
        <property type="protein sequence ID" value="ENSP00000411979.1"/>
        <property type="gene ID" value="ENSG00000100092.25"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000649765.2">
        <molecule id="Q9Y3L3-1"/>
        <property type="protein sequence ID" value="ENSP00000497104.1"/>
        <property type="gene ID" value="ENSG00000100092.25"/>
    </dbReference>
    <dbReference type="GeneID" id="23616"/>
    <dbReference type="KEGG" id="hsa:23616"/>
    <dbReference type="MANE-Select" id="ENST00000649765.2">
        <property type="protein sequence ID" value="ENSP00000497104.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018957.6"/>
        <property type="RefSeq protein sequence ID" value="NP_061830.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003atg.2">
        <molecule id="Q9Y3L3-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:10824"/>
    <dbReference type="ClinPGx" id="PA35732"/>
    <dbReference type="CTD" id="23616"/>
    <dbReference type="DisGeNET" id="23616"/>
    <dbReference type="GeneCards" id="SH3BP1"/>
    <dbReference type="HGNC" id="HGNC:10824">
        <property type="gene designation" value="SH3BP1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100092">
        <property type="expression patterns" value="Tissue enhanced (esophagus)"/>
    </dbReference>
    <dbReference type="MIM" id="617368">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000100092"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000100092"/>
    <dbReference type="eggNOG" id="KOG4270">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158369"/>
    <dbReference type="HOGENOM" id="CLU_013806_2_0_1"/>
    <dbReference type="InParanoid" id="Q9Y3L3"/>
    <dbReference type="OMA" id="WDYFFEG"/>
    <dbReference type="OrthoDB" id="19923at2759"/>
    <dbReference type="PAN-GO" id="Q9Y3L3">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y3L3"/>
    <dbReference type="PathwayCommons" id="Q9Y3L3"/>
    <dbReference type="Reactome" id="R-HSA-9013149">
        <property type="pathway name" value="RAC1 GTPase cycle"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9Y3L3"/>
    <dbReference type="SIGNOR" id="Q9Y3L3"/>
    <dbReference type="Agora" id="ENSG00000100092"/>
    <dbReference type="BioGRID-ORCS" id="23616">
        <property type="hits" value="23 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SH3BP1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9Y3L3"/>
    <dbReference type="GeneWiki" id="SH3BP1"/>
    <dbReference type="GenomeRNAi" id="23616"/>
    <dbReference type="Pharos" id="Q9Y3L3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y3L3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y3L3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000100092">
        <property type="expression patterns" value="Expressed in granulocyte and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y3L3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005912">
        <property type="term" value="C:adherens junction"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005923">
        <property type="term" value="C:bicellular tight junction"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031252">
        <property type="term" value="C:cell leading edge"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030027">
        <property type="term" value="C:lamellipodium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001891">
        <property type="term" value="C:phagocytic cup"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030215">
        <property type="term" value="F:semaphorin receptor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017124">
        <property type="term" value="F:SH3 domain binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007015">
        <property type="term" value="P:actin filament organization"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034329">
        <property type="term" value="P:cell junction assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016477">
        <property type="term" value="P:cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045198">
        <property type="term" value="P:establishment of epithelial cell apical/basal polarity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051058">
        <property type="term" value="P:negative regulation of small GTPase mediated signal transduction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006911">
        <property type="term" value="P:phagocytosis, engulfment"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043547">
        <property type="term" value="P:positive regulation of GTPase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032956">
        <property type="term" value="P:regulation of actin cytoskeleton organization"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030834">
        <property type="term" value="P:regulation of actin filament depolymerization"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043535">
        <property type="term" value="P:regulation of blood vessel endothelial cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035020">
        <property type="term" value="P:regulation of Rac protein signal transduction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051056">
        <property type="term" value="P:regulation of small GTPase mediated signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097178">
        <property type="term" value="P:ruffle assembly"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071526">
        <property type="term" value="P:semaphorin-plexin signaling pathway"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd07620">
        <property type="entry name" value="BAR_SH3BP1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.555.10:FF:000001">
        <property type="entry name" value="Rho GTPase activating protein 44"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1270.60:FF:000053">
        <property type="entry name" value="SH3 domain-binding protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1270.60">
        <property type="entry name" value="Arfaptin homology (AH) domain/BAR domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.555.10">
        <property type="entry name" value="Rho GTPase activation protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027267">
        <property type="entry name" value="AH/BAR_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004148">
        <property type="entry name" value="BAR_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR047165">
        <property type="entry name" value="RHG17/44/SH3BP1-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008936">
        <property type="entry name" value="Rho_GTPase_activation_prot"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000198">
        <property type="entry name" value="RhoGAP_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14130">
        <property type="entry name" value="3BP-1 RELATED RHOGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14130:SF12">
        <property type="entry name" value="BARGIN-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03114">
        <property type="entry name" value="BAR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00620">
        <property type="entry name" value="RhoGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00721">
        <property type="entry name" value="BAR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00324">
        <property type="entry name" value="RhoGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF103657">
        <property type="entry name" value="BAR/IMD domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48350">
        <property type="entry name" value="GTPase activation domain, GAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51021">
        <property type="entry name" value="BAR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50238">
        <property type="entry name" value="RHOGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0581">Phagocytosis</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <keyword id="KW-0796">Tight junction</keyword>
    <feature type="chain" id="PRO_0000056723" description="SH3 domain-binding protein 1">
        <location>
            <begin position="1"/>
            <end position="701"/>
        </location>
    </feature>
    <feature type="domain" description="BAR" evidence="4">
        <location>
            <begin position="17"/>
            <end position="262"/>
        </location>
    </feature>
    <feature type="domain" description="Rho-GAP" evidence="3">
        <location>
            <begin position="276"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with CGNL1" evidence="7">
        <location>
            <begin position="1"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="160"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with CD2AP" evidence="7">
        <location>
            <begin position="470"/>
            <end position="701"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="496"/>
            <end position="701"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding" evidence="2">
        <location>
            <begin position="616"/>
            <end position="625"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="5">
        <location>
            <begin position="1"/>
            <end position="10"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="508"/>
            <end position="522"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="570"/>
            <end position="579"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="587"/>
            <end position="596"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="618"/>
            <end position="630"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="641"/>
            <end position="652"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="666"/>
            <end position="677"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="682"/>
            <end position="692"/>
        </location>
    </feature>
    <feature type="site" description="Arginine finger; crucial for GTP hydrolysis by stabilizing the transition state" evidence="3">
        <location>
            <position position="312"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="175"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17 18">
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="18">
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="14 17 18">
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15 16 17">
        <location>
            <position position="550"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="601"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="17">
        <location>
            <position position="626"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="653"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011373" description="In isoform 2." evidence="10">
        <original>DQAQLDAASVSSI</original>
        <variation>TEPARELGSQTLC</variation>
        <location>
            <begin position="440"/>
            <end position="452"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011374" description="In isoform 2." evidence="10">
        <location>
            <begin position="453"/>
            <end position="701"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033450" description="In dbSNP:rs929038.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033451" description="In dbSNP:rs2269548.">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="656"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Probable loss of the GTPase activator activity. Loss of function in cell migration." evidence="6">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="312"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="D3ZFJ3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P55194"/>
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    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00172"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00361"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21658605"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22891260"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="24841563"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="26465210"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="23223568"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:10824"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="19367720"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="701" mass="75713" checksum="877D144E81F0F974" modified="2004-08-16" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-01-01" modified="2026-01-28" version="227" xmlns="https://uniprot.org/uniprot">
    <accession>P14060</accession>
    <accession>A8K691</accession>
    <accession>Q14545</accession>
    <accession>Q8IV65</accession>
    <name>3BHS1_HUMAN</name>
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        <recommendedName>
            <fullName>3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 1</fullName>
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        <alternativeName>
            <fullName evidence="10">3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type I</fullName>
            <shortName>3-beta-HSD I</shortName>
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        <alternativeName>
            <fullName evidence="11">3-beta-hydroxy-5-ene steroid dehydrogenase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">3-beta-hydroxy-Delta(5)-steroid dehydrogenase</fullName>
            <ecNumber evidence="5">1.1.1.145</ecNumber>
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        <alternativeName>
            <fullName evidence="13">3-beta-hydroxysteroid 3-dehydrogenase</fullName>
            <ecNumber evidence="5">1.1.1.270</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Delta-5-3-ketosteroid isomerase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Dihydrotestosterone oxidoreductase</fullName>
            <ecNumber evidence="5">1.1.1.210</ecNumber>
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        <alternativeName>
            <fullName evidence="13">Steroid Delta-isomerase</fullName>
            <ecNumber evidence="5">5.3.3.1</ecNumber>
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        <alternativeName>
            <fullName evidence="11">Trophoblast antigen FDO161G</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">HSD3B1</name>
        <name type="synonym">3BH</name>
        <name type="synonym">HSDB3A</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase.</title>
            <authorList>
                <person name="Luu-The V."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 2-30</scope>
    </reference>
    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Placenta</tissue>
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    </reference>
    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="2082186"/>
            <dbReference type="DOI" id="10.1210/mend-4-12-1850"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <dbReference type="PubMed" id="2243100"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ASN-367</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
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                <person name="Dumont M."/>
                <person name="Van L.T."/>
                <person name="Dupont E."/>
                <person name="Pelletier G."/>
                <person name="Labrie F."/>
            </authorList>
            <dbReference type="PubMed" id="1401999"/>
            <dbReference type="DOI" id="10.1111/1523-1747.ep12616131"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
    </reference>
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                <person name="Tashiro H."/>
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                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
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                <person name="Ohmori Y."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ASN-367</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
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            <dbReference type="PubMed" id="10391209"/>
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        <scope>VARIANTS VAL-79 AND LEU-286</scope>
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        <scope>ERRATUM OF PUBMED:10391209</scope>
    </reference>
    <comment type="function">
        <text evidence="5 7 13">A bifunctional enzyme responsible for the oxidation and isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-oxo-Delta(4)-steroids, an essential step in steroid hormone biosynthesis. Specifically catalyzes the conversion of pregnenolone to progesterone, 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to 4-androstenedione, and androstenediol to testosterone. Additionally, catalyzes the interconversion between 3beta-hydroxy and 3-oxo-5alpha-androstane steroids controlling the bioavalability of the active forms. Specifically converts dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Also converts androstanedione, a precursor of testosterone and estrone, to epiandrosterone (PubMed:1401999, PubMed:2139411). Expected to use NAD(+) as preferred electron donor for the 3beta-hydroxy-steroid dehydrogenase activity and NADPH for the 3-ketosteroid reductase activity (Probable).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-steroid + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:24076"/>
            <dbReference type="ChEBI" id="CHEBI:1722"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:47907"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.145"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>pregnenolone + NAD(+) = pregn-5-ene-3,20-dione + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43924"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16581"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:63837"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-ene-3,17-dione + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43932"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28689"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:83865"/>
            <dbReference type="EC" id="1.1.1.145"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>androst-5-en-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-androst-5-en-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:56932"/>
            <dbReference type="ChEBI" id="CHEBI:2710"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:141179"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a 3beta-hydroxysteroid + NADP(+) = a 3-oxosteroid + NADPH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:34787"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:36836"/>
            <dbReference type="ChEBI" id="CHEBI:47788"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="EC" id="1.1.1.270"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADPH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16297"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16330"/>
            <dbReference type="ChEBI" id="CHEBI:18329"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="EC" id="1.1.1.210"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>3beta-hydroxy-5alpha-androstan-17-one + NADP(+) = 5alpha-androstan-3,17-dione + NADPH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:56916"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15994"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="ChEBI" id="CHEBI:541975"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid</text>
            <dbReference type="Rhea" id="RHEA:14709"/>
            <dbReference type="ChEBI" id="CHEBI:47907"/>
            <dbReference type="ChEBI" id="CHEBI:47909"/>
            <dbReference type="EC" id="5.3.3.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>pregn-5-ene-3,20-dione = progesterone</text>
            <dbReference type="Rhea" id="RHEA:43928"/>
            <dbReference type="ChEBI" id="CHEBI:17026"/>
            <dbReference type="ChEBI" id="CHEBI:63837"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>androst-5-ene-3,17-dione = androst-4-ene-3,17-dione</text>
            <dbReference type="Rhea" id="RHEA:43936"/>
            <dbReference type="ChEBI" id="CHEBI:16422"/>
            <dbReference type="ChEBI" id="CHEBI:83865"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>17beta-hydroxy-androst-5-en-3-one = testosterone</text>
            <dbReference type="Rhea" id="RHEA:56936"/>
            <dbReference type="ChEBI" id="CHEBI:17347"/>
            <dbReference type="ChEBI" id="CHEBI:141179"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>5alpha-androstane-3beta,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:42184"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16330"/>
            <dbReference type="ChEBI" id="CHEBI:18329"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">0.13 uM for dehydroepiandrosterone (in the presence of NAD(+))</KM>
            <KM evidence="5">0.33 uM for pregnenolone (in the presence of NAD(+))</KM>
            <KM evidence="5">2.1 uM for dihydrotestosterone (in the presence of NADH)</KM>
            <Vmax evidence="5">0.93 nmol/min/mg enzyme for dehydroepiandrosterone oxidation in the presence of NAD(+)</Vmax>
            <Vmax evidence="5">2.43 nmol/min/mg enzyme for pregnenolone oxidation in the presence of NAD(+)</Vmax>
            <Vmax evidence="5">14.12 nmol/min/mg enzyme for dihydrotestosterone reduction in the presence of NADH</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="5">Steroid hormone biosynthesis.</text>
    </comment>
    <comment type="pathway">
        <text evidence="5">Steroid metabolism.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-13059134">
            <id>Q13520</id>
            <label>AQP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-1049597">
            <id>P27797</id>
            <label>CALR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-351007">
            <id>P36957</id>
            <label>DLST</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-348399">
            <id>P22607</id>
            <label>FGFR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-351506">
            <id>P06396</id>
            <label>GSN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-1055945">
            <id>Q8TDX7</id>
            <label>NEK7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-12243266">
            <id>Q7RTY0</id>
            <label>SLC16A13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17426018">
            <id>P14060</id>
        </interactant>
        <interactant intactId="EBI-8638294">
            <id>Q9NUH8</id>
            <label>TMEM14B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Endoplasmic reticulum membrane</location>
            <topology>Single-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Mitochondrion membrane</location>
            <topology>Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Placenta and skin (PubMed:1401999). Predominantly expressed in mammary gland tissue.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the 3-beta-HSD family.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAA36001" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="1.1.1.145" evidence="5"/>
    <dbReference type="EC" id="1.1.1.270" evidence="5"/>
    <dbReference type="EC" id="1.1.1.210" evidence="5"/>
    <dbReference type="EC" id="5.3.3.1" evidence="5"/>
    <dbReference type="EMBL" id="M27137">
        <property type="protein sequence ID" value="AAA36015.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M28392">
        <property type="protein sequence ID" value="AAA36001.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M28162">
        <property type="protein sequence ID" value="AAA36001.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M28391">
        <property type="protein sequence ID" value="AAA36001.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X53321">
        <property type="protein sequence ID" value="CAA37408.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M35493">
        <property type="protein sequence ID" value="AAA51538.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M63397">
        <property type="protein sequence ID" value="AAA51662.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M63395">
        <property type="protein sequence ID" value="AAA51662.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M63396">
        <property type="protein sequence ID" value="AAA51662.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M38180">
        <property type="protein sequence ID" value="AAA51831.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X55997">
        <property type="protein sequence ID" value="CAA39469.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S45679">
        <property type="protein sequence ID" value="AAB23543.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291556">
        <property type="protein sequence ID" value="BAF84245.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031999">
        <property type="protein sequence ID" value="AAH31999.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS903.1"/>
    <dbReference type="PIR" id="A36551">
        <property type="entry name" value="DEHUHS"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000853.1">
        <property type="nucleotide sequence ID" value="NM_000862.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001315544.1">
        <property type="nucleotide sequence ID" value="NM_001328615.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P14060"/>
    <dbReference type="SMR" id="P14060"/>
    <dbReference type="BioGRID" id="109516">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="FunCoup" id="P14060">
        <property type="interactions" value="93"/>
    </dbReference>
    <dbReference type="IntAct" id="P14060">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000358421"/>
    <dbReference type="BindingDB" id="P14060"/>
    <dbReference type="ChEMBL" id="CHEMBL1958"/>
    <dbReference type="DrugBank" id="DB01536">
        <property type="generic name" value="Androstenedione"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14538">
        <property type="generic name" value="Hydrocortisone aceponate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14539">
        <property type="generic name" value="Hydrocortisone acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14540">
        <property type="generic name" value="Hydrocortisone butyrate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14541">
        <property type="generic name" value="Hydrocortisone cypionate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14542">
        <property type="generic name" value="Hydrocortisone phosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14543">
        <property type="generic name" value="Hydrocortisone probutate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14544">
        <property type="generic name" value="Hydrocortisone valerate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01708">
        <property type="generic name" value="Prasterone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09070">
        <property type="generic name" value="Tibolone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01108">
        <property type="generic name" value="Trilostane"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P14060"/>
    <dbReference type="SwissLipids" id="SLP:000001297"/>
    <dbReference type="GlyGen" id="P14060">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P14060"/>
    <dbReference type="PhosphoSitePlus" id="P14060"/>
    <dbReference type="BioMuta" id="HSD3B1"/>
    <dbReference type="DMDM" id="112767"/>
    <dbReference type="jPOST" id="P14060"/>
    <dbReference type="MassIVE" id="P14060"/>
    <dbReference type="PaxDb" id="9606-ENSP00000358421"/>
    <dbReference type="PeptideAtlas" id="P14060"/>
    <dbReference type="ProteomicsDB" id="53017"/>
    <dbReference type="Antibodypedia" id="33912">
        <property type="antibodies" value="365 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3283"/>
    <dbReference type="Ensembl" id="ENST00000369413.8">
        <property type="protein sequence ID" value="ENSP00000358421.3"/>
        <property type="gene ID" value="ENSG00000203857.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000528909.1">
        <property type="protein sequence ID" value="ENSP00000432268.1"/>
        <property type="gene ID" value="ENSG00000203857.10"/>
    </dbReference>
    <dbReference type="GeneID" id="3283"/>
    <dbReference type="KEGG" id="hsa:3283"/>
    <dbReference type="MANE-Select" id="ENST00000369413.8">
        <property type="protein sequence ID" value="ENSP00000358421.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000862.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000853.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001ehv.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5217"/>
    <dbReference type="ClinPGx" id="PA29486"/>
    <dbReference type="CTD" id="3283"/>
    <dbReference type="DisGeNET" id="3283"/>
    <dbReference type="GeneCards" id="HSD3B1"/>
    <dbReference type="HGNC" id="HGNC:5217">
        <property type="gene designation" value="HSD3B1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000203857">
        <property type="expression patterns" value="Tissue enriched (placenta)"/>
    </dbReference>
    <dbReference type="MalaCards" id="HSD3B1"/>
    <dbReference type="MIM" id="109715">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000203857"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000203857"/>
    <dbReference type="eggNOG" id="KOG1430">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161374"/>
    <dbReference type="HOGENOM" id="CLU_007383_6_3_1"/>
    <dbReference type="InParanoid" id="P14060"/>
    <dbReference type="OMA" id="YVENCTY"/>
    <dbReference type="OrthoDB" id="1925334at2759"/>
    <dbReference type="PAN-GO" id="P14060">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P14060"/>
    <dbReference type="BioCyc" id="MetaCyc:HS08829-MONOMER"/>
    <dbReference type="BRENDA" id="1.1.1.145">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="5.3.3.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P14060"/>
    <dbReference type="Reactome" id="R-HSA-193048">
        <property type="pathway name" value="Androgen biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-193993">
        <property type="pathway name" value="Mineralocorticoid biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-194002">
        <property type="pathway name" value="Glucocorticoid biosynthesis"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P14060"/>
    <dbReference type="SignaLink" id="P14060"/>
    <dbReference type="SIGNOR" id="P14060"/>
    <dbReference type="Agora" id="ENSG00000203857"/>
    <dbReference type="BioGRID-ORCS" id="3283">
        <property type="hits" value="24 hits in 1115 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HSD3B1"/>
    <dbReference type="GenomeRNAi" id="3283"/>
    <dbReference type="Pharos" id="P14060">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P14060"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="P14060">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000203857">
        <property type="expression patterns" value="Expressed in placenta and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P14060">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045171">
        <property type="term" value="C:intercellular bridge"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015630">
        <property type="term" value="C:microtubule cytoskeleton"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005758">
        <property type="term" value="C:mitochondrial intermembrane space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0030868">
        <property type="term" value="C:smooth endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003854">
        <property type="term" value="F:3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000253">
        <property type="term" value="F:3-beta-hydroxysteroid 3-dehydrogenase (NADP+) activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
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    <dbReference type="GO" id="GO:0047024">
        <property type="term" value="F:5-alpha-androstane-3-beta,17-beta-diol dehydrogenase (NADP+) activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
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    <dbReference type="GO" id="GO:0016616">
        <property type="term" value="F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0004769">
        <property type="term" value="F:steroid Delta-isomerase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
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    <dbReference type="GO" id="GO:0006702">
        <property type="term" value="P:androgen biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0008207">
        <property type="term" value="P:C21-steroid hormone metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006703">
        <property type="term" value="P:estrogen biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006701">
        <property type="term" value="P:progesterone biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006694">
        <property type="term" value="P:steroid biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd09811">
        <property type="entry name" value="3b-HSD_HSDB1_like_SDR_e"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.720:FF:000220">
        <property type="entry name" value="3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.720">
        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002225">
        <property type="entry name" value="3Beta_OHSteriod_DH/Estase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050177">
        <property type="entry name" value="Lipid_A_modif_metabolic_enz"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43245">
        <property type="entry name" value="BIFUNCTIONAL POLYMYXIN RESISTANCE PROTEIN ARNA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43245:SF51">
        <property type="entry name" value="SHORT CHAIN DEHYDROGENASE_REDUCTASE FAMILY 42E, MEMBER 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01073">
        <property type="entry name" value="3Beta_HSD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51735">
        <property type="entry name" value="NAD(P)-binding Rossmann-fold domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0413">Isomerase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0511">Multifunctional enzyme</keyword>
    <keyword id="KW-0520">NAD</keyword>
    <keyword id="KW-0521">NADP</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0753">Steroid metabolism</keyword>
    <keyword id="KW-0755">Steroidogenesis</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="initiator methionine" description="Removed" evidence="9">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000087774" description="3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 1">
        <location>
            <begin position="2"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="288"/>
            <end position="308"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="2">
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="10"/>
            <end position="15"/>
        </location>
        <ligand>
            <name>NADP(+)</name>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="155"/>
        </location>
        <ligand>
            <name>NADP(+)</name>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="159"/>
        </location>
        <ligand>
            <name>NADP(+)</name>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_048096" description="In dbSNP:rs3088283.">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048097" description="In dbSNP:rs4986952.">
        <original>R</original>
        <variation>I</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014174" description="In dbSNP:rs6201." evidence="4">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048098" description="In dbSNP:rs6684974.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014175" description="In dbSNP:rs6205." evidence="4">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="286"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000005" description="In dbSNP:rs1047303." evidence="6 8">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="367"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P22071"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q12068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10391209"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="1401999"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="2139411"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="2243100"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="2779585"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="1401999"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="1920284"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0000305" key="13">
        <source>
            <dbReference type="PubMed" id="1401999"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="HGNC" id="HGNC:5217"/>
        </source>
    </evidence>
    <sequence length="373" mass="42252" checksum="2C76616E7EA7433A" modified="2007-01-23" version="2">MTGWSCLVTGAGGFLGQRIIRLLVKEKELKEIRVLDKAFGPELREEFSKLQNKTKLTVLEGDILDEPFLKRACQDVSVIIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFIYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPAPYPHSKKLAEKAVLAANGWNLKNGGTLYTCALRPMYIYGEGSRFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALQDPKKAPSIRGQFYYISDDTPHQSYDNLNYTLSKEFGLRLDSRWSFPLSLMYWIGFLLEIVSFLLRPIYTYRPPFNRHIVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLVDRHKETLKSKTQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-01-24" modified="2026-01-28" version="179" xmlns="https://uniprot.org/uniprot">
    <accession>Q66LE6</accession>
    <accession>A8KAK0</accession>
    <accession>Q5SQJ2</accession>
    <accession>Q9P1Y7</accession>
    <name>2ABD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A subunit B isoform B55-delta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform PR55-delta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform R2-delta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit B isoform delta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R2D</name>
        <name type="synonym">KIAA1541</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
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                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2000" name="DNA Res." volume="7" first="143" last="150">
            <title>Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Ishikawa K."/>
                <person name="Hirosawa M."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="10819331"/>
            <dbReference type="DOI" id="10.1093/dnares/7.2.143"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-453</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2015" name="FEBS Lett." volume="589" first="1150" last="1155">
            <title>HSF1 transcriptional activity is modulated by IER5 and PP2A/B55.</title>
            <authorList>
                <person name="Ishikawa Y."/>
                <person name="Kawabata S."/>
                <person name="Sakurai H."/>
            </authorList>
            <dbReference type="PubMed" id="25816751"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2015.03.019"/>
        </citation>
        <scope>INTERACTION WITH IER5</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5">Substrate-recognition subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit. Involved in chromosome clustering during late mitosis by mediating dephosphorylation of MKI67 (By similarity). The activity of PP2A complexes containing PPP2R2D (PR55-delta) fluctuate during the cell cycle: the activity is high in interphase and low in mitosis (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 6">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with ENSA (when phosphorylated at 'Ser-67') and ARPP19 (when phosphorylated at 'Ser-62'), leading to inhibit PP2A activity (By similarity). Interacts with IER5 (PubMed:25816751).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717262">
            <id>Q66LE6</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717262">
            <id>Q66LE6</id>
        </interactant>
        <interactant intactId="EBI-14032793">
            <id>Q76S40</id>
            <label>ORF2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the phosphatase 2A regulatory subunit B family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA96065" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK293065">
        <property type="protein sequence ID" value="BAF85754.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL732395">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047379">
        <property type="protein sequence ID" value="AAH47379.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB040974">
        <property type="protein sequence ID" value="BAA96065.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS73224.1"/>
    <dbReference type="RefSeq" id="NP_001278239.1">
        <property type="nucleotide sequence ID" value="NM_001291310.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060931.2">
        <property type="nucleotide sequence ID" value="NM_018461.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q66LE6"/>
    <dbReference type="SMR" id="Q66LE6"/>
    <dbReference type="BioGRID" id="120946">
        <property type="interactions" value="176"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q66LE6">
        <property type="interactions" value="2167"/>
    </dbReference>
    <dbReference type="IntAct" id="Q66LE6">
        <property type="interactions" value="150"/>
    </dbReference>
    <dbReference type="MINT" id="Q66LE6"/>
    <dbReference type="STRING" id="9606.ENSP00000399970"/>
    <dbReference type="iPTMnet" id="Q66LE6"/>
    <dbReference type="PhosphoSitePlus" id="Q66LE6"/>
    <dbReference type="BioMuta" id="PPP2R2D"/>
    <dbReference type="DMDM" id="74736328"/>
    <dbReference type="jPOST" id="Q66LE6"/>
    <dbReference type="MassIVE" id="Q66LE6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000399970"/>
    <dbReference type="PeptideAtlas" id="Q66LE6"/>
    <dbReference type="PRIDE" id="Q66LE6"/>
    <dbReference type="ProteomicsDB" id="65964"/>
    <dbReference type="Pumba" id="Q66LE6"/>
    <dbReference type="Antibodypedia" id="55293">
        <property type="antibodies" value="56 antibodies from 14 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55844"/>
    <dbReference type="Ensembl" id="ENST00000455566.6">
        <property type="protein sequence ID" value="ENSP00000399970.2"/>
        <property type="gene ID" value="ENSG00000175470.21"/>
    </dbReference>
    <dbReference type="GeneID" id="55844"/>
    <dbReference type="KEGG" id="hsa:55844"/>
    <dbReference type="MANE-Select" id="ENST00000455566.6">
        <property type="protein sequence ID" value="ENSP00000399970.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018461.5"/>
        <property type="RefSeq protein sequence ID" value="NP_060931.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc031wxk.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23732"/>
    <dbReference type="ClinPGx" id="PA134899040"/>
    <dbReference type="CTD" id="55844"/>
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    <dbReference type="GeneCards" id="PPP2R2D"/>
    <dbReference type="HGNC" id="HGNC:23732">
        <property type="gene designation" value="PPP2R2D"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000175470">
        <property type="expression patterns" value="Tissue enhanced (pancreas)"/>
    </dbReference>
    <dbReference type="MIM" id="613992">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000175470"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000175470"/>
    <dbReference type="eggNOG" id="KOG1354">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182864"/>
    <dbReference type="HOGENOM" id="CLU_021713_3_3_1"/>
    <dbReference type="InParanoid" id="Q66LE6"/>
    <dbReference type="OMA" id="LSHHDTI"/>
    <dbReference type="OrthoDB" id="6274823at2759"/>
    <dbReference type="PAN-GO" id="Q66LE6">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q66LE6"/>
    <dbReference type="PathwayCommons" id="Q66LE6"/>
    <dbReference type="Reactome" id="R-HSA-2465910">
        <property type="pathway name" value="MASTL Facilitates Mitotic Progression"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q66LE6"/>
    <dbReference type="SIGNOR" id="Q66LE6"/>
    <dbReference type="Agora" id="ENSG00000175470"/>
    <dbReference type="BioGRID-ORCS" id="55844">
        <property type="hits" value="3 hits in 257 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PPP2R2D">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="55844"/>
    <dbReference type="Pharos" id="Q66LE6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q66LE6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q66LE6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000175470">
        <property type="expression patterns" value="Expressed in body of pancreas and 175 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q66LE6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000159">
        <property type="term" value="C:protein phosphatase type 2A complex"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140767">
        <property type="term" value="F:enzyme-substrate adaptor activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019888">
        <property type="term" value="F:protein phosphatase regulator activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0051301">
        <property type="term" value="P:cell division"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010458">
        <property type="term" value="P:exit from mitosis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000278">
        <property type="term" value="P:mitotic cell cycle"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051983">
        <property type="term" value="P:regulation of chromosome segregation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="2.130.10.10:FF:000002">
        <property type="entry name" value="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000009">
        <property type="entry name" value="PP2A_PR55"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018067">
        <property type="entry name" value="PP2A_PR55_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11871">
        <property type="entry name" value="PROTEIN PHOSPHATASE PP2A REGULATORY SUBUNIT B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037309">
        <property type="entry name" value="PP2A_PR55"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00600">
        <property type="entry name" value="PP2APR55"/>
    </dbReference>
    <dbReference type="SMART" id="SM00320">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="7"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01024">
        <property type="entry name" value="PR55_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01025">
        <property type="entry name" value="PR55_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0131">Cell cycle</keyword>
    <keyword id="KW-0132">Cell division</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0498">Mitosis</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000071433" description="Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform">
        <location>
            <begin position="1"/>
            <end position="453"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1">
        <location>
            <begin position="32"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2">
        <location>
            <begin position="97"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3">
        <location>
            <begin position="181"/>
            <end position="219"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4">
        <location>
            <begin position="230"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5">
        <location>
            <begin position="289"/>
            <end position="327"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6">
        <location>
            <begin position="344"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7">
        <location>
            <begin position="420"/>
            <end position="452"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="308"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057127" description="In dbSNP:rs34473884.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF85754." evidence="7" ref="1">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF85754." evidence="7" ref="1">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="311"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF85754." evidence="7" ref="1">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF85754." evidence="7" ref="1">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="449"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P36877"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P56932"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q7ZX64"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="Q925E7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="25816751"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <sequence length="453" mass="52042" checksum="0669CDB80AF4400E" modified="2004-10-11" version="1">MAGAGGGGCPAGGNDFQWCFSQVKGAIDEDVAEADIISTVEFNYSGDLLATGDKGGRVVIFQREQENKSRPHSRGEYNVYSTFQSHEPEFDYLKSLEIEEKINKIRWLPQQNAAHFLLSTNDKTIKLWKISERDKRAEGYNLKDEDGRLRDPFRITALRVPILKPMDLMVEASPRRIFANAHTYHINSISVNSDHETYLSADDLRINLWHLEITDRSFNIVDIKPANMEELTEVITAAEFHPHQCNVFVYSSSKGTIRLCDMRSSALCDRHSKFFEEPEDPSSRSFFSEIISSISDVKFSHSGRYMMTRDYLSVKVWDLNMESRPVETHQVHEYLRSKLCSLYENDCIFDKFECCWNGSDSAIMTGSYNNFFRMFDRDTRRDVTLEASRESSKPRASLKPRKVCTGGKRRKDEISVDSLDFNKKILHTAWHPVDNVIAVAATNNLYIFQDKIN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-04-01" modified="2026-01-28" version="218" xmlns="https://uniprot.org/uniprot">
    <accession>P30154</accession>
    <accession>A8MY67</accession>
    <accession>B0YJ69</accession>
    <accession>B4DGQ6</accession>
    <accession>B4DK91</accession>
    <accession>B4DWW5</accession>
    <accession>F8W8G1</accession>
    <accession>O75620</accession>
    <accession>Q8NHV8</accession>
    <name>2AAB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>PP2A subunit A isoform PR65-beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PP2A subunit A isoform R1-beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">PPP2R1B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Gene" volume="217" first="107" last="116">
            <title>Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23.</title>
            <authorList>
                <person name="Baysal B.E."/>
                <person name="Farr J.E."/>
                <person name="Goss J.R."/>
                <person name="Devlin B."/>
                <person name="Richard C.W. III"/>
            </authorList>
            <dbReference type="PubMed" id="9795170"/>
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    <comment type="function">
        <text>The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 5 6">PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with IPO9. Interacts with SGO1. Interacts with RAF1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-712311">
            <id>P67775</id>
            <label>PPP2CA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-302388">
            <id>P30153</id>
            <label>PPP2R1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-1048931">
            <id>P63151</id>
            <label>PPP2R2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-641666">
            <id>Q15172</id>
            <label>PPP2R5A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-1266156">
            <id>Q13362</id>
            <label>PPP2R5C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-396563">
            <id>Q14738</id>
            <label>PPP2R5D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-968374">
            <id>Q16537</id>
            <label>PPP2R5E</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-1036803">
            <id>P11233</id>
            <label>RALA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-79859">
            <id>O08785</id>
            <label>Clock</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-357094">
            <id>P30154</id>
        </interactant>
        <interactant intactId="EBI-4404185">
            <id>O08722</id>
            <label>Unc5b</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11058011">
            <id>P30154-2</id>
        </interactant>
        <interactant intactId="EBI-12593112">
            <id>O75190-2</id>
            <label>DNAJB6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11058011">
            <id>P30154-2</id>
        </interactant>
        <interactant intactId="EBI-948266">
            <id>O14901</id>
            <label>KLF11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P30154-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P30154-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_036460"/>
        </isoform>
        <isoform>
            <id>P30154-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043379 VSP_036460"/>
        </isoform>
        <isoform>
            <id>P30154-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_045275"/>
        </isoform>
        <isoform>
            <id>P30154-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_046684"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text>Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the phosphatase 2A regulatory subunit A family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAA59983" version="1"/>
        </conflict>
        <text>Contaminating sequence. Sequence of unknown origin in the N-terminal part.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAG59103" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF083439">
        <property type="protein sequence ID" value="AAC63525.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC63525.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC69624.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF163473">
        <property type="protein sequence ID" value="AAG39644.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK294716">
        <property type="protein sequence ID" value="BAG57867.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAG59103.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAG63177.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH27596.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="M65254">
        <property type="protein sequence ID" value="AAA59983.1"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_001177563.2"/>
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        <property type="nucleotide sequence ID" value="NM_002716.4"/>
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        <property type="nucleotide sequence ID" value="NM_181699.3"/>
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        <property type="nucleotide sequence ID" value="NM_181700.2"/>
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    <dbReference type="PDB" id="9MF5">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A=1-601"/>
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    <dbReference type="PDBsum" id="9MF5"/>
    <dbReference type="AlphaFoldDB" id="P30154"/>
    <dbReference type="EMDB" id="EMD-48224"/>
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    <dbReference type="CORUM" id="P30154"/>
    <dbReference type="DIP" id="DIP-36616N"/>
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        <property type="interactions" value="2439"/>
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        <property type="interactions" value="149"/>
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    <dbReference type="MINT" id="P30154"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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        <molecule id="P30154-2"/>
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        <property type="gene ID" value="ENSG00000137713.17"/>
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        <property type="protein sequence ID" value="ENSP00000343317.6"/>
        <property type="gene ID" value="ENSG00000137713.17"/>
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        <molecule id="P30154-5"/>
        <property type="protein sequence ID" value="ENSP00000376775.2"/>
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        <property type="protein sequence ID" value="ENSP00000410671.2"/>
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        <property type="RefSeq protein sequence ID" value="NP_002707.3"/>
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        <property type="gene designation" value="PPP2R1B"/>
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        <property type="type" value="gene"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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            <position position="500"/>
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        <location>
            <position position="504"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022906" description="In a colon adenocarcinoma; dbSNP:rs1318084062." evidence="7">
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        <location>
            <position position="545"/>
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    <feature type="sequence conflict" description="In Ref. 9; AAA59983." evidence="10" ref="9">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="74"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAC63525, 3; AAG39644 and 9; AAA59983." evidence="10" ref="1 3 9">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="178"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAG57867." evidence="10" ref="4">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="211"/>
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    <feature type="sequence conflict" description="In Ref. 9; AAA59983." evidence="10" ref="9">
        <original>Q</original>
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        <location>
            <position position="411"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAG57867." evidence="10" ref="4">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="503"/>
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        <source>
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        <source>
            <dbReference type="PubMed" id="10896920"/>
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    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11996789"/>
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    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12670497"/>
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    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16541025"/>
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        <source>
            <dbReference type="PubMed" id="9765152"/>
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    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="22814378"/>
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    <sequence length="601" mass="66214" checksum="86AB20D7505210B0" modified="2006-10-17" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-08-01" modified="2026-01-28" version="232" xmlns="https://uniprot.org/uniprot">
    <accession>P26439</accession>
    <accession>A2RRA5</accession>
    <accession>Q16010</accession>
    <accession>Q53GD4</accession>
    <accession>Q6AI10</accession>
    <accession>Q6LDB9</accession>
    <accession>Q99890</accession>
    <accession>Q9UD08</accession>
    <name>3BHS2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="25">3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type II</fullName>
            <shortName>3-beta-HSD II</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>3-beta-HSD adrenal and gonadal type</fullName>
        </alternativeName>
        <domain>
            <recommendedName>
                <fullName>3-beta-hydroxy-Delta(5)-steroid dehydrogenase</fullName>
                <ecNumber evidence="12">1.1.1.145</ecNumber>
            </recommendedName>
            <alternativeName>
                <fullName>3-beta-hydroxy-5-ene steroid dehydrogenase</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Progesterone reductase</fullName>
            </alternativeName>
        </domain>
        <domain>
            <recommendedName>
                <fullName>Steroid Delta-isomerase</fullName>
                <ecNumber evidence="26">5.3.3.1</ecNumber>
            </recommendedName>
            <alternativeName>
                <fullName>Delta-5-3-ketosteroid isomerase</fullName>
            </alternativeName>
        </domain>
    </protein>
    <gene>
        <name evidence="27" type="primary">HSD3B2</name>
        <name type="synonym">HSDB3B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="DNA Cell Biol." volume="10" first="701" last="711">
            <title>Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity.</title>
            <authorList>
                <person name="Lachance Y."/>
                <person name="Luu-The V."/>
                <person name="Verreault H."/>
                <person name="Dumont M."/>
                <person name="Rheaume E."/>
                <person name="Leblanc G."/>
                <person name="Labrie F."/>
            </authorList>
            <dbReference type="PubMed" id="1741954"/>
            <dbReference type="DOI" id="10.1089/dna.1991.10.701"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1991" name="Mol. Endocrinol." volume="5" first="1147" last="1157">
            <title>Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads.</title>
            <authorList>
                <person name="Rheaume E."/>
                <person name="Lachance Y."/>
                <person name="Zhao H.-F."/>
                <person name="Breton N."/>
                <person name="Dumont M."/>
                <person name="de Launoit Y."/>
                <person name="Trudel C."/>
                <person name="Luu-The V."/>
                <person name="Simard J."/>
                <person name="Labrie F."/>
            </authorList>
            <dbReference type="PubMed" id="1944309"/>
            <dbReference type="DOI" id="10.1210/mend-5-8-1147"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT GLN-94</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Suzuki Y."/>
                <person name="Sugano S."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Takeda T."/>
                <person name="Sakaki Y."/>
                <person name="Tanaka A."/>
                <person name="Yokoyama S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
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        <scope>VARIANT AH2 LEU-341</scope>
        <scope>CHARACTERIZATION OF VARIANT AH2 LEU-341</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2012" name="Gene" volume="503" first="215" last="221">
            <title>In silico structural, functional and pathogenicity evaluation of a novel mutation: an overview of HSD3B2 gene mutations.</title>
            <authorList>
                <person name="Rabbani B."/>
                <person name="Mahdieh N."/>
                <person name="Haghi Ashtiani M.T."/>
                <person name="Setoodeh A."/>
                <person name="Rabbani A."/>
            </authorList>
            <dbReference type="PubMed" id="22579964"/>
            <dbReference type="DOI" id="10.1016/j.gene.2012.04.080"/>
        </citation>
        <scope>VARIANT AH2 PRO-82</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2015" name="J. Clin. Endocrinol. Metab." volume="100" first="E191" last="E196">
            <title>A novel missense mutation in the HSD3B2 gene, underlying nonsalt-wasting congenital adrenal hyperplasia. new insight into the structure-function relationships of 3beta-hydroxysteroid dehidrogenase type II.</title>
            <authorList>
                <person name="Baquedano M.S."/>
                <person name="Ciaccio M."/>
                <person name="Marino R."/>
                <person name="Perez Garrido N."/>
                <person name="Ramirez P."/>
                <person name="Maceiras M."/>
                <person name="Turjanski A."/>
                <person name="Defelipe L.A."/>
                <person name="Rivarola M.A."/>
                <person name="Belgorosky A."/>
            </authorList>
            <dbReference type="PubMed" id="25322271"/>
            <dbReference type="DOI" id="10.1210/jc.2014-2676"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANT AH2 VAL-250</scope>
        <scope>CHARACTERIZATION OF VARIANT AH2 VAL-250</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <comment type="function">
        <text evidence="8">3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="26">
            <text>a 3beta-hydroxy-Delta(5)-steroid + NAD(+) = a 3-oxo-Delta(5)-steroid + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:24076"/>
            <dbReference type="ChEBI" id="CHEBI:1722"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:47907"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.145"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="26">
            <text>a 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid</text>
            <dbReference type="Rhea" id="RHEA:14709"/>
            <dbReference type="ChEBI" id="CHEBI:47907"/>
            <dbReference type="ChEBI" id="CHEBI:47909"/>
            <dbReference type="EC" id="5.3.3.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>pregnenolone + NAD(+) = pregn-5-ene-3,20-dione + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43924"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16581"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:63837"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:43925"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>pregn-5-ene-3,20-dione = progesterone</text>
            <dbReference type="Rhea" id="RHEA:43928"/>
            <dbReference type="ChEBI" id="CHEBI:17026"/>
            <dbReference type="ChEBI" id="CHEBI:63837"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:43929"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>3beta-hydroxyandrost-5-en-17-one + NAD(+) = androst-5-ene-3,17-dione + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43932"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28689"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:83865"/>
            <dbReference type="EC" id="1.1.1.145"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:43933"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>androst-5-ene-3,17-dione = androst-4-ene-3,17-dione</text>
            <dbReference type="Rhea" id="RHEA:43936"/>
            <dbReference type="ChEBI" id="CHEBI:16422"/>
            <dbReference type="ChEBI" id="CHEBI:83865"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:43937"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="12">1.84 uM for pregnenolone</KM>
            <Vmax evidence="12">0.16 pmol/min/mg enzyme toward pregnenolone</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="12">Lipid metabolism; steroid biosynthesis.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21761225">
            <id>P26439</id>
        </interactant>
        <interactant intactId="EBI-1955541">
            <id>Q53GS7</id>
            <label>GLE1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21761225">
            <id>P26439</id>
        </interactant>
        <interactant intactId="EBI-5235340">
            <id>Q7Z699</id>
            <label>SPRED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12">Endoplasmic reticulum membrane</location>
            <topology evidence="2">Single-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Mitochondrion membrane</location>
            <topology evidence="2">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P26439-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P26439-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_037399 VSP_037400"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in adrenal gland, testis and ovary.</text>
    </comment>
    <comment type="disease" evidence="3 4 5 6 10 11 12 13 14 15 16 17 18 19 20 21 22 23">
        <disease id="DI-00042">
            <name>Adrenal hyperplasia 2</name>
            <acronym>AH2</acronym>
            <description>A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life.</description>
            <dbReference type="MIM" id="201810"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text evidence="7">Mild HSD3B2 deficiency in hyperandrogenic females is associated with characteristic traits of polycystic ovary syndrome, such as insulin resistance and luteinizing hormone hypersecretion.</text>
    </comment>
    <comment type="similarity">
        <text evidence="25">Belongs to the 3-beta-HSD family.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAC60600" version="1"/>
        </conflict>
        <text>The frameshift is caused by a single nucleotide insertion which is found in AH2.</text>
    </comment>
    <dbReference type="EC" id="1.1.1.145" evidence="12"/>
    <dbReference type="EC" id="5.3.3.1" evidence="26"/>
    <dbReference type="EMBL" id="M77144">
        <property type="protein sequence ID" value="AAA36014.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M67466">
        <property type="protein sequence ID" value="AAA36016.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR627415">
        <property type="protein sequence ID" value="CAH10504.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK222997">
        <property type="protein sequence ID" value="BAD96717.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359553">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471122">
        <property type="protein sequence ID" value="EAW56700.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC038419">
        <property type="protein sequence ID" value="AAH38419.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC131488">
        <property type="protein sequence ID" value="AAI31489.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S80140">
        <property type="protein sequence ID" value="AAD14329.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S60309">
        <property type="protein sequence ID" value="AAC60599.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S60310">
        <property type="protein sequence ID" value="AAC60600.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS902.1">
        <molecule id="P26439-1"/>
    </dbReference>
    <dbReference type="PIR" id="A39488">
        <property type="entry name" value="DEHUH2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000189.1">
        <molecule id="P26439-1"/>
        <property type="nucleotide sequence ID" value="NM_000198.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159592.1">
        <molecule id="P26439-1"/>
        <property type="nucleotide sequence ID" value="NM_001166120.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P26439"/>
    <dbReference type="SMR" id="P26439"/>
    <dbReference type="BioGRID" id="109517">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="CORUM" id="P26439"/>
    <dbReference type="FunCoup" id="P26439">
        <property type="interactions" value="96"/>
    </dbReference>
    <dbReference type="IntAct" id="P26439">
        <property type="interactions" value="20"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000445122"/>
    <dbReference type="BindingDB" id="P26439"/>
    <dbReference type="ChEMBL" id="CHEMBL3670"/>
    <dbReference type="DrugBank" id="DB01285">
        <property type="generic name" value="Corticotropin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00603">
        <property type="generic name" value="Medroxyprogesterone acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00717">
        <property type="generic name" value="Norethisterone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09070">
        <property type="generic name" value="Tibolone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01108">
        <property type="generic name" value="Trilostane"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P26439"/>
    <dbReference type="SwissLipids" id="SLP:000001296"/>
    <dbReference type="GlyGen" id="P26439">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P26439"/>
    <dbReference type="PhosphoSitePlus" id="P26439"/>
    <dbReference type="BioMuta" id="HSD3B2"/>
    <dbReference type="DMDM" id="112770"/>
    <dbReference type="jPOST" id="P26439"/>
    <dbReference type="MassIVE" id="P26439"/>
    <dbReference type="PaxDb" id="9606-ENSP00000445122"/>
    <dbReference type="PeptideAtlas" id="P26439"/>
    <dbReference type="ProteomicsDB" id="54346">
        <molecule id="P26439-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="54347">
        <molecule id="P26439-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="33908">
        <property type="antibodies" value="183 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3284"/>
    <dbReference type="Ensembl" id="ENST00000369416.4">
        <molecule id="P26439-1"/>
        <property type="protein sequence ID" value="ENSP00000358424.3"/>
        <property type="gene ID" value="ENSG00000203859.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000543831.5">
        <molecule id="P26439-1"/>
        <property type="protein sequence ID" value="ENSP00000445122.1"/>
        <property type="gene ID" value="ENSG00000203859.11"/>
    </dbReference>
    <dbReference type="GeneID" id="3284"/>
    <dbReference type="KEGG" id="hsa:3284"/>
    <dbReference type="MANE-Select" id="ENST00000369416.4">
        <property type="protein sequence ID" value="ENSP00000358424.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000198.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000189.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001eht.4">
        <molecule id="P26439-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5218"/>
    <dbReference type="ClinPGx" id="PA29487"/>
    <dbReference type="CTD" id="3284"/>
    <dbReference type="DisGeNET" id="3284"/>
    <dbReference type="GeneCards" id="HSD3B2"/>
    <dbReference type="HGNC" id="HGNC:5218">
        <property type="gene designation" value="HSD3B2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000203859">
        <property type="expression patterns" value="Tissue enriched (adrenal)"/>
    </dbReference>
    <dbReference type="MalaCards" id="HSD3B2"/>
    <dbReference type="MIM" id="201810">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="613890">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000203859"/>
    <dbReference type="Orphanet" id="90791">
        <property type="disease" value="Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000203859"/>
    <dbReference type="eggNOG" id="KOG1430">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161374"/>
    <dbReference type="HOGENOM" id="CLU_007383_6_3_1"/>
    <dbReference type="InParanoid" id="P26439"/>
    <dbReference type="OMA" id="GGKFYFV"/>
    <dbReference type="OrthoDB" id="1925334at2759"/>
    <dbReference type="PAN-GO" id="P26439">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P26439"/>
    <dbReference type="BioCyc" id="MetaCyc:HS10943-MONOMER"/>
    <dbReference type="BRENDA" id="1.1.1.145">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="5.3.3.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P26439"/>
    <dbReference type="Reactome" id="R-HSA-193048">
        <property type="pathway name" value="Androgen biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-193993">
        <property type="pathway name" value="Mineralocorticoid biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-194002">
        <property type="pathway name" value="Glucocorticoid biosynthesis"/>
    </dbReference>
    <dbReference type="SignaLink" id="P26439"/>
    <dbReference type="SIGNOR" id="P26439"/>
    <dbReference type="UniPathway" id="UPA00062"/>
    <dbReference type="Agora" id="ENSG00000203859"/>
    <dbReference type="BioGRID-ORCS" id="3284">
        <property type="hits" value="8 hits in 1117 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="HSD3B2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HSD3B2"/>
    <dbReference type="GenomeRNAi" id="3284"/>
    <dbReference type="Pharos" id="P26439">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P26439"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="P26439">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000203859">
        <property type="expression patterns" value="Expressed in right adrenal gland and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P26439">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045171">
        <property type="term" value="C:intercellular bridge"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015630">
        <property type="term" value="C:microtubule cytoskeleton"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005758">
        <property type="term" value="C:mitochondrial intermembrane space"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030868">
        <property type="term" value="C:smooth endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003854">
        <property type="term" value="F:3-beta-hydroxy-Delta5-steroid dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016616">
        <property type="term" value="F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004769">
        <property type="term" value="F:steroid Delta-isomerase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006702">
        <property type="term" value="P:androgen biosynthetic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008207">
        <property type="term" value="P:C21-steroid hormone metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006694">
        <property type="term" value="P:steroid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd09811">
        <property type="entry name" value="3b-HSD_HSDB1_like_SDR_e"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.720:FF:000220">
        <property type="entry name" value="3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.720">
        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002225">
        <property type="entry name" value="3Beta_OHSteriod_DH/Estase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050177">
        <property type="entry name" value="Lipid_A_modif_metabolic_enz"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43245">
        <property type="entry name" value="BIFUNCTIONAL POLYMYXIN RESISTANCE PROTEIN ARNA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43245:SF51">
        <property type="entry name" value="SHORT CHAIN DEHYDROGENASE_REDUCTASE FAMILY 42E, MEMBER 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01073">
        <property type="entry name" value="3Beta_HSD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51735">
        <property type="entry name" value="NAD(P)-binding Rossmann-fold domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0954">Congenital adrenal hyperplasia</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0413">Isomerase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0511">Multifunctional enzyme</keyword>
    <keyword id="KW-0520">NAD</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0755">Steroidogenesis</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000087775" description="3 beta-hydroxysteroid dehydrogenase/Delta 5--&gt;4-isomerase type 2">
        <location>
            <begin position="1"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="287"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="158"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_037399" description="In isoform 2." evidence="24">
        <original>GTQLLLEACVQASVPVFIYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLYTCALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNP</original>
        <variation>ELQNKIKLTVLEGDILDEPFLKRACQDVSVVIHTACIIDVFGVTHRQSIMNVNVKGRVAWGGDKARWGNEDQKEGQEGKRSLSIEHLLCSGPSDFADHYQLGELKAAIFSFIDEKTRTEQ</variation>
        <location>
            <begin position="103"/>
            <end position="222"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037400" description="In isoform 2." evidence="24">
        <location>
            <begin position="223"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010517" description="In AH2; activity abolished; dbSNP:rs28934880." evidence="3 5">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010518" description="In AH2; nonsalt-wasting form; dbSNP:rs28934880." evidence="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010519" description="In AH2; activity abolished." evidence="3 17">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048099" description="In dbSNP:rs4986954.">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070028" description="In AH2." evidence="11">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010520" description="In AH2; dbSNP:rs757033996." evidence="3 21">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014818" description="In dbSNP:rs6211." evidence="9">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010521" description="In AH2; nonsalt-wasting form; dbSNP:rs1388517943." evidence="3 13">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010522" description="In AH2; activity abolished." evidence="3 16">
        <original>L</original>
        <variation>W</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010523" description="In AH2; nonsalt-wasting form; dbSNP:rs587628683." evidence="3 4 18">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000006" description="In AH2; activity abolished; dbSNP:rs80358219." evidence="3 6 22">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010524" description="In AH2; nonsalt-wasting form; dbSNP:rs779418168." evidence="3">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010525" description="In AH2; late onset; almost normal activity; dbSNP:rs35486059." evidence="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010526" description="In AH2; nonsalt-wasting form; dbSNP:rs762479018." evidence="3 19">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="173"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010527" description="In AH2; activity abolished." evidence="3 16">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000007" description="In AH2." evidence="3 14">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="205"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010528" description="In AH2; late onset; partial loss of activity; dbSNP:rs759422374." evidence="3">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010529" description="In AH2; late onset; partial loss of activity." evidence="3">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010530" description="In AH2; nonsalt-wasting form; activity abolished." evidence="3">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010531" description="In AH2; activity abolished; dbSNP:rs765547422." evidence="3 4">
        <original>P</original>
        <variation>Q</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015411" description="In AH2; dbSNP:rs80358220." evidence="6">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010532" description="In AH2; activity abolished.">
        <location>
            <begin position="231"/>
            <end position="238"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010533" description="In AH2; mild; 100% of activity; dbSNP:rs35887327." evidence="3 23">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000008" description="In AH2; loss of 88% of activity." evidence="3 22">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083841" description="In AH2; nonsalt-wasting form; loss of 75% of enzymatic activity for the conversion of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione; no effect on endoplasmic reticulum location." evidence="12">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="250"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000009" description="In AH2; activity abolished; dbSNP:rs1399005702." evidence="3 22">
        <original>Y</original>
        <variation>N</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000010" description="In AH2; activity abolished; dbSNP:rs1411029929." evidence="3 20">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010534" description="In AH2; activity abolished; dbSNP:rs80358221." evidence="3 4">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000011" description="In AH2; activity abolished." evidence="3 15">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010535" description="In AH2; nonsalt-wasting form; activity abolished." evidence="3">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_065665" description="In AH2; strongly reduced activity; dbSNP:rs121964897." evidence="10">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="341"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AAD14329." evidence="25" ref="8">
        <original>RT</original>
        <variation>KI</variation>
        <location>
            <begin position="52"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AAD14329." evidence="25" ref="8">
        <original>HRE</original>
        <variation>RRQ</variation>
        <location>
            <begin position="92"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD96717." evidence="25" ref="4">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="232"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10599696"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10651755"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10843183"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12050213"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="14764797"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="1741954"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18252794"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="22579964"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="25322271"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="7608265"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="7633426"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="7633460"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="7833923"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="7893703"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="7962268"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="8060486"/>
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    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="8126127"/>
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    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="8185809"/>
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    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="8316254"/>
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    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="9719627"/>
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    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="17974005"/>
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    </evidence>
    <evidence type="ECO:0000305" key="25"/>
    <evidence type="ECO:0000305" key="26">
        <source>
            <dbReference type="PubMed" id="25322271"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="27">
        <source>
            <dbReference type="HGNC" id="HGNC:5218"/>
        </source>
    </evidence>
    <sequence length="372" mass="42052" checksum="8E0D933488988451" modified="2007-01-23" version="2">MGWSCLVTGAGGLLGQRIVRLLVEEKELKEIRALDKAFRPELREEFSKLQNRTKLTVLEGDILDEPFLKRACQDVSVVIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVFIYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPTPYPYSKKLAEKAVLAANGWNLKNGDTLYTCALRPTYIYGEGGPFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRALRDPKKAPSVRGQFYYISDDTPHQSYDNLNYILSKEFGLRLDSRWSLPLTLMYWIGFLLEVVSFLLSPIYSYQPPFNRHTVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSLVDRHKETLKSKTQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>P31937</accession>
    <accession>Q546Z2</accession>
    <accession>Q9UDN3</accession>
    <name>3HIDH_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>3-hydroxyisobutyrate dehydrogenase, mitochondrial</fullName>
            <shortName>HIBADH</shortName>
            <ecNumber>1.1.1.31</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">HIBADH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2002-07" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and identification of human gene 1 transactivated by hepatitis C virus NS5A protein.</title>
            <authorList>
                <person name="Liu Y."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
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                <person name="Sugiyama T."/>
                <person name="Irie R."/>
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                <person name="Kimura K."/>
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                <person name="Sekine M."/>
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                <person name="Fujimori K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11427100">
            <id>P31937</id>
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        <interactant intactId="EBI-1564650">
            <id>Q14108</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-1058865">
            <id>O75396</id>
            <label>SEC22B</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        <interactant intactId="EBI-4402330">
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    <comment type="interaction">
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        <interactant intactId="EBI-11957067">
            <id>Q6UX34</id>
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    <comment type="interaction">
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            <id>P31937</id>
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        <interactant intactId="EBI-355727">
            <id>P02786</id>
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    <comment type="interaction">
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            <id>P31937</id>
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        <interactant intactId="EBI-13082040">
            <id>Q9BZW4</id>
            <label>TM6SF2</label>
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    <comment type="interaction">
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            <id>P31937</id>
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        <interactant intactId="EBI-8638294">
            <id>Q9NUH8</id>
            <label>TMEM14B</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P31937</id>
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        <interactant intactId="EBI-347385">
            <id>Q9H0R3</id>
            <label>TMEM222</label>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11427100">
            <id>P31937</id>
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        <interactant intactId="EBI-2852148">
            <id>Q9H2L4</id>
            <label>TMEM60</label>
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    <comment type="interaction">
        <interactant intactId="EBI-11427100">
            <id>P31937</id>
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        <interactant intactId="EBI-2548832">
            <id>Q8N661</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P31937</id>
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        <interactant intactId="EBI-2819725">
            <id>Q9Y5Z9</id>
            <label>UBIAD1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-11427100">
            <id>P31937</id>
        </interactant>
        <interactant intactId="EBI-520113">
            <id>P63027</id>
            <label>VAMP2</label>
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    <comment type="interaction">
        <interactant intactId="EBI-11427100">
            <id>P31937</id>
        </interactant>
        <interactant intactId="EBI-10191195">
            <id>O95183</id>
            <label>VAMP5</label>
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    <comment type="interaction">
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            <id>P31937</id>
        </interactant>
        <interactant intactId="EBI-718439">
            <id>O95159</id>
            <label>ZFPL1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Detected in skin fibroblasts.</text>
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    <comment type="similarity">
        <text evidence="6">Belongs to the HIBADH-related family. 3-hydroxyisobutyrate dehydrogenase subfamily.</text>
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    <dbReference type="KEGG" id="hsa:11112"/>
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        <property type="type" value="gene"/>
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    </dbReference>
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        <property type="pathway name" value="Branched-chain amino acid catabolism"/>
    </dbReference>
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    <dbReference type="UniPathway" id="UPA00362"/>
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        <property type="hits" value="16 hits in 1159 CRISPR screens"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 7"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in kidney epithelium and 190 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P31937">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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        <property type="term" value="C:mitochondrion"/>
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        <property type="project" value="FlyBase"/>
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        <property type="term" value="F:3-hydroxyisobutyrate dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="F:NAD binding"/>
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        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0006574">
        <property type="term" value="P:L-valine catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="entry name" value="N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase, domain 2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
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        <property type="entry name" value="HIBADH"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="3-HYDROXYISOBUTYRATE DEHYDROGENASE, MITOCHONDRIAL"/>
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    </dbReference>
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        <property type="entry name" value="3-HYDROXYISOBUTYRATE DEHYDROGENASE-RELATED"/>
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        <property type="entry name" value="NAD_binding_11"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NAD_binding_2"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="6-phosphogluconate dehydrogenase C-terminal domain-like"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="3_HYDROXYISOBUT_DH"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0520">NAD</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="4">
        <location>
            <begin position="1"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000007158" description="3-hydroxyisobutyrate dehydrogenase, mitochondrial">
        <location>
            <begin position="37"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="active site" evidence="1">
        <location>
            <position position="209"/>
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    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="40"/>
            <end position="68"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="103"/>
            <end position="104"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="108"/>
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        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="134"/>
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        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="284"/>
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        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="145"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="238"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="238"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="297"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="42"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="51"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
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                <person name="Brenner S.E."/>
            </authorList>
            <dbReference type="PubMed" id="14759258"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-2-r8"/>
        </citation>
        <scope>SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S)</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278 AND SER-427</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-278 AND SER-416</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="submission" date="2005-11" db="PDB data bank">
            <title>Solution structure of the SH2 domain of human SH3BP2 protein.</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 444-558</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2001" name="Nat. Genet." volume="28" first="125" last="126">
            <title>Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism.</title>
            <authorList>
                <person name="Ueki Y."/>
                <person name="Tiziani V."/>
                <person name="Santanna C."/>
                <person name="Fukai N."/>
                <person name="Maulik C."/>
                <person name="Garfinkle J."/>
                <person name="Ninomiya C."/>
                <person name="doAmaral C."/>
                <person name="Peters H."/>
                <person name="Habal M."/>
                <person name="Rhee-Morris L."/>
                <person name="Doss J.B."/>
                <person name="Kreiborg S."/>
                <person name="Olsen B.R."/>
                <person name="Reichenberger E."/>
            </authorList>
            <dbReference type="PubMed" id="11381256"/>
            <dbReference type="DOI" id="10.1038/88832"/>
        </citation>
        <scope>VARIANTS CRBM GLN-415; PRO-415; ARG-418; HIS-418; LEU-418; ARG-420 AND GLU-420</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2003" name="Am. J. Med. Genet. A" volume="121" first="37" last="40">
            <title>Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism.</title>
            <authorList>
                <person name="Lo B."/>
                <person name="Faiyaz-Ul-Haque M."/>
                <person name="Kennedy S."/>
                <person name="Aviv R."/>
                <person name="Tsui L.-C."/>
                <person name="Teebi A.S."/>
            </authorList>
            <dbReference type="PubMed" id="12900899"/>
            <dbReference type="DOI" id="10.1002/ajmg.a.20226"/>
        </citation>
        <scope>VARIANT CRBM ARG-420</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2003" name="Cleft Palate Craniofac. J." volume="40" first="632" last="638">
            <title>A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in a case of nonfamilial cherubism.</title>
            <authorList>
                <person name="Imai Y."/>
                <person name="Kanno K."/>
                <person name="Moriya T."/>
                <person name="Kayano S."/>
                <person name="Seino H."/>
                <person name="Matsubara Y."/>
                <person name="Yamada A."/>
            </authorList>
            <dbReference type="PubMed" id="14577811"/>
            <dbReference type="DOI" id="10.1597/1545-1569_2003_040_0632_ammits_2.0.co_2"/>
        </citation>
        <scope>VARIANT CRBM ARG-418</scope>
    </reference>
    <comment type="function">
        <text>Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-751783">
            <id>Q9UJU6</id>
            <label>DBNL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-1379503">
            <id>P10721</id>
            <label>KIT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-346595">
            <id>Q96B97</id>
            <label>SH3KBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-4398527">
            <id>Q9H2K2</id>
            <label>TNKS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-625518">
            <id>P15498</id>
            <label>VAV1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-297549">
            <id>P52735</id>
            <label>VAV2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727062">
            <id>P78314</id>
        </interactant>
        <interactant intactId="EBI-359854">
            <id>P27348</id>
            <label>YWHAQ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12304031">
            <id>P78314-3</id>
        </interactant>
        <interactant intactId="EBI-12748199">
            <id>Q14247-3</id>
            <label>CTTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12304031">
            <id>P78314-3</id>
        </interactant>
        <interactant intactId="EBI-12192777">
            <id>Q9UJU6-2</id>
            <label>DBNL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12304031">
            <id>P78314-3</id>
        </interactant>
        <interactant intactId="EBI-750369">
            <id>P14317</id>
            <label>HCLS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12304031">
            <id>P78314-3</id>
        </interactant>
        <interactant intactId="EBI-741792">
            <id>O00160</id>
            <label>MYO1F</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P78314-1</id>
            <name>1</name>
            <name>Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P78314-2</id>
            <name>2</name>
            <name>Short</name>
            <sequence type="described" ref="VSP_004085 VSP_004086"/>
        </isoform>
        <isoform>
            <id>P78314-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043636"/>
        </isoform>
        <isoform>
            <id>P78314-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_055046"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9">Expressed in a variety of tissues including lung, liver, skeletal muscle, kidney and pancreas.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated. Phosphorylation at Tyr-448 may stimulate the activity of the LYN kinase (By similarity).</text>
    </comment>
    <comment type="disease" evidence="6 7 8">
        <disease id="DI-00296">
            <name>Cherubism</name>
            <acronym>CRBM</acronym>
            <description>An autosomal dominant syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.</description>
            <dbReference type="MIM" id="118400"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="12">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <dbReference type="EMBL" id="AF000936">
        <property type="protein sequence ID" value="AAB59973.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="U56386">
        <property type="protein sequence ID" value="AAB72034.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AB000462">
        <property type="protein sequence ID" value="BAA19119.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AB000463">
        <property type="protein sequence ID" value="BAA19120.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK299996">
        <property type="protein sequence ID" value="BAG61816.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK312286">
        <property type="protein sequence ID" value="BAG35213.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL121750">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82509.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82510.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82511.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82512.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC022996">
        <property type="protein sequence ID" value="AAH22996.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS33944.1">
        <molecule id="P78314-1"/>
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    <dbReference type="CCDS" id="CCDS54715.1">
        <molecule id="P78314-3"/>
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    <dbReference type="CCDS" id="CCDS54716.1">
        <molecule id="P78314-4"/>
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    <dbReference type="RefSeq" id="NP_001116153.1">
        <molecule id="P78314-1"/>
        <property type="nucleotide sequence ID" value="NM_001122681.2"/>
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    <dbReference type="RefSeq" id="NP_001139327.1">
        <molecule id="P78314-3"/>
        <property type="nucleotide sequence ID" value="NM_001145855.2"/>
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    <dbReference type="RefSeq" id="NP_001139328.1">
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        <property type="nucleotide sequence ID" value="NM_001145856.2"/>
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    <dbReference type="RefSeq" id="NP_003014.3">
        <molecule id="P78314-1"/>
        <property type="nucleotide sequence ID" value="NM_003023.4"/>
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    <dbReference type="PDB" id="2CR4">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=446-558"/>
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    <dbReference type="PDB" id="3TWR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.55 A"/>
        <property type="chains" value="E/F/G/H=410-425"/>
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    <dbReference type="PDBsum" id="2CR4"/>
    <dbReference type="PDBsum" id="3TWR"/>
    <dbReference type="AlphaFoldDB" id="P78314"/>
    <dbReference type="SMR" id="P78314"/>
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        <property type="interactions" value="38"/>
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    <dbReference type="FunCoup" id="P78314">
        <property type="interactions" value="419"/>
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    <dbReference type="IntAct" id="P78314">
        <property type="interactions" value="27"/>
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    <dbReference type="MINT" id="P78314"/>
    <dbReference type="STRING" id="9606.ENSP00000424846"/>
    <dbReference type="GlyGen" id="P78314">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
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    <dbReference type="iPTMnet" id="P78314"/>
    <dbReference type="PhosphoSitePlus" id="P78314"/>
    <dbReference type="BioMuta" id="SH3BP2"/>
    <dbReference type="DMDM" id="3023207"/>
    <dbReference type="jPOST" id="P78314"/>
    <dbReference type="MassIVE" id="P78314"/>
    <dbReference type="PaxDb" id="9606-ENSP00000422168"/>
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    <dbReference type="ProteomicsDB" id="12870"/>
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        <molecule id="P78314-3"/>
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    <dbReference type="Pumba" id="P78314"/>
    <dbReference type="Antibodypedia" id="8898">
        <property type="antibodies" value="201 antibodies from 30 providers"/>
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    <dbReference type="DNASU" id="6452"/>
    <dbReference type="Ensembl" id="ENST00000435136.8">
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        <property type="protein sequence ID" value="ENSP00000403231.3"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000502260.6">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000425537.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000503219.7">
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        <property type="protein sequence ID" value="ENSP00000422796.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000503393.8">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000422168.3"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000504294.6">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000423275.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000508385.6">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000424917.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000511747.6">
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        <property type="protein sequence ID" value="ENSP00000424846.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000512014.6">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000424105.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000513020.6">
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        <property type="protein sequence ID" value="ENSP00000424072.1"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="Ensembl" id="ENST00000513095.6">
        <molecule id="P78314-1"/>
        <property type="protein sequence ID" value="ENSP00000423823.2"/>
        <property type="gene ID" value="ENSG00000087266.19"/>
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    <dbReference type="GeneID" id="6452"/>
    <dbReference type="KEGG" id="hsa:6452"/>
    <dbReference type="MANE-Select" id="ENST00000503393.8">
        <property type="protein sequence ID" value="ENSP00000422168.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001122681.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001116153.1"/>
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    <dbReference type="UCSC" id="uc003gfi.5">
        <molecule id="P78314-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:10825"/>
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    <dbReference type="CTD" id="6452"/>
    <dbReference type="DisGeNET" id="6452"/>
    <dbReference type="GeneCards" id="SH3BP2"/>
    <dbReference type="GeneReviews" id="SH3BP2"/>
    <dbReference type="HGNC" id="HGNC:10825">
        <property type="gene designation" value="SH3BP2"/>
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    <dbReference type="HPA" id="ENSG00000087266">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="SH3BP2"/>
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        <property type="type" value="phenotype"/>
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    <dbReference type="MIM" id="602104">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000087266"/>
    <dbReference type="Orphanet" id="184">
        <property type="disease" value="Cherubism"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000087266"/>
    <dbReference type="eggNOG" id="ENOG502RF2Z">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00390000002216"/>
    <dbReference type="HOGENOM" id="CLU_040124_0_0_1"/>
    <dbReference type="InParanoid" id="P78314"/>
    <dbReference type="OrthoDB" id="10254483at2759"/>
    <dbReference type="PAN-GO" id="P78314">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P78314"/>
    <dbReference type="PathwayCommons" id="P78314"/>
    <dbReference type="SignaLink" id="P78314"/>
    <dbReference type="SIGNOR" id="P78314"/>
    <dbReference type="Agora" id="ENSG00000087266"/>
    <dbReference type="BioGRID-ORCS" id="6452">
        <property type="hits" value="19 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SH3BP2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P78314"/>
    <dbReference type="GenomeRNAi" id="6452"/>
    <dbReference type="Pharos" id="P78314">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P78314"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="P78314">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000087266">
        <property type="expression patterns" value="Expressed in granulocyte and 137 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P78314">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001784">
        <property type="term" value="F:phosphotyrosine residue binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="CAFA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017124">
        <property type="term" value="F:SH3 domain binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd13308">
        <property type="entry name" value="PH_3BP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd10359">
        <property type="entry name" value="SH2_SH3BP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.505.10:FF:000043">
        <property type="entry name" value="SH3 domain binding protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000147">
        <property type="entry name" value="SH3 domain-binding protein 2 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.505.10">
        <property type="entry name" value="SH2 domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000980">
        <property type="entry name" value="SH2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036860">
        <property type="entry name" value="SH2_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035848">
        <property type="entry name" value="SH3BP2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035847">
        <property type="entry name" value="SH3BP2_SH2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15126:SF4">
        <property type="entry name" value="SH3 DOMAIN-BINDING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15126">
        <property type="entry name" value="SH3-BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00017">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00252">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55550">
        <property type="entry name" value="SH2 domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50001">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0727">SH2 domain</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <feature type="chain" id="PRO_0000064365" description="SH3 domain-binding protein 2">
        <location>
            <begin position="1"/>
            <end position="561"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="3">
        <location>
            <begin position="26"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="domain" description="SH2" evidence="4">
        <location>
            <begin position="457"/>
            <end position="555"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="160"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="333"/>
            <end position="451"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding">
        <location>
            <begin position="201"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="5">
        <location>
            <begin position="170"/>
            <end position="188"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="202"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="233"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="252"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="342"/>
            <end position="354"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by SYK" evidence="2">
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by SYK" evidence="2">
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13 14 15">
        <location>
            <position position="278"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="416"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="14">
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by SYK" evidence="2">
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043636" description="In isoform 3." evidence="10">
        <original>M</original>
        <variation>MASLGPRTPAPSRSRGRRAMCWVSTISFM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055046" description="In isoform 4." evidence="12">
        <original>M</original>
        <variation>MAGSGPRPRSWGRREAGARDEAAAAGGRGPGPCRCSQGRRAWIAPGKPAMPAAWTPFM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_004085" description="In isoform 2." evidence="10 11">
        <original>VMRAAEETTSNNVFPFK</original>
        <variation>QPRPQPAQALSQTEAGP</variation>
        <location>
            <begin position="81"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_004086" description="In isoform 2." evidence="10 11">
        <location>
            <begin position="98"/>
            <end position="561"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013257" description="In CRBM; dbSNP:rs121909149." evidence="6">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013258" description="In CRBM; dbSNP:rs121909149." evidence="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013259" description="In CRBM; dbSNP:rs121909146." evidence="6">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013260" description="In CRBM; dbSNP:rs121909146." evidence="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013261" description="In CRBM; dbSNP:rs121909146." evidence="6 8">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013262" description="In CRBM; dbSNP:rs28938171." evidence="6">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="420"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013263" description="In CRBM; dbSNP:rs28938170." evidence="6 7">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="420"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAB59973." evidence="12" ref="3">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAB59973." evidence="12" ref="3">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAB59973." evidence="12" ref="3">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAB59973." evidence="12" ref="3">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="turn" evidence="16">
        <location>
            <begin position="455"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="464"/>
            <end position="474"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="485"/>
            <end position="489"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="496"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="turn" evidence="16">
        <location>
            <begin position="503"/>
            <end position="505"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="506"/>
            <end position="508"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="514"/>
            <end position="516"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="519"/>
            <end position="525"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="527"/>
            <end position="530"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="531"/>
            <end position="538"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="544"/>
            <end position="548"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="553"/>
            <end position="556"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q06649"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00191"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="11381256"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="12900899"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="14577811"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="9734812"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="9734812"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="2CR4"/>
        </source>
    </evidence>
    <sequence length="561" mass="62244" checksum="69E6846A4F6D8F15" modified="1998-07-15" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-24" modified="2026-01-28" version="186" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H2F3</accession>
    <accession>Q96M28</accession>
    <accession>Q9BSN9</accession>
    <name>3BHS7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">3 beta-hydroxysteroid dehydrogenase type 7</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>3 beta-hydroxysteroid dehydrogenase type VII</fullName>
            <shortName>3-beta-HSD VII</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>3-beta-hydroxy-Delta(5)-C27 steroid oxidoreductase</fullName>
            <shortName>C(27) 3-beta-HSD</shortName>
            <ecNumber>1.1.1.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Cholest-5-ene-3-beta,7-alpha-diol 3-beta-dehydrogenase</fullName>
            <ecNumber evidence="4">1.1.1.181</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9" type="primary">HSD3B7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="J. Clin. Invest." volume="106" first="1175" last="1184">
            <title>The bile acid synthetic gene 3beta-hydroxy-delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis.</title>
            <authorList>
                <person name="Schwarz M."/>
                <person name="Wright A.C."/>
                <person name="Davis D.L."/>
                <person name="Nazer H."/>
                <person name="Bjorkhem I."/>
                <person name="Russell D.W."/>
            </authorList>
            <dbReference type="PubMed" id="11067870"/>
            <dbReference type="DOI" id="10.1172/jci10902"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>INVOLVEMENT IN CBAS1</scope>
        <scope>VARIANT ALA-250</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Stomach</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <authorList>
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                <person name="Sutton G."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="6">
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            <title>Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.</title>
            <authorList>
                <person name="Cheng J.B."/>
                <person name="Jacquemin E."/>
                <person name="Gerhardt M."/>
                <person name="Nazer H."/>
                <person name="Cresteil D."/>
                <person name="Heubi J.E."/>
                <person name="Setchell K.D."/>
                <person name="Russell D.W."/>
            </authorList>
            <dbReference type="PubMed" id="12679481"/>
            <dbReference type="DOI" id="10.1210/jc.2002-021580"/>
        </citation>
        <scope>VARIANTS CBAS1 SER-19 AND LYS-147</scope>
        <scope>CHARACTERIZATION OF VARIANT CBAS1 LYS-147</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several different C(19/21) steroids as substrates. Involved in bile acid synthesis (PubMed:11067870). Plays a key role in cell positioning and movement in lymphoid tissues by mediating degradation of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC): 7-alpha,25-OHC acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>7alpha-hydroxycholesterol + NAD(+) = 7alpha-hydroxycholest-4-en-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11896"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17500"/>
            <dbReference type="ChEBI" id="CHEBI:17899"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.181"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:11897"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>7alpha,25-dihydroxycholesterol + NAD(+) = 7alpha,25-dihydroxy-4-cholesten-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:47156"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:37623"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:81013"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47157"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>(25R)-cholest-5-en-3beta,7alpha,26-triol + NAD(+) = (25R)-7alpha,26-dihydroxycholest-4-en-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:47180"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:76592"/>
            <dbReference type="ChEBI" id="CHEBI:87476"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>(24S)-7alpha-dihydroxycholesterol + NAD(+) = (24S)-7alpha,24-dihydroxycholest-4-en-3-one + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:47200"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:37640"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:63838"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47201"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="4">Lipid metabolism; steroid biosynthesis.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10173507">
            <id>Q6UY14-3</id>
            <label>ADAMTSL4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-712648">
            <id>O95994</id>
            <label>AGR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
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        <interactant intactId="EBI-12224467">
            <id>Q9NYG5-2</id>
            <label>ANAPC11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-743771">
            <id>Q92624</id>
            <label>APPBP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-948603">
            <id>Q03989</id>
            <label>ARID5A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-18394052">
            <id>Q8WXK4-2</id>
            <label>ASB12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
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        <interactant intactId="EBI-8648738">
            <id>Q8WVV5</id>
            <label>BTN2A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
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        <interactant intactId="EBI-7317823">
            <id>Q6P5X5</id>
            <label>C22orf39</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-372265">
            <id>P21964</id>
            <label>COMT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10192698">
            <id>Q02930-3</id>
            <label>CREB5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-3867333">
            <id>A8MQ03</id>
            <label>CYSRT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-536772">
            <id>Q12805</id>
            <label>EFEMP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-743414">
            <id>O95967</id>
            <label>EFEMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-949532">
            <id>Q9UHF1</id>
            <label>EGFL7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-18535450">
            <id>Q9GZR5</id>
            <label>ELOVL4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-718638">
            <id>Q92979</id>
            <label>EMG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-947973">
            <id>P98095</id>
            <label>FBLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-374781">
            <id>O76003</id>
            <label>GLRX3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-740785">
            <id>P49639</id>
            <label>HOXA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-18053395">
            <id>Q7Z5P4</id>
            <label>HSD17B13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-396343">
            <id>O00629</id>
            <label>KPNA4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10981970">
            <id>Q5T749</id>
            <label>KPRP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10171697">
            <id>Q6A162</id>
            <label>KRT40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-9996498">
            <id>O43790</id>
            <label>KRT86</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-11749135">
            <id>Q8IUG1</id>
            <label>KRTAP1-3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10172290">
            <id>P60409</id>
            <label>KRTAP10-7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918847">
            <id>Q9H2F3</id>
        </interactant>
        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
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        <organismsDiffer>false</organismsDiffer>
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        <interactant intactId="EBI-3918154">
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            <label>RGS17</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>O43597</id>
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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            <id>Q8N720</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location>Endoplasmic reticulum membrane</location>
            <topology>Multi-pass membrane protein</topology>
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        <event type="alternative splicing"/>
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    <comment type="disease" evidence="4 5">
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        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
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        <text evidence="7">Belongs to the 3-beta-HSD family.</text>
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    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000087791" description="3 beta-hydroxysteroid dehydrogenase type 7">
        <location>
            <begin position="1"/>
            <end position="369"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="289"/>
            <end position="309"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="311"/>
            <end position="331"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="163"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_042658" description="In isoform 2." evidence="6">
        <original>VRGGLPLVTCALRPTGIYGEGHQIMRDFYRQGLRLGGWLFRAIPASVEHGRVYVGNVAWMHVLAARELEQRATLMGGQVYFCYDGSPYRSYEDFNMEFLGPCGLRLVGARPLLPYWLLVFLAALNALLQWLLRPLVLYAPLLNPYTLAVANTTFTVSTDKAQRHFGYEPLFSWEDSRTRTILWVQAATGSAQ</original>
        <variation>AMLPGCTCWQPGSWSSGQP</variation>
        <location>
            <begin position="178"/>
            <end position="369"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054775" description="In CBAS1." evidence="5">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054776" description="In CBAS1; loss of activity; dbSNP:rs104894518." evidence="5">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031040" description="In dbSNP:rs9938550." evidence="4">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="250"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048100" description="In dbSNP:rs34212827.">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG37824." evidence="7" ref="1">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG37824." evidence="7" ref="1">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="329"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9EQC1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11067870"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12679481"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="11067870"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:18324"/>
        </source>
    </evidence>
    <sequence length="369" mass="41016" checksum="7254A5DAAFAC23E7" modified="2004-05-24" version="2">MADSAQAQKLVYLVTGGCGFLGEHVVRMLLQREPRLGELRVFDQHLGPWLEELKTGPVRVTAIQGDVTQAHEVAAAVAGAHVVIHTAGLVDVFGRASPKTIHEVNVQGTRNVIEACVQTGTRFLVYTSSMEVVGPNTKGHPFYRGNEDTPYEAVHRHPYPCSKALAEWLVLEANGRKVRGGLPLVTCALRPTGIYGEGHQIMRDFYRQGLRLGGWLFRAIPASVEHGRVYVGNVAWMHVLAARELEQRATLMGGQVYFCYDGSPYRSYEDFNMEFLGPCGLRLVGARPLLPYWLLVFLAALNALLQWLLRPLVLYAPLLNPYTLAVANTTFTVSTDKAQRHFGYEPLFSWEDSRTRTILWVQAATGSAQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-05" modified="2026-01-28" version="156" xmlns="https://uniprot.org/uniprot">
    <accession>Q7L8J4</accession>
    <accession>B4DQ94</accession>
    <accession>Q96FI5</accession>
    <accession>Q9BQH8</accession>
    <accession>Q9C0E3</accession>
    <name>3BP5L_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>SH3 domain-binding protein 5-like</fullName>
            <shortName>SH3BP-5-like</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">SH3BP5L</name>
        <name type="synonym">KIAA1720</name>
        <name type="ORF">UNQ2766/PRO7133</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
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                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
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                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Colon</tissue>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="8">
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            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
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                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-343; SER-350 AND SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
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                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358 AND SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-13; SER-30; SER-343; SER-350 AND SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30 AND SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2018" name="Nat. Commun." volume="9" first="3772" last="3772">
            <title>Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.</title>
            <authorList>
                <person name="Jenkins M.L."/>
                <person name="Margaria J.P."/>
                <person name="Stariha J.T.B."/>
                <person name="Hoffmann R.M."/>
                <person name="McPhail J.A."/>
                <person name="Hamelin D.J."/>
                <person name="Boulanger M.J."/>
                <person name="Hirsch E."/>
                <person name="Burke J.E."/>
            </authorList>
            <dbReference type="PubMed" id="30217979"/>
            <dbReference type="DOI" id="10.1038/s41467-018-06196-z"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Functions as a guanine nucleotide exchange factor (GEF) for RAB11A.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
        </interactant>
        <interactant intactId="EBI-6624398">
            <id>P06307</id>
            <label>CCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-11752486">
            <id>Q86XR8-3</id>
            <label>CEP57</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-359031">
            <id>Q15006</id>
            <label>EMC2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-7225287">
            <id>Q96MY7</id>
            <label>FAM161B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
        </interactant>
        <interactant intactId="EBI-5280197">
            <id>O75400-2</id>
            <label>PRPF40A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
        </interactant>
        <interactant intactId="EBI-722234">
            <id>Q15907</id>
            <label>RAB11B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
        </interactant>
        <interactant intactId="EBI-1056404">
            <id>P61106</id>
            <label>RAB14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
        </interactant>
        <interactant intactId="EBI-1050500">
            <id>P57735</id>
            <label>RAB25</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-3921347">
            <id>P51687</id>
            <label>SUOX</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-359815">
            <id>P31946</id>
            <label>YWHAB</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-747389">
            <id>Q7L8J4</id>
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        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="alternative products">
        <event type="alternative splicing"/>
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            <id>Q7L8J4-1</id>
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            <id>Q7L8J4-2</id>
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            <sequence type="described" ref="VSP_056075"/>
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    <comment type="similarity">
        <text evidence="6">Belongs to the SH3BP5 family.</text>
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        <property type="protein sequence ID" value="AAQ88818.1"/>
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        <property type="protein sequence ID" value="BAG60856.1"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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    <dbReference type="EMBL" id="CH471257">
        <property type="protein sequence ID" value="EAW57534.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC010871">
        <property type="protein sequence ID" value="AAH10871.1"/>
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        <property type="protein sequence ID" value="AAH17254.1"/>
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    <dbReference type="CCDS" id="CCDS31126.1">
        <molecule id="Q7L8J4-1"/>
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    <dbReference type="RefSeq" id="NP_001309391.1">
        <property type="nucleotide sequence ID" value="NM_001322462.1"/>
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    <dbReference type="RefSeq" id="NP_085148.1">
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        <property type="nucleotide sequence ID" value="NM_030645.3"/>
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        <property type="interactions" value="35"/>
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        <property type="interactions" value="1820"/>
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        <property type="interactions" value="32"/>
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    <dbReference type="ProteomicsDB" id="68837">
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    <dbReference type="Pumba" id="Q7L8J4"/>
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    <dbReference type="DNASU" id="80851"/>
    <dbReference type="Ensembl" id="ENST00000366472.6">
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        <property type="protein sequence ID" value="ENSP00000355428.5"/>
        <property type="gene ID" value="ENSG00000175137.12"/>
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    <dbReference type="GeneID" id="80851"/>
    <dbReference type="KEGG" id="hsa:80851"/>
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        <property type="protein sequence ID" value="ENSP00000355428.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_030645.3"/>
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    <dbReference type="UCSC" id="uc001iew.2">
        <molecule id="Q7L8J4-1"/>
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    <dbReference type="AGR" id="HGNC:29360"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000175137"/>
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        <property type="hits" value="19 hits in 1151 CRISPR screens"/>
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        <property type="development level" value="Tdark"/>
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        <property type="component" value="Chromosome 1"/>
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    <dbReference type="ExpressionAtlas" id="Q7L8J4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
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        <property type="term" value="F:guanyl-nucleotide exchange factor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="F:protein kinase inhibitor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0035556">
        <property type="term" value="P:intracellular signal transduction"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="InterPro" id="IPR007940">
        <property type="entry name" value="SH3BP5"/>
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    <dbReference type="PANTHER" id="PTHR19423">
        <property type="entry name" value="SH3 DOMAIN-BINDING PROTEIN 5"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR19423:SF8">
        <property type="entry name" value="SH3 DOMAIN-BINDING PROTEIN 5-LIKE"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF05276">
        <property type="entry name" value="SH3BP5"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0344">Guanine-nucleotide releasing factor</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000317508" description="SH3 domain-binding protein 5-like">
        <location>
            <begin position="1"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="273"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="362"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="59"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="169"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="18"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="3">
        <location>
            <begin position="297"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="317"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="384"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="10">
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 11">
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 10">
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 10">
        <location>
            <position position="350"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="9">
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 8 9 10 11">
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056075" description="In isoform 2." evidence="5">
        <original>MAELRQVPGGRETPQGELRPEVVEDEVPRSPVAEEPGGGGSSSSEAKLSPREEEELDPRIQ</original>
        <variation>MYQVPDRQESFWQSPYLLSFPECLTSFPW</variation>
        <location>
            <begin position="1"/>
            <end position="61"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q99LH9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="30217979"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="393" mass="43499" checksum="3693431765F90FDC" modified="2004-07-05" version="1">MAELRQVPGGRETPQGELRPEVVEDEVPRSPVAEEPGGGGSSSSEAKLSPREEEELDPRIQEELEHLNQASEEINQVELQLDEARTTYRRILQESARKLNTQGSHLGSCIEKARPYYEARRLAKEAQQETQKAALRYERAVSMHNAAREMVFVAEQGVMADKNRLDPTWQEMLNHATCKVNEAEEERLRGEREHQRVTRLCQQAEARVQALQKTLRRAIGKSRPYFELKAQFSQILEEHKAKVTELEQQVAQAKTRYSVALRNLEQISEQIHARRRGGLPPHPLGPRRSSPVGAEAGPEDMEDGDSGIEGAEGAGLEEGSSLGPGPAPDTDTLSLLSLRTVASDLQKCDSVEHLRGLSDHVSLDGQELGTRSGGRRGSDGGARGGRHQRSVSL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>P46952</accession>
    <accession>A6NE56</accession>
    <accession>B4DIN2</accession>
    <accession>Q53QZ7</accession>
    <accession>Q8N6N9</accession>
    <name>3HAO_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">3-hydroxyanthranilate 3,4-dioxygenase</fullName>
            <ecNumber evidence="1 4">1.13.11.6</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">3-hydroxyanthranilate oxygenase</fullName>
            <shortName evidence="1">3-HAO</shortName>
            <shortName evidence="9">h3HAO</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">3-hydroxyanthranilic acid dioxygenase</fullName>
            <shortName evidence="1">HAD</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="1 12" type="primary">HAAO</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="J. Biol. Chem." volume="269" first="13792" last="13797">
            <title>Molecular cloning and functional expression of human 3-hydroxyanthranilic-acid dioxygenase.</title>
            <authorList>
                <person name="Malherbe P."/>
                <person name="Kohler C."/>
                <person name="da Prada M."/>
                <person name="Lang G."/>
                <person name="Kiefer V."/>
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            </authorList>
            <dbReference type="PubMed" id="7514594"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(17)36717-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>COFACTOR</scope>
        <scope>VARIANT VAL-37</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT VAL-37</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2004-07" db="EMBL/GenBank/DDBJ databases">
            <title>Full-length cDNA libraries and normalization.</title>
            <authorList>
                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
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                <person name="Ovcharenko I."/>
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            <dbReference type="PubMed" id="15815621"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT VAL-37</scope>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
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    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2017" name="N. Engl. J. Med." volume="377" first="544" last="552">
            <title>NAD deficiency, congenital malformations, and niacin supplementation.</title>
            <authorList>
                <person name="Shi H."/>
                <person name="Enriquez A."/>
                <person name="Rapadas M."/>
                <person name="Martin E.M.M.A."/>
                <person name="Wang R."/>
                <person name="Moreau J."/>
                <person name="Lim C.K."/>
                <person name="Szot J.O."/>
                <person name="Ip E."/>
                <person name="Hughes J.N."/>
                <person name="Sugimoto K."/>
                <person name="Humphreys D.T."/>
                <person name="McInerney-Leo A.M."/>
                <person name="Leo P.J."/>
                <person name="Maghzal G.J."/>
                <person name="Halliday J."/>
                <person name="Smith J."/>
                <person name="Colley A."/>
                <person name="Mark P.R."/>
                <person name="Collins F."/>
                <person name="Sillence D.O."/>
                <person name="Winlaw D.S."/>
                <person name="Ho J.W.K."/>
                <person name="Guillemin G.J."/>
                <person name="Brown M.A."/>
                <person name="Kikuchi K."/>
                <person name="Thomas P.Q."/>
                <person name="Stocker R."/>
                <person name="Giannoulatou E."/>
                <person name="Chapman G."/>
                <person name="Duncan E.L."/>
                <person name="Sparrow D.B."/>
                <person name="Dunwoodie S.L."/>
            </authorList>
            <dbReference type="PubMed" id="28792876"/>
            <dbReference type="DOI" id="10.1056/nejmoa1616361"/>
        </citation>
        <scope>INVOLVEMENT IN VCRL1</scope>
        <scope>FUNCTION</scope>
        <scope>PATHWAY</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>VARIANTS VCRL1 162-ASP--GLY-286 DEL AND 186-TRP--GLY-286 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANTS VCRL1 162-ASP--GLY-286 DEL AND 186-TRP--GLY-286 DEL</scope>
    </reference>
    <reference key="10">
        <citation type="submission" date="2007-08" db="PDB data bank">
            <title>Crystal structure of human 3-hydroxyanthranilate 3,4-dioxygenase.</title>
            <authorList>
                <consortium name="Center for eukaryotic structural genomics (CESG)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH NICKEL IONS</scope>
    </reference>
    <reference evidence="13 14" key="11">
        <citation type="journal article" date="2017" name="Acta Crystallogr. D" volume="73" first="340" last="348">
            <title>Crystal structures of human 3-hydroxyanthranilate 3,4-dioxygenase with native and non-native metals bound in the active site.</title>
            <authorList>
                <person name="Pidugu L.S."/>
                <person name="Neu H."/>
                <person name="Wong T.L."/>
                <person name="Pozharski E."/>
                <person name="Molloy J.L."/>
                <person name="Michel S.L."/>
                <person name="Toth E.A."/>
            </authorList>
            <dbReference type="PubMed" id="28375145"/>
            <dbReference type="DOI" id="10.1107/s2059798317002029"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH IRON</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 4">Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1 3 4">
            <text>3-hydroxyanthranilate + O2 = (2Z,4Z)-2-amino-3-carboxymuconate 6-semialdehyde</text>
            <dbReference type="Rhea" id="RHEA:17953"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:36559"/>
            <dbReference type="ChEBI" id="CHEBI:77612"/>
            <dbReference type="EC" id="1.13.11.6"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1 2 4">
            <name>Fe(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29033"/>
        </cofactor>
    </comment>
    <comment type="pathway">
        <text evidence="1 3">Cofactor biosynthesis; NAD(+) biosynthesis; quinolinate from L-kynurenine: step 3/3.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 5">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743215">
            <id>P46952</id>
        </interactant>
        <interactant intactId="EBI-10209663">
            <id>Q8IVA8</id>
            <label>GAD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743215">
            <id>P46952</id>
        </interactant>
        <interactant intactId="EBI-743184">
            <id>Q99259</id>
            <label>GAD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743215">
            <id>P46952</id>
        </interactant>
        <interactant intactId="EBI-752420">
            <id>Q9NUX5</id>
            <label>POT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Cytoplasm</location>
            <location evidence="11">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P46952-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P46952-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_036239"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="3">
        <disease id="DI-05094">
            <name>Vertebral, cardiac, renal, and limb defects syndrome 1</name>
            <acronym>VCRL1</acronym>
            <description>An autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the 3-HAO family.</text>
    </comment>
    <dbReference type="EC" id="1.13.11.6" evidence="1 4"/>
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        <property type="protein sequence ID" value="CAA82618.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CR457063">
        <property type="protein sequence ID" value="CAG33344.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CR624693">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK295693">
        <property type="protein sequence ID" value="BAG58544.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC098824">
        <property type="protein sequence ID" value="AAY14701.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAX00309.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC029510">
        <property type="protein sequence ID" value="AAH29510.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="A54070"/>
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        <property type="nucleotide sequence ID" value="NM_012205.3"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A=2-286"/>
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    <dbReference type="PDB" id="5TK5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.88 A"/>
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    <dbReference type="PDB" id="5TKQ">
        <property type="method" value="X-ray"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Jelly Rolls"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0223">Dioxygenase</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0408">Iron</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
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            <begin position="1"/>
            <end position="286"/>
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            <begin position="1"/>
            <end position="160"/>
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        <location>
            <begin position="161"/>
            <end position="177"/>
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            <begin position="178"/>
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    <feature type="binding site" evidence="1">
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            <position position="43"/>
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        <ligand>
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    <feature type="binding site" evidence="1 2 13">
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            <position position="47"/>
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        <ligand>
            <name>Fe cation</name>
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    <feature type="binding site" evidence="1 2 13">
        <location>
            <position position="53"/>
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        <ligand>
            <name>Fe cation</name>
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</entry>
<entry dataset="Swiss-Prot" created="2002-01-23" modified="2026-01-28" version="193" xmlns="https://uniprot.org/uniprot">
    <accession>O60239</accession>
    <accession>B3KQW6</accession>
    <accession>Q5JWV9</accession>
    <name>3BP5_HUMAN</name>
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        <recommendedName>
            <fullName>SH3 domain-binding protein 5</fullName>
            <shortName>SH3BP-5</shortName>
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            <fullName>SH3 domain-binding protein that preferentially associates with BTK</fullName>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1998" name="Biochem. Biophys. Res. Commun." volume="245" first="337" last="343">
            <title>Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (Btk).</title>
            <authorList>
                <person name="Matsushita M."/>
                <person name="Yamadori T."/>
                <person name="Kato S."/>
                <person name="Takemoto Y."/>
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                <person name="Baba Y."/>
                <person name="Hashimoto S."/>
                <person name="Sekine S."/>
                <person name="Arai S."/>
                <person name="Kunikata T."/>
                <person name="Kurimoto M."/>
                <person name="Kishimoto T."/>
                <person name="Tsukada S."/>
            </authorList>
            <dbReference type="PubMed" id="9571151"/>
            <dbReference type="DOI" id="10.1006/bbrc.1998.8420"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 10-455 (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH BTK</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1999" name="Proc. Natl. Acad. Sci. U.S.A." volume="96" first="6341" last="6346">
            <title>Bruton's tyrosine kinase activity is negatively regulated by Sab, the Btk-SH3 domain-binding protein.</title>
            <authorList>
                <person name="Yamadori T."/>
                <person name="Baba Y."/>
                <person name="Mastushita M."/>
                <person name="Hashimoto S."/>
                <person name="Kurosaki M."/>
                <person name="Kurosaki T."/>
                <person name="Kishimoto T."/>
                <person name="Tsukada S."/>
            </authorList>
            <dbReference type="PubMed" id="10339589"/>
            <dbReference type="DOI" id="10.1073/pnas.96.11.6341"/>
        </citation>
        <scope>INTERACTION WITH BTK</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="Biochem. J." volume="367" first="577" last="585">
            <title>A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab (SH3BP5), associates with mitochondria.</title>
            <authorList>
                <person name="Wiltshire C."/>
                <person name="Matsushita M."/>
                <person name="Tsukada S."/>
                <person name="Gillespie D.A."/>
                <person name="May G.H."/>
            </authorList>
            <dbReference type="PubMed" id="12167088"/>
            <dbReference type="DOI" id="10.1042/bj20020553"/>
        </citation>
        <scope>INTERACTION WITH MAPK8; MAPK9 AND MAPK10</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF LEU-347; LEU-349; LEU-434 AND LEU-436</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="Nat. Biotechnol." volume="24" first="1285" last="1292">
            <title>A probability-based approach for high-throughput protein phosphorylation analysis and site localization.</title>
            <authorList>
                <person name="Beausoleil S.A."/>
                <person name="Villen J."/>
                <person name="Gerber S.A."/>
                <person name="Rush J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="16964243"/>
            <dbReference type="DOI" id="10.1038/nbt1240"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
            <authorList>
                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2015" name="Dev. Cell" volume="35" first="211" last="221">
            <title>REI-1 is a guanine nucleotide exchange factor regulating RAB-11 localization and function in C. elegans embryos.</title>
            <authorList>
                <person name="Sakaguchi A."/>
                <person name="Sato M."/>
                <person name="Sato K."/>
                <person name="Gengyo-Ando K."/>
                <person name="Yorimitsu T."/>
                <person name="Nakai J."/>
                <person name="Hara T."/>
                <person name="Sato K."/>
                <person name="Sato K."/>
            </authorList>
            <dbReference type="PubMed" id="26506309"/>
            <dbReference type="DOI" id="10.1016/j.devcel.2015.09.013"/>
        </citation>
        <scope>INTERACTION WITH RAB11A</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="11" key="15">
        <citation type="journal article" date="2018" name="Nat. Commun." volume="9" first="3772" last="3772">
            <title>Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.</title>
            <authorList>
                <person name="Jenkins M.L."/>
                <person name="Margaria J.P."/>
                <person name="Stariha J.T.B."/>
                <person name="Hoffmann R.M."/>
                <person name="McPhail J.A."/>
                <person name="Hamelin D.J."/>
                <person name="Boulanger M.J."/>
                <person name="Hirsch E."/>
                <person name="Burke J.E."/>
            </authorList>
            <dbReference type="PubMed" id="30217979"/>
            <dbReference type="DOI" id="10.1038/s41467-018-06196-z"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-265 IN COMPLEX WITH RAB11A</scope>
        <scope>FUNCTION</scope>
        <scope>COILED COIL</scope>
        <scope>DOMAIN</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF 52-LEU--GLN-54 AND 250-LEU-GLU-251</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6 7 8">Functions as a guanine nucleotide exchange factor (GEF) with specificity for RAB11A and RAB25 (PubMed:26506309, PubMed:30217979). Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 5 6 7 8">Interacts with BTK (PubMed:10339589, PubMed:9571151). Interacts with all isoforms of MAPK8, MAPK9, MAPK10 and MAPK12 (PubMed:12167088). Interacts with GDP-bound and nucleotide-free forms of RAB11A (PubMed:26506309, PubMed:30217979).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-624860">
            <id>O60239</id>
        </interactant>
        <interactant intactId="EBI-624835">
            <id>Q06187</id>
            <label>BTK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-624860">
            <id>O60239</id>
        </interactant>
        <interactant intactId="EBI-9091197">
            <id>Q8IY31-3</id>
            <label>IFT20</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-624860">
            <id>O60239</id>
        </interactant>
        <interactant intactId="EBI-3911716">
            <id>Q9ULW6</id>
            <label>NAP1L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cytoplasmic vesicle membrane</location>
            <topology evidence="7">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Mitochondrion</location>
        </subcellularLocation>
        <text evidence="7">Colocalizes with RAB11A on cytoplasmic vesicle membranes.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O60239-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O60239-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_042854"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Highly expressed in testis and ovaries. It is also expressed in a variety of tissues including spleen, lymph node, thymus, bone marrow, fetal liver, colon, small intestine and prostate.</text>
    </comment>
    <comment type="domain">
        <text evidence="7">The N-terminal half of the protein mediates interaction with RAB11A and functions as a guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the SH3BP5 family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA25922" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK090524">
        <property type="protein sequence ID" value="BAG52178.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC087590">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL117422">
        <property type="protein sequence ID" value="CAI46220.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471055">
        <property type="protein sequence ID" value="EAW64225.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010123">
        <property type="protein sequence ID" value="AAH10123.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB005047">
        <property type="protein sequence ID" value="BAA25922.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS2625.2">
        <molecule id="O60239-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43055.1">
        <molecule id="O60239-2"/>
    </dbReference>
    <dbReference type="PIR" id="JE0086">
        <property type="entry name" value="JE0086"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001018009.2">
        <molecule id="O60239-2"/>
        <property type="nucleotide sequence ID" value="NM_001018009.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004835.2">
        <molecule id="O60239-1"/>
        <property type="nucleotide sequence ID" value="NM_004844.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047305200.1">
        <molecule id="O60239-2"/>
        <property type="nucleotide sequence ID" value="XM_047449244.1"/>
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    <dbReference type="RefSeq" id="XP_047305201.1">
        <molecule id="O60239-2"/>
        <property type="nucleotide sequence ID" value="XM_047449245.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204429.1">
        <molecule id="O60239-2"/>
        <property type="nucleotide sequence ID" value="XM_054348454.1"/>
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    <dbReference type="RefSeq" id="XP_054204430.1">
        <molecule id="O60239-2"/>
        <property type="nucleotide sequence ID" value="XM_054348455.1"/>
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    <dbReference type="PDB" id="4H3B">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.08 A"/>
        <property type="chains" value="B/D=341-350"/>
    </dbReference>
    <dbReference type="PDB" id="6DJL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="B/C/D/E=1-265"/>
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    <dbReference type="PDB" id="6IXE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.35 A"/>
        <property type="chains" value="A=41-266"/>
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    <dbReference type="PDB" id="6IXF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B=41-266"/>
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    <dbReference type="PDB" id="6IXG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.80 A"/>
        <property type="chains" value="A/B=41-266"/>
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    <dbReference type="PDB" id="6IXV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.80 A"/>
        <property type="chains" value="A/B/C/D=10-276"/>
    </dbReference>
    <dbReference type="PDBsum" id="4H3B"/>
    <dbReference type="PDBsum" id="6DJL"/>
    <dbReference type="PDBsum" id="6IXE"/>
    <dbReference type="PDBsum" id="6IXF"/>
    <dbReference type="PDBsum" id="6IXG"/>
    <dbReference type="PDBsum" id="6IXV"/>
    <dbReference type="AlphaFoldDB" id="O60239"/>
    <dbReference type="SMR" id="O60239"/>
    <dbReference type="BioGRID" id="114853">
        <property type="interactions" value="29"/>
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    <dbReference type="ELM" id="O60239"/>
    <dbReference type="FunCoup" id="O60239">
        <property type="interactions" value="1493"/>
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    <dbReference type="IntAct" id="O60239">
        <property type="interactions" value="23"/>
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    <dbReference type="STRING" id="9606.ENSP00000373301"/>
    <dbReference type="GlyGen" id="O60239">
        <property type="glycosylation" value="1 site"/>
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    <dbReference type="iPTMnet" id="O60239"/>
    <dbReference type="PhosphoSitePlus" id="O60239"/>
    <dbReference type="BioMuta" id="SH3BP5"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000373301"/>
    <dbReference type="PeptideAtlas" id="O60239"/>
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        <molecule id="O60239-1"/>
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    <dbReference type="ProteomicsDB" id="49269">
        <molecule id="O60239-2"/>
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    <dbReference type="Pumba" id="O60239"/>
    <dbReference type="TopDownProteomics" id="O60239-1">
        <molecule id="O60239-1"/>
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    <dbReference type="Antibodypedia" id="26718">
        <property type="antibodies" value="162 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="9467"/>
    <dbReference type="Ensembl" id="ENST00000383791.8">
        <molecule id="O60239-1"/>
        <property type="protein sequence ID" value="ENSP00000373301.3"/>
        <property type="gene ID" value="ENSG00000131370.17"/>
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    <dbReference type="Ensembl" id="ENST00000408919.7">
        <molecule id="O60239-2"/>
        <property type="protein sequence ID" value="ENSP00000386231.3"/>
        <property type="gene ID" value="ENSG00000131370.17"/>
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    <dbReference type="Ensembl" id="ENST00000426925.5">
        <molecule id="O60239-2"/>
        <property type="protein sequence ID" value="ENSP00000388553.1"/>
        <property type="gene ID" value="ENSG00000131370.17"/>
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    <dbReference type="GeneID" id="9467"/>
    <dbReference type="KEGG" id="hsa:9467"/>
    <dbReference type="MANE-Select" id="ENST00000383791.8">
        <property type="protein sequence ID" value="ENSP00000373301.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004844.5"/>
        <property type="RefSeq protein sequence ID" value="NP_004835.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003bzp.3">
        <molecule id="O60239-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:10827"/>
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    <dbReference type="GeneCards" id="SH3BP5"/>
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        <property type="gene designation" value="SH3BP5"/>
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    <dbReference type="HPA" id="ENSG00000131370">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="SH3BP5"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000131370"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000018500"/>
    <dbReference type="HOGENOM" id="CLU_048895_1_0_1"/>
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    <dbReference type="OMA" id="ECFDDEP"/>
    <dbReference type="OrthoDB" id="446789at2759"/>
    <dbReference type="PAN-GO" id="O60239">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O60239"/>
    <dbReference type="PathwayCommons" id="O60239"/>
    <dbReference type="SignaLink" id="O60239"/>
    <dbReference type="SIGNOR" id="O60239"/>
    <dbReference type="Agora" id="ENSG00000131370"/>
    <dbReference type="BioGRID-ORCS" id="9467">
        <property type="hits" value="16 hits in 1159 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SH3BP5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="O60239"/>
    <dbReference type="GeneWiki" id="SH3BP5"/>
    <dbReference type="GenomeRNAi" id="9467"/>
    <dbReference type="Pharos" id="O60239">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O60239"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="O60239">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000131370">
        <property type="expression patterns" value="Expressed in adrenal tissue and 213 other cell types or tissues"/>
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        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0030659">
        <property type="term" value="C:cytoplasmic vesicle membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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    <dbReference type="GO" id="GO:0016604">
        <property type="term" value="C:nuclear body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005085">
        <property type="term" value="F:guanyl-nucleotide exchange factor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0004860">
        <property type="term" value="F:protein kinase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
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        <property type="term" value="F:SH3 domain binding"/>
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        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0035556">
        <property type="term" value="P:intracellular signal transduction"/>
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        <property type="project" value="MGI"/>
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        <property type="project" value="ProtInc"/>
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        <property type="entry name" value="SH3BP5"/>
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        <property type="entry name" value="SH3 DOMAIN-BINDING PROTEIN 5"/>
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        <property type="entry name" value="SH3BP5"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
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            <begin position="1"/>
            <end position="455"/>
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            <begin position="1"/>
            <end position="63"/>
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    <feature type="region of interest" description="Sufficient for interaction with RAB11A and for guanine nucleotide exchange activity" evidence="7">
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            <begin position="31"/>
            <end position="265"/>
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    <feature type="region of interest" description="Disordered" evidence="3">
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            <begin position="259"/>
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    <feature type="region of interest" description="Disordered" evidence="3">
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            <begin position="306"/>
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    <feature type="region of interest" description="Disordered" evidence="3">
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            <begin position="369"/>
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    <feature type="coiled-coil region" evidence="7">
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            <begin position="44"/>
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    <feature type="coiled-coil region" evidence="7">
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            <begin position="97"/>
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    <feature type="coiled-coil region" evidence="7">
        <location>
            <begin position="154"/>
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            <begin position="211"/>
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            <begin position="1"/>
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            <begin position="22"/>
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
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            <begin position="42"/>
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            <begin position="306"/>
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            <begin position="320"/>
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            <begin position="380"/>
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            <begin position="403"/>
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            <position position="351"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="1">
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            <position position="418"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="12 13">
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            <position position="421"/>
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        <location>
            <begin position="1"/>
            <end position="157"/>
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    <feature type="mutagenesis site" description="Loss of guanine nucleotide exchange factor activity." evidence="7">
        <original>LNQ</original>
        <variation>AAA</variation>
        <location>
            <begin position="52"/>
            <end position="54"/>
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    <feature type="mutagenesis site" description="Loss of guanine nucleotide exchange factor activity." evidence="7">
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        <variation>AK</variation>
        <location>
            <begin position="250"/>
            <end position="251"/>
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    <feature type="mutagenesis site" description="Loss of phosphorylation and binding by phospho-JNK; when associated with A-349." evidence="5">
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        <variation>A</variation>
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            <position position="347"/>
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    <feature type="mutagenesis site" description="Loss of phosphorylation and binding by phospho-JNK; when associated with A-347." evidence="5">
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        <variation>A</variation>
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            <position position="434"/>
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    <feature type="mutagenesis site" description="No change of phosphorylation or binding by phospho-JNK; when associated with A-434." evidence="5">
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        <variation>A</variation>
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            <position position="436"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="44"/>
            <end position="91"/>
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    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="93"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="96"/>
            <end position="98"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="99"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="147"/>
            <end position="151"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="153"/>
            <end position="200"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="202"/>
            <end position="260"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q91Y80"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9Z131"/>
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    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10339589"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12167088"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="26506309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="30217979"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="9571151"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PDB" id="6DJL"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="16964243"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="6DJL"/>
        </source>
    </evidence>
    <sequence length="455" mass="50425" checksum="5C8CA4861D66346B" modified="2007-01-23" version="2">MDAALKRSRSEEPAEILPPARDEEEEEEEGMEQGLEEEEEVDPRIQGELEKLNQSTDDINRRETELEDARQKFRSVLVEATVKLDELVKKIGKAVEDSKPYWEARRVARQAQLEAQKATQDFQRATEVLRAAKETISLAEQRLLEDDKRQFDSAWQEMLNHATQRVMEAEQTKTRSELVHKETAARYNAAMGRMRQLEKKLKRAINKSKPYFELKAKYYVQLEQLKKTVDDLQAKLTLAKGEYKMALKNLEMISDEIHERRRSSAMGPRGCGVGAEGSSTSVEDLPGSKPEPDAISVASEAFEDDSCSNFVSEDDSETQSVSSFSSGPTSPSEMPDQFPAVVRPGSLDLPSPVSLSEFGMMFPVLGPRSECSGASSPECEVERGDRAEGAENKTSDKANNNRGLSSSSGSGGSSKSQSSTSPEGQALENRMKQLSLQCSKGRDGIIADIKMVQIG</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="241" xmlns="https://uniprot.org/uniprot">
    <accession>P29372</accession>
    <accession>G5E9E2</accession>
    <accession>Q13770</accession>
    <accession>Q15275</accession>
    <accession>Q15961</accession>
    <accession>Q5J9I4</accession>
    <accession>Q96BZ6</accession>
    <accession>Q96S33</accession>
    <accession>Q9NNX5</accession>
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            <fullName>DNA-3-methyladenine glycosylase</fullName>
            <ecNumber>3.2.2.21</ecNumber>
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        <alternativeName>
            <fullName>3-alkyladenine DNA glycosylase</fullName>
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            <fullName>3-methyladenine DNA glycosidase</fullName>
        </alternativeName>
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            <fullName>ADPG</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>N-methylpurine-DNA glycosylase</fullName>
        </alternativeName>
    </protein>
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        <name type="primary">MPG</name>
        <name type="synonym">AAG</name>
        <name type="synonym">ANPG</name>
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        <name type="scientific">Homo sapiens</name>
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        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Proc. Natl. Acad. Sci. U.S.A." volume="88" first="9127" last="9131">
            <title>Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16.</title>
            <authorList>
                <person name="Samson L."/>
                <person name="Derfler B."/>
                <person name="Boosalis M."/>
                <person name="Call K."/>
            </authorList>
            <dbReference type="PubMed" id="1924375"/>
            <dbReference type="DOI" id="10.1073/pnas.88.20.9127"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="Proc. Natl. Acad. Sci. U.S.A." volume="90" first="3437" last="3441">
            <title>Structure of the human 3-methyladenine DNA glycosylase gene and localization close to the 16p telomere.</title>
            <authorList>
                <person name="Vickers M.A."/>
                <person name="Vyas P."/>
                <person name="Harris P.C."/>
                <person name="Simmons D.L."/>
                <person name="Higgs D.R."/>
            </authorList>
            <dbReference type="PubMed" id="8475094"/>
            <dbReference type="DOI" id="10.1073/pnas.90.8.3437"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-02" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of a human cell proliferation gene 11.</title>
            <authorList>
                <person name="Kim J.W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS GLN-22; HIS-71; VAL-258 AND SER-298</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="Hum. Mol. Genet." volume="10" first="339" last="352">
            <title>Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16.</title>
            <authorList>
                <person name="Daniels R.J."/>
                <person name="Peden J.F."/>
                <person name="Lloyd C."/>
                <person name="Horsley S.W."/>
                <person name="Clark K."/>
                <person name="Tufarelli C."/>
                <person name="Kearney L."/>
                <person name="Buckle V.J."/>
                <person name="Doggett N.A."/>
                <person name="Flint J."/>
                <person name="Higgs D.R."/>
            </authorList>
            <dbReference type="PubMed" id="11157797"/>
            <dbReference type="DOI" id="10.1093/hmg/10.4.339"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Nature" volume="432" first="988" last="994">
            <title>The sequence and analysis of duplication-rich human chromosome 16.</title>
            <authorList>
                <person name="Martin J."/>
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                <person name="Prabhakar S."/>
                <person name="She X."/>
                <person name="Xie G."/>
                <person name="Hellsten U."/>
                <person name="Chan Y.M."/>
                <person name="Altherr M."/>
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                <person name="Aerts A."/>
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                <person name="Black S."/>
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                <person name="Branscomb E."/>
                <person name="Brown N.C."/>
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                <person name="Caoile C."/>
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                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Jewett P.B."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Krawczyk M.-C."/>
                <person name="Leyba T."/>
                <person name="Longmire J.L."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Lowry S."/>
                <person name="Ludeman T."/>
                <person name="Manohar C.F."/>
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                <person name="Munk A.C."/>
                <person name="Nandkeshwar R.D."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Parson-Quintana B."/>
                <person name="Ramirez L."/>
                <person name="Rash S."/>
                <person name="Retterer J."/>
                <person name="Ricke D.O."/>
                <person name="Robinson D.L."/>
                <person name="Rodriguez A."/>
                <person name="Salamov A."/>
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                <person name="Scott D."/>
                <person name="Shough T."/>
                <person name="Stallings R.L."/>
                <person name="Stalvey M."/>
                <person name="Sutherland R.D."/>
                <person name="Tapia R."/>
                <person name="Tesmer J.G."/>
                <person name="Thayer N."/>
                <person name="Thompson L.S."/>
                <person name="Tice H."/>
                <person name="Torney D.C."/>
                <person name="Tran-Gyamfi M."/>
                <person name="Tsai M."/>
                <person name="Ulanovsky L.E."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="White P.S."/>
                <person name="Williams A.L."/>
                <person name="Wills P.L."/>
                <person name="Wu J.-R."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="DeJong P."/>
                <person name="Bruce D."/>
                <person name="Doggett N.A."/>
                <person name="Deaven L."/>
                <person name="Schmutz J."/>
                <person name="Grimwood J."/>
                <person name="Richardson P."/>
                <person name="Rokhsar D.S."/>
                <person name="Eichler E.E."/>
                <person name="Gilna P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
                <person name="Pennacchio L.A."/>
            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
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                <person name="Halldorsson B.V."/>
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                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
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                <person name="Zhong F."/>
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                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1991" name="J. Biol. Chem." volume="266" first="15710" last="15715">
            <title>Cloning and expression in Escherichia coli of a human cDNA encoding the DNA repair protein N-methylpurine-DNA glycosylase.</title>
            <authorList>
                <person name="Chakravarti D."/>
                <person name="Ibeanu G.C."/>
                <person name="Tano K."/>
                <person name="Mitra S."/>
            </authorList>
            <dbReference type="PubMed" id="1874728"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)98467-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 28-298 (ISOFORMS 1/2)</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1991" name="Biochem. Biophys. Res. Commun." volume="176" first="1170" last="1177">
            <title>Human cDNA expressing a functional DNA glycosylase excising 3-methyladenine and 7-methylguanine.</title>
            <authorList>
                <person name="O'Connor T.R."/>
                <person name="Laval J."/>
            </authorList>
            <dbReference type="PubMed" id="1645538"/>
            <dbReference type="DOI" id="10.1016/0006-291x(91)90408-y"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 69-298 (ISOFORMS 1/2)</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1993" name="Mamm. Genome" volume="4" first="314" last="323">
            <title>Homology of a 130-kb region enclosing the alpha-globin gene cluster, the alpha-locus controlling region, and two non-globin genes in human and mouse.</title>
            <authorList>
                <person name="Kielman M.F."/>
                <person name="Smits R."/>
                <person name="Devi T.S."/>
                <person name="Fodde R."/>
                <person name="Bernini L.F."/>
            </authorList>
            <dbReference type="PubMed" id="8318735"/>
            <dbReference type="DOI" id="10.1007/bf00357090"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 230-298 (ISOFORMS 1/2)</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2003" name="Proc. Natl. Acad. Sci. U.S.A." volume="100" first="12859" last="12864">
            <title>Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin.</title>
            <authorList>
                <person name="Watanabe S."/>
                <person name="Ichimura T."/>
                <person name="Fujita N."/>
                <person name="Tsuruzoe S."/>
                <person name="Ohki I."/>
                <person name="Shirakawa M."/>
                <person name="Kawasuji M."/>
                <person name="Nakao M."/>
            </authorList>
            <dbReference type="PubMed" id="14555760"/>
            <dbReference type="DOI" id="10.1073/pnas.2131819100"/>
        </citation>
        <scope>INTERACTION WITH MBD1</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="DNA Repair" volume="12" first="177" last="187">
            <title>Alkyladenine DNA glycosylase (AAG) localizes to mitochondria and interacts with mitochondrial single-stranded binding protein (mtSSB).</title>
            <authorList>
                <person name="van Loon B."/>
                <person name="Samson L.D."/>
            </authorList>
            <dbReference type="PubMed" id="23290262"/>
            <dbReference type="DOI" id="10.1016/j.dnarep.2012.11.009"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH SSBP1</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="17">
        <citation type="journal article" date="1998" name="Cell" volume="95" first="249" last="258">
            <title>Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision.</title>
            <authorList>
                <person name="Lau A.Y."/>
                <person name="Scharer O.D."/>
                <person name="Samson L."/>
                <person name="Verdine G.L."/>
                <person name="Ellenberger T."/>
            </authorList>
            <dbReference type="PubMed" id="9790531"/>
            <dbReference type="DOI" id="10.1016/s0092-8674(00)81755-9"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 80-199</scope>
    </reference>
    <comment type="function">
        <text>Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>Hydrolysis of alkylated DNA, releasing 3-methyladenine, 3-methylguanine, 7-methylguanine and 7-methyladenine.</text>
            <dbReference type="EC" id="3.2.2.21"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Binding to SSBP1 in mitochondria inhibits glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrates.</text>
    </comment>
    <comment type="subunit">
        <text>Binds MBD1. Binds SSBP1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1043398">
            <id>P29372</id>
        </interactant>
        <interactant intactId="EBI-742664">
            <id>Q9BPX1</id>
            <label>HSD17B14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1043398">
            <id>P29372</id>
        </interactant>
        <interactant intactId="EBI-977302">
            <id>P04156</id>
            <label>PRNP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10695618">
            <id>P29372-4</id>
        </interactant>
        <interactant intactId="EBI-742664">
            <id>Q9BPX1</id>
            <label>HSD17B14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10695618">
            <id>P29372-4</id>
        </interactant>
        <interactant intactId="EBI-744248">
            <id>P40692</id>
            <label>MLH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Mitochondrion matrix</location>
            <location evidence="3">Mitochondrion nucleoid</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P29372-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P29372-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_003249 VSP_035485"/>
        </isoform>
        <isoform>
            <id>P29372-4</id>
            <name>3</name>
            <sequence type="described" ref="VSP_003249"/>
        </isoform>
        <isoform>
            <id>P29372-5</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046678"/>
        </isoform>
        <text>Experimental confirmation may be lacking for some isoforms.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the DNA glycosylase MPG family.</text>
    </comment>
    <dbReference type="EC" id="3.2.2.21"/>
    <dbReference type="EMBL" id="M74905">
        <property type="protein sequence ID" value="AAA58627.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L10752">
        <property type="protein sequence ID" value="AAF77073.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY258284">
        <property type="protein sequence ID" value="AAP82229.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY305873">
        <property type="protein sequence ID" value="AAQ95215.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF499437">
        <property type="protein sequence ID" value="AAM14628.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AE006462">
        <property type="protein sequence ID" value="AAK61213.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z69720">
        <property type="protein sequence ID" value="CAA93540.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z69720">
        <property type="protein sequence ID" value="CAI95610.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471112">
        <property type="protein sequence ID" value="EAW85871.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014991">
        <property type="protein sequence ID" value="AAH14991.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S51033">
        <property type="protein sequence ID" value="AAB19537.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X56528">
        <property type="protein sequence ID" value="CAA39875.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M71215">
        <property type="protein sequence ID" value="AAA58369.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M99626">
        <property type="protein sequence ID" value="AAB46421.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS32345.1">
        <molecule id="P29372-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32346.1">
        <molecule id="P29372-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42087.1">
        <molecule id="P29372-5"/>
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    <dbReference type="PIR" id="A40798">
        <property type="entry name" value="A40798"/>
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    <dbReference type="PIR" id="A41230">
        <property type="entry name" value="A41230"/>
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    <dbReference type="PIR" id="A47471">
        <property type="entry name" value="A47471"/>
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    <dbReference type="PIR" id="JN0062">
        <property type="entry name" value="JN0062"/>
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    <dbReference type="RefSeq" id="NP_001015052.1">
        <molecule id="P29372-4"/>
        <property type="nucleotide sequence ID" value="NM_001015052.3"/>
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    <dbReference type="RefSeq" id="NP_001015054.1">
        <molecule id="P29372-5"/>
        <property type="nucleotide sequence ID" value="NM_001015054.3"/>
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    <dbReference type="RefSeq" id="NP_002425.2">
        <molecule id="P29372-1"/>
        <property type="nucleotide sequence ID" value="NM_002434.4"/>
    </dbReference>
    <dbReference type="PDB" id="1BNK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=80-295"/>
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    <dbReference type="PDB" id="1EWN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=80-298"/>
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    <dbReference type="PDB" id="1F4R">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A=80-298"/>
    </dbReference>
    <dbReference type="PDB" id="1F6O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A=80-298"/>
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    <dbReference type="PDB" id="3QI5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=84-298"/>
    </dbReference>
    <dbReference type="PDB" id="3UBY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=84-298"/>
    </dbReference>
    <dbReference type="PDB" id="7XFH">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="K=1-298"/>
    </dbReference>
    <dbReference type="PDB" id="7XFJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="K=1-298"/>
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    <dbReference type="PDB" id="7XFM">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="K=1-298"/>
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    <dbReference type="PDBsum" id="1BNK"/>
    <dbReference type="PDBsum" id="1EWN"/>
    <dbReference type="PDBsum" id="1F4R"/>
    <dbReference type="PDBsum" id="1F6O"/>
    <dbReference type="PDBsum" id="3QI5"/>
    <dbReference type="PDBsum" id="3UBY"/>
    <dbReference type="PDBsum" id="7XFH"/>
    <dbReference type="PDBsum" id="7XFJ"/>
    <dbReference type="PDBsum" id="7XFM"/>
    <dbReference type="AlphaFoldDB" id="P29372"/>
    <dbReference type="EMDB" id="EMD-33172"/>
    <dbReference type="EMDB" id="EMD-33174"/>
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    <dbReference type="SMR" id="P29372"/>
    <dbReference type="BioGRID" id="110490">
        <property type="interactions" value="113"/>
    </dbReference>
    <dbReference type="FunCoup" id="P29372">
        <property type="interactions" value="704"/>
    </dbReference>
    <dbReference type="IntAct" id="P29372">
        <property type="interactions" value="60"/>
    </dbReference>
    <dbReference type="MINT" id="P29372"/>
    <dbReference type="STRING" id="9606.ENSP00000219431"/>
    <dbReference type="BindingDB" id="P29372"/>
    <dbReference type="ChEMBL" id="CHEMBL3396943"/>
    <dbReference type="DrugBank" id="DB00515">
        <property type="generic name" value="Cisplatin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01593">
        <property type="generic name" value="Zinc"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14487">
        <property type="generic name" value="Zinc acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14533">
        <property type="generic name" value="Zinc chloride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14548">
        <property type="generic name" value="Zinc sulfate, unspecified form"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P29372"/>
    <dbReference type="GlyGen" id="P29372">
        <property type="glycosylation" value="10 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P29372"/>
    <dbReference type="PhosphoSitePlus" id="P29372"/>
    <dbReference type="SwissPalm" id="P29372"/>
    <dbReference type="BioMuta" id="MPG"/>
    <dbReference type="jPOST" id="P29372"/>
    <dbReference type="MassIVE" id="P29372"/>
    <dbReference type="PaxDb" id="9606-ENSP00000219431"/>
    <dbReference type="PeptideAtlas" id="P29372"/>
    <dbReference type="ProteomicsDB" id="33913"/>
    <dbReference type="ProteomicsDB" id="54553">
        <molecule id="P29372-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="54554">
        <molecule id="P29372-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62987"/>
    <dbReference type="Pumba" id="P29372"/>
    <dbReference type="TopDownProteomics" id="P29372-1">
        <molecule id="P29372-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="1865">
        <property type="antibodies" value="421 antibodies from 35 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="4350"/>
    <dbReference type="Ensembl" id="ENST00000219431.4">
        <molecule id="P29372-1"/>
        <property type="protein sequence ID" value="ENSP00000219431.4"/>
        <property type="gene ID" value="ENSG00000103152.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000356432.8">
        <molecule id="P29372-4"/>
        <property type="protein sequence ID" value="ENSP00000348809.4"/>
        <property type="gene ID" value="ENSG00000103152.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000397817.5">
        <molecule id="P29372-5"/>
        <property type="protein sequence ID" value="ENSP00000380918.1"/>
        <property type="gene ID" value="ENSG00000103152.12"/>
    </dbReference>
    <dbReference type="GeneID" id="4350"/>
    <dbReference type="KEGG" id="hsa:4350"/>
    <dbReference type="MANE-Select" id="ENST00000356432.8">
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        <property type="protein sequence ID" value="ENSP00000348809.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001015052.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001015052.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002cfm.4">
        <molecule id="P29372-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:7211"/>
    <dbReference type="ClinPGx" id="PA30917"/>
    <dbReference type="CTD" id="4350"/>
    <dbReference type="DisGeNET" id="4350"/>
    <dbReference type="GeneCards" id="MPG"/>
    <dbReference type="HGNC" id="HGNC:7211">
        <property type="gene designation" value="MPG"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000103152">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="156565">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000103152"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000103152"/>
    <dbReference type="eggNOG" id="KOG4486">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00390000009825"/>
    <dbReference type="HOGENOM" id="CLU_060471_0_0_1"/>
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    <dbReference type="OMA" id="VEAYHHT"/>
    <dbReference type="OrthoDB" id="6353017at2759"/>
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        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="P29372"/>
    <dbReference type="BRENDA" id="3.2.2.21">
        <property type="organism ID" value="2681"/>
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    <dbReference type="Reactome" id="R-HSA-110330">
        <property type="pathway name" value="Recognition and association of DNA glycosylase with site containing an affected purine"/>
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    <dbReference type="Reactome" id="R-HSA-110331">
        <property type="pathway name" value="Cleavage of the damaged purine"/>
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    <dbReference type="Reactome" id="R-HSA-110357">
        <property type="pathway name" value="Displacement of DNA glycosylase by APEX1"/>
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    <dbReference type="SABIO-RK" id="P29372"/>
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    <dbReference type="SIGNOR" id="P29372"/>
    <dbReference type="Agora" id="ENSG00000103152"/>
    <dbReference type="BioGRID-ORCS" id="4350">
        <property type="hits" value="9 hits in 1158 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="MPG">
        <property type="organism name" value="human"/>
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    <dbReference type="EvolutionaryTrace" id="P29372"/>
    <dbReference type="GeneWiki" id="MPG_(gene)"/>
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        <property type="development level" value="Tchem"/>
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    <dbReference type="PRO" id="PR:P29372"/>
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        <property type="component" value="Chromosome 16"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000103152">
        <property type="expression patterns" value="Expressed in ascending aorta and 194 other cell types or tissues"/>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
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        <property type="entry name" value="Putative 3-methyladenine DNA glycosylase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Methylpurine-DNA glycosylase (MPG)"/>
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        <property type="entry name" value="3MGH"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Formyl_transferase-like_C_sf"/>
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        <property type="entry name" value="MPG"/>
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        <property type="entry name" value="MPG_sf"/>
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        <property type="entry name" value="3mg"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="DNA-3-METHYLADENINE GLYCOSYLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10429:SF0">
        <property type="entry name" value="DNA-3-METHYLADENINE GLYCOSYLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02245">
        <property type="entry name" value="Pur_DNA_glyco"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50486">
        <property type="entry name" value="FMT C-terminal domain-like"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0227">DNA damage</keyword>
    <keyword id="KW-0234">DNA repair</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1135">Mitochondrion nucleoid</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="17"/>
        </location>
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    <feature type="chain" id="PRO_0000100065" description="DNA-3-methyladenine glycosylase">
        <location>
            <begin position="18"/>
            <end position="298"/>
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    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="65"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="2">
        <location>
            <begin position="9"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="9">
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046678" description="In isoform 4." evidence="8">
        <location>
            <begin position="1"/>
            <end position="17"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_003249" description="In isoform 2 and isoform 3." evidence="5 6 7">
        <original>MVTPALQMKKPK</original>
        <variation>MPARSGA</variation>
        <location>
            <begin position="1"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035485" description="In isoform 2." evidence="5 6">
        <original>QL</original>
        <variation>HV</variation>
        <location>
            <begin position="195"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019138" description="In dbSNP:rs3176383." evidence="4">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014831" description="In dbSNP:rs2308315.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014832" description="In dbSNP:rs2266607." evidence="4">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050096" description="In dbSNP:rs25671.">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014833" description="In dbSNP:rs2308313.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014834" description="In dbSNP:rs2308312.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014835" description="In dbSNP:rs769193." evidence="4">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014836" description="In dbSNP:rs2234949." evidence="4">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAK61213." evidence="8" ref="5">
        <original>Q</original>
        <variation>QV</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAB19537." evidence="8" ref="9">
        <original>GQP</original>
        <variation>ARA</variation>
        <location>
            <begin position="29"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAB19537." evidence="8" ref="9">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AAA58369/CAA39875." evidence="8" ref="10">
        <original>GPY</original>
        <variation>SKD</variation>
        <location>
            <begin position="69"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AAA58369/CAA39875." evidence="8" ref="10">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA58627." evidence="8" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AAA58369." evidence="8" ref="10">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="82"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="88"/>
            <end position="91"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="95"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="102"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="106"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="turn" evidence="13">
        <location>
            <begin position="112"/>
            <end position="114"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="116"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="129"/>
            <end position="131"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="138"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="145"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="152"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="155"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="162"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="165"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="173"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="178"/>
            <end position="188"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="190"/>
            <end position="199"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="211"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="214"/>
            <end position="217"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="218"/>
            <end position="224"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="229"/>
            <end position="231"/>
        </location>
    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="236"/>
            <end position="238"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="240"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="253"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="256"/>
            <end position="259"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="262"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="268"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="276"/>
            <end position="279"/>
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    <feature type="turn" evidence="12">
        <location>
            <begin position="290"/>
            <end position="292"/>
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    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="23290262"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="8475094"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="11">
        <source>
            <dbReference type="PDB" id="1F6O"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="12">
        <source>
            <dbReference type="PDB" id="3UBY"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="7XFH"/>
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    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="7XFM"/>
        </source>
    </evidence>
    <sequence length="298" mass="32869" checksum="BEA8C4CB250D572B" modified="2008-09-23" version="3" precursor="true">MVTPALQMKKPKQFCRRMGQKKQRPARAGQPHSSSDAAQAPAEQPHSSSDAAQAPCPRERCLGPPTTPGPYRSIYFSSPKGHLTRLGLEFFDQPAVPLARAFLGQVLVRRLPNGTELRGRIVETEAYLGPEDEAAHSRGGRQTPRNRGMFMKPGTLYVYIIYGMYFCMNISSQGDGACVLLRALEPLEGLETMRQLRSTLRKGTASRVLKDRELCSGPSKLCQALAINKSFDQRDLAQDEAVWLERGPLEPSEPAVVAAARVGVGHAGEWARKPLRFYVRGSPWVSVVDRVAEQDTQA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-09-19" modified="2026-01-28" version="167" xmlns="https://uniprot.org/uniprot">
    <accession>O60516</accession>
    <name>4EBP3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Eukaryotic translation initiation factor 4E-binding protein 3</fullName>
            <shortName>4E-BP3</shortName>
            <shortName>eIF4E-binding protein 3</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">EIF4EBP3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="14002" last="14007">
            <title>4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family.</title>
            <authorList>
                <person name="Poulin F."/>
                <person name="Gingras A.-C."/>
                <person name="Olsen H."/>
                <person name="Chevalier S."/>
                <person name="Sonenberg N."/>
            </authorList>
            <dbReference type="PubMed" id="9593750"/>
            <dbReference type="DOI" id="10.1074/jbc.273.22.14002"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>MUTAGENESIS OF TYR-40 AND LEU-45</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lymph</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2012" name="FEBS Lett." volume="586" first="2260" last="2266">
            <title>4E-BP3 regulates eIF4E-mediated nuclear mRNA export and interacts with replication protein A2.</title>
            <authorList>
                <person name="Chen C.C."/>
                <person name="Lee J.C."/>
                <person name="Chang M.C."/>
            </authorList>
            <dbReference type="PubMed" id="22684010"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2012.05.059"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RPA2</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3">Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: the hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repression of translation. In contrast, the hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (By similarity). Inhibits EIF4E-mediated mRNA nuclear export (PubMed:22684010).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4">Interacts with EIF4E (PubMed:9593750). Interacts with RPA2 (in unphosphorylated form via N-terminus); the interaction enhances EIF4EBP3-mediated inhibition of EIF4E-mediated mRNA nuclear export (PubMed:22684010).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-746950">
            <id>O60516</id>
        </interactant>
        <interactant intactId="EBI-73440">
            <id>P06730</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-746950">
            <id>O60516</id>
        </interactant>
        <interactant intactId="EBI-621404">
            <id>P15927</id>
            <label>RPA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-746950">
            <id>O60516</id>
        </interactant>
        <interactant intactId="EBI-934970">
            <id>Q80ZJ3</id>
            <label>Eif4e2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Expression is highest in skeletal muscle, heart, kidney, and pancreas, whereas there is very little expression in brain and thymus.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">Phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the eIF4E-binding protein family.</text>
    </comment>
    <dbReference type="EMBL" id="AF038869">
        <property type="protein sequence ID" value="AAC39761.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010881">
        <property type="protein sequence ID" value="AAH10881.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC069293">
        <property type="protein sequence ID" value="AAH69293.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC073751">
        <property type="protein sequence ID" value="AAH73751.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4226.1"/>
    <dbReference type="RefSeq" id="NP_003723.1">
        <property type="nucleotide sequence ID" value="NM_003732.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O60516"/>
    <dbReference type="SMR" id="O60516"/>
    <dbReference type="BioGRID" id="114190">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="ELM" id="O60516"/>
    <dbReference type="FunCoup" id="O60516">
        <property type="interactions" value="50"/>
    </dbReference>
    <dbReference type="IntAct" id="O60516">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="MINT" id="O60516"/>
    <dbReference type="STRING" id="9606.ENSP00000308472"/>
    <dbReference type="iPTMnet" id="O60516"/>
    <dbReference type="PhosphoSitePlus" id="O60516"/>
    <dbReference type="BioMuta" id="EIF4EBP3"/>
    <dbReference type="jPOST" id="O60516"/>
    <dbReference type="MassIVE" id="O60516"/>
    <dbReference type="PaxDb" id="9606-ENSP00000308472"/>
    <dbReference type="PeptideAtlas" id="O60516"/>
    <dbReference type="ProteomicsDB" id="49454"/>
    <dbReference type="Antibodypedia" id="34915">
        <property type="antibodies" value="135 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8637"/>
    <dbReference type="Ensembl" id="ENST00000310331.3">
        <property type="protein sequence ID" value="ENSP00000308472.2"/>
        <property type="gene ID" value="ENSG00000243056.2"/>
    </dbReference>
    <dbReference type="GeneID" id="8637"/>
    <dbReference type="KEGG" id="hsa:8637"/>
    <dbReference type="MANE-Select" id="ENST00000310331.3">
        <property type="protein sequence ID" value="ENSP00000308472.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003732.3"/>
        <property type="RefSeq protein sequence ID" value="NP_003723.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003lfy.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:3290"/>
    <dbReference type="ClinPGx" id="PA27718"/>
    <dbReference type="CTD" id="8637"/>
    <dbReference type="DisGeNET" id="8637"/>
    <dbReference type="GeneCards" id="EIF4EBP3"/>
    <dbReference type="HGNC" id="HGNC:3290">
        <property type="gene designation" value="EIF4EBP3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000243056">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="603483">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000243056"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000243056"/>
    <dbReference type="eggNOG" id="ENOG502S03G">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163328"/>
    <dbReference type="HOGENOM" id="CLU_111706_0_0_1"/>
    <dbReference type="InParanoid" id="O60516"/>
    <dbReference type="OMA" id="KQAKSCP"/>
    <dbReference type="OrthoDB" id="19729at2759"/>
    <dbReference type="PAN-GO" id="O60516">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O60516"/>
    <dbReference type="PathwayCommons" id="O60516"/>
    <dbReference type="SignaLink" id="O60516"/>
    <dbReference type="SIGNOR" id="O60516"/>
    <dbReference type="Agora" id="ENSG00000243056"/>
    <dbReference type="BioGRID-ORCS" id="8637">
        <property type="hits" value="9 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="EIF4EBP3"/>
    <dbReference type="GenomeRNAi" id="8637"/>
    <dbReference type="Pharos" id="O60516">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O60516"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="O60516">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000243056">
        <property type="expression patterns" value="Expressed in right uterine tube and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016281">
        <property type="term" value="C:eukaryotic translation initiation factor 4F complex"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008190">
        <property type="term" value="F:eukaryotic initiation factor 4E binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030371">
        <property type="term" value="F:translation repressor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045947">
        <property type="term" value="P:negative regulation of translational initiation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008606">
        <property type="entry name" value="EIF4EBP"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12669">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12669:SF5">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEIN 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05456">
        <property type="entry name" value="eIF_4EBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0652">Protein synthesis inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <feature type="chain" id="PRO_0000190518" description="Eukaryotic translation initiation factor 4E-binding protein 3">
        <location>
            <begin position="1"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="81"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="YXXXXLphi motif" evidence="4">
        <location>
            <begin position="40"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="TOS motif" evidence="1">
        <location>
            <begin position="96"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="2">
        <location>
            <begin position="85"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with EIF4E." evidence="4">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with EIF4E." evidence="4">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q13541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="22684010"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="9593750"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="100" mass="10873" checksum="FD29A7F3829E546E" modified="1998-08-01" version="1">MSTSTSCPIPGGRDQLPDCYSTTPGGTLYATTPGGTRIIYDRKFLLECKNSPIARTPPCCLPQIPGVTTPPTAPLSKLEELKEQETEEEIPDDAQFEMDI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-08-02" modified="2026-01-28" version="201" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NRA8</accession>
    <accession>B1AKL2</accession>
    <accession>B1AKL3</accession>
    <accession>B2RBF1</accession>
    <accession>Q8NCF2</accession>
    <accession>Q9H708</accession>
    <name>4ET_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="20">Eukaryotic translation initiation factor 4E transporter</fullName>
            <shortName evidence="20">4E-T</shortName>
            <shortName evidence="20">eIF4E transporter</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Eukaryotic translation initiation factor 4E nuclear import factor 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="25" type="primary">EIF4ENIF1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-136; SER-138; SER-345; SER-564 AND SER-951</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-301; SER-513; SER-564 AND SER-951</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-951</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION AT SER-301; SER-374; SER-513; SER-587; SER-693 AND SER-752</scope>
        <scope>MUTAGENESIS OF SER-301; SER-374; SER-513; SER-587; SER-693 AND SER-752</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-74; SER-78; SER-115; SER-417; SER-513; SER-564; SER-587 AND SER-951</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353 AND SER-951</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH EIF4E AND EIF4E2</scope>
        <scope>DOMAIN</scope>
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            <title>Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated silencing.</title>
            <authorList>
                <person name="Kamenska A."/>
                <person name="Lu W.T."/>
                <person name="Kubacka D."/>
                <person name="Broomhead H."/>
                <person name="Minshall N."/>
                <person name="Bushell M."/>
                <person name="Standart N."/>
            </authorList>
            <dbReference type="PubMed" id="24335285"/>
            <dbReference type="DOI" id="10.1093/nar/gkt1265"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF TYR-30</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="Cell Rep." volume="11" first="1425" last="1436">
            <title>The eIF4E-Binding protein 4E-T is a component of the mRNA decay machinery that bridges the 5' and 3' termini of target mRNAs.</title>
            <authorList>
                <person name="Nishimura T."/>
                <person name="Padamsi Z."/>
                <person name="Fakim H."/>
                <person name="Milette S."/>
                <person name="Dunham W.H."/>
                <person name="Gingras A.C."/>
                <person name="Fabian M.R."/>
            </authorList>
            <dbReference type="PubMed" id="26027925"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2015.04.065"/>
        </citation>
        <scope>INTERACTION WITH DDX6; CNOT1; PATL1 AND LSM14A</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2015" name="PLoS ONE" volume="10" first="e0123352" last="e0123352">
            <title>Phosphorylation of eIF4E confers resistance to cellular stress and DNA-damaging agents through an interaction with 4E-T: a rationale for novel therapeutic approaches.</title>
            <authorList>
                <person name="Martinez A."/>
                <person name="Sese M."/>
                <person name="Losa J.H."/>
                <person name="Robichaud N."/>
                <person name="Sonenberg N."/>
                <person name="Aasen T."/>
                <person name="Ramon Y Cajal S."/>
            </authorList>
            <dbReference type="PubMed" id="25923732"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0123352"/>
        </citation>
        <scope>INTERACTION WITH EIF4E</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2016" name="Nucleic Acids Res." volume="44" first="6318" last="6334">
            <title>The DDX6-4E-T interaction mediates translational repression and P-body assembly.</title>
            <authorList>
                <person name="Kamenska A."/>
                <person name="Simpson C."/>
                <person name="Vindry C."/>
                <person name="Broomhead H."/>
                <person name="Benard M."/>
                <person name="Ernoult-Lange M."/>
                <person name="Lee B.P."/>
                <person name="Harries L.W."/>
                <person name="Weil D."/>
                <person name="Standart N."/>
            </authorList>
            <dbReference type="PubMed" id="27342281"/>
            <dbReference type="DOI" id="10.1093/nar/gkw565"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>INTERACTION WITH DDX6; CSDE1 AND CNOT1</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-410</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2017" name="Proc. Natl. Acad. Sci. U.S.A." volume="114" first="5425" last="5430">
            <title>Cap-binding protein 4EHP effects translation silencing by microRNAs.</title>
            <authorList>
                <person name="Chapat C."/>
                <person name="Jafarnejad S.M."/>
                <person name="Matta-Camacho E."/>
                <person name="Hesketh G.G."/>
                <person name="Gelbart I.A."/>
                <person name="Attig J."/>
                <person name="Gkogkas C.G."/>
                <person name="Alain T."/>
                <person name="Stern-Ginossar N."/>
                <person name="Fabian M.R."/>
                <person name="Gingras A.C."/>
                <person name="Duchaine T.F."/>
                <person name="Sonenberg N."/>
            </authorList>
            <dbReference type="PubMed" id="28487484"/>
            <dbReference type="DOI" id="10.1073/pnas.1701488114"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH EIF4E AND EIF4E2</scope>
        <scope>MUTAGENESIS OF 30-TYR--LEU-36 AND TYR-30</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2017" name="Sci. Rep." volume="7" first="42853" last="42853">
            <title>Dual mechanisms regulate the nucleocytoplasmic localization of human DDX6.</title>
            <authorList>
                <person name="Huang J.H."/>
                <person name="Ku W.C."/>
                <person name="Chen Y.C."/>
                <person name="Chang Y.L."/>
                <person name="Chu C.Y."/>
            </authorList>
            <dbReference type="PubMed" id="28216671"/>
            <dbReference type="DOI" id="10.1038/srep42853"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH DDX6</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2019" name="Am. J. Hum. Genet." volume="105" first="509" last="525">
            <title>Rare de novo missense variants in RNA helicase DDX6 cause intellectual disability and dysmorphic features and lead to P-body defects and RNA dysregulation.</title>
            <authorList>
                <person name="Balak C."/>
                <person name="Benard M."/>
                <person name="Schaefer E."/>
                <person name="Iqbal S."/>
                <person name="Ramsey K."/>
                <person name="Ernoult-Lange M."/>
                <person name="Mattioli F."/>
                <person name="Llaci L."/>
                <person name="Geoffroy V."/>
                <person name="Courel M."/>
                <person name="Naymik M."/>
                <person name="Bachman K.K."/>
                <person name="Pfundt R."/>
                <person name="Rump P."/>
                <person name="Ter Beest J."/>
                <person name="Wentzensen I.M."/>
                <person name="Monaghan K.G."/>
                <person name="McWalter K."/>
                <person name="Richholt R."/>
                <person name="Le Bechec A."/>
                <person name="Jepsen W."/>
                <person name="De Both M."/>
                <person name="Belnap N."/>
                <person name="Boland A."/>
                <person name="Piras I.S."/>
                <person name="Deleuze J.F."/>
                <person name="Szelinger S."/>
                <person name="Dollfus H."/>
                <person name="Chelly J."/>
                <person name="Muller J."/>
                <person name="Campbell A."/>
                <person name="Lal D."/>
                <person name="Rangasamy S."/>
                <person name="Mandel J.L."/>
                <person name="Narayanan V."/>
                <person name="Huentelman M."/>
                <person name="Weil D."/>
                <person name="Piton A."/>
            </authorList>
            <dbReference type="PubMed" id="31422817"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2019.07.010"/>
        </citation>
        <scope>INTERACTION WITH DDX6</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2019" name="Genes Dev." volume="33" first="1355" last="1360">
            <title>Molecular basis for GIGYF-Me31B complex assembly in 4EHP-mediated translational repression.</title>
            <authorList>
                <person name="Peter D."/>
                <person name="Ruscica V."/>
                <person name="Bawankar P."/>
                <person name="Weber R."/>
                <person name="Helms S."/>
                <person name="Valkov E."/>
                <person name="Igreja C."/>
                <person name="Izaurralde E."/>
            </authorList>
            <dbReference type="PubMed" id="31439631"/>
            <dbReference type="DOI" id="10.1101/gad.329219.119"/>
        </citation>
        <scope>INTERACTION WITH DDX6</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="2020" name="Genes Dev." volume="34" first="847" last="860">
            <title>4E-T-bound mRNAs are stored in a silenced and deadenylated form.</title>
            <authorList>
                <person name="Raesch F."/>
                <person name="Weber R."/>
                <person name="Izaurralde E."/>
                <person name="Igreja C."/>
            </authorList>
            <dbReference type="PubMed" id="32354837"/>
            <dbReference type="DOI" id="10.1101/gad.336073.119"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH CSDE1; DDX6; CNOT1; PATL1 AND LSM14A</scope>
    </reference>
    <reference evidence="26" key="32">
        <citation type="journal article" date="2015" name="Cell Rep." volume="13" first="703" last="711">
            <title>Structure of a human 4E-T/DDX6/CNOT1 complex reveals the different interplay of DDX6-binding proteins with the CCR4-NOT complex.</title>
            <authorList>
                <person name="Ozgur S."/>
                <person name="Basquin J."/>
                <person name="Kamenska A."/>
                <person name="Filipowicz W."/>
                <person name="Standart N."/>
                <person name="Conti E."/>
            </authorList>
            <dbReference type="PubMed" id="26489469"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2015.09.033"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 199-239 IN COMPLEX WITH DDX6 AND CNOT1</scope>
        <scope>INTERACTION WITH DDX6 AND CNOT1</scope>
    </reference>
    <reference evidence="27" key="33">
        <citation type="journal article" date="2018" name="EMBO J." volume="37" first="0" last="0">
            <title>Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes.</title>
            <authorList>
                <person name="Brandmann T."/>
                <person name="Fakim H."/>
                <person name="Padamsi Z."/>
                <person name="Youn J.Y."/>
                <person name="Gingras A.C."/>
                <person name="Fabian M.R."/>
                <person name="Jinek M."/>
            </authorList>
            <dbReference type="PubMed" id="29510985"/>
            <dbReference type="DOI" id="10.15252/embj.201797869"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 954-985 IN COMPLEX WITH LSM14A</scope>
        <scope>INTERACTION WITH LSM14A</scope>
        <scope>MUTAGENESIS OF 955-LEU--TRP-958; TRP-958; PHE-959; SER-961; SER-970; 978-VAL--LEU-981; VAL-978 AND GLU-982</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 4 7 9 13 14 15 19">EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:27342281, PubMed:32354837). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:24335285, PubMed:32354837). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (PubMed:27342281, PubMed:32354837). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). Promotes miRNA-mediated translational repression (PubMed:24335285, PubMed:27342281, PubMed:28487484). Required for the formation of P-bodies (PubMed:16157702, PubMed:22966201, PubMed:27342281, PubMed:32354837). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (PubMed:32354837). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (PubMed:10856257, PubMed:28216671).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 5 8 9 10 11 12 13 14 15 16 17 18 19">Interacts (via YXXXXLphi motif) with EIF4E (PubMed:10856257, PubMed:16157702, PubMed:23991149, PubMed:24335285, PubMed:25923732, PubMed:28487484). Interacts (via YXXXXLphi motif) with EIF4E2 (PubMed:23991149, PubMed:28487484). Interacts with DDX6 (PubMed:26027925, PubMed:26489469, PubMed:27342281, PubMed:28216671, PubMed:31422817, PubMed:31439631, PubMed:32354837). Interacts with CSDE1/UNR (PubMed:27342281, PubMed:32354837). Interacts with CNOT1; promoting association with the CCR4-NOT complex (PubMed:26027925, PubMed:26489469, PubMed:27342281, PubMed:32354837). Interacts with LSM14A; promoting EIF4ENIF1 localization to P-bodies (PubMed:26027925, PubMed:29510985, PubMed:32354837). Interacts with PATL1 (PubMed:26027925, PubMed:32354837). Interacts with importin beta only in the presence of importin alpha, suggesting a direct interaction with importin alpha (PubMed:10856257). Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-749051">
            <id>Q8IYR0</id>
            <label>CFAP206</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-351257">
            <id>P26196</id>
            <label>DDX6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>17</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-745369">
            <id>Q9H4E7</id>
            <label>DEF6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-740376">
            <id>Q86UW9</id>
            <label>DTX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-743105">
            <id>Q5JVL4</id>
            <label>EFHC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-73440">
            <id>P06730</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-32715456">
            <id>P06730-1</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-398610">
            <id>O60573</id>
            <label>EIF4E2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-32715389">
            <id>O60573-1</id>
            <label>EIF4E2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-2339898">
            <id>Q9NW38</id>
            <label>FANCL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-352986">
            <id>P52597</id>
            <label>HNRNPF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-742756">
            <id>P08727</id>
            <label>KRT19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-739909">
            <id>Q969R5</id>
            <label>L3MBTL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-536879">
            <id>O43482</id>
            <label>OIP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-12754095">
            <id>P86480</id>
            <label>PRR20D</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
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        <interactant intactId="EBI-5235340">
            <id>Q7Z699</id>
            <label>SPRED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-740781">
            <id>Q9BT92</id>
            <label>TCHP</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
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        <interactant intactId="EBI-948354">
            <id>Q6DKK2</id>
            <label>TTC19</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
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        <interactant intactId="EBI-359793">
            <id>P40222</id>
            <label>TXLNA</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
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        <interactant intactId="EBI-743272">
            <id>O75604</id>
            <label>USP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
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        <interactant intactId="EBI-3796">
            <id>P53286</id>
            <label>BTN2</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-7968">
            <id>P40956</id>
            <label>GTS1</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-301024">
            <id>Q9NRA8</id>
        </interactant>
        <interactant intactId="EBI-6863741">
            <id>PRO_0000037548</id>
            <dbReference type="UniProtKB" id="Q9WMX2"/>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11531709">
            <id>Q9NRA8-2</id>
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        <interactant intactId="EBI-7968">
            <id>P40956</id>
            <label>GTS1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 7 8 9 19">Cytoplasm</location>
            <location evidence="4 7 8 9 19">P-body</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3 6 14">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3 6 14">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Nucleus</location>
            <location evidence="6">PML body</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Nucleus speckle</location>
        </subcellularLocation>
        <text evidence="3 4 6">Predominantly cytoplasmic (PubMed:10856257). Mainly localizes to processing bodies (P-bodies) (PubMed:16157702). Shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner (PubMed:10856257). Localization to nuclear foci and speckles requires active transcription (PubMed:22090346).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NRA8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NRA8-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_003783 VSP_003784 VSP_047042"/>
        </isoform>
        <isoform>
            <id>Q9NRA8-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_047042"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Widely expressed.</text>
    </comment>
    <comment type="domain">
        <text evidence="13 14">Intrinsically disordered protein with multiple low-complexity regions that confer binding to multiple RNA translation, deadenylation and decapping factors.</text>
    </comment>
    <comment type="domain">
        <text evidence="3 4 8 9">The YXXXXLphi motif mediates interaction with eIF4E (EIF4E and EIF4E2).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1 7">Phosphorylation by MAPK8/JNK1 and or MAPK9/JNK2 in response to oxidative stress promotes P-body assembly (PubMed:22966201). Phosphorylated during meiotic maturation (By similarity).</text>
    </comment>
    <comment type="similarity">
        <text evidence="23">Belongs to the 4E-T/EIF4E-T family.</text>
    </comment>
    <comment type="sequence caution" evidence="23">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB15092" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="23">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC11194" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF240775">
        <property type="protein sequence ID" value="AAF81693.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456386">
        <property type="protein sequence ID" value="CAG30272.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK025254">
        <property type="protein sequence ID" value="BAB15092.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074768">
        <property type="protein sequence ID" value="BAC11194.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314636">
        <property type="protein sequence ID" value="BAG37198.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL096701">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471095">
        <property type="protein sequence ID" value="EAW59977.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC032941">
        <property type="protein sequence ID" value="AAH32941.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033028">
        <property type="protein sequence ID" value="AAH33028.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13898.1">
        <molecule id="Q9NRA8-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54520.1">
        <molecule id="Q9NRA8-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001157973.1">
        <molecule id="Q9NRA8-1"/>
        <property type="nucleotide sequence ID" value="NM_001164501.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001157974.1">
        <molecule id="Q9NRA8-2"/>
        <property type="nucleotide sequence ID" value="NM_001164502.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_062817.2">
        <molecule id="Q9NRA8-1"/>
        <property type="nucleotide sequence ID" value="NM_019843.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261743.1">
        <molecule id="Q9NRA8-3"/>
        <property type="nucleotide sequence ID" value="XM_005261686.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261744.1">
        <molecule id="Q9NRA8-3"/>
        <property type="nucleotide sequence ID" value="XM_005261687.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054181774.1">
        <molecule id="Q9NRA8-3"/>
        <property type="nucleotide sequence ID" value="XM_054325799.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054181775.1">
        <molecule id="Q9NRA8-3"/>
        <property type="nucleotide sequence ID" value="XM_054325800.1"/>
    </dbReference>
    <dbReference type="PDB" id="5ANR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="C=199-239"/>
    </dbReference>
    <dbReference type="PDB" id="6F9W">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.62 A"/>
        <property type="chains" value="B=954-985"/>
    </dbReference>
    <dbReference type="PDB" id="6X2R">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="D=434-448"/>
    </dbReference>
    <dbReference type="PDBsum" id="5ANR"/>
    <dbReference type="PDBsum" id="6F9W"/>
    <dbReference type="PDBsum" id="6X2R"/>
    <dbReference type="AlphaFoldDB" id="Q9NRA8"/>
    <dbReference type="SMR" id="Q9NRA8"/>
    <dbReference type="BioGRID" id="121148">
        <property type="interactions" value="327"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9NRA8"/>
    <dbReference type="FunCoup" id="Q9NRA8">
        <property type="interactions" value="4307"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NRA8">
        <property type="interactions" value="133"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NRA8"/>
    <dbReference type="STRING" id="9606.ENSP00000380659"/>
    <dbReference type="GlyGen" id="Q9NRA8">
        <property type="glycosylation" value="6 sites, 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NRA8"/>
    <dbReference type="MetOSite" id="Q9NRA8"/>
    <dbReference type="PhosphoSitePlus" id="Q9NRA8"/>
    <dbReference type="BioMuta" id="EIF4ENIF1"/>
    <dbReference type="DMDM" id="22095430"/>
    <dbReference type="jPOST" id="Q9NRA8"/>
    <dbReference type="MassIVE" id="Q9NRA8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000380659"/>
    <dbReference type="PeptideAtlas" id="Q9NRA8"/>
    <dbReference type="ProteomicsDB" id="3074"/>
    <dbReference type="ProteomicsDB" id="82323">
        <molecule id="Q9NRA8-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82324">
        <molecule id="Q9NRA8-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9NRA8"/>
    <dbReference type="Antibodypedia" id="279">
        <property type="antibodies" value="303 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="56478"/>
    <dbReference type="Ensembl" id="ENST00000330125.10">
        <molecule id="Q9NRA8-1"/>
        <property type="protein sequence ID" value="ENSP00000328103.5"/>
        <property type="gene ID" value="ENSG00000184708.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000344710.9">
        <molecule id="Q9NRA8-2"/>
        <property type="protein sequence ID" value="ENSP00000342927.5"/>
        <property type="gene ID" value="ENSG00000184708.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000397525.5">
        <molecule id="Q9NRA8-1"/>
        <property type="protein sequence ID" value="ENSP00000380659.1"/>
        <property type="gene ID" value="ENSG00000184708.19"/>
    </dbReference>
    <dbReference type="GeneID" id="56478"/>
    <dbReference type="KEGG" id="hsa:56478"/>
    <dbReference type="MANE-Select" id="ENST00000330125.10">
        <property type="protein sequence ID" value="ENSP00000328103.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_019843.4"/>
        <property type="RefSeq protein sequence ID" value="NP_062817.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003akz.3">
        <molecule id="Q9NRA8-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16687"/>
    <dbReference type="ClinPGx" id="PA38410"/>
    <dbReference type="CTD" id="56478"/>
    <dbReference type="DisGeNET" id="56478"/>
    <dbReference type="GeneCards" id="EIF4ENIF1"/>
    <dbReference type="HGNC" id="HGNC:16687">
        <property type="gene designation" value="EIF4ENIF1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184708">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="EIF4ENIF1"/>
    <dbReference type="MIM" id="607445">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184708"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184708"/>
    <dbReference type="eggNOG" id="ENOG502QRQE">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012071"/>
    <dbReference type="InParanoid" id="Q9NRA8"/>
    <dbReference type="OMA" id="WITRGSW"/>
    <dbReference type="OrthoDB" id="8916892at2759"/>
    <dbReference type="PAN-GO" id="Q9NRA8">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NRA8"/>
    <dbReference type="PathwayCommons" id="Q9NRA8"/>
    <dbReference type="SignaLink" id="Q9NRA8"/>
    <dbReference type="SIGNOR" id="Q9NRA8"/>
    <dbReference type="Agora" id="ENSG00000184708"/>
    <dbReference type="BioGRID-ORCS" id="56478">
        <property type="hits" value="56 hits in 1163 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="232F8A39">
        <property type="entry name" value="P-body"/>
    </dbReference>
    <dbReference type="CD-CODE" id="804901D1">
        <property type="entry name" value="Nuclear speckle"/>
    </dbReference>
    <dbReference type="CD-CODE" id="B5B9A610">
        <property type="entry name" value="PML body"/>
    </dbReference>
    <dbReference type="CD-CODE" id="DEE660B4">
        <property type="entry name" value="Stress granule"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="EIF4ENIF1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="EIF4ENIF1"/>
    <dbReference type="GenomeRNAi" id="56478"/>
    <dbReference type="Pharos" id="Q9NRA8">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NRA8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NRA8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184708">
        <property type="expression patterns" value="Expressed in secondary oocyte and 196 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NRA8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016607">
        <property type="term" value="C:nuclear speck"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000932">
        <property type="term" value="C:P-body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016605">
        <property type="term" value="C:PML body"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019900">
        <property type="term" value="F:kinase binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003729">
        <property type="term" value="F:mRNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005049">
        <property type="term" value="F:nuclear export signal receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035278">
        <property type="term" value="P:miRNA-mediated gene silencing by inhibition of translation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048255">
        <property type="term" value="P:mRNA stabilization"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0106289">
        <property type="term" value="P:negative regulation of deadenylation-dependent decapping of nuclear-transcribed mRNA"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045665">
        <property type="term" value="P:negative regulation of neuron differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017148">
        <property type="term" value="P:negative regulation of translation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030182">
        <property type="term" value="P:neuron differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033962">
        <property type="term" value="P:P-body assembly"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060213">
        <property type="term" value="P:positive regulation of nuclear-transcribed mRNA poly(A) tail shortening"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006606">
        <property type="term" value="P:protein import into nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019827">
        <property type="term" value="P:stem cell population maintenance"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006412">
        <property type="term" value="P:translation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018862">
        <property type="entry name" value="eIF4E-T"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12269">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E TRANSPORTER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12269:SF1">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E TRANSPORTER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF10477">
        <property type="entry name" value="EIF4E-T"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0943">RNA-mediated gene silencing</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000064381" description="Eukaryotic translation initiation factor 4E transporter">
        <location>
            <begin position="1"/>
            <end position="985"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with CSDE1" evidence="13">
        <location>
            <begin position="131"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="208"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with DDX6" evidence="13">
        <location>
            <begin position="219"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with LSM14A" evidence="11">
        <location>
            <begin position="448"/>
            <end position="490"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="664"/>
            <end position="693"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with PATL1" evidence="11">
        <location>
            <begin position="695"/>
            <end position="713"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="707"/>
            <end position="803"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="922"/>
            <end position="953"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with LSM14A" evidence="11">
        <location>
            <begin position="940"/>
            <end position="985"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="YXXXXLphi motif" evidence="3 9">
        <location>
            <begin position="30"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="24">
        <location>
            <begin position="195"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="24">
        <location>
            <begin position="438"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="24">
        <location>
            <begin position="613"/>
            <end position="638"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="707"/>
            <end position="717"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="725"/>
            <end position="735"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="2">
        <location>
            <begin position="736"/>
            <end position="746"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="2">
        <location>
            <begin position="754"/>
            <end position="776"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="31 32 34">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="34">
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="34">
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="34">
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29">
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29">
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29">
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 32">
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29">
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="35">
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="374"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="34">
        <location>
            <position position="417"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="30">
        <location>
            <position position="486"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 32 34">
        <location>
            <position position="513"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29 31 32 34">
        <location>
            <position position="564"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 31 34">
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 31">
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="752"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="28">
        <location>
            <position position="920"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29 32 33 34 35">
        <location>
            <position position="951"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="36">
        <location>
            <position position="410"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_003783" description="In isoform 2." evidence="22">
        <location>
            <begin position="100"/>
            <end position="262"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_003784" description="In isoform 2." evidence="22">
        <location>
            <begin position="493"/>
            <end position="504"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_047042" description="In isoform 2 and isoform 3." evidence="21 22">
        <original>Q</original>
        <variation>QQ</variation>
        <location>
            <position position="616"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with EIF4E2." evidence="8 15">
        <original>YTKEELL</original>
        <variation>ATKEEAA</variation>
        <location>
            <begin position="30"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with EIF4E and EIF4E2. Impaired ability to repress mRNA translation." evidence="3 4 9 15">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with EIF4E2." evidence="8">
        <original>LL</original>
        <variation>AA</variation>
        <location>
            <begin position="35"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly reduced interaction with EIF4E and EIF4E2." evidence="8">
        <original>KYDSDGVW</original>
        <variation>ADSDAA</variation>
        <location>
            <begin position="54"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes the nuclear localization." evidence="3">
        <original>RR</original>
        <variation>NS</variation>
        <location>
            <begin position="195"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-374, A-513, A-587, A-693 and A-752." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-301, A-513, A-587, A-693 and A-752." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="374"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-301, A-374, A-587, A-693 and A-752." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="513"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-301, A-374, A-513, A-693 and A-752." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-301, A-374, A-513, A-587 and A-752." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In S6A mutant; abolished phosphorylation by MAPK8/JNK1; impaired P-body assembly in response to oxidative stress when associated with A-301, A-374, A-513, A-587 and A-693." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="752"/>
        </location>
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    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>LAKW</original>
        <variation>AAKA</variation>
        <location>
            <begin position="955"/>
            <end position="958"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="958"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="959"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with LSM14A." evidence="16">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="961"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with LSM14A." evidence="16">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="970"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>VDEL</original>
        <variation>ADEA</variation>
        <location>
            <begin position="978"/>
            <end position="981"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="978"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with LSM14A." evidence="16">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="982"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF81693." evidence="23" ref="1">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH33028." evidence="23" ref="6">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="825"/>
        </location>
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    <feature type="helix" evidence="37">
        <location>
            <begin position="220"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="helix" evidence="39">
        <location>
            <begin position="435"/>
            <end position="443"/>
        </location>
    </feature>
    <feature type="helix" evidence="38">
        <location>
            <begin position="955"/>
            <end position="957"/>
        </location>
    </feature>
    <feature type="helix" evidence="38">
        <location>
            <begin position="961"/>
            <end position="965"/>
        </location>
    </feature>
    <feature type="strand" evidence="38">
        <location>
            <begin position="975"/>
            <end position="977"/>
        </location>
    </feature>
    <feature type="helix" evidence="38">
        <location>
            <begin position="978"/>
            <end position="984"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9EST3"/>
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    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10856257"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16157702"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16699599"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="22090346"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22966201"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="23991149"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="24335285"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="25923732"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="26027925"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="26489469"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="27342281"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="28216671"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="28487484"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="29510985"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="31422817"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="31439631"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="32354837"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="10856257"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000305" key="23"/>
    <evidence type="ECO:0000305" key="24">
        <source>
            <dbReference type="PubMed" id="10856257"/>
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    </evidence>
    <evidence type="ECO:0000312" key="25">
        <source>
            <dbReference type="HGNC" id="HGNC:16687"/>
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    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="5ANR"/>
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    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PDB" id="6F9W"/>
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    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PubMed" id="18088087"/>
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    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PubMed" id="19608861"/>
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    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PubMed" id="19690332"/>
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    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PubMed" id="20068231"/>
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    </evidence>
    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PubMed" id="21406692"/>
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    </evidence>
    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007744" key="35">
        <source>
            <dbReference type="PubMed" id="24275569"/>
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    </evidence>
    <evidence type="ECO:0007744" key="36">
        <source>
            <dbReference type="PubMed" id="28112733"/>
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    </evidence>
    <evidence type="ECO:0007829" key="37">
        <source>
            <dbReference type="PDB" id="5ANR"/>
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    </evidence>
    <evidence type="ECO:0007829" key="38">
        <source>
            <dbReference type="PDB" id="6F9W"/>
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    </evidence>
    <evidence type="ECO:0007829" key="39">
        <source>
            <dbReference type="PDB" id="6X2R"/>
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    </evidence>
    <sequence length="985" mass="108201" checksum="4C898E0488903C04" modified="2002-08-02" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-08-01" modified="2026-01-28" version="254" xmlns="https://uniprot.org/uniprot">
    <accession>P08195</accession>
    <accession>J3KPF3</accession>
    <accession>Q13543</accession>
    <name>4F2_HUMAN</name>
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        <recommendedName>
            <fullName evidence="59">Amino acid transporter heavy chain SLC3A2</fullName>
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        <alternativeName>
            <fullName evidence="57">4F2 cell-surface antigen heavy chain</fullName>
            <shortName evidence="54">4F2hc</shortName>
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        <alternativeName>
            <fullName evidence="56">4F2 heavy chain antigen</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="58">Lymphocyte activation antigen 4F2 large subunit</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="55">Solute carrier family 3 member 2</fullName>
        </alternativeName>
        <cdAntigenName>CD98</cdAntigenName>
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    <gene>
        <name evidence="62" type="primary">SLC3A2</name>
        <name type="synonym">MDU1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="6526" last="6530">
            <title>Molecular cloning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen: a type II membrane glycoprotein involved in normal and neoplastic cell growth.</title>
            <authorList>
                <person name="Quackenbush E."/>
                <person name="Clabby M."/>
                <person name="Gottesdiener K.M."/>
                <person name="Barbosa J."/>
                <person name="Jones N.H."/>
                <person name="Strominger J.L."/>
                <person name="Speck S."/>
                <person name="Leiden J.M."/>
            </authorList>
            <dbReference type="PubMed" id="3476959"/>
            <dbReference type="DOI" id="10.1073/pnas.84.18.6526"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="8618" last="8618">
            <authorList>
                <person name="Quackenbush E."/>
                <person name="Clabby M."/>
                <person name="Gottesdiener K.M."/>
                <person name="Barbosa J."/>
                <person name="Jones N.H."/>
                <person name="Strominger J.L."/>
                <person name="Speck S."/>
                <person name="Leiden J.M."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:3476959</scope>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1987" name="J. Biol. Chem." volume="262" first="9574" last="9580">
            <title>Primary structure of the human 4F2 antigen heavy chain predicts a transmembrane protein with a cytoplasmic NH2 terminus.</title>
            <authorList>
                <person name="Teixeira S."/>
                <person name="di Grandi S."/>
                <person name="Kuehn L.C."/>
            </authorList>
            <dbReference type="PubMed" id="3036867"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)47972-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="9204" last="9208">
            <title>Cloning, sequence analysis, and expression of the large subunit of the human lymphocyte activation antigen 4F2.</title>
            <authorList>
                <person name="Lumadue J.A."/>
                <person name="Glick A.B."/>
                <person name="Ruddle F.H."/>
            </authorList>
            <dbReference type="PubMed" id="3480538"/>
            <dbReference type="DOI" id="10.1073/pnas.84.24.9204"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
        <source>
            <tissue>Fibroblast</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1988" name="Mol. Cell. Biol." volume="8" first="3809" last="3819">
            <title>Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.</title>
            <authorList>
                <person name="Gottesdiener K.M."/>
                <person name="Karpinski B.A."/>
                <person name="Lindsten T."/>
                <person name="Strominger J.L."/>
                <person name="Jones N.H."/>
                <person name="Thompson C.B."/>
                <person name="Leiden J.M."/>
            </authorList>
            <dbReference type="PubMed" id="3265470"/>
            <dbReference type="DOI" id="10.1128/mcb.8.9.3809-3819.1988"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2001" name="Biochim. Biophys. Acta" volume="1514" first="291" last="302">
            <title>Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.</title>
            <authorList>
                <person name="Yanagida O."/>
                <person name="Kanai Y."/>
                <person name="Chairoungdua A."/>
                <person name="Kim D.K."/>
                <person name="Segawa H."/>
                <person name="Nii T."/>
                <person name="Cha S.H."/>
                <person name="Matsuo H."/>
                <person name="Fukushima J."/>
                <person name="Fukasawa Y."/>
                <person name="Tani Y."/>
                <person name="Taketani Y."/>
                <person name="Uchino H."/>
                <person name="Kim J.Y."/>
                <person name="Inatomi J."/>
                <person name="Okayasu I."/>
                <person name="Miyamoto K."/>
                <person name="Takeda E."/>
                <person name="Goya T."/>
                <person name="Endou H."/>
            </authorList>
            <dbReference type="PubMed" id="11557028"/>
            <dbReference type="DOI" id="10.1016/s0005-2736(01)00384-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH SLC7A5</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
                <person name="Bruford E."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Eichler E."/>
                <person name="FitzGerald M.G."/>
                <person name="Jaffe D.B."/>
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                <person name="Park H.-S."/>
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                <person name="Hattori M."/>
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                <person name="Sakaki Y."/>
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            <dbReference type="PubMed" id="17724034"/>
            <dbReference type="DOI" id="10.1074/jbc.m704524200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 111-529</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF CYS-109</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="63 64" key="62">
        <citation type="journal article" date="2019" name="Nature" volume="568" first="127" last="130">
            <title>Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex.</title>
            <authorList>
                <person name="Yan R."/>
                <person name="Zhao X."/>
                <person name="Lei J."/>
                <person name="Zhou Q."/>
            </authorList>
            <dbReference type="PubMed" id="30867591"/>
            <dbReference type="DOI" id="10.1038/s41586-019-1011-z"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) (ISOFORM 1) IN COMPLEX WITH SLC7A5</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>TOPOLOGY</scope>
        <scope>GLYCOSYLATION AT ASN-264; ASN-280; ASN-323 AND ASN-405</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF ARG-81; 133-GLN--ALA-529 AND LYS-431</scope>
    </reference>
    <reference evidence="65 66" key="63">
        <citation type="journal article" date="2020" name="Cell Discov." volume="6" first="82" last="82">
            <title>Structural insight into the substrate recognition and transport mechanism of the human LAT2-4F2hc complex.</title>
            <authorList>
                <person name="Yan R."/>
                <person name="Zhou J."/>
                <person name="Li Y."/>
                <person name="Lei J."/>
                <person name="Zhou Q."/>
            </authorList>
            <dbReference type="PubMed" id="33298890"/>
            <dbReference type="DOI" id="10.1038/s41421-020-00207-4"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) (ISOFORM 1) IN COMPLEX WITH SLC7A8; TRYPTOPHAN AND LEUCINE</scope>
        <scope>GLYCOSYLATION AT ASN-264; ASN-280; ASN-323 AND ASN-405</scope>
        <scope>FUNCTION</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="67 68 69 70" key="64">
        <citation type="journal article" date="2021" name="Cell Discov." volume="7" first="16" last="16">
            <title>Mechanism of substrate transport and inhibition of the human LAT1-4F2hc amino acid transporter.</title>
            <authorList>
                <person name="Yan R."/>
                <person name="Li Y."/>
                <person name="Muller J."/>
                <person name="Zhang Y."/>
                <person name="Singer S."/>
                <person name="Xia L."/>
                <person name="Zhong X."/>
                <person name="Gertsch J."/>
                <person name="Altmann K.H."/>
                <person name="Zhou Q."/>
            </authorList>
            <dbReference type="PubMed" id="33758168"/>
            <dbReference type="DOI" id="10.1038/s41421-021-00247-4"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 2-507 (ISOFORM 1) IN COMPLEX WITH SLC7A8</scope>
        <scope>GLYCOSYLATION AT ASN-264; ASN-280; ASN-323 AND ASN-405</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="72 73" key="65">
        <citation type="journal article" date="2021" name="Nat. Commun." volume="12" first="7147" last="7147">
            <title>Molecular basis for redox control by the human cystine/glutamate antiporter system xc.</title>
            <authorList>
                <person name="Parker J.L."/>
                <person name="Deme J.C."/>
                <person name="Kolokouris D."/>
                <person name="Kuteyi G."/>
                <person name="Biggin P.C."/>
                <person name="Lea S.M."/>
                <person name="Newstead S."/>
            </authorList>
            <dbReference type="PubMed" id="34880232"/>
            <dbReference type="DOI" id="10.1038/s41467-021-27414-1"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 2-630 (ISOFORM 1) IN COMPLEX WITH SLC7A11</scope>
        <scope>GLYCOSYLATION AT ASN-264; ASN-280; ASN-323 AND ASN-405</scope>
    </reference>
    <reference evidence="71" key="66">
        <citation type="journal article" date="2022" name="Cell Res." volume="32" first="687" last="690">
            <title>The structure of erastin-bound xCT-4F2hc complexreveals molecular mechanisms underlying erastin-induced ferroptosis.</title>
            <authorList>
                <person name="Yan R."/>
                <person name="Xie E."/>
                <person name="Li Y."/>
                <person name="Li J."/>
                <person name="Zhang Y."/>
                <person name="Chi X."/>
                <person name="Hu X."/>
                <person name="Xu L."/>
                <person name="Hou T."/>
                <person name="Stockwell B.R."/>
                <person name="Min J."/>
                <person name="Zhou Q."/>
                <person name="Wang F."/>
            </authorList>
            <dbReference type="PubMed" id="35352032"/>
            <dbReference type="DOI" id="10.1038/s41422-022-00642-w"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 2-630 (ISOFORM 1) IN COMPLEX WITH SLC7A11</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>GLYCOSYLATION AT ASN-264; ASN-280; ASN-323 AND ASN-405</scope>
    </reference>
    <comment type="function">
        <text evidence="2 5 6 7 8 9 10 11 12 14 16 17 19 22 23 24 35 38 40 41 42 46 50 51 52">Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115).</text>
    </comment>
    <comment type="function">
        <text evidence="37">(Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis.</text>
    </comment>
    <comment type="function">
        <text evidence="43">(Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 7 9 10 11 12 13 16 17 18 19 21 23 28 35 38 41 42 46 47 50 51 52">Disulfide-linked heterodimer with a non-glycosylated catalytic light subunit (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 or SLC7A11) (PubMed:10574970, PubMed:10903140, PubMed:11311135, PubMed:11557028, PubMed:12117417, PubMed:12225859, PubMed:15769744, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:35352032, PubMed:9751058, PubMed:9829974). Interacts with TLCD3A/CT120 (PubMed:12270127). Interacts with ICAM1 (PubMed:12716892). Constitutively and specifically associates with beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), but minimally with alpha-4/beta-1 (PubMed:11696247). Interacts with LAPTM4B; recruits SLC3A2 and SLC7A5/LAT1 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).</text>
    </comment>
    <comment type="subunit">
        <text evidence="37">(Microbial infection) Interacts with hepatitis C virus/HCV envelope glycoprotein E2; the interaction may facilitate viral entry into host cell.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-702356">
            <id>P08195</id>
        </interactant>
        <interactant intactId="EBI-15639515">
            <id>O15354</id>
            <label>GPR37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-702356">
            <id>P08195</id>
        </interactant>
        <interactant intactId="EBI-3843348">
            <id>Q9UPY5</id>
            <label>SLC7A11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-702356">
            <id>P08195</id>
        </interactant>
        <interactant intactId="EBI-6138761">
            <id>Q01650</id>
            <label>SLC7A5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-702356">
            <id>P08195</id>
        </interactant>
        <interactant intactId="EBI-2849880">
            <id>Q9UM01</id>
            <label>SLC7A7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-702356">
            <id>P08195</id>
        </interactant>
        <interactant intactId="EBI-14022357">
            <id>O52302</id>
            <label>sepZ</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11614088">
            <id>P08195-1</id>
        </interactant>
        <interactant intactId="EBI-6138761">
            <id>Q01650</id>
            <label>SLC7A5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="14">Apical cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 10 11 12 17 23 26 35 44 45 48 51">Cell membrane</location>
            <topology evidence="38">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="35 49">Lysosome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="27">Melanosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Basolateral cell membrane</location>
        </subcellularLocation>
        <text evidence="1 9 14 27 35 50">Localized at the plasma membrane when associated with SLC7A5/LAT1 or SLC7A8/LAT2 (PubMed:11311135, PubMed:9751058). Localized to the apical membrane of placental syncytiotrophoblastic cells (PubMed:11742812). Recruited to lysosomes by LAPTM4B (PubMed:25998567). Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065). Located selectively at cell-cell adhesion sites (By similarity). Colocalized with SLC7A8/LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. Expressed in both luminal and abluminal membranes of brain capillary endothelial cells (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P08195-2</id>
            <name>2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P08195-1</id>
            <name>1</name>
            <sequence type="described" ref="VSP_062646"/>
        </isoform>
        <isoform>
            <id>P08195-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_062647"/>
        </isoform>
        <isoform>
            <id>P08195-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_062648"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10 11 14 19 21 24 26 39 45">Expressed ubiquitously in all tissues tested with highest levels detected in kidney, placenta and testis and weakest level in thymus. During gestation, expression in the placenta was significantly stronger at full-term than at the mid-trimester stage. Expressed in HUVECS and at low levels in resting peripheral blood T-lymphocytes and quiescent fibroblasts. Also expressed in fetal liver and in the astrocytic process of primary astrocytic gliomas. Expressed in retinal endothelial cells and in the intestinal epithelial cell line C2BBe1.</text>
    </comment>
    <comment type="induction">
        <text evidence="14 32 34 36 37 39 45">Expression is induced in resting peripheral blood T-lymphocytes following PHA stimulation. Expression increases at the time of maximal DNA synthesis, in fibroblasts stimulated to divide. Expression and the uptake of leucine is stimulated in mononuclear, cytotrophoblast-like choriocarcinoma cells by combined treatment with PMA and calcium ionophore. Up-regulated in response to hydrogen peroxide (PubMed:30341327). Highly expressed in various cancer types (PubMed:19292886, PubMed:23116296, PubMed:28350098).</text>
    </comment>
    <comment type="induction">
        <text evidence="37">(Microbial infection) Up-regulated upon hepatitis C virus/HCV infection via NS3-A4 viral protein complex; the up-regulation is mediated by oxidative stress (PubMed:30341327). Up-regulation of the complex formed by SLC3A2 and SLC7A5/LAT1 upon hepatitis C virus/HCV infection (PubMed:30341327).</text>
    </comment>
    <comment type="PTM">
        <text evidence="48">N-glycosylated; N-glycosylation is crucial for trafficking and stability of SLC3A2 to the plasma membrane.</text>
    </comment>
    <comment type="PTM">
        <text evidence="29">Phosphorylation on Ser-305; Ser-307 or Ser-309 and on Ser-426 or Ser-430 by ecto-protein kinases favors heterotypic cell-cell interactions.</text>
    </comment>
    <comment type="mass spectrometry" mass="57944.93" method="MALDI" evidence="15"/>
    <comment type="similarity">
        <text evidence="59">Belongs to the SLC3A transporter family.</text>
    </comment>
    <dbReference type="EMBL" id="J02939">
        <property type="protein sequence ID" value="AAA52497.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J02769">
        <property type="protein sequence ID" value="AAA51540.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03569">
        <property type="protein sequence ID" value="AAA35536.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21904">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21898">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21899">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21900">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21901">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21902">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21903">
        <property type="protein sequence ID" value="AAA35489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB018010">
        <property type="protein sequence ID" value="BAA84649.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP001160">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471076">
        <property type="protein sequence ID" value="EAW74118.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001061">
        <property type="protein sequence ID" value="AAH01061.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC003000">
        <property type="protein sequence ID" value="AAH03000.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BE794697">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31588.1">
        <molecule id="P08195-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31589.1">
        <molecule id="P08195-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31590.1">
        <molecule id="P08195-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8039.2">
        <molecule id="P08195-1"/>
    </dbReference>
    <dbReference type="PIR" id="A28455">
        <property type="entry name" value="SAHU4F"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001012680.1">
        <molecule id="P08195-5"/>
        <property type="nucleotide sequence ID" value="NM_001012662.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001012682.1">
        <molecule id="P08195-3"/>
        <property type="nucleotide sequence ID" value="NM_001012664.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001013269.1">
        <molecule id="P08195-2"/>
        <property type="nucleotide sequence ID" value="NM_001013251.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002385.3">
        <molecule id="P08195-1"/>
        <property type="nucleotide sequence ID" value="NM_002394.5"/>
    </dbReference>
    <dbReference type="PDB" id="2DH2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=111-529"/>
    </dbReference>
    <dbReference type="PDB" id="2DH3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=111-529"/>
    </dbReference>
    <dbReference type="PDB" id="6IRS">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="6IRT">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="6JMQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.31 A"/>
        <property type="chains" value="B=-"/>
    </dbReference>
    <dbReference type="PDB" id="6JMR">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.10 A"/>
        <property type="chains" value="B=-"/>
    </dbReference>
    <dbReference type="PDB" id="6S8V">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="B/D=111-529"/>
    </dbReference>
    <dbReference type="PDB" id="7B00">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.98 A"/>
        <property type="chains" value="B=1-529"/>
    </dbReference>
    <dbReference type="PDB" id="7CCS">
        <property type="method" value="EM"/>
        <property type="resolution" value="6.20 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7CMH">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7CMI">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7DF1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.81 A"/>
        <property type="chains" value="A/B/C/D=111-529"/>
    </dbReference>
    <dbReference type="PDB" id="7DSK">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7DSL">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7DSN">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7DSQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7EPZ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7P9U">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="7P9V">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="8A6L">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.18 A"/>
        <property type="chains" value="A=-"/>
    </dbReference>
    <dbReference type="PDB" id="8G0M">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="A=111-529"/>
    </dbReference>
    <dbReference type="PDB" id="8IDA">
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006865">
        <property type="term" value="P:amino acid transport"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006816">
        <property type="term" value="P:calcium ion transport"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005975">
        <property type="term" value="P:carbohydrate metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0015818">
        <property type="term" value="P:isoleucine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904273">
        <property type="term" value="P:L-alanine import across plasma membrane"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="ARUK-UCL"/>
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    <dbReference type="GO" id="GO:1902024">
        <property type="term" value="P:L-histidine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:1903801">
        <property type="term" value="P:L-leucine import across plasma membrane"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="ARUK-UCL"/>
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    <dbReference type="GO" id="GO:0015820">
        <property type="term" value="P:L-leucine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015821">
        <property type="term" value="P:methionine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015823">
        <property type="term" value="P:phenylalanine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015824">
        <property type="term" value="P:proline transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0043330">
        <property type="term" value="P:response to exogenous dsRNA"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0046718">
        <property type="term" value="P:symbiont entry into host cell"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070327">
        <property type="term" value="P:thyroid hormone transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015827">
        <property type="term" value="P:tryptophan transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015828">
        <property type="term" value="P:tyrosine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015829">
        <property type="term" value="P:valine transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd11345">
        <property type="entry name" value="AmyAc_SLC3A2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.1180:FF:000012">
        <property type="entry name" value="4F2 cell-surface antigen heavy chain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.20.20.80:FF:000061">
        <property type="entry name" value="4F2 cell-surface antigen heavy chain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.20.20.80">
        <property type="entry name" value="Glycosidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.1180">
        <property type="entry name" value="Golgi alpha-mannosidase II"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017853">
        <property type="entry name" value="GH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006047">
        <property type="entry name" value="GH13_cat_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013780">
        <property type="entry name" value="Glyco_hydro_b"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042280">
        <property type="entry name" value="SLC3A2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR031984">
        <property type="entry name" value="SLC3A2_N"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46673">
        <property type="entry name" value="4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46673:SF1">
        <property type="entry name" value="4F2 CELL-SURFACE ANTIGEN HEAVY CHAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00128">
        <property type="entry name" value="Alpha-amylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16028">
        <property type="entry name" value="SLC3A2_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR02045">
        <property type="entry name" value="F138DOMAIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00642">
        <property type="entry name" value="Aamy"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51445">
        <property type="entry name" value="(Trans)glycosidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51011">
        <property type="entry name" value="Glycosyl hydrolase domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0029">Amino-acid transport</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-1183">Host cell receptor for virus entry</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="initiator methionine" description="Removed" evidence="74 76 77">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000064383" description="Amino acid transporter heavy chain SLC3A2">
        <location>
            <begin position="2"/>
            <end position="529"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="8 38">
        <location>
            <begin position="2"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="38">
        <location>
            <begin position="84"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="8 38">
        <location>
            <begin position="105"/>
            <end position="529"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="15"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylserine" evidence="74 76 77">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="76 79">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="3">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="79">
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="75 79">
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="61">
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="61">
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="61">
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="61">
        <location>
            <position position="426"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="61">
        <location>
            <position position="430"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="20 31 33 38 41 42 46 47 63 66 67 71 73">
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="20 25 31 33 38 41 42 46 47 63 66 67 71 73">
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="20 25 30 33 38 41 42 46 47 63 66 67 71 73">
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="31 33 38 41 42 46 47 63 65 67 71 73">
        <location>
            <position position="405"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-63 in SLC7A5; C-57 in SLC7A11 and C-53 in SLC7A8)" evidence="38 41 47 60 71">
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)">
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="80">
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_062646" description="In isoform 1.">
        <original>M</original>
        <variation>MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDPLPSASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_062647" description="In isoform 3.">
        <original>M</original>
        <variation>MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_062648" description="In isoform 5.">
        <original>M</original>
        <variation>MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSETGSDCVTQAGLQLLASSDPPALASKNAEVTVETGFHHVSQADIEFLTSIDPTASASGSAGITGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly decreased leucine transport activity." evidence="38">
        <original>R</original>
        <variation>A</variation>
        <variation>E</variation>
        <variation>K</variation>
        <variation>L</variation>
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes dimerization, leucine uptake and interaction with beta-1 integrins." evidence="13 28 51">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Nearly abolishes leucine transport activity." evidence="38">
        <location>
            <begin position="133"/>
            <end position="529"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-280; Q-323 and Q-405." evidence="48">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264; Q-323 and Q-405." evidence="48">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264 Q-280 and Q-405." evidence="48">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on dimerization, leucine uptake or interaction with beta-1 integrins." evidence="13 51">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs both the stability and the trafficking of SLC3A2 to the plasma membrane; when associated with Q-264 Q-280 and Q-323." evidence="48">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="405"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly decreased leucine transport activity." evidence="38">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAA51540." evidence="59" ref="3">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="122"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAA35489." evidence="59" ref="5">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>GE</original>
        <variation>PQ</variation>
        <location>
            <begin position="311"/>
            <end position="312"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>G</original>
        <variation>P</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAA35489." evidence="59" ref="5">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="508"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA35536." evidence="59" ref="4">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="helix" evidence="84">
        <location>
            <begin position="66"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="strand" evidence="90">
        <location>
            <begin position="74"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="helix" evidence="84">
        <location>
            <begin position="77"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="helix" evidence="84">
        <location>
            <begin position="82"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="117"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="123"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="129"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="helix" evidence="84">
        <location>
            <begin position="135"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="140"/>
            <end position="144"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="147"/>
            <end position="152"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="156"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="164"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="turn" evidence="86">
        <location>
            <begin position="171"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="174"/>
            <end position="179"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="181"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="186"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="202"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="turn" evidence="83">
        <location>
            <begin position="209"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="213"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="strand" evidence="82">
        <location>
            <begin position="218"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="222"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="243"/>
            <end position="246"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="249"/>
            <end position="251"/>
        </location>
    </feature>
    <feature type="strand" evidence="92">
        <location>
            <begin position="252"/>
            <end position="254"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="255"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="274"/>
            <end position="278"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="284"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="turn" evidence="85">
        <location>
            <begin position="292"/>
            <end position="294"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="298"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="strand" evidence="87">
        <location>
            <begin position="302"/>
            <end position="304"/>
        </location>
    </feature>
    <feature type="strand" evidence="83">
        <location>
            <begin position="305"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="311"/>
            <end position="324"/>
        </location>
    </feature>
    <feature type="turn" evidence="83">
        <location>
            <begin position="325"/>
            <end position="327"/>
        </location>
    </feature>
    <feature type="strand" evidence="84">
        <location>
            <begin position="330"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="strand" evidence="89">
        <location>
            <begin position="336"/>
            <end position="338"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="340"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="346"/>
            <end position="348"/>
        </location>
    </feature>
    <feature type="helix" evidence="83">
        <location>
            <begin position="349"/>
            <end position="356"/>
        </location>
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<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="202" xmlns="https://uniprot.org/uniprot">
    <accession>P28221</accession>
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    <reference key="1">
        <citation type="journal article" date="1991" name="Mol. Pharmacol." volume="40" first="143" last="148">
            <title>Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor.</title>
            <authorList>
                <person name="Hamblin M.W."/>
                <person name="Metcalf M.A."/>
            </authorList>
            <dbReference type="PubMed" id="1652050"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1992" name="Proc. Natl. Acad. Sci. U.S.A." volume="89" first="3630" last="3634">
            <title>Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta.</title>
            <authorList>
                <person name="Weinshank R.L."/>
                <person name="Zgombick J.M."/>
                <person name="Macchi M.J."/>
                <person name="Branchek T.A."/>
                <person name="Hartig P.R."/>
            </authorList>
            <dbReference type="PubMed" id="1565658"/>
            <dbReference type="DOI" id="10.1073/pnas.89.8.3630"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
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            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Eye</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="1828434"/>
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        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <dbReference type="PubMed" id="10452531"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
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            <dbReference type="PubMed" id="18476671"/>
            <dbReference type="DOI" id="10.1021/cr078224o"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
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            <dbReference type="PubMed" id="20945968"/>
            <dbReference type="DOI" id="10.33549/physiolres.931903"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.99 ANGSTROMS) OF 2-377 IN COMPLEX WITH SEROTONON; GNB1; GNG2 AND GNAI1</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>FUNCTION</scope>
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        <scope>VARIANT LEU-265</scope>
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        <scope>ERRATUM OF PUBMED:10391209</scope>
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    <comment type="function">
        <text evidence="6 7 8 10 12 13">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). HTR1D is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:33762731). Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity (PubMed:18476671, PubMed:20945968). May also play a role in regulating the release of other neurotransmitters (PubMed:18476671, PubMed:20945968). May play a role in vasoconstriction (PubMed:18476671, PubMed:20945968).</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Homodimer. Heterodimer with HTR1B.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 7 8">Cell membrane</location>
            <topology evidence="6 7 8">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9">Detected in brain neocortex and caudate nucleus (at protein level).</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA35491.1"/>
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        <property type="protein sequence ID" value="AAA60315.1"/>
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        <property type="protein sequence ID" value="AAM21126.1"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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        <property type="entry name" value="A53279"/>
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        <property type="nucleotide sequence ID" value="NM_000864.5"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
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        <property type="interactions" value="3"/>
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    <dbReference type="STRING" id="9606.ENSP00000363748"/>
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    <accession>P46098</accession>
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    <accession>Q99918</accession>
    <accession>Q9BSZ9</accession>
    <name>5HT3A_HUMAN</name>
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            <fullName evidence="16">5-hydroxytryptamine receptor 3A</fullName>
            <shortName>5-HT3-A</shortName>
            <shortName>5-HT3A</shortName>
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        <alternativeName>
            <fullName>5-hydroxytryptamine receptor 3</fullName>
            <shortName>5-HT-3</shortName>
            <shortName>5-HT3R</shortName>
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        <alternativeName>
            <fullName>Serotonin receptor 3A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Serotonin-gated ion channel receptor</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="18" type="primary">HTR3A</name>
        <name type="synonym">5HT3R</name>
        <name type="synonym">HTR3</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="Mol. Pharmacol." volume="48" first="407" last="416">
            <title>Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species.</title>
            <authorList>
                <person name="Miyake A."/>
                <person name="Mochizuki S."/>
                <person name="Takemoto Y."/>
                <person name="Akuzawa S."/>
            </authorList>
            <dbReference type="PubMed" id="7565620"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
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    <reference key="2">
        <citation type="journal article" date="1995" name="Mol. Pharmacol." volume="48" first="1054" last="1062">
            <title>Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit.</title>
            <authorList>
                <person name="Belelli D."/>
                <person name="Balcarek J.M."/>
                <person name="Hope A.G."/>
                <person name="Peters J.A."/>
                <person name="Lambert J.J."/>
                <person name="Blackburn T.P."/>
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            <dbReference type="PubMed" id="8848005"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Amygdala</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1998" name="Ann. N. Y. Acad. Sci." volume="861" first="234" last="235">
            <title>Molecular cloning of alternatively spliced human 5HT3 receptor cDNAs.</title>
            <authorList>
                <person name="Bruess M."/>
                <person name="Goethert M."/>
                <person name="Hayer M."/>
                <person name="Bonisch H."/>
            </authorList>
            <dbReference type="PubMed" id="9928262"/>
            <dbReference type="DOI" id="10.1111/j.1749-6632.1998.tb10196.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Amygdala</tissue>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2000" name="Neuropharmacology" volume="39" first="308" last="315">
            <title>Exon-intron organization of the human 5-HT3A receptor gene.</title>
            <authorList>
                <person name="Bruess M."/>
                <person name="Eucker T."/>
                <person name="Goethert M."/>
                <person name="Bonisch H."/>
            </authorList>
            <dbReference type="PubMed" id="10670426"/>
            <dbReference type="DOI" id="10.1016/s0028-3908(99)00116-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
    <reference key="5">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <source>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Small intestine</tissue>
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        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>REGION</scope>
        <scope>MUTAGENESIS OF ARG-432; ARG-436 AND ARG-440</scope>
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            <dbReference type="PubMed" id="15809299"/>
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        <scope>INTERACTION WITH RIC3</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF TRP-178</scope>
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        <scope>VARIANT THR-33</scope>
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        <scope>VARIANTS HIS-344; ARG-391 AND GLN-409</scope>
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    <comment type="function">
        <text evidence="4 5 9 10">Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 9 10">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>Mg(2+)(in) = Mg(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29827"/>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 9 10">Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3B or HTR3C or HTR3D or HTR3E. The homomeric complex is functional but exhibits low conductance with modified voltage dependence, and decreased agonist and antagonist affinity. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo (PubMed:10521471, PubMed:15809299, PubMed:17392525, PubMed:9950429). Interacts with RIC3 (PubMed:15809299).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
        </interactant>
        <interactant intactId="EBI-9008753">
            <id>Q8WXA8</id>
            <label>HTR3C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
        </interactant>
        <interactant intactId="EBI-9008717">
            <id>Q70Z44</id>
            <label>HTR3D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
        </interactant>
        <interactant intactId="EBI-11174612">
            <id>A5X5Y0-1</id>
            <label>HTR3E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
        </interactant>
        <interactant intactId="EBI-11163690">
            <id>A5X5Y0-3</id>
            <label>HTR3E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="17">Postsynaptic cell membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="17">Cell membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P46098-1</id>
            <name>1</name>
            <name>5-HT3R-AS</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P46098-2</id>
            <name>2</name>
            <name>5-HT3R-AL</name>
            <sequence type="described" ref="VSP_000078"/>
        </isoform>
        <isoform>
            <id>P46098-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_042214"/>
        </isoform>
        <isoform>
            <id>P46098-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_043484"/>
        </isoform>
        <isoform>
            <id>P46098-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_043484 VSP_000078"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Expressed in cerebral cortex, amygdala, hippocampus, and testis. Detected in monocytes of the spleen and tonsil, in small and large intestine, uterus, prostate, ovary and placenta.</text>
    </comment>
    <comment type="domain">
        <text evidence="5">The HA-stretch region of HTR3A seems to be responsible for the low conductance of HTR3A homomers compared to that of HTR3A/HTR3B heteromers.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3A sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="D49394">
        <property type="protein sequence ID" value="BAA08387.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S82612">
        <property type="protein sequence ID" value="AAB37533.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ003078">
        <property type="protein sequence ID" value="CAA05851.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ003079">
        <property type="protein sequence ID" value="CAA05852.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ005205">
        <property type="protein sequence ID" value="CAA06442.3"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF498984">
        <property type="protein sequence ID" value="AAM21131.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007204">
        <property type="protein sequence ID" value="AAP35868.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CD014118">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299973">
        <property type="protein sequence ID" value="BAG61798.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP000908">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67238.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67240.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002354">
        <property type="protein sequence ID" value="AAH02354.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004453">
        <property type="protein sequence ID" value="AAH04453.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53710.1">
        <molecule id="P46098-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8365.3">
        <molecule id="P46098-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8366.3">
        <molecule id="P46098-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000860.3">
        <molecule id="P46098-1"/>
        <property type="nucleotide sequence ID" value="NM_000869.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001155244.1">
        <molecule id="P46098-3"/>
        <property type="nucleotide sequence ID" value="NM_001161772.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_998786.3">
        <molecule id="P46098-2"/>
        <property type="nucleotide sequence ID" value="NM_213621.4"/>
    </dbReference>
    <dbReference type="PDB" id="8AXD">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.98 A"/>
        <property type="chains" value="A/B/C/D/E=27-478"/>
    </dbReference>
    <dbReference type="PDB" id="8BL8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.21 A"/>
        <property type="chains" value="A/B/C/D/E=29-478"/>
    </dbReference>
    <dbReference type="PDB" id="8BLA">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B/C/D/E=29-478"/>
    </dbReference>
    <dbReference type="PDB" id="8BLB">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B/C/D/E=29-478"/>
    </dbReference>
    <dbReference type="PDBsum" id="8AXD"/>
    <dbReference type="PDBsum" id="8BL8"/>
    <dbReference type="PDBsum" id="8BLA"/>
    <dbReference type="PDBsum" id="8BLB"/>
    <dbReference type="AlphaFoldDB" id="P46098"/>
    <dbReference type="EMDB" id="EMD-15699"/>
    <dbReference type="EMDB" id="EMD-16103"/>
    <dbReference type="EMDB" id="EMD-16104"/>
    <dbReference type="EMDB" id="EMD-16105"/>
    <dbReference type="SMR" id="P46098"/>
    <dbReference type="BioGRID" id="109591">
        <property type="interactions" value="118"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2175">
        <property type="entry name" value="5-hydroxytryptamine-3A receptor complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-271">
        <property type="entry name" value="5-hydroxytryptamine-3A/B receptor complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-272">
        <property type="entry name" value="5-hydroxytryptamine-3A/D receptor complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-273">
        <property type="entry name" value="5-hydroxytryptamine-3A/E receptor complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-276">
        <property type="entry name" value="5-hydroxytryptamine-3A/C receptor complex"/>
    </dbReference>
    <dbReference type="CORUM" id="P46098"/>
    <dbReference type="FunCoup" id="P46098">
        <property type="interactions" value="308"/>
    </dbReference>
    <dbReference type="IntAct" id="P46098">
        <property type="interactions" value="118"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000347754"/>
    <dbReference type="BindingDB" id="P46098"/>
    <dbReference type="ChEMBL" id="CHEMBL1899"/>
    <dbReference type="DrugBank" id="DB00969">
        <property type="generic name" value="Alosetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00543">
        <property type="generic name" value="Amoxapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01238">
        <property type="generic name" value="Aripiprazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14185">
        <property type="generic name" value="Aripiprazole lauroxil"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01156">
        <property type="generic name" value="Bupropion"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09061">
        <property type="generic name" value="Cannabidiol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04885">
        <property type="generic name" value="Cilansetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00604">
        <property type="generic name" value="Cisapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00363">
        <property type="generic name" value="Clozapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05642">
        <property type="generic name" value="DDP-225"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05049">
        <property type="generic name" value="DDP733"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00757">
        <property type="generic name" value="Dolasetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00988">
        <property type="generic name" value="Dopamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12141">
        <property type="generic name" value="Gilteritinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00889">
        <property type="generic name" value="Granisetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01221">
        <property type="generic name" value="Ketamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00555">
        <property type="generic name" value="Lamotrigine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01202">
        <property type="generic name" value="Levetiracetam"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00408">
        <property type="generic name" value="Loxapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01043">
        <property type="generic name" value="Memantine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00333">
        <property type="generic name" value="Methadone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01233">
        <property type="generic name" value="Metoclopramide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00334">
        <property type="generic name" value="Olanzapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00904">
        <property type="generic name" value="Ondansetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00377">
        <property type="generic name" value="Palonosetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00715">
        <property type="generic name" value="Paroxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00721">
        <property type="generic name" value="Procaine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01224">
        <property type="generic name" value="Quetiapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09290">
        <property type="generic name" value="Ramosetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04917">
        <property type="generic name" value="Renzapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00728">
        <property type="generic name" value="Rocuronium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08839">
        <property type="generic name" value="Serotonin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09304">
        <property type="generic name" value="Setiptiline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13025">
        <property type="generic name" value="Tiapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB06422">
        <property type="generic name" value="Ticalopride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00726">
        <property type="generic name" value="Trimipramine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11699">
        <property type="generic name" value="Tropisetron"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01199">
        <property type="generic name" value="Tubocurarine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09068">
        <property type="generic name" value="Vortioxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00246">
        <property type="generic name" value="Ziprasidone"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P46098"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="373"/>
    <dbReference type="TCDB" id="1.A.9.2.1">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P46098">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P46098">
        <property type="glycosylation" value="7 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P46098"/>
    <dbReference type="PhosphoSitePlus" id="P46098"/>
    <dbReference type="BioMuta" id="HTR3A"/>
    <dbReference type="DMDM" id="1168222"/>
    <dbReference type="MassIVE" id="P46098"/>
    <dbReference type="PaxDb" id="9606-ENSP00000347754"/>
    <dbReference type="Antibodypedia" id="18364">
        <property type="antibodies" value="413 antibodies from 35 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3359"/>
    <dbReference type="Ensembl" id="ENST00000299961.5">
        <molecule id="P46098-3"/>
        <property type="protein sequence ID" value="ENSP00000299961.4"/>
        <property type="gene ID" value="ENSG00000166736.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000355556.6">
        <molecule id="P46098-5"/>
        <property type="protein sequence ID" value="ENSP00000347754.2"/>
        <property type="gene ID" value="ENSG00000166736.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000375498.6">
        <molecule id="P46098-4"/>
        <property type="protein sequence ID" value="ENSP00000364648.2"/>
        <property type="gene ID" value="ENSG00000166736.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000504030.7">
        <molecule id="P46098-1"/>
        <property type="protein sequence ID" value="ENSP00000424189.2"/>
        <property type="gene ID" value="ENSG00000166736.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000506841.6">
        <molecule id="P46098-2"/>
        <property type="protein sequence ID" value="ENSP00000424776.2"/>
        <property type="gene ID" value="ENSG00000166736.13"/>
    </dbReference>
    <dbReference type="GeneID" id="3359"/>
    <dbReference type="KEGG" id="hsa:3359"/>
    <dbReference type="MANE-Select" id="ENST00000504030.7">
        <property type="protein sequence ID" value="ENSP00000424189.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000869.6"/>
        <property type="RefSeq protein sequence ID" value="NP_000860.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010rxa.3">
        <molecule id="P46098-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5297"/>
    <dbReference type="ClinPGx" id="PA29555"/>
    <dbReference type="CTD" id="3359"/>
    <dbReference type="DisGeNET" id="3359"/>
    <dbReference type="GeneCards" id="HTR3A"/>
    <dbReference type="HGNC" id="HGNC:5297">
        <property type="gene designation" value="HTR3A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000166736">
        <property type="expression patterns" value="Group enriched (brain, intestine, lymphoid tissue, pancreas, salivary gland)"/>
    </dbReference>
    <dbReference type="MalaCards" id="HTR3A"/>
    <dbReference type="MIM" id="182139">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166736"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000166736"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157705"/>
    <dbReference type="HOGENOM" id="CLU_018074_5_0_1"/>
    <dbReference type="InParanoid" id="P46098"/>
    <dbReference type="OMA" id="KFFVVIR"/>
    <dbReference type="OrthoDB" id="410315at2759"/>
    <dbReference type="PAN-GO" id="P46098">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P46098"/>
    <dbReference type="PathwayCommons" id="P46098"/>
    <dbReference type="Reactome" id="R-HSA-112314">
        <property type="pathway name" value="Neurotransmitter receptors and postsynaptic signal transmission"/>
    </dbReference>
    <dbReference type="SignaLink" id="P46098"/>
    <dbReference type="SIGNOR" id="P46098"/>
    <dbReference type="Agora" id="ENSG00000166736"/>
    <dbReference type="BioGRID-ORCS" id="3359">
        <property type="hits" value="7 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HTR3A"/>
    <dbReference type="GenomeRNAi" id="3359"/>
    <dbReference type="Pharos" id="P46098">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P46098"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="P46098">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000166736">
        <property type="expression patterns" value="Expressed in dorsal root ganglion and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P46098">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032154">
        <property type="term" value="C:cleavage furrow"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904602">
        <property type="term" value="C:serotonin-activated cation-selective channel complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902495">
        <property type="term" value="C:transmembrane transporter complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005231">
        <property type="term" value="F:excitatory extracellular ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099507">
        <property type="term" value="F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051378">
        <property type="term" value="F:serotonin binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022850">
        <property type="term" value="F:serotonin-gated monoatomic cation channel activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098662">
        <property type="term" value="P:inorganic cation transmembrane transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007210">
        <property type="term" value="P:serotonin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140227">
        <property type="term" value="P:serotonin-gated cation-selective signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="CDD" id="cd19011">
        <property type="entry name" value="LGIC_ECD_5-HT3A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19063">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000020">
        <property type="entry name" value="5-hydroxytryptamine (serotonin) receptor 3A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.70.170.10:FF:000017">
        <property type="entry name" value="5-hydroxytryptamine receptor 3A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008132">
        <property type="entry name" value="5HT3_rcpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008133">
        <property type="entry name" value="5HT3_rcpt_A"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049944">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
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    <keyword id="KW-0406">Ion transport</keyword>
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    <keyword id="KW-0472">Membrane</keyword>
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            <begin position="1"/>
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    <feature type="chain" id="PRO_0000000408" description="5-hydroxytryptamine receptor 3A">
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            <begin position="456"/>
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    <feature type="region of interest" description="HA-stretch; determines single-channel conductance in 5-HT3 receptors" evidence="5">
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            <begin position="393"/>
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            <position position="104"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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            <position position="186"/>
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            <begin position="157"/>
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            <position position="306"/>
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            <position position="33"/>
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            <position position="253"/>
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            <position position="178"/>
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            <position position="46"/>
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            <position position="321"/>
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            <begin position="93"/>
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            <begin position="107"/>
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            <begin position="112"/>
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            <begin position="120"/>
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            <begin position="125"/>
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            <begin position="136"/>
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            <begin position="143"/>
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            <begin position="162"/>
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            <begin position="168"/>
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            <begin position="185"/>
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            <begin position="193"/>
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<entry dataset="Swiss-Prot" created="2003-09-19" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>Q13541</accession>
    <accession>B2R502</accession>
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            <fullName>Eukaryotic translation initiation factor 4E-binding protein 1</fullName>
            <shortName>4E-BP1</shortName>
            <shortName>eIF4E-binding protein 1</shortName>
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        <alternativeName>
            <fullName>Phosphorylated heat- and acid-stable protein regulated by insulin 1</fullName>
            <shortName>PHAS-I</shortName>
        </alternativeName>
    </protein>
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        <name type="primary">EIF4EBP1</name>
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        <name type="scientific">Homo sapiens</name>
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        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Nature" volume="371" first="762" last="767">
            <title>Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.</title>
            <authorList>
                <person name="Pause A."/>
                <person name="Belsham G.J."/>
                <person name="Gingras A.-C."/>
                <person name="Donze O."/>
                <person name="Lin T.-A."/>
                <person name="Lawrence J.C. Jr."/>
                <person name="Sonenberg N."/>
            </authorList>
            <dbReference type="PubMed" id="7935836"/>
            <dbReference type="DOI" id="10.1038/371762a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>PHOSPHORYLATION</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference evidence="23" key="2">
        <citation type="submission" date="2000-06" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of multiple genes and immunogenic epitopes of pancreatic cancer cells.</title>
            <authorList>
                <person name="Ito M."/>
                <person name="Shichijo S."/>
                <person name="Tsuda N."/>
                <person name="Ochi M."/>
                <person name="Harashima N."/>
                <person name="Saito N."/>
                <person name="Itoh K."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference evidence="23" key="3">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference evidence="23" key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
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            <dbReference type="DOI" id="10.1016/j.molcel.2012.04.004"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>UBIQUITINATION AT LYS-57</scope>
        <scope>PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70</scope>
        <scope>MUTAGENESIS OF THR-37; THR-46; LYS-57; 59-LEU-MET-60; SER-65; LYS-69; THR-70 AND LYS-105</scope>
    </reference>
    <reference key="26">
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            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
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                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; SER-65; THR-70; SER-101 AND SER-112</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="28">
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            <title>Characterization of the Raptor/4E-BP1 interaction by chemical cross-linking coupled with mass spectrometry analysis.</title>
            <authorList>
                <person name="Coffman K."/>
                <person name="Yang B."/>
                <person name="Lu J."/>
                <person name="Tetlow A.L."/>
                <person name="Pelliccio E."/>
                <person name="Lu S."/>
                <person name="Guo D.C."/>
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            </authorList>
            <dbReference type="PubMed" id="24403073"/>
            <dbReference type="DOI" id="10.1074/jbc.m113.482067"/>
        </citation>
        <scope>INTERACTION WITH RPTOR</scope>
        <scope>PHOSPHORYLATION BY MTOR</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70 AND THR-77</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="30">
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            <title>Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.</title>
            <authorList>
                <person name="Nguyen J.T."/>
                <person name="Ray C."/>
                <person name="Fox A.L."/>
                <person name="Mendonca D.B."/>
                <person name="Kim J.K."/>
                <person name="Krebsbach P.H."/>
            </authorList>
            <dbReference type="PubMed" id="29750193"/>
            <dbReference type="DOI" id="10.1126/sciadv.aao5838"/>
        </citation>
        <scope>PHOSPHORYLATION AT THR-37; THR-46; SER-65 AND THR-70</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="1998" name="Protein Sci." volume="7" first="1639" last="1642">
            <title>The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein.</title>
            <authorList>
                <person name="Fletcher C.M."/>
                <person name="Wagner G."/>
            </authorList>
            <dbReference type="PubMed" id="9684899"/>
            <dbReference type="DOI" id="10.1002/pro.5560070720"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 4-118</scope>
    </reference>
    <reference key="32">
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            <title>Structural basis for mRNA cap-binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods.</title>
            <authorList>
                <person name="Tomoo K."/>
                <person name="Matsushita Y."/>
                <person name="Fujisaki H."/>
                <person name="Abiko F."/>
                <person name="Shen X."/>
                <person name="Taniguchi T."/>
                <person name="Miyagawa H."/>
                <person name="Kitamura K."/>
                <person name="Miura K."/>
                <person name="Ishida T."/>
            </authorList>
            <dbReference type="PubMed" id="16271312"/>
            <dbReference type="DOI" id="10.1016/j.bbapap.2005.07.023"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-70 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG</scope>
    </reference>
    <reference key="33">
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            <title>Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms.</title>
            <authorList>
                <person name="Rosettani P."/>
                <person name="Knapp S."/>
                <person name="Vismara M.-G."/>
                <person name="Rusconi L."/>
                <person name="Cameron A.D."/>
            </authorList>
            <dbReference type="PubMed" id="17368478"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2007.02.019"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-67 IN COMPLEX WITH EIF4E2 AND MRNA CAP ANALOG</scope>
    </reference>
    <reference key="34">
        <citation type="journal article" date="2007" name="J. Mol. Biol." volume="372" first="7" last="15">
            <title>Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives.</title>
            <authorList>
                <person name="Brown C.J."/>
                <person name="McNae I."/>
                <person name="Fischer P.M."/>
                <person name="Walkinshaw M.D."/>
            </authorList>
            <dbReference type="PubMed" id="17631896"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2007.06.033"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-64 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG</scope>
    </reference>
    <reference evidence="24" key="35">
        <citation type="journal article" date="2015" name="Mol. Cell" volume="57" first="1074" last="1087">
            <title>Molecular architecture of 4E-BP translational inhibitors bound to eIF4E.</title>
            <authorList>
                <person name="Peter D."/>
                <person name="Igreja C."/>
                <person name="Weber R."/>
                <person name="Wohlbold L."/>
                <person name="Weiler C."/>
                <person name="Ebertsch L."/>
                <person name="Weichenrieder O."/>
                <person name="Izaurralde E."/>
            </authorList>
            <dbReference type="PubMed" id="25702871"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2015.01.017"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 50-83 IN COMPLEX WITH EIF4E</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>PHOSPHORYLATION AT SER-65 AND THR-70</scope>
    </reference>
    <reference evidence="25" key="36">
        <citation type="journal article" date="2017" name="Nature" volume="552" first="368" last="373">
            <title>Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.</title>
            <authorList>
                <person name="Yang H."/>
                <person name="Jiang X."/>
                <person name="Li B."/>
                <person name="Yang H.J."/>
                <person name="Miller M."/>
                <person name="Yang A."/>
                <person name="Dhar A."/>
                <person name="Pavletich N.P."/>
            </authorList>
            <dbReference type="PubMed" id="29236692"/>
            <dbReference type="DOI" id="10.1038/nature25023"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.43 ANGSTROMS) IN COMPLEX WITH MLST8; MTOR; RPTOR AND RHEB</scope>
        <scope>PHOSPHORYLATION AT THR-37 AND THR-46</scope>
        <scope>INTERACTION WITH RTOR</scope>
        <scope>MUTAGENESIS OF GLN-113</scope>
    </reference>
    <comment type="function">
        <text evidence="12 13 18">Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 9 10 11 12 14 15 16 18 19">Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:12150926, PubMed:16271312, PubMed:17368478, PubMed:17631896, PubMed:22578813, PubMed:25702871, PubMed:7935836, PubMed:8521827). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827, PubMed:24403073, PubMed:29236692).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-528269">
            <id>Q9UKV8</id>
            <label>AGO2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-742054">
            <id>Q96D03</id>
            <label>DDIT4L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-73440">
            <id>P06730</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>37</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-32715456">
            <id>P06730-1</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-18394358">
            <id>A6NMX2</id>
            <label>EIF4E1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-398610">
            <id>O60573</id>
            <label>EIF4E2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-32715389">
            <id>O60573-1</id>
            <label>EIF4E2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-11959475">
            <id>P25791-3</id>
            <label>LMO2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-2864512">
            <id>P50221</id>
            <label>MEOX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-359260">
            <id>P42345</id>
            <label>MTOR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-79165">
            <id>Q9NRD5</id>
            <label>PICK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-12029004">
            <id>P78424</id>
            <label>POU6F2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-307352">
            <id>Q04864</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-10829018">
            <id>Q04864-2</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-1567928">
            <id>Q8N122</id>
            <label>RPTOR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-533224">
            <id>P15884</id>
            <label>TCF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-625509">
            <id>Q8N720</id>
            <label>ZNF655</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-74090">
            <id>Q13541</id>
        </interactant>
        <interactant intactId="EBI-1571628">
            <id>Q9JLN9</id>
            <label>Mtor</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Nucleus</location>
        </subcellularLocation>
        <text evidence="2">Localization to the nucleus is unaffected by phosphorylation status.</text>
    </comment>
    <comment type="domain">
        <text evidence="7 14">The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 7 12 14 16 18 20">Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF (PubMed:12588975, PubMed:12747827, PubMed:22578813, PubMed:24403073, PubMed:29236692, PubMed:7935836, PubMed:9465032). Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E (PubMed:12588975, PubMed:12747827, PubMed:22578813, PubMed:24403073, PubMed:29236692, PubMed:7935836, PubMed:9465032).</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the eIF4E-binding protein family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/40432/EIF4EBP1"/>
    </comment>
    <dbReference type="EMBL" id="L36055">
        <property type="protein sequence ID" value="AAA62269.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB044548">
        <property type="protein sequence ID" value="BAB18650.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007162">
        <property type="protein sequence ID" value="AAP35826.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456769">
        <property type="protein sequence ID" value="CAG33050.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312011">
        <property type="protein sequence ID" value="BAG34949.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63341.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63342.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004459">
        <property type="protein sequence ID" value="AAH04459.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC058073">
        <property type="protein sequence ID" value="AAH58073.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS6100.1"/>
    <dbReference type="PIR" id="S50866">
        <property type="entry name" value="S50866"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004086.1">
        <property type="nucleotide sequence ID" value="NM_004095.4"/>
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    <dbReference type="PDB" id="1EJ4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="B=51-64"/>
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    <dbReference type="PDB" id="1EJH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="E/F/G/H=54-66"/>
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    <dbReference type="PDB" id="1WKW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="B=47-66"/>
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    <dbReference type="PDB" id="2JGB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="B=51-67"/>
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    <dbReference type="PDB" id="2JGC">
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        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="B=51-67"/>
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        <property type="resolution" value="2.10 A"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="29750193"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="7935836"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="8521827"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="9465032"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21"/>
    <evidence type="ECO:0000305" key="22">
        <source>
            <dbReference type="PubMed" id="22578813"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="23">
        <source>
            <dbReference type="EMBL" id="BAB18650.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PDB" id="4UED"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PDB" id="6BCU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PubMed" id="17525332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PubMed" id="18220336"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="35">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="36">
        <source>
            <dbReference type="PDB" id="2JGB"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="37">
        <source>
            <dbReference type="PDB" id="4UED"/>
        </source>
    </evidence>
    <sequence length="118" mass="12580" checksum="1682A6BA74132966" modified="2007-01-23" version="3">MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLMECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="194" xmlns="https://uniprot.org/uniprot">
    <accession>P50406</accession>
    <accession>Q13640</accession>
    <accession>Q5TGZ1</accession>
    <name>5HT6R_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="12">5-hydroxytryptamine receptor 6</fullName>
            <shortName evidence="11">5-HT-6</shortName>
            <shortName evidence="11">5-HT6</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="11">Serotonin receptor 6</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">HTR6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Neurochem." volume="66" first="47" last="56">
            <title>Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.</title>
            <authorList>
                <person name="Kohen R."/>
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            <dbReference type="PubMed" id="8522988"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Corpus striatum</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-10" db="EMBL/GenBank/DDBJ databases">
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                <person name="Kopatz S.A."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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                <person name="Mashreghi-Mohammadi M."/>
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                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
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                <person name="O'Dell C.N."/>
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                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
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                <person name="Pelan S."/>
                <person name="Phelps K."/>
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                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
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                <person name="Saenphimmachak C."/>
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                <person name="Skuce C.D."/>
                <person name="Smith M."/>
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                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
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                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1995" name="FEBS Lett." volume="370" first="215" last="221">
            <title>Expression of serotonin receptor mRNAs in blood vessels.</title>
            <authorList>
                <person name="Ullmer C."/>
                <person name="Schmuck K."/>
                <person name="Kalkman H.O."/>
                <person name="Luebbert H."/>
            </authorList>
            <dbReference type="PubMed" id="7656980"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)00828-w"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 215-280</scope>
        <source>
            <tissue>Corpus striatum</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2012" name="EMBO Mol. Med." volume="4" first="1043" last="1056">
            <title>5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia.</title>
            <authorList>
                <person name="Meffre J."/>
                <person name="Chaumont-Dubel S."/>
                <person name="Mannoury la Cour C."/>
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            </authorList>
            <dbReference type="PubMed" id="23027611"/>
            <dbReference type="DOI" id="10.1002/emmm.201201410"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH MTOR; RPTOR AND NF1</scope>
    </reference>
    <reference evidence="15" key="8">
        <citation type="journal article" date="2022" name="Mol. Cell" volume="82" first="2681" last="2695">
            <title>GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.</title>
            <authorList>
                <person name="Huang S."/>
                <person name="Xu P."/>
                <person name="Shen D.D."/>
                <person name="Simon I.A."/>
                <person name="Mao C."/>
                <person name="Tan Y."/>
                <person name="Zhang H."/>
                <person name="Harpsoee K."/>
                <person name="Li H."/>
                <person name="Zhang Y."/>
                <person name="You C."/>
                <person name="Yu X."/>
                <person name="Jiang Y."/>
                <person name="Zhang Y."/>
                <person name="Gloriam D.E."/>
                <person name="Xu H.E."/>
            </authorList>
            <dbReference type="PubMed" id="35714614"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2022.05.031"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 2-440 IN COMPLEX WITH SEROTONIN; GNB1; GNB2 AND GNAS2</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-106; CYS-110; SER-111; LEU-182; ALA-192; TRP-281; PHE-284; PHE-285 AND TYR-310</scope>
    </reference>
    <reference evidence="16" key="9">
        <citation type="journal article" date="2023" name="Proc. Natl. Acad. Sci. U.S.A." volume="120" first="e2209917120" last="e2209917120">
            <title>Structural insights into constitutive activity of 5-HT6 receptor.</title>
            <authorList>
                <person name="He L."/>
                <person name="Zhao Q."/>
                <person name="Qi J."/>
                <person name="Wang Y."/>
                <person name="Han W."/>
                <person name="Chen Z."/>
                <person name="Cong Y."/>
                <person name="Wang S."/>
            </authorList>
            <dbReference type="PubMed" id="36989299"/>
            <dbReference type="DOI" id="10.1073/pnas.2209917120"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 24-345 IN COMPLEX WITH SEROTONIN; GNB1 AND GNB2</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-106 AND TRP-281</scope>
    </reference>
    <reference evidence="17" key="10">
        <citation type="journal article" date="2023" name="Biochem. Biophys. Res. Commun." volume="671" first="327" last="334">
            <title>Structural insight into the selective agonist ST1936 binding of serotonin receptor 5-HT6.</title>
            <authorList>
                <person name="Pei Y."/>
                <person name="Wen X."/>
                <person name="Guo S.C."/>
                <person name="Yang Z.S."/>
                <person name="Zhang R."/>
                <person name="Xiao P."/>
                <person name="Sun J.P."/>
            </authorList>
            <dbReference type="PubMed" id="37327704"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2023.05.126"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.09 ANGSTROMS) IN COMPLEX WITH GNB1; GNB2 AND GNAS2</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF SER-111; PHE-188; PHE-284 AND TYR-310</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 6 7 8 9 10">G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35714614, PubMed:36989299, PubMed:37327704, PubMed:8522988). Also has a high affinity for tricyclic psychotropic drugs (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35714614). HTR6 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:35714614, PubMed:37327704). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of mTOR signaling (PubMed:23027611).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 6">Interacts with MTOR, RPTOR and NF1 (PubMed:23027611). Interacts with CDK5 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1182222">
            <id>P50406</id>
        </interactant>
        <interactant intactId="EBI-515315">
            <id>P06241</id>
            <label>FYN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1182222">
            <id>P50406</id>
        </interactant>
        <interactant intactId="EBI-764611">
            <id>P46821</id>
            <label>MAP1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1182222">
            <id>P50406</id>
        </interactant>
        <interactant intactId="EBI-726123">
            <id>P51513</id>
            <label>NOVA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Cell membrane</location>
            <topology evidence="7 8 9">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Expressed in several human brain regions, most prominently in the caudate nucleus.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">Specificity for G(s) G alpha proteins is determined by the length of transmembrane regions 5 and 6 (TM5 and TM6).</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="L41147">
        <property type="protein sequence ID" value="AAA92622.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY429105">
        <property type="protein sequence ID" value="AAR07900.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <original>A</original>
        <variation>Y</variation>
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            <position position="192"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished G-protein coupled receptor activity in response to serotonin." evidence="7 8">
        <original>W</original>
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            <position position="281"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished G-protein coupled receptor activity in response to serotonin." evidence="7 9">
        <original>F</original>
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            <position position="284"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="7">
        <original>F</original>
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            <position position="285"/>
        </location>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="7 9">
        <original>Y</original>
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            <position position="310"/>
        </location>
    </feature>
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        <original>V</original>
        <variation>M</variation>
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            <position position="247"/>
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        <location>
            <begin position="32"/>
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    <feature type="helix" evidence="18">
        <location>
            <begin position="55"/>
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    <feature type="helix" evidence="18">
        <location>
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    <feature type="helix" evidence="18">
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    <feature type="helix" evidence="18">
        <location>
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    <feature type="helix" evidence="18">
        <location>
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    <feature type="helix" evidence="18">
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            <dbReference type="PubMed" id="23027611"/>
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            <dbReference type="HGNC" id="HGNC:5301"/>
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            <dbReference type="PDB" id="7XTB"/>
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            <dbReference type="PDB" id="7YS6"/>
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    </evidence>
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            <dbReference type="PDB" id="8JLZ"/>
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    </evidence>
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            <dbReference type="PDB" id="7YS6"/>
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    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="8JLZ"/>
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    <sequence length="440" mass="46954" checksum="C888F47650C1D2EF" modified="1996-10-01" version="1">MVPEPGPTANSTPAWGAGPPSAPGGSGWVAAALCVVIALTAAANSLLIALICTQPALRNTSNFFLVSLFTSDLMVGLVVMPPAMLNALYGRWVLARGLCLLWTAFDVMCCSASILNLCLISLDRYLLILSPLRYKLRMTPLRALALVLGAWSLAALASFLPLLLGWHELGHARPPVPGQCRLLASLPFVLVASGLTFFLPSGAICFTYCRILLAARKQAVQVASLTTGMASQASETLQVPRTPRPGVESADSRRLATKHSRKALKASLTLGILLGMFFVTWLPFFVANIVQAVCDCISPGLFDVLTWLGYCNSTMNPIIYPLFMRDFKRALGRFLPCPRCPRERQASLASPSLRTSHSGPRPGLSLQQVLPLPLPPDSDSDSDAGSGGSSGLRLTAQLLLPGEATQDPPLPTRAAAAVNFFNIDPAEPELRPHPLGIPTN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="232" xmlns="https://uniprot.org/uniprot">
    <accession>P28223</accession>
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    <accession>B4DZ79</accession>
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            <taxon>Vertebrata</taxon>
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            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
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            <dbReference type="PubMed" id="8035173"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            <tissue>Brain</tissue>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Testis</tissue>
            <tissue>Thalamus</tissue>
        </source>
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        <scope>INTERACTION WITH GRM2</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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    <comment type="function">
        <text evidence="2 10 12 13 14 15 16 19 20 22">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity).</text>
    </comment>
    <comment type="function">
        <text evidence="17">(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="20 22">G-protein coupled receptor activity is regulated by lipids: oleamide increases HTR2A-mediated activity (PubMed:35084960). Inhibited by IHCH-7179 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and as an antagonist inhibitor for HTR2A (PubMed:38552625).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 11 12 15 16">Interacts (via C-terminus) with MPDZ and PATJ (PubMed:11150294, PubMed:14988405). May interact (via C-terminus) with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2 (PubMed:14988405). Interacts with GRM2 and DRD2; this may affect signaling (PubMed:18297054, PubMed:21645528, PubMed:22300836).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
        </interactant>
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
            <label>HTR2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
        </interactant>
        <interactant intactId="EBI-7474947">
            <id>P41595</id>
            <label>HTR2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
        </interactant>
        <interactant intactId="EBI-994141">
            <id>P28335</id>
            <label>HTR2C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
        </interactant>
        <interactant intactId="EBI-311035">
            <id>Q86UL8</id>
            <label>MAGI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
        </interactant>
        <interactant intactId="EBI-821405">
            <id>O75970</id>
            <label>MPDZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15573967">
            <id>P28223-1</id>
        </interactant>
        <interactant intactId="EBI-10232876">
            <id>Q14416</id>
            <label>GRM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15573967">
            <id>P28223-1</id>
        </interactant>
        <interactant intactId="EBI-21299643">
            <id>P28335-1</id>
            <label>HTR2C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15573967">
            <id>P28223-1</id>
        </interactant>
        <interactant intactId="EBI-397744">
            <id>P18654</id>
            <label>Rps6ka3</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="19">Cell membrane</location>
            <topology evidence="21">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Dendrite</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Axon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasmic vesicle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Membrane</location>
            <location evidence="1">Caveola</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Presynapse</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P28223-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P28223-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046663"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="12">Detected in brain cortex (at protein level). Detected in blood platelets.</text>
    </comment>
    <comment type="domain">
        <text evidence="9 11">The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="19">Binds lysergic acid diethylamine (LSD) in the orthosteric pocket (PubMed:28129538). Bound LSD dissociates extremely slowly, with a residence time of about 221 minutes at 37 degrees Celsius (PubMed:28129538).</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <original>D</original>
        <variation>N</variation>
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    <accession>E1P503</accession>
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        <name evidence="15" type="primary">HTR1E</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
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                <person name="Zgombick J.M."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <dbReference type="PubMed" id="14574404"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-363</scope>
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            <dbReference type="PubMed" id="14744596"/>
            <dbReference type="DOI" id="10.1016/j.ejphar.2003.11.019"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Chem. Rev." volume="108" first="1614" last="1641">
            <title>Serotonin receptors.</title>
            <authorList>
                <person name="Nichols D.E."/>
                <person name="Nichols C.D."/>
            </authorList>
            <dbReference type="PubMed" id="18476671"/>
            <dbReference type="DOI" id="10.1021/cr078224o"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="J. Pharmacol. Exp. Ther." volume="337" first="860" last="867">
            <title>Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships.</title>
            <authorList>
                <person name="Klein M.T."/>
                <person name="Dukat M."/>
                <person name="Glennon R.A."/>
                <person name="Teitler M."/>
            </authorList>
            <dbReference type="PubMed" id="21422162"/>
            <dbReference type="DOI" id="10.1124/jpet.111.179606"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2011" name="Physiol. Res." volume="60" first="15" last="25">
            <title>Serotonin receptors - from molecular biology to clinical applications.</title>
            <authorList>
                <person name="Pytliak M."/>
                <person name="Vargova V."/>
                <person name="Mechirova V."/>
                <person name="Felsoci M."/>
            </authorList>
            <dbReference type="PubMed" id="20945968"/>
            <dbReference type="DOI" id="10.33549/physiolres.931903"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2022" name="Cell Discov." volume="8" first="50" last="50">
            <title>Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A.</title>
            <authorList>
                <person name="Tan Y."/>
                <person name="Xu P."/>
                <person name="Huang S."/>
                <person name="Yang G."/>
                <person name="Zhou F."/>
                <person name="He X."/>
                <person name="Ma H."/>
                <person name="Xu H.E."/>
                <person name="Jiang Y."/>
            </authorList>
            <dbReference type="PubMed" id="35610220"/>
            <dbReference type="DOI" id="10.1038/s41421-022-00412-3"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF GLU-311</scope>
    </reference>
    <reference evidence="16" key="14">
        <citation type="journal article" date="2021" name="Nature" volume="592" first="469" last="473">
            <title>Structural insights into the lipid and ligand regulation of serotonin receptors.</title>
            <authorList>
                <person name="Xu P."/>
                <person name="Huang S."/>
                <person name="Zhang H."/>
                <person name="Mao C."/>
                <person name="Zhou X.E."/>
                <person name="Cheng X."/>
                <person name="Simon I.A."/>
                <person name="Shen D.D."/>
                <person name="Yen H.Y."/>
                <person name="Robinson C.V."/>
                <person name="Harpsoee K."/>
                <person name="Svensson B."/>
                <person name="Guo J."/>
                <person name="Jiang H."/>
                <person name="Gloriam D.E."/>
                <person name="Melcher K."/>
                <person name="Jiang Y."/>
                <person name="Zhang Y."/>
                <person name="Xu H.E."/>
            </authorList>
            <dbReference type="PubMed" id="33762731"/>
            <dbReference type="DOI" id="10.1038/s41586-021-03376-8"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.0 ANGSTROMS) OF 2-365 IN COMPLEX WITH GNAI1; GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="22" first="231" last="238">
            <title>Characterization of single-nucleotide polymorphisms in coding regions of human genes.</title>
            <authorList>
                <person name="Cargill M."/>
                <person name="Altshuler D."/>
                <person name="Ireland J."/>
                <person name="Sklar P."/>
                <person name="Ardlie K."/>
                <person name="Patil N."/>
                <person name="Shaw N."/>
                <person name="Lane C.R."/>
                <person name="Lim E.P."/>
                <person name="Kalyanaraman N."/>
                <person name="Nemesh J."/>
                <person name="Ziaugra L."/>
                <person name="Friedland L."/>
                <person name="Rolfe A."/>
                <person name="Warrington J."/>
                <person name="Lipshutz R."/>
                <person name="Daley G.Q."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="10391209"/>
            <dbReference type="DOI" id="10.1038/10290"/>
        </citation>
        <scope>VARIANT PHE-262</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="23" first="373" last="373">
            <authorList>
                <person name="Cargill M."/>
                <person name="Altshuler D."/>
                <person name="Ireland J."/>
                <person name="Sklar P."/>
                <person name="Ardlie K."/>
                <person name="Patil N."/>
                <person name="Shaw N."/>
                <person name="Lane C.R."/>
                <person name="Lim E.P."/>
                <person name="Kalyanaraman N."/>
                <person name="Nemesh J."/>
                <person name="Ziaugra L."/>
                <person name="Friedland L."/>
                <person name="Rolfe A."/>
                <person name="Warrington J."/>
                <person name="Lipshutz R."/>
                <person name="Daley G.Q."/>
                <person name="Lander E.S."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:10391209</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7 8 9 10 11 12">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). Also functions as a receptor for various alkaloids and psychoactive substances (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). HTR1E is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:33762731, PubMed:35610220).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1043151">
            <id>P28566</id>
        </interactant>
        <interactant intactId="EBI-356231">
            <id>P06576</id>
            <label>ATP5F1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1043151">
            <id>P28566</id>
        </interactant>
        <interactant intactId="EBI-748397">
            <id>P50222</id>
            <label>MEOX2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P28566</id>
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        <interactant intactId="EBI-748974">
            <id>Q96CV9</id>
            <label>OPTN</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 7 8 9 10">Cell membrane</location>
            <topology evidence="6 7 8 9 10">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Detected in brain.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="M91467">
        <property type="protein sequence ID" value="AAA58353.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAA77558.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAA58355.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM21127.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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        <property type="protein sequence ID" value="EAW48616.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW48617.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH69751.1"/>
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        <property type="protein sequence ID" value="BAA94458.1"/>
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        <property type="entry name" value="A45260"/>
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        <property type="nucleotide sequence ID" value="NM_000865.3"/>
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        <property type="nucleotide sequence ID" value="XM_011535789.3"/>
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    <dbReference type="RefSeq" id="XP_054211290.1">
        <property type="nucleotide sequence ID" value="XM_054355315.1"/>
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    <dbReference type="PDB" id="7E33">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="R=2-365"/>
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    <dbReference type="PDB" id="8UGY">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.31 A"/>
        <property type="chains" value="R=20-358"/>
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    <dbReference type="PDB" id="8UH3">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.31 A"/>
        <property type="chains" value="D=1-365"/>
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        <property type="interactions" value="8"/>
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        <property type="interactions" value="919"/>
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        <property type="generic name" value="Aripiprazole"/>
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        <property type="generic name" value="Aripiprazole lauroxil"/>
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        <property type="generic name" value="Clozapine"/>
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        <property type="generic name" value="Dihydroergocornine"/>
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    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
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        <property type="generic name" value="Dihydroergotamine"/>
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        <property type="generic name" value="Ergoloid mesylate"/>
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        <property type="generic name" value="Gilteritinib"/>
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        <property type="generic name" value="Ketamine"/>
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        <property type="generic name" value="Lecozotan"/>
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        <property type="generic name" value="Loxapine"/>
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        <property type="generic name" value="m-Chlorophenylpiperazine"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_000865.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000856.1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="7tm_1"/>
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        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Euteleostomi</taxon>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <reference key="2">
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            <dbReference type="PubMed" id="1610347"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="1348246"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)42612-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="4">
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            </authorList>
            <dbReference type="PubMed" id="1559993"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)42552-5"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
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                <person name="Weinshank R.L."/>
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            <dbReference type="PubMed" id="1565658"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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                <person name="Demchyshyn L."/>
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            <dbReference type="PubMed" id="1351684"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="7">
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                <person name="Veldman S.A."/>
                <person name="Bienkowski M.J."/>
            </authorList>
            <dbReference type="PubMed" id="1328844"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <citation type="journal article" date="2004" name="Mol. Biol. Evol." volume="21" first="936" last="944">
            <title>Human-specific amino acid changes found in 103 protein-coding genes.</title>
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            </authorList>
            <dbReference type="PubMed" id="15014171"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="9">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
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                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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                <person name="Gillson C.J."/>
                <person name="Glithero R.J."/>
                <person name="Grafham D.V."/>
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                <person name="Howe K.L."/>
                <person name="Howell G.R."/>
                <person name="Huckle E."/>
                <person name="Humphray S.J."/>
                <person name="Humphries M.D."/>
                <person name="Hunt A.R."/>
                <person name="Johnson C.M."/>
                <person name="Joy A.A."/>
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                <person name="Keenan S.J."/>
                <person name="Kimberley A.M."/>
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                <person name="Langford C."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Leversha M."/>
                <person name="Lloyd C.R."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J.E."/>
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                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Maslen G.L."/>
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                <person name="McCann O.T."/>
                <person name="McLaren S.J."/>
                <person name="McLay K."/>
                <person name="McMurray A."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Niblett D."/>
                <person name="Nickerson T."/>
                <person name="Novik K.L."/>
                <person name="Oliver K."/>
                <person name="Overton-Larty E.K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Phillips S."/>
                <person name="Plumb R.W."/>
                <person name="Porter K.M."/>
                <person name="Ramsey Y."/>
                <person name="Ranby S.A."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Searle S.M."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Skuce C.D."/>
                <person name="Smith S."/>
                <person name="Smith M."/>
                <person name="Spraggon L."/>
                <person name="Squares S.L."/>
                <person name="Steward C.A."/>
                <person name="Sycamore N."/>
                <person name="Tamlyn-Hall G."/>
                <person name="Tester J."/>
                <person name="Theaker A.J."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tubby B."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="West A.P."/>
                <person name="White S.S."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker H."/>
                <person name="Wild A."/>
                <person name="Willey D.J."/>
                <person name="Wilmer T.E."/>
                <person name="Wood J.M."/>
                <person name="Wray P.W."/>
                <person name="Wyatt J.C."/>
                <person name="Young L."/>
                <person name="Younger R.M."/>
                <person name="Bentley D.R."/>
                <person name="Coulson A."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Sulston J.E."/>
                <person name="Dunham I."/>
                <person name="Rogers J."/>
                <person name="Beck S."/>
            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="11">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="12">
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            <authorList>
                <person name="Ng G.Y.K."/>
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                <person name="O'Dowd B.F."/>
            </authorList>
            <dbReference type="PubMed" id="8218242"/>
            <dbReference type="DOI" id="10.1021/bi00094a032"/>
        </citation>
        <scope>PALMITOYLATION</scope>
        <scope>PHOSPHORYLATION</scope>
        <scope>FUNCTION</scope>
    </reference>
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            <authorList>
                <person name="Xie Z."/>
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                <person name="O'Dowd B.F."/>
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            </authorList>
            <dbReference type="PubMed" id="10452531"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(99)00918-7"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="14">
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            <authorList>
                <person name="Edvinsson L."/>
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                <person name="Malmsjo M."/>
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            <dbReference type="PubMed" id="15853772"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="15">
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            <authorList>
                <person name="Nichols D.E."/>
                <person name="Nichols C.D."/>
            </authorList>
            <dbReference type="PubMed" id="18476671"/>
            <dbReference type="DOI" id="10.1021/cr078224o"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="16">
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            <authorList>
                <person name="Pytliak M."/>
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            </authorList>
            <dbReference type="PubMed" id="20945968"/>
            <dbReference type="DOI" id="10.33549/physiolres.931903"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="17">
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            <authorList>
                <person name="Wacker D."/>
                <person name="Wang C."/>
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                <person name="Jiang Y."/>
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            </authorList>
            <dbReference type="PubMed" id="23519215"/>
            <dbReference type="DOI" id="10.1126/science.1232808"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="18">
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            <authorList>
                <person name="Tan Y."/>
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            <dbReference type="PubMed" id="35610220"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF SER-334</scope>
    </reference>
    <reference evidence="26 27" key="19">
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            <authorList>
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                <person name="Yang L."/>
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            <dbReference type="PubMed" id="23519210"/>
            <dbReference type="DOI" id="10.1126/science.1232807"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 33-239 AND 306-390 IN COMPLEXES WITH ERGOTAMINE AND DIHYDROERGOTAMINE</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MEMBRANE TOPOLOGY</scope>
        <scope>DOMAIN</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF LEU-126; ASP-129; ILE-130; CYS-133; THR-134; VAL-200; VAL-201; THR-203; THR-209; SER-212; ALA-216; TRP-327; PHE-330; PHE-331; SER-334; MET-337; PHE-351; ASP-352; THR-355 AND TYR-359</scope>
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                <person name="Garcia-Nafria J."/>
                <person name="Nehme R."/>
                <person name="Edwards P.C."/>
                <person name="Tate C.G."/>
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            <dbReference type="PubMed" id="29925951"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0241-9"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.78 ANGSTROMS) OF 34-390 IN COMPLEX WITH GNAO1; GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="21">
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            <title>Identification of genetic variation in the human serotonin 1D beta receptor gene.</title>
            <authorList>
                <person name="Nothen M.M."/>
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            </authorList>
            <dbReference type="PubMed" id="7802650"/>
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        </citation>
        <scope>VARIANT CYS-124</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 8 9 10 11 12 13 14 15 16 17 19 23 24">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD) (PubMed:23519210, PubMed:23519215, PubMed:29925951). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). HTR1B is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:29925951, PubMed:35610220). Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29925951). Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior (PubMed:18476671, PubMed:20945968). Besides, plays a role in vasoconstriction of cerebral arteries (PubMed:15853772).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5">Homodimer (PubMed:10452531). Heterodimer with HTR1D (PubMed:10452531).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056863">
            <id>P28222</id>
        </interactant>
        <interactant intactId="EBI-77797">
            <id>P35609</id>
            <label>ACTN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056863">
            <id>P28222</id>
        </interactant>
        <interactant intactId="EBI-724076">
            <id>Q99750</id>
            <label>MDFI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6 7 8 9 10 11 13 14 15">Cell membrane</location>
            <topology evidence="5 6 7 8 9 10 11 13 14 15">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8 9 12">Detected in cerebral artery smooth muscle cells (at protein level). Detected in brain cortex, striatum, amygdala, medulla, hippocampus, caudate nucleus and putamen.</text>
    </comment>
    <comment type="domain">
        <text evidence="14">Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.</text>
    </comment>
    <comment type="domain">
        <text evidence="14">A residue in the 7th transmembrane region (Thr-355 in human, 'Asn-351' in mouse and rat) is important for species-specific sensitivity to various agonists.</text>
    </comment>
    <comment type="PTM">
        <text evidence="19">Phosphorylated. Desensitization of the receptor may be mediated by its phosphorylation.</text>
    </comment>
    <comment type="PTM">
        <text evidence="19">Palmitoylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="BAA01763.1"/>
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        <property type="protein sequence ID" value="AAA36029.1"/>
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        <property type="generic name" value="Aripiprazole lauroxil"/>
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        <property type="generic name" value="Asenapine"/>
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        <property type="generic name" value="Dihydroergocristine"/>
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        <property type="generic name" value="Eltoprazine"/>
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        <property type="generic name" value="Ergoloid mesylate"/>
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            <position position="201"/>
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        <location>
            <position position="24"/>
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        <location>
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            <begin position="122"/>
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    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="14">
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        <variation>A</variation>
        <location>
            <position position="129"/>
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    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="14">
        <original>I</original>
        <variation>A</variation>
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="14">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="201"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="216"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="14">
        <original>W</original>
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        <location>
            <position position="327"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="14">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="330"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="331"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="334"/>
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    <feature type="mutagenesis site" description="Reduced G(i)/(o)-coupled receptor activity." evidence="17">
        <original>S</original>
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        <location>
            <position position="334"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>M</original>
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        <location>
            <position position="337"/>
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    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="351"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>D</original>
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        <location>
            <position position="352"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="355"/>
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    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="14">
        <original>Y</original>
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            <position position="359"/>
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    <feature type="helix" evidence="29">
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</entry>
<entry dataset="Swiss-Prot" created="2003-09-19" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>Q13542</accession>
    <name>4EBP2_HUMAN</name>
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            <fullName evidence="8">Eukaryotic translation initiation factor 4E-binding protein 2</fullName>
            <shortName evidence="8">4E-BP2</shortName>
            <shortName evidence="8">eIF4E-binding protein 2</shortName>
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        <name evidence="15" type="primary">EIF4EBP2</name>
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        <name type="scientific">Homo sapiens</name>
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        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="1994" name="Nature" volume="371" first="762" last="767">
            <title>Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.</title>
            <authorList>
                <person name="Pause A."/>
                <person name="Belsham G.J."/>
                <person name="Gingras A.-C."/>
                <person name="Donze O."/>
                <person name="Lin T.-A."/>
                <person name="Lawrence J.C. Jr."/>
                <person name="Sonenberg N."/>
            </authorList>
            <dbReference type="PubMed" id="7935836"/>
            <dbReference type="DOI" id="10.1038/371762a0"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference evidence="14" key="2">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference evidence="12" key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue evidence="12">Lung</tissue>
            <tissue evidence="13">Uterus</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-46</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
            <authorList>
                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2013" name="Structure" volume="21" first="2186" last="2196">
            <title>Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a dynamic bipartite interface.</title>
            <authorList>
                <person name="Lukhele S."/>
                <person name="Bah A."/>
                <person name="Lin H."/>
                <person name="Sonenberg N."/>
                <person name="Forman-Kay J.D."/>
            </authorList>
            <dbReference type="PubMed" id="24207126"/>
            <dbReference type="DOI" id="10.1016/j.str.2013.08.030"/>
        </citation>
        <scope>DOMAIN</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>MUTAGENESIS OF 54-TYR--LEU-59</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2019" name="Proc. Natl. Acad. Sci. U.S.A." volume="116" first="4218" last="4227">
            <title>Phosphoregulated FMRP phase separation models activity-dependent translation through bidirectional control of mRNA granule formation.</title>
            <authorList>
                <person name="Tsang B."/>
                <person name="Arsenault J."/>
                <person name="Vernon R.M."/>
                <person name="Lin H."/>
                <person name="Sonenberg N."/>
                <person name="Wang L.Y."/>
                <person name="Bah A."/>
                <person name="Forman-Kay J.D."/>
            </authorList>
            <dbReference type="PubMed" id="30765518"/>
            <dbReference type="DOI" id="10.1073/pnas.1814385116"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="J. Pept. Sci." volume="17" first="650" last="657">
            <title>Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms: crystal structure of eIF4E binding region of 4E-BP2 and its comparison with that of 4E-BP1.</title>
            <authorList>
                <person name="Fukuyo A."/>
                <person name="In Y."/>
                <person name="Ishida T."/>
                <person name="Tomoo K."/>
            </authorList>
            <dbReference type="PubMed" id="21661078"/>
            <dbReference type="DOI" id="10.1002/psc.1384"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 47-65 IN COMPLEX WITH EIF4E</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2015" name="Nature" volume="519" first="106" last="109">
            <title>Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch.</title>
            <authorList>
                <person name="Bah A."/>
                <person name="Vernon R.M."/>
                <person name="Siddiqui Z."/>
                <person name="Krzeminski M."/>
                <person name="Muhandiram R."/>
                <person name="Zhao C."/>
                <person name="Sonenberg N."/>
                <person name="Kay L.E."/>
                <person name="Forman-Kay J.D."/>
            </authorList>
            <dbReference type="PubMed" id="25533957"/>
            <dbReference type="DOI" id="10.1038/nature13999"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 18-62</scope>
        <scope>PHOSPHORYLATION AT THR-37; THR-46; SER-65; THR-70 AND SER-83</scope>
        <scope>DOMAIN</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH EIF4E</scope>
        <scope>MUTAGENESIS OF THR-37; GLY-39; THR-46 AND GLY-48</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 6">Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:30765518). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:25533957, PubMed:30765518). EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 4 5 7">Hypophosphorylated EIF4EBP2 interacts with EIF4E; phosphorylation of EIF4EBP2 by mTORC1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:21661078, PubMed:24207126, PubMed:25533957, PubMed:7935836). Interacts with RPTOR; promoting phosphorylation by mTORC1 (By similarity). Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-935137">
            <id>Q13542</id>
        </interactant>
        <interactant intactId="EBI-73440">
            <id>P06730</id>
            <label>EIF4E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>19</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="domain">
        <text evidence="2">The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.</text>
    </comment>
    <comment type="domain">
        <text evidence="4 5">Intrinsically disordered protein that undergoes folding upon phosphorylation (PubMed:25533957). Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82) (PubMed:24207126, PubMed:25533957). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).</text>
    </comment>
    <comment type="PTM">
        <text evidence="3 4 5">Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions (PubMed:24207126, PubMed:25533957). First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957). Phosphorylated in response to insulin, EGF and PDGF.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain. Deamidation promotes interaction with RPTOR, subsequent phosphorylation by mTORC1 and increased translation, leading to impair kinetics of excitatory synaptic transmission. Deamidation takes place during postnatal development, when the PI3K-Akt-mTOR signaling is reduced, suggesting it acts as a compensatory mechanism to promote translation despite attenuated PI3K-Akt-mTOR signaling in neuron development. Deamidation converts Asn residues into a mixture of Asp and isoaspartate; interactions with PCMT1 is required to prevent isoaspartate accumulation and convert isoaspartate to Asp.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the eIF4E-binding protein family.</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/168/"/>
        <text>A question of perspective - Issue 168 of April 2015</text>
    </comment>
    <dbReference type="EMBL" id="L36056">
        <property type="protein sequence ID" value="AAA62270.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAP35981.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC005057">
        <property type="protein sequence ID" value="AAH05057.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="S50867"/>
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        <property type="nucleotide sequence ID" value="NM_004096.5"/>
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    <dbReference type="PDB" id="2MX4">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=18-62"/>
    </dbReference>
    <dbReference type="PDB" id="3AM7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="B=47-65"/>
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    <dbReference type="PDBsum" id="2MX4"/>
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        <property type="interactions" value="35"/>
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    <dbReference type="DIP" id="DIP-36572N"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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        <property type="antibodies" value="274 antibodies from 30 providers"/>
    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000362314.4"/>
        <property type="gene ID" value="ENSG00000148730.8"/>
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    <dbReference type="GeneID" id="1979"/>
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        <property type="protein sequence ID" value="ENSP00000362314.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004096.5"/>
        <property type="RefSeq protein sequence ID" value="NP_004087.1"/>
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        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:3289"/>
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        <property type="gene designation" value="EIF4EBP2"/>
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    <dbReference type="HPA" id="ENSG00000148730">
        <property type="expression patterns" value="Low tissue specificity"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
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        <property type="hits" value="19 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="671877C5">
        <property type="entry name" value="Synthetic Condensate 000209"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="EIF4EBP2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q13542"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 10"/>
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    <dbReference type="RNAct" id="Q13542">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000148730">
        <property type="expression patterns" value="Expressed in buccal mucosa cell and 216 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q13542">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
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    <dbReference type="GO" id="GO:0071598">
        <property type="term" value="C:neuronal ribonucleoprotein granule"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098794">
        <property type="term" value="C:postsynapse"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008190">
        <property type="term" value="F:eukaryotic initiation factor 4E binding"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030371">
        <property type="term" value="F:translation repressor activity"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0008286">
        <property type="term" value="P:insulin receptor signaling pathway"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
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        <property type="term" value="P:memory"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0050804">
        <property type="term" value="P:modulation of chemical synaptic transmission"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="P:negative regulation of translational initiation"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="P:social behavior"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031929">
        <property type="term" value="P:TOR signaling"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006412">
        <property type="term" value="P:translation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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    <dbReference type="DisProt" id="DP01293"/>
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        <property type="entry name" value="EIF4EBP"/>
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    <dbReference type="PANTHER" id="PTHR12669">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12669:SF4">
        <property type="entry name" value="EUKARYOTIC TRANSLATION INITIATION FACTOR 4E-BINDING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05456">
        <property type="entry name" value="eIF_4EBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0652">Protein synthesis inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <feature type="chain" id="PRO_0000190516" description="Eukaryotic translation initiation factor 4E-binding protein 2">
        <location>
            <begin position="1"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="10 11">
        <location>
            <begin position="1"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="10 11">
        <location>
            <begin position="65"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="YXXXXLphi motif" evidence="4 5">
        <location>
            <begin position="54"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Secondary EIF4E binding site" evidence="4 5">
        <location>
            <begin position="78"/>
            <end position="82"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="TOS motif" evidence="2">
        <location>
            <begin position="116"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by MTOR" evidence="5 16 17">
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by MTOR" evidence="5 16">
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by MTOR" evidence="5">
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by MTOR" evidence="5">
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="5">
        <location>
            <position position="83"/>
        </location>
    </feature>
    <feature type="modified residue" description="Deamidated asparagine" evidence="1">
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="modified residue" description="Deamidated asparagine" evidence="1">
        <location>
            <position position="102"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-46 or E-46." evidence="5">
        <original>T</original>
        <variation>D</variation>
        <variation>E</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-48." evidence="5">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Acidic residues do not mimic phosphorylation state. Does not induce folding of the intrinsically disordered protein; when associated with D-37 or E-37." evidence="5">
        <original>T</original>
        <variation>D</variation>
        <variation>E</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes folding of the intrinsically disordered protein without affecting greatly affinity for EIF4E even when the protein is fully phosphorylated; when associated with V-39." evidence="5">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired binding to EIF4E." evidence="4">
        <original>YDRKFLL</original>
        <variation>AAAAAAA</variation>
        <location>
            <begin position="54"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired binding to EIF4E." evidence="4">
        <original>IPGVT</original>
        <variation>AAAAA</variation>
        <location>
            <begin position="78"/>
            <end position="82"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="19"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="27"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="42"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="56"/>
            <end position="60"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P70445"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q13541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="21661078"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="24207126"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="25533957"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="30765518"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="7935836"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="7935836"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="24207126"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="25533957"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="EMBL" id="AAH05057.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="EMBL" id="AAH50633.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="EMBL" id="AAP35981.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:3289"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="2MX4"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="3AM7"/>
        </source>
    </evidence>
    <sequence length="120" mass="12939" checksum="B8F109261A504193" modified="1996-11-01" version="1">MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPGGTRIIYDRKFLLDRRNSPMAQTPPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>P30939</accession>
    <name>5HT1F_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10">5-hydroxytryptamine receptor 1F</fullName>
            <shortName evidence="10">5-HT-1F</shortName>
            <shortName evidence="10">5-HT1F</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="10">Serotonin receptor 1F</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">HTR1F</name>
        <name evidence="11" type="synonym">HTR1EL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Proc. Natl. Acad. Sci. U.S.A." volume="90" first="2184" last="2188">
            <title>Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes.</title>
            <authorList>
                <person name="Lovenberg T.W."/>
                <person name="Erlander M.G."/>
                <person name="Baron B.M."/>
                <person name="Racke M."/>
                <person name="Slone A.L."/>
                <person name="Siegel B.W."/>
                <person name="Craft C.M."/>
                <person name="Burns J.E."/>
                <person name="Danielson P.E."/>
                <person name="Sutcliffe G.J."/>
            </authorList>
            <dbReference type="PubMed" id="8384716"/>
            <dbReference type="DOI" id="10.1073/pnas.90.6.2184"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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                <person name="Puhl H.L. III"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <title>Serotonin receptors.</title>
            <authorList>
                <person name="Nichols D.E."/>
                <person name="Nichols C.D."/>
            </authorList>
            <dbReference type="PubMed" id="18476671"/>
            <dbReference type="DOI" id="10.1021/cr078224o"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="7">
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            <title>Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships.</title>
            <authorList>
                <person name="Klein M.T."/>
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            <dbReference type="PubMed" id="21422162"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <reference key="8">
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                <person name="Tan Y."/>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF GLU-313</scope>
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            <dbReference type="DOI" id="10.33549/physiolres.931903"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference evidence="13" key="10">
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            <dbReference type="DOI" id="10.1038/s41422-021-00527-4"/>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.4 ANGSTROMS) IN COMPLEX WITH GNAI1; GNB1 AND GNG2</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-103; ILE-104; CYS-107; THR-108; THR-182; TRP-306; PHE-309; PHE-310; GLU-313 AND TYR-337</scope>
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    <comment type="function">
        <text evidence="5 6 7 8 9">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:21422162, PubMed:34239069, PubMed:8380639, PubMed:8384716). Also functions as a receptor for various alkaloids and psychoactive substances (PubMed:21422162, PubMed:8380639, PubMed:8384716). Receptor for lasmiditan, a drug for the treatment of acute migraine (PubMed:34239069). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:34239069). HTR1F is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:34239069, PubMed:35610220).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 8 9">Cell membrane</location>
            <topology evidence="8 9">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA36605.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="entry name" value="A47321"/>
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        <property type="nucleotide sequence ID" value="NM_000866.5"/>
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        <property type="nucleotide sequence ID" value="NM_001322208.2"/>
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    <dbReference type="RefSeq" id="NP_001309138.1">
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        <property type="nucleotide sequence ID" value="NM_001322210.2"/>
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        <property type="nucleotide sequence ID" value="XM_054346412.1"/>
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    <dbReference type="RefSeq" id="XP_054202388.1">
        <property type="nucleotide sequence ID" value="XM_054346413.1"/>
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        <property type="method" value="EM"/>
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        <property type="generic name" value="Dihydroergocornine"/>
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<entry dataset="Swiss-Prot" created="2007-12-04" modified="2026-01-28" version="185" xmlns="https://uniprot.org/uniprot">
    <accession>O95264</accession>
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        <name type="scientific">Homo sapiens</name>
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    <reference key="1">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="30799" last="30810">
            <title>The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit.</title>
            <authorList>
                <person name="Dubin A.E."/>
                <person name="Huvar R."/>
                <person name="D'Andrea M.R."/>
                <person name="Pyati J."/>
                <person name="Zhu J.Y."/>
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                <person name="Lovenberg T.W."/>
                <person name="Erlander M.G."/>
            </authorList>
            <dbReference type="PubMed" id="10521471"/>
            <dbReference type="DOI" id="10.1074/jbc.274.43.30799"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Nature" volume="397" first="359" last="363">
            <title>The 5-HT3B subunit is a major determinant of serotonin-receptor function.</title>
            <authorList>
                <person name="Davies P.A."/>
                <person name="Pistis M."/>
                <person name="Hanna M.C."/>
                <person name="Peters J.A."/>
                <person name="Lambert J.J."/>
                <person name="Hales T.G."/>
                <person name="Kirkness E.F."/>
            </authorList>
            <dbReference type="PubMed" id="9950429"/>
            <dbReference type="DOI" id="10.1038/16941"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="Gene" volume="386" first="52" last="62">
            <title>Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine.</title>
            <authorList>
                <person name="Tzvetkov M.V."/>
                <person name="Meineke C."/>
                <person name="Oetjen E."/>
                <person name="Hirsch-Ernst K."/>
                <person name="Brockmoller J."/>
            </authorList>
            <dbReference type="PubMed" id="17010535"/>
            <dbReference type="DOI" id="10.1016/j.gene.2006.08.002"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT SER-129</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2007-02" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NHLBI resequencing and genotyping service (RS&amp;G)"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="321" last="324">
            <title>A cytoplasmic region determines single-channel conductance in 5-HT3 receptors.</title>
            <authorList>
                <person name="Kelley S.P."/>
                <person name="Dunlop J.I."/>
                <person name="Kirkness E.F."/>
                <person name="Lambert J.J."/>
                <person name="Peters J.A."/>
            </authorList>
            <dbReference type="PubMed" id="12867984"/>
            <dbReference type="DOI" id="10.1038/nature01788"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>REGION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2007" name="Mol. Pharmacol." volume="72" first="8" last="17">
            <title>Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E.</title>
            <authorList>
                <person name="Niesler B."/>
                <person name="Walstab J."/>
                <person name="Combrink S."/>
                <person name="Moeller D."/>
                <person name="Kapeller J."/>
                <person name="Rietdorf J."/>
                <person name="Boenisch H."/>
                <person name="Goethert M."/>
                <person name="Rappold G."/>
                <person name="Bruess M."/>
            </authorList>
            <dbReference type="PubMed" id="17392525"/>
            <dbReference type="DOI" id="10.1124/mol.106.032144"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="J. Neurochem." volume="116" first="975" last="983">
            <title>The identification of N-glycosylated residues of the human 5-HT3B receptor subunit: importance for cell membrane expression.</title>
            <authorList>
                <person name="Massoura A.N."/>
                <person name="Dover T.J."/>
                <person name="Newman A.S."/>
                <person name="Barnes N.M."/>
            </authorList>
            <dbReference type="PubMed" id="21138434"/>
            <dbReference type="DOI" id="10.1111/j.1471-4159.2010.07129.x"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
        <scope>GLYCOSYLATION AT ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203</scope>
        <scope>MUTAGENESIS OF ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="Am. J. Med. Genet. B Neuropsychiatr. Genet." volume="131" first="1" last="5">
            <title>Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients.</title>
            <authorList>
                <person name="Frank B."/>
                <person name="Niesler B."/>
                <person name="Noethen M.M."/>
                <person name="Neidt H."/>
                <person name="Propping P."/>
                <person name="Bondy B."/>
                <person name="Rietschel M."/>
                <person name="Maier W."/>
                <person name="Albus M."/>
                <person name="Rappold G."/>
            </authorList>
            <dbReference type="PubMed" id="15389765"/>
            <dbReference type="DOI" id="10.1002/ajmg.b.30070"/>
        </citation>
        <scope>VARIANTS SER-129; ARG-156 AND ILE-183</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2004" name="Clin. Rheumatol." volume="23" first="338" last="344">
            <title>Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients.</title>
            <authorList>
                <person name="Frank B."/>
                <person name="Niesler B."/>
                <person name="Bondy B."/>
                <person name="Spaeth M."/>
                <person name="Pongratz D.E."/>
                <person name="Ackenheil M."/>
                <person name="Fischer C."/>
                <person name="Rappold G."/>
            </authorList>
            <dbReference type="PubMed" id="15293096"/>
            <dbReference type="DOI" id="10.1007/s10067-004-0927-2"/>
        </citation>
        <scope>VARIANTS SER-129; ARG-156 AND ILE-183</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2006" name="Biol. Psychiatry" volume="60" first="192" last="201">
            <title>Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression.</title>
            <authorList>
                <person name="Yamada K."/>
                <person name="Hattori E."/>
                <person name="Iwayama Y."/>
                <person name="Ohnishi T."/>
                <person name="Ohba H."/>
                <person name="Toyota T."/>
                <person name="Takao H."/>
                <person name="Minabe Y."/>
                <person name="Nakatani N."/>
                <person name="Higuchi T."/>
                <person name="Detera-Wadleigh S.D."/>
                <person name="Yoshikawa T."/>
            </authorList>
            <dbReference type="PubMed" id="16487942"/>
            <dbReference type="DOI" id="10.1016/j.biopsych.2005.11.008"/>
        </citation>
        <scope>VARIANTS SER-129; THR-143 AND ILE-183</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Nature" volume="468" first="1061" last="1066">
            <title>A population-specific HTR2B stop codon predisposes to severe impulsivity.</title>
            <authorList>
                <person name="Bevilacqua L."/>
                <person name="Doly S."/>
                <person name="Kaprio J."/>
                <person name="Yuan Q."/>
                <person name="Tikkanen R."/>
                <person name="Paunio T."/>
                <person name="Zhou Z."/>
                <person name="Wedenoja J."/>
                <person name="Maroteaux L."/>
                <person name="Diaz S."/>
                <person name="Belmer A."/>
                <person name="Hodgkinson C.A."/>
                <person name="Dell'osso L."/>
                <person name="Suvisaari J."/>
                <person name="Coccaro E."/>
                <person name="Rose R.J."/>
                <person name="Peltonen L."/>
                <person name="Virkkunen M."/>
                <person name="Goldman D."/>
            </authorList>
            <dbReference type="PubMed" id="21179162"/>
            <dbReference type="DOI" id="10.1038/nature09629"/>
        </citation>
        <scope>VARIANT ARG-156</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 9 12">Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 9 12">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="9 12">Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="16">Postsynaptic cell membrane</location>
            <topology evidence="10">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="10">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="10">Presumably retained within the endoplasmic reticulum unless complexed with HTR3A.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O95264-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O95264-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_029796"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 12">Expressed in the brain cortex, in the caudate nucleus, the hippocampus, the thalamus and the amygdala. Detected in the kidney and testis as well as in monocytes of the spleen, small and large intestine, uterus, prostate, ovary and placenta.</text>
    </comment>
    <comment type="domain">
        <text evidence="4">The HA-stretch region of HTR3B seems to confer increased conductance to HTR3A/HTR3B heteromers compared to that of HTR3A homomers.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10">N-glycosylation required for membrane localization.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3B sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AF169255">
        <property type="protein sequence ID" value="AAF03691.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF080582">
        <property type="protein sequence ID" value="AAD12242.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AM293589">
        <property type="protein sequence ID" value="CAL25321.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF444985">
        <property type="protein sequence ID" value="ACA06001.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314268">
        <property type="protein sequence ID" value="BAG36930.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8364.1">
        <molecule id="O95264-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS86249.1">
        <molecule id="O95264-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001350492.1">
        <molecule id="O95264-2"/>
        <property type="nucleotide sequence ID" value="NM_001363563.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006019.1">
        <molecule id="O95264-1"/>
        <property type="nucleotide sequence ID" value="NM_006028.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O95264"/>
    <dbReference type="SMR" id="O95264"/>
    <dbReference type="BioGRID" id="114615">
        <property type="interactions" value="54"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-271">
        <property type="entry name" value="5-hydroxytryptamine-3A/B receptor complex"/>
    </dbReference>
    <dbReference type="CORUM" id="O95264"/>
    <dbReference type="FunCoup" id="O95264">
        <property type="interactions" value="216"/>
    </dbReference>
    <dbReference type="IntAct" id="O95264">
        <property type="interactions" value="20"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000260191"/>
    <dbReference type="BindingDB" id="O95264"/>
    <dbReference type="ChEMBL" id="CHEMBL3895"/>
    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00988">
        <property type="generic name" value="Dopamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12141">
        <property type="generic name" value="Gilteritinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00715">
        <property type="generic name" value="Paroxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08839">
        <property type="generic name" value="Serotonin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09304">
        <property type="generic name" value="Setiptiline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13025">
        <property type="generic name" value="Tiapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00246">
        <property type="generic name" value="Ziprasidone"/>
    </dbReference>
    <dbReference type="DrugCentral" id="O95264"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="374"/>
    <dbReference type="TCDB" id="1.A.9.2.5">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O95264">
        <property type="glycosylation" value="6 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O95264">
        <property type="glycosylation" value="6 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O95264"/>
    <dbReference type="PhosphoSitePlus" id="O95264"/>
    <dbReference type="BioMuta" id="HTR3B"/>
    <dbReference type="MassIVE" id="O95264"/>
    <dbReference type="PaxDb" id="9606-ENSP00000260191"/>
    <dbReference type="PeptideAtlas" id="O95264"/>
    <dbReference type="TopDownProteomics" id="O95264-1">
        <molecule id="O95264-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="18362">
        <property type="antibodies" value="170 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="9177"/>
    <dbReference type="Ensembl" id="ENST00000260191.8">
        <molecule id="O95264-1"/>
        <property type="protein sequence ID" value="ENSP00000260191.2"/>
        <property type="gene ID" value="ENSG00000149305.8"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000537778.5">
        <molecule id="O95264-2"/>
        <property type="protein sequence ID" value="ENSP00000443118.1"/>
        <property type="gene ID" value="ENSG00000149305.8"/>
    </dbReference>
    <dbReference type="GeneID" id="9177"/>
    <dbReference type="KEGG" id="hsa:9177"/>
    <dbReference type="MANE-Select" id="ENST00000260191.8">
        <property type="protein sequence ID" value="ENSP00000260191.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006028.5"/>
        <property type="RefSeq protein sequence ID" value="NP_006019.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001pok.4">
        <molecule id="O95264-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5298"/>
    <dbReference type="ClinPGx" id="PA29556"/>
    <dbReference type="CTD" id="9177"/>
    <dbReference type="DisGeNET" id="9177"/>
    <dbReference type="GeneCards" id="HTR3B"/>
    <dbReference type="HGNC" id="HGNC:5298">
        <property type="gene designation" value="HTR3B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000149305">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="604654">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000149305"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000149305"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158478"/>
    <dbReference type="HOGENOM" id="CLU_018074_5_0_1"/>
    <dbReference type="InParanoid" id="O95264"/>
    <dbReference type="OMA" id="NMANEVP"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="O95264">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O95264"/>
    <dbReference type="PathwayCommons" id="O95264"/>
    <dbReference type="Reactome" id="R-HSA-112314">
        <property type="pathway name" value="Neurotransmitter receptors and postsynaptic signal transmission"/>
    </dbReference>
    <dbReference type="SignaLink" id="O95264"/>
    <dbReference type="SIGNOR" id="O95264"/>
    <dbReference type="Agora" id="ENSG00000149305"/>
    <dbReference type="BioGRID-ORCS" id="9177">
        <property type="hits" value="14 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HTR3B"/>
    <dbReference type="GenomeRNAi" id="9177"/>
    <dbReference type="Pharos" id="O95264">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O95264"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="O95264">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000149305">
        <property type="expression patterns" value="Expressed in prefrontal cortex and 45 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O95264">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="CACAO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904602">
        <property type="term" value="C:serotonin-activated cation-selective channel complex"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902495">
        <property type="term" value="C:transmembrane transporter complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005231">
        <property type="term" value="F:excitatory extracellular ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022850">
        <property type="term" value="F:serotonin-gated monoatomic cation channel activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098662">
        <property type="term" value="P:inorganic cation transmembrane transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0007210">
        <property type="term" value="P:serotonin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0140227">
        <property type="term" value="P:serotonin-gated cation-selective signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
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    <dbReference type="CDD" id="cd19012">
        <property type="entry name" value="LGIC_ECD_5-HT3B"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd19063">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.70.170.10:FF:000017">
        <property type="entry name" value="5-hydroxytryptamine receptor 3A"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.20.58.390:FF:000056">
        <property type="entry name" value="5-hydroxytryptamine receptor 3B"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR008132">
        <property type="entry name" value="5HT3_rcpt"/>
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    <dbReference type="InterPro" id="IPR008134">
        <property type="entry name" value="5HT3_rcpt_B"/>
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    <dbReference type="InterPro" id="IPR049944">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
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    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
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    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
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    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
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        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
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        <property type="entry name" value="Neuro_actylchol_rec"/>
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        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
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        <property type="entry name" value="LIC"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="5HT3BRECEPTR"/>
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        <property type="entry name" value="5HT3RECEPTOR"/>
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        <property type="entry name" value="NRIONCHANNEL"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="21"/>
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    <feature type="chain" id="PRO_0000312289" description="5-hydroxytryptamine receptor 3B">
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            <begin position="22"/>
            <end position="441"/>
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    <feature type="topological domain" description="Extracellular" evidence="10">
        <location>
            <begin position="22"/>
            <end position="238"/>
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    <feature type="transmembrane region" description="Helical; Name=1" evidence="2">
        <location>
            <begin position="239"/>
            <end position="259"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="10">
        <location>
            <begin position="260"/>
            <end position="268"/>
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    <feature type="transmembrane region" description="Helical; Name=2" evidence="2">
        <location>
            <begin position="269"/>
            <end position="286"/>
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    <feature type="topological domain" description="Extracellular" evidence="10">
        <location>
            <begin position="287"/>
            <end position="303"/>
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    <feature type="transmembrane region" description="Helical; Name=3" evidence="2">
        <location>
            <begin position="304"/>
            <end position="324"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="10">
        <location>
            <begin position="325"/>
            <end position="414"/>
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    <feature type="transmembrane region" description="Helical; Name=4" evidence="2">
        <location>
            <begin position="415"/>
            <end position="435"/>
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    <feature type="topological domain" description="Extracellular" evidence="10">
        <location>
            <begin position="436"/>
            <end position="441"/>
        </location>
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    <feature type="region of interest" description="HA-stretch; determines single-channel conductance in 5-HT3 receptors" evidence="4">
        <location>
            <begin position="381"/>
            <end position="413"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10">
        <location>
            <position position="52"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10">
        <location>
            <position position="96"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10">
        <location>
            <position position="138"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10">
        <location>
            <position position="168"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10">
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            <position position="203"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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            <position position="287"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="155"/>
            <end position="169"/>
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    </feature>
    <feature type="splice variant" id="VSP_029796" description="In isoform 2." evidence="13">
        <original>MLSSVMAPLWACILVAA</original>
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        <location>
            <begin position="1"/>
            <end position="17"/>
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    <feature type="sequence variant" id="VAR_037472" description="In dbSNP:rs1176744." evidence="5 6 7 8">
        <original>Y</original>
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            <position position="129"/>
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    <feature type="sequence variant" id="VAR_037473" description="In dbSNP:rs34550504." evidence="7">
        <original>I</original>
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        <location>
            <position position="143"/>
        </location>
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    <feature type="sequence variant" id="VAR_037474" description="In dbSNP:rs72466469." evidence="5 6 11">
        <original>S</original>
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        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037475" description="In dbSNP:rs17116138." evidence="5 6 7">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced molecular weight. Very little expression in the cell membrane." evidence="10">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced molecular weight. Very little expression in the cell membrane." evidence="10">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced molecular weight. Very little expression in the cell membrane." evidence="10">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced molecular weight and cell membrane expression." evidence="10">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced molecular weight. Very little expression in the cell membrane." evidence="10">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P23979"/>
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    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10521471"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12867984"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15293096"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15389765"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16487942"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17010535"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17392525"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="21138434"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="21179162"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="9950429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="17010535"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="10521471"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="9950429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="17">
        <source>
            <dbReference type="HGNC" id="HGNC:5298"/>
        </source>
    </evidence>
    <sequence length="441" mass="50292" checksum="2ED59E4E11400648" modified="1999-05-01" version="1" precursor="true">MLSSVMAPLWACILVAAGILATDTHHPQDSALYHLSKQLLQKYHKEVRPVYNWTKATTVYLDLFVHAILDVDAENQILKTSVWYQEVWNDEFLSWNSSMFDEIREISLPLSAIWAPDIIINEFVDIERYPDLPYVYVNSSGTIENYKPIQVVSACSLETYAFPFDVQNCSLTFKSILHTVEDVDLAFLRSPEDIQHDKKAFLNDSEWELLSVSSTYSILQSSAGGFAQIQFNVVMRRHPLVYVVSLLIPSIFLMLVDLGSFYLPPNCRARIVFKTSVLVGYTVFRVNMSNQVPRSVGSTPLIGHFFTICMAFLVLSLAKSIVLVKFLHDEQRGGQEQPFLCLRGDTDADRPRVEPRAQRAVVTESSLYGEHLAQPGTLKEVWSQLQSISNYLQTQDQTDQQEAEWLVLLSRFDRLLFQSYLFMLGIYTITLCSLWALWGGV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-31" modified="2026-01-28" version="178" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y6E2</accession>
    <accession>A4D123</accession>
    <accession>Q3B779</accession>
    <accession>Q96JW5</accession>
    <accession>Q9H3F7</accession>
    <name>5MP1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">eIF5-mimic protein 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Basic leucine zipper and W2 domain-containing protein 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">BZW2</name>
        <name evidence="9" type="synonym">5MP1</name>
        <name type="ORF">HSPC028</name>
        <name type="ORF">MSTP017</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1998-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Zhao B."/>
                <person name="Xu Y.Y."/>
                <person name="Liu Y.Q."/>
                <person name="Wang X.Y."/>
                <person name="Liu B."/>
                <person name="Ye J."/>
                <person name="Song L."/>
                <person name="Zhao Y."/>
                <person name="Cao H.Q."/>
                <person name="Zhao X.W."/>
                <person name="Gao Y."/>
                <person name="Zhang C.L."/>
                <person name="Zhang J."/>
                <person name="Liu L.S."/>
                <person name="Ding J.F."/>
                <person name="Gao R.L."/>
                <person name="Wu Q.Y."/>
                <person name="Qiang B.Q."/>
                <person name="Yuan J.G."/>
                <person name="Liew C.C."/>
                <person name="Zhao M.S."/>
                <person name="Hui R.T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Genome Res." volume="10" first="1546" last="1560">
            <title>Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.</title>
            <authorList>
                <person name="Zhang Q.-H."/>
                <person name="Ye M."/>
                <person name="Wu X.-Y."/>
                <person name="Ren S.-X."/>
                <person name="Zhao M."/>
                <person name="Zhao C.-J."/>
                <person name="Fu G."/>
                <person name="Shen Y."/>
                <person name="Fan H.-Y."/>
                <person name="Lu G."/>
                <person name="Zhong M."/>
                <person name="Xu X.-R."/>
                <person name="Han Z.-G."/>
                <person name="Zhang J.-W."/>
                <person name="Tao J."/>
                <person name="Huang Q.-H."/>
                <person name="Zhou J."/>
                <person name="Hu G.-X."/>
                <person name="Gu J."/>
                <person name="Chen S.-J."/>
                <person name="Chen Z."/>
            </authorList>
            <dbReference type="PubMed" id="11042152"/>
            <dbReference type="DOI" id="10.1101/gr.140200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Umbilical cord blood</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-412 AND SER-414</scope>
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        <scope>FUNCTION</scope>
        <scope>NOMENCLATURE</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH EIF3E AND EIF2S2</scope>
        <scope>MUTAGENESIS OF 401-PHE--GLU-411</scope>
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        <scope>INTERACTION WITH EIF2S2</scope>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH EIF2S2 AND EIF3C</scope>
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    <comment type="function">
        <text evidence="3 5 6 7">Translation initiation regulator which represses non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (PubMed:21745818, PubMed:28981728, PubMed:29470543, PubMed:34260931). Increases the accuracy of translation initiation by impeding EIF5-dependent translation from non-AUG codons by competing with it for interaction with EIF2S2 within the 43S pre-initiation complex (PIC) in an EIF3C-binding dependent manner (PubMed:21745818, PubMed:28981728, PubMed:34260931).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 7">Interacts with EIF3E (PubMed:21745818). Interacts with EIF2S2 (PubMed:21745818, PubMed:25147208, PubMed:34260931). Interacts with EIF3C (PubMed:34260931).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Y6E2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y6E2-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055568 VSP_055569"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the BZW family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAI07758" version="1"/>
        </conflict>
        <text>Contaminating sequence. Potential poly-A sequence.</text>
    </comment>
    <dbReference type="EMBL" id="AF110323">
        <property type="protein sequence ID" value="AAG39278.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF083246">
        <property type="protein sequence ID" value="AAD39844.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001218">
        <property type="protein sequence ID" value="BAA91562.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027837">
        <property type="protein sequence ID" value="BAB55401.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236948">
        <property type="protein sequence ID" value="EAL24285.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471073">
        <property type="protein sequence ID" value="EAW93675.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471073">
        <property type="protein sequence ID" value="EAW93678.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC003056">
        <property type="protein sequence ID" value="AAH03056.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008453">
        <property type="protein sequence ID" value="AAH08453.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009597">
        <property type="protein sequence ID" value="AAH09597.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC107757">
        <property type="protein sequence ID" value="AAI07758.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5362.1">
        <molecule id="Q9Y6E2-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001153239.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="NM_001159767.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001349646.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="NM_001362717.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_054757.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="NM_014038.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006715770.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="XM_006715707.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006715771.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="XM_006715708.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054213961.1">
        <molecule id="Q9Y6E2-1"/>
        <property type="nucleotide sequence ID" value="XM_054357986.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9Y6E2"/>
    <dbReference type="SMR" id="Q9Y6E2"/>
    <dbReference type="BioGRID" id="118793">
        <property type="interactions" value="139"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y6E2">
        <property type="interactions" value="1824"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y6E2"/>
    <dbReference type="STRING" id="9606.ENSP00000397249"/>
    <dbReference type="GlyGen" id="Q9Y6E2">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y6E2"/>
    <dbReference type="MetOSite" id="Q9Y6E2"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y6E2"/>
    <dbReference type="SwissPalm" id="Q9Y6E2"/>
    <dbReference type="BioMuta" id="BZW2"/>
    <dbReference type="DMDM" id="74762077"/>
    <dbReference type="jPOST" id="Q9Y6E2"/>
    <dbReference type="MassIVE" id="Q9Y6E2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000397249"/>
    <dbReference type="PeptideAtlas" id="Q9Y6E2"/>
    <dbReference type="ProteomicsDB" id="86659">
        <molecule id="Q9Y6E2-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9Y6E2"/>
    <dbReference type="Antibodypedia" id="11817">
        <property type="antibodies" value="106 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="28969"/>
    <dbReference type="Ensembl" id="ENST00000258761.8">
        <molecule id="Q9Y6E2-1"/>
        <property type="protein sequence ID" value="ENSP00000258761.3"/>
        <property type="gene ID" value="ENSG00000136261.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000433922.6">
        <molecule id="Q9Y6E2-1"/>
        <property type="protein sequence ID" value="ENSP00000397249.2"/>
        <property type="gene ID" value="ENSG00000136261.17"/>
    </dbReference>
    <dbReference type="GeneID" id="28969"/>
    <dbReference type="KEGG" id="hsa:28969"/>
    <dbReference type="MANE-Select" id="ENST00000258761.8">
        <property type="protein sequence ID" value="ENSP00000258761.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014038.3"/>
        <property type="RefSeq protein sequence ID" value="NP_054757.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003stj.3">
        <molecule id="Q9Y6E2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18808"/>
    <dbReference type="ClinPGx" id="PA38690"/>
    <dbReference type="CTD" id="28969"/>
    <dbReference type="DisGeNET" id="28969"/>
    <dbReference type="GeneCards" id="BZW2"/>
    <dbReference type="HGNC" id="HGNC:18808">
        <property type="gene designation" value="BZW2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000136261">
        <property type="expression patterns" value="Tissue enhanced (heart muscle, skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MIM" id="619275">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000136261"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000136261"/>
    <dbReference type="eggNOG" id="KOG2297">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012561"/>
    <dbReference type="HOGENOM" id="CLU_032849_0_1_1"/>
    <dbReference type="InParanoid" id="Q9Y6E2"/>
    <dbReference type="OMA" id="HCVFFAI"/>
    <dbReference type="OrthoDB" id="1727522at2759"/>
    <dbReference type="PAN-GO" id="Q9Y6E2">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y6E2"/>
    <dbReference type="PathwayCommons" id="Q9Y6E2"/>
    <dbReference type="SignaLink" id="Q9Y6E2"/>
    <dbReference type="SIGNOR" id="Q9Y6E2"/>
    <dbReference type="Agora" id="ENSG00000136261"/>
    <dbReference type="BioGRID-ORCS" id="28969">
        <property type="hits" value="16 hits in 1163 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="BZW2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="BZW2"/>
    <dbReference type="GenomeRNAi" id="28969"/>
    <dbReference type="Pharos" id="Q9Y6E2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y6E2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y6E2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000136261">
        <property type="expression patterns" value="Expressed in skeletal muscle tissue of biceps brachii and 208 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y6E2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045296">
        <property type="term" value="F:cadherin binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006446">
        <property type="term" value="P:regulation of translational initiation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd11560">
        <property type="entry name" value="W2_eIF5C_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.180:FF:000006">
        <property type="entry name" value="Basic leucine zipper and W2 domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.180">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016024">
        <property type="entry name" value="ARM-type_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051245">
        <property type="entry name" value="eIF5-mimic_regulator"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR057397">
        <property type="entry name" value="HEAT_5MP1_2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043510">
        <property type="entry name" value="W2_5MP1/2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003307">
        <property type="entry name" value="W2_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14208">
        <property type="entry name" value="BASIC LEUCINE ZIPPER AND W2 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14208:SF7">
        <property type="entry name" value="EIF5-MIMIC PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF25504">
        <property type="entry name" value="HEAT_5MP1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02020">
        <property type="entry name" value="W2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00515">
        <property type="entry name" value="eIF5C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48371">
        <property type="entry name" value="ARM repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51363">
        <property type="entry name" value="W2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <feature type="chain" id="PRO_0000254618" description="eIF5-mimic protein 1">
        <location>
            <begin position="1"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="domain" description="W2" evidence="1">
        <location>
            <begin position="248"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="13">
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12 14 15 16">
        <location>
            <position position="412"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12 15 16">
        <location>
            <position position="414"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055568" description="In isoform 2." evidence="8">
        <original>IAASFAVKLFKAWMAEKDAN</original>
        <variation>NEAPVFSPVRQQKKNKVTDS</variation>
        <location>
            <begin position="182"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055569" description="In isoform 2." evidence="8">
        <location>
            <begin position="202"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033642" description="In dbSNP:rs35233079.">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced interaction with EIF3C." evidence="7">
        <original>KWYKEAHVAKGK</original>
        <variation>QWYQEAQVAQGQ</variation>
        <location>
            <begin position="380"/>
            <end position="391"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced interaction with EIF2S2." evidence="3 7">
        <original>FVEWLQNAEEE</original>
        <variation>AAEAAQNAAAA</variation>
        <location>
            <begin position="401"/>
            <end position="411"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG39278." evidence="10" ref="1">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00695"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="21745818"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="25147208"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="28981728"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="29470543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="34260931"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="21745818"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <sequence length="419" mass="48162" checksum="7ABFE7A51501E721" modified="1999-11-01" version="1">MNKHQKPVLTGQRFKTRKRDEKEKFEPTVFRDTLVQGLNEAGDDLEAVAKFLDSTGSRLDYRRYADTLFDILVAGSMLAPGGTRIDDGDKTKMTNHCVFSANEDHETIRNYAQVFNKLIRRYKYLEKAFEDEMKKLLLFLKAFSETEQTKLAMLSGILLGNGTLPATILTSLFTDSLVKEGIAASFAVKLFKAWMAEKDANSVTSSLRKANLDKRLLELFPVNRQSVDHFAKYFTDAGLKELSDFLRVQQSLGTRKELQKELQERLSQECPIKEVVLYVKEEMKRNDLPETAVIGLLWTCIMNAVEWNKKEELVAEQALKHLKQYAPLLAVFSSQGQSELILLQKVQEYCYDNIHFMKAFQKIVVLFYKADVLSEEAILKWYKEAHVAKGKSVFLDQMKKFVEWLQNAEEESESEGEEN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>P34969</accession>
    <accession>B5BUP6</accession>
    <accession>P78336</accession>
    <accession>P78372</accession>
    <accession>P78516</accession>
    <accession>Q5VX01</accession>
    <accession>Q5VX02</accession>
    <accession>Q5VX03</accession>
    <name>5HT7R_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">5-hydroxytryptamine receptor 7</fullName>
            <shortName evidence="12">5-HT-7</shortName>
            <shortName evidence="12">5-HT7</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>5-HT-X</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">Serotonin receptor 7</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13 15" type="primary">HTR7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="J. Neurochem." volume="68" first="1372" last="1381">
            <title>Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization.</title>
            <authorList>
                <person name="Heidmann D.E.A."/>
                <person name="Metcalf M.A."/>
                <person name="Kohen R."/>
                <person name="Hamblin M.W."/>
            </authorList>
            <dbReference type="PubMed" id="9084407"/>
            <dbReference type="DOI" id="10.1046/j.1471-4159.1997.68041372.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="J. Biol. Chem." volume="268" first="23422" last="23426">
            <title>Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.</title>
            <authorList>
                <person name="Bard J.A."/>
                <person name="Zgombick J.M."/>
                <person name="Adham N."/>
                <person name="Vaysse P."/>
                <person name="Branchek T.A."/>
                <person name="Weinshank R.L."/>
            </authorList>
            <dbReference type="PubMed" id="8226867"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)49479-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A)</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Fetal brain</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-12" db="EMBL/GenBank/DDBJ databases">
            <title>Isolation of cDNA coding for 5-hydroxytryptamine receptor 7, transcript variant b (HTR7B).</title>
            <authorList>
                <person name="King M.M."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A)</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.2 ANGSTROMS) OF 2-432 IN COMPLEX WITH GNB1; GNB2 AND GNAS2</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-162; CYS-166; THR-167; ILE-233; THR-240; SER-243; TRP-340; PHE-343; PHE-344 AND TYR-374</scope>
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    <comment type="function">
        <text evidence="5 6">G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35714614, PubMed:8226867). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35714614, PubMed:8226867). HTR7 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:35714614).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625020">
            <id>P34969</id>
        </interactant>
        <interactant intactId="EBI-352602">
            <id>P43243</id>
            <label>MATR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P34969-1</id>
            <name>D</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P34969-2</id>
            <name>A</name>
            <sequence type="described" ref="VSP_001857"/>
        </isoform>
        <isoform>
            <id>P34969-3</id>
            <name>B</name>
            <sequence type="described" ref="VSP_001856"/>
        </isoform>
        <text>Isoform A and isoform B appear to be expressed at higher levels.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform A</molecule>
        <text evidence="7">Predominant isoform in spleen, caudate and hippocampus.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform B</molecule>
        <text evidence="7">Expressed at lower levels.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform D</molecule>
        <text evidence="7">Minor isoform in terms of expression.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Specificity for G(s) G alpha proteins is determined by the length of transmembrane regions 5 and 6 (TM5 and TM6).</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="U68487">
        <property type="protein sequence ID" value="AAB48393.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68488">
        <property type="protein sequence ID" value="AAB48394.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68492">
        <property type="protein sequence ID" value="AAF07218.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68493">
        <property type="protein sequence ID" value="AAF07217.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68492">
        <property type="protein sequence ID" value="AAF07217.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68493">
        <property type="protein sequence ID" value="AAB48397.2"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U68492">
        <property type="protein sequence ID" value="AAB48397.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L21195">
        <property type="protein sequence ID" value="AAC37538.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY493988">
        <property type="protein sequence ID" value="AAR87480.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292606">
        <property type="protein sequence ID" value="BAF85295.1"/>
        <property type="molecule type" value="mRNA"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
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    <feature type="disulfide bond" evidence="3 5 16">
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            <position position="92"/>
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            <position position="448"/>
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    <feature type="mutagenesis site" description="Abolished G-protein coupled receptor activity in response to serotonin." evidence="5">
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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            <position position="233"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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            <position position="240"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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        <location>
            <position position="243"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
        <original>W</original>
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            <position position="340"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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            <position position="343"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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            <position position="344"/>
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity in response to serotonin." evidence="5">
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            <position position="374"/>
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    <feature type="helix" evidence="17">
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q13639"/>
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            <dbReference type="PubMed" id="8226867"/>
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            <dbReference type="PubMed" id="9084407"/>
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            <dbReference type="PubMed" id="9154233"/>
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            <dbReference type="HGNC" id="HGNC:5302"/>
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            <dbReference type="PDB" id="7XTC"/>
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    <sequence length="479" mass="53555" checksum="1F62E985EADE1F23" modified="2000-05-30" version="2">MMDVNSSGRPDLYGHLRSFLLPEVGRGLPDLSPDGGADPVAGSWAPHLLSEVTASPAPTWDAPPDNASGCGEQINYGRVEKVVIGSILTLITLLTIAGNCLVVISVCFVKKLRQPSNYLIVSLALADLSVAVAVMPFVSVTDLIGGKWIFGHFFCNVFIAMDVMCCTASIMTLCVISIDRYLGITRPLTYPVRQNGKCMAKMILSVWLLSASITLPPLFGWAQNVNDDKVCLISQDFGYTIYSTAVAFYIPMSVMLFMYYQIYKAARKSAAKHKFPGFPRVEPDSVIALNGIVKLQKEVEECANLSRLLKHERKNISIFKREQKAATTLGIIVGAFTVCWLPFFLLSTARPFICGTSCSCIPLWVERTFLWLGYANSLINPFIYAFFNRDLRTTYRSLLQCQYRNINRKLSAAGMHEALKLAERPERPEFVLRACTRRVLLRPEKRPPVSVWVLQSPDHHNWLADKMLTTVEKKVMIHD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="171" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BXI3</accession>
    <accession>Q3SYB9</accession>
    <accession>Q5TG98</accession>
    <accession>Q9BWT8</accession>
    <name>5NT1A_HUMAN</name>
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        <recommendedName>
            <fullName>Cytosolic 5'-nucleotidase 1A</fullName>
            <shortName>cN1A</shortName>
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            <ecNumber evidence="3">3.1.3.89</ecNumber>
            <ecNumber evidence="3">3.1.3.99</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">5'-deoxynucleotidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Cytosolic 5'-nucleotidase IA</fullName>
            <shortName>cN-I</shortName>
            <shortName>cN-IA</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">NT5C1A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="10498" last="10504">
            <title>Human cytosolic 5'-nucleotidase I: characterization and role in nucleoside analog resistance.</title>
            <authorList>
                <person name="Hunsucker S.A."/>
                <person name="Spychala J."/>
                <person name="Mitchell B.S."/>
            </authorList>
            <dbReference type="PubMed" id="11133996"/>
            <dbReference type="DOI" id="10.1074/jbc.m011218200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2001-03" db="EMBL/GenBank/DDBJ databases">
            <title>5'-nucleotidase I from human heart.</title>
            <authorList>
                <person name="Lowenstein J.M."/>
                <person name="Huang J."/>
                <person name="Steiner A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="3">
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            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
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                <person name="Dunham A."/>
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                <person name="King A."/>
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                <person name="Lad H."/>
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                <person name="Mashreghi-Mohammadi M."/>
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                <person name="McLaren S."/>
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                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
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                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
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                <person name="Rouse G."/>
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                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
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                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
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                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
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                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
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            <title>Kinetics of adenylate metabolism in human and rat myocardium.</title>
            <authorList>
                <person name="Tavenier M."/>
                <person name="Skladanowski A.C."/>
                <person name="De Abreu R.A."/>
                <person name="de Jong J.W."/>
            </authorList>
            <dbReference type="PubMed" id="7599155"/>
            <dbReference type="DOI" id="10.1016/0304-4165(95)98595-c"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="6">
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            <title>Soluble forms of 5'-nucleotidase in rat and human heart.</title>
            <authorList>
                <person name="Skladanowski A.C."/>
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            <dbReference type="PubMed" id="8967393"/>
            <dbReference type="DOI" id="10.1152/ajpheart.1996.270.4.h1493"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>COFACTOR</scope>
        <scope>TISSUE SPECIFICITY</scope>
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    <reference key="7">
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            <authorList>
                <person name="Jedrzejewska A."/>
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            <dbReference type="PubMed" id="34814800"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 5 6">Catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside (PubMed:11133996, PubMed:34814800, PubMed:7599155, PubMed:8967393). AMP is the major substrate but can also hydrolyze dCMP and IMP (PubMed:11133996, PubMed:34814800, PubMed:7599155, PubMed:8967393).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4 5 6">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a 2'-deoxyribonucleoside 5'-phosphate + H2O = a 2'-deoxyribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:36167"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18274"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:65317"/>
            <dbReference type="EC" id="3.1.3.89"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>IMP + H2O = inosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:27718"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="EC" id="3.1.3.99"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4 5 6">
            <text>AMP + H2O = adenosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29375"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>dCMP + H2O = 2'-deoxycytidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29363"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15698"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57566"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="3 6">Activated by ADP.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">2.96 mM for AMP</KM>
            <KM evidence="5">5320 uM for AMP</KM>
            <KM evidence="6">1.46 mM for AMP</KM>
            <KM evidence="3">0.193 mM for dCMP</KM>
            <KM evidence="3">12.11 mM for IMP</KM>
            <Vmax evidence="3">7.7 umol/min/mg enzyme for AMP</Vmax>
            <Vmax evidence="3">18.1 umol/min/mg enzyme for dCMP</Vmax>
            <Vmax evidence="3">33.2 umol/min/mg enzyme for IMP</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="6">Optimum pH is 7.0.</text>
        </phDependence>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10441581">
            <id>Q9BXI3</id>
        </interactant>
        <interactant intactId="EBI-295634">
            <id>Q16543</id>
            <label>CDC37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10441581">
            <id>Q9BXI3</id>
        </interactant>
        <interactant intactId="EBI-741158">
            <id>Q96HA8</id>
            <label>NTAQ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 6">Highly expressed in skeletal muscle. Detected at intermediate levels in heart, brain, kidney and pancreas.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the 5'-nucleotidase type 3 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.3.5" evidence="3 4 5 6"/>
    <dbReference type="EC" id="3.1.3.89" evidence="3"/>
    <dbReference type="EC" id="3.1.3.99" evidence="3"/>
    <dbReference type="EMBL" id="AF331801">
        <property type="protein sequence ID" value="AAK01294.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028778">
        <property type="protein sequence ID" value="AAK30000.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL035404">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC103879">
        <property type="protein sequence ID" value="AAI03880.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC103880">
        <property type="protein sequence ID" value="AAI03881.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS440.1"/>
    <dbReference type="RefSeq" id="NP_115915.1">
        <property type="nucleotide sequence ID" value="NM_032526.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BXI3"/>
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        <property type="interactions" value="31"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BXI3">
        <property type="interactions" value="794"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BXI3">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000235628"/>
    <dbReference type="DEPOD" id="NT5C1A"/>
    <dbReference type="iPTMnet" id="Q9BXI3"/>
    <dbReference type="PhosphoSitePlus" id="Q9BXI3"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000235628"/>
    <dbReference type="PeptideAtlas" id="Q9BXI3"/>
    <dbReference type="ProteomicsDB" id="79426"/>
    <dbReference type="Antibodypedia" id="54865">
        <property type="antibodies" value="192 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84618"/>
    <dbReference type="Ensembl" id="ENST00000235628.2">
        <property type="protein sequence ID" value="ENSP00000235628.1"/>
        <property type="gene ID" value="ENSG00000116981.5"/>
    </dbReference>
    <dbReference type="GeneID" id="84618"/>
    <dbReference type="KEGG" id="hsa:84618"/>
    <dbReference type="MANE-Select" id="ENST00000235628.2">
        <property type="protein sequence ID" value="ENSP00000235628.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032526.3"/>
        <property type="RefSeq protein sequence ID" value="NP_115915.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001cdq.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17819"/>
    <dbReference type="ClinPGx" id="PA31799"/>
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    <dbReference type="GeneCards" id="NT5C1A"/>
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        <property type="gene designation" value="NT5C1A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000116981">
        <property type="expression patterns" value="Group enriched (skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MIM" id="610525">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000116981"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000116981"/>
    <dbReference type="eggNOG" id="ENOG502QRJF">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000017767"/>
    <dbReference type="HOGENOM" id="CLU_060123_0_0_1"/>
    <dbReference type="InParanoid" id="Q9BXI3"/>
    <dbReference type="OMA" id="YQIEHED"/>
    <dbReference type="OrthoDB" id="9994138at2759"/>
    <dbReference type="PAN-GO" id="Q9BXI3">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BXI3"/>
    <dbReference type="BioCyc" id="MetaCyc:HS04074-MONOMER"/>
    <dbReference type="BRENDA" id="3.1.3.5">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9BXI3"/>
    <dbReference type="Reactome" id="R-HSA-73621">
        <property type="pathway name" value="Pyrimidine catabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-74259">
        <property type="pathway name" value="Purine catabolism"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9BXI3"/>
    <dbReference type="SignaLink" id="Q9BXI3"/>
    <dbReference type="Agora" id="ENSG00000116981"/>
    <dbReference type="BioGRID-ORCS" id="84618">
        <property type="hits" value="19 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84618"/>
    <dbReference type="Pharos" id="Q9BXI3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BXI3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BXI3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000116981">
        <property type="expression patterns" value="Expressed in gastrocnemius and 85 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002953">
        <property type="term" value="F:5'-deoxynucleotidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008253">
        <property type="term" value="F:5'-nucleotidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000287">
        <property type="term" value="F:magnesium ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000166">
        <property type="term" value="F:nucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046085">
        <property type="term" value="P:adenosine metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000255">
        <property type="term" value="P:allantoin metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006196">
        <property type="term" value="P:AMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046059">
        <property type="term" value="P:dAMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046055">
        <property type="term" value="P:dGMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006204">
        <property type="term" value="P:IMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009116">
        <property type="term" value="P:nucleoside metabolic process"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR010394">
        <property type="entry name" value="5-nucleotidase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR31367">
        <property type="entry name" value="CYTOSOLIC 5'-NUCLEOTIDASE 1 FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR31367:SF2">
        <property type="entry name" value="CYTOSOLIC 5'-NUCLEOTIDASE 1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF06189">
        <property type="entry name" value="5-nucleotidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0546">Nucleotide metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000144795" description="Cytosolic 5'-nucleotidase 1A">
        <location>
            <begin position="1"/>
            <end position="368"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="1">
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAK30000." evidence="8" ref="2">
        <location>
            <begin position="9"/>
            <end position="11"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11133996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="34814800"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="7599155"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="8967393"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="11133996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="7599155"/>
        </source>
    </evidence>
    <sequence length="368" mass="41021" checksum="7FB3CCEED50BA50D" modified="2001-06-01" version="1">MEPGQPREPQEPREPGPGAETAAAPVWEEAKIFYDNLAPKKKPKSPKPQNAVTIAVSSRALFRMDEEQQIYTEQGVEEYVRYQLEHENEPFSPGPAFPFVKALEAVNRRLRELYPDSEDVFDIVLMTNNHAQVGVRLINSINHYDLFIERFCMTGGNSPICYLKAYHTNLYLSADAEKVREAIDEGIAAATIFSPSRDVVVSQSQLRVAFDGDAVLFSDESERIVKAHGLDRFFEHEKAHENKPLAQGPLKGFLEALGRLQKKFYSKGLRLECPIRTYLVTARSAASSGARALKTLRSWGLETDEALFLAGAPKGPLLEKIRPHIFFDDQMFHVAGAQEMGTVAAHVPYGVAQTPRRTAPAKQAPSAQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="179" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WXA8</accession>
    <accession>A2RRR5</accession>
    <name>5HT3C_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10">5-hydroxytryptamine receptor 3C</fullName>
            <shortName>5-HT3-C</shortName>
            <shortName>5-HT3C</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Serotonin receptor 3C</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">HTR3C</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="Gene" volume="310" first="101" last="111">
            <title>Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E.</title>
            <authorList>
                <person name="Niesler B."/>
                <person name="Frank B."/>
                <person name="Kapeller J."/>
                <person name="Rappold G.A."/>
            </authorList>
            <dbReference type="PubMed" id="12801637"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(03)00503-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS LYS-163 AND ALA-405</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2007" name="Mol. Pharmacol." volume="72" first="8" last="17">
            <title>Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E.</title>
            <authorList>
                <person name="Niesler B."/>
                <person name="Walstab J."/>
                <person name="Combrink S."/>
                <person name="Moeller D."/>
                <person name="Kapeller J."/>
                <person name="Rietdorf J."/>
                <person name="Boenisch H."/>
                <person name="Goethert M."/>
                <person name="Rappold G."/>
                <person name="Bruess M."/>
            </authorList>
            <dbReference type="PubMed" id="17392525"/>
            <dbReference type="DOI" id="10.1124/mol.106.032144"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] MET-128</scope>
    </reference>
    <comment type="function">
        <text evidence="8">Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="8">Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008753">
            <id>Q8WXA8</id>
        </interactant>
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
            <label>HTR3A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Postsynaptic cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="8">Presumably retained within the endoplasmic reticulum unless complexed with HTR3A.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed in many tissues including adult brain, colon, intestine, lung, muscle and stomach as well as fetal colon and kidney.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The HA-stretch region of HTR3C seems to confer increased conductance to HTR3A/HTR3C heteropentamers compared to that of HTR3A homopentamers.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3C sub-subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="AAL66182.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="EAW78305.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAI31800.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="organism name" value="human"/>
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        <property type="pathway name" value="Neurotransmitter receptors and postsynaptic signal transmission"/>
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        <property type="hits" value="14 hits in 1145 CRISPR screens"/>
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        <property type="component" value="Chromosome 3"/>
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        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 12 other cell types or tissues"/>
    </dbReference>
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        <property type="term" value="C:neuron projection"/>
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        <property type="term" value="P:inorganic cation transmembrane transport"/>
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        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="4">
        <location>
            <begin position="1"/>
            <end position="27"/>
        </location>
    </feature>
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        <location>
            <begin position="28"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="28"/>
            <end position="248"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="4">
        <location>
            <begin position="249"/>
            <end position="269"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="270"/>
            <end position="282"/>
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    <feature type="transmembrane region" description="Helical; Name=2" evidence="4">
        <location>
            <begin position="283"/>
            <end position="303"/>
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    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="304"/>
            <end position="306"/>
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    <feature type="transmembrane region" description="Helical; Name=3" evidence="4">
        <location>
            <begin position="307"/>
            <end position="329"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="330"/>
            <end position="424"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="4">
        <location>
            <begin position="425"/>
            <end position="445"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="446"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="380"/>
            <end position="405"/>
        </location>
    </feature>
    <feature type="region of interest" description="HA-stretch; determines single-channel conductance in 5-HT3 receptors" evidence="3">
        <location>
            <begin position="401"/>
            <end position="423"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="384"/>
            <end position="399"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="162"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037552" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs142791028." evidence="7">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
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        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037477" description="In dbSNP:rs6807362." evidence="6">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="405"/>
        </location>
    </feature>
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        <source>
            <dbReference type="UniProtKB" id="O95264"/>
        </source>
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        <source>
            <dbReference type="UniProtKB" id="P46098"/>
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    </evidence>
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        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
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        <source>
            <dbReference type="PubMed" id="12801637"/>
        </source>
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        <source>
            <dbReference type="PubMed" id="16959974"/>
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        <source>
            <dbReference type="PubMed" id="17392525"/>
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        <source>
            <dbReference type="PubMed" id="17392525"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="HGNC" id="HGNC:24003"/>
        </source>
    </evidence>
    <sequence length="447" mass="50220" checksum="E99260743598E596" modified="2008-01-15" version="2" precursor="true">MEGGWPARQSALLCLTVSLLLQGRGDAFTINCSGFDQHGVDPAVFQAVFDRKAFRPFTNYSIPTRVNISFTLSAILGVDAQLQLLTSFLWMDLVWDNPFINWNPKECVGINKLTVLAENLWLPDIFIVESMDVDQTPSGLTAYISSEGRIKYDKPMRVTSICNLDIFYFPFDQQNCTFTFSSFLYTVDSMLLGMDKEVWEITDTSRKVIQTQGEWELLGINKATPKMSMGNNLYDQIMFYVAIRRRPSLYIINLLVPSSFLVAIDALSFYLPAESENRAPFKITLLLGYNVFLLMMNDLLPASGTPLISVYFALCLSLMVVSLLETVFITYLLHVATTQPPPMPRWLHSLLLHCTSPGRCCPTAPQKGNKGLGLTLTHLPGPKEPGELAGKKLGPRETEPDGGSGWTKTQLMELWVQFSHAMDTLLFRLYLLFMASSILTVIVLWNT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="169" xmlns="https://uniprot.org/uniprot">
    <accession>Q96P26</accession>
    <accession>B5MCR0</accession>
    <accession>B7ZVX7</accession>
    <accession>Q53RX2</accession>
    <accession>Q8N9W3</accession>
    <accession>Q8NA26</accession>
    <accession>Q96DU5</accession>
    <accession>Q96KE6</accession>
    <accession>Q96M25</accession>
    <accession>Q96SA3</accession>
    <name>5NT1B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Cytosolic 5'-nucleotidase 1B</fullName>
            <shortName>cN1B</shortName>
            <ecNumber evidence="2">3.1.3.5</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Autoimmune infertility-related protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Cytosolic 5'-nucleotidase IB</fullName>
            <shortName>cN-IB</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">NT5C1B</name>
        <name type="synonym">AIRP</name>
        <name type="ORF">FKSG85</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2001-03" db="EMBL/GenBank/DDBJ databases">
            <title>Isolation of a novel human testis cDNA encoding a polypeptide related to autoimmune infertility.</title>
            <authorList>
                <person name="Setiady Y.Y."/>
                <person name="Pujianto D.A."/>
                <person name="Ekowati A.L."/>
                <person name="Harahap A."/>
                <person name="Marzuki S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2001-09" db="EMBL/GenBank/DDBJ databases">
            <title>Homo sapiens cytosolic nucleotidase Ib alpha mRNA.</title>
            <authorList>
                <person name="Ji Y."/>
                <person name="Mitchell B.S."/>
                <person name="Spychala J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Graves T.A."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Pepin K.H."/>
                <person name="Minx P."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
                <person name="Strong C.M."/>
                <person name="Grewal N."/>
                <person name="Goyea E."/>
                <person name="Hou S."/>
                <person name="Levy A."/>
                <person name="Martinka S."/>
                <person name="Mead K."/>
                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Shah N."/>
                <person name="Swearengen-Shahid S."/>
                <person name="Snider J."/>
                <person name="Strong J.T."/>
                <person name="Thompson J."/>
                <person name="Yoakum M."/>
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                <person name="Trani L."/>
                <person name="Radionenko M."/>
                <person name="Waligorski J.E."/>
                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
                <person name="Nelson J.O."/>
                <person name="Osborne J."/>
                <person name="Ding L."/>
                <person name="Meyer R."/>
                <person name="Sabo A."/>
                <person name="Shotland Y."/>
                <person name="Sinha P."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Jones T.A."/>
                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
                <person name="Schmutz J."/>
                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
                <person name="Huang X."/>
                <person name="McPherson J.D."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2001-02" db="EMBL/GenBank/DDBJ databases">
            <title>Identification and characterization of FKSG85 which encodes a nucleotidase protein.</title>
            <authorList>
                <person name="Wang Y.-G."/>
                <person name="Gong L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 312-610</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2001" name="Biochim. Biophys. Acta" volume="1521" first="12" last="18">
            <title>Cloning of a mouse cytosolic 5'-nucleotidase-I identifies a new gene related to human autoimmune infertility-related protein.</title>
            <authorList>
                <person name="Sala-Newby G.B."/>
                <person name="Newby A.C."/>
            </authorList>
            <dbReference type="PubMed" id="11690631"/>
            <dbReference type="DOI" id="10.1016/s0167-4781(01)00278-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 325-601</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, AMP is the major substrate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>AMP + H2O = adenosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29375"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Activated by ADP.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96P26-1</id>
            <name>1</name>
            <name>CN-Ib alpha</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96P26-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_010201"/>
        </isoform>
        <isoform>
            <id>Q96P26-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_010202"/>
        </isoform>
        <isoform>
            <id>Q96P26-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_010203"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Highly expressed in testis, placenta and pancreas. Detected at lower levels in heart, kidney, liver and lung.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the 5'-nucleotidase type 3 family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAK39108" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAK83285" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC04103" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAC44363" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.3.5" evidence="2"/>
    <dbReference type="EMBL" id="AF356185">
        <property type="protein sequence ID" value="AAK39108.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF417165">
        <property type="protein sequence ID" value="AAL11910.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093234">
        <property type="protein sequence ID" value="BAC04103.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093464">
        <property type="protein sequence ID" value="BAC04174.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK057444">
        <property type="protein sequence ID" value="BAB71489.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC079148">
        <property type="protein sequence ID" value="AAX93260.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAX00853.1"/>
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            <begin position="9"/>
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            <begin position="236"/>
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    <feature type="active site" description="Nucleophile" evidence="1">
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            <position position="467"/>
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            <begin position="1"/>
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            <begin position="41"/>
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    <feature type="splice variant" id="VSP_010203" description="In isoform 4." evidence="6">
        <original>LGSIAAYGFNKKFSS</original>
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            <begin position="596"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL11910." evidence="9" ref="2">
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            <position position="351"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAC04174." evidence="9" ref="3">
        <original>V</original>
        <variation>I</variation>
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            <position position="362"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 8; CAC44363." evidence="9" ref="8">
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        <location>
            <position position="528"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAK39108." evidence="9" ref="1">
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            <position position="552"/>
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        <source>
            <dbReference type="UniProtKB" id="Q91YE9"/>
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        <source>
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        <source>
            <dbReference type="PubMed" id="15489334"/>
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    <sequence length="610" mass="68804" checksum="EEC0BE9E5498B3E9" modified="2004-05-10" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-31" modified="2026-01-28" version="170" xmlns="https://uniprot.org/uniprot">
    <accession>Q7L1Q6</accession>
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    <accession>B4DWF7</accession>
    <accession>Q14281</accession>
    <accession>Q15394</accession>
    <accession>Q9BUY0</accession>
    <name>5MP2_HUMAN</name>
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        <recommendedName>
            <fullName evidence="8">eIF5-mimic protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Basic leucine zipper and W2 domain-containing protein 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein Orf</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">BZW1</name>
        <name evidence="8" type="synonym">5MP2</name>
        <name type="synonym">BZAP45</name>
        <name type="synonym">KIAA0005</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="27" last="35">
            <title>Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.</title>
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            </authorList>
            <dbReference type="PubMed" id="7584026"/>
            <dbReference type="DOI" id="10.1093/dnares/1.1.27"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
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                <person name="Fujimori K."/>
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                <person name="Watanabe M."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
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                <person name="Senoh A."/>
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                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
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                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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        <text evidence="3 4 5">Translation initiation regulator which represses repeat-associated non-AUG (RAN) initiated translation probably by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (PubMed:29470543, PubMed:34260931). Enhances histone H4 gene transcription but does not seem to bind DNA directly (PubMed:11524015).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1046727">
            <id>Q7L1Q6</id>
        </interactant>
        <interactant intactId="EBI-1051021">
            <id>Q9Y6E2</id>
            <label>BZW2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1046727">
            <id>Q7L1Q6</id>
        </interactant>
        <interactant intactId="EBI-1050964">
            <id>O43586</id>
            <label>PSTPIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21557060">
            <id>Q7L1Q6-2</id>
        </interactant>
        <interactant intactId="EBI-356015">
            <id>Q14204</id>
            <label>DYNC1H1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21557060">
            <id>Q7L1Q6-2</id>
        </interactant>
        <interactant intactId="EBI-2432309">
            <id>Q92876</id>
            <label>KLK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q7L1Q6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q7L1Q6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_021266"/>
        </isoform>
        <isoform>
            <id>Q7L1Q6-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043568"/>
        </isoform>
        <isoform>
            <id>Q7L1Q6-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_043569"/>
        </isoform>
    </comment>
    <comment type="developmental stage">
        <text evidence="3">Expressed in day 3 embryo.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the BZW family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA02795" version="2"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="D13630">
        <property type="protein sequence ID" value="BAA02795.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK297227">
        <property type="protein sequence ID" value="BAG59710.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301511">
        <property type="protein sequence ID" value="BAG63019.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007163">
        <property type="protein sequence ID" value="AAX93286.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001804">
        <property type="protein sequence ID" value="AAH01804.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC026303">
        <property type="protein sequence ID" value="AAH26303.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z70221">
        <property type="protein sequence ID" value="CAA94180.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56154.1">
        <molecule id="Q7L1Q6-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56155.1">
        <molecule id="Q7L1Q6-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56156.1">
        <molecule id="Q7L1Q6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001193996.1">
        <molecule id="Q7L1Q6-1"/>
        <property type="nucleotide sequence ID" value="NM_001207067.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001193997.1">
        <molecule id="Q7L1Q6-3"/>
        <property type="nucleotide sequence ID" value="NM_001207068.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001193998.1">
        <molecule id="Q7L1Q6-4"/>
        <property type="nucleotide sequence ID" value="NM_001207069.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308617.1">
        <molecule id="Q7L1Q6-1"/>
        <property type="nucleotide sequence ID" value="NM_001321688.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308619.1">
        <molecule id="Q7L1Q6-1"/>
        <property type="nucleotide sequence ID" value="NM_001321690.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308620.1">
        <property type="nucleotide sequence ID" value="NM_001321691.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308622.1">
        <property type="nucleotide sequence ID" value="NM_001321693.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308623.1">
        <property type="nucleotide sequence ID" value="NM_001321694.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055485.2">
        <molecule id="Q7L1Q6-2"/>
        <property type="nucleotide sequence ID" value="NM_014670.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q7L1Q6"/>
    <dbReference type="SMR" id="Q7L1Q6"/>
    <dbReference type="BioGRID" id="115042">
        <property type="interactions" value="194"/>
    </dbReference>
    <dbReference type="CORUM" id="Q7L1Q6"/>
    <dbReference type="FunCoup" id="Q7L1Q6">
        <property type="interactions" value="2811"/>
    </dbReference>
    <dbReference type="IntAct" id="Q7L1Q6">
        <property type="interactions" value="60"/>
    </dbReference>
    <dbReference type="MINT" id="Q7L1Q6"/>
    <dbReference type="STRING" id="9606.ENSP00000394316"/>
    <dbReference type="GlyGen" id="Q7L1Q6">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q7L1Q6"/>
    <dbReference type="MetOSite" id="Q7L1Q6"/>
    <dbReference type="PhosphoSitePlus" id="Q7L1Q6"/>
    <dbReference type="SwissPalm" id="Q7L1Q6"/>
    <dbReference type="BioMuta" id="BZW1"/>
    <dbReference type="DMDM" id="74738534"/>
    <dbReference type="jPOST" id="Q7L1Q6"/>
    <dbReference type="MassIVE" id="Q7L1Q6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000394316"/>
    <dbReference type="PeptideAtlas" id="Q7L1Q6"/>
    <dbReference type="ProteomicsDB" id="68744">
        <molecule id="Q7L1Q6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="68745">
        <molecule id="Q7L1Q6-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="68746">
        <molecule id="Q7L1Q6-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="68747">
        <molecule id="Q7L1Q6-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q7L1Q6"/>
    <dbReference type="TopDownProteomics" id="Q7L1Q6-1">
        <molecule id="Q7L1Q6-1"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="Q7L1Q6-2">
        <molecule id="Q7L1Q6-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="47644">
        <property type="antibodies" value="85 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="9689"/>
    <dbReference type="Ensembl" id="ENST00000409226.5">
        <molecule id="Q7L1Q6-4"/>
        <property type="protein sequence ID" value="ENSP00000386837.1"/>
        <property type="gene ID" value="ENSG00000082153.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409600.6">
        <molecule id="Q7L1Q6-1"/>
        <property type="protein sequence ID" value="ENSP00000386474.1"/>
        <property type="gene ID" value="ENSG00000082153.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000452790.6">
        <molecule id="Q7L1Q6-3"/>
        <property type="protein sequence ID" value="ENSP00000394316.2"/>
        <property type="gene ID" value="ENSG00000082153.19"/>
    </dbReference>
    <dbReference type="GeneID" id="9689"/>
    <dbReference type="KEGG" id="hsa:9689"/>
    <dbReference type="MANE-Select" id="ENST00000409600.6">
        <property type="protein sequence ID" value="ENSP00000386474.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001207067.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001193996.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002uwc.4">
        <molecule id="Q7L1Q6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18380"/>
    <dbReference type="ClinPGx" id="PA38535"/>
    <dbReference type="CTD" id="9689"/>
    <dbReference type="DisGeNET" id="9689"/>
    <dbReference type="GeneCards" id="BZW1"/>
    <dbReference type="HGNC" id="HGNC:18380">
        <property type="gene designation" value="BZW1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000082153">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="619252">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000082153"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000082153"/>
    <dbReference type="eggNOG" id="KOG2297">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012561"/>
    <dbReference type="HOGENOM" id="CLU_032849_0_1_1"/>
    <dbReference type="InParanoid" id="Q7L1Q6"/>
    <dbReference type="OrthoDB" id="1727522at2759"/>
    <dbReference type="PAN-GO" id="Q7L1Q6">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7L1Q6"/>
    <dbReference type="PathwayCommons" id="Q7L1Q6"/>
    <dbReference type="SignaLink" id="Q7L1Q6"/>
    <dbReference type="Agora" id="ENSG00000082153"/>
    <dbReference type="BioGRID-ORCS" id="9689">
        <property type="hits" value="35 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="BZW1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="BZW1"/>
    <dbReference type="GenomeRNAi" id="9689"/>
    <dbReference type="Pharos" id="Q7L1Q6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7L1Q6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7L1Q6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000082153">
        <property type="expression patterns" value="Expressed in palpebral conjunctiva and 211 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q7L1Q6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045296">
        <property type="term" value="F:cadherin binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006446">
        <property type="term" value="P:regulation of translational initiation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd11560">
        <property type="entry name" value="W2_eIF5C_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.180:FF:000006">
        <property type="entry name" value="Basic leucine zipper and W2 domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.180">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016024">
        <property type="entry name" value="ARM-type_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051245">
        <property type="entry name" value="eIF5-mimic_regulator"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR057397">
        <property type="entry name" value="HEAT_5MP1_2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043510">
        <property type="entry name" value="W2_5MP1/2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003307">
        <property type="entry name" value="W2_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14208">
        <property type="entry name" value="BASIC LEUCINE ZIPPER AND W2 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14208:SF0">
        <property type="entry name" value="EIF5-MIMIC PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF25504">
        <property type="entry name" value="HEAT_5MP1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02020">
        <property type="entry name" value="W2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00515">
        <property type="entry name" value="eIF5C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48371">
        <property type="entry name" value="ARM repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51363">
        <property type="entry name" value="W2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000254609" description="eIF5-mimic protein 2">
        <location>
            <begin position="1"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="domain" description="W2" evidence="1">
        <location>
            <begin position="247"/>
            <end position="414"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="2">
        <location>
            <begin position="1"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="16">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 11 12 13 14 15">
        <location>
            <position position="411"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12">
        <location>
            <position position="413"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="18">
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043568" description="In isoform 3." evidence="6">
        <original>M</original>
        <variation>MYGAPGAPAQSASVTVVRSLRRPPPQATGVSFM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043569" description="In isoform 4." evidence="6">
        <original>M</original>
        <variation>MVSFM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021266" description="In isoform 2." evidence="7">
        <location>
            <begin position="286"/>
            <end position="351"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00695"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11524015"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="29470543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="34260931"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="21745818"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="16964243"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="18318008"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <sequence length="419" mass="48043" checksum="9E952D52F5796F60" modified="2004-07-05" version="1">MNNQKQQKPTLSGQRFKTRKRDEKERFDPTQFQDCIIQGLTETGTDLEAVAKFLDASGAKLDYRRYAETLFDILVAGGMLAPGGTLADDMMRTDVCVFAAQEDLETMQAFAQVFNKLIRRYKYLEKGFEDEVKKLLLFLKGFSESERNKLAMLTGVLLANGTLNASILNSLYNENLVKEGVSAAFAVKLFKSWINEKDINAVAASLRKVSMDNRLMELFPANKQSVEHFTKYFTEAGLKELSEYVRNQQTIGARKELQKELQEQMSRGDPFKDIILYVKEEMKKNNIPEPVVIGIVWSSVMSTVEWNKKEELVAEQAIKHLKQYSPLLAAFTTQGQSELTLLLKIQEYCYDNIHFMKAFQKIVVLFYKAEVLSEEPILKWYKDAHVAKGKSVFLEQMKKFVEWLKNAEEESESEAEEGD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-12-04" modified="2026-01-28" version="173" xmlns="https://uniprot.org/uniprot">
    <accession>Q70Z44</accession>
    <accession>C9J2I6</accession>
    <accession>J3QT78</accession>
    <accession>Q495N5</accession>
    <accession>Q495N6</accession>
    <accession>Q7Z6B3</accession>
    <name>5HT3D_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">5-hydroxytryptamine receptor 3D</fullName>
            <shortName>5-HT3-D</shortName>
            <shortName>5-HT3D</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Serotonin receptor 3D</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">HTR3D</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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                <person name="Niesler B."/>
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            <dbReference type="PubMed" id="12801637"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(03)00503-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
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            </authorList>
            <dbReference type="PubMed" id="17392525"/>
            <dbReference type="DOI" id="10.1124/mol.106.032144"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANT GLY-171</scope>
    </reference>
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            <title>The DNA sequence, annotation and analysis of human chromosome 3.</title>
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                <person name="Yu J."/>
                <person name="Sudbrak R."/>
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                <person name="Chen R."/>
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                <person name="Zhou Y."/>
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            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <scope>VARIANTS HIS-225 AND HIS-435</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="7">Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008717">
            <id>Q70Z44</id>
        </interactant>
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
            <label>HTR3A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Postsynaptic cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="7">Presumably retained within the endoplasmic reticulum unless complexed with HTR3A.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q70Z44-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q70Z44-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_029798 VSP_029799 VSP_029801"/>
        </isoform>
        <isoform>
            <id>Q70Z44-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_029797 VSP_029800 VSP_029801"/>
        </isoform>
        <isoform>
            <id>Q70Z44-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_044828 VSP_044829 VSP_044830 VSP_029801"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expressed in liver, as well as fetal and adult colon and kidney.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The HA-stretch region of HTR3D seems to confer increased conductance to HTR3A/HTR3D heteropentamers compared to that of HTR3A homopentamers.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3D sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AJ437318">
        <property type="protein sequence ID" value="CAD24817.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY159812">
        <property type="protein sequence ID" value="AAO38166.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC068644">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC131235">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101090">
        <property type="protein sequence ID" value="AAI01091.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101091">
        <property type="protein sequence ID" value="AAI01092.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3249.1">
        <molecule id="Q70Z44-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46966.1">
        <molecule id="Q70Z44-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54685.1">
        <molecule id="Q70Z44-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS93429.1">
        <molecule id="Q70Z44-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138615.1">
        <molecule id="Q70Z44-4"/>
        <property type="nucleotide sequence ID" value="NM_001145143.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001157118.1">
        <molecule id="Q70Z44-1"/>
        <property type="nucleotide sequence ID" value="NM_001163646.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001397780.1">
        <molecule id="Q70Z44-3"/>
        <property type="nucleotide sequence ID" value="NM_001410851.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_872343.2">
        <property type="nucleotide sequence ID" value="NM_182537.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q70Z44"/>
    <dbReference type="SMR" id="Q70Z44"/>
    <dbReference type="BioGRID" id="128355">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-272">
        <property type="entry name" value="5-hydroxytryptamine-3A/D receptor complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q70Z44"/>
    <dbReference type="FunCoup" id="Q70Z44">
        <property type="interactions" value="192"/>
    </dbReference>
    <dbReference type="IntAct" id="Q70Z44">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000371929"/>
    <dbReference type="BindingDB" id="Q70Z44"/>
    <dbReference type="ChEMBL" id="CHEMBL2094132"/>
    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12141">
        <property type="generic name" value="Gilteritinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00715">
        <property type="generic name" value="Paroxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09304">
        <property type="generic name" value="Setiptiline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13025">
        <property type="generic name" value="Tiapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00246">
        <property type="generic name" value="Ziprasidone"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q70Z44"/>
    <dbReference type="TCDB" id="1.A.9.2.3">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q70Z44">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q70Z44">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q70Z44"/>
    <dbReference type="PhosphoSitePlus" id="Q70Z44"/>
    <dbReference type="BioMuta" id="HTR3D"/>
    <dbReference type="DMDM" id="338817899"/>
    <dbReference type="jPOST" id="Q70Z44"/>
    <dbReference type="MassIVE" id="Q70Z44"/>
    <dbReference type="PaxDb" id="9606-ENSP00000371929"/>
    <dbReference type="PeptideAtlas" id="Q70Z44"/>
    <dbReference type="ProteomicsDB" id="68580">
        <molecule id="Q70Z44-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="56799">
        <property type="antibodies" value="47 antibodies from 13 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="200909"/>
    <dbReference type="Ensembl" id="ENST00000382489.3">
        <molecule id="Q70Z44-1"/>
        <property type="protein sequence ID" value="ENSP00000371929.3"/>
        <property type="gene ID" value="ENSG00000186090.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000428798.7">
        <molecule id="Q70Z44-4"/>
        <property type="protein sequence ID" value="ENSP00000405409.2"/>
        <property type="gene ID" value="ENSG00000186090.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000453435.1">
        <molecule id="Q70Z44-3"/>
        <property type="protein sequence ID" value="ENSP00000389268.1"/>
        <property type="gene ID" value="ENSG00000186090.11"/>
    </dbReference>
    <dbReference type="GeneID" id="200909"/>
    <dbReference type="KEGG" id="hsa:200909"/>
    <dbReference type="MANE-Select" id="ENST00000428798.7">
        <molecule id="Q70Z44-4"/>
        <property type="protein sequence ID" value="ENSP00000405409.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001145143.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001138615.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010hxp.4">
        <molecule id="Q70Z44-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24004"/>
    <dbReference type="ClinPGx" id="PA134866755"/>
    <dbReference type="CTD" id="200909"/>
    <dbReference type="DisGeNET" id="200909"/>
    <dbReference type="GeneCards" id="HTR3D"/>
    <dbReference type="HGNC" id="HGNC:24004">
        <property type="gene designation" value="HTR3D"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000186090">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="MIM" id="610122">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000186090"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000186090"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156739"/>
    <dbReference type="HOGENOM" id="CLU_018074_5_2_1"/>
    <dbReference type="InParanoid" id="Q70Z44"/>
    <dbReference type="OMA" id="WKCAGIT"/>
    <dbReference type="OrthoDB" id="6097796at2759"/>
    <dbReference type="PAN-GO" id="Q70Z44">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q70Z44"/>
    <dbReference type="PathwayCommons" id="Q70Z44"/>
    <dbReference type="Reactome" id="R-HSA-112314">
        <property type="pathway name" value="Neurotransmitter receptors and postsynaptic signal transmission"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q70Z44"/>
    <dbReference type="SIGNOR" id="Q70Z44"/>
    <dbReference type="Agora" id="ENSG00000186090"/>
    <dbReference type="BioGRID-ORCS" id="200909">
        <property type="hits" value="15 hits in 1140 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="HTR3D">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HTR3D"/>
    <dbReference type="GenomeRNAi" id="200909"/>
    <dbReference type="Pharos" id="Q70Z44">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q70Z44"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q70Z44">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000186090">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 2 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q70Z44">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904602">
        <property type="term" value="C:serotonin-activated cation-selective channel complex"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902495">
        <property type="term" value="C:transmembrane transporter complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005231">
        <property type="term" value="F:excitatory extracellular ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022850">
        <property type="term" value="F:serotonin-gated monoatomic cation channel activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="CACAO"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098662">
        <property type="term" value="P:inorganic cation transmembrane transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007210">
        <property type="term" value="P:serotonin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140227">
        <property type="term" value="P:serotonin-gated cation-selective signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
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    <dbReference type="CDD" id="cd19063">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.20.58.390:FF:000143">
        <property type="entry name" value="5-hydroxytryptamine receptor 3D"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="LGIC_TM_5-HT3"/>
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        <property type="entry name" value="Neur_chan_lig-bd"/>
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        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
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        <property type="entry name" value="Neur_channel"/>
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        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
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        <property type="entry name" value="Neuro_actylchol_rec"/>
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        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
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        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
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        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
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        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000312293" description="5-hydroxytryptamine receptor 3D">
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            <begin position="25"/>
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    <feature type="topological domain" description="Extracellular" evidence="3">
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            <begin position="25"/>
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    <feature type="transmembrane region" description="Helical; Name=1" evidence="3">
        <location>
            <begin position="233"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="254"/>
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    <feature type="transmembrane region" description="Helical; Name=2" evidence="3">
        <location>
            <begin position="265"/>
            <end position="285"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="286"/>
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        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="3">
        <location>
            <begin position="307"/>
            <end position="327"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="328"/>
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    <feature type="transmembrane region" description="Helical; Name=4" evidence="3">
        <location>
            <begin position="432"/>
            <end position="452"/>
        </location>
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    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="453"/>
            <end position="454"/>
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    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="363"/>
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        </location>
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    <feature type="region of interest" description="HA-stretch; determines single-channel conductance in 5-HT3 receptors" evidence="2">
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            <begin position="399"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="66"/>
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    <feature type="splice variant" id="VSP_029797" description="In isoform 3." evidence="8">
        <location>
            <begin position="1"/>
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        <location>
            <begin position="1"/>
            <end position="135"/>
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    <feature type="splice variant" id="VSP_044828" description="In isoform 4." evidence="10">
        <original>MQKHSPGPPALALLSQSLLTTGNGDTLIINCPGFGQH</original>
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            <begin position="1"/>
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        <location>
            <begin position="38"/>
            <end position="98"/>
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    <feature type="splice variant" id="VSP_044830" description="In isoform 4." evidence="10">
        <original>A</original>
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            <position position="171"/>
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        <original>RAWRRMSRSFQIHHRTSFRTRREWVLLGIQKRTIKVTVATNQYEQAIFH</original>
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            <begin position="172"/>
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    <feature type="splice variant" id="VSP_029800" description="In isoform 3." evidence="8">
        <original>H</original>
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        <location>
            <position position="220"/>
        </location>
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    <feature type="splice variant" id="VSP_029801" description="In isoform 2, isoform 3 and isoform 4." evidence="8 9">
        <original>APLALMQTPLPA</original>
        <variation>RPHPSRDQKR</variation>
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            <begin position="295"/>
            <end position="306"/>
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    </feature>
    <feature type="sequence variant" id="VAR_037478" description="In dbSNP:rs6443930." evidence="7">
        <original>A</original>
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        <location>
            <position position="171"/>
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    <feature type="sequence variant" id="VAR_037479" description="In dbSNP:rs1000952." evidence="6">
        <original>R</original>
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        <location>
            <position position="225"/>
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    </feature>
    <feature type="sequence variant" id="VAR_037480" description="In dbSNP:rs6789754." evidence="6">
        <original>R</original>
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            <position position="435"/>
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    <feature type="sequence conflict" description="In Ref. 4; AAI01092." evidence="10" ref="4">
        <original>S</original>
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        <location>
            <position position="155"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAO38166." evidence="10" ref="2">
        <original>K</original>
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        <location>
            <position position="368"/>
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    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O95264"/>
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    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P46098"/>
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    </evidence>
    <evidence type="ECO:0000255" key="3"/>
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        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12801637"/>
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        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="17392525"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="17392525"/>
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    </evidence>
    <evidence type="ECO:0000305" key="10"/>
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        <source>
            <dbReference type="PubMed" id="17392525"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:24004"/>
        </source>
    </evidence>
    <sequence length="454" mass="50191" checksum="8B12F6CC31C4446C" modified="2011-06-28" version="3" precursor="true">MQKHSPGPPALALLSQSLLTTGNGDTLIINCPGFGQHRVDPAAFQAVFDRKAIGPVTNYSVATHVNISFTLSAIWNCYSRIHTFNCHHARPWHNQFVQWNPDECGGIKKSGMATENLWLSDVFIEESVDQTPAGLMASMSIVKATSNTISQCGWSASANWTPSISPSMDRARAWRRMSRSFQIHHRTSFRTRREWVLLGIQKRTIKVTVATNQYEQAIFHVAIRRRCRPSPYVVNFLVPSGILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVAPLALMQTPLPAGVYFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCPTAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEAELTGGSEWTRAQREHEAQKQHSVELWVQFSHAMDALLFRLYLLFMASSIITVICLWNT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-12-04" modified="2026-01-28" version="149" xmlns="https://uniprot.org/uniprot">
    <accession>A5X5Y0</accession>
    <accession>A8IKD7</accession>
    <accession>E9PGF1</accession>
    <accession>Q495G1</accession>
    <accession>Q495G3</accession>
    <accession>Q6V706</accession>
    <accession>Q6V707</accession>
    <accession>Q7Z6B2</accession>
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        <recommendedName>
            <fullName evidence="15">5-hydroxytryptamine receptor 3E</fullName>
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            <shortName>5-HT3E</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Serotonin receptor 3E</fullName>
        </alternativeName>
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        <name evidence="16" type="primary">HTR3E</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Niesler B."/>
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            <dbReference type="PubMed" id="12801637"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(03)00503-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Gene" volume="319" first="137" last="148">
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            <authorList>
                <person name="Karnovsky A.M."/>
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                <person name="Roberds S.L."/>
            </authorList>
            <dbReference type="PubMed" id="14597179"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(03)00803-5"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="Mol. Pharmacol." volume="72" first="8" last="17">
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            <authorList>
                <person name="Niesler B."/>
                <person name="Walstab J."/>
                <person name="Combrink S."/>
                <person name="Moeller D."/>
                <person name="Kapeller J."/>
                <person name="Rietdorf J."/>
                <person name="Boenisch H."/>
                <person name="Goethert M."/>
                <person name="Rappold G."/>
                <person name="Bruess M."/>
            </authorList>
            <dbReference type="PubMed" id="17392525"/>
            <dbReference type="DOI" id="10.1124/mol.106.032144"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3)</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2009" name="J. Neurochem." volume="108" first="384" last="396">
            <title>Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function.</title>
            <authorList>
                <person name="Holbrook J.D."/>
                <person name="Gill C.H."/>
                <person name="Zebda N."/>
                <person name="Spencer J.P."/>
                <person name="Leyland R."/>
                <person name="Rance K.H."/>
                <person name="Trinh H."/>
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                <person name="Kelly F.M."/>
                <person name="Yusaf S.P."/>
                <person name="Courtenay N."/>
                <person name="Luck J."/>
                <person name="Rhodes A."/>
                <person name="Modha S."/>
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            </authorList>
            <dbReference type="PubMed" id="19012743"/>
            <dbReference type="DOI" id="10.1111/j.1471-4159.2008.05775.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANT THR-71</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1194" last="1198">
            <title>The DNA sequence, annotation and analysis of human chromosome 3.</title>
            <authorList>
                <person name="Muzny D.M."/>
                <person name="Scherer S.E."/>
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                <person name="Yu J."/>
                <person name="Sudbrak R."/>
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                <person name="Zhou J."/>
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            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="7">Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11174612">
            <id>A5X5Y0-1</id>
        </interactant>
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
            <label>HTR3A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11163690">
            <id>A5X5Y0-3</id>
        </interactant>
        <interactant intactId="EBI-9008743">
            <id>P46098</id>
            <label>HTR3A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="15">Postsynaptic cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7 8">Cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="7">Presumably retained within the endoplasmic reticulum unless complexed with HTR3A.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>A5X5Y0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>A5X5Y0-2</id>
            <name>2</name>
            <name>5-HT3c1</name>
            <sequence type="described" ref="VSP_029804"/>
        </isoform>
        <isoform>
            <id>A5X5Y0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_029803"/>
        </isoform>
        <isoform>
            <id>A5X5Y0-4</id>
            <name>4</name>
            <name>5-HT3c1 long</name>
            <sequence type="described" ref="VSP_029803 VSP_029804"/>
        </isoform>
        <isoform>
            <id>A5X5Y0-6</id>
            <name>5</name>
            <name>HTR3E_V3</name>
            <sequence type="described" ref="VSP_029803 VSP_029804 VSP_045573"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Expressed in adult colon and intestine.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The HA-stretch region of HTR3E seems to confer increased conductance to HTR3A/HTR3E heteropentamers compared to that of HTR3A homopentamers.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3E sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AY349352">
        <property type="protein sequence ID" value="AAQ93476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY349353">
        <property type="protein sequence ID" value="AAQ93477.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY159813">
        <property type="protein sequence ID" value="AAO38167.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ644022">
        <property type="protein sequence ID" value="ABG35128.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EU165354">
        <property type="protein sequence ID" value="ABW05298.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC131235">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101182">
        <property type="protein sequence ID" value="AAI01183.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101183">
        <property type="protein sequence ID" value="AAI01184.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101185">
        <property type="protein sequence ID" value="AAI01186.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3251.1">
        <molecule id="A5X5Y0-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58868.1">
        <molecule id="A5X5Y0-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58869.1">
        <molecule id="A5X5Y0-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58870.1">
        <molecule id="A5X5Y0-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58871.1">
        <molecule id="A5X5Y0-6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001243542.1">
        <molecule id="A5X5Y0-1"/>
        <property type="nucleotide sequence ID" value="NM_001256613.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001243543.1">
        <molecule id="A5X5Y0-6"/>
        <property type="nucleotide sequence ID" value="NM_001256614.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_872395.2">
        <molecule id="A5X5Y0-3"/>
        <property type="nucleotide sequence ID" value="NM_182589.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_938055.1">
        <molecule id="A5X5Y0-2"/>
        <property type="nucleotide sequence ID" value="NM_198313.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_938056.1">
        <molecule id="A5X5Y0-4"/>
        <property type="nucleotide sequence ID" value="NM_198314.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="A5X5Y0"/>
    <dbReference type="SMR" id="A5X5Y0"/>
    <dbReference type="BioGRID" id="130056">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-273">
        <property type="entry name" value="5-hydroxytryptamine-3A/E receptor complex"/>
    </dbReference>
    <dbReference type="CORUM" id="A5X5Y0"/>
    <dbReference type="FunCoup" id="A5X5Y0">
        <property type="interactions" value="207"/>
    </dbReference>
    <dbReference type="IntAct" id="A5X5Y0">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000406050"/>
    <dbReference type="BindingDB" id="A5X5Y0"/>
    <dbReference type="ChEMBL" id="CHEMBL4296087"/>
    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12141">
        <property type="generic name" value="Gilteritinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00715">
        <property type="generic name" value="Paroxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09304">
        <property type="generic name" value="Setiptiline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13025">
        <property type="generic name" value="Tiapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00246">
        <property type="generic name" value="Ziprasidone"/>
    </dbReference>
    <dbReference type="DrugCentral" id="A5X5Y0"/>
    <dbReference type="GlyCosmos" id="A5X5Y0">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="A5X5Y0">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="A5X5Y0"/>
    <dbReference type="PhosphoSitePlus" id="A5X5Y0"/>
    <dbReference type="BioMuta" id="HTR3E"/>
    <dbReference type="MassIVE" id="A5X5Y0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000406050"/>
    <dbReference type="PeptideAtlas" id="A5X5Y0"/>
    <dbReference type="Antibodypedia" id="33787">
        <property type="antibodies" value="126 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="285242"/>
    <dbReference type="Ensembl" id="ENST00000335304.6">
        <molecule id="A5X5Y0-3"/>
        <property type="protein sequence ID" value="ENSP00000335511.2"/>
        <property type="gene ID" value="ENSG00000186038.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000415389.6">
        <molecule id="A5X5Y0-1"/>
        <property type="protein sequence ID" value="ENSP00000401444.2"/>
        <property type="gene ID" value="ENSG00000186038.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000425359.6">
        <molecule id="A5X5Y0-2"/>
        <property type="protein sequence ID" value="ENSP00000401900.2"/>
        <property type="gene ID" value="ENSG00000186038.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000436361.6">
        <molecule id="A5X5Y0-4"/>
        <property type="protein sequence ID" value="ENSP00000395833.2"/>
        <property type="gene ID" value="ENSG00000186038.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000440596.2">
        <molecule id="A5X5Y0-6"/>
        <property type="protein sequence ID" value="ENSP00000406050.2"/>
        <property type="gene ID" value="ENSG00000186038.9"/>
    </dbReference>
    <dbReference type="GeneID" id="285242"/>
    <dbReference type="KEGG" id="hsa:285242"/>
    <dbReference type="MANE-Select" id="ENST00000415389.6">
        <property type="protein sequence ID" value="ENSP00000401444.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001256613.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001243542.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003fml.5">
        <molecule id="A5X5Y0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24005"/>
    <dbReference type="ClinPGx" id="PA134900226"/>
    <dbReference type="CTD" id="285242"/>
    <dbReference type="DisGeNET" id="285242"/>
    <dbReference type="GeneCards" id="HTR3E"/>
    <dbReference type="HGNC" id="HGNC:24005">
        <property type="gene designation" value="HTR3E"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000186038">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="MIM" id="610123">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000186038"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000186038"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163899"/>
    <dbReference type="HOGENOM" id="CLU_018074_5_2_1"/>
    <dbReference type="InParanoid" id="A5X5Y0"/>
    <dbReference type="OMA" id="QFWIPDI"/>
    <dbReference type="OrthoDB" id="6097796at2759"/>
    <dbReference type="PAN-GO" id="A5X5Y0">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="A5X5Y0"/>
    <dbReference type="PathwayCommons" id="A5X5Y0"/>
    <dbReference type="Reactome" id="R-HSA-112314">
        <property type="pathway name" value="Neurotransmitter receptors and postsynaptic signal transmission"/>
    </dbReference>
    <dbReference type="SignaLink" id="A5X5Y0"/>
    <dbReference type="SIGNOR" id="A5X5Y0"/>
    <dbReference type="Agora" id="ENSG00000186038"/>
    <dbReference type="BioGRID-ORCS" id="285242">
        <property type="hits" value="10 hits in 1140 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HTR3E"/>
    <dbReference type="GenomeRNAi" id="285242"/>
    <dbReference type="Pharos" id="A5X5Y0">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A5X5Y0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="A5X5Y0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000186038">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 16 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="A5X5Y0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904602">
        <property type="term" value="C:serotonin-activated cation-selective channel complex"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902495">
        <property type="term" value="C:transmembrane transporter complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005231">
        <property type="term" value="F:excitatory extracellular ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022850">
        <property type="term" value="F:serotonin-gated monoatomic cation channel activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="CACAO"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098662">
        <property type="term" value="P:inorganic cation transmembrane transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007210">
        <property type="term" value="P:serotonin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140227">
        <property type="term" value="P:serotonin-gated cation-selective signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="CDD" id="cd19013">
        <property type="entry name" value="LGIC_ECD_5-HT3C_E"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19063">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000042">
        <property type="entry name" value="5-hydroxytryptamine receptor 3C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.70.170.10:FF:000026">
        <property type="entry name" value="5-hydroxytryptamine receptor 3C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049944">
        <property type="entry name" value="LGIC_TM_5-HT3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038050">
        <property type="entry name" value="Neuro_actylchol_rec"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018000">
        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="4">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000312294" description="5-hydroxytryptamine receptor 3E">
        <location>
            <begin position="26"/>
            <end position="456"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="26"/>
            <end position="248"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="4">
        <location>
            <begin position="249"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="270"/>
            <end position="282"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="4">
        <location>
            <begin position="283"/>
            <end position="303"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="304"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="4">
        <location>
            <begin position="308"/>
            <end position="328"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="329"/>
            <end position="433"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="4">
        <location>
            <begin position="434"/>
            <end position="454"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="455"/>
            <end position="456"/>
        </location>
    </feature>
    <feature type="region of interest" description="HA-stretch; determines single-channel conductance in 5-HT3 receptors" evidence="3">
        <location>
            <begin position="401"/>
            <end position="432"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="175"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="162"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029803" description="In isoform 3, isoform 4 and isoform 5." evidence="9 10 11 12 13">
        <original>MEGSWFHRKRFSFYLLLGFLLQ</original>
        <variation>MLAFILSRATPRPALGPLSYREHRVALLHLTHSMSTT</variation>
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            <begin position="1"/>
            <end position="22"/>
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    </feature>
    <feature type="splice variant" id="VSP_029804" description="In isoform 2, isoform 4 and isoform 5." evidence="10 13">
        <location>
            <begin position="79"/>
            <end position="93"/>
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    </feature>
    <feature type="splice variant" id="VSP_045573" description="In isoform 5." evidence="13">
        <original>E</original>
        <variation>ELCVSRAGQREVPSPGSHRDHSLPLGP</variation>
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            <position position="129"/>
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    </feature>
    <feature type="sequence variant" id="VAR_037481" description="In dbSNP:rs7627615." evidence="8">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="71"/>
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    </feature>
    <feature type="sequence variant" id="VAR_037482" description="In dbSNP:rs13324468.">
        <original>A</original>
        <variation>T</variation>
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            <position position="430"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAI01183/AAI01184." evidence="14" ref="6">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="44"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="O95264"/>
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    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P46098"/>
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    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12801637"/>
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    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="14597179"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="17392525"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="19012743"/>
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    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="12801637"/>
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    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14597179"/>
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    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="17392525"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="19012743"/>
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    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="17392525"/>
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    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:24005"/>
        </source>
    </evidence>
    <sequence length="456" mass="51438" checksum="4BFA6561BA309E83" modified="2007-07-10" version="1" precursor="true">MEGSWFHRKRFSFYLLLGFLLQGRGVTFTINCSGFGQHGADPTALNSVFNRKPFRPVTNISVPTQVNISFAMSAILDVNEQLHLLSSFLWLEMVWDNPFISWNPEECEGITKMSMAAKNLWLPDIFIIELMDVDKTPKGLTAYVSNEGRIRYKKPMKVDSICNLDIFYFPFDQQNCTLTFSSFLYTVDSMLLDMEKEVWEITDASRNILQTHGEWELLGLSKATAKLSRGGNLYDQIVFYVAIRRRPSLYVINLLVPSGFLVAIDALSFYLPVKSGNRVPFKITLLLGYNVFLLMMSDLLPTSGTPLIGVYFALCLSLMVGSLLETIFITHLLHVATTQPPPLPRWLHSLLLHCNSPGRCCPTAPQKENKGPGLTPTHLPGVKEPEVSAGQMPGPAEAELTGGSEWTRAQREHEAQKQHSVELWLQFSHAMDAMLFRLYLLFMASSIITVICLWNT</sequence>
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<entry dataset="Swiss-Prot" created="1988-11-01" modified="2026-01-28" version="216" xmlns="https://uniprot.org/uniprot">
    <accession>P08908</accession>
    <accession>Q6LAE7</accession>
    <name>5HT1A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>5-hydroxytryptamine receptor 1A</fullName>
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            <shortName evidence="25">5-HT1A</shortName>
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        <alternativeName>
            <fullName evidence="24">G-21</fullName>
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        <alternativeName>
            <fullName>Serotonin receptor 1A</fullName>
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    <gene>
        <name evidence="27" type="primary">HTR1A</name>
        <name type="synonym">ADRB2RL1</name>
        <name type="synonym">ADRBRL1</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 200-365</scope>
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        <scope>VARIANTS SER-22 AND VAL-28</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="Biochim. Biophys. Acta" volume="1852" first="2585" last="2592">
            <title>The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity.</title>
            <authorList>
                <person name="Tena-Campos M."/>
                <person name="Ramon E."/>
                <person name="Borroto-Escuela D.O."/>
                <person name="Fuxe K."/>
                <person name="Garriga P."/>
            </authorList>
            <dbReference type="PubMed" id="26365466"/>
            <dbReference type="DOI" id="10.1016/j.bbadis.2015.09.003"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH GRP39 AND GALR1</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="1998" name="Am. J. Med. Genet." volume="81" first="434" last="439">
            <title>Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia.</title>
            <authorList>
                <person name="Kawanishi Y."/>
                <person name="Harada S."/>
                <person name="Tachikawa H."/>
                <person name="Okubo T."/>
                <person name="Shiraishi H."/>
            </authorList>
            <dbReference type="PubMed" id="9754630"/>
            <dbReference type="DOI" id="10.1002/(sici)1096-8628(19980907)81:5&lt;434::aid-ajmg13&gt;3.0.co;2-d"/>
        </citation>
        <scope>VARIANTS LEU-16 AND ASP-273</scope>
    </reference>
    <comment type="function">
        <text evidence="7 11 12 13 14 15 16 18 19 21 22 23">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="12 14 15 16">G-protein coupled receptor activity is regulated by lipids: phosphatidylinositol 4-phosphate increases HTR1A-mediated activity (PubMed:33762731). Binding to aripiprazol drug is regulated by cholesterol, which shapes the ligand-binding pocket, determining the specificity for aripiprazol (PubMed:33762731). Activated by IHCH-7179 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and as an antagonist inhibitor for HTR2A (PubMed:38552625). Activated by SEP-363856 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and TAAR1 (PubMed:37935376, PubMed:37935377).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 8 9">Heterodimer; heterodimerizes with GPER1 (PubMed:23300088). Interacts with YIF1B (By similarity). Interacts with GPR39 and GALR1 (PubMed:26365466).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6570214">
            <id>P08908</id>
        </interactant>
        <interactant intactId="EBI-1028277">
            <id>P11362</id>
            <label>FGFR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6570214">
            <id>P08908</id>
        </interactant>
        <interactant intactId="EBI-7165599">
            <id>O43194</id>
            <label>GPR39</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 9 10 11 19">Cell membrane</location>
            <topology evidence="7 10 11 19">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Dendrite</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10 19">Detected in lymph nodes, thymus and spleen. Detected in activated T-cells, but not in resting T-cells.</text>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-03472">
            <name>Periodic fever, menstrual cycle-dependent</name>
            <acronym>PFMC</acronym>
            <description>A condition characterized by recurrent fevers up to 40 degrees Celsius associated with the luteal phase of the menstrual cycle. Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines.</description>
            <dbReference type="MIM" id="614674"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.</text>
    </comment>
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    <dbReference type="STRING" id="9606.ENSP00000316244"/>
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        <property type="generic name" value="2,5-Dimethoxyamphetamine"/>
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    <dbReference type="DrugBank" id="DB01484">
        <property type="generic name" value="4-Bromo-2,5-dimethoxyamphetamine"/>
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    <accession>Q62221</accession>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="1994" name="FEBS Lett." volume="342" first="85" last="90">
            <title>Cloning and functional characterization of the human 5-HT2B serotonin receptor.</title>
            <authorList>
                <person name="Schmuck K."/>
                <person name="Ullmer C."/>
                <person name="Engels P."/>
                <person name="Luebbert H."/>
            </authorList>
            <dbReference type="PubMed" id="8143856"/>
            <dbReference type="DOI" id="10.1016/0014-5793(94)80590-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="FEBS Lett." volume="352" first="393" last="399">
            <title>The human serotonin 5-HT2B receptor: pharmacological link between 5-HT2 and 5-HT1D receptors.</title>
            <authorList>
                <person name="Choi D.S."/>
                <person name="Birraux G."/>
                <person name="Launay J.-M."/>
                <person name="Maroteaux L."/>
            </authorList>
            <dbReference type="PubMed" id="7926008"/>
            <dbReference type="DOI" id="10.1016/0014-5793(94)00968-6"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1994" name="Mol. Pharmacol." volume="46" first="227" last="234">
            <title>Molecular cloning, functional expression, and mRNA tissue distribution of the human 5-hydroxytryptamine2B receptor.</title>
            <authorList>
                <person name="Kursar J.D."/>
                <person name="Nelson D.L."/>
                <person name="Wainscott D.B."/>
                <person name="Baez M."/>
            </authorList>
            <dbReference type="PubMed" id="8078486"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2000" name="Mol. Cell. Probes" volume="14" first="47" last="52">
            <title>Mutation screening of human 5-HT(2B) receptor gene in early-onset obsessive-compulsive disorder.</title>
            <authorList>
                <person name="Kim S.J."/>
                <person name="Veenstra-VanderWeele J."/>
                <person name="Hanna G.L."/>
                <person name="Gonen D."/>
                <person name="Leventhal B.L."/>
                <person name="Cook E.H. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="10722792"/>
            <dbReference type="DOI" id="10.1006/mcpr.1999.0281"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2002-07" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
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                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Arita M."/>
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                <person name="Musashino K."/>
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                <person name="Oshima A."/>
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                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
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    </reference>
    <comment type="function">
        <text evidence="1 5 6 7 8 9 10 11 12 13 14 15 16 17">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:18703043, PubMed:23519210, PubMed:7926008, PubMed:8078486, PubMed:8143856, PubMed:8882600). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:7926008, PubMed:8078486, PubMed:8143856). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). HTR2B is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:8078486, PubMed:8143856, PubMed:8882600). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development (By similarity). Protects cardiomyocytes against apoptosis (By similarity). Plays a role in the adaptation of pulmonary arteries to chronic hypoxia (By similarity). Plays a role in vasoconstriction (By similarity). Required for normal osteoblast function and proliferation, and for maintaining normal bone density (By similarity). Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts (via C-terminus) with MPDZ.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7474947">
            <id>P41595</id>
        </interactant>
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
            <label>HTR2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7474947">
            <id>P41595</id>
        </interactant>
        <interactant intactId="EBI-994141">
            <id>P28335</id>
            <label>HTR2C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 8 9 11 14 15 16">Cell membrane</location>
            <topology evidence="9 10 11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Synapse</location>
            <location evidence="1">Synaptosome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 14 15 16 17">Ubiquitous. Detected in liver, kidney, heart, pulmonary artery, and intestine. Detected at lower levels in blood, placenta and brain, especially in cerebellum, occipital cortex and frontal cortex.</text>
    </comment>
    <comment type="domain">
        <text evidence="9 10 11">Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="7">A variation at a single nucleotide base, which results in an erroneous stop codon and affects Gln-20, triggers non-sense mediated RNA decay, such that no HTR2B-receptor protein is expressed. It is associated with impulsive behavior and co-segregates with disorders characterized by impulsivity. However, the presence of this variant is not in itself sufficient to cause impulsive behavior: male sex, testosterone level, alcohol and stress exposure are other factors playing important roles.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="11">Binds lysergic acid diethylamine (LSD) in the orthosteric pocket, but is not the principal LSD receptor in the brain. Bound LSD dissociates extremely slowly, with a residence time of about 46 minutes at 37 degrees Celsius.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/127"/>
        <text>On the spur of a whim - Issue 127 of March 2011</text>
    </comment>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAX93128.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="BAG36482.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="EAW70949.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH63123.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="S49442"/>
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        <property type="nucleotide sequence ID" value="NM_000867.4"/>
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        <property type="nucleotide sequence ID" value="NM_001320758.1"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="XM_047444114.1"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="XM_054341694.1"/>
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        <property type="resolution" value="2.80 A"/>
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        <property type="resolution" value="3.00 A"/>
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        <property type="interactions" value="28"/>
    </dbReference>
    <dbReference type="CORUM" id="P41595"/>
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        <property type="interactions" value="798"/>
    </dbReference>
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    <dbReference type="STRING" id="9606.ENSP00000258400"/>
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        <property type="generic name" value="5-methoxy-N,N-dimethyltryptamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00543">
        <property type="generic name" value="Amoxapine"/>
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    <dbReference type="DrugBank" id="DB09128">
        <property type="generic name" value="Brexpiprazole"/>
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    <dbReference type="DrugBank" id="DB01200">
        <property type="generic name" value="Bromocriptine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00248">
        <property type="generic name" value="Cabergoline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB06016">
        <property type="generic name" value="Cariprazine"/>
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    <dbReference type="DrugBank" id="DB00477">
        <property type="generic name" value="Chlorpromazine"/>
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    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
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    <dbReference type="DrugBank" id="DB01242">
        <property type="generic name" value="Clomipramine"/>
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    <dbReference type="DrugBank" id="DB00924">
        <property type="generic name" value="Cyclobenzaprine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00434">
        <property type="generic name" value="Cyproheptadine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11274">
        <property type="generic name" value="Dihydro-alpha-ergocryptine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00320">
        <property type="generic name" value="Dihydroergotamine"/>
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    <dbReference type="DrugBank" id="DB01142">
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    </dbReference>
    <dbReference type="DrugBank" id="DB05492">
        <property type="generic name" value="Epicept NP-1"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00696">
        <property type="generic name" value="Ergotamine"/>
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        <property type="generic name" value="Lysergic acid diethylamide"/>
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        <property type="generic name" value="m-Chlorophenylpiperazine"/>
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        <property type="generic name" value="Methylergometrine"/>
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        <property type="generic name" value="Methysergide"/>
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        <property type="generic name" value="Mianserin"/>
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        <property type="generic name" value="Midomafetamine"/>
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        <property type="generic name" value="OPC-28326"/>
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        <property type="generic name" value="Pizotifen"/>
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        <property type="generic name" value="PRX-08066"/>
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        <property type="development level" value="Tclin"/>
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        <property type="component" value="Chromosome 2"/>
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    </dbReference>
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        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="evidence" value="ECO:0000318"/>
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    </dbReference>
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        <property type="term" value="C:G protein-coupled serotonin receptor complex"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
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        <property type="project" value="HPA"/>
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            <end position="192"/>
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            <end position="239"/>
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            <end position="324"/>
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            <end position="345"/>
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            <end position="360"/>
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            <end position="382"/>
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        <location>
            <begin position="383"/>
            <end position="481"/>
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    </feature>
    <feature type="short sequence motif" description="DRY motif; important for ligand-induced conformation changes" evidence="20 21">
        <location>
            <begin position="152"/>
            <end position="154"/>
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    </feature>
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            <begin position="212"/>
            <end position="215"/>
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            <begin position="376"/>
            <end position="380"/>
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            <begin position="479"/>
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    <feature type="binding site" evidence="9 23 24">
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            <position position="135"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:190463"/>
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            <position position="140"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:190463"/>
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    <feature type="site" description="Hydrophobic barrier that decreases the speed of ligand binding and dissociation" evidence="11">
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            <position position="209"/>
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            <position position="397"/>
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        <location>
            <position position="30"/>
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    </feature>
    <feature type="disulfide bond" evidence="3 9 10 11 12 13 23 24 25 26 27 28 29 30 31 32">
        <location>
            <begin position="128"/>
            <end position="207"/>
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    <feature type="disulfide bond" evidence="3 9 10 11 12 13 23 24 25 26 27 28 29 30 31 32">
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            <end position="353"/>
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    <feature type="sequence variant" id="VAR_064576" description="In dbSNP:rs77982984." evidence="7">
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        <location>
            <position position="388"/>
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        <location>
            <position position="421"/>
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    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
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        <variation>A</variation>
        <location>
            <position position="132"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes agonist binding." evidence="8">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="135"/>
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    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
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        <location>
            <position position="136"/>
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    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="139"/>
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    <feature type="mutagenesis site" description="Decreased agonist binding." evidence="8 12">
        <original>T</original>
        <variation>V</variation>
        <variation>A</variation>
        <location>
            <position position="140"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="208"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding. Strongly increases dissociation of bound lysergic acid diethylamine, without affecting binding affinity. Reduces signaling via arrestins, but has no effect on signaling via the phosphatidylinositol-calcium second messenger system." evidence="8 11">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="209"/>
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    <feature type="mutagenesis site" description="Impairs protein folding and stability. Strongly reduced cell surface expression." evidence="8">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="211"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="217"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>M</original>
        <variation>A</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect agonist binding." evidence="8 12">
        <original>A</original>
        <variation>G</variation>
        <variation>S</variation>
        <location>
            <position position="225"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="337"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="340"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="348"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="363"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on agonist binding." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="366"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly decreases agonist binding." evidence="8">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="370"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA85319." evidence="19" ref="2">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="452"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAH63123." evidence="19" ref="9">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="477"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="40"/>
            <end position="49"/>
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    </feature>
    <feature type="helix" evidence="33">
        <location>
            <begin position="54"/>
            <end position="63"/>
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    </feature>
    <feature type="helix" evidence="33">
        <location>
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    <sequence length="481" mass="54298" checksum="CDA4447ECDBA3B46" modified="1995-11-01" version="1">MALSYRVSELQSTIPEHILQSTFVHVISSNWSGLQTESIPEEMKQIVEEQGNKLHWAALLILMVIIPTIGGNTLVILAVSLEKKLQYATNYFLMSLAVADLLVGLFVMPIALLTIMFEAMWPLPLVLCPAWLFLDVLFSTASIMHLCAISVDRYIAIKKPIQANQYNSRATAFIKITVVWLISIGIAIPVPIKGIETDVDNPNNITCVLTKERFGDFMLFGSLAAFFTPLAIMIVTYFLTIHALQKKAYLVKNKPPQRLTWLTVSTVFQRDETPCSSPEKVAMLDGSRKDKALPNSGDETLMRRTSTIGKKSVQTISNEQRASKVLGIVFFLFLLMWCPFFITNITLVLCDSCNQTTLQMLLEIFVWIGYVSSGVNPLVYTLFNKTFRDAFGRYITCNYRATKSVKTLRKRSSKIYFRNPMAENSKFFKKHGIRNGINPAMYQSPMRLRSSTIQSSSIILLDTLLLTENEGDKTEEQVSYV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-09-13" modified="2026-01-28" version="204" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H0P0</accession>
    <accession>A8K253</accession>
    <accession>B2RAA5</accession>
    <accession>B8ZZC4</accession>
    <accession>Q6IPZ1</accession>
    <accession>Q6NXS6</accession>
    <accession>Q7L3G6</accession>
    <accession>Q9P0P5</accession>
    <accession>Q9UC42</accession>
    <accession>Q9UC43</accession>
    <accession>Q9UC44</accession>
    <accession>Q9UC45</accession>
    <name>5NT3A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19 20">Cytosolic 5'-nucleotidase 3A</fullName>
            <ecNumber evidence="7 11">3.1.3.5</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20">7-methylguanosine phosphate-specific 5'-nucleotidase</fullName>
            <shortName>7-methylguanosine nucleotidase</shortName>
            <ecNumber evidence="11">3.1.3.91</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Cytosolic 5'-nucleotidase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Cytosolic 5'-nucleotidase III</fullName>
            <shortName>cN-III</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Pyrimidine 5'-nucleotidase 1</fullName>
            <shortName>P5'N-1</shortName>
            <shortName>P5N-1</shortName>
            <shortName>PN-I</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Uridine 5'-monophosphate hydrolase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>p36</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">NT5C3A</name>
        <name type="synonym">NT5C3</name>
        <name type="synonym">P5N1</name>
        <name type="synonym">UMPH1</name>
        <name type="ORF">HSPC233</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Blood" volume="96" first="1596" last="1598">
            <title>Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, is identical to p36, a protein associated to lupus inclusion formation in response to alpha-interferon.</title>
            <authorList>
                <person name="Amici A."/>
                <person name="Emanuelli M."/>
                <person name="Raffaelli N."/>
                <person name="Ruggieri S."/>
                <person name="Saccucci F."/>
                <person name="Magni G."/>
            </authorList>
            <dbReference type="PubMed" id="10942414"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>PROTEIN SEQUENCE OF 92-111; 131-155; 226-240; 268-296 AND 313-332</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Blood" volume="97" first="3327" last="3332">
            <title>Genetic basis of hemolytic anemia caused by pyrimidine 5' nucleotidase deficiency.</title>
            <authorList>
                <person name="Marinaki A.M."/>
                <person name="Escuredo E."/>
                <person name="Duley J.A."/>
                <person name="Simmonds H.A."/>
                <person name="Amici A."/>
                <person name="Naponelli V."/>
                <person name="Magni G."/>
                <person name="Seip M."/>
                <person name="Ben-Bassat I."/>
                <person name="Harley E.H."/>
                <person name="Thein S.L."/>
                <person name="Rees D.C."/>
            </authorList>
            <dbReference type="PubMed" id="11369620"/>
            <dbReference type="DOI" id="10.1182/blood.v97.11.3327"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT P5ND VAL-137</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
                <person name="Wellenreuther R."/>
                <person name="Gassenhuber J."/>
                <person name="Glassl S."/>
                <person name="Ansorge W."/>
                <person name="Boecher M."/>
                <person name="Bloecker H."/>
                <person name="Bauersachs S."/>
                <person name="Blum H."/>
                <person name="Lauber J."/>
                <person name="Duesterhoeft A."/>
                <person name="Beyer A."/>
                <person name="Koehrer K."/>
                <person name="Strack N."/>
                <person name="Mewes H.-W."/>
                <person name="Ottenwaelder B."/>
                <person name="Obermaier B."/>
                <person name="Tampe J."/>
                <person name="Heubner D."/>
                <person name="Wambutt R."/>
                <person name="Korn B."/>
                <person name="Klein M."/>
                <person name="Poustka A."/>
            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
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                <person name="Obayashi M."/>
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                <person name="Yamamoto J."/>
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                <person name="Isono Y."/>
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                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
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                <person name="Sugawara M."/>
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                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
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                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
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                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
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                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
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                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Brain cortex</tissue>
            <tissue>Thalamus</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
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                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
            <authorList>
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            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.67 ANGSTROMS) OF 64-336 IN COMPLEX WITH PHOSPHATE AND MAGNESIUM IONS</scope>
        <scope>ACTIVE SITE</scope>
        <scope>METAL BINDING</scope>
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        <scope>VARIANT P5ND SER-229</scope>
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        <scope>VARIANTS P5ND PRO-181 AND ARG-280</scope>
        <scope>IDENTIFICATION OF ISOFORM 4</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>CHARACTERIZATION OF VARIANTS P5ND PRO-181 AND ARG-280</scope>
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        <scope>VARIANT P5ND GLY-95</scope>
    </reference>
    <comment type="function">
        <text evidence="7 11">Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP) (PubMed:24603684). CMP seems to be the preferred substrate (PubMed:15968458).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>N(7)-methyl-GMP + H2O = N(7)-methylguanosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:37107"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:20794"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58285"/>
            <dbReference type="EC" id="3.1.3.91"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>CMP + H2O = cytidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29367"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17562"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
            <dbReference type="EC" id="3.1.3.91"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="11">15 uM for m(7)GMP (at 37 degrees Celsius)</KM>
            <KM evidence="7">66 uM for CMP</KM>
            <KM evidence="11">80 uM for CMP (at 37 degrees Celsius)</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="9">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918356">
            <id>Q9H0P0</id>
        </interactant>
        <interactant intactId="EBI-2806959">
            <id>Q6ICB0</id>
            <label>DESI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3918356">
            <id>Q9H0P0</id>
        </interactant>
        <interactant intactId="EBI-947187">
            <id>Q9UHD9</id>
            <label>UBQLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="18">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location>Endoplasmic reticulum</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H0P0-4</id>
            <name>2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H0P0-1</id>
            <name>1</name>
            <name>P5N-I</name>
            <sequence type="described" ref="VSP_021565"/>
        </isoform>
        <isoform>
            <id>Q9H0P0-2</id>
            <name>3</name>
            <name>p36</name>
            <sequence type="described" ref="VSP_015623"/>
        </isoform>
        <isoform>
            <id>Q9H0P0-3</id>
            <name>4</name>
            <name>P5N-R</name>
            <sequence type="described" ref="VSP_015624"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 5">Isoforms 1, 3 and 4 are expressed in reticulocytes. Isoform 4 is hardly detectable in bone marrow and fetal liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="13">Isoform 2 is induced by interferon alpha in Raji cells in association with lupus inclusions.</text>
    </comment>
    <comment type="disease" evidence="3 4 5 6 7 8 10 12">
        <disease id="DI-02118">
            <name>P5N deficiency</name>
            <acronym>P5ND</acronym>
            <description>Autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.</description>
            <dbReference type="MIM" id="266120"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="18">Belongs to the pyrimidine 5'-nucleotidase family.</text>
    </comment>
    <comment type="sequence caution" evidence="18">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAF36153" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="18">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAG33630" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.3.5" evidence="7 11"/>
    <dbReference type="EC" id="3.1.3.91" evidence="11"/>
    <dbReference type="EMBL" id="AF312735">
        <property type="protein sequence ID" value="AAG33630.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136716">
        <property type="protein sequence ID" value="CAB66650.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290118">
        <property type="protein sequence ID" value="BAF82807.1"/>
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        <property type="antibodies" value="179 antibodies from 27 providers"/>
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        <property type="gene designation" value="NT5C3A"/>
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        <property type="expression patterns" value="Tissue enhanced (skeletal)"/>
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        <property type="type" value="phenotype"/>
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        <property type="disease" value="Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency"/>
    </dbReference>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    </dbReference>
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        <property type="pathway name" value="Pyrimidine catabolism"/>
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        <property type="hits" value="55 hits in 1131 CRISPR screens"/>
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        <property type="component" value="Chromosome 7"/>
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        <property type="molecule type" value="protein"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="project" value="FlyBase"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000166">
        <property type="term" value="F:nucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000215">
        <property type="term" value="F:tRNA 2'-phosphotransferase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006248">
        <property type="term" value="P:CMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006249">
        <property type="term" value="P:dCMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046074">
        <property type="term" value="P:dTMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0046079">
        <property type="term" value="P:dUMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0006213">
        <property type="term" value="P:pyrimidine nucleoside metabolic process"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046050">
        <property type="term" value="P:UMP catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="CDD" id="cd07504">
        <property type="entry name" value="HAD_5NT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.150.340:FF:000001">
        <property type="entry name" value="Cytosolic 5-nucleotidase 3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1000:FF:000032">
        <property type="entry name" value="Cytosolic 5-nucleotidase 3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1000">
        <property type="entry name" value="HAD superfamily/HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.150.340">
        <property type="entry name" value="Pyrimidine 5'-nucleotidase (UMPH-1), N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036412">
        <property type="entry name" value="HAD-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023214">
        <property type="entry name" value="HAD_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006434">
        <property type="entry name" value="Pyrimidine_nucleotidase_eu"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01544">
        <property type="entry name" value="HAD-SF-IE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13045">
        <property type="entry name" value="5'-NUCLEOTIDASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13045:SF14">
        <property type="entry name" value="CYTOSOLIC 5'-NUCLEOTIDASE 3A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05822">
        <property type="entry name" value="UMPH-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDG01128">
        <property type="entry name" value="C1.4:_5'-Nucleotidase_Like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDS00003">
        <property type="entry name" value="Haloacid_Dehalogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56784">
        <property type="entry name" value="HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0546">Nucleotide metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="chain" id="PRO_0000064387" description="Cytosolic 5'-nucleotidase 3A">
        <location>
            <begin position="1"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="9">
        <location>
            <position position="88"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="9">
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <position position="88"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <position position="90"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="135"/>
        </location>
        <ligand>
            <name>CMP</name>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="135"/>
        </location>
        <ligand>
            <name>N(7)-methyl-GMP</name>
            <dbReference type="ChEBI" id="CHEBI:58285"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="156"/>
        </location>
        <ligand>
            <name>N(7)-methyl-GMP</name>
            <dbReference type="ChEBI" id="CHEBI:58285"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <begin position="203"/>
            <end position="204"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="252"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <position position="277"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="278"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_015624" description="In isoform 4." evidence="16">
        <location>
            <begin position="1"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021565" description="In isoform 1." evidence="14 17">
        <original>MRAPSMDRAAVARVGAVASASVCALVAGVVLAQYIFTLKRKTGRKTKIIE</original>
        <variation>MTNQESAVHVK</variation>
        <location>
            <begin position="1"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_015623" description="In isoform 3." evidence="14 15">
        <location>
            <begin position="1"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073160" description="In P5ND; dbSNP:rs766577643." evidence="12">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073161" description="In P5ND; reduced catalytic activity especially towards UMP." evidence="10">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023511" description="In P5ND; reduced catalytic activity; dbSNP:rs104894025." evidence="3 6">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023512" description="In P5ND; reduced catalytic activity in vitro; reduced protein stability in vivo, probably through increased proteasomal degradation." evidence="5 6 8">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073162" description="In P5ND; reduced catalytic activity especially towards UMP." evidence="8 10">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023513" description="In P5ND; almost complete loss of catalytic activity; dbSNP:rs104894028." evidence="4 6 7">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023514" description="In P5ND; greatly reduced catalytic activity; dbSNP:rs104894029." evidence="5 6 7">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073163" description="In P5ND." evidence="8 10">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="297"/>
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    <feature type="mutagenesis site" description="Loss of nucleotidase and phosphotransferase activity." evidence="7">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="88"/>
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    <feature type="mutagenesis site" description="Almost complete loss of nucleotidase and phosphotransferase activity." evidence="7">
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    <feature type="mutagenesis site" description="Loss of nucleotidase and phosphotransferase activity." evidence="7">
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            <position position="90"/>
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    <feature type="mutagenesis site" description="No effect on nucleotidase activity. Almost complete loss of phosphotransferase activity." evidence="7">
        <original>E</original>
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            <position position="135"/>
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    <feature type="mutagenesis site" description="No effect on nucleotidase and phosphotransferase activity." evidence="7">
        <original>D</original>
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            <position position="232"/>
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    <feature type="mutagenesis site" description="Almost complete loss of nucleotidase and phosphotransferase activity." evidence="7">
        <original>F</original>
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            <position position="233"/>
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    <feature type="mutagenesis site" description="No effect on nucleotidase and phosphotransferase activity." evidence="7">
        <original>D</original>
        <variation>N</variation>
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            <position position="234"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="18" ref="10">
        <original>R</original>
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            <position position="95"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="18" ref="10">
        <original>E</original>
        <variation>Q</variation>
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            <position position="144"/>
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    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="18" ref="10">
        <original>N</original>
        <variation>R</variation>
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            <position position="329"/>
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            <begin position="65"/>
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            <begin position="80"/>
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    <feature type="turn" evidence="21">
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    <feature type="strand" evidence="21">
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    <feature type="helix" evidence="21">
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            <begin position="106"/>
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    <feature type="helix" evidence="21">
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            <begin position="118"/>
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    <feature type="strand" evidence="21">
        <location>
            <begin position="138"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="142"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="167"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="170"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="185"/>
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            <begin position="199"/>
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            <begin position="207"/>
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            <begin position="224"/>
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    <feature type="strand" evidence="21">
        <location>
            <begin position="231"/>
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        <location>
            <begin position="237"/>
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            <begin position="315"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
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            <dbReference type="UniProtKB" id="Q9W197"/>
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        <source>
            <dbReference type="PubMed" id="24603684"/>
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    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="2VKQ"/>
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</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>Q13639</accession>
    <accession>C4WYH4</accession>
    <accession>Q546Q1</accession>
    <accession>Q684M0</accession>
    <accession>Q712M9</accession>
    <accession>Q96KH9</accession>
    <accession>Q96KI0</accession>
    <accession>Q9H199</accession>
    <accession>Q9NY73</accession>
    <accession>Q9UBM6</accession>
    <accession>Q9UBT4</accession>
    <accession>Q9UE22</accession>
    <accession>Q9UE23</accession>
    <accession>Q9UQR6</accession>
    <name>5HT4R_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">5-hydroxytryptamine receptor 4</fullName>
            <shortName evidence="11">5-HT-4</shortName>
            <shortName evidence="11">5-HT4</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="11">Serotonin receptor 4</fullName>
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        <name evidence="14" type="primary">HTR4</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="J. Neurochem." volume="70" first="2252" last="2261">
            <title>Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus.</title>
            <authorList>
                <person name="Blondel O."/>
                <person name="Gastineau M."/>
                <person name="Dahmoune Y."/>
                <person name="Langlois M."/>
                <person name="Fischmeister R."/>
            </authorList>
            <dbReference type="PubMed" id="9603189"/>
            <dbReference type="DOI" id="10.1046/j.1471-4159.1998.70062252.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(B); 5-HT4(C) AND 5-HT4(D))</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Intestine</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="1997-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and expression of 5-HT4 receptor species and splice variants.</title>
            <authorList>
                <person name="Van den Wyngaert I."/>
                <person name="Gommeren W."/>
                <person name="Jurzak M."/>
                <person name="Verhasselt P."/>
                <person name="Gordon R."/>
                <person name="Leysen J."/>
                <person name="Luyten W."/>
                <person name="Bender E."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(B))</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="NeuroReport" volume="8" first="3189" last="3195">
            <title>Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase.</title>
            <authorList>
                <person name="Claeysen S."/>
                <person name="Faye P."/>
                <person name="Sebben M."/>
                <person name="Lemaire S."/>
                <person name="Bockaert J."/>
                <person name="Dumuis A."/>
            </authorList>
            <dbReference type="PubMed" id="9351641"/>
            <dbReference type="DOI" id="10.1097/00001756-199710200-00002"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(A))</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="1998-12" db="EMBL/GenBank/DDBJ databases">
            <title>Molecular cloning of the human serotonin receptor 5-HT4(b) and pharmacological comparison with the cloned human 5-HT4(a) receptor.</title>
            <authorList>
                <person name="Syversveen T."/>
                <person name="Bach T."/>
                <person name="Kvingedal A.M."/>
                <person name="Krobert K.A."/>
                <person name="Kaumann A.J."/>
                <person name="Levy F.O."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(B))</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="Mol. Pharmacol." volume="55" first="910" last="920">
            <title>Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain.</title>
            <authorList>
                <person name="Claeysen S."/>
                <person name="Sebben M."/>
                <person name="Becamel C."/>
                <person name="Bockaert J."/>
                <person name="Dumuis A."/>
            </authorList>
            <dbReference type="PubMed" id="10220570"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E))</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2002" name="Neuropharmacology" volume="42" first="60" last="73">
            <title>Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants.</title>
            <authorList>
                <person name="Vilaro M.T."/>
                <person name="Domenech T."/>
                <person name="Palacios J.M."/>
                <person name="Mengod G."/>
            </authorList>
            <dbReference type="PubMed" id="11750916"/>
            <dbReference type="DOI" id="10.1016/s0028-3908(01)00154-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A); 5-HT4(B); 5-HT4(E) AND 5-HT4(G))</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Naunyn Schmiedebergs Arch. Pharmacol." volume="369" first="616" last="628">
            <title>Cloning, pharmacological characterisation and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i).</title>
            <authorList>
                <person name="Brattelid T."/>
                <person name="Kvingedal A.M."/>
                <person name="Krobert K.A."/>
                <person name="Andressen K.W."/>
                <person name="Bach T."/>
                <person name="Hystad M.E."/>
                <person name="Kaumann A.J."/>
                <person name="Levy F.O."/>
            </authorList>
            <dbReference type="PubMed" id="15118808"/>
            <dbReference type="DOI" id="10.1007/s00210-004-0919-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(E) AND 5-HT4(I))</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="submission" date="2007-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning, expression and characterisation of a novel rat 5-HT4 receptor splice variant (5-HT4c1).</title>
            <authorList>
                <person name="Reid A.M."/>
                <person name="Kelsell R.E."/>
                <person name="Houp J.A."/>
                <person name="Kelly F.M."/>
                <person name="Medhurst A.D."/>
                <person name="Cox H.M."/>
                <person name="Calver A.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4C1)</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="Nature" volume="431" first="268" last="274">
            <title>The DNA sequence and comparative analysis of human chromosome 5.</title>
            <authorList>
                <person name="Schmutz J."/>
                <person name="Martin J."/>
                <person name="Terry A."/>
                <person name="Couronne O."/>
                <person name="Grimwood J."/>
                <person name="Lowry S."/>
                <person name="Gordon L.A."/>
                <person name="Scott D."/>
                <person name="Xie G."/>
                <person name="Huang W."/>
                <person name="Hellsten U."/>
                <person name="Tran-Gyamfi M."/>
                <person name="She X."/>
                <person name="Prabhakar S."/>
                <person name="Aerts A."/>
                <person name="Altherr M."/>
                <person name="Bajorek E."/>
                <person name="Black S."/>
                <person name="Branscomb E."/>
                <person name="Caoile C."/>
                <person name="Challacombe J.F."/>
                <person name="Chan Y.M."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Goodstein D."/>
                <person name="Grigoriev I."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Martinez D."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nandkeshwar R."/>
                <person name="Noonan J.P."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Priest J."/>
                <person name="Ramirez L."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="Wheeler J."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="Dickson M."/>
                <person name="Cheng J.-F."/>
                <person name="Eichler E.E."/>
                <person name="Olsen A."/>
                <person name="Pennacchio L.A."/>
                <person name="Rokhsar D.S."/>
                <person name="Richardson P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="10">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Florea L."/>
                <person name="Halpern A.L."/>
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                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
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                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5-HT4(B))</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2000" name="J. Neurochem." volume="74" first="478" last="489">
            <title>Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant.</title>
            <authorList>
                <person name="Bender E."/>
                <person name="Pindon A."/>
                <person name="van Oers I."/>
                <person name="Zhang Y.B."/>
                <person name="Gommeren W."/>
                <person name="Verhasselt P."/>
                <person name="Jurzak M."/>
                <person name="Leysen J."/>
                <person name="Luyten W."/>
            </authorList>
            <dbReference type="PubMed" id="10646498"/>
            <dbReference type="DOI" id="10.1046/j.1471-4159.2000.740478.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 10-388 (ISOFORM 5-HT4(F))</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1995" name="FEBS Lett." volume="370" first="215" last="221">
            <title>Expression of serotonin receptor mRNAs in blood vessels.</title>
            <authorList>
                <person name="Ullmer C."/>
                <person name="Schmuck K."/>
                <person name="Kalkman H.O."/>
                <person name="Luebbert H."/>
            </authorList>
            <dbReference type="PubMed" id="7656980"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)00828-w"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 112-255</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2000" name="Br. J. Pharmacol." volume="130" first="527" last="538">
            <title>Exploration of the ligand binding site of the human 5-HT(4) receptor by site-directed mutagenesis and molecular modeling.</title>
            <authorList>
                <person name="Mialet J."/>
                <person name="Dahmoune Y."/>
                <person name="Lezoualc'h F."/>
                <person name="Berque-Bestel I."/>
                <person name="Eftekhari P."/>
                <person name="Hoebeke J."/>
                <person name="Sicsic S."/>
                <person name="Langlois M."/>
                <person name="Fischmeister R."/>
            </authorList>
            <dbReference type="PubMed" id="10821780"/>
            <dbReference type="DOI" id="10.1038/sj.bjp.0703356"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ASP-100; SER-197 AND TYR-302</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2005" name="Biochem. Pharmacol." volume="70" first="1009" last="1018">
            <title>A high-affinity monoclonal antibody with functional activity against the 5-hydroxytryptaminergic (5-HT4) receptor.</title>
            <authorList>
                <person name="Kamel R."/>
                <person name="Eftekhari P."/>
                <person name="Garcia S."/>
                <person name="Berthouze M."/>
                <person name="Berque-Bestel I."/>
                <person name="Peter J.C."/>
                <person name="Lezoualc'h F."/>
                <person name="Hoebeke J."/>
            </authorList>
            <dbReference type="PubMed" id="16102731"/>
            <dbReference type="DOI" id="10.1016/j.bcp.2005.07.005"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2009" name="EMBO J." volume="28" first="2706" last="2718">
            <title>Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling.</title>
            <authorList>
                <person name="Barthet G."/>
                <person name="Carrat G."/>
                <person name="Cassier E."/>
                <person name="Barker B."/>
                <person name="Gaven F."/>
                <person name="Pillot M."/>
                <person name="Framery B."/>
                <person name="Pellissier L.P."/>
                <person name="Augier J."/>
                <person name="Kang D.S."/>
                <person name="Claeysen S."/>
                <person name="Reiter E."/>
                <person name="Baneres J.L."/>
                <person name="Benovic J.L."/>
                <person name="Marin P."/>
                <person name="Bockaert J."/>
                <person name="Dumuis A."/>
            </authorList>
            <dbReference type="PubMed" id="19661922"/>
            <dbReference type="DOI" id="10.1038/emboj.2009.215"/>
        </citation>
        <scope>INTERACTION WITH GRK5</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference evidence="15 16 17" key="17">
        <citation type="journal article" date="2022" name="Mol. Cell" volume="82" first="2681" last="2695">
            <title>GPCRs steer Gi and Gs selectivity via TM5-TM6 switches as revealed by structures of serotonin receptors.</title>
            <authorList>
                <person name="Huang S."/>
                <person name="Xu P."/>
                <person name="Shen D.D."/>
                <person name="Simon I.A."/>
                <person name="Mao C."/>
                <person name="Tan Y."/>
                <person name="Zhang H."/>
                <person name="Harpsoee K."/>
                <person name="Li H."/>
                <person name="Zhang Y."/>
                <person name="You C."/>
                <person name="Yu X."/>
                <person name="Jiang Y."/>
                <person name="Zhang Y."/>
                <person name="Gloriam D.E."/>
                <person name="Xu H.E."/>
            </authorList>
            <dbReference type="PubMed" id="35714614"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2022.05.031"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.1 ANGSTROMS) OF 2-388 IN COMPLEX WITH SEROTONIN; GNB1; GNB2 AND GNAS2</scope>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF ASP-100; THR-104; THR-105; PHE-186; ALA-193; TRP-272; PHE-275 AND TYR-302</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2012" name="Nat. Genet." volume="44" first="200" last="205">
            <title>Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.</title>
            <authorList>
                <person name="Rademakers R."/>
                <person name="Baker M."/>
                <person name="Nicholson A.M."/>
                <person name="Rutherford N.J."/>
                <person name="Finch N."/>
                <person name="Soto-Ortolaza A."/>
                <person name="Lash J."/>
                <person name="Wider C."/>
                <person name="Wojtas A."/>
                <person name="DeJesus-Hernandez M."/>
                <person name="Adamson J."/>
                <person name="Kouri N."/>
                <person name="Sundal C."/>
                <person name="Shuster E.A."/>
                <person name="Aasly J."/>
                <person name="MacKenzie J."/>
                <person name="Roeber S."/>
                <person name="Kretzschmar H.A."/>
                <person name="Boeve B.F."/>
                <person name="Knopman D.S."/>
                <person name="Petersen R.C."/>
                <person name="Cairns N.J."/>
                <person name="Ghetti B."/>
                <person name="Spina S."/>
                <person name="Garbern J."/>
                <person name="Tselis A.C."/>
                <person name="Uitti R."/>
                <person name="Das P."/>
                <person name="Van Gerpen J.A."/>
                <person name="Meschia J.F."/>
                <person name="Levy S."/>
                <person name="Broderick D.F."/>
                <person name="Graff-Radford N."/>
                <person name="Ross O.A."/>
                <person name="Miller B.B."/>
                <person name="Swerdlow R.H."/>
                <person name="Dickson D.W."/>
                <person name="Wszolek Z.K."/>
            </authorList>
            <dbReference type="PubMed" id="22197934"/>
            <dbReference type="DOI" id="10.1038/ng.1027"/>
        </citation>
        <scope>VARIANT LEU-27</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6 9 10">G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:10821780, PubMed:16102731, PubMed:35714614, PubMed:9603189). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:16102731, PubMed:35714614). HTR4 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:16102731, PubMed:35714614).</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin).</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform 5-HT4(A)</molecule>
        <text evidence="1">Interacts with MAGI2, MPP3, NHERF1 and SNX27 isoforms 1 and 2 (By similarity). Forms a complex including NHERF1 and EZR (By similarity).</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform 5-HT4(E)</molecule>
        <text evidence="1">Interacts with PATJ, NOS1 and SEC23A.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656425">
            <id>Q13639</id>
        </interactant>
        <interactant intactId="EBI-15639515">
            <id>O15354</id>
            <label>GPR37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656425">
            <id>Q13639</id>
        </interactant>
        <interactant intactId="EBI-740397">
            <id>O60269</id>
            <label>GPRIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6656425">
            <id>Q13639</id>
        </interactant>
        <interactant intactId="EBI-6656425">
            <id>Q13639</id>
            <label>HTR4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cell membrane</location>
            <topology evidence="9">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endosome membrane</location>
            <topology evidence="9">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">Interaction with SNX27 mediates recruitment to early endosomes, while interaction with NHERF1 and EZR might target the protein to specialized subcellular regions, such as microvilli.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q13639-1</id>
            <name>5-HT4(B)</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13639-2</id>
            <name>5-HT4(A)</name>
            <name>5-HT4S</name>
            <sequence type="described" ref="VSP_001849"/>
        </isoform>
        <isoform>
            <id>Q13639-3</id>
            <name>5-HT4(C)</name>
            <sequence type="described" ref="VSP_001848"/>
        </isoform>
        <isoform>
            <id>Q13639-4</id>
            <name>5-HT4(D)</name>
            <sequence type="described" ref="VSP_001847"/>
        </isoform>
        <isoform>
            <id>Q13639-5</id>
            <name>5-HT4(E)</name>
            <name>H5-HT4(g)</name>
            <sequence type="described" ref="VSP_001846"/>
        </isoform>
        <isoform>
            <id>Q13639-6</id>
            <name>5-HT4(F)</name>
            <sequence type="described" ref="VSP_001845"/>
        </isoform>
        <isoform>
            <id>Q13639-7</id>
            <name>5-HT4(G)</name>
            <sequence type="described" ref="VSP_001850"/>
        </isoform>
        <isoform>
            <id>Q13639-8</id>
            <name>5-HT4(I)</name>
            <sequence type="described" ref="VSP_043316"/>
        </isoform>
        <isoform>
            <id>Q13639-9</id>
            <name>5-HT4c1</name>
            <sequence type="described" ref="VSP_047862"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 5-HT4(A)</molecule>
        <text evidence="5">Expressed in ileum, brain, and atrium, but not in the ventricle.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 5-HT4(E)</molecule>
        <text evidence="5">Mainly expressed in atria and cardiac ventricle.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 5-HT4(I)</molecule>
        <text evidence="5">Expressed in all cardiovascular tissues analyzed.</text>
    </comment>
    <comment type="domain">
        <text evidence="9">Specificity for G(s) G alpha proteins is determined by the length of transmembrane regions 5 and 6 (TM5 and TM6).</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="Y08756">
        <property type="protein sequence ID" value="CAA70002.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y12505">
        <property type="protein sequence ID" value="CAA73107.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y12506">
        <property type="protein sequence ID" value="CAA73108.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y12507">
        <property type="protein sequence ID" value="CAA73109.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y10437">
        <property type="protein sequence ID" value="CAA71462.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y13584">
        <property type="protein sequence ID" value="CAA73911.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y09586">
        <property type="protein sequence ID" value="CAA70774.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ131724">
        <property type="protein sequence ID" value="CAC20411.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ011371">
        <property type="protein sequence ID" value="CAA09600.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ278979">
        <property type="protein sequence ID" value="CAC22248.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ278980">
        <property type="protein sequence ID" value="CAC22249.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ278981">
        <property type="protein sequence ID" value="CAC22250.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ278982">
        <property type="protein sequence ID" value="CAC22251.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ131725">
        <property type="protein sequence ID" value="CAC79533.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AJ131726">
        <property type="protein sequence ID" value="CAC79538.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ633645">
        <property type="protein sequence ID" value="CAG17627.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AM712912">
        <property type="protein sequence ID" value="CAN84676.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008627">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011390">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091971">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC114939">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61800.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61801.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471062">
        <property type="protein sequence ID" value="EAW61804.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC074755">
        <property type="protein sequence ID" value="AAH74755.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC095497">
        <property type="protein sequence ID" value="AAH95497.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ243213">
        <property type="protein sequence ID" value="CAB71316.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z48150">
        <property type="protein sequence ID" value="CAA88167.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34270.1">
        <molecule id="Q13639-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34271.1">
        <molecule id="Q13639-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34272.1">
        <molecule id="Q13639-8"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34273.2">
        <molecule id="Q13639-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4291.1">
        <molecule id="Q13639-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS75353.1">
        <molecule id="Q13639-9"/>
    </dbReference>
    <dbReference type="PIR" id="S66493">
        <property type="entry name" value="S66493"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000861.1">
        <molecule id="Q13639-1"/>
        <property type="nucleotide sequence ID" value="NM_000870.7"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035259.1">
        <molecule id="Q13639-2"/>
        <property type="nucleotide sequence ID" value="NM_001040169.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035262.2">
        <molecule id="Q13639-3"/>
        <property type="nucleotide sequence ID" value="NM_001040172.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035263.1">
        <molecule id="Q13639-8"/>
        <property type="nucleotide sequence ID" value="NM_001040173.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273339.1">
        <molecule id="Q13639-9"/>
        <property type="nucleotide sequence ID" value="NM_001286410.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_955525.1">
        <molecule id="Q13639-5"/>
        <property type="nucleotide sequence ID" value="NM_199453.3"/>
    </dbReference>
    <dbReference type="PDB" id="5EM9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="B=264-268"/>
    </dbReference>
    <dbReference type="PDB" id="7XT8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="R=2-388"/>
    </dbReference>
    <dbReference type="PDB" id="7XT9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="R=2-388"/>
    </dbReference>
    <dbReference type="PDB" id="7XTA">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="R=2-388"/>
    </dbReference>
    <dbReference type="PDBsum" id="5EM9"/>
    <dbReference type="PDBsum" id="7XT8"/>
    <dbReference type="PDBsum" id="7XT9"/>
    <dbReference type="PDBsum" id="7XTA"/>
    <dbReference type="AlphaFoldDB" id="Q13639"/>
    <dbReference type="EMDB" id="EMD-33442"/>
    <dbReference type="EMDB" id="EMD-33443"/>
    <dbReference type="EMDB" id="EMD-33444"/>
    <dbReference type="SMR" id="Q13639"/>
    <dbReference type="BioGRID" id="109592">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="CORUM" id="Q13639"/>
    <dbReference type="FunCoup" id="Q13639">
        <property type="interactions" value="1345"/>
    </dbReference>
    <dbReference type="IntAct" id="Q13639">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="MINT" id="Q13639"/>
    <dbReference type="STRING" id="9606.ENSP00000353915"/>
    <dbReference type="BindingDB" id="Q13639"/>
    <dbReference type="ChEMBL" id="CHEMBL1875"/>
    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08810">
        <property type="generic name" value="Cinitapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00604">
        <property type="generic name" value="Cisapride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12853">
        <property type="generic name" value="DA-6886"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00320">
        <property type="generic name" value="Dihydroergotamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12725">
        <property type="generic name" value="Felcisetrag"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12141">
        <property type="generic name" value="Gilteritinib"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-1003">Cell membrane</keyword>
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    <keyword id="KW-0675">Receptor</keyword>
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            <begin position="1"/>
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        <location>
            <begin position="1"/>
            <end position="19"/>
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            <begin position="20"/>
            <end position="44"/>
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            <end position="54"/>
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            <begin position="55"/>
            <end position="78"/>
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    </feature>
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        <location>
            <begin position="79"/>
            <end position="92"/>
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    </feature>
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            <begin position="93"/>
            <end position="117"/>
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    </feature>
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            <begin position="118"/>
            <end position="133"/>
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    </feature>
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            <begin position="134"/>
            <end position="157"/>
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    </feature>
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            <begin position="158"/>
            <end position="188"/>
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    </feature>
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            <begin position="189"/>
            <end position="212"/>
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    </feature>
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            <begin position="213"/>
            <end position="257"/>
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    </feature>
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            <begin position="258"/>
            <end position="283"/>
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    </feature>
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            <begin position="284"/>
            <end position="290"/>
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    </feature>
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            <begin position="291"/>
            <end position="314"/>
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    </feature>
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            <begin position="315"/>
            <end position="388"/>
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    </feature>
    <feature type="binding site" evidence="9 15">
        <location>
            <position position="100"/>
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        <ligand>
            <name>serotonin</name>
            <dbReference type="ChEBI" id="CHEBI:350546"/>
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    </feature>
    <feature type="binding site" evidence="9 15">
        <location>
            <position position="279"/>
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        <ligand>
            <name>serotonin</name>
            <dbReference type="ChEBI" id="CHEBI:350546"/>
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        <location>
            <position position="7"/>
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    </feature>
    <feature type="disulfide bond" evidence="3 9 15 16 17">
        <location>
            <begin position="93"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001845" description="In isoform 5-HT4(F)." evidence="13">
        <original>L</original>
        <variation>LERSLNQGLGQDFHA</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001847" description="In isoform 5-HT4(D)." evidence="13">
        <original>RDAVECGGQWESQCHPPATSPLVAAQPSDT</original>
        <variation>SSGTETDRRNFGIRKRRLTKPS</variation>
        <location>
            <begin position="359"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001846" description="In isoform 5-HT4(E)." evidence="13">
        <original>RDAVECGGQWESQCHPPATSPLVAAQPSDT</original>
        <variation>SGCSPVSSFLLLFCNRPVPV</variation>
        <location>
            <begin position="359"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_047862" description="In isoform 5-HT4c1." evidence="12">
        <original>RDAVECGGQWESQCHPPATSPLVAAQPSDT</original>
        <variation>SSGTETDRKKLWNKEEKIDQTIQMPKRKRKKKASLSYEDLILLGRKSCFREGK</variation>
        <location>
            <begin position="359"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043316" description="In isoform 5-HT4(I)." evidence="13">
        <original>R</original>
        <variation>RTDFLFDRDILARYWTKPARAGPFSGTLSIRCLTARKPVLG</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001849" description="In isoform 5-HT4(A)." evidence="13">
        <original>DAVECGGQWESQCHPPATSPLVAAQPSDT</original>
        <variation>YTVLHRGHHQELEKLPIHNDPESLESCF</variation>
        <location>
            <begin position="360"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001848" description="In isoform 5-HT4(C)." evidence="13">
        <original>DAVECGGQWESQCHPPATSPLVAAQPSDT</original>
        <variation>F</variation>
        <location>
            <begin position="360"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001850" description="In isoform 5-HT4(G)." evidence="13">
        <location>
            <begin position="360"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067412" description="In a patient with diffuse leukoencephalopathy with spheroids; uncertain significance; dbSNP:rs199508638." evidence="8">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_049364" description="In dbSNP:rs34826744.">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished G-protein coupled receptor activity." evidence="9">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In D3.32N mutant; abolihed binding to serotonin." evidence="4">
        <original>D</original>
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    <feature type="mutagenesis site" description="Abolished G-protein coupled receptor activity." evidence="9">
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    <feature type="mutagenesis site" description="Decreased G-protein coupled receptor activity." evidence="9">
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        <variation>V</variation>
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            <position position="302"/>
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        <location>
            <begin position="22"/>
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    </feature>
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<entry dataset="Swiss-Prot" created="1996-02-01" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>P47898</accession>
    <accession>Q2M2D2</accession>
    <name>5HT5A_HUMAN</name>
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            <fullName evidence="8">5-hydroxytryptamine receptor 5A</fullName>
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            <shortName evidence="7">5-HT-5A</shortName>
            <shortName evidence="7">5-HT5A</shortName>
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        <name evidence="11" type="primary">HTR5A</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="FEBS Lett." volume="355" first="242" last="246">
            <title>Cloning and characterisation of the human 5-HT5A serotonin receptor.</title>
            <authorList>
                <person name="Rees S."/>
                <person name="den Daas I."/>
                <person name="Foord S."/>
                <person name="Goodson S."/>
                <person name="Bull D."/>
                <person name="Kilpatrick G."/>
                <person name="Lee M."/>
            </authorList>
            <dbReference type="PubMed" id="7988681"/>
            <dbReference type="DOI" id="10.1016/0014-5793(94)01209-1"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] CYS-262</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1998" name="Eur. J. Pharmacol." volume="361" first="299" last="309">
            <title>The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells.</title>
            <authorList>
                <person name="Francken B.J."/>
                <person name="Jurzak M."/>
                <person name="Vanhauwe J.F."/>
                <person name="Luyten W.H."/>
                <person name="Leysen J.E."/>
            </authorList>
            <dbReference type="PubMed" id="9865521"/>
            <dbReference type="DOI" id="10.1016/s0014-2999(98)00744-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="12 13 14 15" key="6">
        <citation type="journal article" date="2022" name="Nat. Struct. Mol. Biol." volume="29" first="677" last="687">
            <title>Inactive and active state structures template selective tools for the human 5-HT5A receptor.</title>
            <authorList>
                <person name="Zhang S."/>
                <person name="Chen H."/>
                <person name="Zhang C."/>
                <person name="Yang Y."/>
                <person name="Popov P."/>
                <person name="Liu J."/>
                <person name="Krumm B.E."/>
                <person name="Cao C."/>
                <person name="Kim K."/>
                <person name="Xiong Y."/>
                <person name="Katritch V."/>
                <person name="Shoichet B.K."/>
                <person name="Jin J."/>
                <person name="Fay J.F."/>
                <person name="Roth B.L."/>
            </authorList>
            <dbReference type="PubMed" id="35835867"/>
            <dbReference type="DOI" id="10.1038/s41594-022-00796-6"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-357</scope>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.73 ANGSTROMS) OF 22-357 IN COMPLEX WITH 5-CARBOXAMIDOTRYPTAMINE AGONIST; GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF SER-142; ILE-143; MET-147; ARG-154; SER-204; ILE-223; 226-ALA-ALA-227; ALA-226; ALA-227; ARG-230; ARG-282; ALA-284; MET-286; VAL-287 AND ASN-342</scope>
    </reference>
    <reference evidence="16" key="7">
        <citation type="journal article" date="2022" name="Cell Discov." volume="8" first="50" last="50">
            <title>Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A.</title>
            <authorList>
                <person name="Tan Y."/>
                <person name="Xu P."/>
                <person name="Huang S."/>
                <person name="Yang G."/>
                <person name="Zhou F."/>
                <person name="He X."/>
                <person name="Ma H."/>
                <person name="Xu H.E."/>
                <person name="Jiang Y."/>
            </authorList>
            <dbReference type="PubMed" id="35610220"/>
            <dbReference type="DOI" id="10.1038/s41421-022-00412-3"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.1 ANGSTROMS) OF 2-357 IN COMPLEX WITH 5-CARBOXAMIDOTRYPTAMINE AGONIST; GNAI1 GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-121 AND GLU-305</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6">G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35610220, PubMed:35835867, PubMed:9865521). Also functions as a receptor for ergot alkaloid derivatives and other psychoactive substances (PubMed:35835867). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35610220, PubMed:35835867, PubMed:9865521). HTR5A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:35610220, PubMed:35835867, PubMed:9865521).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cell membrane</location>
            <topology evidence="4 5">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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<entry dataset="Swiss-Prot" created="1991-05-01" modified="2026-01-28" version="236" xmlns="https://uniprot.org/uniprot">
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            <fullName evidence="14 15">Thymidylate 5'-phosphatase</fullName>
        </alternativeName>
        <cdAntigenName>CD73</cdAntigenName>
    </protein>
    <gene>
        <name type="primary">NT5E</name>
        <name type="synonym">NT5</name>
        <name type="synonym">NTE</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>PARTIAL PROTEIN SEQUENCE</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-113</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-311; ASN-333 AND ASN-403</scope>
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            <tissue>Liver</tissue>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-333</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 27-549 IN COMPLEX WITH ZN(2+)</scope>
        <scope>ZINC-BINDING</scope>
        <scope>COFACTOR</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.13 ANGSTROMS) OF 27-549 IN COMPLEX WITH GMP</scope>
        <scope>CMP</scope>
        <scope>DCMP</scope>
        <scope>UMP AND IMP</scope>
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        <scope>VARIANT CALJA TYR-358</scope>
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        <scope>FUNCTION</scope>
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    <comment type="function">
        <text evidence="7 8 9 10 11">Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate (PubMed:21933152, PubMed:22997138, PubMed:23142347, PubMed:24887587, PubMed:34403084). Shows a preference for ribonucleotide monophosphates over their equivalent deoxyribose forms (PubMed:34403084). Other substrates include IMP, UMP, GMP, CMP, dAMP, dCMP, dTMP, NAD and NMN (PubMed:21933152, PubMed:22997138, PubMed:23142347, PubMed:24887587, PubMed:34403084).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 9 10 11">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>a 2'-deoxyribonucleoside 5'-phosphate + H2O = a 2'-deoxyribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:36167"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18274"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:65317"/>
            <dbReference type="EC" id="3.1.3.89"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>dTMP + H2O = thymidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:11080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17748"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:63528"/>
            <dbReference type="EC" id="3.1.3.35"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>CMP + H2O = cytidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29367"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17562"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
            <dbReference type="EC" id="3.1.3.91"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>IMP + H2O = inosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:27718"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="EC" id="3.1.3.99"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 9 10 11">
            <text>AMP + H2O = adenosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29375"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>GMP + H2O = guanosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:27714"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16750"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58115"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>UMP + H2O = uridine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29359"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16704"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57865"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 11">
            <text>dAMP + H2O = 2'-deoxyadenosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29371"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17256"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58245"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>dCMP + H2O = 2'-deoxycytidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29363"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15698"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57566"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8 9 11">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="8 9 11">Inhibited by adenosine 5'-(alpha,beta-methylene)-diphosphate (AMPCP).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="11">10.5 uM for AMP</KM>
            <KM evidence="9">6.62 uM for AMP</KM>
            <KM evidence="8">3.8 uM for AMP</KM>
            <KM evidence="8">6.5 uM for GMP</KM>
            <KM evidence="8">7.1 uM for IMP</KM>
            <KM evidence="8">8 uM for dTMP</KM>
            <KM evidence="8">31.6 uM for UMP</KM>
            <KM evidence="8">56.4 uM for CMP</KM>
            <KM evidence="8">114 uM for dAMP</KM>
            <KM evidence="8">880 uM for NMN</KM>
            <Vmax evidence="11">301.2 umol/min/mg enzyme for AMP</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="8 9">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6393623">
            <id>P21589</id>
        </interactant>
        <interactant intactId="EBI-13044680">
            <id>Q9Y225-2</id>
            <label>RNF24</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6393623">
            <id>P21589</id>
        </interactant>
        <interactant intactId="EBI-2129267">
            <id>Q8WWF5</id>
            <label>ZNRF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 10">Cell membrane</location>
            <topology evidence="5">Lipid-anchor</topology>
            <topology evidence="5">GPI-anchor</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P21589-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P21589-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043076"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="4 10">
        <disease id="DI-03016">
            <name>Calcification of joints and arteries</name>
            <acronym>CALJA</acronym>
            <description>A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands.</description>
            <dbReference type="MIM" id="211800"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="16">Belongs to the 5'-nucleotidase family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44492/NT5E"/>
    </comment>
    <dbReference type="EC" id="3.1.3.35" evidence="8 11"/>
    <dbReference type="EC" id="3.1.3.5" evidence="7 8 9 10 11"/>
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    <dbReference type="EC" id="3.1.3.99" evidence="8 11"/>
    <dbReference type="EMBL" id="X55740">
        <property type="protein sequence ID" value="CAA39271.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK075008">
        <property type="protein sequence ID" value="BAG52050.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL135903">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL589666">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U21730">
        <property type="protein sequence ID" value="AAA96950.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF069067">
        <property type="protein sequence ID" value="AAC98672.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5002.1">
        <molecule id="P21589-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56439.1">
        <molecule id="P21589-2"/>
    </dbReference>
    <dbReference type="PIR" id="S11032">
        <property type="entry name" value="S11032"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001191742.1">
        <molecule id="P21589-2"/>
        <property type="nucleotide sequence ID" value="NM_001204813.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002517.1">
        <molecule id="P21589-1"/>
        <property type="nucleotide sequence ID" value="NM_002526.4"/>
    </dbReference>
    <dbReference type="PDB" id="4H1S">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=27-549"/>
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    <dbReference type="PDB" id="4H1Y">
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        <property type="resolution" value="1.58 A"/>
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        <property type="resolution" value="1.70 A"/>
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        <property type="resolution" value="1.85 A"/>
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        <property type="resolution" value="1.48 A"/>
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        <property type="interactions" value="101"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-59992N"/>
    <dbReference type="FunCoup" id="P21589">
        <property type="interactions" value="607"/>
    </dbReference>
    <dbReference type="IntAct" id="P21589">
        <property type="interactions" value="54"/>
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    <dbReference type="MINT" id="P21589"/>
    <dbReference type="STRING" id="9606.ENSP00000257770"/>
    <dbReference type="BindingDB" id="P21589"/>
    <dbReference type="ChEMBL" id="CHEMBL5957"/>
    <dbReference type="DrugBank" id="DB03148">
        <property type="generic name" value="Adenosine 5'-methylenediphosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00201">
        <property type="generic name" value="Caffeine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00987">
        <property type="generic name" value="Cytarabine"/>
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    <dbReference type="DrugBank" id="DB12946">
        <property type="generic name" value="DPCPX"/>
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    <dbReference type="DrugBank" id="DB00651">
        <property type="generic name" value="Dyphylline"/>
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    <dbReference type="DrugBank" id="DB00824">
        <property type="generic name" value="Enprofylline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00806">
        <property type="generic name" value="Pentoxifylline"/>
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    <dbReference type="DrugBank" id="DB19160">
        <property type="generic name" value="Quemliclustat"/>
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    <dbReference type="DrugBank" id="DB01412">
        <property type="generic name" value="Theobromine"/>
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    <dbReference type="DrugBank" id="DB00277">
        <property type="generic name" value="Theophylline"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1232"/>
    <dbReference type="DEPOD" id="NT5E"/>
    <dbReference type="GlyCosmos" id="P21589">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P21589">
        <property type="glycosylation" value="5 sites, 24 N-linked glycans (3 sites), 1 O-linked glycan (1 site)"/>
    </dbReference>
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    <dbReference type="PhosphoSitePlus" id="P21589"/>
    <dbReference type="SwissPalm" id="P21589"/>
    <dbReference type="BioMuta" id="NT5E"/>
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    <reference key="1">
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            <title>Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes.</title>
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        <scope>VARIANT CYS-23</scope>
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            <tissue>Hippocampus</tissue>
            <tissue>Placenta</tissue>
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    <reference key="3">
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            </authorList>
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            <dbReference type="DOI" id="10.1006/geno.1996.0397"/>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT CYS-23</scope>
        <source>
            <tissue>Brain</tissue>
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                <person name="Niswender C.M."/>
                <person name="Sanders-Bush E."/>
                <person name="Emeson R.B."/>
            </authorList>
            <dbReference type="PubMed" id="9928237"/>
            <dbReference type="DOI" id="10.1111/j.1749-6632.1998.tb10171.x"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>RNA EDITING OF POSITIONS 156; 158 AND 160</scope>
        <scope>VARIANT CYS-23</scope>
        <source>
            <tissue>Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT CYS-23</scope>
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            <tissue>Brain</tissue>
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            <title>Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C).</title>
            <authorList>
                <person name="Lappalainen J."/>
                <person name="Zhang L."/>
                <person name="Dean M."/>
                <person name="Oz M."/>
                <person name="Ozaki N."/>
                <person name="Yu D."/>
                <person name="Virkkunen M."/>
                <person name="Weight F."/>
                <person name="Linnoila M."/>
                <person name="Goldman D."/>
            </authorList>
            <dbReference type="PubMed" id="7557992"/>
            <dbReference type="DOI" id="10.1006/geno.1995.1042"/>
        </citation>
        <scope>VARIANT CYS-23</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="1999" name="Am. J. Med. Genet." volume="88" first="126" last="130">
            <title>Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability.</title>
            <authorList>
                <person name="Samochowiec J."/>
                <person name="Smolka M."/>
                <person name="Winterer G."/>
                <person name="Rommelspacher H."/>
                <person name="Schmidt L.G."/>
                <person name="Sander T."/>
            </authorList>
            <dbReference type="PubMed" id="10206230"/>
            <dbReference type="DOI" id="10.1002/(sici)1096-8628(19990416)88:2&lt;126::aid-ajmg6&gt;3.3.co;2-d"/>
        </citation>
        <scope>VARIANT CYS-23</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="1999" name="Am. J. Med. Genet." volume="88" first="621" last="627">
            <title>Unified approach to the analysis of genetic variation in serotonergic pathways.</title>
            <authorList>
                <person name="Marshall S.E."/>
                <person name="Bird T.G."/>
                <person name="Hart K."/>
                <person name="Welsh K.I."/>
            </authorList>
            <dbReference type="PubMed" id="10581480"/>
            <dbReference type="DOI" id="10.1002/(sici)1096-8628(19991215)88:6&lt;621::aid-ajmg9&gt;3.0.co;2-h"/>
        </citation>
        <scope>VARIANT CYS-23</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="22" first="231" last="238">
            <title>Characterization of single-nucleotide polymorphisms in coding regions of human genes.</title>
            <authorList>
                <person name="Cargill M."/>
                <person name="Altshuler D."/>
                <person name="Ireland J."/>
                <person name="Sklar P."/>
                <person name="Ardlie K."/>
                <person name="Patil N."/>
                <person name="Shaw N."/>
                <person name="Lane C.R."/>
                <person name="Lim E.P."/>
                <person name="Kalyanaraman N."/>
                <person name="Nemesh J."/>
                <person name="Ziaugra L."/>
                <person name="Friedland L."/>
                <person name="Rolfe A."/>
                <person name="Warrington J."/>
                <person name="Lipshutz R."/>
                <person name="Daley G.Q."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="10391209"/>
            <dbReference type="DOI" id="10.1038/10290"/>
        </citation>
        <scope>VARIANT CYS-23</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="23" first="373" last="373">
            <authorList>
                <person name="Cargill M."/>
                <person name="Altshuler D."/>
                <person name="Ireland J."/>
                <person name="Sklar P."/>
                <person name="Ardlie K."/>
                <person name="Patil N."/>
                <person name="Shaw N."/>
                <person name="Lane C.R."/>
                <person name="Lim E.P."/>
                <person name="Kalyanaraman N."/>
                <person name="Nemesh J."/>
                <person name="Ziaugra L."/>
                <person name="Friedland L."/>
                <person name="Rolfe A."/>
                <person name="Warrington J."/>
                <person name="Lipshutz R."/>
                <person name="Daley G.Q."/>
                <person name="Lander E.S."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:10391209</scope>
    </reference>
    <comment type="function">
        <text evidence="1 10 16 17 19 21">G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="19">Inhibited by inverse agonist ritanserin.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 12 13 14">Interacts with MPDZ (PubMed:11150294). Interacts with ARRB2 (PubMed:16319069). Interacts with MPP3; this interaction stabilizes the receptor at the plasma membrane and prevents the desensitization of the HTR2C receptor-mediated calcium response (PubMed:14988405, PubMed:16914526).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-12172273">
            <id>O95406</id>
            <label>CNIH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-357481">
            <id>Q12959</id>
            <label>DLG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-80389">
            <id>P78352</id>
            <label>DLG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-4319440">
            <id>P54849</id>
            <label>EMP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-6656333">
            <id>P28223</id>
            <label>HTR2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-7474947">
            <id>P41595</id>
            <label>HTR2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-994141">
            <id>P28335</id>
            <label>HTR2C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-311035">
            <id>Q86UL8</id>
            <label>MAGI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-821405">
            <id>O75970</id>
            <label>MPDZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-1188341">
            <id>P49286</id>
            <label>MTNR1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-2823239">
            <id>Q9NUM3</id>
            <label>SLC39A9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-1045825">
            <id>P55061</id>
            <label>TMBIM6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-994141">
            <id>P28335</id>
        </interactant>
        <interactant intactId="EBI-348587">
            <id>Q9BVK8</id>
            <label>TMEM147</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21299643">
            <id>P28335-1</id>
        </interactant>
        <interactant intactId="EBI-15573967">
            <id>P28223-1</id>
            <label>HTR2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10 16 17 21">Cell membrane</location>
            <topology evidence="10 16 17 21">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P28335-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P28335-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_045171"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="22">Detected in brain.</text>
    </comment>
    <comment type="domain">
        <text evidence="9">The PDZ domain-binding motif is involved in the interaction with MPDZ.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9">N-glycosylated.</text>
    </comment>
    <comment type="RNA editing">
        <location>
            <position position="156" evidence="23"/>
        </location>
        <location>
            <position position="158" evidence="23"/>
        </location>
        <location>
            <position position="160" evidence="23"/>
        </location>
        <text>Partially edited. RNA editing generates receptor isoforms that differ in their ability to interact with the phospholipase C signaling cascade in a transfected cell line, suggesting that this RNA processing event may contribute to the modulation of serotonergic neurotransmission in the central nervous system.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA60317.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAB40898.1"/>
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        <property type="molecule type" value="mRNA"/>
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            <begin position="312"/>
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    <feature type="topological domain" description="Extracellular" evidence="19 30">
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            <begin position="337"/>
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    <feature type="transmembrane region" description="Helical; Name=7" evidence="19 30">
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            <begin position="348"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="19 30">
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            <begin position="371"/>
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    <feature type="region of interest" description="Disordered" evidence="5">
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            <begin position="274"/>
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    <feature type="short sequence motif" description="DRY motif; important for ligand-induced conformation changes" evidence="2">
        <location>
            <begin position="151"/>
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    <feature type="short sequence motif" description="NPxxY motif; important for ligand-induced conformation changes and signaling" evidence="2">
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            <begin position="364"/>
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    <feature type="short sequence motif" description="PDZ-binding">
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            <begin position="287"/>
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    <feature type="binding site" evidence="19 30">
        <location>
            <position position="139"/>
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        <ligand>
            <name>ergotamine</name>
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    <feature type="binding site" evidence="19 30">
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            <position position="209"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:190463"/>
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        <location>
            <position position="39"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
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            <position position="204"/>
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            <begin position="127"/>
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    <feature type="disulfide bond" evidence="4 19 30">
        <location>
            <begin position="337"/>
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    <feature type="splice variant" id="VSP_045171" description="In isoform 2." evidence="25">
        <original>YVAIRNPIEHSRFNSRTKAIMKIAIVWAISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDFLKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVCSGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVENLELPVNPSSVVSERISSV</original>
        <variation>CISSYPCDWTEGRRKGVREQHDVRAQRPKFRSYWVLRSFLHTADDYGDYVLPDHLRSAPTSFDVTARPHRGTAWTKSGFPEVLQEEYGRGRELCKP</variation>
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            <begin position="153"/>
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    <feature type="sequence variant" id="VAR_003450" description="In dbSNP:rs6318." evidence="6 7 8 11 15 18 20 21 22 23 24">
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        <location>
            <position position="23"/>
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    <feature type="sequence variant" id="VAR_010166" description="In RNA edited version.">
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            <position position="156"/>
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    <feature type="sequence variant" id="VAR_010167" description="In RNA edited version.">
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            <position position="158"/>
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    <feature type="sequence variant" id="VAR_010168" description="In RNA edited version; dbSNP:rs781938388.">
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        <location>
            <position position="160"/>
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        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="159"/>
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    <feature type="mutagenesis site" description="Decreased binding to inverse agonist ritanserin." evidence="19">
        <original>G</original>
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        <location>
            <position position="218"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreased binding to inverse agonist ritanserin." evidence="19">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="223"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreased binding to inverse agonist ritanserin." evidence="19">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="320"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreased binding to inverse agonist ritanserin." evidence="19">
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        <variation>F</variation>
        <variation>Y</variation>
        <location>
            <position position="324"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreased binding to inverse agonist ritanserin." evidence="19">
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        <location>
            <position position="354"/>
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        <original>S</original>
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        <location>
            <position position="456"/>
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    <feature type="mutagenesis site" description="No effect on interaction with MPDZ." evidence="9">
        <original>S</original>
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        <location>
            <position position="456"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with MPDZ." evidence="9">
        <original>S</original>
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        <location>
            <position position="457"/>
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    <feature type="mutagenesis site" description="Loss of interaction with MPDZ." evidence="9">
        <original>V</original>
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        <location>
            <position position="458"/>
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    <feature type="turn" evidence="33">
        <location>
            <begin position="48"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="56"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="61"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="82"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="87"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="107"/>
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    </feature>
    <feature type="turn" evidence="34">
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            <begin position="116"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="126"/>
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    </feature>
    <feature type="helix" evidence="35">
        <location>
            <begin position="159"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="167"/>
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    <feature type="helix" evidence="34">
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            <begin position="188"/>
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    </feature>
    <feature type="helix" evidence="34">
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            <begin position="197"/>
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    </feature>
    <feature type="strand" evidence="34">
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            <begin position="200"/>
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    <feature type="turn" evidence="34">
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            <begin position="203"/>
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            <begin position="338"/>
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    <feature type="helix" evidence="34">
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    <evidence type="ECO:0000250" key="1">
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    <evidence type="ECO:0000255" key="4">
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    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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        <source>
            <dbReference type="PubMed" id="14702039"/>
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            <dbReference type="PubMed" id="1722404"/>
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    <evidence type="ECO:0000303" key="27">
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        <source>
            <dbReference type="HGNC" id="HGNC:5295"/>
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    </evidence>
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        <source>
            <dbReference type="PDB" id="6BQG"/>
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        <source>
            <dbReference type="PDB" id="6BQG"/>
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        <source>
            <dbReference type="PDB" id="6BQH"/>
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        <source>
            <dbReference type="PDB" id="6BQG"/>
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        <source>
            <dbReference type="PDB" id="6BQH"/>
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    <evidence type="ECO:0007829" key="35">
        <source>
            <dbReference type="PDB" id="8DPF"/>
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    <sequence length="458" mass="51805" checksum="0622E8F8AE55696D" modified="2022-02-23" version="2" precursor="true">MVNLRNAVHSFLVHLIGLLVWQSDISVSPVAAIVTDIFNTSDGGRFKFPDGVQNWPALSIVIIIIMTIGGNILVIMAVSMEKKLHNATNYFLMSLAIADMLVGLLVMPLSLLAILYDYVWPLPRYLCPVWISLDVLFSTASIMHLCAISLDRYVAIRNPIEHSRFNSRTKAIMKIAIVWAISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDFLKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVCSGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVENLELPVNPSSVVSERISSV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-04-08" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q969T7</accession>
    <accession>A8MWB9</accession>
    <accession>C9JKC4</accession>
    <accession>Q7L3B7</accession>
    <name>5NT3B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">7-methylguanosine phosphate-specific 5'-nucleotidase</fullName>
            <shortName>7-methylguanosine nucleotidase</shortName>
            <ecNumber evidence="4">3.1.3.91</ecNumber>
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        <alternativeName>
            <fullName>Cytosolic 5'-nucleotidase 3B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">Cytosolic 5'-nucleotidase III-like protein</fullName>
            <shortName>cN-III-like protein</shortName>
            <ecNumber evidence="4">3.1.3.5</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>N(7)-methylguanylate 5'-phosphatase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">NT5C3B</name>
        <name type="synonym">NT5C3L</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
            <authorList>
                <person name="Zody M.C."/>
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                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
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                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANTS VAL-209 AND CYS-213</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANTS VAL-209 AND CYS-213</scope>
        <source>
            <tissue>Liver</tissue>
            <tissue>Lung</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-256</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2013" name="J. Biol. Chem." volume="288" first="2441" last="2451">
            <title>Identification of Drosophila and Human 7-Methyl GMP-specific Nucleotidases.</title>
            <authorList>
                <person name="Buschmann J."/>
                <person name="Moritz B."/>
                <person name="Jeske M."/>
                <person name="Lilie H."/>
                <person name="Schierhorn A."/>
                <person name="Wahle E."/>
            </authorList>
            <dbReference type="PubMed" id="23223233"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.426700"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="PLoS ONE" volume="9" first="90915" last="90915">
            <title>Crystal structures of the novel cytosolic 5'-nucleotidase IIIB explain its preference for m7GMP.</title>
            <authorList>
                <person name="Monecke T."/>
                <person name="Buschmann J."/>
                <person name="Neumann P."/>
                <person name="Wahle E."/>
                <person name="Ficner R."/>
            </authorList>
            <dbReference type="PubMed" id="24603684"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0090915"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5">Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate (PubMed:23223233, PubMed:24603684). The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids (PubMed:23223233). Also has weak activity for CMP (PubMed:23223233, PubMed:24603684). UMP and purine nucleotides are poor substrates (PubMed:23223233).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>N(7)-methyl-GMP + H2O = N(7)-methylguanosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:37107"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:20794"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58285"/>
            <dbReference type="EC" id="3.1.3.91"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>CMP + H2O = cytidine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29367"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17562"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
            <dbReference type="EC" id="3.1.3.91"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">7.8 uM for m(7)GMP (at 37 degrees Celsius)</KM>
            <KM evidence="5">8 uM for m(7)GMP (at 37 degrees Celsius)</KM>
            <KM evidence="4 5">79 uM for CMP (at 37 degrees Celsius)</KM>
            <KM evidence="4">355 uM for GMP (at 37 degrees Celsius)</KM>
            <KM evidence="4">456 uM for AMP (at 37 degrees Celsius)</KM>
            <KM evidence="4">439 uM for UMP (at 37 degrees Celsius)</KM>
            <Vmax evidence="4">0.41 umol/min/mg enzyme with m(7)GMP as substrate</Vmax>
            <Vmax evidence="4">12.0 umol/min/mg enzyme with CMP as substrate</Vmax>
            <Vmax evidence="4">0.13 umol/min/mg enzyme with GMP as substrate</Vmax>
            <Vmax evidence="4">0.07 umol/min/mg enzyme with AMP as substrate</Vmax>
            <Vmax evidence="4">10.7 umol/min/mg enzyme with UMP as substrate</Vmax>
            <text>kcat is 0.24 sec(-1) with m(7)GMP. kcat is 7 sec(-1) with CMP. kcat is 0.07 sec(-1) with GMP. kcat is 0.04 sec(-1) with AMP. kcat is 6.2 sec(-1) with UMP.</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="4">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q969T7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q969T7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046297"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the pyrimidine 5'-nucleotidase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.3.91" evidence="4"/>
    <dbReference type="EC" id="3.1.3.5" evidence="4"/>
    <dbReference type="EMBL" id="AC091172">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471152">
        <property type="protein sequence ID" value="EAW60771.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC013742">
        <property type="protein sequence ID" value="AAH13742.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014132">
        <property type="protein sequence ID" value="AAH14132.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016971">
        <property type="protein sequence ID" value="AAH16971.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067788">
        <property type="protein sequence ID" value="AAH67788.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11410.2">
        <molecule id="Q969T7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_443167.4">
        <molecule id="Q969T7-1"/>
        <property type="nucleotide sequence ID" value="NM_052935.4"/>
    </dbReference>
    <dbReference type="PDB" id="7ZEE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.36 A"/>
        <property type="chains" value="A=1-300"/>
    </dbReference>
    <dbReference type="PDB" id="7ZEG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.56 A"/>
        <property type="chains" value="A/B=1-300"/>
    </dbReference>
    <dbReference type="PDB" id="7ZEH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A/B/C/D=1-300"/>
    </dbReference>
    <dbReference type="PDBsum" id="7ZEE"/>
    <dbReference type="PDBsum" id="7ZEG"/>
    <dbReference type="PDBsum" id="7ZEH"/>
    <dbReference type="AlphaFoldDB" id="Q969T7"/>
    <dbReference type="SMR" id="Q969T7"/>
    <dbReference type="BioGRID" id="125410">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q969T7">
        <property type="interactions" value="1030"/>
    </dbReference>
    <dbReference type="IntAct" id="Q969T7">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000389948"/>
    <dbReference type="BindingDB" id="Q969T7"/>
    <dbReference type="ChEMBL" id="CHEMBL4295921"/>
    <dbReference type="DEPOD" id="NT5C3B"/>
    <dbReference type="GlyGen" id="Q969T7">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q969T7"/>
    <dbReference type="PhosphoSitePlus" id="Q969T7"/>
    <dbReference type="BioMuta" id="NT5C3B"/>
    <dbReference type="DMDM" id="476007845"/>
    <dbReference type="jPOST" id="Q969T7"/>
    <dbReference type="MassIVE" id="Q969T7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000389948"/>
    <dbReference type="PeptideAtlas" id="Q969T7"/>
    <dbReference type="ProteomicsDB" id="10565"/>
    <dbReference type="ProteomicsDB" id="75844">
        <molecule id="Q969T7-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q969T7"/>
    <dbReference type="Antibodypedia" id="28986">
        <property type="antibodies" value="73 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="115024"/>
    <dbReference type="Ensembl" id="ENST00000435506.7">
        <molecule id="Q969T7-1"/>
        <property type="protein sequence ID" value="ENSP00000389948.2"/>
        <property type="gene ID" value="ENSG00000141698.18"/>
    </dbReference>
    <dbReference type="GeneID" id="115024"/>
    <dbReference type="KEGG" id="hsa:115024"/>
    <dbReference type="MANE-Select" id="ENST00000435506.7">
        <property type="protein sequence ID" value="ENSP00000389948.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_052935.5"/>
        <property type="RefSeq protein sequence ID" value="NP_443167.4"/>
    </dbReference>
    <dbReference type="UCSC" id="uc021txo.2">
        <molecule id="Q969T7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28300"/>
    <dbReference type="CTD" id="115024"/>
    <dbReference type="GeneCards" id="NT5C3B"/>
    <dbReference type="HGNC" id="HGNC:28300">
        <property type="gene designation" value="NT5C3B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000141698">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="620041">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000141698"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000141698"/>
    <dbReference type="eggNOG" id="KOG3128">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012959"/>
    <dbReference type="InParanoid" id="Q969T7"/>
    <dbReference type="OMA" id="HIPWIYL"/>
    <dbReference type="OrthoDB" id="10014216at2759"/>
    <dbReference type="PAN-GO" id="Q969T7">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q969T7"/>
    <dbReference type="Reactome" id="R-HSA-429958">
        <property type="pathway name" value="mRNA decay by 3' to 5' exoribonuclease"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q969T7"/>
    <dbReference type="SignaLink" id="Q969T7"/>
    <dbReference type="Agora" id="ENSG00000141698"/>
    <dbReference type="BioGRID-ORCS" id="115024">
        <property type="hits" value="16 hits in 1144 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="NT5C3B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="115024"/>
    <dbReference type="Pharos" id="Q969T7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q969T7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q969T7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000141698">
        <property type="expression patterns" value="Expressed in nucleus accumbens and 186 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q969T7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008253">
        <property type="term" value="F:5'-nucleotidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000287">
        <property type="term" value="F:magnesium ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000166">
        <property type="term" value="F:nucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000288">
        <property type="term" value="P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009117">
        <property type="term" value="P:nucleotide metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd07504">
        <property type="entry name" value="HAD_5NT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.150.340:FF:000001">
        <property type="entry name" value="Cytosolic 5-nucleotidase 3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1000:FF:000032">
        <property type="entry name" value="Cytosolic 5-nucleotidase 3-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1000">
        <property type="entry name" value="HAD superfamily/HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.150.340">
        <property type="entry name" value="Pyrimidine 5'-nucleotidase (UMPH-1), N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036412">
        <property type="entry name" value="HAD-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023214">
        <property type="entry name" value="HAD_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006434">
        <property type="entry name" value="Pyrimidine_nucleotidase_eu"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01544">
        <property type="entry name" value="HAD-SF-IE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13045">
        <property type="entry name" value="5'-NUCLEOTIDASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13045:SF15">
        <property type="entry name" value="7-METHYLGUANOSINE PHOSPHATE-SPECIFIC 5'-NUCLEOTIDASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05822">
        <property type="entry name" value="UMPH-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDG01128">
        <property type="entry name" value="C1.4:_5'-Nucleotidase_Like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDS00003">
        <property type="entry name" value="Haloacid_Dehalogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56784">
        <property type="entry name" value="HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0546">Nucleotide metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000328948" description="7-methylguanosine phosphate-specific 5'-nucleotidase">
        <location>
            <begin position="1"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="2">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="2">
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="41"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="43"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="88"/>
        </location>
        <ligand>
            <name>CMP</name>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="88"/>
        </location>
        <ligand>
            <name>N(7)-methyl-GMP</name>
            <dbReference type="ChEBI" id="CHEBI:58285"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="156"/>
            <end position="157"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="205"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="230"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="10">
        <location>
            <position position="256"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046297" description="In isoform 2." evidence="7">
        <location>
            <begin position="1"/>
            <end position="8"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042582" description="In dbSNP:rs1046403." evidence="3 6">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042583" description="In dbSNP:rs1046404." evidence="3 6">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="7"/>
            <end position="9"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="18"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="33"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="36"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="42"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="49"/>
            <end position="51"/>
        </location>
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    <name>6PGL_HUMAN</name>
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            <fullName evidence="3">6-phosphogluconolactonase</fullName>
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        <name evidence="4" type="primary">PGLS</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eutheria</taxon>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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    <reference key="1">
        <citation type="journal article" date="1999" name="FEBS Lett." volume="459" first="223" last="226">
            <title>Identification of the cDNA encoding human 6-phosphogluconolactonase, the enzyme catalyzing the second step of the pentose phosphate pathway.</title>
            <authorList>
                <person name="Collard F."/>
                <person name="Collet J.-F."/>
                <person name="Gerin I."/>
                <person name="Veiga-da-Cunha M."/>
                <person name="van Schaftingen E."/>
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            <dbReference type="PubMed" id="10518023"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(99)01247-8"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
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    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Uterus</tissue>
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    <reference key="3">
        <citation type="submission" date="2008-12" db="UniProtKB">
            <authorList>
                <person name="Lubec G."/>
                <person name="Vishwanath V."/>
                <person name="Chen W.-Q."/>
                <person name="Sun Y."/>
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        <scope>PROTEIN SEQUENCE OF 41-72 AND 82-96</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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            <tissue>Brain</tissue>
            <tissue>Cajal-Retzius cell</tissue>
            <tissue>Fetal brain cortex</tissue>
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    <reference key="4">
        <citation type="submission" date="1998-08" db="EMBL/GenBank/DDBJ databases">
            <title>Full-insert sequence of mapped XREF EST.</title>
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                <person name="Barrow I.K.-P."/>
                <person name="Boguski M.S."/>
                <person name="Touchman J.W."/>
                <person name="Spencer F."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 97-242</scope>
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    <reference key="5">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
            <authorList>
                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
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            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
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            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-180</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-49</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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    <reference key="9">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12556"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57955"/>
            <dbReference type="ChEBI" id="CHEBI:58759"/>
            <dbReference type="EC" id="3.1.1.31"/>
        </reaction>
    </comment>
    <comment type="pathway">
        <text evidence="2">Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 2/3.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11307753">
            <id>O95336</id>
        </interactant>
        <interactant intactId="EBI-718504">
            <id>Q13867</id>
            <label>BLMH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11307753">
            <id>O95336</id>
        </interactant>
        <interactant intactId="EBI-750109">
            <id>Q9NYB0</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.</text>
    </comment>
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1360">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005900">
        <property type="entry name" value="6-phosphogluconolactonase_DevB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039104">
        <property type="entry name" value="6PGL"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006148">
        <property type="entry name" value="Glc/Gal-6P_isomerase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037171">
        <property type="entry name" value="NagB/RpiA_transferase-like"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01198">
        <property type="entry name" value="pgl"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11054">
        <property type="entry name" value="6-PHOSPHOGLUCONOLACTONASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11054:SF0">
        <property type="entry name" value="6-PHOSPHOGLUCONOLACTONASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01182">
        <property type="entry name" value="Glucosamine_iso"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF100950">
        <property type="entry name" value="NagB/RpiA/CoA transferase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="5 8">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000090078" description="6-phosphogluconolactonase">
        <location>
            <begin position="2"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="5 8">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="6">
        <location>
            <position position="180"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="10518023"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:8903"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="5">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <sequence length="258" mass="27547" checksum="A753FB7E662116DD" modified="2000-05-30" version="2">MAAPAPGLISVFSSSQELGAALAQLVAQRAACCLAGARARFALGLSGGSLVSMLARELPAAVAPAGPASLARWTLGFCDERLVPFDHAESTYGLYRTHLLSRLPIPESQVITINPELPVEEAAEDYAKKLRQAFQGDSIPVFDLLILGVGPDGHTCSLFPDHPLLQEREKIVAPISDSPKPPPQRVTLTLPVLNAARTVIFVATGEGKAAVLKRILEDQEENPLPAALVQPHTGKLCWFLDEAAARLLTVPFEKHSTL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="224" xmlns="https://uniprot.org/uniprot">
    <accession>P52209</accession>
    <accession>A8K2Y9</accession>
    <accession>B4DQJ8</accession>
    <accession>Q9BWD8</accession>
    <name>6PGD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>6-phosphogluconate dehydrogenase, decarboxylating</fullName>
            <ecNumber>1.1.1.44</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PGD</name>
        <name type="synonym">PGDH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
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                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="submission" date="2009-09" db="PDB data bank">
            <title>Structure of human phosphogluconate dehydrogenase in complex with NADPH at 2.53 A.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.53 ANGSTROMS) IN COMPLEX WITH NADP</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.</text>
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    <comment type="catalytic activity">
        <reaction>
            <text>6-phospho-D-gluconate + NADP(+) = D-ribulose 5-phosphate + CO2 + NADPH</text>
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        </reaction>
    </comment>
    <comment type="pathway">
        <text>Carbohydrate degradation; pentose phosphate pathway; D-ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step 3/3.</text>
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    <comment type="subunit">
        <text evidence="3">Homodimer.</text>
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        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
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    </comment>
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        <event type="alternative splicing"/>
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    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the 6-phosphogluconate dehydrogenase family.</text>
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    <sequence length="483" mass="53140" checksum="6CEFC0077D1283E3" modified="2007-01-23" version="3">MAQADIALIGLAVMGQNLILNMNDHGFVVCAFNRTVSKVDDFLANEAKGTKVVGAQSLKEMVSKLKKPRRIILLVKAGQAVDDFIEKLVPLLDTGDIIIDGGNSEYRDTTRRCRDLKAKGILFVGSGVSGGEEGARYGPSLMPGGNKEAWPHIKTIFQGIAAKVGTGEPCCDWVGDEGAGHFVKMVHNGIEYGDMQLICEAYHLMKDVLGMAQDEMAQAFEDWNKTELDSFLIEITANILKFQDTDGKHLLPKIRDSAGQKGTGKWTAISALEYGVPVTLIGEAVFARCLSSLKDERIQASKKLKGPQKFQFDGDKKSFLEDIRKALYASKIISYAQGFMLLRQAATEFGWTLNYGGIALMWRGGCIIRSVFLGKIKDAFDRNPELQNLLLDDFFKSAVENCQDSWRRAVSTGVQAGIPMPCFTTALSFYDGYRHEMLPASLIQAQRDYFGAHTYELLAKPGQFIHTNWTGHGGTVSSSSYNA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="213" xmlns="https://uniprot.org/uniprot">
    <accession>P49902</accession>
    <accession>B7Z382</accession>
    <accession>D3DR91</accession>
    <accession>Q5JUV5</accession>
    <name>5NTC_HUMAN</name>
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        <recommendedName>
            <fullName evidence="18">Cytosolic purine 5'-nucleotidase</fullName>
            <ecNumber evidence="4 5 6 11">3.1.3.5</ecNumber>
            <ecNumber evidence="4 5 6 11">3.1.3.99</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="14">Cytosolic 5'-nucleotidase II</fullName>
            <shortName evidence="14">cN-II</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="16">Cytosolic IMP/GMP-specific 5'-nucleotidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="18">Cytosolic nucleoside phosphotransferase 5'N</fullName>
            <ecNumber evidence="6 11">2.7.1.77</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="15">High Km 5'-nucleotidase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="20" type="primary">NT5C2</name>
        <name type="synonym">NT5B</name>
        <name type="synonym">NT5CP</name>
        <name type="synonym">PNT5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Biochem. Biophys. Res. Commun." volume="205" first="917" last="922">
            <title>Molecular cloning of human cytosolic purine 5'-nucleotidase.</title>
            <authorList>
                <person name="Oka J."/>
                <person name="Matsumoto A."/>
                <person name="Hosokawa Y."/>
                <person name="Inoue S."/>
            </authorList>
            <dbReference type="PubMed" id="7999131"/>
            <dbReference type="DOI" id="10.1006/bbrc.1994.2752"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
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                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="3">
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    <comment type="function">
        <text evidence="4 5 6 11">Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705). In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine (PubMed:1659319, PubMed:9371705). Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705). Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency (PubMed:1659319, PubMed:9371705). Through these activities regulates the purine nucleoside/nucleotide pools within the cell (PubMed:10092873, PubMed:12907246, PubMed:1659319, PubMed:9371705).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5 6 7 11">
            <text>a ribonucleoside 5'-phosphate + H2O = a ribonucleoside + phosphate</text>
            <dbReference type="Rhea" id="RHEA:12484"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="EC" id="3.1.3.5"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:12485"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>a 2'-deoxyribonucleoside + a ribonucleoside 5'-phosphate = a ribonucleoside + a 2'-deoxyribonucleoside 5'-phosphate</text>
            <dbReference type="Rhea" id="RHEA:19961"/>
            <dbReference type="ChEBI" id="CHEBI:18254"/>
            <dbReference type="ChEBI" id="CHEBI:18274"/>
            <dbReference type="ChEBI" id="CHEBI:58043"/>
            <dbReference type="ChEBI" id="CHEBI:65317"/>
            <dbReference type="EC" id="2.7.1.77"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5 6 11">
            <text>IMP + H2O = inosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:27718"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="EC" id="3.1.3.99"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:27719"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>GMP + H2O = guanosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:27714"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16750"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58115"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:27715"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>dIMP + H2O = 2'-deoxyinosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29383"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28997"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:61194"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:29384"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6">
            <text>dGMP + H2O = 2'-deoxyguanosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:29379"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17172"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57673"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:29380"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>XMP + H2O = xanthosine + phosphate</text>
            <dbReference type="Rhea" id="RHEA:28530"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18107"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57464"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:28531"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>inosine + GMP = guanosine + IMP</text>
            <dbReference type="Rhea" id="RHEA:69584"/>
            <dbReference type="ChEBI" id="CHEBI:16750"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:58115"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>dGMP + inosine = 2'-deoxyguanosine + IMP</text>
            <dbReference type="Rhea" id="RHEA:69580"/>
            <dbReference type="ChEBI" id="CHEBI:17172"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:57673"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>dIMP + inosine = 2'-deoxyinosine + IMP</text>
            <dbReference type="Rhea" id="RHEA:69572"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:28997"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:61194"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>inosine + UMP = uridine + IMP</text>
            <dbReference type="Rhea" id="RHEA:69588"/>
            <dbReference type="ChEBI" id="CHEBI:16704"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:57865"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>inosine + CMP = cytidine + IMP</text>
            <dbReference type="Rhea" id="RHEA:69592"/>
            <dbReference type="ChEBI" id="CHEBI:17562"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>inosine + AMP = IMP + adenosine</text>
            <dbReference type="Rhea" id="RHEA:69596"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="7 8 21 22 23 24 25 27 28 29 30">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="7 8 21 22 23 24 25 27 28 29 30">Binds 1 Mg(2+) ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="4 6 8">Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate (PubMed:10092873, PubMed:1659319, PubMed:21396942). Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding (PubMed:21396942). Inhibited by inorganic phosphate (PubMed:10092873).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">20 uM for IMP (in presence of the allosteric activator ATP)</KM>
            <KM evidence="6">83 uM for IMP (in absence of allosteric activator)</KM>
            <Vmax evidence="6">36.7 nmol/min/mg enzyme for the hydrolysis of IMP</Vmax>
            <Vmax evidence="4">0.54 umol/min/mg enzyme for the hydrolysis of IMP (in absence of allosteric activator)</Vmax>
            <Vmax evidence="4">16.5 umol/min/mg enzyme for the hydrolysis of IMP (in the presence of 3 mM ATP)</Vmax>
            <Vmax evidence="6">25.0 nmol/min/mg enzyme for the hydrolysis dGMP (in presence of the allosteric activator ATP)</Vmax>
            <Vmax evidence="6">18.6 nmol/min/mg enzyme for the transfer of phosphate from dIMP to inosine (in presence of the allosteric activator ATP)</Vmax>
            <Vmax evidence="6">15.2 nmol/min/mg enzyme for the transfer of phosphate from GMP to inosine (in presence of the allosteric activator ATP)</Vmax>
            <Vmax evidence="6">14.6 nmol/min/mg enzyme for the transfer of phosphate from IMP to inosine (in presence of the allosteric activator ATP)</Vmax>
            <Vmax evidence="6">14.1 nmol/min/mg enzyme for the transfer of phosphate from dGMP to inosine (in presence of the allosteric activator ATP)</Vmax>
            <Vmax evidence="6">4.9 nmol/min/mg enzyme for the transfer of phosphate from UMP to inosine (in presence of the allosteric activator ATP)</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 8">Homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-355815">
            <id>P48047</id>
            <label>ATP5PO</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-740459">
            <id>P51116</id>
            <label>FXR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-748515">
            <id>Q8IVS8</id>
            <label>GLYCTK</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-2558745">
            <id>Q7L9L4</id>
            <label>MOB1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-751703">
            <id>Q86TA1</id>
            <label>MOB3B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-9679267">
            <id>Q70IA8</id>
            <label>MOB3C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-744782">
            <id>Q9Y5B8</id>
            <label>NME7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-740486">
            <id>Q6ZVK8</id>
            <label>NUDT18</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-727004">
            <id>O00560</id>
            <label>SDCBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742084">
            <id>P49902</id>
        </interactant>
        <interactant intactId="EBI-725924">
            <id>Q9NRS6</id>
            <label>SNX15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>P49902</id>
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        <interactant intactId="EBI-10082">
            <id>P39518</id>
            <label>FAA2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Cytoplasm</location>
            <location evidence="11">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P49902-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P49902-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054235"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="11">Widely expressed.</text>
    </comment>
    <comment type="disease" evidence="9 10">
        <disease id="DI-04024">
            <name>Spastic paraplegia 45, autosomal recessive</name>
            <acronym>SPG45</acronym>
            <description>A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest intellectual disability, contractures and learning disability.</description>
            <dbReference type="MIM" id="613162"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the 5'(3')-deoxyribonucleotidase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.3.5" evidence="4 5 6 11"/>
    <dbReference type="EC" id="3.1.3.99" evidence="4 5 6 11"/>
    <dbReference type="EC" id="2.7.1.77" evidence="6 11"/>
    <dbReference type="EMBL" id="D38524">
        <property type="protein sequence ID" value="BAA07529.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK295593">
        <property type="protein sequence ID" value="BAH12118.1"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>P05408</accession>
    <accession>P01164</accession>
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        <citation type="journal article" date="1988" name="FEBS Lett." volume="234" first="160" last="164">
            <title>Cloning and sequence analysis of human pituitary cDNA encoding the novel polypeptide 7B2.</title>
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            <dbReference type="DOI" id="10.1016/0014-5793(88)81324-3"/>
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    <reference key="2">
        <citation type="journal article" date="1991" name="Biochem. Biophys. Res. Commun." volume="174" first="156" last="162">
            <title>The production by alternate splicing of two mRNAs differing by one codon could be an intrinsic property of neuroendocrine protein 7B2 gene expression in man.</title>
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                <person name="Paquet L."/>
                <person name="Lazure C."/>
                <person name="Seidah N.G."/>
                <person name="Chretien M."/>
                <person name="Mbikay M."/>
            </authorList>
            <dbReference type="PubMed" id="1989596"/>
            <dbReference type="DOI" id="10.1016/0006-291x(91)90499-w"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>PROTEIN SEQUENCE OF 125-140 (ISOFORM 1)</scope>
        <scope>PROTEIN SEQUENCE OF 126-132 (ISOFORM 2)</scope>
        <source>
            <tissue>Pituitary</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2000-05" db="EMBL/GenBank/DDBJ databases">
            <title>Human neuroendocrine protein 7B2 genomic organization.</title>
            <authorList>
                <person name="Jackson R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
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                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G."/>
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                <person name="Halpern A.L."/>
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                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1996" name="Eur. J. Biochem." volume="236" first="60" last="67">
            <title>Structural organization of the gene encoding the neuroendocrine chaperone 7B2.</title>
            <authorList>
                <person name="Braks J.A."/>
                <person name="Broers C.A."/>
                <person name="Danger J.M."/>
                <person name="Martens G.J.M."/>
            </authorList>
            <dbReference type="PubMed" id="8617287"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1996.00060.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 61-92</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1983" name="Arch. Biochem. Biophys." volume="225" first="525" last="534">
            <title>Isolation and NH2-terminal sequence of a highly conserved human and porcine pituitary protein belonging to a new superfamily. Immunocytochemical localization in pars distalis and pars nervosa of the pituitary and in the supraoptic nucleus of the hypothalamus.</title>
            <authorList>
                <person name="Seidah N.G."/>
                <person name="Hsi K.L."/>
                <person name="de Serres G."/>
                <person name="Rochemont J."/>
                <person name="Hamelin J."/>
                <person name="Antakly T."/>
                <person name="Cantin M."/>
                <person name="Chretien M."/>
            </authorList>
            <dbReference type="PubMed" id="6625600"/>
            <dbReference type="DOI" id="10.1016/0003-9861(83)90063-2"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 27-103</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1994" name="Cell" volume="78" first="263" last="273">
            <title>7B2 is a neuroendocrine chaperone that transiently interacts with prohormone convertase PC2 in the secretory pathway.</title>
            <authorList>
                <person name="Braks J.A."/>
                <person name="Martens G.J.M."/>
            </authorList>
            <dbReference type="PubMed" id="7913882"/>
            <dbReference type="DOI" id="10.1016/0092-8674(94)90296-8"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PCSK2</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2001" name="Biochem. J." volume="357" first="329" last="342">
            <title>Neuroendocrine secretory protein 7B2: structure, expression and functions.</title>
            <authorList>
                <person name="Mbikay M."/>
                <person name="Seidah N.G."/>
                <person name="Chretien M."/>
            </authorList>
            <dbReference type="PubMed" id="11439082"/>
            <dbReference type="DOI" id="10.1042/0264-6021:3570329"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Interacts with PCSK2/PC2 early in the secretory pathway. Dissociation occurs at later stages.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-722635">
            <id>P05408</id>
        </interactant>
        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-722635">
            <id>P05408</id>
        </interactant>
        <interactant intactId="EBI-741480">
            <id>Q9UMX0</id>
            <label>UBQLN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-722635">
            <id>P05408</id>
        </interactant>
        <interactant intactId="EBI-10173939">
            <id>Q9UMX0-2</id>
            <label>UBQLN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-722635">
            <id>P05408</id>
        </interactant>
        <interactant intactId="EBI-947187">
            <id>Q9UHD9</id>
            <label>UBQLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Secreted</location>
        </subcellularLocation>
        <text evidence="1">Neuroendocrine and endocrine secretory granules.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P05408-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P05408-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011754"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="2">Proteolytically cleaved in the Golgi by a furin-like convertase to generate bioactive peptides.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Sulfated on tyrosine residues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the 7B2 family.</text>
    </comment>
    <dbReference type="EMBL" id="Y00757">
        <property type="protein sequence ID" value="CAA68726.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ290438">
        <property type="protein sequence ID" value="CAB90397.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ290439">
        <property type="protein sequence ID" value="CAB90397.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ290440">
        <property type="protein sequence ID" value="CAB90397.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ290441">
        <property type="protein sequence ID" value="CAB90397.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ290442">
        <property type="protein sequence ID" value="CAB90397.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR541824">
        <property type="protein sequence ID" value="CAG46623.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471125">
        <property type="protein sequence ID" value="EAW92262.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC005349">
        <property type="protein sequence ID" value="AAH05349.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093053">
        <property type="protein sequence ID" value="AAH93053.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45207.1">
        <molecule id="P05408-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45208.1">
        <molecule id="P05408-2"/>
    </dbReference>
    <dbReference type="PIR" id="S01008">
        <property type="entry name" value="PUHU"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138229.1">
        <molecule id="P05408-1"/>
        <property type="nucleotide sequence ID" value="NM_001144757.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003011.1">
        <molecule id="P05408-2"/>
        <property type="nucleotide sequence ID" value="NM_003020.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P05408"/>
    <dbReference type="SMR" id="P05408"/>
    <dbReference type="BioGRID" id="112345">
        <property type="interactions" value="27"/>
    </dbReference>
    <dbReference type="FunCoup" id="P05408">
        <property type="interactions" value="284"/>
    </dbReference>
    <dbReference type="IntAct" id="P05408">
        <property type="interactions" value="23"/>
    </dbReference>
    <dbReference type="MINT" id="P05408"/>
    <dbReference type="STRING" id="9606.ENSP00000300175"/>
    <dbReference type="MEROPS" id="I21.001"/>
    <dbReference type="iPTMnet" id="P05408"/>
    <dbReference type="PhosphoSitePlus" id="P05408"/>
    <dbReference type="BioMuta" id="SCG5"/>
    <dbReference type="DMDM" id="23830842"/>
    <dbReference type="jPOST" id="P05408"/>
    <dbReference type="MassIVE" id="P05408"/>
    <dbReference type="PaxDb" id="9606-ENSP00000300175"/>
    <dbReference type="PeptideAtlas" id="P05408"/>
    <dbReference type="ProteomicsDB" id="51834">
        <molecule id="P05408-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="51835">
        <molecule id="P05408-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2202">
        <property type="antibodies" value="150 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="6447"/>
    <dbReference type="Ensembl" id="ENST00000300175.9">
        <molecule id="P05408-1"/>
        <property type="protein sequence ID" value="ENSP00000300175.4"/>
        <property type="gene ID" value="ENSG00000166922.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000413748.6">
        <molecule id="P05408-2"/>
        <property type="protein sequence ID" value="ENSP00000388560.2"/>
        <property type="gene ID" value="ENSG00000166922.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000614359.1">
        <molecule id="P05408-1"/>
        <property type="protein sequence ID" value="ENSP00000482615.1"/>
        <property type="gene ID" value="ENSG00000277614.1"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000632219.1">
        <molecule id="P05408-1"/>
        <property type="protein sequence ID" value="ENSP00000488109.1"/>
        <property type="gene ID" value="ENSG00000281931.1"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000632674.1">
        <molecule id="P05408-2"/>
        <property type="protein sequence ID" value="ENSP00000488509.1"/>
        <property type="gene ID" value="ENSG00000281931.1"/>
    </dbReference>
    <dbReference type="GeneID" id="6447"/>
    <dbReference type="KEGG" id="hsa:6447"/>
    <dbReference type="MANE-Select" id="ENST00000300175.9">
        <property type="protein sequence ID" value="ENSP00000300175.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001144757.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001138229.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001zgz.3">
        <molecule id="P05408-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:10816"/>
    <dbReference type="ClinPGx" id="PA35724"/>
    <dbReference type="CTD" id="6447"/>
    <dbReference type="DisGeNET" id="6447"/>
    <dbReference type="GeneCards" id="SCG5"/>
    <dbReference type="HGNC" id="HGNC:10816">
        <property type="gene designation" value="SCG5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000166922">
        <property type="expression patterns" value="Tissue enhanced (brain, choroid plexus, pituitary gland)"/>
    </dbReference>
    <dbReference type="MalaCards" id="SCG5"/>
    <dbReference type="MIM" id="173120">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166922"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000166922"/>
    <dbReference type="eggNOG" id="KOG4187">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000009816"/>
    <dbReference type="InParanoid" id="P05408"/>
    <dbReference type="OMA" id="LGKWNKN"/>
    <dbReference type="OrthoDB" id="9922675at2759"/>
    <dbReference type="PAN-GO" id="P05408">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P05408"/>
    <dbReference type="PathwayCommons" id="P05408"/>
    <dbReference type="SignaLink" id="P05408"/>
    <dbReference type="Agora" id="ENSG00000166922"/>
    <dbReference type="BioGRID-ORCS" id="6447">
        <property type="hits" value="67 hits in 1149 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SCG5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="SCG5"/>
    <dbReference type="GenomeRNAi" id="6447"/>
    <dbReference type="Pharos" id="P05408">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P05408"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="P05408">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000166922">
        <property type="expression patterns" value="Expressed in islet of Langerhans and 100 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P05408">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030141">
        <property type="term" value="C:secretory granule"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004857">
        <property type="term" value="F:enzyme inhibitor activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030234">
        <property type="term" value="F:enzyme regulator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005525">
        <property type="term" value="F:GTP binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051082">
        <property type="term" value="F:unfolded protein binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006886">
        <property type="term" value="P:intracellular protein transport"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007218">
        <property type="term" value="P:neuropeptide signaling pathway"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016486">
        <property type="term" value="P:peptide hormone processing"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046883">
        <property type="term" value="P:regulation of hormone secretion"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007945">
        <property type="entry name" value="Secretogranin_V"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12738">
        <property type="entry name" value="NEUROENDOCRINE PROTEIN 7B2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12738:SF0">
        <property type="entry name" value="NEUROENDOCRINE PROTEIN 7B2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05281">
        <property type="entry name" value="Secretogranin_V"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0143">Chaperone</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0527">Neuropeptide</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0765">Sulfation</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="5">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000041" description="Neuroendocrine protein 7B2">
        <location>
            <begin position="27"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000042" description="N-terminal peptide" evidence="1">
        <location>
            <begin position="27"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000000043" description="C-terminal peptide" evidence="3">
        <location>
            <begin position="200"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="174"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="205"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="3">
        <location>
            <begin position="120"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011754" description="In isoform 2." evidence="7 8 9 10">
        <location>
            <position position="126"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH05349." evidence="11" ref="6">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P01165"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P12961"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P18844"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="6625600"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="7913882"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="1989596"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="3134253"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <sequence length="212" mass="23730" checksum="A459702055C0FE84" modified="2002-10-10" version="2" precursor="true">MVSRMVSTMLSGLLFWLASGWTPAFAYSPRTPDRVSEADIQRLLHGVMEQLGIARPRVEYPAHQAMNLVGPQSIEGGAHEGLQHLGPFGNIPNIVAELTGDNIPKDFSEDQGYPDPPNPCPVGKTADDGCLENTPDTAEFSREFQLHQHLFDPEHDYPGLGKWNKKLLYEKMKGGERRKRRSVNPYLQGQRLDNVVAKKSVPHFSDEDKDPE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2012-10-03" modified="2026-01-28" version="67" xmlns="https://uniprot.org/uniprot">
    <accession>P0DKL9</accession>
    <name>A14EL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ARL14 effector protein-like</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ARL14EPL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="431" first="268" last="274">
            <title>The DNA sequence and comparative analysis of human chromosome 5.</title>
            <authorList>
                <person name="Schmutz J."/>
                <person name="Martin J."/>
                <person name="Terry A."/>
                <person name="Couronne O."/>
                <person name="Grimwood J."/>
                <person name="Lowry S."/>
                <person name="Gordon L.A."/>
                <person name="Scott D."/>
                <person name="Xie G."/>
                <person name="Huang W."/>
                <person name="Hellsten U."/>
                <person name="Tran-Gyamfi M."/>
                <person name="She X."/>
                <person name="Prabhakar S."/>
                <person name="Aerts A."/>
                <person name="Altherr M."/>
                <person name="Bajorek E."/>
                <person name="Black S."/>
                <person name="Branscomb E."/>
                <person name="Caoile C."/>
                <person name="Challacombe J.F."/>
                <person name="Chan Y.M."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Goodstein D."/>
                <person name="Grigoriev I."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Martinez D."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nandkeshwar R."/>
                <person name="Noonan J.P."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Priest J."/>
                <person name="Ramirez L."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="Wheeler J."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="Dickson M."/>
                <person name="Cheng J.-F."/>
                <person name="Eichler E.E."/>
                <person name="Olsen A."/>
                <person name="Pennacchio L.A."/>
                <person name="Rokhsar D.S."/>
                <person name="Richardson P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <dbReference type="EMBL" id="AC034236">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS59490.1"/>
    <dbReference type="RefSeq" id="NP_001182510.1">
        <property type="nucleotide sequence ID" value="NM_001195581.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001380903.1">
        <property type="nucleotide sequence ID" value="NM_001393974.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P0DKL9"/>
    <dbReference type="SMR" id="P0DKL9"/>
    <dbReference type="BioGRID" id="569315">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="FunCoup" id="P0DKL9">
        <property type="interactions" value="30"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000472409"/>
    <dbReference type="iPTMnet" id="P0DKL9"/>
    <dbReference type="PhosphoSitePlus" id="P0DKL9"/>
    <dbReference type="BioMuta" id="ARL14EPL"/>
    <dbReference type="DMDM" id="408387568"/>
    <dbReference type="MassIVE" id="P0DKL9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000472409"/>
    <dbReference type="PeptideAtlas" id="P0DKL9"/>
    <dbReference type="DNASU" id="644100"/>
    <dbReference type="Ensembl" id="ENST00000601302.3">
        <property type="protein sequence ID" value="ENSP00000472409.1"/>
        <property type="gene ID" value="ENSG00000268223.7"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000686077.1">
        <property type="protein sequence ID" value="ENSP00000510304.1"/>
        <property type="gene ID" value="ENSG00000268223.7"/>
    </dbReference>
    <dbReference type="GeneID" id="644100"/>
    <dbReference type="KEGG" id="hsa:644100"/>
    <dbReference type="MANE-Select" id="ENST00000686077.1">
        <property type="protein sequence ID" value="ENSP00000510304.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001195581.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001182510.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc021yct.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:44201"/>
    <dbReference type="CTD" id="644100"/>
    <dbReference type="GeneCards" id="ARL14EPL"/>
    <dbReference type="HGNC" id="HGNC:44201">
        <property type="gene designation" value="ARL14EPL"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000268223">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000268223"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000268223"/>
    <dbReference type="eggNOG" id="KOG4850">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160347"/>
    <dbReference type="HOGENOM" id="CLU_105549_2_0_1"/>
    <dbReference type="InParanoid" id="P0DKL9"/>
    <dbReference type="OMA" id="WVYDDIV"/>
    <dbReference type="OrthoDB" id="5984406at2759"/>
    <dbReference type="PAN-GO" id="P0DKL9">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P0DKL9"/>
    <dbReference type="PathwayCommons" id="P0DKL9"/>
    <dbReference type="SignaLink" id="P0DKL9"/>
    <dbReference type="Agora" id="ENSG00000268223"/>
    <dbReference type="BioGRID-ORCS" id="644100">
        <property type="hits" value="12 hits in 1052 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ARL14EPL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="644100"/>
    <dbReference type="Pharos" id="P0DKL9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P0DKL9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="P0DKL9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000268223">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 12 other cell types or tissues"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029264">
        <property type="entry name" value="ARF7EP_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR053130">
        <property type="entry name" value="ARL14_effector"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46804">
        <property type="entry name" value="ADP RIBOSYLATION FACTOR LIKE GTPASE 14 EFFECTOR PROTEIN LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46804:SF4">
        <property type="entry name" value="ARL14 EFFECTOR PROTEIN-LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14949">
        <property type="entry name" value="ARF7EP_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000419646" description="ARL14 effector protein-like">
        <location>
            <begin position="1"/>
            <end position="152"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <sequence length="152" mass="17712" checksum="3B63487B4316267E" modified="2012-10-03" version="1">MNEQSEKNNSIQERHTDHSFPEKNCQIGQKQLQQIERQLKCLAFRNPGPQVADFNPETRQQKKKARMSKMNEYFSTKYKIMRKYDKSGRLICNDADLCDCLEKNCLGCFYPCPKCNSNKCGPECRCNRRWVYDAIVTESGEVISTLPFNVPD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="174" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IZ83</accession>
    <accession>B4DLQ1</accession>
    <accession>C9JBH6</accession>
    <accession>Q86YF0</accession>
    <accession>Q8IYL4</accession>
    <accession>Q8TEI8</accession>
    <name>A16A1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aldehyde dehydrogenase family 16 member A1</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ALDH16A1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2002-01" db="EMBL/GenBank/DDBJ databases">
            <title>The nucleotide sequence of a long cDNA clone isolated from human spleen.</title>
            <authorList>
                <person name="Jikuya H."/>
                <person name="Takano J."/>
                <person name="Nomura N."/>
                <person name="Kikuno R."/>
                <person name="Nagase T."/>
                <person name="Ohara O."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT VAL-227</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="428" first="529" last="535">
            <title>The DNA sequence and biology of human chromosome 19.</title>
            <authorList>
                <person name="Grimwood J."/>
                <person name="Gordon L.A."/>
                <person name="Olsen A.S."/>
                <person name="Terry A."/>
                <person name="Schmutz J."/>
                <person name="Lamerdin J.E."/>
                <person name="Hellsten U."/>
                <person name="Goodstein D."/>
                <person name="Couronne O."/>
                <person name="Tran-Gyamfi M."/>
                <person name="Aerts A."/>
                <person name="Altherr M."/>
                <person name="Ashworth L."/>
                <person name="Bajorek E."/>
                <person name="Black S."/>
                <person name="Branscomb E."/>
                <person name="Caenepeel S."/>
                <person name="Carrano A.V."/>
                <person name="Caoile C."/>
                <person name="Chan Y.M."/>
                <person name="Christensen M."/>
                <person name="Cleland C.A."/>
                <person name="Copeland A."/>
                <person name="Dalin E."/>
                <person name="Dehal P."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Garcia C."/>
                <person name="Georgescu A.M."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Ho I."/>
                <person name="Huang W."/>
                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Larionov V."/>
                <person name="Leem S.-H."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Lowry S."/>
                <person name="Malfatti S."/>
                <person name="Martinez D."/>
                <person name="McCready P.M."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nelson K."/>
                <person name="Nolan M."/>
                <person name="Ovcharenko I."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Popkie A.P."/>
                <person name="Predki P."/>
                <person name="Quan G."/>
                <person name="Ramirez L."/>
                <person name="Rash S."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="She X."/>
                <person name="Smith D."/>
                <person name="Slezak T."/>
                <person name="Solovyev V."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="Wagner M."/>
                <person name="Wheeler J."/>
                <person name="Wu K."/>
                <person name="Xie G."/>
                <person name="Yang J."/>
                <person name="Dubchak I."/>
                <person name="Furey T.S."/>
                <person name="DeJong P."/>
                <person name="Dickson M."/>
                <person name="Gordon D."/>
                <person name="Eichler E.E."/>
                <person name="Pennacchio L.A."/>
                <person name="Richardson P."/>
                <person name="Stubbs L."/>
                <person name="Rokhsar D.S."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
                <person name="Lucas S.M."/>
            </authorList>
            <dbReference type="PubMed" id="15057824"/>
            <dbReference type="DOI" id="10.1038/nature02399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT VAL-227</scope>
        <source>
            <tissue>Lymph</tissue>
            <tissue>Skin</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="Neurogenetics" volume="10" first="217" last="228">
            <title>Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1.</title>
            <authorList>
                <person name="Hanna M.C."/>
                <person name="Blackstone C."/>
            </authorList>
            <dbReference type="PubMed" id="19184135"/>
            <dbReference type="DOI" id="10.1007/s10048-009-0172-6"/>
        </citation>
        <scope>INTERACTION WITH SPG21</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="subunit">
        <text evidence="2">Interacts with SPG21.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044483">
            <id>Q8IZ83</id>
        </interactant>
        <interactant intactId="EBI-1048152">
            <id>Q9Y315</id>
            <label>DERA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044483">
            <id>Q8IZ83</id>
        </interactant>
        <interactant intactId="EBI-12000556">
            <id>Q9Y2H0-1</id>
            <label>DLGAP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044483">
            <id>Q8IZ83</id>
        </interactant>
        <interactant intactId="EBI-22310682">
            <id>P0DPK4</id>
            <label>NOTCH2NLC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IZ83-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IZ83-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_029982 VSP_029983"/>
        </isoform>
        <isoform>
            <id>Q8IZ83-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043280"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the aldehyde dehydrogenase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="6">The active site cysteine and glutamate residues are not conserved in this protein. Its activity is therefore unsure.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH35641" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="BAB84962" version="1"/>
        </conflict>
        <text>Wrong choice of frame.</text>
    </comment>
    <dbReference type="EMBL" id="AK074136">
        <property type="protein sequence ID" value="BAB84962.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK297101">
        <property type="protein sequence ID" value="BAG59613.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010619">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014895">
        <property type="protein sequence ID" value="AAH14895.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035641">
        <property type="protein sequence ID" value="AAH35641.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC042142">
        <property type="protein sequence ID" value="AAH42142.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12766.1">
        <molecule id="Q8IZ83-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46141.1">
        <molecule id="Q8IZ83-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138868.1">
        <molecule id="Q8IZ83-3"/>
        <property type="nucleotide sequence ID" value="NM_001145396.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_699160.2">
        <molecule id="Q8IZ83-1"/>
        <property type="nucleotide sequence ID" value="NM_153329.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8IZ83"/>
    <dbReference type="SASBDB" id="Q8IZ83"/>
    <dbReference type="SMR" id="Q8IZ83"/>
    <dbReference type="BioGRID" id="125959">
        <property type="interactions" value="76"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8IZ83">
        <property type="interactions" value="295"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8IZ83">
        <property type="interactions" value="30"/>
    </dbReference>
    <dbReference type="MINT" id="Q8IZ83"/>
    <dbReference type="STRING" id="9606.ENSP00000293350"/>
    <dbReference type="ChEMBL" id="CHEMBL4295896"/>
    <dbReference type="GlyCosmos" id="Q8IZ83">
        <property type="glycosylation" value="2 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8IZ83">
        <property type="glycosylation" value="3 sites, 2 O-linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8IZ83"/>
    <dbReference type="MetOSite" id="Q8IZ83"/>
    <dbReference type="PhosphoSitePlus" id="Q8IZ83"/>
    <dbReference type="BioMuta" id="ALDH16A1"/>
    <dbReference type="DMDM" id="269849532"/>
    <dbReference type="jPOST" id="Q8IZ83"/>
    <dbReference type="MassIVE" id="Q8IZ83"/>
    <dbReference type="PaxDb" id="9606-ENSP00000293350"/>
    <dbReference type="PeptideAtlas" id="Q8IZ83"/>
    <dbReference type="ProteomicsDB" id="71287">
        <molecule id="Q8IZ83-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71288">
        <molecule id="Q8IZ83-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71289">
        <molecule id="Q8IZ83-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8IZ83"/>
    <dbReference type="Antibodypedia" id="32011">
        <property type="antibodies" value="105 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="126133"/>
    <dbReference type="Ensembl" id="ENST00000293350.9">
        <molecule id="Q8IZ83-1"/>
        <property type="protein sequence ID" value="ENSP00000293350.3"/>
        <property type="gene ID" value="ENSG00000161618.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000455361.6">
        <molecule id="Q8IZ83-3"/>
        <property type="protein sequence ID" value="ENSP00000410142.1"/>
        <property type="gene ID" value="ENSG00000161618.11"/>
    </dbReference>
    <dbReference type="GeneID" id="126133"/>
    <dbReference type="KEGG" id="hsa:126133"/>
    <dbReference type="MANE-Select" id="ENST00000293350.9">
        <property type="protein sequence ID" value="ENSP00000293350.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_153329.4"/>
        <property type="RefSeq protein sequence ID" value="NP_699160.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002pnt.4">
        <molecule id="Q8IZ83-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28114"/>
    <dbReference type="ClinPGx" id="PA134903503"/>
    <dbReference type="CTD" id="126133"/>
    <dbReference type="DisGeNET" id="126133"/>
    <dbReference type="GeneCards" id="ALDH16A1"/>
    <dbReference type="HGNC" id="HGNC:28114">
        <property type="gene designation" value="ALDH16A1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000161618">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="613358">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000161618"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000161618"/>
    <dbReference type="eggNOG" id="KOG2450">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161135"/>
    <dbReference type="HOGENOM" id="CLU_018339_0_0_1"/>
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    <dbReference type="OMA" id="MDYGPAP"/>
    <dbReference type="OrthoDB" id="310895at2759"/>
    <dbReference type="PAN-GO" id="Q8IZ83">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8IZ83"/>
    <dbReference type="PathwayCommons" id="Q8IZ83"/>
    <dbReference type="SignaLink" id="Q8IZ83"/>
    <dbReference type="Agora" id="ENSG00000161618"/>
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        <property type="hits" value="16 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="B5B9A610">
        <property type="entry name" value="PML body"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ALDH16A1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ALDH16A1"/>
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    <dbReference type="Pharos" id="Q8IZ83">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8IZ83"/>
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        <property type="component" value="Chromosome 19"/>
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    <dbReference type="RNAct" id="Q8IZ83">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000161618">
        <property type="expression patterns" value="Expressed in granulocyte and 143 other cell types or tissues"/>
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    <dbReference type="ExpressionAtlas" id="Q8IZ83">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004029">
        <property type="term" value="F:aldehyde dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.605.10:FF:000044">
        <property type="entry name" value="Aldehyde dehydrogenase 16 family member A1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.40.309.10:FF:000029">
        <property type="entry name" value="Aldehyde dehydrogenase family 16 member A1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.40.605.10">
        <property type="entry name" value="Aldehyde Dehydrogenase, Chain A, domain 1"/>
        <property type="match status" value="2"/>
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    <dbReference type="Gene3D" id="3.40.309.10">
        <property type="entry name" value="Aldehyde Dehydrogenase, Chain A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016161">
        <property type="entry name" value="Ald_DH/histidinol_DH"/>
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    <dbReference type="InterPro" id="IPR016163">
        <property type="entry name" value="Ald_DH_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016162">
        <property type="entry name" value="Ald_DH_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011408">
        <property type="entry name" value="Aldehyde_DH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015590">
        <property type="entry name" value="Aldehyde_DH_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11699">
        <property type="entry name" value="ALDEHYDE DEHYDROGENASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00171">
        <property type="entry name" value="Aldedh"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF036490">
        <property type="entry name" value="Aldedh_dupl"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53720">
        <property type="entry name" value="ALDH-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000312986" description="Aldehyde dehydrogenase family 16 member A1">
        <location>
            <begin position="1"/>
            <end position="802"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029982" description="In isoform 2." evidence="5">
        <original>EGRALRRSLAGECAELGLALGTESLLLLTDTADVDSAVEGVVDAAWSDRGPGGLR</original>
        <variation>VPSGQGSWRNAAGGRKAPPAAELGGVPRKGVPFDGAWRESVRSWAWRWGRSRCCC</variation>
        <location>
            <begin position="254"/>
            <end position="308"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043280" description="In isoform 3." evidence="4">
        <location>
            <begin position="254"/>
            <end position="304"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029983" description="In isoform 2." evidence="5">
        <location>
            <begin position="309"/>
            <end position="802"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037638" description="In dbSNP:rs3745312.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037639" description="In dbSNP:rs1320303." evidence="1 3">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="19184135"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="802" mass="85127" checksum="2820628CD0EF5823" modified="2009-11-24" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="235" xmlns="https://uniprot.org/uniprot">
    <accession>P02763</accession>
    <accession>B7ZKQ5</accession>
    <accession>Q5T539</accession>
    <accession>Q5U067</accession>
    <accession>Q8TC16</accession>
    <name>A1AG1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-1-acid glycoprotein 1</fullName>
            <shortName>AGP 1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Orosomucoid-1</fullName>
            <shortName>OMD 1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ORM1</name>
        <name type="synonym">AGP1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1985" name="Nucleic Acids Res." volume="13" first="3941" last="3952">
            <title>Structure of the human alpha 1-acid glycoprotein gene: sequence homology with other human acute phase protein genes.</title>
            <authorList>
                <person name="Dente L."/>
                <person name="Ciliberto G."/>
                <person name="Cortese R."/>
            </authorList>
            <dbReference type="PubMed" id="2409529"/>
            <dbReference type="DOI" id="10.1093/nar/13.11.3941"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT GLN-38</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1986" name="Gene" volume="44" first="127" last="131">
            <title>Molecular cloning and nucleotide sequence of human alpha 1 acid glycoprotein cDNA.</title>
            <authorList>
                <person name="Board P.G."/>
                <person name="Jones I.M."/>
                <person name="Bentley A.K."/>
            </authorList>
            <dbReference type="PubMed" id="3770479"/>
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            <title>Selective binding of imatinib to the genetic variants of human alpha1-acid glycoprotein.</title>
            <authorList>
                <person name="Fitos I."/>
                <person name="Visy J."/>
                <person name="Zsila F."/>
                <person name="Mady G."/>
                <person name="Simonyi M."/>
            </authorList>
            <dbReference type="PubMed" id="17008009"/>
            <dbReference type="DOI" id="10.1016/j.bbagen.2006.08.015"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2006" name="J. Proteome Res." volume="5" first="1493" last="1503">
            <title>Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.</title>
            <authorList>
                <person name="Ramachandran P."/>
                <person name="Boontheung P."/>
                <person name="Xie Y."/>
                <person name="Sondej M."/>
                <person name="Wong D.T."/>
                <person name="Loo J.A."/>
            </authorList>
            <dbReference type="PubMed" id="16740002"/>
            <dbReference type="DOI" id="10.1021/pr050492k"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93</scope>
        <source>
            <tissue>Saliva</tissue>
        </source>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2007" name="Biochim. Biophys. Acta" volume="1770" first="797" last="809">
            <title>The drug binding site of human alpha1-acid glycoprotein: insight from induced circular dichroism and electronic absorption spectra.</title>
            <authorList>
                <person name="Zsila F."/>
                <person name="Iwao Y."/>
            </authorList>
            <dbReference type="PubMed" id="17321687"/>
            <dbReference type="DOI" id="10.1016/j.bbagen.2007.01.009"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2009" name="J. Proteome Res." volume="8" first="651" last="661">
            <title>Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.</title>
            <authorList>
                <person name="Chen R."/>
                <person name="Jiang X."/>
                <person name="Sun D."/>
                <person name="Han G."/>
                <person name="Wang F."/>
                <person name="Ye M."/>
                <person name="Wang L."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="19159218"/>
            <dbReference type="DOI" id="10.1021/pr8008012"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93 AND ASN-103</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2009" name="Nat. Methods" volume="6" first="809" last="811">
            <title>Enrichment of glycopeptides for glycan structure and attachment site identification.</title>
            <authorList>
                <person name="Nilsson J."/>
                <person name="Rueetschi U."/>
                <person name="Halim A."/>
                <person name="Hesse C."/>
                <person name="Carlsohn E."/>
                <person name="Brinkmalm G."/>
                <person name="Larson G."/>
            </authorList>
            <dbReference type="PubMed" id="19838169"/>
            <dbReference type="DOI" id="10.1038/nmeth.1392"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33 AND ASN-72</scope>
        <scope>STRUCTURE OF CARBOHYDRATES</scope>
        <source>
            <tissue>Cerebrospinal fluid</tissue>
        </source>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="1" last="17">
            <title>Human urinary glycoproteomics; attachment site specific analysis of N- and O-linked glycosylations by CID and ECD.</title>
            <authorList>
                <person name="Halim A."/>
                <person name="Nilsson J."/>
                <person name="Ruetschi U."/>
                <person name="Hesse C."/>
                <person name="Larson G."/>
            </authorList>
            <dbReference type="PubMed" id="22171320"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.013649"/>
        </citation>
        <scope>GLYCOSYLATION AT ASN-33</scope>
        <scope>STRUCTURE OF CARBOHYDRATES</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2008" name="J. Mol. Biol." volume="384" first="393" last="405">
            <title>The 1.8-A crystal structure of alpha1-acid glycoprotein (Orosomucoid) solved by UV RIP reveals the broad drug-binding activity of this human plasma lipocalin.</title>
            <authorList>
                <person name="Schonfeld D.L."/>
                <person name="Ravelli R.B."/>
                <person name="Mueller U."/>
                <person name="Skerra A."/>
            </authorList>
            <dbReference type="PubMed" id="18823996"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2008.09.020"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 20-201</scope>
        <scope>DOMAIN</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="1997" name="Hum. Genet." volume="99" first="393" last="398">
            <title>Human orosomucoid polymorphism: molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S.</title>
            <authorList>
                <person name="Yuasa I."/>
                <person name="Umetsu K."/>
                <person name="Vogt U."/>
                <person name="Nakamura H."/>
                <person name="Nanba E."/>
                <person name="Tamaki N."/>
                <person name="Irizawa Y."/>
            </authorList>
            <dbReference type="PubMed" id="9050929"/>
            <dbReference type="DOI" id="10.1007/s004390050378"/>
        </citation>
        <scope>VARIANTS GLN-38 AND MET-174</scope>
    </reference>
    <comment type="function">
        <text evidence="10 11">Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-976767">
            <id>P02763</id>
        </interactant>
        <interactant intactId="EBI-3911979">
            <id>P19652</id>
            <label>ORM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-976767">
            <id>P02763</id>
        </interactant>
        <interactant intactId="EBI-953978">
            <id>P05121</id>
            <label>SERPINE1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed by the liver and secreted in plasma.</text>
    </comment>
    <comment type="induction">
        <text>Synthesis is controlled by glucocorticoids, interleukin-1 and interleukin-6, It increases 5- to 50-fold upon inflammation.</text>
    </comment>
    <comment type="domain">
        <text evidence="12">Contains a beta-barrel that binds various ligands in its interior.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1 2 3 5 7 8 9 13 14 15">N-glycosylated. N-glycan heterogeneity at Asn-33: Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor).</text>
    </comment>
    <comment type="polymorphism">
        <text>Three common alleles of ORM1 are known. ORM1*F1 has Gln-38/Val-174; ORM1*F2 has Gln-38/Met-174 and ORM1*S has Arg-38/Val-174. The sequence shown is that of allele ORM1*S.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the calycin superfamily. Lipocalin family.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA29229" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X02544">
        <property type="protein sequence ID" value="CAA26397.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M13692">
        <property type="protein sequence ID" value="AAA35515.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X05779">
        <property type="protein sequence ID" value="CAA29229.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA29229.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X06676">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BT019790">
        <property type="protein sequence ID" value="AAV38593.1"/>
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        <property type="protein sequence ID" value="BAG34972.1"/>
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        <property type="protein sequence ID" value="EAW87416.1"/>
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        <property type="protein sequence ID" value="AAI04819.1"/>
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        <property type="protein sequence ID" value="AAI04821.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI43314.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH26238.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="OMHU1"/>
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        <property type="nucleotide sequence ID" value="NM_000607.4"/>
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    <dbReference type="PDB" id="3KQ0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=19-201"/>
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    <dbReference type="PDBsum" id="3KQ0"/>
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    <dbReference type="DrugBank" id="DB05812">
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    <dbReference type="DrugBank" id="DB00346">
        <property type="generic name" value="Alfuzosin"/>
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    <dbReference type="DrugBank" id="DB00278">
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        <property type="generic name" value="Belumosudil"/>
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    <dbReference type="DrugBank" id="DB01086">
        <property type="generic name" value="Benzocaine"/>
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    <dbReference type="DrugBank" id="DB09128">
        <property type="generic name" value="Brexpiprazole"/>
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    <dbReference type="DrugBank" id="DB01156">
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    <dbReference type="DrugBank" id="DB00490">
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    <dbReference type="DrugBank" id="DB11148">
        <property type="generic name" value="Butamben"/>
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    <dbReference type="DrugBank" id="DB08907">
        <property type="generic name" value="Canagliflozin"/>
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        <property type="generic name" value="Chloroquine"/>
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    <dbReference type="DrugBank" id="DB00477">
        <property type="generic name" value="Chlorpromazine"/>
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    <dbReference type="DrugBank" id="DB01190">
        <property type="generic name" value="Clindamycin"/>
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    <dbReference type="DrugBank" id="DB00349">
        <property type="generic name" value="Clobazam"/>
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    <dbReference type="DrugBank" id="DB00363">
        <property type="generic name" value="Clozapine"/>
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    <dbReference type="DrugBank" id="DB05239">
        <property type="generic name" value="Cobimetinib"/>
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    <dbReference type="DrugBank" id="DB00907">
        <property type="generic name" value="Cocaine"/>
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    <dbReference type="DrugBank" id="DB08865">
        <property type="generic name" value="Crizotinib"/>
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    <dbReference type="DrugBank" id="DB00080">
        <property type="generic name" value="Daptomycin"/>
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    <dbReference type="DrugBank" id="DB01264">
        <property type="generic name" value="Darunavir"/>
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    <dbReference type="DrugBank" id="DB11637">
        <property type="generic name" value="Delamanid"/>
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    <dbReference type="DrugBank" id="DB01151">
        <property type="generic name" value="Desipramine"/>
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    <dbReference type="DrugBank" id="DB00343">
        <property type="generic name" value="Diltiazem"/>
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    <dbReference type="DrugBank" id="DB00975">
        <property type="generic name" value="Dipyridamole"/>
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    <dbReference type="DrugBank" id="DB00280">
        <property type="generic name" value="Disopyramide"/>
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    <dbReference type="DrugBank" id="DB08930">
        <property type="generic name" value="Dolutegravir"/>
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    <dbReference type="DrugBank" id="DB01142">
        <property type="generic name" value="Doxepin"/>
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    <dbReference type="DrugBank" id="DB00476">
        <property type="generic name" value="Duloxetine"/>
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    <dbReference type="DrugBank" id="DB01126">
        <property type="generic name" value="Dutasteride"/>
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    <dbReference type="DrugBank" id="DB12147">
        <property type="generic name" value="Erdafitinib"/>
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    <dbReference type="DrugBank" id="DB00530">
        <property type="generic name" value="Erlotinib"/>
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    <dbReference type="DrugBank" id="DB12235">
        <property type="generic name" value="Estetrol"/>
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    <dbReference type="DrugBank" id="DB12466">
        <property type="generic name" value="Favipiravir"/>
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    <dbReference type="DrugBank" id="DB00813">
        <property type="generic name" value="Fentanyl"/>
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    <dbReference type="DrugBank" id="DB00950">
        <property type="generic name" value="Fexofenadine"/>
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    <dbReference type="DrugBank" id="DB01195">
        <property type="generic name" value="Flecainide"/>
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    <dbReference type="DrugBank" id="DB00472">
        <property type="generic name" value="Fluoxetine"/>
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    <dbReference type="DrugBank" id="DB08906">
        <property type="generic name" value="Fluticasone furoate"/>
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    <dbReference type="DrugBank" id="DB15149">
        <property type="generic name" value="Futibatinib"/>
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    <dbReference type="DrugBank" id="DB00317">
        <property type="generic name" value="Gefitinib"/>
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    <dbReference type="DrugBank" id="DB11978">
        <property type="generic name" value="Glasdegib"/>
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    <dbReference type="DrugBank" id="DB00986">
        <property type="generic name" value="Glycopyrronium"/>
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    <dbReference type="DrugBank" id="DB11575">
        <property type="generic name" value="Grazoprevir"/>
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        <property type="generic name" value="Irbesartan"/>
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        <property type="generic name" value="Istradefylline"/>
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    <dbReference type="DrugBank" id="DB08820">
        <property type="generic name" value="Ivacaftor"/>
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    <dbReference type="DrugBank" id="DB09236">
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    <dbReference type="DrugBank" id="DB00281">
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    <dbReference type="DrugBank" id="DB01627">
        <property type="generic name" value="Lincomycin"/>
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    <dbReference type="DrugBank" id="DB01601">
        <property type="generic name" value="Lopinavir"/>
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    <dbReference type="DrugBank" id="DB12674">
        <property type="generic name" value="Lurbinectedin"/>
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    <dbReference type="DrugBank" id="DB08932">
        <property type="generic name" value="Macitentan"/>
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<entry dataset="Swiss-Prot" created="1987-03-20" modified="2026-01-28" version="212" xmlns="https://uniprot.org/uniprot">
    <accession>P04217</accession>
    <accession>A8K052</accession>
    <accession>Q68CK0</accession>
    <accession>Q8IYJ6</accession>
    <accession>Q96P39</accession>
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            <fullName>Alpha-1B-glycoprotein</fullName>
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        <alternativeName>
            <fullName>Alpha-1-B glycoprotein</fullName>
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        <name type="primary">A1BG</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-52</scope>
        <source>
            <tissue>Mammary gland</tissue>
        </source>
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            <dbReference type="PubMed" id="15057824"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="5">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Ovary</tissue>
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            <dbReference type="PubMed" id="3458201"/>
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        <scope>PROTEIN SEQUENCE OF 22-495</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>GLYCOSYLATION AT ASN-44; ASN-179; ASN-363 AND ASN-371</scope>
        <scope>VARIANT ARG-52</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="15461460"/>
            <dbReference type="DOI" id="10.1021/bi048823e"/>
        </citation>
        <scope>INTERACTION WITH CRISP3</scope>
    </reference>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44 AND ASN-179</scope>
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            <tissue>Plasma</tissue>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44; ASN-179; ASN-363 AND ASN-371</scope>
        <source>
            <tissue>Plasma</tissue>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44</scope>
        <scope>STRUCTURE OF CARBOHYDRATES</scope>
        <source>
            <tissue>Cerebrospinal fluid</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
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    <comment type="subunit">
        <text evidence="4">Interacts with CRISP3.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P04217-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P04217-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_040323"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Plasma.</text>
    </comment>
    <dbReference type="EMBL" id="AB073611">
        <property type="protein sequence ID" value="BAD38648.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF414429">
        <property type="protein sequence ID" value="AAL07469.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK289417">
        <property type="protein sequence ID" value="BAF82106.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010642">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012313">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035719">
        <property type="protein sequence ID" value="AAH35719.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12976.1">
        <molecule id="P04217-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_570602.2">
        <molecule id="P04217-1"/>
        <property type="nucleotide sequence ID" value="NM_130786.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P04217"/>
    <dbReference type="SMR" id="P04217"/>
    <dbReference type="BioGRID" id="106523">
        <property type="interactions" value="39"/>
    </dbReference>
    <dbReference type="FunCoup" id="P04217">
        <property type="interactions" value="116"/>
    </dbReference>
    <dbReference type="IntAct" id="P04217">
        <property type="interactions" value="25"/>
    </dbReference>
    <dbReference type="MINT" id="P04217"/>
    <dbReference type="STRING" id="9606.ENSP00000263100"/>
    <dbReference type="DrugBank" id="DB09130">
        <property type="generic name" value="Copper"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01593">
        <property type="generic name" value="Zinc"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14487">
        <property type="generic name" value="Zinc acetate"/>
    </dbReference>
    <dbReference type="MEROPS" id="I43.950"/>
    <dbReference type="GlyConnect" id="780">
        <property type="glycosylation" value="9 N-Linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P04217">
        <property type="glycosylation" value="5 sites, 18 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P04217">
        <property type="glycosylation" value="9 sites, 26 N-linked glycans (4 sites), 3 O-linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P04217"/>
    <dbReference type="PhosphoSitePlus" id="P04217"/>
    <dbReference type="SwissPalm" id="P04217"/>
    <dbReference type="BioMuta" id="A1BG"/>
    <dbReference type="DMDM" id="317373553"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00022895"/>
    <dbReference type="CPTAC" id="non-CPTAC-1064"/>
    <dbReference type="jPOST" id="P04217"/>
    <dbReference type="MassIVE" id="P04217"/>
    <dbReference type="PaxDb" id="9606-ENSP00000263100"/>
    <dbReference type="PeptideAtlas" id="P04217"/>
    <dbReference type="PRIDE" id="P04217"/>
    <dbReference type="ProteomicsDB" id="51684">
        <molecule id="P04217-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="51685">
        <molecule id="P04217-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="3284">
        <property type="antibodies" value="435 antibodies from 37 providers"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000263100.8">
        <molecule id="P04217-1"/>
        <property type="protein sequence ID" value="ENSP00000263100.2"/>
        <property type="gene ID" value="ENSG00000121410.13"/>
    </dbReference>
    <dbReference type="GeneID" id="1"/>
    <dbReference type="KEGG" id="hsa:1"/>
    <dbReference type="MANE-Select" id="ENST00000263100.8">
        <property type="protein sequence ID" value="ENSP00000263100.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_130786.4"/>
        <property type="RefSeq protein sequence ID" value="NP_570602.2"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5"/>
    <dbReference type="ClinPGx" id="PA24356"/>
    <dbReference type="CTD" id="1"/>
    <dbReference type="DisGeNET" id="1"/>
    <dbReference type="GeneCards" id="A1BG"/>
    <dbReference type="HGNC" id="HGNC:5">
        <property type="gene designation" value="A1BG"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000121410">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="138670">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000121410"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000121410"/>
    <dbReference type="eggNOG" id="ENOG502RYEX">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01150000286974"/>
    <dbReference type="HOGENOM" id="CLU_042929_1_0_1"/>
    <dbReference type="InParanoid" id="P04217"/>
    <dbReference type="OMA" id="FWGLPMG"/>
    <dbReference type="OrthoDB" id="9450204at2759"/>
    <dbReference type="PAN-GO" id="P04217">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P04217"/>
    <dbReference type="PathwayCommons" id="P04217"/>
    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P04217"/>
    <dbReference type="Agora" id="ENSG00000121410"/>
    <dbReference type="BioGRID-ORCS" id="1">
        <property type="hits" value="15 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="A1BG">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="A1BG_(gene)"/>
    <dbReference type="GenomeRNAi" id="1"/>
    <dbReference type="Pharos" id="P04217">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P04217"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="P04217">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000121410">
        <property type="expression patterns" value="Expressed in right lobe of liver and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P04217">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072562">
        <property type="term" value="C:blood microparticle"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904813">
        <property type="term" value="C:ficolin-1-rich granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031093">
        <property type="term" value="C:platelet alpha granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034774">
        <property type="term" value="C:secretory granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002764">
        <property type="term" value="P:immune response-regulating signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd16843">
        <property type="entry name" value="IgC2_D1_D2_LILR_KIR_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd05751">
        <property type="entry name" value="IgC2_D1_LILR_KIR_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.10:FF:002341">
        <property type="entry name" value="Alpha-1-B glycoprotein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.10:FF:002892">
        <property type="entry name" value="Alpha-1-B glycoprotein"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Killer cell immunoglobulin-like receptor"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.10">
        <property type="entry name" value="Immunoglobulins"/>
        <property type="match status" value="5"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016332">
        <property type="entry name" value="A1B_glyco/leuk_Ig-like_rcpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007110">
        <property type="entry name" value="Ig-like_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036179">
        <property type="entry name" value="Ig-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013783">
        <property type="entry name" value="Ig-like_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050412">
        <property type="entry name" value="Ig-like_Receptors_ImmuneReg"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003599">
        <property type="entry name" value="Ig_sub"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003598">
        <property type="entry name" value="Ig_sub2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11738:SF184">
        <property type="entry name" value="ALPHA-1B-GLYCOPROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11738">
        <property type="entry name" value="MHC CLASS I NK CELL RECEPTOR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13895">
        <property type="entry name" value="Ig_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF001979">
        <property type="entry name" value="Alpha_1B_glycoprot_prd"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00409">
        <property type="entry name" value="IG"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="SMART" id="SM00408">
        <property type="entry name" value="IGc2"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48726">
        <property type="entry name" value="Immunoglobulin"/>
        <property type="match status" value="5"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50835">
        <property type="entry name" value="IG_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0393">Immunoglobulin domain</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="7">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000014502" description="Alpha-1B-glycoprotein">
        <location>
            <begin position="22"/>
            <end position="495"/>
        </location>
    </feature>
    <feature type="domain" description="Ig-like V-type 1">
        <location>
            <begin position="22"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="domain" description="Ig-like V-type 2">
        <location>
            <begin position="114"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="domain" description="Ig-like V-type 3">
        <location>
            <begin position="207"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="domain" description="Ig-like V-type 4">
        <location>
            <begin position="300"/>
            <end position="397"/>
        </location>
    </feature>
    <feature type="domain" description="Ig-like V-type 5">
        <location>
            <begin position="398"/>
            <end position="495"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="3 5 6 7">
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3 5 7">
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5 7">
        <location>
            <position position="363"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5 7">
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="11">
        <location>
            <begin position="49"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1 7">
        <location>
            <begin position="139"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1 7">
        <location>
            <begin position="232"/>
            <end position="279"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1 7">
        <location>
            <begin position="325"/>
            <end position="374"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="11">
        <location>
            <begin position="423"/>
            <end position="470"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_040323" description="In isoform 2." evidence="9">
        <location>
            <begin position="1"/>
            <end position="122"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018369" description="In dbSNP:rs893184." evidence="2 7 8">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018370" description="In dbSNP:rs2241788.">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="395"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL07469." evidence="10" ref="2">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL07469." evidence="10" ref="2">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="127"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL07469." evidence="10" ref="2">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAF82106." evidence="10" ref="3">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="304"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL07469." evidence="10" ref="2">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="413"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAL07469." evidence="10" ref="2">
        <original>VR</original>
        <variation>IP</variation>
        <location>
            <begin position="446"/>
            <end position="447"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00114"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="14760718"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15461460"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16335952"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="19838169"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="3458201"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="3458201"/>
        </source>
    </evidence>
    <sequence length="495" mass="54254" checksum="8E611BDC3BC824C8" modified="2011-01-11" version="4" precursor="true">MSMLVVFLLLWGVTWGPVTEAAIFYETQPSLWAESESLLKPLANVTLTCQAHLETPDFQLFKNGVAQEPVHLDSPAIKHQFLLTGDTQGRYRCRSGLSTGWTQLSKLLELTGPKSLPAPWLSMAPVSWITPGLKTTAVCRGVLRGVTFLLRREGDHEFLEVPEAQEDVEATFPVHQPGNYSCSYRTDGEGALSEPSATVTIEELAAPPPPVLMHHGESSQVLHPGNKVTLTCVAPLSGVDFQLRRGEKELLVPRSSTSPDRIFFHLNAVALGDGGHYTCRYRLHDNQNGWSGDSAPVELILSDETLPAPEFSPEPESGRALRLRCLAPLEGARFALVREDRGGRRVHRFQSPAGTEALFELHNISVADSANYSCVYVDLKPPFGGSAPSERLELHVDGPPPRPQLRATWSGAVLAGRDAVLRCEGPIPDVTFELLREGETKAVKTVRTPGAAANLELIFVGPQHAGNYRCRYRSWVPHTFESELSDPVELLVAES</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1991-02-01" modified="2026-01-28" version="173" xmlns="https://uniprot.org/uniprot">
    <accession>P20848</accession>
    <accession>A0A0G2JPK4</accession>
    <accession>S4UD68</accession>
    <name>A1ATR_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Alpha-1-antitrypsin-related protein</fullName>
            <shortName evidence="6">AAT-related protein</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Protease inhibitor 1-like</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Serpin A2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">SERPINA2</name>
        <name type="synonym">ARGS</name>
        <name evidence="6 7" type="synonym">ATR</name>
        <name evidence="7" type="synonym">PIL</name>
        <name type="synonym">SERPINA2P</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="Genomics" volume="2" first="165" last="173">
            <title>Molecular structure and sequence homology of a gene related to alpha 1-antitrypsin in the human genome.</title>
            <authorList>
                <person name="Bao J.J."/>
                <person name="Reed-Fourquet L."/>
                <person name="Sifers R.N."/>
                <person name="Kidd V.J."/>
                <person name="Woo S.L.C."/>
            </authorList>
            <dbReference type="PubMed" id="2842251"/>
            <dbReference type="DOI" id="10.1016/0888-7543(88)90099-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference evidence="9" key="2">
        <citation type="journal article" date="2013" name="PLoS ONE" volume="8" first="E66889" last="E66889">
            <title>SERPINA2 is a novel gene with a divergent function from SERPINA1.</title>
            <authorList>
                <person name="Marques P.I."/>
                <person name="Ferreira Z."/>
                <person name="Martins M."/>
                <person name="Figueiredo J."/>
                <person name="Silva D.I."/>
                <person name="Castro P."/>
                <person name="Morales-Hojas R."/>
                <person name="Simoes-Correia J."/>
                <person name="Seixas S."/>
            </authorList>
            <dbReference type="PubMed" id="23826168"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0066889"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANTS PRO-330 AND LYS-342</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>INTERACTION WITH CANX AND PDIA3</scope>
        <source>
            <tissue evidence="9">Testis</tissue>
        </source>
    </reference>
    <reference evidence="10" key="3">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
                <person name="Pepin K."/>
                <person name="Artiguenave F."/>
                <person name="Robert C."/>
                <person name="Cruaud C."/>
                <person name="Bruels T."/>
                <person name="Jaillon O."/>
                <person name="Friedlander L."/>
                <person name="Samson G."/>
                <person name="Brottier P."/>
                <person name="Cure S."/>
                <person name="Segurens B."/>
                <person name="Aniere F."/>
                <person name="Samain S."/>
                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
                <person name="Dubois I."/>
                <person name="Friedman C."/>
                <person name="Gouyvenoux M."/>
                <person name="James R."/>
                <person name="Madan A."/>
                <person name="Mairey-Estrada B."/>
                <person name="Mangenot S."/>
                <person name="Martins N."/>
                <person name="Menard M."/>
                <person name="Oztas S."/>
                <person name="Ratcliffe A."/>
                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
                <person name="Magdelenat G."/>
                <person name="Pateau E."/>
                <person name="Petit E."/>
                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
                <person name="Vega-Czarny N."/>
                <person name="Bataille E."/>
                <person name="Bluet E."/>
                <person name="Bordelais I."/>
                <person name="Dubois M."/>
                <person name="Dumont C."/>
                <person name="Guerin T."/>
                <person name="Haffray S."/>
                <person name="Hammadi R."/>
                <person name="Muanga J."/>
                <person name="Pellouin V."/>
                <person name="Robert D."/>
                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
                <person name="Roy A."/>
                <person name="Sainte-Marthe L."/>
                <person name="Verdier J."/>
                <person name="Verdier-Discala C."/>
                <person name="Hillier L.W."/>
                <person name="Fulton L."/>
                <person name="McPherson J."/>
                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
                <person name="Waterston R."/>
                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1997" name="Mamm. Genome" volume="8" first="913" last="916">
            <title>Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1.</title>
            <authorList>
                <person name="Rollini P."/>
                <person name="Fournier R.E."/>
            </authorList>
            <dbReference type="PubMed" id="9383284"/>
            <dbReference type="DOI" id="10.1007/s003359900610"/>
        </citation>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2007" name="Mol. Biol. Evol." volume="24" first="587" last="598">
            <title>Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2.</title>
            <authorList>
                <person name="Seixas S."/>
                <person name="Suriano G."/>
                <person name="Carvalho F."/>
                <person name="Seruca R."/>
                <person name="Rocha J."/>
                <person name="Di Rienzo A."/>
            </authorList>
            <dbReference type="PubMed" id="17135331"/>
            <dbReference type="DOI" id="10.1093/molbev/msl187"/>
        </citation>
        <scope>POLYMORPHISM</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text>Putative serine protease inhibitor.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts with CANX and PDIA3.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Endoplasmic reticulum</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 4">Expressed in the liver, leukocytes and testis. Also detected in brain, colon, uterus, esophagus, spleen, trachea, kidney and lung.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">Glycosylated.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="3 4 5">The SERPINA2 gene is highly polymorphic. Deletions, frameshift mutations and a critical start codon variation (ATG-&gt;ATA, dbSNP:rs1956172) have been found in some populations. Population studies suggest that a pseudogenization process may be ongoing in humans (PubMed:17135331, PubMed:23826168, PubMed:9383284). 3 potentially functional alleles, V1, V2 and V3, have been described in the literature. The sequence shown in this entry is that of allele V2 (PubMed:23826168).</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the serpin family.</text>
    </comment>
    <dbReference type="EMBL" id="M19684">
        <property type="protein sequence ID" value="AAA51544.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M19685">
        <property type="protein sequence ID" value="AAA51544.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JX680599">
        <property type="protein sequence ID" value="AGI62067.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC235087">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="PIR" id="A28882">
        <property type="entry name" value="A28882"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006211.2">
        <property type="nucleotide sequence ID" value="NM_006220.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P20848"/>
    <dbReference type="SMR" id="P20848"/>
    <dbReference type="FunCoup" id="P20848">
        <property type="interactions" value="83"/>
    </dbReference>
    <dbReference type="IntAct" id="P20848">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="BindingDB" id="P20848"/>
    <dbReference type="ChEMBL" id="CHEMBL4879431"/>
    <dbReference type="MEROPS" id="I04.952"/>
    <dbReference type="GlyCosmos" id="P20848">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P20848">
        <property type="glycosylation" value="4 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P20848"/>
    <dbReference type="PhosphoSitePlus" id="P20848"/>
    <dbReference type="BioMuta" id="SERPINA2"/>
    <dbReference type="DMDM" id="112891"/>
    <dbReference type="jPOST" id="P20848"/>
    <dbReference type="MassIVE" id="P20848"/>
    <dbReference type="PeptideAtlas" id="P20848"/>
    <dbReference type="ProteomicsDB" id="53815"/>
    <dbReference type="DNASU" id="390502"/>
    <dbReference type="Ensembl" id="ENST00000616052.3">
        <property type="protein sequence ID" value="ENSP00000477957.2"/>
        <property type="gene ID" value="ENSG00000274821.5"/>
    </dbReference>
    <dbReference type="GeneID" id="390502"/>
    <dbReference type="KEGG" id="hsa:390502"/>
    <dbReference type="MANE-Select" id="ENST00000616052.3">
        <property type="protein sequence ID" value="ENSP00000477957.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006220.3"/>
        <property type="RefSeq protein sequence ID" value="NP_006211.2"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:8985"/>
    <dbReference type="CTD" id="390502"/>
    <dbReference type="DisGeNET" id="390502"/>
    <dbReference type="GeneCards" id="SERPINA2"/>
    <dbReference type="HGNC" id="HGNC:8985">
        <property type="gene designation" value="SERPINA2"/>
    </dbReference>
    <dbReference type="MIM" id="107410">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="InParanoid" id="P20848"/>
    <dbReference type="OrthoDB" id="9518664at2759"/>
    <dbReference type="PAN-GO" id="P20848">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P20848"/>
    <dbReference type="BioGRID-ORCS" id="390502">
        <property type="hits" value="2 hits in 39 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="390502"/>
    <dbReference type="Pharos" id="P20848">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P20848"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="P20848">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004867">
        <property type="term" value="F:serine-type endopeptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd19550">
        <property type="entry name" value="serpinA2_PIL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.39.10:FF:000003">
        <property type="entry name" value="alpha-1-antitrypsin isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.497.10:FF:000001">
        <property type="entry name" value="Serine protease inhibitor"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.39.10">
        <property type="entry name" value="Alpha-1-antitrypsin, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.497.10">
        <property type="entry name" value="Antithrombin, subunit I, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023795">
        <property type="entry name" value="Serpin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023796">
        <property type="entry name" value="Serpin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000215">
        <property type="entry name" value="Serpin_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036186">
        <property type="entry name" value="Serpin_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042178">
        <property type="entry name" value="Serpin_sf_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042185">
        <property type="entry name" value="Serpin_sf_2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461:SF289">
        <property type="entry name" value="ALPHA-1-ANTITRYPSIN-RELATED PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461">
        <property type="entry name" value="SERINE PROTEASE INHIBITOR, SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00079">
        <property type="entry name" value="Serpin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00093">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56574">
        <property type="entry name" value="Serpins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00284">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000032410" description="Alpha-1-antitrypsin-related protein">
        <location>
            <begin position="22"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="site" description="Reactive bond" evidence="2">
        <location>
            <begin position="385"/>
            <end position="386"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070190" description="In allele V1 and allele V3; dbSNP:rs2089497656." evidence="4">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070191" description="In allele V1; dbSNP:rs2089497643." evidence="4">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544 and 2; AGI62067." evidence="8" ref="1 2">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544." evidence="8" ref="1">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544." evidence="8" ref="1">
        <original>ELADLSQTSN</original>
        <variation>SWLIYHNQH</variation>
        <location>
            <begin position="67"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544." evidence="8" ref="1">
        <original>A</original>
        <variation>R</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544 and 2; AGI62067." evidence="8" ref="1 2">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51544." evidence="8" ref="1">
        <original>DD</original>
        <variation>EY</variation>
        <location>
            <begin position="403"/>
            <end position="404"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="17135331"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="23826168"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="9383284"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="2842251"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="9383284"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="EMBL" id="AGI62067.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="Proteomes" id="UP000005640"/>
        </source>
    </evidence>
    <sequence length="421" mass="47707" checksum="33A46EF9896FC91D" modified="2022-08-03" version="2" precursor="true">MPFSVSWGILLLAGLCCLVPSSLVEDPQEDAAQKTDTSHHDQGDWEDLACQKISYNVTDLAFDLYKELADLSQTSNVLVTPTSVAMAFAMLSLGTKADTRTEILEGLNVNLTETPEAKIHECFQQVLQALSRPDTRLQLTTGSSLFVNKSMKLVDTFLEDTKKLYHSEASSINFRDTEEAKEQINNYVEKRTGRKVVDLVKHLKKDTSLALVDYISFHGKWKDKFKAEHIMVEGFHVDDKTIIRVPMINHLGRFDIHRDRELSSWVLAQHYVGNATAFFILPDPKKMWQLEEKLTYSHLENIQRAFDIRSINLHFPKLSISGTYKLKRVLRNLGITKIFSNEADLSGVSQEAPLKLSKAVHVAVLTIDEKGTEATGAPHLEEKAWSKYQTVMFNRPFLVIIKDDITNFPLFIGKVVNPTQK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1991-02-01" modified="2026-01-28" version="219" xmlns="https://uniprot.org/uniprot">
    <accession>P19652</accession>
    <accession>B2R5L2</accession>
    <accession>Q16571</accession>
    <accession>Q5T538</accession>
    <accession>Q6IB74</accession>
    <name>A1AG2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-1-acid glycoprotein 2</fullName>
            <shortName>AGP 2</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Orosomucoid-2</fullName>
            <shortName>OMD 2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ORM2</name>
        <name type="synonym">AGP2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="EMBO J." volume="6" first="2289" last="2296">
            <title>Structure and expression of the genes coding for human alpha 1-acid glycoprotein.</title>
            <authorList>
                <person name="Dente L."/>
                <person name="Pizza M.G."/>
                <person name="Metspalu A."/>
                <person name="Cortese R."/>
            </authorList>
            <dbReference type="PubMed" id="2822385"/>
            <dbReference type="DOI" id="10.1002/j.1460-2075.1987.tb02503.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1988" name="Gene" volume="66" first="97" last="106">
            <title>Structure and characterisation of a duplicated human alpha 1 acid glycoprotein gene.</title>
            <authorList>
                <person name="Merritt C.M."/>
                <person name="Board P.G."/>
            </authorList>
            <dbReference type="PubMed" id="2970990"/>
            <dbReference type="DOI" id="10.1016/0378-1119(88)90228-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
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        <scope>DOMAIN</scope>
    </reference>
    <comment type="function">
        <text evidence="8">Functions as a transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3911979">
            <id>P19652</id>
        </interactant>
        <interactant intactId="EBI-976767">
            <id>P02763</id>
            <label>ORM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed by the liver and secreted in plasma.</text>
    </comment>
    <comment type="induction">
        <text>Synthesis is controlled by glucocorticoids, interleukin-1 and interleukin-6, It increases 5- to 50-fold upon inflammation.</text>
    </comment>
    <comment type="domain">
        <text evidence="8">Contains a beta-barrel that binds various ligands in its interior.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1 2 3 4 5 6 7 9">N-glycosylated. N-glycan heterogeneity at Asn-33: Hex5HexNAc4 (minor), Hex6HexNAc5 (major) and dHex1Hex6HexNAc5 (minor).</text>
    </comment>
    <comment type="polymorphism">
        <text>Many different variants of ORM2 are known.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the calycin superfamily. Lipocalin family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA29873" version="2"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA29874" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X06675">
        <property type="protein sequence ID" value="CAA29874.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X05780">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06674">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06676">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06677">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06678">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06679">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X06680">
        <property type="protein sequence ID" value="CAA29873.2"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X05784">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21540">
        <property type="protein sequence ID" value="AAA51549.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312226">
        <property type="protein sequence ID" value="BAG35159.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456930">
        <property type="protein sequence ID" value="CAG33211.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL356796">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471090">
        <property type="protein sequence ID" value="EAW87417.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015964">
        <property type="protein sequence ID" value="AAH15964.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC056239">
        <property type="protein sequence ID" value="AAH56239.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6804.1"/>
    <dbReference type="PIR" id="JT0326">
        <property type="entry name" value="OMHU2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000599.1">
        <property type="nucleotide sequence ID" value="NM_000608.4"/>
    </dbReference>
    <dbReference type="PDB" id="3APU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=19-201"/>
    </dbReference>
    <dbReference type="PDB" id="3APV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="A/B=19-201"/>
    </dbReference>
    <dbReference type="PDB" id="3APW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=19-201"/>
    </dbReference>
    <dbReference type="PDB" id="3APX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=19-201"/>
    </dbReference>
    <dbReference type="PDB" id="7OUB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.82 A"/>
        <property type="chains" value="B=19-190"/>
    </dbReference>
    <dbReference type="PDBsum" id="3APU"/>
    <dbReference type="PDBsum" id="3APV"/>
    <dbReference type="PDBsum" id="3APW"/>
    <dbReference type="PDBsum" id="3APX"/>
    <dbReference type="PDBsum" id="7OUB"/>
    <dbReference type="AlphaFoldDB" id="P19652"/>
    <dbReference type="SMR" id="P19652"/>
    <dbReference type="BioGRID" id="111047">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="FunCoup" id="P19652">
        <property type="interactions" value="81"/>
    </dbReference>
    <dbReference type="IntAct" id="P19652">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000394936"/>
    <dbReference type="ChEMBL" id="CHEMBL5958"/>
    <dbReference type="DrugBank" id="DB12001">
        <property type="generic name" value="Abemaciclib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11703">
        <property type="generic name" value="Acalabrutinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00404">
        <property type="generic name" value="Alprazolam"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00278">
        <property type="generic name" value="Argatroban"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB06216">
        <property type="generic name" value="Asenapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01072">
        <property type="generic name" value="Atazanavir"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00289">
        <property type="generic name" value="Atomoxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01086">
        <property type="generic name" value="Benzocaine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00748">
        <property type="generic name" value="Carbinoxamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00608">
        <property type="generic name" value="Chloroquine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00477">
        <property type="generic name" value="Chlorpromazine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00907">
        <property type="generic name" value="Cocaine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08865">
        <property type="generic name" value="Crizotinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00280">
        <property type="generic name" value="Disopyramide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08930">
        <property type="generic name" value="Dolutegravir"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00476">
        <property type="generic name" value="Duloxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12147">
        <property type="generic name" value="Erdafitinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12466">
        <property type="generic name" value="Favipiravir"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00813">
        <property type="generic name" value="Fentanyl"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00950">
        <property type="generic name" value="Fexofenadine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01195">
        <property type="generic name" value="Flecainide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11978">
        <property type="generic name" value="Glasdegib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00986">
        <property type="generic name" value="Glycopyrronium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01611">
        <property type="generic name" value="Hydroxychloroquine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09053">
        <property type="generic name" value="Ibrutinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09262">
        <property type="generic name" value="Imidafenacin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00458">
        <property type="generic name" value="Imipramine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00808">
        <property type="generic name" value="Indapamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00332">
        <property type="generic name" value="Ipratropium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01029">
        <property type="generic name" value="Irbesartan"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11757">
        <property type="generic name" value="Istradefylline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00598">
        <property type="generic name" value="Labetalol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00281">
        <property type="generic name" value="Lidocaine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08932">
        <property type="generic name" value="Macitentan"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01203">
        <property type="generic name" value="Nadolol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11828">
        <property type="generic name" value="Neratinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01115">
        <property type="generic name" value="Nifedipine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12005">
        <property type="generic name" value="Nirogacestat"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00497">
        <property type="generic name" value="Oxycodone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14582">
        <property type="generic name" value="Patisiran"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00960">
        <property type="generic name" value="Pindolol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00409">
        <property type="generic name" value="Remoxipride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01045">
        <property type="generic name" value="Rifampin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14840">
        <property type="generic name" value="Ripretinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00938">
        <property type="generic name" value="Salmeterol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11689">
        <property type="generic name" value="Selumetinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01591">
        <property type="generic name" value="Solifenacin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00421">
        <property type="generic name" value="Spironolactone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00857">
        <property type="generic name" value="Terbinafine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00342">
        <property type="generic name" value="Terfenadine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01041">
        <property type="generic name" value="Thalidomide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00512">
        <property type="generic name" value="Vancomycin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11641">
        <property type="generic name" value="Vinflunine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01593">
        <property type="generic name" value="Zinc"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14487">
        <property type="generic name" value="Zinc acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14533">
        <property type="generic name" value="Zinc chloride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14548">
        <property type="generic name" value="Zinc sulfate, unspecified form"/>
    </dbReference>
    <dbReference type="GlyConnect" id="14">
        <property type="glycosylation" value="74 N-Linked glycans (6 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P19652">
        <property type="glycosylation" value="6 sites, 98 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P19652">
        <property type="glycosylation" value="7 sites, 148 N-linked glycans (7 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P19652"/>
    <dbReference type="PhosphoSitePlus" id="P19652"/>
    <dbReference type="BioMuta" id="ORM2"/>
    <dbReference type="DMDM" id="231458"/>
    <dbReference type="jPOST" id="P19652"/>
    <dbReference type="MassIVE" id="P19652"/>
    <dbReference type="PaxDb" id="9606-ENSP00000394936"/>
    <dbReference type="PeptideAtlas" id="P19652"/>
    <dbReference type="ProteomicsDB" id="53685"/>
    <dbReference type="Antibodypedia" id="29909">
        <property type="antibodies" value="261 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5005"/>
    <dbReference type="Ensembl" id="ENST00000431067.4">
        <property type="protein sequence ID" value="ENSP00000394936.2"/>
        <property type="gene ID" value="ENSG00000228278.6"/>
    </dbReference>
    <dbReference type="GeneID" id="5005"/>
    <dbReference type="KEGG" id="hsa:5005"/>
    <dbReference type="MANE-Select" id="ENST00000431067.4">
        <property type="protein sequence ID" value="ENSP00000394936.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000608.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000599.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004bil.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:8499"/>
    <dbReference type="ClinPGx" id="PA32818"/>
    <dbReference type="CTD" id="5005"/>
    <dbReference type="DisGeNET" id="5005"/>
    <dbReference type="GeneCards" id="ORM2"/>
    <dbReference type="HGNC" id="HGNC:8499">
        <property type="gene designation" value="ORM2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000228278">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="138610">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000228278"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000228278"/>
    <dbReference type="eggNOG" id="ENOG502S0Q2">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012130"/>
    <dbReference type="HOGENOM" id="CLU_117688_0_0_1"/>
    <dbReference type="InParanoid" id="P19652"/>
    <dbReference type="OMA" id="NWGLSFY"/>
    <dbReference type="OrthoDB" id="9448848at2759"/>
    <dbReference type="PAN-GO" id="P19652">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P19652"/>
    <dbReference type="PathwayCommons" id="P19652"/>
    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P19652"/>
    <dbReference type="SIGNOR" id="P19652"/>
    <dbReference type="Agora" id="ENSG00000228278"/>
    <dbReference type="BioGRID-ORCS" id="5005">
        <property type="hits" value="12 hits in 1100 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ORM2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P19652"/>
    <dbReference type="GenomeRNAi" id="5005"/>
    <dbReference type="Pharos" id="P19652">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P19652"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="P19652">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000228278">
        <property type="expression patterns" value="Expressed in right lobe of liver and 98 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035578">
        <property type="term" value="C:azurophil granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072562">
        <property type="term" value="C:blood microparticle"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031093">
        <property type="term" value="C:platelet alpha granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035580">
        <property type="term" value="C:specific granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006953">
        <property type="term" value="P:acute-phase response"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032731">
        <property type="term" value="P:positive regulation of interleukin-1 beta production"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032732">
        <property type="term" value="P:positive regulation of interleukin-1 production"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032760">
        <property type="term" value="P:positive regulation of tumor necrosis factor production"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002682">
        <property type="term" value="P:regulation of immune system process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="CDD" id="cd19451">
        <property type="entry name" value="lipocalin_AGP-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.128.20:FF:000012">
        <property type="entry name" value="Alpha-1-acid glycoprotein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.128.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001500">
        <property type="entry name" value="A1A_glycop"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012674">
        <property type="entry name" value="Calycin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000566">
        <property type="entry name" value="Lipocln_cytosolic_FA-bd_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11967">
        <property type="entry name" value="ALPHA-1-ACID GLYCOPROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11967:SF3">
        <property type="entry name" value="ALPHA-1-ACID GLYCOPROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00061">
        <property type="entry name" value="Lipocalin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF036899">
        <property type="entry name" value="AGP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00708">
        <property type="entry name" value="A1AGLPROTEIN"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50814">
        <property type="entry name" value="Lipocalins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0011">Acute phase</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0873">Pyrrolidone carboxylic acid</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0813">Transport</keyword>
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            <begin position="1"/>
            <end position="18"/>
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    <feature type="chain" id="PRO_0000017861" description="Alpha-1-acid glycoprotein 2">
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            <begin position="19"/>
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            <position position="33"/>
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            <position position="56"/>
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            <position position="72"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1 3 4 5 6">
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            <position position="103"/>
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            <begin position="90"/>
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            <position position="38"/>
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        <original>V</original>
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        <location>
            <position position="99"/>
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    <feature type="sequence variant" id="VAR_050173" description="In dbSNP:rs12685968.">
        <original>G</original>
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        <location>
            <position position="141"/>
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    </feature>
    <feature type="sequence variant" id="VAR_050174" description="In dbSNP:rs1126777.">
        <original>C</original>
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            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050175" description="In dbSNP:rs2636890.">
        <original>M</original>
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            <position position="174"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 4; CAG33211." evidence="10" ref="4">
        <original>T</original>
        <variation>I</variation>
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            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAG35159." evidence="10" ref="3">
        <original>E</original>
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            <position position="102"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAG35159." evidence="10" ref="3">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="125"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAG35159." evidence="10" ref="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="162"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 3; BAG35159." evidence="10" ref="3">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="189"/>
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    <feature type="turn" evidence="12">
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            <begin position="20"/>
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            <begin position="24"/>
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            <begin position="33"/>
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            <begin position="41"/>
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    <feature type="helix" evidence="13">
        <location>
            <begin position="53"/>
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    <feature type="strand" evidence="13">
        <location>
            <begin position="62"/>
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    <feature type="turn" evidence="13">
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            <begin position="73"/>
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    <feature type="strand" evidence="13">
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            <begin position="77"/>
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    <feature type="strand" evidence="13">
        <location>
            <begin position="89"/>
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    <feature type="turn" evidence="13">
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            <begin position="101"/>
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    <feature type="strand" evidence="13">
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            <begin position="105"/>
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    <feature type="strand" evidence="13">
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            <begin position="113"/>
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    <feature type="strand" evidence="13">
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            <begin position="170"/>
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            <dbReference type="PubMed" id="19838169"/>
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            <dbReference type="PubMed" id="21349832"/>
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            <dbReference type="PubMed" id="22171320"/>
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            <dbReference type="PDB" id="3APU"/>
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        <source>
            <dbReference type="PDB" id="3APX"/>
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    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="7OUB"/>
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    <sequence length="201" mass="23603" checksum="49167ABCC22933B9" modified="1993-04-01" version="2" precursor="true">MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDRITGKWFYIASAFRNEEYNKSVQEIQATFFYFTPNKTEDTIFLREYQTRQNQCFYNSSYLNVQRENGTVSRYEGGREHVAHLLFLRDTKTLMFGSYLDDEKNWGLSFYADKPETTKEQLGEFYEALDCLCIPRSDVMYTDWKKDKCEPLEKQHEKERKQEEGES</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-04-12" modified="2026-01-28" version="194" xmlns="https://uniprot.org/uniprot">
    <accession>Q676U5</accession>
    <accession>A3EXK9</accession>
    <accession>A3EXL0</accession>
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    <accession>Q6ZVZ5</accession>
    <accession>Q8NCY2</accession>
    <accession>Q96JV5</accession>
    <accession>Q9H619</accession>
    <name>A16L1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="45">Autophagy-related protein 16-1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="44">APG16-like 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="44 46" type="primary">ATG16L1</name>
        <name evidence="43" type="synonym">APG16L</name>
        <name evidence="40" type="ORF">UNQ9393/PRO34307</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-300</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5)</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
        <scope>VARIANT ALA-300</scope>
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            <dbReference type="PubMed" id="12975309"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-607 (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Placenta</tissue>
            <tissue>Small intestine</tissue>
        </source>
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            <dbReference type="DOI" id="10.15252/embj.201798358"/>
        </citation>
        <scope>INTERACTION WITH TRIM16</scope>
    </reference>
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            <title>Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes.</title>
            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="30778222"/>
            <dbReference type="DOI" id="10.1038/s41556-019-0274-9"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ATG5-ATG12 COMPLEX</scope>
        <scope>MUTAGENESIS OF 32-PHE--ILE-36; 308-VAL--VAL-310 AND PHE-467</scope>
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            </authorList>
            <dbReference type="PubMed" id="33087875"/>
            <dbReference type="DOI" id="10.1038/s41418-020-00638-2"/>
        </citation>
        <scope>INTERACTION WITH SPATA33</scope>
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            <title>Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine.</title>
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            <dbReference type="PubMed" id="33909989"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2021.03.020"/>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF LYS-490</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="23202584"/>
            <dbReference type="DOI" id="10.1038/nsmb.2431"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 11-43 IN COMPLEX WITH ATG5 AND ATG12</scope>
        <scope>INTERACTION WITH ATG5</scope>
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                <person name="Metlagel Z."/>
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            </authorList>
            <dbReference type="PubMed" id="24191030"/>
            <dbReference type="DOI" id="10.1073/pnas.1314755110"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 11-43 IN COMPLEX WITH ATG3; ATG5 AND ATG12</scope>
        <scope>INTERACTION WITH ATG5</scope>
    </reference>
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            <dbReference type="PubMed" id="25484072"/>
            <dbReference type="DOI" id="10.4161/15548627.2014.984276"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-69</scope>
        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH ATG5</scope>
        <scope>MUTAGENESIS OF ILE-17; LEU-21; ARG-24 AND ILE-36</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 1-69</scope>
        <scope>INTERACTION WITH ATG5</scope>
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            <dbReference type="PubMed" id="17484864"/>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
    </reference>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
    </reference>
    <reference key="37">
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            <dbReference type="PubMed" id="18499543"/>
            <dbReference type="DOI" id="10.1016/j.dld.2008.03.022"/>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
    </reference>
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            <title>Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease in German children.</title>
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                <person name="Lacher M."/>
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            <dbReference type="PubMed" id="19659808"/>
            <dbReference type="DOI" id="10.1111/j.1651-2227.2009.01438.x"/>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
    </reference>
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                <person name="Amre D.K."/>
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            <dbReference type="PubMed" id="18985712"/>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
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                <person name="Strisciuglio C."/>
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            <dbReference type="PubMed" id="24656308"/>
            <dbReference type="DOI" id="10.1016/j.dld.2014.02.016"/>
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        <scope>VARIANT ALA-300</scope>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO IBD10</scope>
    </reference>
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            <dbReference type="PubMed" id="24553140"/>
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        <scope>CHARACTERIZATION OF VARIANT ALA-300</scope>
        <scope>FUNCTION IN AUTOPHAGY</scope>
        <scope>CLEAVAGE BY CASP3</scope>
        <scope>MUTAGENESIS OF ASP-299</scope>
    </reference>
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            <title>WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1.</title>
            <authorList>
                <person name="Dooley H.C."/>
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            <dbReference type="PubMed" id="24954904"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2014.05.021"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH WIPI2 AND RB1CC1</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF GLU-226 AND GLU-230</scope>
    </reference>
    <reference key="43">
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            <title>RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.</title>
            <authorList>
                <person name="Pantoom S."/>
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            <dbReference type="PubMed" id="32960676"/>
            <dbReference type="DOI" id="10.1080/15548627.2020.1822629"/>
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        <scope>INTERACTION WITH RAB33B</scope>
        <scope>MUTAGENESIS OF ASN-206 AND ASN-209</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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                <person name="Grimm W.A."/>
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            <dbReference type="PubMed" id="25645662"/>
            <dbReference type="DOI" id="10.1136/gutjnl-2014-308735"/>
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        <scope>CHARACTERIZATION OF VARIANT ALA-300</scope>
        <scope>FUNCTION</scope>
    </reference>
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                <person name="Boada-Romero E."/>
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            <dbReference type="PubMed" id="27273576"/>
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        <scope>CHARACTERIZATION OF VARIANT ALA-300</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TMEM59</scope>
    </reference>
    <comment type="function">
        <text evidence="1 10 13 16 19 20 22 23 25 27 32 34 36 39">Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP) (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576, PubMed:29317426, PubMed:30778222, PubMed:33909989). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling (PubMed:29317426, PubMed:30778222). During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8 (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). Thereby, controls the elongation of the nascent autophagosomal membrane (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). As part of the ATG8 conjugation system with ATG5 and ATG12, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8 (PubMed:33909989). Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (By similarity). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (PubMed:22749352, PubMed:25645662). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340). Instead, promotes an autophagy-dependent antibacterial pathway together with NOD1 or NOD2 (PubMed:20637199). Plays a role in regulating morphology and function of Paneth cell (PubMed:18849966).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 14 15 16 17 18 19 20 21 25 26 28 29 30 31 32 33 34 35 36 37 38">Homodimer (PubMed:25484072). Homooligomer (By similarity). Heterooligomer with ATG16L2 (By similarity). Interacts with WIPI1 (PubMed:28561066). Interacts with WIPI2 (PubMed:24954904, PubMed:28561066). Interacts with RB1CC1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23262492, PubMed:23392225, PubMed:24954904). Interacts with ATG5 (PubMed:23202584, PubMed:24191030, PubMed:25484072, PubMed:26812546). Part of the minor complex composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this complex interacts with ATG3 leading to disruption of ATG7 interaction and promotion of ATG8-like proteins lipidation (PubMed:23202584, PubMed:24191030, PubMed:26083323, PubMed:29317426, PubMed:30778222). Part of the major complex composed of 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa) (PubMed:23202584, PubMed:26083323, PubMed:29317426, PubMed:30778222). Interacts with RAB33B (GTP- and GDP-bound forms); the complex consists of a tetramer where two RAB33B molecules bind independently one molecule of the ATG16L1 homodimer; the interaction promotes ATG12-ATG5-ATG16L1 complex recruitment to phagophores (PubMed:21808068, PubMed:32960676). Interacts (via WD repeats) with TMEM59; the interaction mediates unconventional autophagic activity of TMEM59 (PubMed:23376921, PubMed:27273576). Interacts with TLR2 (PubMed:23376921). Interacts (via WD repeats) with MEFV (PubMed:26347139). Interacts with PPP1CA; the interaction dephosphorylates ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex (PubMed:26083323). Interacts (via N-terminal) with CLTC (PubMed:20639872). Interacts with NOD1 (By similarity). Interacts with NOD2 (PubMed:20637199). Interacts with TUFM (PubMed:22749352). Interacts with TRIM16 (PubMed:30143514). Interacts (via WD repeats) with SPATA33 (PubMed:33087875). Interacts with IRGM (PubMed:25891078).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-746742">
            <id>O94817</id>
            <label>ATG12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
            <label>ATG16L1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-1047414">
            <id>Q9H1Y0</id>
            <label>ATG5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-720116">
            <id>P60520</id>
            <label>GABARAPL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-373144">
            <id>Q9GZQ8</id>
            <label>MAP1LC3B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-2603996">
            <id>Q9BXW4</id>
            <label>MAP1LC3C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-744685">
            <id>Q14088</id>
            <label>RAB33A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-3048549">
            <id>Q9H082</id>
            <label>RAB33B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-1047793">
            <id>Q8TDY2</id>
            <label>RB1CC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-535909">
            <id>Q676U5</id>
        </interactant>
        <interactant intactId="EBI-7054441">
            <id>Q9BXS4</id>
            <label>TMEM59</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-52363471">
            <id>Q676U5-1</id>
        </interactant>
        <interactant intactId="EBI-6115771">
            <id>Q9BYX4</id>
            <label>IFIH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-52363471">
            <id>Q676U5-1</id>
        </interactant>
        <interactant intactId="EBI-6374482">
            <id>Q9NX02</id>
            <label>NLRP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-52363471">
            <id>Q676U5-1</id>
        </interactant>
        <interactant intactId="EBI-527670">
            <id>P21580</id>
            <label>TNFAIP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="20">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="14 20 37">Preautophagosomal structure membrane</location>
            <topology evidence="45">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="34">Endosome membrane</location>
            <topology evidence="45">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="34">Lysosome membrane</location>
            <topology evidence="45">Peripheral membrane protein</topology>
        </subcellularLocation>
        <text evidence="1 34 37">Recruited to omegasomes membranes by WIPI2 (By similarity). Omegasomes are endoplasmic reticulum connected strutures at the origin of preautophagosomal structures (By similarity). Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5 (By similarity). Also localizes to discrete punctae along the ciliary axoneme (By similarity). Upon activation of non-canonical autophagy, recruited to single-membrane endolysosomal compartments (PubMed:29317426). Under starved conditions, the ATG12-ATG5-ATG16L1 complex is translocated to phagophores driven by RAB33B (PubMed:32960676).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q676U5-1</id>
            <name>1</name>
            <name>APG16L beta</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q676U5-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_013386"/>
        </isoform>
        <isoform>
            <id>Q676U5-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_013387 VSP_013388"/>
        </isoform>
        <isoform>
            <id>Q676U5-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_013389 VSP_013390"/>
        </isoform>
        <isoform>
            <id>Q676U5-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_013389 VSP_013386"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="1 34">The WD repeats are required for non-canonical autophagy but not for canonical autophagy (PubMed:29317426). The WD repeats are required for the recruitment of LRRK2 to stressed lysosomes (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="23">Proteolytic cleavage by activated CASP3 leads to degradation and may regulate autophagy upon cellular stress and apoptotic stimuli.</text>
    </comment>
    <comment type="PTM">
        <text evidence="29">Phosphorylation at Ser-139 promotes association with the ATG12-ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.</text>
    </comment>
    <comment type="disease" evidence="5 6 7 8 9 11 12 24">
        <disease id="DI-02658">
            <name>Inflammatory bowel disease 10</name>
            <acronym>IBD10</acronym>
            <description>A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.</description>
            <dbReference type="MIM" id="611081"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="45">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="45">Belongs to the WD repeat ATG16 family.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="BAB15448" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB55412" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AY398617">
        <property type="protein sequence ID" value="AAR32130.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF079889">
        <property type="protein sequence ID" value="ABN48554.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF079890">
        <property type="protein sequence ID" value="ABN48555.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358182">
        <property type="protein sequence ID" value="AAQ88549.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK026330">
        <property type="protein sequence ID" value="BAB15448.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027854">
        <property type="protein sequence ID" value="BAB55412.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK123876">
        <property type="protein sequence ID" value="BAC85713.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC013726">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471063">
        <property type="protein sequence ID" value="EAW71034.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC071846">
        <property type="protein sequence ID" value="AAH71846.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL834526">
        <property type="protein sequence ID" value="CAD39182.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2502.2">
        <molecule id="Q676U5-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2503.2">
        <molecule id="Q676U5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54438.1">
        <molecule id="Q676U5-5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001177195.1">
        <property type="nucleotide sequence ID" value="NM_001190266.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001177196.1">
        <property type="nucleotide sequence ID" value="NM_001190267.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060444.3">
        <molecule id="Q676U5-2"/>
        <property type="nucleotide sequence ID" value="NM_017974.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_110430.5">
        <molecule id="Q676U5-1"/>
        <property type="nucleotide sequence ID" value="NM_030803.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942593.2">
        <molecule id="Q676U5-5"/>
        <property type="nucleotide sequence ID" value="NM_198890.3"/>
    </dbReference>
    <dbReference type="PDB" id="4GDK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="C/F=11-43"/>
    </dbReference>
    <dbReference type="PDB" id="4GDL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.88 A"/>
        <property type="chains" value="C=11-43"/>
    </dbReference>
    <dbReference type="PDB" id="4NAW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="C/G/K/O=11-43"/>
    </dbReference>
    <dbReference type="PDB" id="4TQ0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="B/D/F=1-69"/>
    </dbReference>
    <dbReference type="PDB" id="5D7G">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="B/D/F/H=1-69"/>
    </dbReference>
    <dbReference type="PDB" id="5NPV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="B/D=11-307"/>
    </dbReference>
    <dbReference type="PDB" id="5NPW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="B/D/F/H=11-307"/>
    </dbReference>
    <dbReference type="PDB" id="5NUV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.55 A"/>
        <property type="chains" value="A=303-607"/>
    </dbReference>
    <dbReference type="PDB" id="5ZYX">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=12-31"/>
    </dbReference>
    <dbReference type="PDB" id="7F69">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="C=207-236"/>
    </dbReference>
    <dbReference type="PDB" id="7W36">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="B=13-33"/>
    </dbReference>
    <dbReference type="PDB" id="7XFR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.76 A"/>
        <property type="chains" value="B/D=124-188"/>
    </dbReference>
    <dbReference type="PDB" id="8ZQG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.77 A"/>
        <property type="chains" value="C/D=124-188"/>
    </dbReference>
    <dbReference type="PDB" id="9J54">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.61 A"/>
        <property type="chains" value="B/D=235-247"/>
    </dbReference>
    <dbReference type="PDB" id="9JF2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.76 A"/>
        <property type="chains" value="C/D=235-247"/>
    </dbReference>
    <dbReference type="PDBsum" id="4GDK"/>
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    <dbReference type="PDBsum" id="4NAW"/>
    <dbReference type="PDBsum" id="4TQ0"/>
    <dbReference type="PDBsum" id="5D7G"/>
    <dbReference type="PDBsum" id="5NPV"/>
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    <dbReference type="PDBsum" id="8ZQG"/>
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    <dbReference type="PDBsum" id="9JF2"/>
    <dbReference type="AlphaFoldDB" id="Q676U5"/>
    <dbReference type="SMR" id="Q676U5"/>
    <dbReference type="BioGRID" id="120375">
        <property type="interactions" value="1142"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-200">
        <property type="entry name" value="ATG12-ATG5-ATG16L1 complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q676U5"/>
    <dbReference type="DIP" id="DIP-27552N"/>
    <dbReference type="DIP" id="DIP-50290N"/>
    <dbReference type="FunCoup" id="Q676U5">
        <property type="interactions" value="2957"/>
    </dbReference>
    <dbReference type="IntAct" id="Q676U5">
        <property type="interactions" value="1181"/>
    </dbReference>
    <dbReference type="MINT" id="Q676U5"/>
    <dbReference type="STRING" id="9606.ENSP00000375873"/>
    <dbReference type="TCDB" id="9.A.15.2.1">
        <property type="family name" value="the autophagy-related phagophore-formation transporter (apt) family"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q676U5"/>
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    <dbReference type="SwissPalm" id="Q676U5"/>
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    <dbReference type="MassIVE" id="Q676U5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000375872"/>
    <dbReference type="PeptideAtlas" id="Q676U5"/>
    <dbReference type="ProteomicsDB" id="65982">
        <molecule id="Q676U5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65983">
        <molecule id="Q676U5-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65984">
        <molecule id="Q676U5-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65985">
        <molecule id="Q676U5-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65986">
        <molecule id="Q676U5-5"/>
    </dbReference>
    <dbReference type="Pumba" id="Q676U5"/>
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        <property type="antibodies" value="881 antibodies from 43 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55054"/>
    <dbReference type="Ensembl" id="ENST00000347464.9">
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        <property type="protein sequence ID" value="ENSP00000318259.6"/>
        <property type="gene ID" value="ENSG00000085978.23"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000373525.9">
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        <property type="protein sequence ID" value="ENSP00000362625.5"/>
        <property type="gene ID" value="ENSG00000085978.23"/>
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    <dbReference type="Ensembl" id="ENST00000392017.9">
        <molecule id="Q676U5-1"/>
        <property type="protein sequence ID" value="ENSP00000375872.4"/>
        <property type="gene ID" value="ENSG00000085978.23"/>
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    <dbReference type="Ensembl" id="ENST00000392020.8">
        <molecule id="Q676U5-2"/>
        <property type="protein sequence ID" value="ENSP00000375875.4"/>
        <property type="gene ID" value="ENSG00000085978.23"/>
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    <dbReference type="Ensembl" id="ENST00000625501.3">
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        <property type="protein sequence ID" value="ENSP00000487542.1"/>
        <property type="gene ID" value="ENSG00000281089.3"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000626623.2">
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        <property type="protein sequence ID" value="ENSP00000487298.1"/>
        <property type="gene ID" value="ENSG00000281089.3"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000630066.2">
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        <property type="protein sequence ID" value="ENSP00000487446.1"/>
        <property type="gene ID" value="ENSG00000281089.3"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000630204.2">
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        <property type="protein sequence ID" value="ENSP00000487455.1"/>
        <property type="gene ID" value="ENSG00000281089.3"/>
    </dbReference>
    <dbReference type="GeneID" id="55054"/>
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        <property type="protein sequence ID" value="ENSP00000375872.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_030803.7"/>
        <property type="RefSeq protein sequence ID" value="NP_110430.5"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002vtx.3">
        <molecule id="Q676U5-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:21498"/>
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        <property type="gene designation" value="ATG16L1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000085978">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ATG16L1"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="type" value="phenotype"/>
    </dbReference>
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    <dbReference type="OrthoDB" id="6262491at2759"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q676U5"/>
    <dbReference type="PathwayCommons" id="Q676U5"/>
    <dbReference type="Reactome" id="R-HSA-1632852">
        <property type="pathway name" value="Macroautophagy"/>
    </dbReference>
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    <dbReference type="Agora" id="ENSG00000085978"/>
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        <property type="hits" value="18 hits in 1168 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ATG16L1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q676U5"/>
    <dbReference type="GeneWiki" id="ATG16L1"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q676U5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q676U5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000085978">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 149 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q676U5">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034274">
        <property type="term" value="C:Atg12-Atg5-Atg16 complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005776">
        <property type="term" value="C:autophagosome"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000421">
        <property type="term" value="C:autophagosome membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
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    <dbReference type="PANTHER" id="PTHR19878">
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    <dbReference type="PANTHER" id="PTHR19878:SF6">
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    <dbReference type="Pfam" id="PF08614">
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        <property type="match status" value="5"/>
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    <dbReference type="PRINTS" id="PR00320">
        <property type="entry name" value="GPROTEINBRPT"/>
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    <dbReference type="SMART" id="SM00320">
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    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
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        <property type="match status" value="3"/>
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    <dbReference type="PROSITE" id="PS50082">
        <property type="entry name" value="WD_REPEATS_2"/>
        <property type="match status" value="6"/>
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    <dbReference type="PROSITE" id="PS50294">
        <property type="entry name" value="WD_REPEATS_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0072">Autophagy</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000050848" description="Autophagy-related protein 16-1">
        <location>
            <begin position="1"/>
            <end position="607"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1" evidence="3">
        <location>
            <begin position="320"/>
            <end position="359"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2" evidence="3">
        <location>
            <begin position="364"/>
            <end position="403"/>
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    </feature>
    <feature type="repeat" description="WD 3" evidence="3">
        <location>
            <begin position="406"/>
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    </feature>
    <feature type="repeat" description="WD 4" evidence="3">
        <location>
            <begin position="447"/>
            <end position="484"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5" evidence="3">
        <location>
            <begin position="486"/>
            <end position="525"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6" evidence="3">
        <location>
            <begin position="532"/>
            <end position="573"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7" evidence="3">
        <location>
            <begin position="575"/>
            <end position="607"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with ATG5" evidence="26">
        <location>
            <begin position="13"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="region of interest" description="WIPI2-binding" evidence="25">
        <location>
            <begin position="207"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="region of interest" description="RB1CC1-binding" evidence="20 25">
        <location>
            <begin position="230"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="78"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Caspase cleavage" evidence="23">
        <location>
            <begin position="296"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CK2" evidence="29">
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="48">
        <location>
            <position position="269"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="47 48 49">
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013389" description="In isoform 4 and isoform 5." evidence="41 44">
        <location>
            <begin position="70"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013386" description="In isoform 2 and isoform 5." evidence="41 42 44">
        <location>
            <begin position="266"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013390" description="In isoform 4." evidence="41">
        <location>
            <begin position="334"/>
            <end position="368"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013387" description="In isoform 3." evidence="40">
        <original>IKTVFAGSSCNDIVCTEQCVMSGHFDKK</original>
        <variation>EEIQSLCLCICLDVSVEVCVCTSEPAFM</variation>
        <location>
            <begin position="443"/>
            <end position="470"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013388" description="In isoform 3." evidence="40">
        <location>
            <begin position="471"/>
            <end position="607"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021834" description="Risk factor for IBD10; has no effect on the stability of the protein under normal conditions; enhances the cleavage and the degradation mediated by activated CASP3; results in reduced autophagy and defective clearance of intestinal pathogens; impairs interaction with TMEM59; slows TMEM59 intracellular trafficking; increases production of type I IFNs; dbSNP:rs2241880." evidence="4 5 7 8 9 11 12 23 24 27 32">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_053386" description="In dbSNP:rs1866878.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with ATG5." evidence="26">
        <original>I</original>
        <variation>W</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with ATG5." evidence="26">
        <original>L</original>
        <variation>W</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with ATG5." evidence="26">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In FII mutant; abolished binding to membranes and lipidation to ATG8 family proteins." evidence="36">
        <original>FEEII</original>
        <variation>AEEAA</variation>
        <location>
            <begin position="32"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces interaction with ATG5." evidence="26">
        <original>I</original>
        <variation>W</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes phosphorylation. Impairs interaction with ATG12-ATG5 complex." evidence="29">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased binding affinity by 36-fold with RAB33B. Decreased binding affinity by 254-fold with RAB33B and colocalization to phagophore; when associated with A-209. No change in interaction with ATG5-ATG12 complex; when associated with A-209." evidence="37">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased binding affinity by 9-fold with RAB33B. Decreased binding affinity by 254-fold with RAB33B and colocalization to phagophore; when associated with A-206. No change in interaction with ATG5-ATG12 complex; when associated with A-209." evidence="37">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs interaction with WIPI2." evidence="25">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs interaction with WIPI2." evidence="25">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="230"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Prevents cleavage by activated CASP3." evidence="23">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In VRV mutant; abolished binding to membranes and lipidation to ATG8 family proteins." evidence="36">
        <original>VRV</original>
        <variation>AAA</variation>
        <location>
            <begin position="308"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished non-canonical autophagy without affecting canonical autophagy." evidence="34 36">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="467"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished non-canonical autophagy without affecting canonical autophagy. Impaired conjugation of phosphatidylserine (PS) to LC3 proteins." evidence="34 39">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="490"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs interaction with PPP1CA; when associated with A-542." evidence="29">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="540"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs interaction with PPP1CA; when associated with A-540." evidence="29">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="542"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; BAB55412." evidence="45" ref="6">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; BAB55412." evidence="45" ref="6">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; BAB55412." evidence="45" ref="6">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="helix" evidence="50">
        <location>
            <begin position="12"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="helix" evidence="50">
        <location>
            <begin position="30"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="helix" evidence="53">
        <location>
            <begin position="127"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="helix" evidence="52">
        <location>
            <begin position="210"/>
            <end position="228"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="313"/>
            <end position="319"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="321"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="325"/>
            <end position="330"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="334"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="346"/>
            <end position="351"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="356"/>
            <end position="362"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="369"/>
            <end position="374"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="378"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="390"/>
            <end position="394"/>
        </location>
    </feature>
    <feature type="turn" evidence="51">
        <location>
            <begin position="395"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="399"/>
            <end position="404"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="411"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="422"/>
            <end position="427"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="430"/>
            <end position="436"/>
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    </feature>
    <feature type="turn" evidence="51">
        <location>
            <begin position="437"/>
            <end position="440"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="441"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="452"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="459"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="469"/>
            <end position="475"/>
        </location>
    </feature>
    <feature type="turn" evidence="51">
        <location>
            <begin position="476"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="strand" evidence="51">
        <location>
            <begin position="480"/>
            <end position="486"/>
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<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="220" xmlns="https://uniprot.org/uniprot">
    <accession>P36639</accession>
    <accession>A4D205</accession>
    <accession>Q6LES7</accession>
    <accession>Q6P0Y6</accession>
    <accession>Q7Z7N6</accession>
    <accession>Q8IV95</accession>
    <accession>Q9UBM0</accession>
    <accession>Q9UBM9</accession>
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            <fullName>2-hydroxy-dATP diphosphatase</fullName>
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        <alternativeName>
            <fullName>7,8-dihydro-8-oxoguanine triphosphatase</fullName>
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        <alternativeName>
            <fullName>8-oxo-dGTPase</fullName>
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            <fullName evidence="36">Methylated purine nucleoside triphosphate hydrolase</fullName>
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            <fullName>Nucleoside diphosphate-linked moiety X motif 1</fullName>
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        <name type="primary">NUDT1</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P18)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
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            <dbReference type="PubMed" id="7713500"/>
            <dbReference type="DOI" id="10.1006/geno.1994.1657"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="9211940"/>
            <dbReference type="DOI" id="10.1074/jbc.272.28.17843"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P18)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <scope>VARIANT MET-83</scope>
    </reference>
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            <dbReference type="PubMed" id="10536140"/>
            <dbReference type="DOI" id="10.1093/nar/27.22.4335"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P18/P21/P22/P26)</scope>
        <scope>ALTERNATIVE INITIATION</scope>
        <scope>POLYMORPHISM</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="12690205"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P18)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Irlbacher H."/>
                <person name="Meyer H."/>
                <person name="Queisser N."/>
                <person name="Bauser M."/>
                <person name="Haegebarth A."/>
                <person name="Gorjanacz M."/>
            </authorList>
            <dbReference type="PubMed" id="28679043"/>
            <dbReference type="DOI" id="10.1021/acschembio.7b00370"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS)</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="51 52 53 54 55 56 57 60" key="29">
        <citation type="journal article" date="2017" name="J. Biol. Chem." volume="292" first="2785" last="2794">
            <title>Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity.</title>
            <authorList>
                <person name="Waz S."/>
                <person name="Nakamura T."/>
                <person name="Hirata K."/>
                <person name="Koga-Ogawa Y."/>
                <person name="Chirifu M."/>
                <person name="Arimori T."/>
                <person name="Tamada T."/>
                <person name="Ikemizu S."/>
                <person name="Nakabeppu Y."/>
                <person name="Yamagata Y."/>
            </authorList>
            <dbReference type="PubMed" id="28035004"/>
            <dbReference type="DOI" id="10.1074/jbc.m116.749713"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) IN COMPLEXES WITH 8-OXO-DGTP AND 2-OXO-DATP</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-120</scope>
    </reference>
    <reference evidence="59" key="30">
        <citation type="journal article" date="2018" name="Nucleic Acids Res." volume="46" first="10888" last="10904">
            <title>MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP.</title>
            <authorList>
                <person name="Jemth A.S."/>
                <person name="Gustafsson R."/>
                <person name="Braeutigam L."/>
                <person name="Henriksson L."/>
                <person name="Vallin K.S.A."/>
                <person name="Sarno A."/>
                <person name="Almloef I."/>
                <person name="Homan E."/>
                <person name="Rasti A."/>
                <person name="Warpman Berglund U."/>
                <person name="Stenmark P."/>
                <person name="Helleday T."/>
            </authorList>
            <dbReference type="PubMed" id="30304478"/>
            <dbReference type="DOI" id="10.1093/nar/gky896"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH O(6)-METHYL-DGMP</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>REGION</scope>
    </reference>
    <reference evidence="61" key="31">
        <citation type="journal article" date="2020" name="J. Biol. Chem." volume="295" first="4761" last="4772">
            <title>MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.</title>
            <authorList>
                <person name="Scaletti E.R."/>
                <person name="Vallin K.S."/>
                <person name="Braeutigam L."/>
                <person name="Sarno A."/>
                <person name="Warpman Berglund U."/>
                <person name="Helleday T."/>
                <person name="Stenmark P."/>
                <person name="Jemth A.S."/>
            </authorList>
            <dbReference type="PubMed" id="32144205"/>
            <dbReference type="DOI" id="10.1074/jbc.ra120.012636"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) IN COMPLEX WITH N(6)-METHYL-AMP</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="2004" name="Endocr. J." volume="51" first="493" last="498">
            <title>Association study of human MTH1 gene polymorphisms with type 1 diabetes mellitus.</title>
            <authorList>
                <person name="Miyako K."/>
                <person name="Kohno H."/>
                <person name="Ihara K."/>
                <person name="Kuromaru R."/>
                <person name="Matsuura N."/>
                <person name="Hara T."/>
            </authorList>
            <dbReference type="PubMed" id="15516784"/>
            <dbReference type="DOI" id="10.1507/endocrj.51.493"/>
        </citation>
        <scope>VARIANT MET-83</scope>
    </reference>
    <reference key="33">
        <citation type="journal article" date="2006" name="Carcinogenesis" volume="27" first="2448" last="2454">
            <title>Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk.</title>
            <authorList>
                <person name="Kohno T."/>
                <person name="Sakiyama T."/>
                <person name="Kunitoh H."/>
                <person name="Goto K."/>
                <person name="Nishiwaki Y."/>
                <person name="Saito D."/>
                <person name="Hirose H."/>
                <person name="Eguchi T."/>
                <person name="Yanagitani N."/>
                <person name="Saito R."/>
                <person name="Sasaki-Matsumura R."/>
                <person name="Mimaki S."/>
                <person name="Toyama K."/>
                <person name="Yamamoto S."/>
                <person name="Kuchiba A."/>
                <person name="Sobue T."/>
                <person name="Ohta T."/>
                <person name="Ohki M."/>
                <person name="Yokota J."/>
            </authorList>
            <dbReference type="PubMed" id="16774934"/>
            <dbReference type="DOI" id="10.1093/carcin/bgl095"/>
        </citation>
        <scope>VARIANT MET-83</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6 7 8 9 13 16 17 18 19 20 21 22 23 24 25 27">Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool (PubMed:10608900, PubMed:12857738, PubMed:22556419, PubMed:24695224, PubMed:24695225, PubMed:26238318, PubMed:28679043, PubMed:7713500, PubMed:8226881). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP (PubMed:10373420). Also has a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:10373420, PubMed:11139615). Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A (PubMed:10373420, PubMed:10608900, PubMed:11756418, PubMed:12857738, PubMed:16607562, PubMed:24695224, PubMed:24695225, PubMed:26999531, PubMed:28035004, PubMed:8226881). Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA (PubMed:30304478, PubMed:32144205). Through this antimutagenic activity protects cells from oxidative stress (PubMed:10608900, PubMed:12857738, PubMed:24695224, PubMed:24695225, PubMed:30304478, PubMed:32144205, PubMed:7713500, PubMed:8226881).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6 7 8 9 13 15 16 17 18 20 21 23 26 27">
            <text>2-oxo-dATP + H2O = 2-oxo-dAMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:31583"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:63212"/>
            <dbReference type="ChEBI" id="CHEBI:77897"/>
            <dbReference type="EC" id="3.6.1.56"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="31">
            <dbReference type="Rhea" id="RHEA:31584"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>2-oxo-ATP + H2O = 2-oxo-AMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67392"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:71395"/>
            <dbReference type="ChEBI" id="CHEBI:172878"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="32">
            <dbReference type="Rhea" id="RHEA:67393"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6 7 8 9 13 15 16 17 18 20 21 23 26 27">
            <text>8-oxo-dGTP + H2O = 8-oxo-dGMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:31575"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:63224"/>
            <dbReference type="ChEBI" id="CHEBI:77896"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="31">
            <dbReference type="Rhea" id="RHEA:31576"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>8-oxo-dATP + H2O = 8-oxo-dAMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:65396"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:71361"/>
            <dbReference type="ChEBI" id="CHEBI:172871"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="32">
            <dbReference type="Rhea" id="RHEA:65397"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="23">
            <text>O(6)-methyl-dGTP + H2O = O(6)-methyl-dGMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67600"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:169974"/>
            <dbReference type="ChEBI" id="CHEBI:169975"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="36">
            <dbReference type="Rhea" id="RHEA:67601"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="24">
            <text>N(6)-methyl-dATP + H2O = N(6)-methyl-dAMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67604"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:169976"/>
            <dbReference type="ChEBI" id="CHEBI:172872"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:67605"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="24">
            <text>N(6)-methyl-ATP + H2O = N(6)-methyl-AMP + diphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67608"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
            <dbReference type="ChEBI" id="CHEBI:172873"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:67609"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1 34">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="1 34">Binds 2 Mg(2+) ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">Inhibited by 2-oxo-dADP and 8-oxo-dGDP.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">8.3 uM for 2-oxo-dATP (at 30 degrees Celsius and pH 8.0)</KM>
            <KM evidence="4">5.7 uM for 2-oxo-dATP (at 30 degrees Celsius and pH 7.2)</KM>
            <KM evidence="7">4.3 uM for 2-oxo-ATP (at 30 degrees Celsius and pH 8.0)</KM>
            <KM evidence="4">13.9 uM for 8-oxo-dATP (at 30 degrees Celsius and pH 8.0)</KM>
            <KM evidence="4">15.2 uM for 8-oxo-dGTP (at 30 degrees Celsius and pH 8.0)</KM>
            <KM evidence="4">12.8 uM for 8-oxo-dGTP (at 30 degrees Celsius and pH 7.2)</KM>
            <KM evidence="15">13.2 uM for 8-oxo-dGTP (at 22 degrees Celsius and pH 7.5)</KM>
            <KM evidence="7">258 uM for dGTP (at 30 degrees Celsius and pH 8.0)</KM>
            <KM evidence="24">40.9 uM for N(6)-methyl-dATP (at pH 7.5)</KM>
            <KM evidence="23">15.6 uM for O(6)-methyl-dGTP (at 22 degrees Celsius and pH 7.5)</KM>
            <KM evidence="24">16.5 uM for O(6)-methyl-dGTP (at pH 7.5)</KM>
            <KM evidence="23">236 uM for O(6)-methyl-GTP (at 22 degrees Celsius and pH 7.5)</KM>
            <text evidence="4 7 23 24">kcat is 13.9 sec(-1) with 2-oxo-dATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 4.7 sec(-1) with 2-oxo-dATP as substrate (at 30 degrees Celsius and pH 7.2) (PubMed:10373420). kcat is 4.7 sec(-1) with 2-oxo-ATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:11139615). kcat is 12.3 sec(-1) with 8-oxo-dGTP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 2.1 sec(-1) with 8-oxo-dGTP as substrate (at 30 degrees Celsius and pH 7.2) (PubMed:10373420). kcat is 10.8 sec(-1) with 8-oxo-dATP as substrate (at 30 degrees Celsius and pH 8.0) (PubMed:10373420). kcat is 5.4 sec(-1) with O(6)-methyl-dGTP as substrate (at pH 7.5) (PubMed:32144205). kcat is 2.0 sec(-1) with N(6)-methyl-dATP as substrate (at pH 7.5) (PubMed:32144205). kcat is 8.2 sec(-1) with O(6)-methyl-dGTP as substrate (PubMed:30304478). kcat is 0.3 sec(-1) with O(6)-methyl-GTP as substrate (PubMed:30304478). Shows the best catalytic efficiency for the 2-oxo-dATP substrate (PubMed:10373420, PubMed:11139615). Shows a similar catalytic efficiency for 8-oxo-dGTP and O(6)-methyl-dGTP (PubMed:30304478).</text>
        </kinetics>
        <phDependence>
            <text evidence="4 7 15">Optimum pH is 7.8-8.2 with 8-oxo-dGTP as substrate, and 8.0-8.5 with 2-oxo-dATP as substrate.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="10 15">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048967">
            <id>P36639</id>
        </interactant>
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
            <label>ACY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1048967">
            <id>P36639</id>
        </interactant>
        <interactant intactId="EBI-10207332">
            <id>V9HWA0</id>
            <label>HEL-S-5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12380931">
            <id>P36639-2</id>
        </interactant>
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
            <label>ACY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12380931">
            <id>P36639-2</id>
        </interactant>
        <interactant intactId="EBI-12414373">
            <id>Q8IVF7-3</id>
            <label>FMNL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12380931">
            <id>P36639-2</id>
        </interactant>
        <interactant intactId="EBI-10242598">
            <id>Q53H54</id>
            <label>TRMT12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-718729">
            <id>P55212</id>
            <label>CASP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-473886">
            <id>O00291</id>
            <label>HIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-712096">
            <id>P30519</id>
            <label>HMOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-352682">
            <id>P04792</id>
            <label>HSPB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-10975473">
            <id>O60333-2</id>
            <label>KIF1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-21591415">
            <id>P13473-2</id>
            <label>LAMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-286642">
            <id>P62826</id>
            <label>RAN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-396669">
            <id>Q9Y3C5</id>
            <label>RNF11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25834643">
            <id>P36639-4</id>
        </interactant>
        <interactant intactId="EBI-720609">
            <id>O76024</id>
            <label>WFS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform p18</molecule>
        <subcellularLocation>
            <location evidence="9 13 26">Cytoplasm</location>
            <location evidence="9 13 26">Cytosol</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="26 33 35">Mitochondrion matrix</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 26">Nucleus</location>
        </subcellularLocation>
        <text evidence="13 26">Mostly present in cytosol (PubMed:7782328). A minor proportion is mitochondrial (PubMed:7782328). A very small amount of the protein is associated with nuclei (PubMed:7782328).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform p26</molecule>
        <subcellularLocation>
            <location evidence="13">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>P36639-4</id>
            <name>p18</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P36639-1</id>
            <name>p26</name>
            <sequence type="described" ref="VSP_061190"/>
        </isoform>
        <isoform>
            <id>P36639-2</id>
            <name>p22</name>
            <sequence type="described" ref="VSP_061189"/>
        </isoform>
        <isoform>
            <id>P36639-3</id>
            <name>p21</name>
            <sequence type="described" ref="VSP_061188"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="28">Widely expressed with highest expression in thymus, testis, embryo and proliferating blood lymphocytes.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="28">In peripheral blood lymphocytes, expressed at much higher levels in proliferating cells than in resting cells.</text>
    </comment>
    <comment type="PTM">
        <text>The N-terminus is blocked.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="5">A polymorphism between Met-1 and Met-19 removes a stop codon before the initiation codon for isoform p22 and gives rise to the production of isoform p26. The allele frequency of isoform p26 is about 20%.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform p26</molecule>
        <text evidence="2">Contains a predicted transit peptide (1-18) for localization to the mitochondrion.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform p26</molecule>
        <text>Derived from a B-type mRNA with a polymorphic alteration (GU--&gt;GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream.</text>
    </comment>
    <comment type="similarity">
        <text evidence="30">Belongs to the Nudix hydrolase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="17 18 22">The role in cancer cell survival is under debate. Was originally considered to play a role as a sanitizing enzyme for oxidized nucleotide pools, and thus important for the survival of cancer cells (PubMed:24695224, PubMed:24695225). A later study indicates that NUDT1 plays a redundant role in eliminating oxidized nucleotides and that it is not essential for cancer cell proliferation and survival (PubMed:28679043).</text>
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        <property type="term" value="F:hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ZFIN"/>
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    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
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        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0106431">
        <property type="term" value="F:N6-methyl-(d)ATP hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
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    <dbReference type="GO" id="GO:0106433">
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        <property type="project" value="RHEA"/>
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    <dbReference type="GO" id="GO:0030515">
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        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0042262">
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006281">
        <property type="term" value="P:DNA repair"/>
        <property type="evidence" value="ECO:0000305"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006152">
        <property type="term" value="P:purine nucleoside catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006979">
        <property type="term" value="P:response to oxidative stress"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd03427">
        <property type="entry name" value="NUDIX_MTH1_Nudt1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.79.10:FF:000043">
        <property type="entry name" value="7,8-dihydro-8-oxoguanine triphosphatase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.79.10">
        <property type="entry name" value="Nucleoside Triphosphate Pyrophosphohydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003563">
        <property type="entry name" value="8ODP"/>
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    <dbReference type="InterPro" id="IPR015797">
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    <dbReference type="PANTHER" id="PTHR43758">
        <property type="entry name" value="7,8-DIHYDRO-8-OXOGUANINE TRIPHOSPHATASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43758:SF2">
        <property type="entry name" value="OXIDIZED PURINE NUCLEOSIDE TRIPHOSPHATE HYDROLASE"/>
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    <dbReference type="Pfam" id="PF00293">
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01403">
        <property type="entry name" value="8OXTPHPHTASE"/>
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    <dbReference type="PRINTS" id="PR00502">
        <property type="entry name" value="NUDIXFAMILY"/>
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00893">
        <property type="entry name" value="NUDIX_BOX"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="chain" id="PRO_0000019944" description="Oxidized purine nucleoside triphosphate hydrolase">
        <location>
            <begin position="1"/>
            <end position="156"/>
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    <feature type="domain" description="Nudix hydrolase" evidence="3">
        <location>
            <begin position="3"/>
            <end position="132"/>
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    </feature>
    <feature type="short sequence motif" description="Nudix box" evidence="3">
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            <begin position="37"/>
            <end position="58"/>
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    </feature>
    <feature type="binding site" evidence="21 52 54 57 60">
        <location>
            <position position="8"/>
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        <ligand>
            <name>2-oxo-dATP</name>
            <dbReference type="ChEBI" id="CHEBI:77897"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="15 39">
        <location>
            <position position="8"/>
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        <ligand>
            <name>8-oxo-dGMP</name>
            <dbReference type="ChEBI" id="CHEBI:63224"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 21 45 51">
        <location>
            <position position="8"/>
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        <ligand>
            <name>8-oxo-dGTP</name>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="24 61">
        <location>
            <position position="8"/>
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        <ligand>
            <name>N(6)-methyl-AMP</name>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
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    </feature>
    <feature type="binding site" evidence="23 59">
        <location>
            <position position="8"/>
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        <ligand>
            <name>O(6)-methyl-dGMP</name>
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    </feature>
    <feature type="binding site" evidence="15 39">
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            <position position="23"/>
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        <ligand>
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        <ligand>
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        <ligand>
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    <feature type="binding site" evidence="20 46">
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        <ligand>
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    </feature>
    <feature type="binding site" evidence="21 52 57">
        <location>
            <position position="33"/>
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        <ligand>
            <name>2-oxo-dATP</name>
            <dbReference type="ChEBI" id="CHEBI:77897"/>
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    </feature>
    <feature type="binding site" evidence="15 39">
        <location>
            <position position="33"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:63224"/>
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    </feature>
    <feature type="binding site" evidence="20 21 45 51 53 55">
        <location>
            <position position="33"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:77896"/>
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    </feature>
    <feature type="binding site" evidence="23 59">
        <location>
            <position position="33"/>
        </location>
        <ligand>
            <name>O(6)-methyl-dGMP</name>
            <dbReference type="ChEBI" id="CHEBI:169975"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21 52 54 57 60">
        <location>
            <begin position="35"/>
            <end position="38"/>
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        <ligand>
            <name>2-oxo-dATP</name>
            <dbReference type="ChEBI" id="CHEBI:77897"/>
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    </feature>
    <feature type="binding site" evidence="20 46">
        <location>
            <begin position="35"/>
            <end position="38"/>
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        <ligand>
            <name>8-oxo-ATP</name>
            <dbReference type="ChEBI" id="CHEBI:189076"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 21 45 51 53">
        <location>
            <begin position="35"/>
            <end position="38"/>
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        <ligand>
            <name>8-oxo-dGTP</name>
            <dbReference type="ChEBI" id="CHEBI:77896"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="36"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 46">
        <location>
            <position position="52"/>
        </location>
        <ligand>
            <name>8-oxo-ATP</name>
            <dbReference type="ChEBI" id="CHEBI:189076"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="52"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="55"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 46">
        <location>
            <position position="56"/>
        </location>
        <ligand>
            <name>8-oxo-ATP</name>
            <dbReference type="ChEBI" id="CHEBI:189076"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="56"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="100"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21 52 54 57 60">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>2-oxo-dATP</name>
            <dbReference type="ChEBI" id="CHEBI:77897"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 46">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>8-oxo-ATP</name>
            <dbReference type="ChEBI" id="CHEBI:189076"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="15 39">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>8-oxo-dGMP</name>
            <dbReference type="ChEBI" id="CHEBI:63224"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20 21 45 51 53 55">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>8-oxo-dGTP</name>
            <dbReference type="ChEBI" id="CHEBI:77896"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="24 61">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>N(6)-methyl-AMP</name>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="23 59">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
        <ligand>
            <name>O(6)-methyl-dGMP</name>
            <dbReference type="ChEBI" id="CHEBI:169975"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_061188" description="In isoform p21.">
        <original>M</original>
        <variation>MGEPEGSWSGKNPGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_061189" description="In isoform p22.">
        <original>M</original>
        <variation>MSGISPQQMGEPEGSWSGKNPGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_061190" description="In isoform p26.">
        <original>M</original>
        <variation>MYWSNQITRRLGERVQGFMSGISPQQMGEPEGSWSGKNPGTM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068715" description="In dbSNP:rs11547459.">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013757" description="Decreased localization to mitochondrion; dbSNP:rs4866." evidence="11 12 13 14 28">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="83"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 97%." evidence="6">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>G</original>
        <variation>F</variation>
        <location>
            <position position="37"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="39"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 97%." evidence="6">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="40"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 60%." evidence="6">
        <original>G</original>
        <variation>I</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>I</original>
        <variation>K</variation>
        <location>
            <position position="45"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>D</original>
        <variation>P</variation>
        <location>
            <position position="47"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>G</original>
        <variation>M</variation>
        <location>
            <position position="48"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="49"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="53"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="54"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="55"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of ability to prevent DNA damage. Expected to cause loss of enzyme activity." evidence="17">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="56"/>
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    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>E</original>
        <variation>Y</variation>
        <location>
            <position position="56"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="57"/>
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    </feature>
    <feature type="mutagenesis site" description="Greatly reduces or abolishes 2-oxo-dATPase and 8-oxo-dGTPase activities." evidence="8">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="117"/>
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    </feature>
    <feature type="mutagenesis site" description="Enhances 2-oxo-dATPase activity and greatly reduces 8-oxo-dGTPase activity." evidence="8">
        <original>W</original>
        <variation>Y</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of 2-oxo-dATPase activity, reduces 8-oxo-dGTPase activity." evidence="8">
        <original>D</original>
        <variation>A</variation>
        <variation>N</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Mildly decreased 2-oxo-dATPase activity, nearly abolishes 8-oxo-dGTPase activity." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <variation>N</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <location>
            <begin position="151"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <location>
            <begin position="152"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <location>
            <begin position="153"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly enhances 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <location>
            <begin position="154"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Enhances 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly reduces 2-oxo-dATPase and 8-oxo-dGTPase activities and increases thermolability." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="156"/>
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    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="4"/>
            <end position="13"/>
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    </feature>
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    <sequence length="156" mass="17952" checksum="B9FB669FF0ACFF5F" modified="2021-09-29" version="4">MGASRLYTLVLVLQPQRVLLGMKKRGFGAGRWNGFGGKVQEGETIEDGARRELQEESGLTVDALHKVGQIVFEFVGEPELMDVHVFCTDSIQGTPVESDEMRPCWFQLDQIPFKDMWPDDSYWFPLLLQKKKFHGYFKFQGQDTILDYTLREVDTV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-12-20" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
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    <accession>Q9NZD3</accession>
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        <recommendedName>
            <fullName>APOBEC1 complementation factor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>APOBEC1-stimulating protein</fullName>
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        <name type="primary">A1CF</name>
        <name type="synonym">ACF</name>
        <name evidence="23" type="synonym">ASP</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference evidence="18 23" key="1">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="19848" last="19856">
            <title>Purification and molecular cloning of a novel essential component of the apolipoprotein B mRNA editing enzyme-complex.</title>
            <authorList>
                <person name="Lellek H."/>
                <person name="Kirsten R."/>
                <person name="Diehl I."/>
                <person name="Apostel F."/>
                <person name="Buck F."/>
                <person name="Greeve J."/>
            </authorList>
            <dbReference type="PubMed" id="10781591"/>
            <dbReference type="DOI" id="10.1074/jbc.m001786200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH APOBEC1</scope>
        <source>
            <tissue evidence="23">Liver</tissue>
            <tissue evidence="24">Small intestine</tissue>
        </source>
    </reference>
    <reference evidence="18 19" key="2">
        <citation type="journal article" date="2000" name="Mol. Cell. Biol." volume="20" first="1846" last="1854">
            <title>Molecular cloning of APOBEC-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA.</title>
            <authorList>
                <person name="Mehta A."/>
                <person name="Kinter M.T."/>
                <person name="Sherman N.E."/>
                <person name="Driscoll D.M."/>
            </authorList>
            <dbReference type="PubMed" id="10669759"/>
            <dbReference type="DOI" id="10.1128/mcb.20.5.1846-1854.2000"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH APOBEC1</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference evidence="18 20" key="3">
        <citation type="submission" date="2000-05" db="EMBL/GenBank/DDBJ databases">
            <title>Human APOBEC-1 complementation factor related protein.</title>
            <authorList>
                <person name="Sowden M.P."/>
                <person name="Smith H.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference evidence="18 22" key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4)</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference evidence="21" key="5">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
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            </authorList>
            <dbReference type="PubMed" id="15164054"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4)</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="10272" last="10283">
            <title>Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing.</title>
            <authorList>
                <person name="Blanc V."/>
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            </authorList>
            <dbReference type="PubMed" id="11134005"/>
            <dbReference type="DOI" id="10.1074/jbc.m006435200"/>
        </citation>
        <scope>INTERACTION WITH SYNCRIP</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="47338" last="47351">
            <title>Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor.</title>
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            <dbReference type="PubMed" id="11577082"/>
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        </citation>
        <scope>INTERACTION WITH CELF2</scope>
    </reference>
    <reference evidence="18" key="10">
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            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="11718896"/>
            <dbReference type="DOI" id="10.1016/s0167-4781(01)00295-0"/>
        </citation>
        <scope>GENE STRUCTURE</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference evidence="18" key="11">
        <citation type="journal article" date="2002" name="RNA" volume="8" first="69" last="82">
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                <person name="Mehta A."/>
                <person name="Driscoll D.M."/>
            </authorList>
            <dbReference type="PubMed" id="11871661"/>
            <dbReference type="DOI" id="10.1017/s1355838202015649"/>
        </citation>
        <scope>RNA-BINDING DOMAIN</scope>
        <scope>MUTAGENESIS OF PHE-59; PHE-100; PHE-139; PHE-183; TYR-234 AND PHE-270</scope>
    </reference>
    <reference evidence="18" key="12">
        <citation type="journal article" date="2003" name="EMBO J." volume="22" first="3971" last="3982">
            <title>The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay.</title>
            <authorList>
                <person name="Chester A."/>
                <person name="Somasekaram A."/>
                <person name="Tzimina M."/>
                <person name="Jarmuz A."/>
                <person name="Gisbourne J."/>
                <person name="O'Keefe R."/>
                <person name="Scott J."/>
                <person name="Navaratnam N."/>
            </authorList>
            <dbReference type="PubMed" id="12881431"/>
            <dbReference type="DOI" id="10.1093/emboj/cdg369"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="18" key="13">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="41198" last="41204">
            <title>A novel nuclear localization signal in the auxiliary domain of apobec-1 complementation factor regulates nucleocytoplasmic import and shuttling.</title>
            <authorList>
                <person name="Blanc V."/>
                <person name="Kennedy S."/>
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            </authorList>
            <dbReference type="PubMed" id="12896982"/>
            <dbReference type="DOI" id="10.1074/jbc.m302951200"/>
        </citation>
        <scope>NUCLEAR LOCALIZATION SIGNAL</scope>
        <scope>INTERACTION WITH TNPO2</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2014" name="EMBO Rep." volume="15" first="903" last="910">
            <title>C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47.</title>
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                <person name="Fossat N."/>
                <person name="Tourle K."/>
                <person name="Radziewic T."/>
                <person name="Barratt K."/>
                <person name="Liebhold D."/>
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            </authorList>
            <dbReference type="PubMed" id="24916387"/>
            <dbReference type="DOI" id="10.15252/embr.201438450"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RBM47</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-499</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference evidence="18 20" key="16">
        <citation type="submission" date="2005-11" db="PDB data bank">
            <title>Solution structure of the RNA recognition motif of human APOBEC-1 complementation factor, ACF.</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 223-308</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 9 11">Essential component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in APOB mRNA. Binds to APOB mRNA and is probably responsible for docking the catalytic subunit, APOBEC1, to the mRNA to allow it to deaminate its target cytosine. The complex also protects the edited APOB mRNA from nonsense-mediated decay.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 5 6 10 11">Part of the apolipoprotein B mRNA editing complex with APOBEC1 (PubMed:10669759, PubMed:10781591). Interacts with TNPO2; TNPO2 may be responsible for transport of A1CF into the nucleus (PubMed:12896982). Interacts with SYNCRIP (PubMed:11134005). Interacts with CELF2/CUGBP2 (PubMed:11577082). Interacts with RBM47 (PubMed:24916387).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
            <label>ACTMAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-3867333">
            <id>A8MQ03</id>
            <label>CYSRT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-10694655">
            <id>Q7L591-3</id>
            <label>DOK3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-947964">
            <id>Q16610</id>
            <label>ECM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-12012124">
            <id>Q04637-9</id>
            <label>EIF4G1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-701903">
            <id>Q14192</id>
            <label>FHL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-741101">
            <id>Q13643</id>
            <label>FHL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-739395">
            <id>Q16082</id>
            <label>HSPB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-9478422">
            <id>Q96G42</id>
            <label>KLHDC7B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-1047093">
            <id>O76011</id>
            <label>KRT34</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-8487781">
            <id>Q8N6F8</id>
            <label>METTL27</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-536879">
            <id>O43482</id>
            <label>OIP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-949255">
            <id>Q58EX7</id>
            <label>PLEKHG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-1389308">
            <id>Q7Z3K3</id>
            <label>POGZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-307352">
            <id>Q04864</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-10182375">
            <id>Q9UFD9</id>
            <label>RIMBP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-10269322">
            <id>Q8NCR6</id>
            <label>SPMIP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809489">
            <id>Q9NQ94</id>
        </interactant>
        <interactant intactId="EBI-359224">
            <id>Q13077</id>
            <label>TRAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10311892">
            <id>Q9NQ94-2</id>
        </interactant>
        <interactant intactId="EBI-742141">
            <id>O95810</id>
            <label>CAVIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 11">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">Predominantly nuclear where it localizes to heterochromatin. Also cytoplasmic where it is found at the outer surface of the endoplasmic reticulum (By similarity). Shuttles between the nucleus and cytoplasm. May be transported into the nucleus by the nuclear import protein TNPO2/TRN2 or by APOBEC1.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NQ94-1</id>
            <name evidence="4">1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NQ94-2</id>
            <name evidence="3 4">2</name>
            <sequence type="described" ref="VSP_051929"/>
        </isoform>
        <isoform>
            <id>Q9NQ94-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_051926 VSP_051929"/>
        </isoform>
        <isoform>
            <id>Q9NQ94-4</id>
            <name evidence="18">4</name>
            <sequence type="described" ref="VSP_051927 VSP_051929"/>
        </isoform>
        <isoform>
            <id>Q9NQ94-5</id>
            <name evidence="7">5</name>
            <sequence type="described" ref="VSP_051925"/>
        </isoform>
        <isoform>
            <id>Q9NQ94-6</id>
            <name evidence="7">6</name>
            <sequence type="described" ref="VSP_051928"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Widely expressed with highest levels in brain, liver, pancreas, colon and spleen.</text>
    </comment>
    <comment type="domain">
        <text evidence="8">The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="7">Major isoform found in 66-78% of cDNA clones.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 4</molecule>
        <text evidence="7 18">Does not exhibit APOBEC1 complementation activity.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 5</molecule>
        <text evidence="7">Does not exhibit APOBEC1 complementation activity.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 6</molecule>
        <text evidence="7">Minor isoform found in 2-3% of cDNA clones.</text>
    </comment>
    <comment type="sequence caution" evidence="18">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAA91086" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AJ272078">
        <property type="protein sequence ID" value="CAB94754.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ272079">
        <property type="protein sequence ID" value="CAB94755.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF209192">
        <property type="protein sequence ID" value="AAF34824.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF271789">
        <property type="protein sequence ID" value="AAF76221.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF271790">
        <property type="protein sequence ID" value="AAF76222.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000324">
        <property type="protein sequence ID" value="BAA91086.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291982">
        <property type="protein sequence ID" value="BAF84671.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL512366">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL589794">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471083">
        <property type="protein sequence ID" value="EAW54133.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471083">
        <property type="protein sequence ID" value="EAW54134.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471083">
        <property type="protein sequence ID" value="EAW54135.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC130519">
        <property type="protein sequence ID" value="AAI30520.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC144196">
        <property type="protein sequence ID" value="AAI44197.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7241.1">
        <molecule id="Q9NQ94-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7242.1">
        <molecule id="Q9NQ94-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7243.1">
        <molecule id="Q9NQ94-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185747.1">
        <molecule id="Q9NQ94-2"/>
        <property type="nucleotide sequence ID" value="NM_001198818.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185748.1">
        <property type="nucleotide sequence ID" value="NM_001198819.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185749.1">
        <molecule id="Q9NQ94-4"/>
        <property type="nucleotide sequence ID" value="NM_001198820.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001357059.1">
        <molecule id="Q9NQ94-2"/>
        <property type="nucleotide sequence ID" value="NM_001370130.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001357060.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="NM_001370131.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055391.2">
        <molecule id="Q9NQ94-2"/>
        <property type="nucleotide sequence ID" value="NM_014576.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_620310.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="NM_138932.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_620311.1">
        <molecule id="Q9NQ94-4"/>
        <property type="nucleotide sequence ID" value="NM_138933.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005269775.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="XM_005269718.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047281085.1">
        <molecule id="Q9NQ94-4"/>
        <property type="nucleotide sequence ID" value="XM_047425129.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047281086.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="XM_047425130.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054221651.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="XM_054365676.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054221652.1">
        <molecule id="Q9NQ94-4"/>
        <property type="nucleotide sequence ID" value="XM_054365677.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054221653.1">
        <molecule id="Q9NQ94-1"/>
        <property type="nucleotide sequence ID" value="XM_054365678.1"/>
    </dbReference>
    <dbReference type="PDB" id="2CPD">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=223-308"/>
    </dbReference>
    <dbReference type="PDBsum" id="2CPD"/>
    <dbReference type="AlphaFoldDB" id="Q9NQ94"/>
    <dbReference type="SMR" id="Q9NQ94"/>
    <dbReference type="BioGRID" id="119004">
        <property type="interactions" value="42"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1097">
        <property type="entry name" value="C-to-U editosome complex"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NQ94">
        <property type="interactions" value="205"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NQ94">
        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000378868"/>
    <dbReference type="GlyGen" id="Q9NQ94">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NQ94"/>
    <dbReference type="PhosphoSitePlus" id="Q9NQ94"/>
    <dbReference type="BioMuta" id="A1CF"/>
    <dbReference type="DMDM" id="74761651"/>
    <dbReference type="jPOST" id="Q9NQ94"/>
    <dbReference type="MassIVE" id="Q9NQ94"/>
    <dbReference type="PaxDb" id="9606-ENSP00000378868"/>
    <dbReference type="PeptideAtlas" id="Q9NQ94"/>
    <dbReference type="ProteomicsDB" id="82112">
        <molecule id="Q9NQ94-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82113">
        <molecule id="Q9NQ94-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82114">
        <molecule id="Q9NQ94-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82115">
        <molecule id="Q9NQ94-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82116">
        <molecule id="Q9NQ94-5"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82117">
        <molecule id="Q9NQ94-6"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="27897">
        <property type="antibodies" value="180 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="29974"/>
    <dbReference type="Ensembl" id="ENST00000373993.6">
        <molecule id="Q9NQ94-1"/>
        <property type="protein sequence ID" value="ENSP00000363105.1"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000373995.7">
        <molecule id="Q9NQ94-4"/>
        <property type="protein sequence ID" value="ENSP00000363107.3"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000373997.8">
        <molecule id="Q9NQ94-2"/>
        <property type="protein sequence ID" value="ENSP00000363109.3"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000374001.6">
        <molecule id="Q9NQ94-2"/>
        <property type="protein sequence ID" value="ENSP00000363113.1"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000395495.6">
        <molecule id="Q9NQ94-4"/>
        <property type="protein sequence ID" value="ENSP00000378873.2"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000414883.2">
        <molecule id="Q9NQ94-2"/>
        <property type="protein sequence ID" value="ENSP00000397953.2"/>
        <property type="gene ID" value="ENSG00000148584.17"/>
    </dbReference>
    <dbReference type="GeneID" id="29974"/>
    <dbReference type="KEGG" id="hsa:29974"/>
    <dbReference type="MANE-Select" id="ENST00000373997.8">
        <molecule id="Q9NQ94-2"/>
        <property type="protein sequence ID" value="ENSP00000363109.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014576.4"/>
        <property type="RefSeq protein sequence ID" value="NP_055391.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001jjh.4">
        <molecule id="Q9NQ94-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24086"/>
    <dbReference type="ClinPGx" id="PA162375098"/>
    <dbReference type="CTD" id="29974"/>
    <dbReference type="DisGeNET" id="29974"/>
    <dbReference type="GeneCards" id="A1CF"/>
    <dbReference type="HGNC" id="HGNC:24086">
        <property type="gene designation" value="A1CF"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000148584">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="618199">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000148584"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000148584"/>
    <dbReference type="eggNOG" id="KOG0117">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158678"/>
    <dbReference type="HOGENOM" id="CLU_022960_5_1_1"/>
    <dbReference type="InParanoid" id="Q9NQ94"/>
    <dbReference type="OrthoDB" id="3800936at2759"/>
    <dbReference type="PAN-GO" id="Q9NQ94">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NQ94"/>
    <dbReference type="PathwayCommons" id="Q9NQ94"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NQ94"/>
    <dbReference type="Agora" id="ENSG00000148584"/>
    <dbReference type="BioGRID-ORCS" id="29974">
        <property type="hits" value="28 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="A1CF">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NQ94"/>
    <dbReference type="GeneWiki" id="ACF_(gene)"/>
    <dbReference type="GenomeRNAi" id="29974"/>
    <dbReference type="Pharos" id="Q9NQ94">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NQ94"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NQ94">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000148584">
        <property type="expression patterns" value="Expressed in liver and 64 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NQ94">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030895">
        <property type="term" value="C:apolipoprotein B mRNA editing enzyme complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045293">
        <property type="term" value="C:mRNA editing complex"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140767">
        <property type="term" value="F:enzyme-substrate adaptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003729">
        <property type="term" value="F:mRNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003727">
        <property type="term" value="F:single-stranded RNA binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0141166">
        <property type="term" value="P:chromosomal 5-methylcytosine DNA demethylation pathway"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007566">
        <property type="term" value="P:embryo implantation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010609">
        <property type="term" value="P:mRNA localization resulting in post-transcriptional regulation of gene expression"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016556">
        <property type="term" value="P:mRNA modification"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006397">
        <property type="term" value="P:mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000623">
        <property type="term" value="P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050821">
        <property type="term" value="P:protein stabilization"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd19900">
        <property type="entry name" value="DSRM_A1CF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd12486">
        <property type="entry name" value="RRM1_ACF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd12490">
        <property type="entry name" value="RRM2_ACF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd12498">
        <property type="entry name" value="RRM3_ACF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.160.20:FF:000025">
        <property type="entry name" value="APOBEC1 complementation factor isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.330:FF:000022">
        <property type="entry name" value="APOBEC1 complementation factor isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.330:FF:000026">
        <property type="entry name" value="APOBEC1 complementation factor isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.330:FF:000179">
        <property type="entry name" value="APOBEC1 complementation factor isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.160.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.330">
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044461">
        <property type="entry name" value="A1CF_DSRM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034538">
        <property type="entry name" value="ACF_RRM1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006535">
        <property type="entry name" value="HnRNP_R/Q_splicing_fac"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012677">
        <property type="entry name" value="Nucleotide-bd_a/b_plait_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035979">
        <property type="entry name" value="RBD_domain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000504">
        <property type="entry name" value="RRM_dom"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01648">
        <property type="entry name" value="hnRNP-R-Q"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR21245">
        <property type="entry name" value="HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14709">
        <property type="entry name" value="DND1_DSRM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00076">
        <property type="entry name" value="RRM_1"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SMART" id="SM00360">
        <property type="entry name" value="RRM"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54768">
        <property type="entry name" value="dsRNA-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54928">
        <property type="entry name" value="RNA-binding domain, RBD"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50102">
        <property type="entry name" value="RRM"/>
        <property type="match status" value="3"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0507">mRNA processing</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <feature type="chain" id="PRO_0000081482" description="APOBEC1 complementation factor">
        <location>
            <begin position="1"/>
            <end position="594"/>
        </location>
    </feature>
    <feature type="domain" description="RRM 1" evidence="2">
        <location>
            <begin position="56"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="domain" description="RRM 2" evidence="2">
        <location>
            <begin position="136"/>
            <end position="218"/>
        </location>
    </feature>
    <feature type="domain" description="RRM 3" evidence="2">
        <location>
            <begin position="231"/>
            <end position="303"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for nuclear localization" evidence="10">
        <location>
            <begin position="360"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="25">
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051925" description="In isoform 5." evidence="14">
        <location>
            <begin position="1"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051926" description="In isoform 3." evidence="17">
        <original>MESNHKSGDGLSGTQKEAALRALVQRTGYSLVQ</original>
        <variation>MLCSPSFCKLCWKRKK</variation>
        <location>
            <begin position="1"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051927" description="In isoform 4." evidence="15 16">
        <original>MESNHKSGDGLSGTQKEAALRALVQRTGYSLVQ</original>
        <variation>MEAVCLGTCPEPEASMSTAIPGLKKGNNALQSIILQTLLEK</variation>
        <location>
            <begin position="1"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051928" description="In isoform 6." evidence="14">
        <location>
            <begin position="202"/>
            <end position="256"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051929" description="In isoform 2, isoform 3 and isoform 4." evidence="12 13 15 16 17">
        <location>
            <begin position="381"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_052201" description="In dbSNP:rs9073.">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="555"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059821" description="In dbSNP:rs11817448.">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="558"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced RNA binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced RNA binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced RNA binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced RNA binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly reduced RNA binding." evidence="8">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly reduced RNA binding." evidence="8">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF34824." evidence="18" ref="2">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="191"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2 and 3." evidence="18" ref="2 3">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="232"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="244"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="259"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="266"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="276"/>
            <end position="286"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="287"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="294"/>
            <end position="299"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00176"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10669759"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10781591"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11134005"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="11577082"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11718896"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="11871661"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12881431"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12896982"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="24916387"/>
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    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="10669759"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="10781591"/>
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    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="11718896"/>
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    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    <evidence type="ECO:0000303" key="16">
        <source>
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    <evidence type="ECO:0000303" key="17">
        <source ref="3"/>
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    <evidence type="ECO:0000305" key="18"/>
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        <source>
            <dbReference type="EMBL" id="AAF34824.1"/>
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    </evidence>
    <evidence type="ECO:0000312" key="20">
        <source>
            <dbReference type="EMBL" id="AAF76221.1"/>
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    </evidence>
    <evidence type="ECO:0000312" key="21">
        <source>
            <dbReference type="EMBL" id="AL512366"/>
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    </evidence>
    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="EMBL" id="BAA91086.1"/>
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    <evidence type="ECO:0000312" key="23">
        <source>
            <dbReference type="EMBL" id="CAB94754.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="24">
        <source>
            <dbReference type="EMBL" id="CAB94755.1"/>
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    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="2CPD"/>
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    </evidence>
    <sequence length="594" mass="65202" checksum="AA5EF76BD8815807" modified="2000-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="291" xmlns="https://uniprot.org/uniprot">
    <accession>P01009</accession>
    <accession>A6PX14</accession>
    <accession>B2RDQ8</accession>
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    <accession>Q13672</accession>
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    <accession>Q7M4R2</accession>
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    <accession>Q86U19</accession>
    <accession>Q96BF9</accession>
    <accession>Q96ES1</accession>
    <accession>Q9P1P0</accession>
    <accession>Q9UCE6</accession>
    <accession>Q9UCM3</accession>
    <name>A1AT_HUMAN</name>
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        <recommendedName>
            <fullName evidence="52">Alpha-1-antitrypsin</fullName>
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        <alternativeName>
            <fullName>Alpha-1 protease inhibitor</fullName>
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        <alternativeName>
            <fullName>Alpha-1-antiproteinase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Serpin A1</fullName>
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            <recommendedName>
                <fullName>Short peptide from AAT</fullName>
                <shortName>SPAAT</shortName>
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        <name evidence="53" type="primary">SERPINA1</name>
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        <name type="synonym">PI</name>
        <name type="ORF">PRO0684</name>
        <name type="ORF">PRO2209</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
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            <title>Cloning and expression in Escherichia coli of full-length complementary DNA coding for human alpha 1-antitrypsin.</title>
            <authorList>
                <person name="Bollen A."/>
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            </authorList>
            <dbReference type="PubMed" id="6319097"/>
            <dbReference type="DOI" id="10.1089/dna.1983.2.255"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
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            <authorList>
                <person name="Long G.L."/>
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            </authorList>
            <dbReference type="PubMed" id="6093867"/>
            <dbReference type="DOI" id="10.1021/bi00316a003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1984" name="Nature" volume="312" first="77" last="80">
            <title>Synthesis in yeast of a functional oxidation-resistant mutant of human alpha-antitrypsin.</title>
            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="6387509"/>
            <dbReference type="DOI" id="10.1038/312077a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>MUTAGENESIS OF MET-382</scope>
    </reference>
    <reference key="4">
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            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="2985281"/>
            <dbReference type="DOI" id="10.1016/s0092-8674(85)80026-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1986" name="J. Biol. Chem." volume="261" first="15989" last="15994">
            <title>Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene.</title>
            <authorList>
                <person name="Nukiwa T."/>
                <person name="Satoh K."/>
                <person name="Brantly M.L."/>
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                <person name="Crystal R.G."/>
            </authorList>
            <dbReference type="PubMed" id="3491072"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)66664-5"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>CHARACTERIZATION OF VARIANT Z</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1987" name="J. Biol. Chem." volume="262" first="10412" last="10412">
            <authorList>
                <person name="Nukiwa T."/>
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        <scope>ERRATUM OF PUBMED:3491072</scope>
    </reference>
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            <authorList>
                <person name="Shasany A.K."/>
                <person name="Shukla A.K."/>
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                <person name="Tewari L."/>
                <person name="Khanuja S.P."/>
            </authorList>
            <dbReference type="PubMed" id="17650587"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS ALA-237 AND ASP-400</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <title>Characterization of a new variant of alpha1 antitrypsin M Lille (p.Gly148Trp).</title>
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                <person name="Balduyck M."/>
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                <person name="Zerimech F."/>
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                <person name="Verchain S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS TRP-172; ALA-237 AND LYS-366</scope>
        <source>
            <tissue>Lymphocyte</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="submission" date="1998-12" db="EMBL/GenBank/DDBJ databases">
            <title>Functional prediction of the coding sequences of 32 new genes deduced by analysis of cDNA clones from human fetal liver.</title>
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                <person name="Zhang C."/>
                <person name="Yu Y."/>
                <person name="Zhang S."/>
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                <person name="Bi J."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Fetal liver</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="submission" date="2003-02" db="EMBL/GenBank/DDBJ databases">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <source>
            <tissue>Fetal liver</tissue>
            <tissue>Placenta</tissue>
        </source>
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        <scope>GLYCOSYLATION AT ASN-70; ASN-107 AND ASN-271</scope>
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        <scope>VARIANT A1ATD LEU-393</scope>
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        <scope>VARIANT A1ATD GLU-91</scope>
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        <scope>VARIANT A1ATD VAL-280</scope>
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            <title>Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele.</title>
            <authorList>
                <person name="Faber J.-P."/>
                <person name="Poller W."/>
                <person name="Weidinger S."/>
                <person name="Kirchgesser M."/>
                <person name="Schwaab R."/>
                <person name="Bidlingmaier F."/>
                <person name="Olek K."/>
            </authorList>
            <dbReference type="PubMed" id="7977369"/>
        </citation>
        <scope>VARIANTS A1ATD PHE-75 DEL AND ILE-92</scope>
        <scope>VARIANTS THR-58; PHE-69; THR-84; THR-112; ARG-172; TRP-172; GLU-180; PHE-354; ASN-365 AND THR-386</scope>
    </reference>
    <reference key="75">
        <citation type="journal article" date="1997" name="Ann. Hum. Genet." volume="61" first="385" last="391">
            <title>A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI ZBristol) associated with novel electrophoretic properties.</title>
            <authorList>
                <person name="Lovegrove J.U."/>
                <person name="Jeremiah S."/>
                <person name="Gillett G.T."/>
                <person name="Temple I.K."/>
                <person name="Povey S."/>
                <person name="Whitehouse D.B."/>
            </authorList>
            <dbReference type="PubMed" id="9459000"/>
            <dbReference type="DOI" id="10.1046/j.1469-1809.1997.6150385.x"/>
        </citation>
        <scope>VARIANT Z-BRISTOL MET-109</scope>
    </reference>
    <reference key="76">
        <citation type="journal article" date="1998" name="Am. J. Respir. Cell Mol. Biol." volume="18" first="670" last="674">
            <title>Lung polymers in Z alpha1-antitrypsin deficiency-related emphysema.</title>
            <authorList>
                <person name="Elliott P.R."/>
                <person name="Bilton D."/>
                <person name="Lomas D.A."/>
            </authorList>
            <dbReference type="PubMed" id="9569237"/>
            <dbReference type="DOI" id="10.1165/ajrcmb.18.5.3065"/>
        </citation>
        <scope>VARIANT A1ATD LYS-366</scope>
        <scope>CHARACTERIZATION OF VARIANT A1ATD LYS-366</scope>
        <scope>INVOLVEMENT IN A1ATD</scope>
    </reference>
    <reference key="77">
        <citation type="journal article" date="1998" name="Hum. Mutat." volume="12" first="213" last="213">
            <title>Identification and molecular characterization of the new alpha-1-antitrypsin deficient allele PI YBarcelona (Asp256Val and Pro391His).</title>
            <authorList>
                <person name="Jardi R."/>
                <person name="Rodriguez F."/>
                <person name="Miravitlles M."/>
                <person name="Vidal R."/>
                <person name="Cotrina M."/>
                <person name="Quer J."/>
                <person name="Pascual C."/>
                <person name="Weidinger S."/>
            </authorList>
            <dbReference type="PubMed" id="10651487"/>
        </citation>
        <scope>VARIANTS A1ATD VAL-280 AND HIS-415</scope>
        <scope>INVOLVEMENT IN A1ATD</scope>
    </reference>
    <reference key="78">
        <citation type="journal article" date="1999" name="Hum. Mutat." volume="13" first="414" last="414">
            <title>A novel alpha-1-antitrypsin P362H variant found in a population sample from Sao Tome e Principe (Gulf of Guinea, West Africa).</title>
            <authorList>
                <person name="Seixas S."/>
                <person name="Trovoada M.J."/>
                <person name="Santos M.T."/>
                <person name="Rocha J."/>
            </authorList>
        </citation>
        <scope>VARIANT SAO TOME HIS-386</scope>
    </reference>
    <reference key="79">
        <citation type="journal article" date="2000" name="Hum. Mutat." volume="15" first="121" last="122">
            <title>A novel alpha-1-antitrypsin r281del variant found in a population sample from the Basque country.</title>
            <authorList>
                <person name="Seixas S."/>
                <person name="Garcia O."/>
                <person name="Amorim A."/>
                <person name="Rocha J."/>
            </authorList>
            <dbReference type="PubMed" id="10612848"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(200001)15:1&lt;121::aid-humu37&gt;3.0.co;2-u"/>
        </citation>
        <scope>VARIANT BASQUE ARG-305 DEL</scope>
    </reference>
    <reference key="80">
        <citation type="journal article" date="2013" name="PLoS ONE" volume="8" first="E66889" last="E66889">
            <title>SERPINA2 is a novel gene with a divergent function from SERPINA1.</title>
            <authorList>
                <person name="Marques P.I."/>
                <person name="Ferreira Z."/>
                <person name="Martins M."/>
                <person name="Figueiredo J."/>
                <person name="Silva D.I."/>
                <person name="Castro P."/>
                <person name="Morales-Hojas R."/>
                <person name="Simoes-Correia J."/>
                <person name="Seixas S."/>
            </authorList>
            <dbReference type="PubMed" id="23826168"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0066889"/>
        </citation>
        <scope>VARIANTS Z ALA-237 AND LYS-366</scope>
        <scope>VARIANT S VAL-288</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>INTERACTION WITH CANX AND PDIA3</scope>
    </reference>
    <reference key="81">
        <citation type="journal article" date="2014" name="PLoS ONE" volume="9" first="e102617" last="e102617">
            <title>The Z mutation alters the global structural dynamics of alpha1-antitrypsin.</title>
            <authorList>
                <person name="Hughes V.A."/>
                <person name="Meklemburg R."/>
                <person name="Bottomley S.P."/>
                <person name="Wintrode P.L."/>
            </authorList>
            <dbReference type="PubMed" id="25181470"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0102617"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT A1ATD LYS-366</scope>
    </reference>
    <reference key="82">
        <citation type="journal article" date="2016" name="Biochem. Biophys. Res. Commun." volume="470" first="710" last="713">
            <title>The M358R variant of alpha(1)-proteinase inhibitor inhibits coagulation factor VIIa.</title>
            <authorList>
                <person name="Sheffield W.P."/>
                <person name="Bhakta V."/>
            </authorList>
            <dbReference type="PubMed" id="26797521"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2016.01.069"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT PITTSBURGH ARG-382</scope>
    </reference>
    <comment type="function">
        <text>Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.</text>
    </comment>
    <comment type="function">
        <molecule>Short peptide from AAT</molecule>
        <text>Reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 26 36 37">Interacts with CELA2A (PubMed:31358993). Interacts with ERGIC3 and LMAN1/ERGIC53 (PubMed:31142615). Interacts with PRSS1/trypsin (PubMed:11057674). Interacts with PRSS1/Trypsin (PubMed:11057674). The variants S and Z interact with CANX and PDIA3 (PubMed:23826168).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-986345">
            <id>P08246</id>
            <label>ELANE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-781551">
            <id>Q9Y282</id>
            <label>ERGIC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-6447163">
            <id>Q8N7X4</id>
            <label>MAGEB6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-986224">
            <id>P01009</id>
            <label>SERPINA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-714168">
            <id>P43307</id>
            <label>SSR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-12549863">
            <id>O15393</id>
            <label>TMPRSS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-986248">
            <id>P00772</id>
            <label>CELA1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-2615322">
            <id>P71213</id>
            <label>espB</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-986224">
            <id>P01009</id>
        </interactant>
        <interactant intactId="EBI-986385">
            <id>P00760</id>
            <label>PRSS1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Endoplasmic reticulum</location>
        </subcellularLocation>
        <text>The S and Z allele are not secreted effectively and accumulate intracellularly in the endoplasmic reticulum.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Short peptide from AAT</molecule>
        <subcellularLocation>
            <location>Secreted</location>
            <location>Extracellular space</location>
            <location>Extracellular matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P01009-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P01009-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_028889"/>
        </isoform>
        <isoform>
            <id>P01009-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_028890"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="26">Ubiquitous. Expressed in leukocytes and plasma.</text>
    </comment>
    <comment type="domain">
        <text>The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4 6 7 9 10 11 15 16 18 20 26">N-glycosylated. Differential glycosylation produces a number of isoforms. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively di-antennary. Structure of glycans at Asn-70 and Asn-271 is Hex5HexNAc4. The structure of the antennae is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennae are fucosylated, which forms a Lewis-X determinant.</text>
    </comment>
    <comment type="PTM">
        <text>Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.</text>
    </comment>
    <comment type="PTM">
        <text evidence="39">(Microbial infection) Proteolytically processed by Staphylococcus aureus seryl, cysteinyl, and metallo-proteases.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="35">The sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.</text>
    </comment>
    <comment type="disease" evidence="2 8 13 17 21 22 23 25 27 29 30 33 34 38 43 44 46">
        <disease id="DI-02928">
            <name>Alpha-1-antitrypsin deficiency</name>
            <acronym>A1ATD</acronym>
            <description>An autosomal recessive disorder characterized by serum levels of alpha-1-antitrypsin below the normal range, and an increased risk for developing pulmonary emphysema and, to a lesser extent, chronic liver disease. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age.</description>
            <dbReference type="MIM" id="613490"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>The aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="52">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="52">Belongs to the serpin family.</text>
    </comment>
    <comment type="sequence caution" evidence="52">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAD62334" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="52">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAD62585" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Alpha_1-antitrypsin"/>
        <text>Alpha-1 antitrypsin entry</text>
    </comment>
    <dbReference type="EMBL" id="K01396">
        <property type="protein sequence ID" value="AAB59375.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="K02212">
        <property type="protein sequence ID" value="AAB59495.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01683">
        <property type="protein sequence ID" value="CAA25838.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M11465">
        <property type="protein sequence ID" value="AAA51546.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J02619">
        <property type="protein sequence ID" value="AAA51547.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ682455">
        <property type="protein sequence ID" value="ABG73380.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AM048838">
        <property type="protein sequence ID" value="CAJ15161.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF113676">
        <property type="protein sequence ID" value="AAF29581.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF130068">
        <property type="protein sequence ID" value="AAG35496.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX161449">
        <property type="protein sequence ID" value="CAD61914.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX247968">
        <property type="protein sequence ID" value="CAD62306.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX248002">
        <property type="protein sequence ID" value="CAD62334.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX248257">
        <property type="protein sequence ID" value="CAD62585.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315637">
        <property type="protein sequence ID" value="BAG38005.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT019455">
        <property type="protein sequence ID" value="AAV38262.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011991">
        <property type="protein sequence ID" value="AAH11991.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015642">
        <property type="protein sequence ID" value="AAH15642.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00064">
        <property type="protein sequence ID" value="AAB59369.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00066">
        <property type="protein sequence ID" value="AAB59370.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00065">
        <property type="protein sequence ID" value="AAB59370.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00067">
        <property type="protein sequence ID" value="AAB59371.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02920">
        <property type="protein sequence ID" value="CAA26677.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="V00496">
        <property type="protein sequence ID" value="CAA23755.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M26123">
        <property type="protein sequence ID" value="AAA51545.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9925.1">
        <molecule id="P01009-1"/>
    </dbReference>
    <dbReference type="PIR" id="A21853">
        <property type="entry name" value="ITHU"/>
    </dbReference>
    <dbReference type="PIR" id="A61391">
        <property type="entry name" value="A61391"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000286.3">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_000295.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001002235.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001002235.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001002236.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001002236.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121172.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127700.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121173.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127701.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121174.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127702.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121175.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127703.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121176.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127704.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121177.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127705.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121178.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127706.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121179.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="NM_001127707.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016876859.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="XM_017021370.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047287434.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="XM_047431478.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047287435.1">
        <molecule id="P01009-1"/>
        <property type="nucleotide sequence ID" value="XM_047431479.1"/>
    </dbReference>
    <dbReference type="PDB" id="1ATU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=45-418"/>
    </dbReference>
    <dbReference type="PDB" id="1D5S">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A=44-377, B=378-418"/>
    </dbReference>
    <dbReference type="PDB" id="1EZX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=48-382, B=383-418"/>
    </dbReference>
    <dbReference type="PDB" id="1HP7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=25-418"/>
    </dbReference>
    <dbReference type="PDB" id="1IZ2">
        <property type="method" value="X-ray"/>
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        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031012">
        <property type="term" value="C:extracellular matrix"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904813">
        <property type="term" value="C:ficolin-1-rich granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031093">
        <property type="term" value="C:platelet alpha granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002020">
        <property type="term" value="F:protease binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004867">
        <property type="term" value="F:serine-type endopeptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006953">
        <property type="term" value="P:acute-phase response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007596">
        <property type="term" value="P:blood coagulation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd02056">
        <property type="entry name" value="serpinA1_A1AT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="DisProt" id="DP03262"/>
    <dbReference type="FunFam" id="2.30.39.10:FF:000003">
        <property type="entry name" value="alpha-1-antitrypsin isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.497.10:FF:000001">
        <property type="entry name" value="Serine protease inhibitor"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.310.10:FF:000001">
        <property type="entry name" value="Serpin family A member 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.39.10">
        <property type="entry name" value="Alpha-1-antitrypsin, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.497.10">
        <property type="entry name" value="Antithrombin, subunit I, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.10.310.10">
        <property type="entry name" value="Serpins superfamily"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023795">
        <property type="entry name" value="Serpin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023796">
        <property type="entry name" value="Serpin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000215">
        <property type="entry name" value="Serpin_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036186">
        <property type="entry name" value="Serpin_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042178">
        <property type="entry name" value="Serpin_sf_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042185">
        <property type="entry name" value="Serpin_sf_2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461:SF165">
        <property type="entry name" value="ALPHA-1-ANTITRYPSIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461">
        <property type="entry name" value="SERINE PROTEASE INHIBITOR, SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00079">
        <property type="entry name" value="Serpin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00093">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56574">
        <property type="entry name" value="Serpins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00284">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0011">Acute phase</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0094">Blood coagulation</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0272">Extracellular matrix</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0356">Hemostasis</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="14">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000032377" description="Alpha-1-antitrypsin" evidence="40">
        <location>
            <begin position="25"/>
            <end position="418"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000364030" description="Short peptide from AAT">
        <location>
            <begin position="375"/>
            <end position="418"/>
        </location>
    </feature>
    <feature type="region of interest" description="RCL">
        <location>
            <begin position="368"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="site" description="(Microbial infection) Cleavage; by Staphylococcus aureus aureolysin/Aur" evidence="39">
        <location>
            <begin position="352"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="site" description="(Microbial infection) Cleavage; by Staphylococcus aureus serine and cysteine proteinases" evidence="39">
        <location>
            <begin position="354"/>
            <end position="355"/>
        </location>
    </feature>
    <feature type="site" description="Reactive bond">
        <location>
            <begin position="382"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by FAM20C" evidence="31">
        <location>
            <position position="38"/>
        </location>
    </feature>
    <feature type="modified residue" description="S-cysteinyl cysteine">
        <location>
            <position position="256"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="54">
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="4 6 7 9 10 11 16 18 20">
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="10 11 15 16 18">
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="4 6 7 10 11 15 16 18 20">
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028890" description="In isoform 3." evidence="51">
        <location>
            <begin position="307"/>
            <end position="418"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028889" description="In isoform 2." evidence="51">
        <original>AVHKAVLTIDEKGTEAAGAMFLEAIPMSIPPEVKFNKPFVFLMIEQNTKSPLFMGKVVNPTQK</original>
        <variation>VRSP</variation>
        <location>
            <begin position="356"/>
            <end position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090661" description="In A1ATD; uncertain significance; Z-Wrexham." evidence="21">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006979" description="In V-Munich; dbSNP:rs199422212." evidence="24">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051938" description="In dbSNP:rs11558262.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006980" description="In M5-Karlsruhe; dbSNP:rs149319176." evidence="43">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006981" description="In A1ATD; I; dbSNP:rs28931570." evidence="30">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006982" description="In A1ATD; M-Procida; dbSNP:rs28931569." evidence="38">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006983" description="In M6-Bonn; dbSNP:rs199687431." evidence="43">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006984" description="In A1ATD; M-Malton, M-Nichinan and M-Palermo; risk factor for chronic emphysema or infantile liver cirrhosis; very low alpha-1-antitrypsin serum levels." evidence="23 30 34 43">
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006985" description="In A1ATD; S-Iiyama; dbSNP:rs55819880." evidence="13">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006986" description="In M6-Passau; dbSNP:rs111850950." evidence="43">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006987" description="In A1ATD; M-Mineral springs; causes reduced alpha-1-antitrypsin secretion; dbSNP:rs28931568." evidence="17">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006988" description="In A1ATD; QO-Lisbon; very low alpha-1-antitrypsin serum levels; dbSNP:rs1490133295." evidence="43">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011620" description="In Z-Bristol; deficient AA; disrupts the N-glycosylation site N-107; dbSNP:rs199422213." evidence="45">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006989" description="In M5-Berlin; dbSNP:rs886044322." evidence="43">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006990" description="In A1ATD; QO-Ludwigshafen; dbSNP:rs28931572." evidence="22">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006991" description="In M2; associated with D-400; dbSNP:rs709932.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006992" description="In A1ATD; QO-Newport; dbSNP:rs11558261." evidence="21">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006993" description="In V and M-Nichinan; dbSNP:rs112030253." evidence="43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006994" description="In M2-Obernburg; dbSNP:rs112030253." evidence="43 50">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006995" description="In L-Frankfurt; dbSNP:rs864622051." evidence="43">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="180"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036746" description="In Aberrant form." evidence="48">
        <original>QGKIVDLVK</original>
        <variation>GFQNAILVR</variation>
        <location>
            <begin position="190"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006996" description="In X; dbSNP:rs199422208.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006997" description="In M1A and Z; associated with K-366 in Z; dbSNP:rs6647." evidence="12 26 47 50">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006998" description="In F; dbSNP:rs28929470." evidence="19">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006999" description="In A1ATD; P-Duarte/P-Cardiff/P-Lowell; associated with H-415 in Y-Barcelona; dbSNP:rs121912714." evidence="2 30 44">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007000" description="In S and T; dbSNP:rs17580." evidence="26 48">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="288"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009216" description="In Basque." evidence="1">
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007001" description="In S-Munich; dbSNP:rs201788603." evidence="43">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="354"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007002" description="In W-Bethesda; dbSNP:rs1802959." evidence="27">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007003" description="In P-St.Albans/P-Donauwoerth; dbSNP:rs143370956." evidence="43">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007004" description="In A1ATD; Z/Z-Augsburg/Z-Tun; associated with A-237 in Z; changed protein structure; results in protein aggregation into bead-like polymers; dbSNP:rs28929474." evidence="8 25 26 29 46 50">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="366"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007005" description="In Pittsburgh; has antithrombin activity; inhibits factor VIIa activity; causes fatal bleeding diathesis; dbSNP:rs121912713." evidence="5 32 42">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="382"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007006" description="In Sao Tome; dbSNP:rs569384943." evidence="49">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="386"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007007" description="In L-Offenbach; dbSNP:rs12233." evidence="43">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="386"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007008" description="In Christchurch; dbSNP:rs121912712.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="387"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007009" description="In A1ATD; M-Heerlen; dbSNP:rs199422209." evidence="33">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="393"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007010" description="In M2 and M3; associated with H-125 in M2; dbSNP:rs1303." evidence="12 28">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_007011" description="In A1ATD; associated with V-280 in Y-Barcelona." evidence="2">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Oxidation-resistant inhibitor of therapeutic importance." evidence="41">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="382"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA51546." evidence="52" ref="4">
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; BAG38005." evidence="52" ref="11">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 18; AA sequence." evidence="52" ref="18">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 18; AA sequence." evidence="52" ref="18">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAF29581." evidence="52" ref="9">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="61"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; ABG73380." evidence="52" ref="7">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAB59375." evidence="52" ref="1">
        <original>GN</original>
        <variation>DG</variation>
        <location>
            <begin position="139"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA51546." evidence="52" ref="4">
        <original>T</original>
        <variation>H</variation>
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA51546." evidence="52" ref="4">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAB59375." evidence="52" ref="1">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="273"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; ABG73380." evidence="52" ref="7">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA25838." evidence="52" ref="3">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 24; AA sequence." evidence="52" ref="24">
        <original>G</original>
        <variation>L</variation>
        <location>
            <position position="410"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 24; AA sequence." evidence="52" ref="24">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="414"/>
        </location>
    </feature>
    <feature type="turn" evidence="56">
        <location>
            <begin position="48"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="helix" evidence="60">
        <location>
            <begin position="51"/>
            <end position="68"/>
        </location>
    </feature>
    <feature type="strand" evidence="60">
        <location>
            <begin position="70"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="strand" evidence="60">
        <location>
            <begin position="74"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="helix" evidence="60">
        <location>
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</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="169" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NAA4</accession>
    <accession>A5PL30</accession>
    <accession>B2RPK5</accession>
    <accession>Q658V4</accession>
    <accession>Q6PID3</accession>
    <accession>Q8NBG0</accession>
    <name>A16L2_HUMAN</name>
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            <fullName evidence="6">Protein Atg16l2</fullName>
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        <alternativeName>
            <fullName>Autophagy-related protein 16-2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>WD repeat-containing protein 80</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ATG16L2</name>
        <name type="synonym">WDR80</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
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                <person name="Saito K."/>
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                <person name="Iwayanagi T."/>
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                <person name="Hosoiri T."/>
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                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
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                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
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                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Astrocyte</tissue>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Eye</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 297-619</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">May play a role in regulating epithelial homeostasis in an ATG16L1-dependent manner.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homooligomer. Heterooligomer with ATG16L1. Interacts with ATG5. Self-oligomerizes to form a 800-kDa complex composed of ATG12-ATG5 and ATG16L2. Interacts with RAB33B.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytosol</location>
        </subcellularLocation>
        <text evidence="1">Also localizes to discrete punctae along the ciliary axoneme.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NAA4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NAA4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_033904"/>
        </isoform>
        <isoform>
            <id>Q8NAA4-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_033905"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1">Although ATG16L2 is structurally similar to ATG16L1 and is likewise able to form a complex with the autophagy proteins ATG5 and ATG12, overexpression and knockdown studies in mouse suggest that ATG16L2 is not essential for canonical autophagy.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the WD repeat ATG16 family.</text>
    </comment>
    <dbReference type="EMBL" id="AK093017">
        <property type="protein sequence ID" value="BAC04021.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK090597">
        <property type="protein sequence ID" value="BAC03485.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471076">
        <property type="protein sequence ID" value="EAW74876.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471076">
        <property type="protein sequence ID" value="EAW74874.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC036713">
        <property type="protein sequence ID" value="AAH36713.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137489">
        <property type="protein sequence ID" value="AAI37490.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137490">
        <property type="protein sequence ID" value="AAI37491.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC142718">
        <property type="protein sequence ID" value="AAI42719.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC146660">
        <property type="protein sequence ID" value="AAI46661.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832974">
        <property type="protein sequence ID" value="CAH56355.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31634.1">
        <molecule id="Q8NAA4-1"/>
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    <dbReference type="RefSeq" id="NP_001305695.1">
        <molecule id="Q8NAA4-2"/>
        <property type="nucleotide sequence ID" value="NM_001318766.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_203746.1">
        <molecule id="Q8NAA4-1"/>
        <property type="nucleotide sequence ID" value="NM_033388.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011543635.1">
        <molecule id="Q8NAA4-2"/>
        <property type="nucleotide sequence ID" value="XM_011545333.2"/>
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    <dbReference type="RefSeq" id="XP_011543636.1">
        <molecule id="Q8NAA4-2"/>
        <property type="nucleotide sequence ID" value="XM_011545334.2"/>
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    <dbReference type="RefSeq" id="XP_054226395.1">
        <molecule id="Q8NAA4-2"/>
        <property type="nucleotide sequence ID" value="XM_054370420.1"/>
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    <dbReference type="RefSeq" id="XP_054226397.1">
        <molecule id="Q8NAA4-2"/>
        <property type="nucleotide sequence ID" value="XM_054370422.1"/>
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    <dbReference type="AlphaFoldDB" id="Q8NAA4"/>
    <dbReference type="SMR" id="Q8NAA4"/>
    <dbReference type="BioGRID" id="124620">
        <property type="interactions" value="43"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-354">
        <property type="entry name" value="ATG12-ATG5-ATG16L2 complex"/>
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    <dbReference type="FunCoup" id="Q8NAA4">
        <property type="interactions" value="1071"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8NAA4">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="MINT" id="Q8NAA4"/>
    <dbReference type="STRING" id="9606.ENSP00000326340"/>
    <dbReference type="TCDB" id="9.A.15.2.1">
        <property type="family name" value="the autophagy-related phagophore-formation transporter (apt) family"/>
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    <dbReference type="iPTMnet" id="Q8NAA4"/>
    <dbReference type="PhosphoSitePlus" id="Q8NAA4"/>
    <dbReference type="BioMuta" id="ATG16L2"/>
    <dbReference type="DMDM" id="189027648"/>
    <dbReference type="jPOST" id="Q8NAA4"/>
    <dbReference type="MassIVE" id="Q8NAA4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000326340"/>
    <dbReference type="PeptideAtlas" id="Q8NAA4"/>
    <dbReference type="ProteomicsDB" id="72661">
        <molecule id="Q8NAA4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="72662">
        <molecule id="Q8NAA4-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="72663">
        <molecule id="Q8NAA4-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="30896">
        <property type="antibodies" value="186 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="89849"/>
    <dbReference type="Ensembl" id="ENST00000321297.10">
        <molecule id="Q8NAA4-1"/>
        <property type="protein sequence ID" value="ENSP00000326340.5"/>
        <property type="gene ID" value="ENSG00000168010.12"/>
    </dbReference>
    <dbReference type="GeneID" id="89849"/>
    <dbReference type="KEGG" id="hsa:89849"/>
    <dbReference type="MANE-Select" id="ENST00000321297.10">
        <property type="protein sequence ID" value="ENSP00000326340.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_033388.2"/>
        <property type="RefSeq protein sequence ID" value="NP_203746.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001otd.4">
        <molecule id="Q8NAA4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25464"/>
    <dbReference type="ClinPGx" id="PA142672575"/>
    <dbReference type="CTD" id="89849"/>
    <dbReference type="DisGeNET" id="89849"/>
    <dbReference type="GeneCards" id="ATG16L2"/>
    <dbReference type="HGNC" id="HGNC:25464">
        <property type="gene designation" value="ATG16L2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000168010">
        <property type="expression patterns" value="Tissue enhanced (bone marrow, lymphoid tissue)"/>
    </dbReference>
    <dbReference type="MIM" id="618716">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000168010"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000168010"/>
    <dbReference type="eggNOG" id="KOG0288">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000153936"/>
    <dbReference type="InParanoid" id="Q8NAA4"/>
    <dbReference type="OMA" id="PHCAAIN"/>
    <dbReference type="OrthoDB" id="6262491at2759"/>
    <dbReference type="PAN-GO" id="Q8NAA4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NAA4"/>
    <dbReference type="PathwayCommons" id="Q8NAA4"/>
    <dbReference type="Reactome" id="R-HSA-1632852">
        <property type="pathway name" value="Macroautophagy"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8NAA4"/>
    <dbReference type="Agora" id="ENSG00000168010"/>
    <dbReference type="BioGRID-ORCS" id="89849">
        <property type="hits" value="9 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ATG16L2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="89849"/>
    <dbReference type="Pharos" id="Q8NAA4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NAA4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NAA4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000168010">
        <property type="expression patterns" value="Expressed in granulocyte and 145 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8NAA4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034274">
        <property type="term" value="C:Atg12-Atg5-Atg16 complex"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034045">
        <property type="term" value="C:phagophore assembly site membrane"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000045">
        <property type="term" value="P:autophagosome assembly"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016236">
        <property type="term" value="P:macroautophagy"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0039689">
        <property type="term" value="P:negative stranded viral RNA replication"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015031">
        <property type="term" value="P:protein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd22887">
        <property type="entry name" value="Atg16_CCD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd00200">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.130.10.10:FF:000199">
        <property type="entry name" value="autophagy-related protein 16-2 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045160">
        <property type="entry name" value="ATG16"/>
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    <dbReference type="InterPro" id="IPR013923">
        <property type="entry name" value="Autophagy-rel_prot_16_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020472">
        <property type="entry name" value="WD40_PAC1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019775">
        <property type="entry name" value="WD40_repeat_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19878">
        <property type="entry name" value="AUTOPHAGY PROTEIN 16-LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19878:SF7">
        <property type="entry name" value="PROTEIN ATG16L2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08614">
        <property type="entry name" value="ATG16"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00400">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00320">
        <property type="entry name" value="GPROTEINBRPT"/>
    </dbReference>
    <dbReference type="SMART" id="SM00320">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="7"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00678">
        <property type="entry name" value="WD_REPEATS_1"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50082">
        <property type="entry name" value="WD_REPEATS_2"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50294">
        <property type="entry name" value="WD_REPEATS_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000337110" description="Protein Atg16l2">
        <location>
            <begin position="1"/>
            <end position="619"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 1" evidence="2">
        <location>
            <begin position="334"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2" evidence="2">
        <location>
            <begin position="378"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3" evidence="2">
        <location>
            <begin position="420"/>
            <end position="454"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4" evidence="2">
        <location>
            <begin position="455"/>
            <end position="498"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5" evidence="2">
        <location>
            <begin position="500"/>
            <end position="539"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6" evidence="2">
        <location>
            <begin position="546"/>
            <end position="585"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7" evidence="2">
        <location>
            <begin position="589"/>
            <end position="619"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="57"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="116"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="60"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033904" description="In isoform 2." evidence="4">
        <location>
            <begin position="1"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033905" description="In isoform 3." evidence="5">
        <location>
            <begin position="276"/>
            <end position="619"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043605" description="In dbSNP:rs11235604.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="220"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC03485." evidence="6" ref="1">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH36713." evidence="6" ref="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="256"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC03485." evidence="6" ref="1">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC04021." evidence="6" ref="1">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="492"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAH56355." evidence="6" ref="4">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="508"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q6KAU8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="619" mass="68998" checksum="7F2962AA3C6BB850" modified="2008-05-20" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-26" modified="2026-01-28" version="103" xmlns="https://uniprot.org/uniprot">
    <accession>Q96IX9</accession>
    <name>A26L1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 26-like 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Ankyrin repeat domain-containing protein 36B pseudogene 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ANKRD36BP1</name>
        <name type="synonym">ANKRD26L1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Coville G.J."/>
                <person name="Davies J."/>
                <person name="Deadman R."/>
                <person name="Dunn M."/>
                <person name="Earthrowl M."/>
                <person name="Ellington A.G."/>
                <person name="Errington H."/>
                <person name="Frankish A."/>
                <person name="Frankland J."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gay L."/>
                <person name="Ghori M.R.J."/>
                <person name="Gibson R."/>
                <person name="Gilby L.M."/>
                <person name="Gillett W."/>
                <person name="Glithero R.J."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Hammond S."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E."/>
                <person name="Haugen E."/>
                <person name="Heath P.D."/>
                <person name="Holmes S."/>
                <person name="Holt K."/>
                <person name="Howden P.J."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Hunter G."/>
                <person name="Isherwood J."/>
                <person name="James R."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A."/>
                <person name="Kay M."/>
                <person name="Kershaw J.K."/>
                <person name="Kibukawa M."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A.J."/>
                <person name="Lad H."/>
                <person name="Laird G."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-1181367">
            <id>Q01850</id>
            <label>CDR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-1059030">
            <id>O95073</id>
            <label>FSBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-618309">
            <id>Q08379</id>
            <label>GOLGA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-743290">
            <id>Q96ED9</id>
            <label>HOOK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-10171552">
            <id>A1A4E9</id>
            <label>KRT13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-739566">
            <id>P19012</id>
            <label>KRT15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-1047263">
            <id>O76015</id>
            <label>KRT38</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-10171697">
            <id>Q6A162</id>
            <label>KRT40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-10172290">
            <id>P60409</id>
            <label>KRTAP10-7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-741037">
            <id>Q9BRK4</id>
            <label>LZTS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-302345">
            <id>Q8ND90</id>
            <label>PNMA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-307486">
            <id>P63208</id>
            <label>SKP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-355744">
            <id>Q12933</id>
            <label>TRAF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-740098">
            <id>P36406</id>
            <label>TRIM23</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-744859">
            <id>Q96IX9</id>
        </interactant>
        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="caution">
        <text evidence="2">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="AL009051">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007072">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96IX9"/>
    <dbReference type="SMR" id="Q96IX9"/>
    <dbReference type="FunCoup" id="Q96IX9">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96IX9">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q96IX9">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="BioMuta" id="HGNC:28169"/>
    <dbReference type="DMDM" id="74751951"/>
    <dbReference type="MassIVE" id="Q96IX9"/>
    <dbReference type="AGR" id="HGNC:28169"/>
    <dbReference type="GeneCards" id="ANKRD36BP1"/>
    <dbReference type="HGNC" id="HGNC:28169">
        <property type="gene designation" value="ANKRD36BP1"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q96IX9"/>
    <dbReference type="PAN-GO" id="Q96IX9">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96IX9"/>
    <dbReference type="PathwayCommons" id="Q96IX9"/>
    <dbReference type="SignaLink" id="Q96IX9"/>
    <dbReference type="Pharos" id="Q96IX9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96IX9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF50">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 36A-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000318851" description="Putative ankyrin repeat domain-containing protein 26-like 1">
        <location>
            <begin position="1"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="15"/>
            <end position="112"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="119" mass="14172" checksum="E06449B08455E397" modified="2001-12-01" version="1">MGTRTLQFEISDSHEKEEDLLHKNHLMQDEIARLRLEIHTIKNQILEKKYLKDIEIIKRKHEDLQKALKQNGEKSTKTIAHYSGQLTALTDENTMLRSKLEKEKQSRQRLTKWNHTIVD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="87" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NF67</accession>
    <name>A2012_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Putative ankyrin repeat domain-containing protein 20A12</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="3" type="primary">ANKRD20A12P</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
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                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
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                <person name="Hirao M."/>
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                <person name="Mizuno T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
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                <person name="White S."/>
                <person name="Whitehead S.L."/>
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                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="2">Could be the product of a pseudogene.</text>
    </comment>
    <comment type="sequence caution" evidence="2">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC03393" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AK090412">
        <property type="protein sequence ID" value="BAC03393.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL583842">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8NF67"/>
    <dbReference type="SMR" id="Q8NF67"/>
    <dbReference type="IntAct" id="Q8NF67">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="BioMuta" id="HGNC:43603"/>
    <dbReference type="DMDM" id="338817985"/>
    <dbReference type="jPOST" id="Q8NF67"/>
    <dbReference type="MassIVE" id="Q8NF67"/>
    <dbReference type="AGR" id="HGNC:43603"/>
    <dbReference type="GeneCards" id="ANKRD20A12P"/>
    <dbReference type="HGNC" id="HGNC:43603">
        <property type="gene designation" value="ANKRD20A12P"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q8NF67"/>
    <dbReference type="PAN-GO" id="Q8NF67">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q8NF67"/>
    <dbReference type="SignaLink" id="Q8NF67"/>
    <dbReference type="ChiTaRS" id="ANKRD20A12P">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="Q8NF67">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NF67"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NF67">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF1">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000336056" description="Putative ankyrin repeat domain-containing protein 20A12">
        <location>
            <begin position="1"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="65"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="171"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC03393." evidence="2" ref="1">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000305" key="2"/>
    <evidence type="ECO:0000312" key="3">
        <source>
            <dbReference type="HGNC" id="HGNC:43603"/>
        </source>
    </evidence>
    <sequence length="263" mass="31171" checksum="049B7CF47A31915B" modified="2011-06-28" version="3">MKEMYENAEDKVNNSTGKWSCVEERICHLQHENPCIEQQLDDVHQKEDHKEIVTNIQRGFIESGKKDLMLEEKNKKLMNECDHLKESLFQYEREKAERVVVVRQLQQEAADSLKKLTMLESPLEGISHYHINLDETQVPKKKLFQVESQFDDLMVEKEAVSSKCVNLAKENQVFQQKLLSMKKVQQECEKLEEDKKMLEEEILNLKTHMENSMVELSKLQEYKSELDERAMQAVEKLEEIHLQEQAQYKKQLEQLNKDIIQLH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-27" modified="2026-01-28" version="146" xmlns="https://uniprot.org/uniprot">
    <accession>Q5TYW2</accession>
    <accession>Q9H0H6</accession>
    <name>A20A1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Ankyrin repeat domain-containing protein 20A1</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ANKRD20A1</name>
        <name type="synonym">ANKRD20A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <dbReference type="EMBL" id="AL136793">
        <property type="protein sequence ID" value="CAB66727.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX649567">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6620.1"/>
    <dbReference type="RefSeq" id="NP_115626.2">
        <property type="nucleotide sequence ID" value="NM_032250.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5TYW2"/>
    <dbReference type="SMR" id="Q5TYW2"/>
    <dbReference type="BioGRID" id="123947">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5TYW2">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5TYW2">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="MINT" id="Q5TYW2"/>
    <dbReference type="STRING" id="9606.ENSP00000477695"/>
    <dbReference type="GlyGen" id="Q5TYW2">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5TYW2"/>
    <dbReference type="PhosphoSitePlus" id="Q5TYW2"/>
    <dbReference type="BioMuta" id="ANKRD20A1"/>
    <dbReference type="DMDM" id="74746676"/>
    <dbReference type="jPOST" id="Q5TYW2"/>
    <dbReference type="MassIVE" id="Q5TYW2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000477695"/>
    <dbReference type="PeptideAtlas" id="Q5TYW2"/>
    <dbReference type="Antibodypedia" id="73397">
        <property type="antibodies" value="70 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84210"/>
    <dbReference type="Ensembl" id="ENST00000562196.6">
        <property type="protein sequence ID" value="ENSP00000477695.1"/>
        <property type="gene ID" value="ENSG00000260691.8"/>
    </dbReference>
    <dbReference type="GeneID" id="84210"/>
    <dbReference type="KEGG" id="hsa:84210"/>
    <dbReference type="MANE-Select" id="ENST00000562196.6">
        <property type="protein sequence ID" value="ENSP00000477695.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032250.5"/>
        <property type="RefSeq protein sequence ID" value="NP_115626.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004aeu.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23665"/>
    <dbReference type="ClinPGx" id="PA134953648"/>
    <dbReference type="CTD" id="84210"/>
    <dbReference type="GeneCards" id="ANKRD20A1"/>
    <dbReference type="HGNC" id="HGNC:23665">
        <property type="gene designation" value="ANKRD20A1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000260691">
        <property type="expression patterns" value="Tissue enhanced (testis)"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000260691"/>
    <dbReference type="eggNOG" id="KOG0504">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163801"/>
    <dbReference type="HOGENOM" id="CLU_001111_3_0_1"/>
    <dbReference type="InParanoid" id="Q5TYW2"/>
    <dbReference type="OrthoDB" id="6577879at2759"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5TYW2"/>
    <dbReference type="PathwayCommons" id="Q5TYW2"/>
    <dbReference type="SignaLink" id="Q5TYW2"/>
    <dbReference type="Agora" id="ENSG00000260691"/>
    <dbReference type="BioGRID-ORCS" id="84210">
        <property type="hits" value="52 hits in 329 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ANKRD20A1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84210"/>
    <dbReference type="Pharos" id="Q5TYW2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5TYW2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5TYW2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000260691">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5TYW2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="LIFEdb"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000518">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 20A1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000208">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 26"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF1">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="4"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000240834" description="Ankyrin repeat domain-containing protein 20A1">
        <location>
            <begin position="1"/>
            <end position="823"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="66"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="99"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="132"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="165"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 5">
        <location>
            <begin position="198"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="301"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="355"/>
            <end position="402"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="431"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="565"/>
            <end position="724"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="776"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="372"/>
            <end position="384"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="679"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="772"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB66727." evidence="3" ref="1">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="805"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="823" mass="94048" checksum="0AE8585829E6E91B" modified="2004-12-07" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-27" modified="2026-01-28" version="140" xmlns="https://uniprot.org/uniprot">
    <accession>Q5SQ80</accession>
    <name>A20A2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 20A2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Ankyrin repeat domain-containing protein 20A2 pseudogene</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ANKRD20A2P</name>
        <name type="synonym">ANKRD20A2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="369" last="374">
            <title>DNA sequence and analysis of human chromosome 9.</title>
            <authorList>
                <person name="Humphray S.J."/>
                <person name="Oliver K."/>
                <person name="Hunt A.R."/>
                <person name="Plumb R.W."/>
                <person name="Loveland J.E."/>
                <person name="Howe K.L."/>
                <person name="Andrews T.D."/>
                <person name="Searle S."/>
                <person name="Hunt S.E."/>
                <person name="Scott C.E."/>
                <person name="Jones M.C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Ashwell R.I.S."/>
                <person name="Babbage A.K."/>
                <person name="Babbage S."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Barker D.J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Beasley O."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
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                <person name="Carter N.P."/>
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                <person name="Clegg S."/>
                <person name="Collier R.E."/>
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                <person name="Crosier M."/>
                <person name="Cummings A.T."/>
                <person name="Davies J."/>
                <person name="Dhami P."/>
                <person name="Dunn M."/>
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                <person name="Dyer L.W."/>
                <person name="Earthrowl M.E."/>
                <person name="Faulkner L."/>
                <person name="Fleming C.J."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="French L."/>
                <person name="Fricker D.G."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Ghori J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Glison C."/>
                <person name="Grafham D.V."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Guy J."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E.A."/>
                <person name="Heath P.D."/>
                <person name="Henderson C.D."/>
                <person name="Hopkins B.L."/>
                <person name="Howard P.J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A.A."/>
                <person name="Kay M."/>
                <person name="Keenan S."/>
                <person name="Kershaw J.K."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Langford C."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Leversha M."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nisbett J."/>
                <person name="Nordsiek G."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Porter K.M."/>
                <person name="Pandian R."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Povey S."/>
                <person name="Ramsey Y."/>
                <person name="Rand V."/>
                <person name="Scharfe M."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S.K."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C.A."/>
                <person name="Swarbreck D."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Thomas D.W."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="West A.P."/>
                <person name="Whitehead S.L."/>
                <person name="Willey D.L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Ashurst J.L."/>
                <person name="Coulson A."/>
                <person name="Blocker H."/>
                <person name="Durbin R.M."/>
                <person name="Sulston J.E."/>
                <person name="Hubbard T."/>
                <person name="Jackson M.J."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="3">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="AL773545">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX664727">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5SQ80"/>
    <dbReference type="SMR" id="Q5SQ80"/>
    <dbReference type="BioGRID" id="137462">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5SQ80">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5SQ80">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000366826"/>
    <dbReference type="iPTMnet" id="Q5SQ80"/>
    <dbReference type="PhosphoSitePlus" id="Q5SQ80"/>
    <dbReference type="BioMuta" id="ANKRD20A2"/>
    <dbReference type="DMDM" id="74743522"/>
    <dbReference type="jPOST" id="Q5SQ80"/>
    <dbReference type="MassIVE" id="Q5SQ80"/>
    <dbReference type="PaxDb" id="9606-ENSP00000366826"/>
    <dbReference type="PeptideAtlas" id="Q5SQ80"/>
    <dbReference type="Antibodypedia" id="71388">
        <property type="antibodies" value="3 antibodies from 2 providers"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004acd.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31979"/>
    <dbReference type="GeneCards" id="ANKRD20A2P"/>
    <dbReference type="HGNC" id="HGNC:31979">
        <property type="gene designation" value="ANKRD20A2P"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000183148"/>
    <dbReference type="eggNOG" id="KOG0504">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="HOGENOM" id="CLU_001111_3_0_1"/>
    <dbReference type="InParanoid" id="Q5SQ80"/>
    <dbReference type="OMA" id="INVNMLY"/>
    <dbReference type="OrthoDB" id="6577879at2759"/>
    <dbReference type="PAN-GO" id="Q5SQ80">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5SQ80"/>
    <dbReference type="PathwayCommons" id="Q5SQ80"/>
    <dbReference type="BioGRID-ORCS" id="441430">
        <property type="hits" value="358 hits in 595 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="441430"/>
    <dbReference type="Pharos" id="Q5SQ80">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5SQ80"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5SQ80">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000183148">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 102 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5SQ80">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000518">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 20A1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000208">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 26"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF1">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="4"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000240837" description="Putative ankyrin repeat domain-containing protein 20A2">
        <location>
            <begin position="1"/>
            <end position="823"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="66"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="99"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="132"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="165"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 5">
        <location>
            <begin position="198"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="301"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="355"/>
            <end position="402"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="431"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="565"/>
            <end position="724"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="776"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="372"/>
            <end position="384"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:31979"/>
        </source>
    </evidence>
    <sequence length="823" mass="94087" checksum="6C1C478C3EE9B67F" modified="2004-12-21" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-27" modified="2026-01-28" version="146" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VUR7</accession>
    <name>A20A3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 20A3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Ankyrin repeat domain-containing protein 20A3 pseudogene</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ANKRD20A3P</name>
        <name type="synonym">ANKRD20A3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="369" last="374">
            <title>DNA sequence and analysis of human chromosome 9.</title>
            <authorList>
                <person name="Humphray S.J."/>
                <person name="Oliver K."/>
                <person name="Hunt A.R."/>
                <person name="Plumb R.W."/>
                <person name="Loveland J.E."/>
                <person name="Howe K.L."/>
                <person name="Andrews T.D."/>
                <person name="Searle S."/>
                <person name="Hunt S.E."/>
                <person name="Scott C.E."/>
                <person name="Jones M.C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Ashwell R.I.S."/>
                <person name="Babbage A.K."/>
                <person name="Babbage S."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Barker D.J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Beasley O."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Chen Y."/>
                <person name="Clarke G."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Crosier M."/>
                <person name="Cummings A.T."/>
                <person name="Davies J."/>
                <person name="Dhami P."/>
                <person name="Dunn M."/>
                <person name="Dutta I."/>
                <person name="Dyer L.W."/>
                <person name="Earthrowl M.E."/>
                <person name="Faulkner L."/>
                <person name="Fleming C.J."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="French L."/>
                <person name="Fricker D.G."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Ghori J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Glison C."/>
                <person name="Grafham D.V."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Guy J."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E.A."/>
                <person name="Heath P.D."/>
                <person name="Henderson C.D."/>
                <person name="Hopkins B.L."/>
                <person name="Howard P.J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A.A."/>
                <person name="Kay M."/>
                <person name="Keenan S."/>
                <person name="Kershaw J.K."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Langford C."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Leversha M."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nisbett J."/>
                <person name="Nordsiek G."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Porter K.M."/>
                <person name="Pandian R."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Povey S."/>
                <person name="Ramsey Y."/>
                <person name="Rand V."/>
                <person name="Scharfe M."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S.K."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C.A."/>
                <person name="Swarbreck D."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Thomas D.W."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="West A.P."/>
                <person name="Whitehead S.L."/>
                <person name="Willey D.L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Ashurst J.L."/>
                <person name="Coulson A."/>
                <person name="Blocker H."/>
                <person name="Durbin R.M."/>
                <person name="Sulston J.E."/>
                <person name="Hubbard T."/>
                <person name="Jackson M.J."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="3">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="AL513478">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VUR7"/>
    <dbReference type="SMR" id="Q5VUR7"/>
    <dbReference type="BioGRID" id="137457">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5VUR7">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5VUR7">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000482325"/>
    <dbReference type="GlyGen" id="Q5VUR7">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VUR7"/>
    <dbReference type="PhosphoSitePlus" id="Q5VUR7"/>
    <dbReference type="BioMuta" id="ANKRD20A3"/>
    <dbReference type="DMDM" id="74747147"/>
    <dbReference type="jPOST" id="Q5VUR7"/>
    <dbReference type="MassIVE" id="Q5VUR7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000482325"/>
    <dbReference type="PeptideAtlas" id="Q5VUR7"/>
    <dbReference type="Antibodypedia" id="72885">
        <property type="antibodies" value="141 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="441425"/>
    <dbReference type="UCSC" id="uc033cut.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31981"/>
    <dbReference type="GeneCards" id="ANKRD20A3P"/>
    <dbReference type="HGNC" id="HGNC:31981">
        <property type="gene designation" value="ANKRD20A3P"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000276203"/>
    <dbReference type="eggNOG" id="KOG0504">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="HOGENOM" id="CLU_001111_3_0_1"/>
    <dbReference type="InParanoid" id="Q5VUR7"/>
    <dbReference type="OrthoDB" id="6577879at2759"/>
    <dbReference type="PAN-GO" id="Q5VUR7">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VUR7"/>
    <dbReference type="PathwayCommons" id="Q5VUR7"/>
    <dbReference type="BioGRID-ORCS" id="441425">
        <property type="hits" value="27 hits in 292 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="441425"/>
    <dbReference type="Pharos" id="Q5VUR7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VUR7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VUR7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000276203">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 98 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5VUR7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000518">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 20A1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000208">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 26"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF1">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="4"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000240836" description="Putative ankyrin repeat domain-containing protein 20A3">
        <location>
            <begin position="1"/>
            <end position="823"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="66"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="99"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="132"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="165"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 5">
        <location>
            <begin position="198"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="301"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="355"/>
            <end position="402"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="431"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="571"/>
            <end position="724"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="776"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="372"/>
            <end position="384"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:31981"/>
        </source>
    </evidence>
    <sequence length="823" mass="94108" checksum="CC0ED7895CA092E4" modified="2004-12-07" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-27" modified="2026-01-28" version="130" xmlns="https://uniprot.org/uniprot">
    <accession>Q4UJ75</accession>
    <name>A20A4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 20A4</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Ankyrin repeat domain-containing protein 20A4 pseudogene</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ANKRD20A4P</name>
        <name type="synonym">ANKRD20A4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="369" last="374">
            <title>DNA sequence and analysis of human chromosome 9.</title>
            <authorList>
                <person name="Humphray S.J."/>
                <person name="Oliver K."/>
                <person name="Hunt A.R."/>
                <person name="Plumb R.W."/>
                <person name="Loveland J.E."/>
                <person name="Howe K.L."/>
                <person name="Andrews T.D."/>
                <person name="Searle S."/>
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                <person name="Bird C.P."/>
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                <person name="Burford D."/>
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                <person name="Frankish A."/>
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                <person name="Fricker D.G."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Ghori J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Glison C."/>
                <person name="Grafham D.V."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Guy J."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Harrison E.S.I."/>
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                <person name="Heath P.D."/>
                <person name="Henderson C.D."/>
                <person name="Hopkins B.L."/>
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                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A.A."/>
                <person name="Kay M."/>
                <person name="Keenan S."/>
                <person name="Kershaw J.K."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Langford C."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Leversha M."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
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                <person name="McLaren S."/>
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                <person name="McMurray A."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nisbett J."/>
                <person name="Nordsiek G."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Porter K.M."/>
                <person name="Pandian R."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Povey S."/>
                <person name="Ramsey Y."/>
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                <person name="Scharfe M."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S.K."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
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                <person name="Swarbreck D."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Thomas D.W."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="West A.P."/>
                <person name="Whitehead S.L."/>
                <person name="Willey D.L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Ashurst J.L."/>
                <person name="Coulson A."/>
                <person name="Blocker H."/>
                <person name="Durbin R.M."/>
                <person name="Sulston J.E."/>
                <person name="Hubbard T."/>
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                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="3">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="CR769776">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="AlphaFoldDB" id="Q4UJ75"/>
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        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q4UJ75">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="IntAct" id="Q4UJ75">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000349891"/>
    <dbReference type="GlyGen" id="Q4UJ75">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q4UJ75"/>
    <dbReference type="PhosphoSitePlus" id="Q4UJ75"/>
    <dbReference type="BioMuta" id="ANKRD20A4"/>
    <dbReference type="DMDM" id="74753541"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000349891"/>
    <dbReference type="PeptideAtlas" id="Q4UJ75"/>
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        <property type="antibodies" value="5 antibodies from 5 providers"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004afn.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31982"/>
    <dbReference type="GeneCards" id="ANKRD20A4P"/>
    <dbReference type="HGNC" id="HGNC:31982">
        <property type="gene designation" value="ANKRD20A4P"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000172014"/>
    <dbReference type="eggNOG" id="KOG0504">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="HOGENOM" id="CLU_001111_3_0_1"/>
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    <dbReference type="OrthoDB" id="6577879at2759"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
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    <dbReference type="PathwayCommons" id="Q4UJ75"/>
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        <property type="hits" value="25 hits in 242 CRISPR screens"/>
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        <property type="component" value="Chromosome 9"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000172014">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 97 other cell types or tissues"/>
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        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="InterPro" id="IPR039497">
        <property type="entry name" value="CC144C-like_CC_dom"/>
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        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
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        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
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    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="3"/>
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    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF14915">
        <property type="entry name" value="CCDC144C"/>
        <property type="match status" value="2"/>
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    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
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    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
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    <proteinExistence type="uncertain"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000240835" description="Putative ankyrin repeat domain-containing protein 20A4">
        <location>
            <begin position="1"/>
            <end position="823"/>
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    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="66"/>
            <end position="95"/>
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    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="99"/>
            <end position="128"/>
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    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="132"/>
            <end position="161"/>
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    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="165"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 5">
        <location>
            <begin position="198"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="301"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="356"/>
            <end position="405"/>
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    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="431"/>
            <end position="480"/>
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    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="565"/>
            <end position="724"/>
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    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="776"/>
            <end position="806"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="371"/>
            <end position="384"/>
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    </feature>
    <evidence type="ECO:0000255" key="1"/>
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        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
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        <source>
            <dbReference type="HGNC" id="HGNC:31982"/>
        </source>
    </evidence>
    <sequence length="823" mass="94149" checksum="597B760D5733208A" modified="2005-07-05" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-09-02" modified="2026-01-28" version="91" xmlns="https://uniprot.org/uniprot">
    <accession>A0PJZ0</accession>
    <accession>Q4G1B6</accession>
    <name>A20A5_HUMAN</name>
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        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 20A5</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Ankyrin repeat domain-containing protein 20A5 pseudogene</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ANKRD20A5P</name>
        <name type="synonym">ANKRD20A5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2005" name="Nature" volume="437" first="551" last="555">
            <title>DNA sequence and analysis of human chromosome 18.</title>
            <authorList>
                <person name="Nusbaum C."/>
                <person name="Zody M.C."/>
                <person name="Borowsky M.L."/>
                <person name="Kamal M."/>
                <person name="Kodira C.D."/>
                <person name="Taylor T.D."/>
                <person name="Whittaker C.A."/>
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                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Yang X."/>
                <person name="Abouelleil A."/>
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                <person name="Cook A."/>
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                <person name="Hall J.L."/>
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                <person name="Lui A."/>
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                <person name="Naylor J.W."/>
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                <person name="O'Leary S.B."/>
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                <person name="Smith C.L."/>
                <person name="Talamas J.A."/>
                <person name="Topham K."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Wain H.M."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Fujiyama A."/>
                <person name="Hattori M."/>
                <person name="Birren B.W."/>
                <person name="Sakaki Y."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16177791"/>
            <dbReference type="DOI" id="10.1038/nature03983"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="caution">
        <text evidence="1">Could be the product of a pseudogene.</text>
    </comment>
    <comment type="sequence caution" evidence="1">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAH22023" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AP001004">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022023">
        <property type="protein sequence ID" value="AAH22023.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC127726">
        <property type="protein sequence ID" value="AAI27727.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="A0PJZ0"/>
    <dbReference type="SMR" id="A0PJZ0"/>
    <dbReference type="iPTMnet" id="A0PJZ0"/>
    <dbReference type="PhosphoSitePlus" id="A0PJZ0"/>
    <dbReference type="BioMuta" id="HGNC:33833"/>
    <dbReference type="MassIVE" id="A0PJZ0"/>
    <dbReference type="ProteomicsDB" id="74"/>
    <dbReference type="AGR" id="HGNC:33833"/>
    <dbReference type="GeneCards" id="ANKRD20A5P"/>
    <dbReference type="HGNC" id="HGNC:33833">
        <property type="gene designation" value="ANKRD20A5P"/>
    </dbReference>
    <dbReference type="InParanoid" id="A0PJZ0"/>
    <dbReference type="PAN-GO" id="A0PJZ0">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ANKRD20A5P">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="A0PJZ0">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A0PJZ0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
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    <dbReference type="RNAct" id="A0PJZ0">
        <property type="molecule type" value="protein"/>
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    <dbReference type="FunFam" id="1.25.40.20:FF:000208">
        <property type="entry name" value="Ankyrin repeat domain-containing protein 26"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF1">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 20A1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="3"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000348534" description="Putative ankyrin repeat domain-containing protein 20A5">
        <location>
            <begin position="1"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="66"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="99"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="132"/>
            <end position="161"/>
        </location>
    </feature>
    <evidence type="ECO:0000305" key="1"/>
    <sequence length="165" mass="18446" checksum="383D167903D39BB2" modified="2007-01-09" version="1">MKLFGFRSRRGQTVLGSIDHLYTGSGYRIRYSELQKIHKAAVKGDAAEMERCLARRSGDLDALDKQHRTALHLACASGHVKVVTLLVNRKCQIDIYDKENRTPLIQAVHCQEEACAVILLEHGANPNLKDIYGNTALHYAVYSESTSLAEKLLFHGENIEALDKV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-05" modified="2026-01-28" version="133" xmlns="https://uniprot.org/uniprot">
    <accession>A8K2U0</accession>
    <accession>B5MDD1</accession>
    <accession>B7Z7V4</accession>
    <accession>D3DUV3</accession>
    <accession>F5H2Z2</accession>
    <accession>Q2M224</accession>
    <accession>Q6ZW52</accession>
    <accession>Q6ZW53</accession>
    <accession>Q8N1M4</accession>
    <accession>Q96LQ8</accession>
    <name>A2ML1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-2-macroglobulin-like protein 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>C3 and PZP-like alpha-2-macroglobulin domain-containing protein 9</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="10" type="primary">A2ML1</name>
        <name evidence="13" type="synonym">CPAMD9</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANTS GLU-850; TRP-1122; ARG-1229; VAL-1257 AND MET-1312</scope>
        <source>
            <tissue evidence="11">Brain</tissue>
            <tissue>Testis</tissue>
            <tissue evidence="12">Tongue</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS GLU-850; TRP-1122; ARG-1229 AND VAL-1257</scope>
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        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANTS GLU-850; TRP-1122; ARG-1229 AND VAL-1257</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1290-1454</scope>
        <source>
            <tissue evidence="10">Brain</tissue>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2015" name="Nat. Genet." volume="47" first="917" last="920">
            <title>Rare A2ML1 variants confer susceptibility to otitis media.</title>
            <authorList>
                <consortium name="University of Washington Center for Mendelian Genomics"/>
                <person name="Santos-Cortez R.L."/>
                <person name="Chiong C.M."/>
                <person name="Reyes-Quintos M.R."/>
                <person name="Tantoco M.L."/>
                <person name="Wang X."/>
                <person name="Acharya A."/>
                <person name="Abbe I."/>
                <person name="Giese A.P."/>
                <person name="Smith J.D."/>
                <person name="Allen E.K."/>
                <person name="Li B."/>
                <person name="Cutiongco-de la Paz E.M."/>
                <person name="Garcia M.C."/>
                <person name="Llanes E.G."/>
                <person name="Labra P.J."/>
                <person name="Gloria-Cruz T.L."/>
                <person name="Chan A.L."/>
                <person name="Wang G.T."/>
                <person name="Daly K.A."/>
                <person name="Shendure J."/>
                <person name="Bamshad M.J."/>
                <person name="Nickerson D.A."/>
                <person name="Patel J.A."/>
                <person name="Riazuddin S."/>
                <person name="Sale M.M."/>
                <person name="Chonmaitree T."/>
                <person name="Ahmed Z.M."/>
                <person name="Abes G.T."/>
                <person name="Leal S.M."/>
            </authorList>
            <dbReference type="PubMed" id="26121085"/>
            <dbReference type="DOI" id="10.1038/ng.3347"/>
        </citation>
        <scope>INVOLVEMENT IN OM</scope>
        <scope>VARIANTS 255-GLN--GLU-1454 DEL; ALA-296; ARG-356; 893-ARG--GLU-1454 DEL; 972-GLU--GLU-1454 DEL; TRP-1001 AND VAL-1431</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4">Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity). Displays inhibitory activity against chymotrypsin, papain, thermolysin, subtilisin A and, to a lesser extent, elastase but not trypsin. May play an important role during desquamation by inhibiting extracellular proteases.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>A8K2U0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>A8K2U0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_057135"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">In the epidermis, expressed predominantly in the granular layer at the apical edge of keratinocytes (at protein level). Also detected in placenta, testis and thymus but not in epithelia of kidney, lung, small intestine or colon.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="4">Up-regulated during keratinocyte differentiation.</text>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-05294">
            <name>Otitis media</name>
            <acronym>OM</acronym>
            <description>An inflammation of the middle ear resulting in earache, fever, hearing disturbance, and vertigo.</description>
            <dbReference type="MIM" id="166760"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB71612" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC04793" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC85653" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC85654" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK057908">
        <property type="protein sequence ID" value="BAB71612.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK096448">
        <property type="protein sequence ID" value="BAC04793.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK123591">
        <property type="protein sequence ID" value="BAC85653.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK123592">
        <property type="protein sequence ID" value="BAC85654.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290355">
        <property type="protein sequence ID" value="BAF83044.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK302555">
        <property type="protein sequence ID" value="BAH13740.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832139">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006513">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006581">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471116">
        <property type="protein sequence ID" value="EAW88603.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471116">
        <property type="protein sequence ID" value="EAW88606.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093840">
        <property type="protein sequence ID" value="AAH93840.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC112131">
        <property type="protein sequence ID" value="AAI12132.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS73439.1">
        <molecule id="A8K2U0-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8596.2">
        <molecule id="A8K2U0-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269353.2">
        <molecule id="A8K2U0-2"/>
        <property type="nucleotide sequence ID" value="NM_001282424.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_653271.3">
        <molecule id="A8K2U0-1"/>
        <property type="nucleotide sequence ID" value="NM_144670.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016874359.1">
        <molecule id="A8K2U0-1"/>
        <property type="nucleotide sequence ID" value="XM_017018870.2"/>
    </dbReference>
    <dbReference type="PDB" id="7Q1Y">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="4.40 A"/>
        <property type="chains" value="A/B=19-1454"/>
    </dbReference>
    <dbReference type="PDB" id="7Q5Z">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="A=19-1454"/>
    </dbReference>
    <dbReference type="PDB" id="7Q60">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.13 A"/>
        <property type="chains" value="A=19-1454"/>
    </dbReference>
    <dbReference type="PDB" id="7Q61">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.88 A"/>
        <property type="chains" value="A=19-1454"/>
    </dbReference>
    <dbReference type="PDB" id="7Q62">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.18 A"/>
        <property type="chains" value="A/B=19-1454"/>
    </dbReference>
    <dbReference type="PDBsum" id="7Q1Y"/>
    <dbReference type="PDBsum" id="7Q5Z"/>
    <dbReference type="PDBsum" id="7Q60"/>
    <dbReference type="PDBsum" id="7Q61"/>
    <dbReference type="PDBsum" id="7Q62"/>
    <dbReference type="AlphaFoldDB" id="A8K2U0"/>
    <dbReference type="EMDB" id="EMD-13847"/>
    <dbReference type="EMDB" id="EMD-13848"/>
    <dbReference type="EMDB" id="EMD-13849"/>
    <dbReference type="EMDB" id="EMD-13850"/>
    <dbReference type="SMR" id="A8K2U0"/>
    <dbReference type="FunCoup" id="A8K2U0">
        <property type="interactions" value="344"/>
    </dbReference>
    <dbReference type="IntAct" id="A8K2U0">
        <property type="interactions" value="127"/>
    </dbReference>
    <dbReference type="MINT" id="A8K2U0"/>
    <dbReference type="STRING" id="9606.ENSP00000299698"/>
    <dbReference type="MEROPS" id="I39.007"/>
    <dbReference type="GlyConnect" id="1003">
        <property type="glycosylation" value="3 N-Linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="A8K2U0">
        <property type="glycosylation" value="6 sites, 3 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="A8K2U0">
        <property type="glycosylation" value="9 sites, 4 N-linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="A8K2U0"/>
    <dbReference type="PhosphoSitePlus" id="A8K2U0"/>
    <dbReference type="BioMuta" id="A2ML1"/>
    <dbReference type="jPOST" id="A8K2U0"/>
    <dbReference type="MassIVE" id="A8K2U0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000299698"/>
    <dbReference type="PeptideAtlas" id="A8K2U0"/>
    <dbReference type="PRIDE" id="A8K2U0"/>
    <dbReference type="ProteomicsDB" id="1852">
        <molecule id="A8K2U0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="26118"/>
    <dbReference type="Antibodypedia" id="23090">
        <property type="antibodies" value="117 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="144568"/>
    <dbReference type="Ensembl" id="ENST00000299698.12">
        <molecule id="A8K2U0-1"/>
        <property type="protein sequence ID" value="ENSP00000299698.7"/>
        <property type="gene ID" value="ENSG00000166535.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000539547.5">
        <molecule id="A8K2U0-2"/>
        <property type="protein sequence ID" value="ENSP00000438292.1"/>
        <property type="gene ID" value="ENSG00000166535.20"/>
    </dbReference>
    <dbReference type="GeneID" id="144568"/>
    <dbReference type="KEGG" id="hsa:144568"/>
    <dbReference type="MANE-Select" id="ENST00000299698.12">
        <property type="protein sequence ID" value="ENSP00000299698.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_144670.6"/>
        <property type="RefSeq protein sequence ID" value="NP_653271.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001quz.6">
        <molecule id="A8K2U0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23336"/>
    <dbReference type="CTD" id="144568"/>
    <dbReference type="DisGeNET" id="144568"/>
    <dbReference type="GeneCards" id="A2ML1"/>
    <dbReference type="HGNC" id="HGNC:23336">
        <property type="gene designation" value="A2ML1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000166535">
        <property type="expression patterns" value="Tissue enhanced (esophagus, vagina)"/>
    </dbReference>
    <dbReference type="MalaCards" id="A2ML1"/>
    <dbReference type="MIM" id="166760">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="610627">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166535"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000166535"/>
    <dbReference type="eggNOG" id="KOG1366">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163018"/>
    <dbReference type="HOGENOM" id="CLU_001634_0_0_1"/>
    <dbReference type="InParanoid" id="A8K2U0"/>
    <dbReference type="OMA" id="YQNAYLH"/>
    <dbReference type="OrthoDB" id="9998011at2759"/>
    <dbReference type="PAN-GO" id="A8K2U0">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="A8K2U0"/>
    <dbReference type="PathwayCommons" id="A8K2U0"/>
    <dbReference type="SignaLink" id="A8K2U0"/>
    <dbReference type="Agora" id="ENSG00000166535"/>
    <dbReference type="BioGRID-ORCS" id="144568">
        <property type="hits" value="12 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="A2ML1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="144568"/>
    <dbReference type="Pharos" id="A8K2U0">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A8K2U0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="A8K2U0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000166535">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 116 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="A8K2U0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030414">
        <property type="term" value="F:peptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004867">
        <property type="term" value="F:serine-type endopeptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052548">
        <property type="term" value="P:regulation of endopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd02897">
        <property type="entry name" value="A2M_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="DisProt" id="DP03807"/>
    <dbReference type="FunFam" id="2.60.120.1540:FF:000007">
        <property type="entry name" value="Alpha-2-macroglobulin like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.10:FF:000312">
        <property type="entry name" value="Alpha-2-macroglobulin like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.1940:FF:000004">
        <property type="entry name" value="Alpha-2-macroglobulin like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.50.10.20:FF:000001">
        <property type="entry name" value="CD109 isoform 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.1930:FF:000001">
        <property type="entry name" value="CD109 isoform 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.50.10.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.20.130.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.120.1540">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.1930">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.1940">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="6.20.50.160">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.690">
        <property type="entry name" value="Alpha-macroglobulin, receptor-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.10">
        <property type="entry name" value="Immunoglobulins"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009048">
        <property type="entry name" value="A-macroglobulin_rcpt-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036595">
        <property type="entry name" value="A-macroglobulin_rcpt-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050473">
        <property type="entry name" value="A2M/Complement_sys"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011625">
        <property type="entry name" value="A2M_N_BRD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041813">
        <property type="entry name" value="A2M_TED"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR047565">
        <property type="entry name" value="Alpha-macroglob_thiol-ester_cl"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011626">
        <property type="entry name" value="Alpha-macroglobulin_TED"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013783">
        <property type="entry name" value="Ig-like_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014756">
        <property type="entry name" value="Ig_E-set"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001599">
        <property type="entry name" value="Macroglobln_a2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019742">
        <property type="entry name" value="MacrogloblnA2_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002890">
        <property type="entry name" value="MG2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041555">
        <property type="entry name" value="MG3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR040839">
        <property type="entry name" value="MG4"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008930">
        <property type="entry name" value="Terpenoid_cyclase/PrenylTrfase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11412:SF182">
        <property type="entry name" value="ALPHA-2-MACROGLOBULIN-LIKE PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11412">
        <property type="entry name" value="MACROGLOBULIN / COMPLEMENT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00207">
        <property type="entry name" value="A2M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07703">
        <property type="entry name" value="A2M_BRD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07677">
        <property type="entry name" value="A2M_recep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01835">
        <property type="entry name" value="MG2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17791">
        <property type="entry name" value="MG3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17789">
        <property type="entry name" value="MG4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07678">
        <property type="entry name" value="TED_complement"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM01360">
        <property type="entry name" value="A2M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM01359">
        <property type="entry name" value="A2M_N_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM01361">
        <property type="entry name" value="A2M_recep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM01419">
        <property type="entry name" value="Thiol-ester_cl"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF49410">
        <property type="entry name" value="Alpha-macroglobulin receptor domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF81296">
        <property type="entry name" value="E set domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48239">
        <property type="entry name" value="Terpenoid cyclases/Protein prenyltransferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00477">
        <property type="entry name" value="ALPHA_2_MACROGLOBULIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0082">Bait region</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0882">Thioester bond</keyword>
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            <begin position="1"/>
            <end position="17"/>
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            <begin position="18"/>
            <end position="1454"/>
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            <begin position="695"/>
            <end position="726"/>
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            <position position="120"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="281"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="409"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="857"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1020"/>
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    <feature type="disulfide bond" evidence="1">
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            <begin position="40"/>
            <end position="78"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="241"/>
            <end position="291"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="259"/>
            <end position="279"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="464"/>
            <end position="557"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="589"/>
            <end position="769"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="819"/>
            <end position="847"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="845"/>
            <end position="881"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="919"/>
            <end position="1307"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="1075"/>
            <end position="1123"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="1338"/>
            <end position="1453"/>
        </location>
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    <feature type="cross-link" description="Isoglutamyl cysteine thioester (Cys-Gln)" evidence="1">
        <location>
            <begin position="970"/>
            <end position="973"/>
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    <feature type="splice variant" id="VSP_057135" description="In isoform 2." evidence="8">
        <location>
            <begin position="2"/>
            <end position="492"/>
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    </feature>
    <feature type="sequence variant" id="VAR_055463" description="In dbSNP:rs11047499.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="207"/>
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    <feature type="sequence variant" id="VAR_081009" description="Risk factor for otitis media." evidence="6">
        <location>
            <begin position="255"/>
            <end position="1454"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081010" description="In dbSNP:rs192888493." evidence="6">
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        <location>
            <position position="296"/>
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    </feature>
    <feature type="sequence variant" id="VAR_081011" description="May be a risk factor for otitis media; dbSNP:rs863224953." evidence="6">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059083" description="In dbSNP:rs1860926." evidence="3 5 7">
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        <location>
            <position position="850"/>
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    <feature type="sequence variant" id="VAR_081012" description="Risk factor for otitis media." evidence="6">
        <location>
            <begin position="893"/>
            <end position="1454"/>
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    <feature type="sequence variant" id="VAR_055464" description="In dbSNP:rs1558526.">
        <original>C</original>
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            <position position="970"/>
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    <feature type="sequence variant" id="VAR_081013" description="Risk factor for otitis media." evidence="6">
        <location>
            <begin position="972"/>
            <end position="1454"/>
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    <feature type="sequence variant" id="VAR_081014" description="May be a risk factor for otitis media; dbSNP:rs201725377." evidence="6">
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        <location>
            <position position="1001"/>
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    <feature type="sequence variant" id="VAR_071854" description="In dbSNP:rs1860967." evidence="3 5 7">
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            <position position="1122"/>
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    <feature type="sequence variant" id="VAR_055465" description="In dbSNP:rs7959680.">
        <original>T</original>
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        <location>
            <position position="1131"/>
        </location>
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    <feature type="sequence variant" id="VAR_059084" description="In dbSNP:rs10219561." evidence="3 5 7">
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        <location>
            <position position="1229"/>
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    <feature type="sequence variant" id="VAR_071855" description="In dbSNP:rs7308811." evidence="3 5 7">
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            <position position="1257"/>
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    <feature type="sequence variant" id="VAR_071856" description="In dbSNP:rs201083574." evidence="3">
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        <location>
            <position position="1312"/>
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    <feature type="sequence variant" id="VAR_055466" description="In dbSNP:rs7315591.">
        <original>T</original>
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            <position position="1412"/>
        </location>
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    <feature type="sequence variant" id="VAR_081015" description="In dbSNP:rs863224955." evidence="6">
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        <location>
            <position position="1431"/>
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    <feature type="sequence conflict" description="In Ref. 1; BAC85654/BAF83044." evidence="9" ref="1">
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            <position position="733"/>
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    <feature type="sequence conflict" description="In Ref. 2; AL832139." evidence="9" ref="2">
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            <position position="748"/>
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    <feature type="sequence conflict" description="In Ref. 1; BAF83044." evidence="9" ref="1">
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            <position position="1150"/>
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    <feature type="sequence conflict" description="In Ref. 1; BAC85654." evidence="9" ref="1">
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            <position position="1248"/>
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    <feature type="sequence conflict" description="In Ref. 2; AL832139." evidence="9" ref="2">
        <original>P</original>
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            <position position="1452"/>
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        <location>
            <begin position="24"/>
            <end position="32"/>
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    <feature type="strand" evidence="16">
        <location>
            <begin position="35"/>
            <end position="42"/>
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    <feature type="strand" evidence="16">
        <location>
            <begin position="51"/>
            <end position="57"/>
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    <feature type="strand" evidence="16">
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            <begin position="62"/>
            <end position="69"/>
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    <feature type="strand" evidence="16">
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            <begin position="76"/>
            <end position="82"/>
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    <feature type="strand" evidence="16">
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            <end position="102"/>
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    <feature type="strand" evidence="16">
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<entry dataset="Swiss-Prot" created="2007-05-15" modified="2026-01-28" version="88" xmlns="https://uniprot.org/uniprot">
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            <fullName>Uncharacterized protein ADAMTSL4-AS1</fullName>
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            <fullName>ADAMTSL4 antisense RNA 1</fullName>
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            <fullName>ADAMTSL4 antisense gene protein 1</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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    </organism>
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                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
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        <property type="protein sequence ID" value="BAC87085.1"/>
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    </dbReference>
    <dbReference type="EMBL" id="AL356356">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132990">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132992">
        <property type="protein sequence ID" value="AAI32993.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5T5F5"/>
    <dbReference type="BioMuta" id="HGNC:32041"/>
    <dbReference type="DMDM" id="74745067"/>
    <dbReference type="MassIVE" id="Q5T5F5"/>
    <dbReference type="AGR" id="HGNC:32041"/>
    <dbReference type="GeneCards" id="ADAMTSL4-AS1"/>
    <dbReference type="HGNC" id="HGNC:32041">
        <property type="gene designation" value="ADAMTSL4-AS1"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q5T5F5"/>
    <dbReference type="PAN-GO" id="Q5T5F5">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5T5F5"/>
    <dbReference type="ChiTaRS" id="ADAMTSL4-AS1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="Q5T5F5">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5T5F5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5T5F5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000286610" description="Uncharacterized protein ADAMTSL4-AS1">
        <location>
            <begin position="1"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="87"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="119"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC87085." evidence="2" ref="1">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC87085." evidence="2" ref="1">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="129" mass="14090" checksum="4FCA65B2E557F8D5" modified="2004-12-21" version="1">MWLWQDIQCCPAPPSAPPRALEPGRAPPPPGEGLGAGIPSLSPPQKKPQSVGICVRQKGRQKAGLEKGNRKKELRQANCPSLRPQRKGADTRRLPRETRPTKKRTAAAQPFLQLWNPAPHTSNGRTGDL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-25" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NPC4</accession>
    <accession>B2R7C4</accession>
    <accession>Q9P1X5</accession>
    <name>A4GAT_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Lactosylceramide 4-alpha-galactosyltransferase</fullName>
            <ecNumber evidence="5">2.4.1.228</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-1,4-N-acetylglucosaminyltransferase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-1,4-galactosyltransferase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha4Gal-T1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">CD77 synthase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Globotriaosylceramide synthase</fullName>
            <shortName evidence="13">Gb3 synthase</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">P1/Pk synthase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>UDP-galactose:beta-D-galactosyl-beta1-R 4-alpha-D-galactosyltransferase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">A4GALT</name>
        <name type="synonym">A14GALT</name>
        <name type="synonym">A4GALT1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="10591208"/>
            <dbReference type="DOI" id="10.1038/990031"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2016" name="Biochem. Biophys. Res. Commun." volume="470" first="168" last="174">
            <title>Human Gb3/CD77 synthase reveals specificity toward two or four different acceptors depending on amino acid at position 211, creating P(k), P1 and NOR blood group antigens.</title>
            <authorList>
                <person name="Kaczmarek R."/>
                <person name="Duk M."/>
                <person name="Szymczak K."/>
                <person name="Korchagina E."/>
                <person name="Tyborowska J."/>
                <person name="Mikolajczyk K."/>
                <person name="Bovin N."/>
                <person name="Szewczyk B."/>
                <person name="Jaskiewicz E."/>
                <person name="Czerwinski M."/>
            </authorList>
            <dbReference type="PubMed" id="26773500"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2016.01.017"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>CHARACTERIZATION OF VARIANT GLU-211</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2018" name="Cancer Res." volume="78" first="2952" last="2965">
            <title>Transition of Mesenchymal and Epithelial Cancer Cells Depends on alpha1-4 Galactosyltransferase-Mediated Glycosphingolipids.</title>
            <authorList>
                <person name="Jacob F."/>
                <person name="Alam S."/>
                <person name="Konantz M."/>
                <person name="Liang C.Y."/>
                <person name="Kohler R.S."/>
                <person name="Everest-Dass A.V."/>
                <person name="Huang Y.L."/>
                <person name="Rimmer N."/>
                <person name="Fedier A."/>
                <person name="Schoetzau A."/>
                <person name="Lopez M.N."/>
                <person name="Packer N.H."/>
                <person name="Lengerke C."/>
                <person name="Heinzelmann-Schwarz V."/>
            </authorList>
            <dbReference type="PubMed" id="29572228"/>
            <dbReference type="DOI" id="10.1158/0008-5472.can-17-2223"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>MUTAGENESIS OF ASP-194</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2021" name="J. Biol. Chem." volume="296" first="100299" last="100299">
            <title>Human Gb3/CD77 synthase produces P1 glycotope-capped N-glycans, which mediate Shiga toxin 1 but not Shiga toxin 2 cell entry.</title>
            <authorList>
                <person name="Szymczak-Kulus K."/>
                <person name="Weidler S."/>
                <person name="Bereznicka A."/>
                <person name="Mikolajczyk K."/>
                <person name="Kaczmarek R."/>
                <person name="Bednarz B."/>
                <person name="Zhang T."/>
                <person name="Urbaniak A."/>
                <person name="Olczak M."/>
                <person name="Park E.Y."/>
                <person name="Majorczyk E."/>
                <person name="Kapczynska K."/>
                <person name="Lukasiewicz J."/>
                <person name="Wuhrer M."/>
                <person name="Unverzagt C."/>
                <person name="Czerwinski M."/>
            </authorList>
            <dbReference type="PubMed" id="33460651"/>
            <dbReference type="DOI" id="10.1016/j.jbc.2021.100299"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
        <scope>CHARACTERIZATION OF VARIANT GLU-211</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="37752" last="37756">
            <title>Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals.</title>
            <authorList>
                <person name="Furukawa K."/>
                <person name="Iwamura K."/>
                <person name="Uchikawa M."/>
                <person name="Sojka B.N."/>
                <person name="Wiels J."/>
                <person name="Okajima T."/>
                <person name="Urano T."/>
                <person name="Furukawa K."/>
            </authorList>
            <dbReference type="PubMed" id="10993874"/>
            <dbReference type="DOI" id="10.1074/jbc.c000625200"/>
        </citation>
        <scope>VARIANTS VAL-37; LYS-183; ASP-187 AND LEU-251</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2002" name="Transfusion" volume="42" first="48" last="51">
            <title>Three-base deletion and one-base insertion of the alpha(1,4)galactosyltransferase gene responsible for the P phenotype.</title>
            <authorList>
                <person name="Koda Y."/>
                <person name="Soejima M."/>
                <person name="Sato H."/>
                <person name="Maeda Y."/>
                <person name="Kimura H."/>
            </authorList>
            <dbReference type="PubMed" id="11896312"/>
            <dbReference type="DOI" id="10.1046/j.1537-2995.2002.00014.x"/>
        </citation>
        <scope>VARIANT PHE-80 DEL</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2012" name="J. Biol. Chem." volume="287" first="38220" last="38230">
            <title>A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome.</title>
            <authorList>
                <person name="Suchanowska A."/>
                <person name="Kaczmarek R."/>
                <person name="Duk M."/>
                <person name="Lukasiewicz J."/>
                <person name="Smolarek D."/>
                <person name="Majorczyk E."/>
                <person name="Jaskiewicz E."/>
                <person name="Laskowska A."/>
                <person name="Wasniowska K."/>
                <person name="Grodecka M."/>
                <person name="Lisowska E."/>
                <person name="Czerwinski M."/>
            </authorList>
            <dbReference type="PubMed" id="22965229"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.408286"/>
        </citation>
        <scope>VARIANT GLU-211</scope>
        <scope>POLYMORPHISM</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>CHARACTERIZATION OF VARIANT GLU-211</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 5 8 9 10 11">Glycosyltransferase involved in biosynthesis of P1, P(k) and the rare NOR antigens of P1PK histo-blood group system (PubMed:10747952, PubMed:10748143, PubMed:22965229, PubMed:26773500, PubMed:29572228, PubMed:33460651). Catalyzes the transfer of galactose from UDP-alpha-D-galactose in an alpha1,4 linkage to lactosylceramide/beta-D-galactosyl-(1-&gt;4)-beta-D-glucosyl-(1&lt;-&gt;1)-ceramide(d18:1(4E)) to produce globotriaosylceramide/globoside Gb3Cer (d18:1(4E)), also known as P(k) antigen or CD77 (PubMed:10748143, PubMed:10747952, PubMed:26773500, PubMed:29572228, PubMed:22965229). Globoside Gb3Cer/P(k)/CD77 is a root structure in biosynthesis pathway of neutral glycosphingolipids of the globo-series. Broadly expressed in cell membranes of immune cells and other tissues, Gb3Cer/P(k)/CD77 antigen may participate in mechanisms that regulate cell-cell interactions and cell differentiation. In germinal center B cells, Gb3Cer/CD77 interacts with CD19 to drive centroblast-to-centrocyte transition, B cell receptor complex assembly and T follicular helper cell differentiation. In epithelium, Gb3Cer regulates CDH1/E-cadherin-dependent cell-cell adhesion counteracting epithelial-to-mesenchymal transition (By similarity) (PubMed:29572228). Synthesizes P1 glycan epitope (alpha-D-Gal-(1-&gt;4)-beta-D-Gal-(1-&gt;4)-GlcNAc-R) by transferring a galactose moiety to paragloboside nLc4 or to complex-type N-glycans (PubMed:26773500, PubMed:29572228, PubMed:33460651). Generates the rare NOR1 and NOR2 antigens which carry a Gal(alpha1-&gt;4)GalNAc terminal moiety and are both derived from Gb4Cer precursor (PubMed:22965229, PubMed:26773500, PubMed:33460651). Also able to transfer galactose to galactosylceramide/beta-D-Gal-(1&lt;-&gt;1')-Cer (PubMed:10748143).</text>
    </comment>
    <comment type="function">
        <text evidence="5 11">(Microbial infection) P1 and Pk antigens are targeted by Shiga toxins (also called verotoxins), as a way to enter the cell, inhibit protein synthesis and induce apoptosis.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a beta-D-Gal-(1-&gt;4)-beta-D-Glc-(1&lt;-&gt;1)-Cer(d18:1(4E)) + UDP-alpha-D-galactose = a globoside Gb3Cer (d18:1(4E)) + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11924"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17950"/>
            <dbReference type="ChEBI" id="CHEBI:18313"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="EC" id="2.4.1.228"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15 16">
            <dbReference type="Rhea" id="RHEA:11925"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>an N(4)-{beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 UDP-alpha-D-galactose = an N(4)-{alpha-D-Gal-(1-&gt;4)-beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Gal-(1-&gt;4)-beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 UDP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:84931"/>
            <dbReference type="Rhea" id="RHEA-COMP:20022"/>
            <dbReference type="Rhea" id="RHEA-COMP:20459"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:232681"/>
            <dbReference type="ChEBI" id="CHEBI:234056"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:84932"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>a globoside Gb4Cer + UDP-alpha-D-galactose = a globoside NOR1 + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:56184"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:88167"/>
            <dbReference type="ChEBI" id="CHEBI:140614"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16 17">
            <dbReference type="Rhea" id="RHEA:56185"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 9">
            <text>a beta-D-galactosyl-(1-&gt;4)-beta-D-glucosyl-(1&lt;-&gt;1)-ceramide + UDP-alpha-D-galactose = a globoside Gb3Cer + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:56572"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:79208"/>
            <dbReference type="ChEBI" id="CHEBI:88154"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16 17 18">
            <dbReference type="Rhea" id="RHEA:56573"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a beta-D-Gal-(1&lt;-&gt;1')-ceramide + UDP-alpha-D-galactose = alpha-D-Gal-(1-&gt;4)-beta-D-Gal-(1&lt;-&gt;1')-Cer + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60044"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:143593"/>
            <dbReference type="ChEBI" id="CHEBI:143594"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:60045"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">54.5 uM for beta-D-galactosyl-(1-&gt;4)-beta-D-glucosyl-(1&lt;-&gt;1)-ceramide(d18:1(4E))</KM>
            <KM evidence="5">132 uM for beta-D-Gal-(1&lt;-&gt;1')-Cer</KM>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="15 16 17 18">Glycolipid biosynthesis.</text>
    </comment>
    <comment type="pathway">
        <text evidence="19">Protein modification; protein glycosylation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="14">Golgi apparatus membrane</location>
            <topology evidence="14">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Ubiquitous. Highly expressed in kidney, heart, spleen, liver, testis and placenta.</text>
    </comment>
    <comment type="domain">
        <text evidence="10">The conserved DXD motif is required for catalytic activity.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="6 7 8">Genetic variation in A4GALT is responsible for the P1PK system blood group phenotypes [MIM:111400]. Different combinations or absence of the P blood group system antigens define 5 different phenotypes: P1, P2, P1(k), P2(k), and p. Genetic variation in A4GALT determines the p phenotype, which is rare and does not express any antigens. It is also known as null phenotype; p individuals have antibodies against P, P1 and P(k) antigens in their sera. These antibodies are clinically important because they can cause severe transfusion reactions and miscarriage (PubMed:10993874, PubMed:11896312). Genetic variation in A4GALT is also responsible for the NOR polyagglutination syndrome [MIM:111400]. Polyagglutination is the occurrence of red cell agglutination by virtually all human sera, but not by autologous serum or sera from newborns, creating a risk of complications during transfusions of NOR erythrocytes. It is caused by the unusual Gal(alpha1-4)GalNAc glycolipid epitope (PubMed:22965229).</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the glycosyltransferase 32 family.</text>
    </comment>
    <comment type="online information" name="Functional Glycomics Gateway - GTase">
        <link uri="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_428"/>
        <text>Lactosylceramide 4-alpha-galactosyltransferase</text>
    </comment>
    <dbReference type="EC" id="2.4.1.228" evidence="5"/>
    <dbReference type="EMBL" id="AB037883">
        <property type="protein sequence ID" value="BAA95915.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ245581">
        <property type="protein sequence ID" value="CAB93532.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB041418">
        <property type="protein sequence ID" value="BAA94503.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY941797">
        <property type="protein sequence ID" value="AAX20109.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312927">
        <property type="protein sequence ID" value="BAG35771.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z82176">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471138">
        <property type="protein sequence ID" value="EAW73274.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017068">
        <property type="protein sequence ID" value="AAH17068.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14041.1"/>
    <dbReference type="RefSeq" id="NP_001304967.1">
        <property type="nucleotide sequence ID" value="NM_001318038.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_059132.1">
        <property type="nucleotide sequence ID" value="NM_017436.7"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261701.1">
        <property type="nucleotide sequence ID" value="XM_005261644.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261703.1">
        <property type="nucleotide sequence ID" value="XM_005261646.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261704.1">
        <property type="nucleotide sequence ID" value="XM_005261647.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005261705.1">
        <property type="nucleotide sequence ID" value="XM_005261648.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006724328.1">
        <property type="nucleotide sequence ID" value="XM_006724265.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006724329.1">
        <property type="nucleotide sequence ID" value="XM_006724266.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011528535.1">
        <property type="nucleotide sequence ID" value="XM_011530233.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016884320.1">
        <property type="nucleotide sequence ID" value="XM_017028831.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047297368.1">
        <property type="nucleotide sequence ID" value="XM_047441412.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NPC4"/>
    <dbReference type="SMR" id="Q9NPC4"/>
    <dbReference type="BioGRID" id="119825">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NPC4">
        <property type="interactions" value="124"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NPC4">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NPC4"/>
    <dbReference type="STRING" id="9606.ENSP00000384794"/>
    <dbReference type="SwissLipids" id="SLP:000000760"/>
    <dbReference type="CAZy" id="GT32">
        <property type="family name" value="Glycosyltransferase Family 32"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9NPC4">
        <property type="glycosylation" value="4 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NPC4">
        <property type="glycosylation" value="5 sites, 1 N-linked glycan (2 sites), 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NPC4"/>
    <dbReference type="PhosphoSitePlus" id="Q9NPC4"/>
    <dbReference type="BioMuta" id="A4GALT"/>
    <dbReference type="DMDM" id="25452796"/>
    <dbReference type="jPOST" id="Q9NPC4"/>
    <dbReference type="MassIVE" id="Q9NPC4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000384794"/>
    <dbReference type="PeptideAtlas" id="Q9NPC4"/>
    <dbReference type="ProteomicsDB" id="81966"/>
    <dbReference type="Antibodypedia" id="239">
        <property type="antibodies" value="230 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="53947"/>
    <dbReference type="Ensembl" id="ENST00000249005.3">
        <property type="protein sequence ID" value="ENSP00000249005.2"/>
        <property type="gene ID" value="ENSG00000128274.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000381278.4">
        <property type="protein sequence ID" value="ENSP00000370678.3"/>
        <property type="gene ID" value="ENSG00000128274.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000401850.5">
        <property type="protein sequence ID" value="ENSP00000384794.1"/>
        <property type="gene ID" value="ENSG00000128274.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000642412.2">
        <property type="protein sequence ID" value="ENSP00000494127.1"/>
        <property type="gene ID" value="ENSG00000128274.18"/>
    </dbReference>
    <dbReference type="GeneID" id="53947"/>
    <dbReference type="KEGG" id="hsa:53947"/>
    <dbReference type="MANE-Select" id="ENST00000642412.2">
        <property type="protein sequence ID" value="ENSP00000494127.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_017436.7"/>
        <property type="RefSeq protein sequence ID" value="NP_059132.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc062ewk.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18149"/>
    <dbReference type="ClinPGx" id="PA24359"/>
    <dbReference type="CTD" id="53947"/>
    <dbReference type="DisGeNET" id="53947"/>
    <dbReference type="GeneCards" id="A4GALT"/>
    <dbReference type="HGNC" id="HGNC:18149">
        <property type="gene designation" value="A4GALT"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000128274">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="A4GALT"/>
    <dbReference type="MIM" id="111400">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="607922">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000128274"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000128274"/>
    <dbReference type="eggNOG" id="KOG1928">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00510000047981"/>
    <dbReference type="HOGENOM" id="CLU_049512_2_0_1"/>
    <dbReference type="InParanoid" id="Q9NPC4"/>
    <dbReference type="OMA" id="CKDSYVV"/>
    <dbReference type="OrthoDB" id="409543at2759"/>
    <dbReference type="PAN-GO" id="Q9NPC4">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NPC4"/>
    <dbReference type="BioCyc" id="MetaCyc:HS05171-MONOMER"/>
    <dbReference type="BRENDA" id="2.4.1.228">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NPC4"/>
    <dbReference type="Reactome" id="R-HSA-9840309">
        <property type="pathway name" value="Glycosphingolipid biosynthesis"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NPC4"/>
    <dbReference type="UniPathway" id="UPA00378"/>
    <dbReference type="Agora" id="ENSG00000128274"/>
    <dbReference type="BioGRID-ORCS" id="53947">
        <property type="hits" value="14 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="A4GALT">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="A4GALT"/>
    <dbReference type="GenomeRNAi" id="53947"/>
    <dbReference type="Pharos" id="Q9NPC4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NPC4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NPC4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000128274">
        <property type="expression patterns" value="Expressed in apex of heart and 125 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NPC4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000139">
        <property type="term" value="C:Golgi membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008378">
        <property type="term" value="F:galactosyltransferase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050512">
        <property type="term" value="F:lactosylceramide 4-alpha-galactosyltransferase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015643">
        <property type="term" value="F:toxic substance binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001576">
        <property type="term" value="P:globoside biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006688">
        <property type="term" value="P:glycosphingolipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007009">
        <property type="term" value="P:plasma membrane organization"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.550.20:FF:000003">
        <property type="entry name" value="Lactosylceramide 4-alpha-galactosyltransferase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.550.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007652">
        <property type="entry name" value="A1-4-GlycosylTfrase_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051981">
        <property type="entry name" value="Glycosyltransf_32"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007577">
        <property type="entry name" value="GlycoTrfase_DXD_sugar-bd_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029044">
        <property type="entry name" value="Nucleotide-diphossugar_trans"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12042:SF17">
        <property type="entry name" value="LACTOSYLCERAMIDE 4-ALPHA-GALACTOSYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12042">
        <property type="entry name" value="LACTOSYLCERAMIDE 4-ALPHA-GALACTOSYLTRANSFERASE ALPHA- 1,4-GALACTOSYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04572">
        <property type="entry name" value="Gb3_synth"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04488">
        <property type="entry name" value="Gly_transf_sug"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53448">
        <property type="entry name" value="Nucleotide-diphospho-sugar transferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0095">Blood group antigen</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000080578" description="Lactosylceramide 4-alpha-galactosyltransferase">
        <location>
            <begin position="1"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
        <location>
            <begin position="23"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="44"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="DXD motif" evidence="1">
        <location>
            <begin position="192"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014296" description="In dbSNP:rs11541159." evidence="4 6 12">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017507" description="In p individuals." evidence="7">
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022320" description="In dbSNP:rs28915383." evidence="12">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014297" description="In p individuals; complete loss of activity; dbSNP:rs74315453." evidence="4 6">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017508" description="In p individuals; partial loss of activity; dbSNP:rs28940572." evidence="6">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080910" description="In individuals with NOR polyagglutination syndrome; causes the synthesis of both Gal(alpha1-4)Gal and Gal(alpha1-4)GalNAc moieties enabling the expression of P1, Pk and NOR antigens; increases catalytic efficiency; dbSNP:rs397514502." evidence="8 9 11">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017509" description="In p individuals; complete loss of activity; dbSNP:rs28940571." evidence="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes Gb3Cer/P(k) and P1 antigen expression." evidence="10">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="194"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q67BJ4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10747952"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10748143"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10993874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11896312"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="22965229"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="26773500"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="29572228"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="33460651"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="26773500"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="10748143"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="22965229"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17">
        <source>
            <dbReference type="PubMed" id="26773500"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="18">
        <source>
            <dbReference type="PubMed" id="29572228"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="33460651"/>
        </source>
    </evidence>
    <sequence length="353" mass="40499" checksum="8755865BDA5DA205" modified="2000-10-01" version="1">MSKPPDLLLRLLRGAPRQRVCTLFIIGFKFTFFVSIMIYWHVVGEPKEKGQLYNLPAEIPCPTLTPPTPPSHGPTPGNIFFLETSDRTNPNFLFMCSVESAARTHPESHVLVLMKGLPGGNASLPRHLGISLLSCFPNVQMLPLDLRELFRDTPLADWYAAVQGRWEPYLLPVLSDASRIALMWKFGGIYLDTDFIVLKNLRNLTNVLGTQSRYVLNGAFLAFERRHEFMALCMRDFVDHYNGWIWGHQGPQLLTRVFKKWCSIRSLAESRACRGVTTLPPEAFYPIPWQDWKKYFEDINPEELPRLLSATYAVHVWNKKSQGTRFEATSRALLAQLHARYCPTTHEAMKMYL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2016-07-06" modified="2026-01-28" version="63" xmlns="https://uniprot.org/uniprot">
    <accession>U3KPV4</accession>
    <name>A3LT2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">Alpha-1,3-galactosyltransferase 2</fullName>
            <ecNumber evidence="3">2.4.1.87</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Isoglobotriaosylceramide synthase</fullName>
            <shortName evidence="6">iGb3 synthase</shortName>
            <shortName evidence="6">iGb3S</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9" type="primary">A3GALT2</name>
        <name evidence="9" type="synonym">A3GALT2P</name>
        <name evidence="6" type="synonym">IGBS3S</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Sandrin M.S."/>
            </authorList>
            <dbReference type="PubMed" id="18630988"/>
            <dbReference type="DOI" id="10.1371/journal.pbio.0060172"/>
        </citation>
        <scope>MISCELLANEOUS</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2013" name="J. Carbohydr. Chem." volume="32" first="44" last="67">
            <title>Lack of iGb3 and isoglobo-Series glycosphingolipids in pig organs used for xenotransplantation: implications for natural killer T-cell biology.</title>
            <authorList>
                <person name="Tahiri F."/>
                <person name="Li Y."/>
                <person name="Hawke D."/>
                <person name="Ganiko L."/>
                <person name="Almeida I."/>
                <person name="Levery S."/>
                <person name="Zhou D."/>
            </authorList>
            <dbReference type="PubMed" id="23378701"/>
            <dbReference type="DOI" id="10.1080/07328303.2012.741637"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="8">Synthesizes the galactose-alpha(1,3)-galactose group on the glycosphingolipid isoglobotrihexosylceramide or isogloboside 3 (iGb3) by catalyzing the transfer of galactose from UDP-Galactose to its acceptor molecule Gal-beta-1,4-Glc-ceramide. Can also catalyze the addition of galactose to iGb3 itself to form polygalactose structures.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a beta-D-galactosyl-(1-&gt;4)-N-acetyl-beta-D-glucosaminyl derivative + UDP-alpha-D-galactose = an alpha-D-galactosyl-(1-&gt;3)-beta-D-galactosyl-(1-&gt;4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13013"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:133507"/>
            <dbReference type="ChEBI" id="CHEBI:138024"/>
            <dbReference type="EC" id="2.4.1.87"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:13014"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a beta-D-Gal-(1-&gt;4)-beta-D-Glc-(1&lt;-&gt;1)-Cer(d18:1(4E)) + UDP-alpha-D-galactose = an isogloboside iGb3Cer (d18:1(4E)) + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:42000"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17950"/>
            <dbReference type="ChEBI" id="CHEBI:52570"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:42001"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a globoside Gb3Cer + UDP-alpha-D-galactose = a globoside GalGb3Cer + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:56740"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:66914"/>
            <dbReference type="ChEBI" id="CHEBI:88154"/>
            <dbReference type="ChEBI" id="CHEBI:140743"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:56741"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Golgi apparatus</location>
            <location evidence="2">Golgi stack membrane</location>
            <topology evidence="2">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <text evidence="2">Also found in numerous large vesicles throughout the cytoplasm of the soma.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expressed in thymus and monocyte derived dendritic cells.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity).</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the glycosyltransferase 6 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="6">According to a report, the spliced A3GALT2 mRNA is not detected in human tissues (PubMed:18630988). The functional activity of human A3GALT2 tested by expressing a chimeric protein containing the catalytic domain of human A3GALT2 is unable to synthesize isogloboside 3 (iGb3). Futhermore mutagenesis experiments in rat, show that the mutant 'Asn-253' of human A3GALT2 completely eliminates alpha-1,3-galactosyltransferase activity (PubMed:18630988).</text>
    </comment>
    <dbReference type="EC" id="2.4.1.87" evidence="3"/>
    <dbReference type="EMBL" id="AL513327">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS60080.1"/>
    <dbReference type="RefSeq" id="NP_001073907.1">
        <property type="nucleotide sequence ID" value="NM_001080438.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="U3KPV4"/>
    <dbReference type="SMR" id="U3KPV4"/>
    <dbReference type="FunCoup" id="U3KPV4">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000475261"/>
    <dbReference type="GlyCosmos" id="U3KPV4">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="U3KPV4">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="BioMuta" id="A3GALT2"/>
    <dbReference type="MassIVE" id="U3KPV4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000475261"/>
    <dbReference type="Antibodypedia" id="76335">
        <property type="antibodies" value="3 antibodies from 1 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="127550"/>
    <dbReference type="Ensembl" id="ENST00000442999.3">
        <property type="protein sequence ID" value="ENSP00000475261.1"/>
        <property type="gene ID" value="ENSG00000184389.9"/>
    </dbReference>
    <dbReference type="GeneID" id="127550"/>
    <dbReference type="KEGG" id="hsa:127550"/>
    <dbReference type="MANE-Select" id="ENST00000442999.3">
        <property type="protein sequence ID" value="ENSP00000475261.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001080438.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001073907.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc031plq.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30005"/>
    <dbReference type="CTD" id="127550"/>
    <dbReference type="DisGeNET" id="127550"/>
    <dbReference type="GeneCards" id="A3GALT2"/>
    <dbReference type="HGNC" id="HGNC:30005">
        <property type="gene designation" value="A3GALT2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184389">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="MIM" id="619850">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184389"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184389"/>
    <dbReference type="eggNOG" id="ENOG502QW2H">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182858"/>
    <dbReference type="HOGENOM" id="CLU_062445_1_0_1"/>
    <dbReference type="InParanoid" id="U3KPV4"/>
    <dbReference type="OMA" id="RFVFCMD"/>
    <dbReference type="OrthoDB" id="10013941at2759"/>
    <dbReference type="PAN-GO" id="U3KPV4">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="U3KPV4"/>
    <dbReference type="PathwayCommons" id="U3KPV4"/>
    <dbReference type="SignaLink" id="U3KPV4"/>
    <dbReference type="Agora" id="ENSG00000184389"/>
    <dbReference type="BioGRID-ORCS" id="127550">
        <property type="hits" value="11 hits in 1059 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="127550"/>
    <dbReference type="Pharos" id="U3KPV4">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:U3KPV4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="U3KPV4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184389">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 69 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032580">
        <property type="term" value="C:Golgi cisterna membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031982">
        <property type="term" value="C:vesicle"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016757">
        <property type="term" value="F:glycosyltransferase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047276">
        <property type="term" value="F:N-acetyllactosaminide 3-alpha-galactosyltransferase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005975">
        <property type="term" value="P:carbohydrate metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006688">
        <property type="term" value="P:glycosphingolipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd02515">
        <property type="entry name" value="Glyco_transf_6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.550.10:FF:000022">
        <property type="entry name" value="Histo-blood group ABO system transferase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.550.10">
        <property type="entry name" value="Spore Coat Polysaccharide Biosynthesis Protein SpsA, Chain A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005076">
        <property type="entry name" value="Glyco_trans_6"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029044">
        <property type="entry name" value="Nucleotide-diphossugar_trans"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10462:SF33">
        <property type="entry name" value="ALPHA-1,3-GALACTOSYLTRANSFERASE 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10462">
        <property type="entry name" value="GLYCOSYLTRANSFERASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03414">
        <property type="entry name" value="Glyco_transf_6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53448">
        <property type="entry name" value="Nucleotide-diphospho-sugar transferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000436524" description="Alpha-1,3-galactosyltransferase 2">
        <location>
            <begin position="1"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="7">
        <location>
            <begin position="1"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="4">
        <location>
            <begin position="13"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="7">
        <location>
            <begin position="33"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="199"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="201"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="100"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="A0A4Z3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q3V1N9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="23378701"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="18630988"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="23378701"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:30005"/>
        </source>
    </evidence>
    <sequence length="340" mass="38754" checksum="129B673AC0DCE037" modified="2013-11-13" version="1">MALKEGLRAWKRIFWRQILLTLGLLGLFLYGLPKFRHLEALIPMGVCPSATMSQLRDNFTGALRPWARPEVLTCTPWGAPIIWDGSFDPDVAKQEARQQNLTIGLTIFAVGRYLEKYLERFLETAEQHFMAGQSVMYYVFTELPGAVPRVALGPGRRLPVERVARERRWQDVSMARMRTLHAALGGLPGREAHFMFCMDVDQHFSGTFGPEALAESVAQLHSWHYHWPSWLLPFERDAHSAAAMAWGQGDFYNHAAVFGGSVAALRGLTAHCAGGLDWDRARGLEARWHDESHLNKFFWLHKPAKVLSPEFCWSPDIGPRAEIRRPRLLWAPKGYRLLRN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-01-01" modified="2026-01-28" version="234" xmlns="https://uniprot.org/uniprot">
    <accession>P08697</accession>
    <accession>B4E1B7</accession>
    <accession>Q8N5U7</accession>
    <accession>Q9UCG2</accession>
    <accession>Q9UCG3</accession>
    <name>A2AP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-2-antiplasmin</fullName>
            <shortName>Alpha-2-AP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-2-plasmin inhibitor</fullName>
            <shortName>Alpha-2-PI</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Serpin F2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">SERPINF2</name>
        <name type="synonym">AAP</name>
        <name type="synonym">PLI</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="J. Biochem." volume="102" first="1033" last="1041">
            <title>Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence.</title>
            <authorList>
                <person name="Tone M."/>
                <person name="Kikuno R."/>
                <person name="Kume-Iwaki A."/>
                <person name="Hashimoto-Gotoh T."/>
            </authorList>
            <dbReference type="PubMed" id="2830248"/>
            <dbReference type="DOI" id="10.1093/oxfordjournals.jbchem.a122141"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1988" name="Proc. Natl. Acad. Sci. U.S.A." volume="85" first="6836" last="6840">
            <title>Organization of the human alpha 2-plasmin inhibitor gene.</title>
            <authorList>
                <person name="Hirosawa S."/>
                <person name="Nakamura Y."/>
                <person name="Miura O."/>
                <person name="Sumi Y."/>
                <person name="Aoki N."/>
            </authorList>
            <dbReference type="PubMed" id="3166140"/>
            <dbReference type="DOI" id="10.1073/pnas.85.18.6836"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1989" name="Proc. Natl. Acad. Sci. U.S.A." volume="86" first="1612" last="1613">
            <authorList>
                <person name="Hirosawa S."/>
                <person name="Nakamura Y."/>
                <person name="Miura O."/>
                <person name="Sumi Y."/>
                <person name="Aoki N."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:3166140</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT VAL-2</scope>
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        <scope>PROTEIN SEQUENCE OF 481-491</scope>
        <scope>SULFATION AT TYR-484</scope>
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        <scope>REACTIVE SITES</scope>
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        <scope>DISULFIDE BOND</scope>
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            <dbReference type="PubMed" id="14751930"/>
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        </citation>
        <scope>CLEAVAGE BY SOLUBLE FAP FORM</scope>
        <scope>CLEAVAGE SITE</scope>
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        <scope>FUNCTION IN MEMBRANE-ANCHORED SERINE PROTEASE TMPRSS7 INHIBITION</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-126; ASN-295 AND ASN-309</scope>
        <source>
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        <scope>CLEAVAGE BY PLASMA MEMBRANE AND SOLUBLE FAP FORMS</scope>
        <scope>CLEAVAGE SITE</scope>
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        <scope>VARIANT APLID GLU-176 DEL</scope>
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        <scope>VARIANT APLID MET-411</scope>
        <scope>VARIANTS VAL-27; TRP-33 AND LYS-434</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin.</text>
    </comment>
    <comment type="subunit">
        <text>Forms protease inhibiting heterodimer with TMPRSS7.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P08697-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P08697-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043833 VSP_043834"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed by the liver and secreted in plasma.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 8">Proteolytically cleaved at Pro-39 by both the prolyl endopeptidase FAP form and antiplasmin-cleaving enzyme FAP soluble form to generate mature alpha-2-antiplasmin.</text>
    </comment>
    <comment type="disease" evidence="3 13">
        <disease id="DI-00075">
            <name>Alpha-2-plasmin inhibitor deficiency</name>
            <acronym>APLID</acronym>
            <description>An autosomal recessive disorder resulting in severe hemorrhagic diathesis.</description>
            <dbReference type="MIM" id="262850"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the serpin family.</text>
    </comment>
    <dbReference type="EMBL" id="D00174">
        <property type="protein sequence ID" value="BAA00124.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20786">
        <property type="protein sequence ID" value="AAA51554.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20782">
        <property type="protein sequence ID" value="AAA51554.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20783">
        <property type="protein sequence ID" value="AAA51554.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20784">
        <property type="protein sequence ID" value="AAA51554.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20785">
        <property type="protein sequence ID" value="AAA51554.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK303763">
        <property type="protein sequence ID" value="BAG64729.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC130343">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031592">
        <property type="protein sequence ID" value="AAH31592.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J02654">
        <property type="protein sequence ID" value="AAA35543.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D00116">
        <property type="protein sequence ID" value="BAA00070.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11011.1">
        <molecule id="P08697-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54064.1">
        <molecule id="P08697-2"/>
    </dbReference>
    <dbReference type="PIR" id="A31402">
        <property type="entry name" value="ITHUA2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000925.2">
        <molecule id="P08697-1"/>
        <property type="nucleotide sequence ID" value="NM_000934.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159392.1">
        <molecule id="P08697-1"/>
        <property type="nucleotide sequence ID" value="NM_001165920.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159393.1">
        <molecule id="P08697-2"/>
        <property type="nucleotide sequence ID" value="NM_001165921.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P08697"/>
    <dbReference type="SMR" id="P08697"/>
    <dbReference type="BioGRID" id="111360">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="FunCoup" id="P08697">
        <property type="interactions" value="201"/>
    </dbReference>
    <dbReference type="IntAct" id="P08697">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000321853"/>
    <dbReference type="DrugBank" id="DB09130">
        <property type="generic name" value="Copper"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08888">
        <property type="generic name" value="Ocriplasmin"/>
    </dbReference>
    <dbReference type="MEROPS" id="I04.023"/>
    <dbReference type="GlyConnect" id="1002">
        <property type="glycosylation" value="2 N-Linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P08697">
        <property type="glycosylation" value="8 sites, 7 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P08697">
        <property type="glycosylation" value="10 sites, 4 N-linked glycans (1 site), 4 O-linked glycans (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P08697"/>
    <dbReference type="PhosphoSitePlus" id="P08697"/>
    <dbReference type="BioMuta" id="SERPINF2"/>
    <dbReference type="DMDM" id="112907"/>
    <dbReference type="CPTAC" id="non-CPTAC-1065"/>
    <dbReference type="jPOST" id="P08697"/>
    <dbReference type="MassIVE" id="P08697"/>
    <dbReference type="PaxDb" id="9606-ENSP00000321853"/>
    <dbReference type="PeptideAtlas" id="P08697"/>
    <dbReference type="ProteomicsDB" id="52156">
        <molecule id="P08697-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="52157">
        <molecule id="P08697-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="852">
        <property type="antibodies" value="583 antibodies from 39 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5345"/>
    <dbReference type="Ensembl" id="ENST00000324015.7">
        <molecule id="P08697-1"/>
        <property type="protein sequence ID" value="ENSP00000321853.3"/>
        <property type="gene ID" value="ENSG00000167711.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000382061.5">
        <molecule id="P08697-1"/>
        <property type="protein sequence ID" value="ENSP00000371493.4"/>
        <property type="gene ID" value="ENSG00000167711.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000450523.6">
        <molecule id="P08697-2"/>
        <property type="protein sequence ID" value="ENSP00000403877.2"/>
        <property type="gene ID" value="ENSG00000167711.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000453066.6">
        <molecule id="P08697-1"/>
        <property type="protein sequence ID" value="ENSP00000402286.2"/>
        <property type="gene ID" value="ENSG00000167711.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000618883.3">
        <property type="protein sequence ID" value="ENSP00000479005.1"/>
        <property type="gene ID" value="ENSG00000276838.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000622842.2">
        <property type="protein sequence ID" value="ENSP00000481874.1"/>
        <property type="gene ID" value="ENSG00000276838.4"/>
    </dbReference>
    <dbReference type="GeneID" id="5345"/>
    <dbReference type="KEGG" id="hsa:5345"/>
    <dbReference type="MANE-Select" id="ENST00000453066.6">
        <property type="protein sequence ID" value="ENSP00000402286.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000934.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000925.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ftk.1">
        <molecule id="P08697-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9075"/>
    <dbReference type="ClinPGx" id="PA35522"/>
    <dbReference type="CTD" id="5345"/>
    <dbReference type="DisGeNET" id="5345"/>
    <dbReference type="GeneCards" id="SERPINF2"/>
    <dbReference type="HGNC" id="HGNC:9075">
        <property type="gene designation" value="SERPINF2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000167711">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="SERPINF2"/>
    <dbReference type="MIM" id="262850">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="613168">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000167711"/>
    <dbReference type="Orphanet" id="79">
        <property type="disease" value="Congenital alpha2-antiplasmin deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000167711"/>
    <dbReference type="eggNOG" id="KOG2392">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158386"/>
    <dbReference type="HOGENOM" id="CLU_023330_3_2_1"/>
    <dbReference type="InParanoid" id="P08697"/>
    <dbReference type="OMA" id="DMMHAHT"/>
    <dbReference type="OrthoDB" id="9947020at2759"/>
    <dbReference type="PAN-GO" id="P08697">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P08697"/>
    <dbReference type="PathwayCommons" id="P08697"/>
    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75205">
        <property type="pathway name" value="Dissolution of Fibrin Clot"/>
    </dbReference>
    <dbReference type="SignaLink" id="P08697"/>
    <dbReference type="Agora" id="ENSG00000167711"/>
    <dbReference type="BioGRID-ORCS" id="5345">
        <property type="hits" value="8 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SERPINF2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="Alpha_2-antiplasmin"/>
    <dbReference type="GenomeRNAi" id="5345"/>
    <dbReference type="Pharos" id="P08697">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P08697"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="P08697">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000167711">
        <property type="expression patterns" value="Expressed in right lobe of liver and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P08697">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072562">
        <property type="term" value="C:blood microparticle"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031012">
        <property type="term" value="C:extracellular matrix"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005577">
        <property type="term" value="C:fibrinogen complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031093">
        <property type="term" value="C:platelet alpha granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004866">
        <property type="term" value="F:endopeptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002020">
        <property type="term" value="F:protease binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004867">
        <property type="term" value="F:serine-type endopeptidase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006953">
        <property type="term" value="P:acute-phase response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048514">
        <property type="term" value="P:blood vessel morphogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030199">
        <property type="term" value="P:collagen fibril organization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042730">
        <property type="term" value="P:fibrinolysis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002034">
        <property type="term" value="P:maintenance of blood vessel diameter homeostasis by renin-angiotensin"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051918">
        <property type="term" value="P:negative regulation of fibrinolysis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010757">
        <property type="term" value="P:negative regulation of plasminogen activation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045597">
        <property type="term" value="P:positive regulation of cell differentiation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000049">
        <property type="term" value="P:positive regulation of cell-cell adhesion mediated by cadherin"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050820">
        <property type="term" value="P:positive regulation of coagulation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032967">
        <property type="term" value="P:positive regulation of collagen biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070374">
        <property type="term" value="P:positive regulation of ERK1 and ERK2 cascade"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046330">
        <property type="term" value="P:positive regulation of JNK cascade"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048661">
        <property type="term" value="P:positive regulation of smooth muscle cell proliferation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051496">
        <property type="term" value="P:positive regulation of stress fiber assembly"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045944">
        <property type="term" value="P:positive regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071636">
        <property type="term" value="P:positive regulation of transforming growth factor beta production"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd02053">
        <property type="entry name" value="serpinF2_A2AP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.497.10:FF:000003">
        <property type="entry name" value="Serpin family F member 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.39.10">
        <property type="entry name" value="Alpha-1-antitrypsin, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.497.10">
        <property type="entry name" value="Antithrombin, subunit I, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033833">
        <property type="entry name" value="Alpha2AP_serpin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023795">
        <property type="entry name" value="Serpin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023796">
        <property type="entry name" value="Serpin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000215">
        <property type="entry name" value="Serpin_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036186">
        <property type="entry name" value="Serpin_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042178">
        <property type="entry name" value="Serpin_sf_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042185">
        <property type="entry name" value="Serpin_sf_2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461:SF20">
        <property type="entry name" value="ALPHA-2-ANTIPLASMIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11461">
        <property type="entry name" value="SERINE PROTEASE INHIBITOR, SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00079">
        <property type="entry name" value="Serpin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00093">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56574">
        <property type="entry name" value="Serpins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00284">
        <property type="entry name" value="SERPIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0011">Acute phase</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0765">Sulfation</keyword>
    <feature type="signal peptide" evidence="4 14">
        <location>
            <begin position="1"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000032511" evidence="5 8 10 12">
        <location>
            <begin position="28"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000032512" description="Alpha-2-antiplasmin">
        <location>
            <begin position="40"/>
            <end position="491"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="55"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="437"/>
            <end position="491"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by prolyl endopeptidase FAP, antiplasmin-cleaving enzyme FAP soluble form" evidence="5 8">
        <location>
            <begin position="39"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="site" description="Reactive bond for plasmin">
        <location>
            <begin position="403"/>
            <end position="404"/>
        </location>
    </feature>
    <feature type="site" description="Reactive bond for chymotrypsin">
        <location>
            <begin position="404"/>
            <end position="405"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="11">
        <location>
            <position position="484"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="9">
        <location>
            <position position="126"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="9">
        <location>
            <position position="295"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="9">
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="15">
        <location>
            <begin position="70"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-322 in alpha-fibrinogen)">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043833" description="In isoform 2." evidence="16">
        <location>
            <begin position="56"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043834" description="In isoform 2." evidence="16">
        <original>LAL</original>
        <variation>VQP</variation>
        <location>
            <begin position="120"/>
            <end position="122"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_047951" description="In dbSNP:rs2070862." evidence="6">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013252" evidence="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013253" description="In dbSNP:rs2070863." evidence="3">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051956" description="In dbSNP:rs36021516.">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013254" description="In APLID; variant Okinawa; probably blocks intracellular transport of alpha-2-plasmin inhibitor." evidence="13">
        <location>
            <position position="176"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013255" description="In APLID; dbSNP:rs121965062." evidence="3">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="411"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013256" description="In dbSNP:rs1057335." evidence="3">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="434"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061792" description="In dbSNP:rs57360598.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="451"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="17" ref="10">
        <original>L</original>
        <variation>G</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="17" ref="10">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAA35543." evidence="17" ref="7">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="17" ref="10">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="408"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; AA sequence." evidence="17" ref="10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="455"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10583218"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="1385210"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14751930"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15853774"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16223769"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16335952"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="21075"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="2434496"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="2440681"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="2572590"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="8484741"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="9169621"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <sequence length="491" mass="54566" checksum="385A1C90E91A63CB" modified="1990-11-01" version="3" precursor="true">MALLWGLLVLSWSCLQGPCSVFSPVSAMEPLGRQLTSGPNQEQVSPLTLLKLGNQEPGGQTALKSPPGVCSRDPTPEQTHRLARAMMAFTADLFSLVAQTSTCPNLILSPLSVALALSHLALGAQNHTLQRLQQVLHAGSGPCLPHLLSRLCQDLGPGAFRLAARMYLQKGFPIKEDFLEQSEQLFGAKPVSLTGKQEDDLANINQWVKEATEGKIQEFLSGLPEDTVLLLLNAIHFQGFWRNKFDPSLTQRDSFHLDEQFTVPVEMMQARTYPLRWFLLEQPEIQVAHFPFKNNMSFVVLVPTHFEWNVSQVLANLSWDTLHPPLVWERPTKVRLPKLYLKHQMDLVATLSQLGLQELFQAPDLRGISEQSLVVSGVQHQSTLELSEVGVEAAAATSIAMSRMSLSSFSVNRPFLFFIFEDTTGLPLFVGSVRNPNPSAPRELKEQQDSPGNKDFLQSLKGFPRGDKLFGPDLKLVPPMEEDYPQFGSPK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-06-10" modified="2026-01-28" version="111" xmlns="https://uniprot.org/uniprot">
    <accession>A7E2S9</accession>
    <accession>B8ZZL7</accession>
    <name>A30BL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative ankyrin repeat domain-containing protein 30B-like</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ANKRD30BL</name>
        <name type="synonym">NCRNA00164</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Graves T.A."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Pepin K.H."/>
                <person name="Minx P."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
                <person name="Strong C.M."/>
                <person name="Grewal N."/>
                <person name="Goyea E."/>
                <person name="Hou S."/>
                <person name="Levy A."/>
                <person name="Martinka S."/>
                <person name="Mead K."/>
                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Shah N."/>
                <person name="Swearengen-Shahid S."/>
                <person name="Snider J."/>
                <person name="Strong J.T."/>
                <person name="Thompson J."/>
                <person name="Yoakum M."/>
                <person name="Leonard S."/>
                <person name="Pearman C."/>
                <person name="Trani L."/>
                <person name="Radionenko M."/>
                <person name="Waligorski J.E."/>
                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
                <person name="Nelson J.O."/>
                <person name="Osborne J."/>
                <person name="Ding L."/>
                <person name="Meyer R."/>
                <person name="Sabo A."/>
                <person name="Shotland Y."/>
                <person name="Sinha P."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Jones T.A."/>
                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
                <person name="Schmutz J."/>
                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
                <person name="Huang X."/>
                <person name="McPherson J.D."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-258 (ISOFORM 2)</scope>
    </reference>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>A7E2S9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>A7E2S9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_039808"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="3">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <dbReference type="EMBL" id="AC097532">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC098826">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471058">
        <property type="protein sequence ID" value="EAX11682.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC150521">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS86883.1">
        <molecule id="A7E2S9-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001345345.1">
        <molecule id="A7E2S9-1"/>
        <property type="nucleotide sequence ID" value="NM_001358416.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047300869.1">
        <molecule id="A7E2S9-2"/>
        <property type="nucleotide sequence ID" value="XM_047444913.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054198806.1">
        <molecule id="A7E2S9-2"/>
        <property type="nucleotide sequence ID" value="XM_054342831.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="A7E2S9"/>
    <dbReference type="SMR" id="A7E2S9"/>
    <dbReference type="STRING" id="9606.ENSP00000386398"/>
    <dbReference type="GlyGen" id="A7E2S9">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="BioMuta" id="ANKRD30BL"/>
    <dbReference type="jPOST" id="A7E2S9"/>
    <dbReference type="MassIVE" id="A7E2S9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000386398"/>
    <dbReference type="PeptideAtlas" id="A7E2S9"/>
    <dbReference type="Antibodypedia" id="81986">
        <property type="antibodies" value="3 antibodies from 3 providers"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000295181.6">
        <molecule id="A7E2S9-2"/>
        <property type="protein sequence ID" value="ENSP00000295181.6"/>
        <property type="gene ID" value="ENSG00000163046.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409867.6">
        <molecule id="A7E2S9-1"/>
        <property type="protein sequence ID" value="ENSP00000386398.1"/>
        <property type="gene ID" value="ENSG00000163046.16"/>
    </dbReference>
    <dbReference type="GeneID" id="554226"/>
    <dbReference type="KEGG" id="hsa:554226"/>
    <dbReference type="MANE-Select" id="ENST00000409867.6">
        <property type="protein sequence ID" value="ENSP00000386398.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001358416.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001345345.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc061nxe.1">
        <molecule id="A7E2S9-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:35167"/>
    <dbReference type="CTD" id="554226"/>
    <dbReference type="GeneCards" id="ANKRD30BL"/>
    <dbReference type="HGNC" id="HGNC:35167">
        <property type="gene designation" value="ANKRD30BL"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000163046">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000163046"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000163046"/>
    <dbReference type="eggNOG" id="KOG0504">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000164163"/>
    <dbReference type="HOGENOM" id="CLU_000134_9_4_1"/>
    <dbReference type="InParanoid" id="A7E2S9"/>
    <dbReference type="OMA" id="CINWGDA"/>
    <dbReference type="OrthoDB" id="9540030at2759"/>
    <dbReference type="PAN-GO" id="A7E2S9">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="A7E2S9"/>
    <dbReference type="Agora" id="ENSG00000163046"/>
    <dbReference type="ChiTaRS" id="ANKRD30BL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="A7E2S9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A7E2S9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="A7E2S9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000163046">
        <property type="expression patterns" value="Expressed in colonic epithelium and 83 other cell types or tissues"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050657">
        <property type="entry name" value="Ankyrin_repeat_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN 36-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24147:SF63">
        <property type="entry name" value="ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 30A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01415">
        <property type="entry name" value="ANKYRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="3"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000341256" description="Putative ankyrin repeat domain-containing protein 30B-like">
        <location>
            <begin position="1"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="71"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="104"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="137"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="170"/>
            <end position="199"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="216"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="218"/>
            <end position="232"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="243"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039808" description="In isoform 2." evidence="2">
        <original>VHQQLLEYKQKISKNSQNSNPEGTSEGTPDEAAPLAERTPDTAESLVERTPDE</original>
        <variation>TALMLAICHGSSEIVGKLLQQNVDICAEATCGMIAERYAVACGFNL</variation>
        <location>
            <begin position="206"/>
            <end position="258"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="2">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="258" mass="28549" checksum="529F3DEEC99F27E1" modified="2010-10-05" version="3">MERLSAAPVKGQTGPERPSPFSQLVYTNNDSYVIHHGDLRKIHKAASRGQAWKLERMMKKTTMDLNIRDAKKRTALYWACANGHAEVVTLLVDRKCQLDVLDGENRTILMKALQCQREACANILIDSGADPNIVDVYGNTAVHYAVNSENLSVVAKLLSCGADIEVKNKAGHTPLLLAIRKRSEEIVEFLLTKNANANAVDKFKCVHQQLLEYKQKISKNSQNSNPEGTSEGTPDEAAPLAERTPDTAESLVERTPDE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-25" modified="2026-01-28" version="168" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UNA3</accession>
    <accession>Q0VDK1</accession>
    <accession>Q0VDK2</accession>
    <name>A4GCT_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">Alpha-1,4-N-acetylglucosaminyltransferase</fullName>
            <shortName evidence="6">Alpha4GnT</shortName>
            <ecNumber evidence="4">2.4.1.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="8" type="primary">A4GNT</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Proc. Natl. Acad. Sci. U.S.A." volume="96" first="8991" last="8996">
            <title>Expression cloning of a human alpha1, 4-N-acetylglucosaminyltransferase that forms GlcNAcalpha1--&gt;4Galbeta--&gt;R, a glycan specifically expressed in the gastric gland mucous cell-type mucin.</title>
            <authorList>
                <person name="Nakayama J."/>
                <person name="Yeh J.-C."/>
                <person name="Misra A.K."/>
                <person name="Ito S."/>
                <person name="Katsuyama T."/>
                <person name="Fukuda M."/>
            </authorList>
            <dbReference type="PubMed" id="10430883"/>
            <dbReference type="DOI" id="10.1073/pnas.96.16.8991"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ASP-218</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4">Catalyzes the transfer of N-acetylglucosamine (GlcNAc) residues from UDP-N-acetyl-alpha-D-glucosamine donnors to beta (1-&gt;4)-linked or beta-(1-&gt;3)-linked galactose residues on O-glycans like core 2 branched O-glycans (PubMed:10430883). Necessary for the synthesis of type III mucin which is specifically produced in the stomach, duodenum, and pancreatic duct (PubMed:10430883). May protect against inflammation-associated gastric adenocarcinomas (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a beta-D-galactoside + UDP-N-acetyl-alpha-D-glucosamine = an N-acetyl-alpha-D-glucosaminyl-(1-&gt;4)-beta-D-galactosyl derivative + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:85983"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28034"/>
            <dbReference type="ChEBI" id="CHEBI:57705"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:235336"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:85984"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 3-O-{beta-D-galactosyl-(1-&gt;3)-[N-acetyl-beta-D-glucosaminyl-(1-&gt;6)]-N-acetyl-alpha-D-galactosaminyl}-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;3)-[beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-threonyl-[protein] + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86035"/>
            <dbReference type="Rhea" id="RHEA-COMP:14420"/>
            <dbReference type="Rhea" id="RHEA-COMP:20700"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57705"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:139607"/>
            <dbReference type="ChEBI" id="CHEBI:235339"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:86036"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 3-O-{beta-D-Gal-(1-&gt;3)-[beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-threonyl-[protein] + 2 UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;3)-[alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-threonyl-[protein] + 2 UDP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:86039"/>
            <dbReference type="Rhea" id="RHEA-COMP:20698"/>
            <dbReference type="Rhea" id="RHEA-COMP:20699"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57705"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:235337"/>
            <dbReference type="ChEBI" id="CHEBI:235338"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:86040"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 3-O-{beta-D-Gal-(1-&gt;3)-[beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-seryl-[protein] + 2 UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;3)-[alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-seryl-[protein] + 2 UDP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:86043"/>
            <dbReference type="Rhea" id="RHEA-COMP:20707"/>
            <dbReference type="Rhea" id="RHEA-COMP:20708"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57705"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:235340"/>
            <dbReference type="ChEBI" id="CHEBI:235341"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:86044"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>3-O-{beta-D-galactosyl-(1-&gt;3)-[N-acetyl-beta-D-glucosaminyl-(1-&gt;6)]-N-acetyl-alpha-D-galactosaminyl}-L-seryl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = a 3-O-{alpha-D-GlcNAc-(1-&gt;4)-beta-D-Gal-(1-&gt;3)-[beta-D-GlcNAc-(1-&gt;6)]-alpha-D-GalNAc}-L-seryl-[protein] + UDP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86059"/>
            <dbReference type="Rhea" id="RHEA-COMP:14419"/>
            <dbReference type="Rhea" id="RHEA-COMP:20709"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57705"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
            <dbReference type="ChEBI" id="CHEBI:139605"/>
            <dbReference type="ChEBI" id="CHEBI:235342"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:86060"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="4">Protein modification; protein glycosylation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Golgi apparatus membrane</location>
            <topology evidence="3">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Detected in stomach and pancreas.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The conserved DXD motif is involved in enzyme activity.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the glycosyltransferase 32 family.</text>
    </comment>
    <comment type="online information" name="Functional Glycomics Gateway - GTase">
        <link uri="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_532"/>
        <text>Alpha-1,4-N-acetylglucosaminyltransferase</text>
    </comment>
    <dbReference type="EC" id="2.4.1.-" evidence="4"/>
    <dbReference type="EMBL" id="AF141315">
        <property type="protein sequence ID" value="AAD48406.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC119639">
        <property type="protein sequence ID" value="AAI19640.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC119640">
        <property type="protein sequence ID" value="AAI19641.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3097.1"/>
    <dbReference type="RefSeq" id="NP_057245.1">
        <property type="nucleotide sequence ID" value="NM_016161.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016862032.1">
        <property type="nucleotide sequence ID" value="XM_017006543.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016862033.1">
        <property type="nucleotide sequence ID" value="XM_017006544.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054202697.1">
        <property type="nucleotide sequence ID" value="XM_054346722.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054202698.1">
        <property type="nucleotide sequence ID" value="XM_054346723.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9UNA3"/>
    <dbReference type="SMR" id="Q9UNA3"/>
    <dbReference type="BioGRID" id="119330">
        <property type="interactions" value="59"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9UNA3">
        <property type="interactions" value="37"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UNA3">
        <property type="interactions" value="42"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000236709"/>
    <dbReference type="CAZy" id="GT32">
        <property type="family name" value="Glycosyltransferase Family 32"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9UNA3">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UNA3">
        <property type="glycosylation" value="4 sites"/>
    </dbReference>
    <dbReference type="PhosphoSitePlus" id="Q9UNA3"/>
    <dbReference type="BioMuta" id="A4GNT"/>
    <dbReference type="DMDM" id="25452797"/>
    <dbReference type="MassIVE" id="Q9UNA3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000236709"/>
    <dbReference type="PeptideAtlas" id="Q9UNA3"/>
    <dbReference type="Antibodypedia" id="2373">
        <property type="antibodies" value="354 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51146"/>
    <dbReference type="Ensembl" id="ENST00000236709.4">
        <property type="protein sequence ID" value="ENSP00000236709.3"/>
        <property type="gene ID" value="ENSG00000118017.5"/>
    </dbReference>
    <dbReference type="GeneID" id="51146"/>
    <dbReference type="KEGG" id="hsa:51146"/>
    <dbReference type="MANE-Select" id="ENST00000236709.4">
        <property type="protein sequence ID" value="ENSP00000236709.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016161.3"/>
        <property type="RefSeq protein sequence ID" value="NP_057245.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ers.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17968"/>
    <dbReference type="ClinPGx" id="PA134960042"/>
    <dbReference type="CTD" id="51146"/>
    <dbReference type="DisGeNET" id="51146"/>
    <dbReference type="GeneCards" id="A4GNT"/>
    <dbReference type="HGNC" id="HGNC:17968">
        <property type="gene designation" value="A4GNT"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000118017">
        <property type="expression patterns" value="Tissue enriched (stomach)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000118017"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000118017"/>
    <dbReference type="eggNOG" id="KOG1928">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00510000047981"/>
    <dbReference type="HOGENOM" id="CLU_049512_2_0_1"/>
    <dbReference type="InParanoid" id="Q9UNA3"/>
    <dbReference type="OMA" id="IWDCMEN"/>
    <dbReference type="OrthoDB" id="407609at2759"/>
    <dbReference type="PAN-GO" id="Q9UNA3">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UNA3"/>
    <dbReference type="PathwayCommons" id="Q9UNA3"/>
    <dbReference type="Reactome" id="R-HSA-913709">
        <property type="pathway name" value="O-linked glycosylation of mucins"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UNA3"/>
    <dbReference type="UniPathway" id="UPA00378"/>
    <dbReference type="Agora" id="ENSG00000118017"/>
    <dbReference type="BioGRID-ORCS" id="51146">
        <property type="hits" value="6 hits in 1138 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="A4GNT">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="51146"/>
    <dbReference type="Pharos" id="Q9UNA3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UNA3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9UNA3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000118017">
        <property type="expression patterns" value="Expressed in pylorus and 70 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000139">
        <property type="term" value="C:Golgi membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008375">
        <property type="term" value="F:acetylglucosaminyltransferase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005975">
        <property type="term" value="P:carbohydrate metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050673">
        <property type="term" value="P:epithelial cell proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009101">
        <property type="term" value="P:glycoprotein biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050680">
        <property type="term" value="P:negative regulation of epithelial cell proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006493">
        <property type="term" value="P:protein O-linked glycosylation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016266">
        <property type="term" value="P:protein O-linked glycosylation via N-acetyl-galactosamine"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.550.20:FF:000003">
        <property type="entry name" value="Lactosylceramide 4-alpha-galactosyltransferase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.550.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007652">
        <property type="entry name" value="A1-4-GlycosylTfrase_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051981">
        <property type="entry name" value="Glycosyltransf_32"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007577">
        <property type="entry name" value="GlycoTrfase_DXD_sugar-bd_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029044">
        <property type="entry name" value="Nucleotide-diphossugar_trans"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12042:SF16">
        <property type="entry name" value="ALPHA-1,4-N-ACETYLGLUCOSAMINYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12042">
        <property type="entry name" value="LACTOSYLCERAMIDE 4-ALPHA-GALACTOSYLTRANSFERASE ALPHA- 1,4-GALACTOSYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04572">
        <property type="entry name" value="Gb3_synth"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04488">
        <property type="entry name" value="Gly_transf_sug"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53448">
        <property type="entry name" value="Nucleotide-diphospho-sugar transferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000080583" description="Alpha-1,4-N-acetylglucosaminyltransferase">
        <location>
            <begin position="1"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="1"/>
            <end position="4"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
        <location>
            <begin position="5"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="26"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="DXD motif" evidence="2">
        <location>
            <begin position="167"/>
            <end position="169"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022096" description="In dbSNP:rs2246945." evidence="5">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q14BT6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9JI93"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10430883"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="10430883"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:17968"/>
        </source>
    </evidence>
    <sequence length="340" mass="39497" checksum="00D667A8394300AB" modified="2000-05-01" version="1">MRKELQLSLSVTLLLVCGFLYQFTLKSSCLFCLPSFKSHQGLEALLSHRRGIVFLETSERMEPPHLVSCSVESAAKIYPEWPVVFFMKGLTDSTPMPSNSTYPAFSFLSAIDNVFLFPLDMKRLLEDTPLFSWYNQINASAERNWLHISSDASRLAIIWKYGGIYMDTDVISIRPIPEENFLAAQASRYSSNGIFGFLPHHPFLWECMENFVEHYNSAIWGNQGPELMTRMLRVWCKLEDFQEVSDLRCLNISFLHPQRFYPISYREWRRYYEVWDTEPSFNVSYALHLWNHMNQEGRAVIRGSNTLVENLYRKHCPRTYRDLIKGPEGSVTGELGPGNK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>P02750</accession>
    <accession>Q8N4F5</accession>
    <accession>Q96QZ4</accession>
    <name>A2GL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Leucine-rich alpha-2-glycoprotein</fullName>
            <shortName>LRG</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">LRG1</name>
        <name type="synonym">LRG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="J. Leukoc. Biol." volume="72" first="478" last="485">
            <title>Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation.</title>
            <authorList>
                <person name="O'Donnell L.C."/>
                <person name="Druhan L.J."/>
                <person name="Avalos B.R."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-133</scope>
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            <tissue>Colon</tissue>
            <tissue>Kidney</tissue>
            <tissue>Lung</tissue>
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    <reference key="3">
        <citation type="journal article" date="1985" name="Proc. Natl. Acad. Sci. U.S.A." volume="82" first="1906" last="1910">
            <title>Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum.</title>
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                <person name="Takahashi N."/>
                <person name="Takahashi Y."/>
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            <dbReference type="DOI" id="10.1073/pnas.82.7.1906"/>
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        <scope>PROTEIN SEQUENCE OF 36-347</scope>
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    <reference key="4">
        <citation type="journal article" date="2004" name="Proteomics" volume="4" first="454" last="465">
            <title>Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.</title>
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                <person name="Bunkenborg J."/>
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                <person name="Wisniewski J.R."/>
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            <dbReference type="PubMed" id="14760718"/>
            <dbReference type="DOI" id="10.1002/pmic.200300556"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-186</scope>
        <source>
            <tissue>Plasma</tissue>
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    <reference key="5">
        <citation type="journal article" date="2005" name="J. Proteome Res." volume="4" first="2070" last="2080">
            <title>Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.</title>
            <authorList>
                <person name="Liu T."/>
                <person name="Qian W.-J."/>
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                <person name="Camp D.G. II"/>
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                <person name="Smith R.D."/>
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            <dbReference type="PubMed" id="16335952"/>
            <dbReference type="DOI" id="10.1021/pr0502065"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-186; ASN-269 AND ASN-325</scope>
        <source>
            <tissue>Plasma</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="J. Proteome Res." volume="5" first="1493" last="1503">
            <title>Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.</title>
            <authorList>
                <person name="Ramachandran P."/>
                <person name="Boontheung P."/>
                <person name="Xie Y."/>
                <person name="Sondej M."/>
                <person name="Wong D.T."/>
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            <dbReference type="PubMed" id="16740002"/>
            <dbReference type="DOI" id="10.1021/pr050492k"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-186</scope>
        <source>
            <tissue>Saliva</tissue>
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    <reference key="7">
        <citation type="journal article" date="2008" name="Proteomics" volume="8" first="3833" last="3847">
            <title>Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry.</title>
            <authorList>
                <person name="Picariello G."/>
                <person name="Ferranti P."/>
                <person name="Mamone G."/>
                <person name="Roepstorff P."/>
                <person name="Addeo F."/>
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            <dbReference type="DOI" id="10.1002/pmic.200701057"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-186</scope>
        <source>
            <tissue>Milk</tissue>
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    <reference key="8">
        <citation type="journal article" date="2009" name="Mol. Cell. Proteomics" volume="8" first="913" last="923">
            <title>A strategy for precise and large scale identification of core fucosylated glycoproteins.</title>
            <authorList>
                <person name="Jia W."/>
                <person name="Lu Z."/>
                <person name="Fu Y."/>
                <person name="Wang H.P."/>
                <person name="Wang L.H."/>
                <person name="Chi H."/>
                <person name="Yuan Z.F."/>
                <person name="Zheng Z.B."/>
                <person name="Song L.N."/>
                <person name="Han H.H."/>
                <person name="Liang Y.M."/>
                <person name="Wang J.L."/>
                <person name="Cai Y."/>
                <person name="Zhang Y.K."/>
                <person name="Deng Y.L."/>
                <person name="Ying W.T."/>
                <person name="He S.M."/>
                <person name="Qian X.H."/>
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            <dbReference type="DOI" id="10.1074/mcp.m800504-mcp200"/>
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        <scope>GLYCOSYLATION AT ASN-186 AND ASN-325</scope>
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    <reference key="9">
        <citation type="journal article" date="2009" name="Nat. Methods" volume="6" first="809" last="811">
            <title>Enrichment of glycopeptides for glycan structure and attachment site identification.</title>
            <authorList>
                <person name="Nilsson J."/>
                <person name="Rueetschi U."/>
                <person name="Halim A."/>
                <person name="Hesse C."/>
                <person name="Carlsohn E."/>
                <person name="Brinkmalm G."/>
                <person name="Larson G."/>
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            <dbReference type="DOI" id="10.1038/nmeth.1392"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-79 AND ASN-186</scope>
        <scope>STRUCTURE OF CARBOHYDRATES</scope>
        <source>
            <tissue>Cerebrospinal fluid</tissue>
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    <reference key="10">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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<entry dataset="Swiss-Prot" created="2010-03-23" modified="2026-01-28" version="122" xmlns="https://uniprot.org/uniprot">
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                <person name="Workman J.L."/>
                <person name="Dent S.Y."/>
            </authorList>
            <dbReference type="PubMed" id="27601583"/>
            <dbReference type="DOI" id="10.1128/mcb.00193-16"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ENY2 AND USP22</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="4">By binding to ENY2, interferes with the nuclear functions of the deubiquitinase (DUB) module of the SAGA complex which consists of ENY2, ATXN7, ATXN7L3 and the histone deubiquitinating component USP22. Affects USP22 DUB activity toward histones indirectly by changing the subcellular distribution of ENY2 and altering ENY2 availability for ATXN7L3 interaction. Regulates H2B monoubiquitination (H2Bub1) levels through cytoplasmic sequestration of ENY2 resulting in loss of nuclear ENY2-ATXN7L3 association which destabilizes ATXN7L3. Affects protein expression levels of ENY2 and ATXN7L3.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts strongly with ENY2. Interacts weakly with USP22.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="disease">
        <text evidence="3">A chromosomal aberration involving ATXN7L3B has been found in a mother and her two children with varying degrees of neurodevelopmental delay and cerebellar ataxia. One child also exhibits episodes of unresponsiveness suggestive of absence seizures and facial dysmorphism. Deletion at 12q21.1 deletes the entire single exon of ATXN7L3B.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by an expressed retrotransposed copy of the ATXN7L3 locus that emerged prior to the speciation event separating primates and rodents.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the SGF11 family.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAH09111" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <dbReference type="EMBL" id="AC025257">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009111">
        <property type="protein sequence ID" value="AAH09111.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53815.1"/>
    <dbReference type="RefSeq" id="NP_001129734.1">
        <property type="nucleotide sequence ID" value="NM_001136262.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96GX2"/>
    <dbReference type="BioGRID" id="139266">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96GX2">
        <property type="interactions" value="532"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96GX2">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000430000"/>
    <dbReference type="GlyGen" id="Q96GX2">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96GX2"/>
    <dbReference type="PhosphoSitePlus" id="Q96GX2"/>
    <dbReference type="BioMuta" id="ATXN7L3B"/>
    <dbReference type="jPOST" id="Q96GX2"/>
    <dbReference type="MassIVE" id="Q96GX2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000430000"/>
    <dbReference type="PeptideAtlas" id="Q96GX2"/>
    <dbReference type="ProteomicsDB" id="76676"/>
    <dbReference type="Pumba" id="Q96GX2"/>
    <dbReference type="Antibodypedia" id="52794">
        <property type="antibodies" value="49 antibodies from 11 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="552889"/>
    <dbReference type="Ensembl" id="ENST00000519948.4">
        <property type="protein sequence ID" value="ENSP00000430000.2"/>
        <property type="gene ID" value="ENSG00000253719.4"/>
    </dbReference>
    <dbReference type="GeneID" id="552889"/>
    <dbReference type="KEGG" id="hsa:552889"/>
    <dbReference type="MANE-Select" id="ENST00000519948.4">
        <property type="protein sequence ID" value="ENSP00000430000.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001136262.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001129734.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001sxd.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:37931"/>
    <dbReference type="ClinPGx" id="PA165512339"/>
    <dbReference type="CTD" id="552889"/>
    <dbReference type="DisGeNET" id="552889"/>
    <dbReference type="GeneCards" id="ATXN7L3B"/>
    <dbReference type="HGNC" id="HGNC:37931">
        <property type="gene designation" value="ATXN7L3B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000253719">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="615579">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000253719"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000253719"/>
    <dbReference type="eggNOG" id="ENOG502TFV2">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162576"/>
    <dbReference type="HOGENOM" id="CLU_2359075_0_0_1"/>
    <dbReference type="InParanoid" id="Q96GX2"/>
    <dbReference type="OMA" id="GNGPDQE"/>
    <dbReference type="OrthoDB" id="21557at2759"/>
    <dbReference type="PAN-GO" id="Q96GX2">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96GX2"/>
    <dbReference type="PathwayCommons" id="Q96GX2"/>
    <dbReference type="SignaLink" id="Q96GX2"/>
    <dbReference type="Agora" id="ENSG00000253719"/>
    <dbReference type="BioGRID-ORCS" id="552889">
        <property type="hits" value="11 hits in 1143 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ATXN7L3B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="552889"/>
    <dbReference type="Pharos" id="Q96GX2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96GX2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96GX2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000253719">
        <property type="expression patterns" value="Expressed in postcentral gyrus and 218 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010468">
        <property type="term" value="P:regulation of gene expression"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042933">
        <property type="entry name" value="ATXN7L3B"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR47733">
        <property type="entry name" value="ATAXIN-7 LIKE PROTEIN 3B, ATXN7L3B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR47733:SF1">
        <property type="entry name" value="ATAXIN-7-LIKE PROTEIN 3B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0160">Chromosomal rearrangement</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000392529" description="Ataxin-7-like protein 3B">
        <location>
            <begin position="1"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="77"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="92"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q3UD01"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="23475819"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="27601583"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="97" mass="10771" checksum="722ADB410FCEFC9A" modified="2010-03-23" version="2">MEEISLANLDTNKLEAIAQEIYVDLIEDSCLGFCFEVHRAVKCGYFYLEFAETGSVKDFGIQPVEDKGACRLPLCSLPGEPGNGPDQQLQRSPPEFQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2015-04-01" modified="2026-01-28" version="68" xmlns="https://uniprot.org/uniprot">
    <accession>P0DMS8</accession>
    <accession>A2A3P4</accession>
    <accession>P33765</accession>
    <accession>Q6UWU0</accession>
    <accession>Q9BYZ1</accession>
    <name>AA3R_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">Adenosine receptor A3</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="21" type="primary">ADORA3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT LEU-248</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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                <person name="Liang B.T."/>
            </authorList>
            <dbReference type="PubMed" id="9837869"/>
            <dbReference type="DOI" id="10.1096/fasebj.12.15.1785"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2016" name="Nat. Commun." volume="7" first="13561" last="13561">
            <title>Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-kappaB and osteosarcoma progression.</title>
            <authorList>
                <person name="Iyer S.V."/>
                <person name="Ranjan A."/>
                <person name="Elias H.K."/>
                <person name="Parrales A."/>
                <person name="Sasaki H."/>
                <person name="Roy B.C."/>
                <person name="Umar S."/>
                <person name="Tawfik O.W."/>
                <person name="Iwakuma T."/>
            </authorList>
            <dbReference type="PubMed" id="27886186"/>
            <dbReference type="DOI" id="10.1038/ncomms13561"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2021" name="Mol. Cell" volume="81" first="659" last="674">
            <title>N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand.</title>
            <authorList>
                <person name="Ogawa A."/>
                <person name="Nagiri C."/>
                <person name="Shihoya W."/>
                <person name="Inoue A."/>
                <person name="Kawakami K."/>
                <person name="Hiratsuka S."/>
                <person name="Aoki J."/>
                <person name="Ito Y."/>
                <person name="Suzuki T."/>
                <person name="Suzuki T."/>
                <person name="Inoue T."/>
                <person name="Nureki O."/>
                <person name="Tanihara H."/>
                <person name="Tomizawa K."/>
                <person name="Wei F.Y."/>
            </authorList>
            <dbReference type="PubMed" id="33472058"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2020.12.038"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF VAL-169; ILE-253 AND LEU-264</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2024" name="Nat. Commun." volume="15" first="9294" last="9294">
            <title>Structural insights into the agonist selectivity of the adenosine A3 receptor.</title>
            <authorList>
                <person name="Oshima H.S."/>
                <person name="Ogawa A."/>
                <person name="Sano F.K."/>
                <person name="Akasaka H."/>
                <person name="Kawakami T."/>
                <person name="Iwama A."/>
                <person name="Okamoto H.H."/>
                <person name="Nagiri C."/>
                <person name="Wei F.Y."/>
                <person name="Shihoya W."/>
                <person name="Nureki O."/>
            </authorList>
            <dbReference type="PubMed" id="39511145"/>
            <dbReference type="DOI" id="10.1038/s41467-024-53473-1"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF VAL-169 AND ILE-253</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] THR-105</scope>
    </reference>
    <reference evidence="22 23" key="15">
        <citation type="journal article" date="2024" name="Nat. Commun." volume="15" first="3252" last="3252">
            <title>Cryo-EM structures of adenosine receptor A3AR bound to selective agonists.</title>
            <authorList>
                <person name="Cai H."/>
                <person name="Guo S."/>
                <person name="Xu Y."/>
                <person name="Sun J."/>
                <person name="Li J."/>
                <person name="Xia Z."/>
                <person name="Jiang Y."/>
                <person name="Xie X."/>
                <person name="Xu H.E."/>
            </authorList>
            <dbReference type="PubMed" id="38627384"/>
            <dbReference type="DOI" id="10.1038/s41467-024-47207-6"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.19 ANGSTROMS)</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF TYR-15; SER-181 AND SER-247</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="24 25 26" key="16">
        <citation type="journal article" date="2025" name="Nat. Commun." volume="16" first="7674" last="7674">
            <title>Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor.</title>
            <authorList>
                <person name="Zhang L."/>
                <person name="Mobbs J.I."/>
                <person name="Bennetts F.M."/>
                <person name="Venugopal H."/>
                <person name="Nguyen A.T.N."/>
                <person name="Christopoulos A."/>
                <person name="van der Es D."/>
                <person name="Heitman L.H."/>
                <person name="May L.T."/>
                <person name="Glukhova A."/>
                <person name="Thal D.M."/>
            </authorList>
            <dbReference type="PubMed" id="40825947"/>
            <dbReference type="DOI" id="10.1038/s41467-025-62872-x"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) OF 5-318 IN COMPLEX WITH ADENOSINE</scope>
        <scope>FUNCTION</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF TYR-15; SER-73; HIS-95; TYR-265 AND SER-271</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 9 10 11 12 14 15">G protein-coupled receptor (GPCR) for adenosine that plays significant roles in various physiological processes including immune regulation, cardioprotection and neuroprotection (PubMed:38627384, PubMed:40825947, PubMed:9837869). Also acts as a receptor for adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification, which are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs): activated by N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A) (PubMed:33472058, PubMed:39511145). Preferentially couples to the inhibitory G protein (Gi), leading to the suppression of adenylate cyclase activity and a reduction in intracellular cyclic AMP levels (PubMed:33472058, PubMed:38627384). Upon adenosine binding, mediates cardioprotection in cardiomyocytes through anti-apoptotic effects primarily via the ERK1/2 pathway as well as the PI3K pathway (PubMed:9837869). In the central nervous system, participates in the modulation of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus (By similarity). In lung mast cells, receptor activation contributes to the type I allergic response by facilitating mast cell degranulation and histamine release (By similarity). Highly expressed in inflammatory cells such as neutrophils and mast cells, inhibits neutrophil degranulation and reduces superoxide production, thereby modulating inflammatory responses (PubMed:9164961).</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="13">Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase (PubMed:8234299).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cell membrane</location>
            <topology evidence="10 12">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P0DMS8-1</id>
            <name>2</name>
            <name evidence="17">A3AR i2</name>
            <name evidence="17">A3AR</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P0DMS9-2</id>
            <name>1</name>
            <name evidence="17">TMIGD3 i1</name>
            <name evidence="17">A3AR i1</name>
            <sequence type="external"/>
        </isoform>
        <isoform>
            <id>P0DMS9-1</id>
            <name>3</name>
            <name>TMIGD3 i3</name>
            <name>A3AR i3</name>
            <sequence type="external"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Expressed in the lung and bone. Expressed at lower levels in osteosarcoma tissues (at protein level).</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="L20463">
        <property type="protein sequence ID" value="AAA16365.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L22607">
        <property type="protein sequence ID" value="AAA35949.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X76981">
        <property type="protein sequence ID" value="CAA54288.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L77730">
        <property type="protein sequence ID" value="AAB02790.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L77729">
        <property type="protein sequence ID" value="AAB02790.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY136749">
        <property type="protein sequence ID" value="AAN01275.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390195">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC029831">
        <property type="protein sequence ID" value="AAH29831.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY011231">
        <property type="protein sequence ID" value="AAG35155.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS839.1">
        <molecule id="P0DMS8-1"/>
    </dbReference>
    <dbReference type="PIR" id="S38511">
        <property type="entry name" value="S38511"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000668.1">
        <molecule id="P0DMS8-1"/>
        <property type="nucleotide sequence ID" value="NM_000677.4"/>
    </dbReference>
    <dbReference type="PDB" id="8X16">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.29 A"/>
        <property type="chains" value="R=1-318"/>
    </dbReference>
    <dbReference type="PDB" id="8X17">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.19 A"/>
        <property type="chains" value="R=1-318"/>
    </dbReference>
    <dbReference type="PDB" id="9EBH">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="R=2-318"/>
    </dbReference>
    <dbReference type="PDB" id="9EBI">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="R=2-318"/>
    </dbReference>
    <dbReference type="PDB" id="9EHS">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="R=5-318"/>
    </dbReference>
    <dbReference type="PDBsum" id="8X16"/>
    <dbReference type="PDBsum" id="8X17"/>
    <dbReference type="PDBsum" id="9EBH"/>
    <dbReference type="PDBsum" id="9EBI"/>
    <dbReference type="PDBsum" id="9EHS"/>
    <dbReference type="AlphaFoldDB" id="P0DMS8"/>
    <dbReference type="EMDB" id="EMD-37985"/>
    <dbReference type="EMDB" id="EMD-37986"/>
    <dbReference type="EMDB" id="EMD-47879"/>
    <dbReference type="EMDB" id="EMD-47880"/>
    <dbReference type="EMDB" id="EMD-48065"/>
    <dbReference type="SMR" id="P0DMS8"/>
    <dbReference type="CORUM" id="P0DMS8"/>
    <dbReference type="FunCoup" id="P0DMS8">
        <property type="interactions" value="653"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000241356"/>
    <dbReference type="BindingDB" id="P0DMS8"/>
    <dbReference type="ChEMBL" id="CHEMBL256"/>
    <dbReference type="DrugBank" id="DB07954">
        <property type="generic name" value="3-isobutyl-1-methyl-7H-xanthine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02282">
        <property type="generic name" value="5'-S-methyl-5'-thioadenosine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00640">
        <property type="generic name" value="Adenosine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01223">
        <property type="generic name" value="Aminophylline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14018">
        <property type="generic name" value="Bromotheophylline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00201">
        <property type="generic name" value="Caffeine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12306">
        <property type="generic name" value="Cipargamin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12946">
        <property type="generic name" value="DPCPX"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00824">
        <property type="generic name" value="Enprofylline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB07776">
        <property type="generic name" value="Flavone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12010">
        <property type="generic name" value="Fostamatinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12885">
        <property type="generic name" value="Namodenoson"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08849">
        <property type="generic name" value="Nipecotic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05511">
        <property type="generic name" value="Piclidenoson"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB07340">
        <property type="generic name" value="Reversine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08517">
        <property type="generic name" value="Sakuranetin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08839">
        <property type="generic name" value="Serotonin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12569">
        <property type="generic name" value="Tonapofylline"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P0DMS8"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="21"/>
    <dbReference type="GlyCosmos" id="P0DMS8">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P0DMS8">
        <property type="glycosylation" value="3 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P0DMS8"/>
    <dbReference type="PhosphoSitePlus" id="P0DMS8"/>
    <dbReference type="BioMuta" id="ADORA3"/>
    <dbReference type="MassIVE" id="P0DMS8"/>
    <dbReference type="PeptideAtlas" id="P0DMS8"/>
    <dbReference type="Antibodypedia" id="77173">
        <property type="antibodies" value="140 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="140"/>
    <dbReference type="Ensembl" id="ENST00000241356.5">
        <property type="protein sequence ID" value="ENSP00000241356.4"/>
        <property type="gene ID" value="ENSG00000282608.2"/>
    </dbReference>
    <dbReference type="GeneID" id="140"/>
    <dbReference type="KEGG" id="hsa:140"/>
    <dbReference type="MANE-Select" id="ENST00000241356.5">
        <property type="protein sequence ID" value="ENSP00000241356.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000677.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000668.1"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:268"/>
    <dbReference type="CTD" id="140"/>
    <dbReference type="DisGeNET" id="140"/>
    <dbReference type="GeneCards" id="ADORA3"/>
    <dbReference type="HGNC" id="HGNC:268">
        <property type="gene designation" value="ADORA3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000282608">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="600445">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000282608"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000282608"/>
    <dbReference type="GeneTree" id="ENSGT01030000234555"/>
    <dbReference type="HOGENOM" id="CLU_009579_11_5_1"/>
    <dbReference type="InParanoid" id="P0DMS8"/>
    <dbReference type="OMA" id="INCITYF"/>
    <dbReference type="OrthoDB" id="284782at2759"/>
    <dbReference type="PAN-GO" id="P0DMS8">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P0DMS8"/>
    <dbReference type="PathwayCommons" id="P0DMS8"/>
    <dbReference type="Reactome" id="R-HSA-417973">
        <property type="pathway name" value="Adenosine P1 receptors"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418594">
        <property type="pathway name" value="G alpha (i) signalling events"/>
    </dbReference>
    <dbReference type="SignaLink" id="P0DMS8"/>
    <dbReference type="SIGNOR" id="P0DMS8"/>
    <dbReference type="Agora" id="ENSG00000282608"/>
    <dbReference type="BioGRID-ORCS" id="140">
        <property type="hits" value="5 hits in 1136 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="140"/>
    <dbReference type="Pharos" id="P0DMS8">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P0DMS8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="P0DMS8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000282608">
        <property type="expression patterns" value="Expressed in C1 segment of cervical spinal cord and 132 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P0DMS8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030425">
        <property type="term" value="C:dendrite"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042734">
        <property type="term" value="C:presynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098685">
        <property type="term" value="C:Schaffer collateral - CA1 synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001609">
        <property type="term" value="F:G protein-coupled adenosine receptor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007190">
        <property type="term" value="P:activation of adenylate cyclase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001973">
        <property type="term" value="P:G protein-coupled adenosine receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006954">
        <property type="term" value="P:inflammatory response"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030336">
        <property type="term" value="P:negative regulation of cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008285">
        <property type="term" value="P:negative regulation of cell population proliferation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032088">
        <property type="term" value="P:negative regulation of NF-kappaB transcription factor activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099171">
        <property type="term" value="P:presynaptic modulation of chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008016">
        <property type="term" value="P:regulation of heart contraction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014061">
        <property type="term" value="P:regulation of norepinephrine secretion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009611">
        <property type="term" value="P:response to wounding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1070.10:FF:000061">
        <property type="entry name" value="Adenosine receptor A2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1070.10">
        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000466">
        <property type="entry name" value="Adeno_A3_rcpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001634">
        <property type="entry name" value="Adenosn_rcpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000276">
        <property type="entry name" value="GPCR_Rhodpsn"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017452">
        <property type="entry name" value="GPCR_Rhodpsn_7TM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24246:SF2">
        <property type="entry name" value="ADENOSINE RECEPTOR A3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24246">
        <property type="entry name" value="OLFACTORY RECEPTOR AND ADENOSINE RECEPTOR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00001">
        <property type="entry name" value="7tm_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00555">
        <property type="entry name" value="ADENOSINEA3R"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00424">
        <property type="entry name" value="ADENOSINER"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00237">
        <property type="entry name" value="GPCRRHODOPSN"/>
    </dbReference>
    <dbReference type="SMART" id="SM01381">
        <property type="entry name" value="7TM_GPCR_Srsx"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF81321">
        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00237">
        <property type="entry name" value="G_PROTEIN_RECEP_F1_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50262">
        <property type="entry name" value="G_PROTEIN_RECEP_F1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0297">G-protein coupled receptor</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0807">Transducer</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000069010" description="Adenosine receptor A3">
        <location>
            <begin position="1"/>
            <end position="318"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="1"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="15"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="39"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="47"/>
            <end position="69"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="70"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="84"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="107"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="127"/>
            <end position="149"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="150"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="172"/>
            <end position="197"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="198"/>
            <end position="228"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="229"/>
            <end position="254"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="255"/>
            <end position="262"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="263"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="285"/>
            <end position="318"/>
        </location>
    </feature>
    <feature type="binding site" evidence="12 24">
        <location>
            <position position="168"/>
        </location>
        <ligand>
            <name>adenosine</name>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="20">
        <location>
            <position position="169"/>
        </location>
        <ligand>
            <name>N(6)-methyladenosine</name>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="12 24">
        <location>
            <position position="250"/>
        </location>
        <ligand>
            <name>adenosine</name>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="250"/>
        </location>
        <ligand>
            <name>N(6)-methyladenosine</name>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="12 24">
        <location>
            <position position="272"/>
        </location>
        <ligand>
            <name>adenosine</name>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="272"/>
        </location>
        <ligand>
            <name>N(6)-methyladenosine</name>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
        </ligand>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="5">
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="4"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="10 12 22 23 24 25 26">
        <location>
            <begin position="83"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035755" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs746154553." evidence="7">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_049366" description="In dbSNP:rs35511654." evidence="16">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_049367" description="In dbSNP:rs2800889.">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished receptor activation upon ligand binding." evidence="10 12">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly decreased activation by adenosine." evidence="12">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="73"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased activation by adenosine." evidence="12">
        <original>H</original>
        <variation>A</variation>
        <variation>F</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished activation by adenosine and N(6)-methyladenosine (m6A)." evidence="9">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly decreased activation by adenosines containing N(6)-methylated adenine (m6A)." evidence="11">
        <original>V</original>
        <variation>F</variation>
        <variation>N</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished receptor activation upon ligand binding." evidence="10">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished receptor activation upon ligand binding." evidence="10">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased activation by N(6)-methyladenosine (m6A)." evidence="9 11">
        <original>I</original>
        <variation>T</variation>
        <variation>N</variation>
        <variation>Q</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased activation by N(6)-methyladenosine (m6A)." evidence="9">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly decreased activation by adenosine." evidence="12">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased activation by adenosine." evidence="12">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA16365." evidence="19" ref="1">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AAG35155." evidence="19" ref="8">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="175"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="8"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="41"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="46"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="80"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="turn" evidence="28">
        <location>
            <begin position="115"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="118"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="124"/>
            <end position="142"/>
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    </feature>
    <feature type="turn" evidence="28">
        <location>
            <begin position="143"/>
            <end position="148"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="151"/>
            <end position="153"/>
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    <feature type="strand" evidence="27">
        <location>
            <begin position="155"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="158"/>
            <end position="160"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="168"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="174"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="181"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="187"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="224"/>
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    <feature type="turn" evidence="28">
        <location>
            <begin position="253"/>
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            <begin position="261"/>
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    <feature type="helix" evidence="28">
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            <begin position="274"/>
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            <begin position="283"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="287"/>
            <end position="299"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P28647"/>
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        <source>
            <dbReference type="UniProtKB" id="P35342"/>
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        <source>
            <dbReference type="UniProtKB" id="Q28309"/>
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    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q61618"/>
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    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27886186"/>
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        <source>
            <dbReference type="PubMed" id="33472058"/>
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            <dbReference type="PubMed" id="38627384"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="39511145"/>
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    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="40825947"/>
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    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="8234299"/>
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    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="9164961"/>
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="9837869"/>
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    <evidence type="ECO:0000269" key="16">
        <source ref="3"/>
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    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="27886186"/>
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    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="33472058"/>
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    <evidence type="ECO:0000305" key="20">
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            <dbReference type="PubMed" id="39511145"/>
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            <dbReference type="HGNC" id="HGNC:268"/>
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        <source>
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    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="8X17"/>
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    </evidence>
    <sequence length="318" mass="36185" checksum="690E67986130FC28" modified="2015-04-01" version="1">MPNNSTALSLANVTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLIFTHASIMSLLAIAVDRYLRVKLTVRYKRVTTHRRIWLALGLCWLVSFLVGLTPMFGWNMKLTSEYHRNVTFLSCQFVSVMRMDYMVYFSFLTWIFIPLVVMCAIYLDIFYIIRNKLSLNLSNSKETGAFYGREFKTAKSLFLVLFLFALSWLPLSIINCIIYFNGEVPQLVLYMGILLSHANSMMNPIVYAYKIKKFKETYLLILKACVVCHPSDSLDTSIEKNSE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1987-08-13" modified="2026-01-28" version="318" xmlns="https://uniprot.org/uniprot">
    <accession>P05067</accession>
    <accession>B2R5V1</accession>
    <accession>B4DII8</accession>
    <accession>D3DSD1</accession>
    <accession>D3DSD2</accession>
    <accession>D3DSD3</accession>
    <accession>P09000</accession>
    <accession>P78438</accession>
    <accession>Q13764</accession>
    <accession>Q13778</accession>
    <accession>Q13793</accession>
    <accession>Q16011</accession>
    <accession>Q16014</accession>
    <accession>Q16019</accession>
    <accession>Q16020</accession>
    <accession>Q6GSC0</accession>
    <accession>Q8WZ99</accession>
    <accession>Q9BT38</accession>
    <accession>Q9UC33</accession>
    <accession>Q9UCA9</accession>
    <accession>Q9UCB6</accession>
    <accession>Q9UCC8</accession>
    <accession>Q9UCD1</accession>
    <accession>Q9UQ58</accession>
    <name>A4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="151">Amyloid-beta precursor protein</fullName>
            <shortName evidence="151">APP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>ABPP</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>APPI</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alzheimer disease amyloid A4 protein homolog</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alzheimer disease amyloid protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="136">Amyloid precursor protein</fullName>
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        <alternativeName>
            <fullName evidence="3">Amyloid-beta (A4) precursor protein</fullName>
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        <alternativeName>
            <fullName>Amyloid-beta A4 protein</fullName>
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        <alternativeName>
            <fullName>Cerebral vascular amyloid peptide</fullName>
            <shortName>CVAP</shortName>
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        <alternativeName>
            <fullName>PreA4</fullName>
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        <alternativeName>
            <fullName>Protease nexin-II</fullName>
            <shortName>PN-II</shortName>
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            <recommendedName>
                <fullName>N-APP</fullName>
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        <component>
            <recommendedName>
                <fullName evidence="128">Soluble APP-alpha</fullName>
                <shortName evidence="128">S-APP-alpha</shortName>
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        <component>
            <recommendedName>
                <fullName evidence="128">Soluble APP-beta</fullName>
                <shortName evidence="128">S-APP-beta</shortName>
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        <component>
            <recommendedName>
                <fullName>C99</fullName>
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            <alternativeName>
                <fullName evidence="128">Beta-secretase C-terminal fragment</fullName>
                <shortName evidence="128">Beta-CTF</shortName>
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        <component>
            <recommendedName>
                <fullName evidence="135">Amyloid-beta protein 42</fullName>
                <shortName>Abeta42</shortName>
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                <fullName>Beta-APP42</fullName>
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        <component>
            <recommendedName>
                <fullName evidence="135">Amyloid-beta protein 40</fullName>
                <shortName>Abeta40</shortName>
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            <alternativeName>
                <fullName>Beta-APP40</fullName>
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        <component>
            <recommendedName>
                <fullName>C83</fullName>
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            <alternativeName>
                <fullName evidence="128">Alpha-secretase C-terminal fragment</fullName>
                <shortName evidence="128">Alpha-CTF</shortName>
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        <component>
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                <fullName>C80</fullName>
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        <component>
            <recommendedName>
                <fullName>Gamma-secretase C-terminal fragment 59</fullName>
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            <alternativeName>
                <fullName>Amyloid intracellular domain 59</fullName>
                <shortName>AICD-59</shortName>
                <shortName>AID(59)</shortName>
            </alternativeName>
            <alternativeName>
                <fullName>Gamma-CTF(59)</fullName>
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        <component>
            <recommendedName>
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            <alternativeName>
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                <shortName>AICD-57</shortName>
                <shortName>AID(57)</shortName>
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            <alternativeName>
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        <component>
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                <fullName>C31</fullName>
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    </protein>
    <gene>
        <name evidence="151" type="primary">APP</name>
        <name evidence="133" type="synonym">A4</name>
        <name evidence="151" type="synonym">AD1</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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        <scope>PROTEIN SEQUENCE OF 672-701</scope>
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        <scope>PROTEIN SEQUENCE OF 672-713</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 674-770</scope>
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            <tissue>Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 674-703</scope>
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        <scope>PROTEIN SEQUENCE OF 609-713</scope>
        <scope>GLYCOSYLATION AT THR-633; THR-651; THR-652; THR-659; THR-663; SER-667 AND TYR-681</scope>
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        <scope>PROTEIN SEQUENCE OF 691-698</scope>
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        <scope>PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP751)</scope>
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        <scope>PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM APP695)</scope>
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            <tissue>Brain</tissue>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SIGNAL SEQUENCE CLEAVAGE SITE</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>SULFATION</scope>
        <scope>OX-2 MOTIF</scope>
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        <scope>IDENTITY OF APP WITH NEXIN-II</scope>
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        <scope>EXTRACELLULAR ZINC-BINDING DOMAIN</scope>
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        <scope>EXTRACELLULAR COPPER-BINDING DOMAIN</scope>
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        <scope>N-TERMINAL HEPARIN-BINDING DOMAIN</scope>
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        <scope>DISULFIDE BOND FORMATION</scope>
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        <scope>MUTAGENESIS OF TYR-728</scope>
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        <scope>IMPORTANCE OF MET-706 IN FREE RADICAL OXIDATIVE STRESS</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ENDOCYTOSIS SIGNAL</scope>
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        <scope>CLEAVAGE BY BACE1</scope>
        <scope>SUBCELLULAR LOCATION (SOLUBLE APP-BETA)</scope>
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        <scope>IDENTIFICATION OF GAMMA-CTFS BY MASS SPECTROMETRY</scope>
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        <scope>INTERACTION WITH FPR2 (AMYLOID-BETA PROTEIN 42)</scope>
        <scope>SUBCELLULAR LOCATION (AMYLOID-BETA PROTEIN 42)</scope>
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        <scope>INTERACTION WITH APBB1</scope>
        <scope>FUNCTION</scope>
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        <scope>MUTAGENESIS OF TYR-757</scope>
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        <scope>PHOSPHORYLATION AT SER-198 AND SER-206 BY CASEIN KINASES</scope>
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        <scope>MUTAGENESIS OF ASP-739</scope>
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        <scope>INTERACTION WITH APBB1</scope>
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        <scope>PHOSPHORYLATION AT TYR-757</scope>
        <scope>INTERACTION WITH SHC1</scope>
        <scope>MUTAGENESIS OF THR-743 AND TYR-757</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ASSOCIATION OF AMYLOID FIBRILS WITH GCP1</scope>
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        <scope>PROTEOLYTIC CLEAVAGE (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42)</scope>
        <scope>SUBCELLULAR LOCATION (AMYLOID-BETA PROTEIN 40 AND AMYLOID-BETA PROTEIN 42)</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-542</scope>
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        <scope>INTERACTION WITH SORL1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>INTERACTION WITH SORL1</scope>
        <scope>MUTAGENESIS OF 757-TYR--TYR-762</scope>
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        <scope>INTERACTION WITH SORL1</scope>
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        <scope>CAUTION</scope>
        <scope>RETRACTION NOTICE OF PUBMED:19225519</scope>
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        <scope>INTERACTION WITH AGER</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>GLYCOSYLATION AT THR-633; THR-651; THR-652; SER-656; THR-663 AND SER-667 PROTEOLYTIC PROCESSING</scope>
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        <scope>VARIANT AD1 ILE-717</scope>
    </reference>
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        <scope>CHARACTERIZATION OF VARIANTS AD1 GLY-717; ILE-717 AND PHE-717</scope>
        <scope>MUTAGENESIS OF VAL-717</scope>
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            <dbReference type="PubMed" id="9328472"/>
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        <scope>VARIANT AD1 VAL-716</scope>
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            <dbReference type="PubMed" id="9754958"/>
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        <scope>VARIANT AD1 GLY-692</scope>
        <scope>CHARACTERIZATION OF PHENOTYPE</scope>
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            <dbReference type="PubMed" id="10097173"/>
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        </citation>
        <scope>VARIANT AD1 MET-715</scope>
        <scope>CHARACTERIZATION OF VARIANT AD1 MET-715</scope>
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            <dbReference type="PubMed" id="10631141"/>
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        <scope>VARIANT AD1 ILE-717</scope>
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        <scope>VARIANT AD1 PRO-723</scope>
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        <scope>VARIANT AD1 LEU-717</scope>
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        <scope>VARIANT AD1 ILE-714</scope>
        <scope>CHARACTERIZATION OF VARIANTS AD1 ILE-714 AND ILE-717</scope>
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            <dbReference type="PubMed" id="10677483"/>
            <dbReference type="DOI" id="10.1073/pnas.97.4.1456"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT AD1 670-LYS-MET-671 DELINS ASN-LEU</scope>
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            <dbReference type="PubMed" id="11409420"/>
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        <scope>VARIANT CAA-APP ASN-694</scope>
    </reference>
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        <scope>CHARACTERIZATION OF VARIANT AD1 GLY-692</scope>
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        <scope>VARIANT AD1 GLY-693</scope>
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            <dbReference type="PubMed" id="12034808"/>
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        <scope>VARIANT AD1 ALA-714</scope>
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            <dbReference type="PubMed" id="12654973"/>
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        <scope>VARIANT CAA-APP ASN-694</scope>
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            <dbReference type="PubMed" id="15365148"/>
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        <scope>VARIANT AD1 THR-713</scope>
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        <scope>VARIANT CAA-APP VAL-705</scope>
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        <scope>VARIANT AD1 ILE-714</scope>
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                <person name="Bugiani O."/>
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        <scope>VARIANT CAA-APP LYS-693</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 72 91 94">Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.</text>
    </comment>
    <comment type="function">
        <text>Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Amyloid-beta peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with overexpressed HADH2 leads to oxidative stress and neurotoxicity. Also binds GPC1 in lipid rafts.</text>
    </comment>
    <comment type="function">
        <molecule>Amyloid-beta protein 42</molecule>
        <text>More effective reductant than amyloid-beta protein 40. May activate mononuclear phagocytes in the brain and elicit inflammatory responses.</text>
    </comment>
    <comment type="function">
        <text evidence="1">Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain.</text>
    </comment>
    <comment type="function">
        <text>The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3 9 21 24 28 30 33 34 36 38 39 42 43 56 60 64 67 71 74 75 77 80 82 83 86 89 91 92 93 94 95 100 102 111 115 116 118 121 123 125 126">Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1 and, NUMB and DAB1 (By similarity). Binding to DAB1 inhibits its serine phosphorylation (By similarity). Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1. In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1. Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons. Interacts with CPEB1 and AGER (By similarity). Interacts with ANKS1B. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE (PubMed:17051221). Homodimerizes; dimerization is enhanced in the presence of Cu(2+) ions and is promoted by heparin binding (PubMed:25122912, PubMed:20212142). Interacts with PLD3. Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (By similarity). Interacts with SYT7 (By similarity). Interacts (via transmembrane region) with PSEN1; the interaction is direct (PubMed:30630874). Interacts with LRRK2 (PubMed:28720718). Interacts (via cytoplasmic domain) with KIF5B (PubMed:23011729). Interacts (via C-terminus) with APBB2/FE65L1 (via C-terminus) (PubMed:14527950, PubMed:8855266). Interacts (via intracellular domain) with APBB3 (PubMed:10081969). Amyloid-beta associates with HADH2 (PubMed:9338779). Soluble APP binds, via its N-terminal head, to FBLN1.</text>
    </comment>
    <comment type="subunit">
        <molecule>Amyloid-beta protein 40</molecule>
        <text>Interacts with S100A9.</text>
    </comment>
    <comment type="subunit">
        <molecule>Amyloid-beta protein 42</molecule>
        <text evidence="38">Interacts with FPR2.</text>
    </comment>
    <comment type="subunit">
        <molecule>C83</molecule>
        <text evidence="86">Interacts with GSAP.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform APP695</molecule>
        <text evidence="64 67 74 93">Interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides.</text>
    </comment>
    <comment type="subunit">
        <molecule>C99</molecule>
        <text evidence="67">Interacts with SORL1.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform APP751</molecule>
        <text evidence="64">Interacts with SORL1.</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform APP770</molecule>
        <text evidence="64">Interacts with SORL1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77613">
            <id>P05067</id>
        </interactant>
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
            <label>AATF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77613">
            <id>P05067</id>
        </interactant>
        <interactant intactId="EBI-9076211">
            <id>P16112</id>
            <label>ACAN</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-77613">
            <id>P05067</id>
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        <interactant intactId="EBI-353944">
            <id>P60709</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-77613">
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        <interactant intactId="EBI-351428">
            <id>P61158</id>
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        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-77613">
            <id>P05067</id>
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        <interactant intactId="EBI-1536151">
            <id>O14672</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-77613">
            <id>P05067</id>
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        <interactant intactId="EBI-25935864">
            <id>A0AVL1</id>
            <label>ADAM9</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-77613">
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        <interactant intactId="EBI-8588930">
            <id>P18509</id>
            <label>ADCYAP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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            <id>PRO_0000000092</id>
        </interactant>
        <interactant intactId="EBI-711909">
            <id>P02766</id>
            <label>TTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-821758">
            <id>PRO_0000000092</id>
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            <id>P15253</id>
            <label>CALR</label>
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        <organismsDiffer>true</organismsDiffer>
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    <comment type="interaction">
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        <interactant intactId="EBI-79422">
            <id>Q05941</id>
            <label>Chrna7</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-821758">
            <id>PRO_0000000092</id>
        </interactant>
        <interactant intactId="EBI-2548105">
            <id>P03452</id>
            <label>HA</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>PRO_0000000092</id>
        </interactant>
        <interactant intactId="EBI-15728641">
            <id>P97484</id>
            <label>Pirb</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
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            <id>PRO_0000000092</id>
        </interactant>
        <interactant intactId="EBI-25474996">
            <id>K9N5Q8</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>PRO_0000000092</id>
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        <interactant intactId="EBI-25490323">
            <id>PRO_0000449647</id>
            <label>S</label>
            <dbReference type="UniProtKB" id="P0DTC2"/>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-821758">
            <id>PRO_0000000092</id>
        </interactant>
        <interactant intactId="EBI-15982016">
            <id>Q99NH8</id>
            <label>Trem2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1222467">
            <id>P02649</id>
            <label>APOE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
            <label>APP</label>
            <dbReference type="UniProtKB" id="P05067"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>29</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1104674">
            <id>P10909</id>
            <label>CLU</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1044067">
            <id>P49840</id>
            <label>GSK3A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-373586">
            <id>P49841</id>
            <label>GSK3B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-15607031">
            <id>P14735-1</id>
            <label>IDE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1033518">
            <id>P08253</id>
            <label>MMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1387782">
            <id>P08138</id>
            <label>NGFR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-16109799">
            <id>Q5JRX3-1</id>
            <label>PITRM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-716596">
            <id>Q08752</id>
            <label>PPID</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1171329">
            <id>Q92673</id>
            <label>SORL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-3505951">
            <id>O60602</id>
            <label>TLR5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-457650">
            <id>P31696</id>
            <label>AGRN</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>PRO_0000000093</id>
        </interactant>
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            <id>P15253</id>
            <label>CALR</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2431589">
            <id>PRO_0000000093</id>
        </interactant>
        <interactant intactId="EBI-1038810">
            <id>P07174</id>
            <label>Ngfr</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 84 97 147">Cell membrane</location>
            <topology evidence="102 137 147">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="101 145">Membrane</location>
            <topology evidence="101 102 145">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Perikaryon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Cell projection</location>
            <location evidence="12">Growth cone</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="84">Membrane</location>
            <location evidence="84">Clathrin-coated pit</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="84">Early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="84 94">Cytoplasmic vesicle</location>
        </subcellularLocation>
        <text evidence="12 84">Cell surface protein that rapidly becomes internalized via clathrin-coated pits. Only a minor proportion is present at the cell membrane; most of the protein is present in intracellular vesicles (PubMed:20580937). During maturation, the immature APP (N-glycosylated in the endoplasmic reticulum) moves to the Golgi complex where complete maturation occurs (O-glycosylated and sulfated). After alpha-secretase cleavage, soluble APP is released into the extracellular space and the C-terminal is internalized to endosomes and lysosomes. Some APP accumulates in secretory transport vesicles leaving the late Golgi compartment and returns to the cell surface. APP sorts to the basolateral surface in epithelial cells. During neuronal differentiation, the Thr-743 phosphorylated form is located mainly in growth cones, moderately in neurites and sparingly in the cell body (PubMed:10341243). Casein kinase phosphorylation can occur either at the cell surface or within a post-Golgi compartment. Associates with GPC1 in perinuclear compartments. Colocalizes with SORL1 in a vesicular pattern in cytoplasm and perinuclear regions.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>C83</molecule>
        <subcellularLocation>
            <location evidence="56">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="56">Golgi apparatus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="56">Early endosome</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>C99</molecule>
        <subcellularLocation>
            <location evidence="56">Early endosome</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Soluble APP-beta</molecule>
        <subcellularLocation>
            <location evidence="18 97">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Amyloid-beta protein 40</molecule>
        <subcellularLocation>
            <location evidence="63">Cell surface</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Amyloid-beta protein 42</molecule>
        <subcellularLocation>
            <location evidence="38 63">Cell surface</location>
        </subcellularLocation>
        <text evidence="38">Associates with FPR2 at the cell surface and the complex is then rapidly internalized.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Gamma-secretase C-terminal fragment 59</molecule>
        <subcellularLocation>
            <location evidence="36">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="36">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="3 36">Located to both the cytoplasm and nuclei of neurons. It can be translocated to the nucleus through association with APBB1 (Fe65) (PubMed:11544248). In dopaminergic neurons, the phosphorylated Thr-743 form is localized to the nucleus (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P05067-1</id>
            <name>APP770</name>
            <name>PreA4 770</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P05067-2</id>
            <name>APP305</name>
            <sequence type="described" ref="VSP_000005 VSP_000006"/>
        </isoform>
        <isoform>
            <id>P05067-3</id>
            <name>L-APP677</name>
            <sequence type="described" ref="VSP_000002 VSP_000004 VSP_000009"/>
        </isoform>
        <isoform>
            <id>P05067-4</id>
            <name>APP695</name>
            <name>PreA4 695</name>
            <sequence type="described" ref="VSP_000002 VSP_000004"/>
        </isoform>
        <isoform>
            <id>P05067-5</id>
            <name>L-APP696</name>
            <sequence type="described" ref="VSP_000002 VSP_000003 VSP_000009"/>
        </isoform>
        <isoform>
            <id>P05067-6</id>
            <name>APP714</name>
            <sequence type="described" ref="VSP_000002 VSP_000003"/>
        </isoform>
        <isoform>
            <id>P05067-7</id>
            <name>L-APP733</name>
            <sequence type="described" ref="VSP_000007 VSP_000008 VSP_000009"/>
        </isoform>
        <isoform>
            <id>P05067-8</id>
            <name>APP751</name>
            <name>PreA4 751</name>
            <sequence type="described" ref="VSP_000007 VSP_000008"/>
        </isoform>
        <isoform>
            <id>P05067-9</id>
            <name>L-APP752</name>
            <sequence type="described" ref="VSP_000009"/>
        </isoform>
        <isoform>
            <id>P05067-10</id>
            <name>APP639</name>
            <sequence type="described" ref="VSP_009116 VSP_009117 VSP_009118"/>
        </isoform>
        <isoform>
            <id>P05067-11</id>
            <name>11</name>
            <sequence type="described" ref="VSP_045446 VSP_045447"/>
        </isoform>
        <text>Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="49 54 97">Expressed in the brain and in cerebrospinal fluid (at protein level) (PubMed:2649245). Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform APP695 is the predominant form in neuronal tissue, isoform APP751 and isoform APP770 are widely expressed in non-neuronal cells. Isoform APP751 is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes.</text>
    </comment>
    <comment type="induction">
        <text>Increased levels during neuronal differentiation.</text>
    </comment>
    <comment type="domain">
        <text evidence="102">The transmembrane helix undergoes a conformation change and unravels partially when bound to PSEN1, facilitating cleavage by PSEN1.</text>
    </comment>
    <comment type="domain">
        <text evidence="125">The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.</text>
    </comment>
    <comment type="domain">
        <text evidence="94">The GFLD subdomain binds Cu(2+) ions; this promotes homodimerization.</text>
    </comment>
    <comment type="domain">
        <text evidence="13">The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The YENPXY site is also involved in clathrin-mediated endocytosis.</text>
    </comment>
    <comment type="domain">
        <text evidence="98 99">The C-terminal region can bind zinc ions; this favors dimerization and formation of higher oligomers.</text>
    </comment>
    <comment type="domain">
        <text evidence="97">The OX-2 motif shows some similarity to a region in the N-terminus of CD200/MOX2.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18 37 63 102">Proteolytically processed under normal cellular conditions. Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99. Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro) (PubMed:30630874). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE (PubMed:11604391, PubMed:16154999). Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase and all terminating at Gln-686.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.</text>
    </comment>
    <comment type="PTM">
        <text evidence="66 88 90 97 101">N-glycosylated (PubMed:2900137). N- and O-glycosylated (PubMed:2649245). O-glycosylation on Ser and Thr residues with core 1 or possibly core 8 glycans. Partial tyrosine glycosylation (Tyr-681) is found on some minor, short amyloid-beta peptides (amyloid-beta 1-15, 1-16, 1-17, 1-18, 1-19 and 1-20) but not found on amyloid-beta protein 38, amyloid-beta protein 40 nor on amyloid-beta protein 42. Modification on a tyrosine is unusual and is more prevelant in AD patients. Glycans had Neu5AcHex(Neu5Ac)HexNAc-O-Tyr, Neu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr and O-AcNeu5AcNeu5AcHex(Neu5Ac)HexNAc-O-Tyr structures, where O-Ac is O-acetylation of Neu5Ac. Neu5AcNeu5Ac is most likely Neu5Ac 2,8Neu5Ac linked. O-glycosylations in the vicinity of the cleavage sites may influence the proteolytic processing. Appicans are L-APP isoforms with O-linked chondroitin sulfate.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12 27 34 42 100 106 119">Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (PubMed:10341243). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (PubMed:10341243). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (PubMed:11146006, PubMed:8131745). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (PubMed:11517218). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (PubMed:11877420). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP. This phosphorylation is inhibited by heparin (PubMed:8999878).</text>
    </comment>
    <comment type="PTM">
        <text>Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond. In vitro, the APP-Cu(+) complex in the presence of hydrogen peroxide results in an increased production of amyloid-beta-containing peptides.</text>
    </comment>
    <comment type="PTM">
        <text>Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Amyloid-beta peptides are degraded by IDE.</text>
    </comment>
    <comment type="PTM">
        <text evidence="97">Sulfated on tyrosine residues.</text>
    </comment>
    <comment type="mass spectrometry" mass="6461.6" method="MALDI" evidence="45">
        <molecule>Gamma-secretase C-terminal fragment 59</molecule>
    </comment>
    <comment type="mass spectrometry" mass="6451.6" method="MALDI" evidence="45">
        <molecule>Gamma-secretase C-terminal fragment 57</molecule>
    </comment>
    <comment type="disease" evidence="10 17 18 19 20 25 26 31 35 44 50 51 52 55 57 58 61 62 68 69 78 79 81 109 110 112 114 117 122 124">
        <disease id="DI-00085">
            <name>Alzheimer disease 1</name>
            <acronym>AD1</acronym>
            <description>A form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. It can be associated with cerebral amyloid angiopathy. Alzheimer disease can be associated with cerebral amyloid angiopathy.</description>
            <dbReference type="MIM" id="104300"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="32 47 65 85 87">
        <disease id="DI-00097">
            <name>Cerebral amyloid angiopathy, APP-related</name>
            <acronym>CAA-APP</acronym>
            <description>A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.</description>
            <dbReference type="MIM" id="605714"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="98 99">Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. The affinity for copper is much higher than for other transient metals and is increased under acidic conditions. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform APP770</molecule>
        <text>A major isoform.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform L-APP677</molecule>
        <text evidence="136">The L-isoforms are referred to as appicans.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform APP695</molecule>
        <text evidence="136">A major isoform.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform L-APP696</molecule>
        <text evidence="136">The L-isoforms are referred to as appicans.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform L-APP733</molecule>
        <text evidence="136">The L-isoforms are referred to as appicans.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform APP751</molecule>
        <text evidence="136">A major isoform.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the APP family.</text>
    </comment>
    <comment type="caution">
        <text evidence="143 149">Was reported to bind TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (PubMed:19225519). This work was later retracted (PubMed:38110576).</text>
    </comment>
    <comment type="sequence caution" evidence="136">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAA58727" version="1"/>
        </conflict>
        <text>Contamination by an Alu repeat.</text>
    </comment>
    <comment type="online information" name="Alzforum">
        <link uri="https://www.alzforum.org/mutations/app"/>
        <text>APP mutations</text>
    </comment>
    <comment type="online information" name="AD mutations">
        <link uri="https://uantwerpen.vib.be/CMTMutations"/>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Amyloid_beta"/>
        <text>Amyloid beta entry</text>
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    <dbReference type="EMBL" id="Y00264">
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    <keyword id="KW-0034">Amyloid</keyword>
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    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0168">Coated pit</keyword>
    <keyword id="KW-0186">Copper</keyword>
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    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
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    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
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    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0358">Heparin-binding</keyword>
    <keyword id="KW-0408">Iron</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0523">Neurodegeneration</keyword>
    <keyword id="KW-0914">Notch signaling pathway</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-0654">Proteoglycan</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0765">Sulfation</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
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    <feature type="chain" id="PRO_0000000090" description="Soluble APP-beta">
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    <feature type="chain" id="PRO_0000000092" description="Amyloid-beta protein 42" evidence="142">
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    <feature type="chain" id="PRO_0000000093" description="Amyloid-beta protein 40" evidence="140 142">
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            <begin position="688"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000000095" description="P3(42)">
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            <begin position="688"/>
            <end position="713"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000000096" description="P3(40)">
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            <begin position="688"/>
            <end position="711"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000384574" description="C80">
        <location>
            <begin position="691"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000097" description="Gamma-secretase C-terminal fragment 59">
        <location>
            <begin position="712"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000098" description="Gamma-secretase C-terminal fragment 57">
        <location>
            <begin position="714"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000099" description="Gamma-secretase C-terminal fragment 50" evidence="1">
        <location>
            <begin position="721"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000100" description="C31">
        <location>
            <begin position="740"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="136">
        <location>
            <begin position="18"/>
            <end position="701"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="145 146 148">
        <location>
            <begin position="702"/>
            <end position="722"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="136">
        <location>
            <begin position="723"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="domain" description="E1" evidence="6">
        <location>
            <begin position="28"/>
            <end position="189"/>
        </location>
    </feature>
    <feature type="domain" description="BPTI/Kunitz inhibitor" evidence="5">
        <location>
            <begin position="291"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="domain" description="E2" evidence="7">
        <location>
            <begin position="374"/>
            <end position="565"/>
        </location>
    </feature>
    <feature type="region of interest" description="GFLD subdomain" evidence="6">
        <location>
            <begin position="28"/>
            <end position="123"/>
        </location>
    </feature>
    <feature type="region of interest" description="CuBD subdomain" evidence="6">
        <location>
            <begin position="131"/>
            <end position="189"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="8">
        <location>
            <begin position="194"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="region of interest" description="Heparin-binding">
        <location>
            <begin position="391"/>
            <end position="423"/>
        </location>
    </feature>
    <feature type="region of interest" description="Heparin-binding">
        <location>
            <begin position="491"/>
            <end position="522"/>
        </location>
    </feature>
    <feature type="region of interest" description="Collagen-binding" evidence="113">
        <location>
            <begin position="523"/>
            <end position="540"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with PSEN1" evidence="102">
        <location>
            <begin position="695"/>
            <end position="722"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with G(o)-alpha">
        <location>
            <begin position="732"/>
            <end position="751"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for the interaction with KIF5B and for anterograde transport in axons" evidence="72">
        <location>
            <begin position="756"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="OX-2" evidence="97">
        <location>
            <begin position="344"/>
            <end position="365"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Basolateral sorting signal">
        <location>
            <begin position="724"/>
            <end position="734"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="YENPXY motif; contains endocytosis signal" evidence="13">
        <location>
            <begin position="757"/>
            <end position="762"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="8">
        <location>
            <begin position="194"/>
            <end position="207"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="8">
        <location>
            <begin position="228"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="8">
        <location>
            <begin position="268"/>
            <end position="281"/>
        </location>
    </feature>
    <feature type="binding site" evidence="108">
        <location>
            <begin position="96"/>
            <end position="110"/>
        </location>
        <ligand>
            <name>heparin</name>
            <dbReference type="ChEBI" id="CHEBI:28304"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 73 94 160">
        <location>
            <position position="147"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 73 94 160">
        <location>
            <position position="151"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 73 160">
        <location>
            <position position="168"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="150">
        <location>
            <position position="183"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="150">
        <location>
            <position position="186"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="150">
        <location>
            <position position="187"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="29">
        <location>
            <position position="677"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="29 98">
        <location>
            <position position="677"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="139">
        <location>
            <position position="681"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="138 139">
        <location>
            <position position="681"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="29">
        <location>
            <position position="684"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="14 29 98">
        <location>
            <position position="684"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="29">
        <location>
            <position position="685"/>
        </location>
        <ligand>
            <name>Cu(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29036"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="29 98">
        <location>
            <position position="685"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="site" description="Required for Cu(2+) reduction" evidence="6">
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by caspases" evidence="11">
        <location>
            <begin position="197"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by caspases" evidence="11">
        <location>
            <begin position="219"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="site" description="Reactive bond">
        <location>
            <begin position="301"/>
            <end position="302"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by beta-secretase" evidence="141">
        <location>
            <begin position="671"/>
            <end position="672"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by caspase-6; when associated with variant 670-N-L-671">
        <location>
            <begin position="672"/>
            <end position="673"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by ACE" evidence="37 63">
        <location>
            <begin position="678"/>
            <end position="679"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by alpha-secretase" evidence="141">
        <location>
            <begin position="687"/>
            <end position="688"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by theta-secretase" evidence="70">
        <location>
            <begin position="690"/>
            <end position="691"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in free radical propagation" evidence="1">
        <location>
            <position position="704"/>
        </location>
    </feature>
    <feature type="site" description="Susceptible to oxidation" evidence="16">
        <location>
            <position position="706"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by gamma-secretase; site 1" evidence="141">
        <location>
            <begin position="711"/>
            <end position="712"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by gamma-secretase; site 2" evidence="141">
        <location>
            <begin position="713"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by gamma-secretase; site 3" evidence="41 148">
        <location>
            <begin position="720"/>
            <end position="721"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by caspase-6, caspase-8 or caspase-9" evidence="11">
        <location>
            <begin position="739"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CK2" evidence="119">
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CK1" evidence="119">
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="4">
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="4">
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="4">
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by FAM20C" evidence="96">
        <location>
            <position position="441"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="96">
        <location>
            <position position="497"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="729"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by APP-kinase I" evidence="2">
        <location>
            <position position="730"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by CDK5 and MAPK10" evidence="100 106 177">
        <location>
            <position position="743"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="42">
        <location>
            <position position="757"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="66">
        <location>
            <position position="542"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="136">
        <location>
            <position position="571"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine; partial" evidence="88 90">
        <location>
            <position position="633"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine; partial" evidence="88 90">
        <location>
            <position position="651"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine; partial" evidence="88 90">
        <location>
            <position position="652"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (Xyl...) (chondroitin sulfate) serine; in L-APP isoforms" evidence="88">
        <location>
            <position position="656"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (HexNAc...) threonine; partial" evidence="90">
        <location>
            <position position="659"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine; partial" evidence="90 144">
        <location>
            <position position="663"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GalNAc...) serine; partial" evidence="90 144">
        <location>
            <position position="667"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (HexNAc...) tyrosine; partial" evidence="90">
        <location>
            <position position="681"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 155 168 170 171 172">
        <location>
            <begin position="38"/>
            <end position="62"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 155 168 170 171 172">
        <location>
            <begin position="73"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 155 168 171 172">
        <location>
            <begin position="98"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 46 73 76 156 159 160 161 162 163 164 168 172">
        <location>
            <begin position="133"/>
            <end position="187"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 46 73 76 156 159 160 161 162 163 164 168 172">
        <location>
            <begin position="144"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 46 73 76 156 159 160 161 162 163 164 168 172">
        <location>
            <begin position="158"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="152 153 154 157 158 169">
        <location>
            <begin position="291"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="152 153 154 157 158 169 173">
        <location>
            <begin position="300"/>
            <end position="324"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="152 153 154 157 158 169 173">
        <location>
            <begin position="316"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="2">
        <location>
            <position position="763"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045446" description="In isoform 11." evidence="130">
        <original>MLPGLALLLLAAWTARALE</original>
        <variation>MDQLEDLLVLFINY</variation>
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009116" description="In isoform APP639." evidence="129">
        <location>
            <begin position="19"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009117" description="In isoform APP639." evidence="129">
        <location>
            <begin position="289"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000002" description="In isoform APP695, isoform L-APP696, isoform L-APP677 and isoform APP714." evidence="133">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000004" description="In isoform APP695 and isoform L-APP677." evidence="133">
        <location>
            <begin position="290"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000003" description="In isoform L-APP696 and isoform APP714." evidence="136">
        <location>
            <begin position="290"/>
            <end position="345"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000005" description="In isoform APP305." evidence="131">
        <original>VCSEQAETGPCRAMIS</original>
        <variation>KWYKEVHSGQARWLML</variation>
        <location>
            <begin position="290"/>
            <end position="305"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000006" description="In isoform APP305." evidence="131">
        <location>
            <begin position="306"/>
            <end position="770"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045447" description="In isoform 11." evidence="130">
        <original>MSQSLLKTTQEPLARDPVKL</original>
        <variation>I</variation>
        <location>
            <begin position="345"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000007" description="In isoform L-APP733 and isoform APP751." evidence="131 132 134">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000008" description="In isoform L-APP733 and isoform APP751." evidence="131 132 134">
        <location>
            <begin position="346"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009118" description="In isoform APP639." evidence="129">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000009" description="In isoform L-APP677, isoform L-APP696, isoform L-APP733 and isoform L-APP752." evidence="132">
        <location>
            <begin position="637"/>
            <end position="654"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022315" description="In dbSNP:rs45588932." evidence="127">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="501"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010107" description="In a patient with late onset Alzheimer disease; dbSNP:rs63750363." evidence="107">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="665"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000015" description="In AD1; Swedish mutation; highly increases hydrolysis by BACE1 and amyloid-beta proteins production; dbSNP:rs281865161." evidence="18 20 50 57">
        <original>KM</original>
        <variation>NL</variation>
        <location>
            <begin position="670"/>
            <end position="671"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_044424" description="In AD1; dbSNP:rs63750064." evidence="58">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="678"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000016" description="In AD1; Flemish mutation; increases the solubility of processed amyloid-beta peptides and increases the stability of peptide oligomers; dbSNP:rs63750671." evidence="31 51 124">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="692"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014215" description="In AD1; dbSNP:rs63751039." evidence="35 55">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014216" description="In CAA-APP; Italian type; dbSNP:rs63750579." evidence="85">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000017" description="In CAA-APP; Dutch type; dbSNP:rs63750579." evidence="87">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014217" description="In CAA-APP; Iowa type; dbSNP:rs63749810." evidence="32 47">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="694"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032276" description="In CAA-APP; Italian type; dbSNP:rs63750921." evidence="65">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="705"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000019" description="In AD1; dbSNP:rs63750066." evidence="52 61">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="713"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000018" description="In one chronic schizophrenia patient; uncertain significance; dbSNP:rs1800557." evidence="53">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="713"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032277" description="In AD1; dbSNP:rs63750643." evidence="44">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="714"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014218" description="In AD1; increased amyloid-beta protein 42/40 ratio; dbSNP:rs63750973." evidence="26 62">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="714"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010108" description="In AD1; decreased amyloid-beta protein 40/total amyloid-beta; dbSNP:rs63750734." evidence="10">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="715"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000020" description="In AD1; dbSNP:rs63750399." evidence="122">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="716"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000023" description="In AD1; increased amyloid-beta protein 42/40 ratio; dbSNP:rs63750264." evidence="79 109 110 112 117">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000022" description="In AD1; increased amyloid-beta protein 42/40 ratio; dbSNP:rs63749964." evidence="81 112 117">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000021" description="In AD1; increased amyloid-beta protein 42/40 ratio; dbSNP:rs63750264." evidence="17 26 68 69 78 109 112 114 117">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014219" description="In AD1; dbSNP:rs63750264." evidence="25">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010109" description="In AD1; dbSNP:rs63751122." evidence="19">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="723"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced heparin-binding." evidence="108">
        <original>KRGR</original>
        <variation>NQGG</variation>
        <location>
            <begin position="99"/>
            <end position="102"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of the copper binding site in the GFLD subdomain; when associated with A-110." evidence="94">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of the copper binding site in the GFLD subdomain; when associated with A-108." evidence="94">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Binds copper. Forms dimer." evidence="105">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Binds copper. Forms dimer." evidence="105">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Binds copper. No dimer formation. No copper reducing activity." evidence="15 105">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="50% decrease in copper reducing activity." evidence="15">
        <original>HLH</original>
        <variation>ALA</variation>
        <location>
            <begin position="147"/>
            <end position="149"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of a copper binding site; when associated with A-151." evidence="94">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Some decrease in copper reducing activity." evidence="40 105">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Binds copper. Forms dimer." evidence="40 105">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced copper-mediated low-density lipoprotein oxidation." evidence="40 105">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of a copper binding site; when associated with A-147." evidence="94">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced copper-mediated low-density lipoprotein oxidation." evidence="40 105">
        <original>H</original>
        <variation>K</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Binds copper. Forms dimer." evidence="40 105">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduced casein kinase phosphorylation." evidence="23 119">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced casein kinase phosphorylation." evidence="23 119">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced affinity for heparin; when associated with A-503." evidence="59">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced affinity for heparin; when associated with A-499." evidence="59">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="503"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes chondroitin sulfate binding in L-APP733 isoform." evidence="104">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="656"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="60-70% zinc-induced amyloid-beta protein 28 aggregation." evidence="14">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="676"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="60-70% zinc-induced amyloid-beta protein 28 aggregation." evidence="14">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="681"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Only 23% zinc-induced amyloid-beta protein 28 aggregation." evidence="14">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="684"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Causes formation of an artifactual disulfide bond with PSEN1." evidence="102">
        <original>V</original>
        <variation>C</variation>
        <location>
            <position position="695"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced protein oxidation. No hippocampal neuron toxicity.">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="704"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced lipid peroxidation inhibition." evidence="16 120">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="706"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No free radical production. No hippocampal neuron toxicity." evidence="16 120">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="706"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Unchanged amyloid-beta protein 42/total amyloid-beta ratio." evidence="117">
        <original>V</original>
        <variation>C</variation>
        <variation>S</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased amyloid-beta protein 42/total amyloid-beta ratio." evidence="117">
        <original>V</original>
        <variation>K</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased amyloid-beta protein 42/40 ratio. No change in apoptosis after caspase cleavage." evidence="117">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="717"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on APBA1 nor APBB1 binding. Greatly reduces the binding to APPBP2. APP internalization unchanged. No change in amyloid-beta protein 42 secretion." evidence="13 118 125">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="728"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No cleavage by caspases during apoptosis." evidence="11 22 45">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="739"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on FADD-induced apoptosis." evidence="11 22 45">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="739"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Greatly reduces the binding to SHC1 and APBB family members; no effect on NGF-stimulated neurite extension. Loss of phosphorylation by LRRK2." evidence="12 27 34 42 100">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="743"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced NGF-stimulated neurite extension. No effect on APP maturation." evidence="12 27 34 42">
        <original>T</original>
        <variation>E</variation>
        <location>
            <position position="743"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="APP internalization unchanged. No change in amyloid-beta protein 42 secretion." evidence="13">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="756"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on C99 interaction with SORL1." evidence="67">
        <original>YENPTY</original>
        <variation>AENPTA</variation>
        <location>
            <begin position="757"/>
            <end position="762"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Little APP internalization. Reduced amyloid-beta protein 42 secretion." evidence="13 39 42 118">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="757"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of binding to MAPK8IP1, APBA1, APBB1, APPBP2 and SHC1." evidence="13 39 42 118">
        <original>Y</original>
        <variation>G</variation>
        <location>
            <position position="757"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No binding to APBA1, no effect on APBB1 binding. Little APP internalization. Reduced amyloid-beta protein 42 secretion." evidence="13 118">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="759"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Little APP internalization. Reduced amyloid-beta protein 42 secretion." evidence="13">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="760"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of binding to APBA1 and APBB1. APP internalization unchanged. No change in amyloid-beta protein 42 secretion." evidence="13 118">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="762"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA31830." evidence="136" ref="3">
        <original>AR</original>
        <variation>VW</variation>
        <location>
            <begin position="15"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 36; AAA51722." evidence="136" ref="36">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="647"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 23; AAB26263/AAB26264." evidence="136" ref="23">
        <location>
            <position position="724"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 23; AAB26263/AAB26264/AAB26265." evidence="136" ref="23">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="731"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 31; AAA35540." evidence="136" ref="31">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="757"/>
        </location>
    </feature>
    <feature type="helix" evidence="189">
        <location>
            <begin position="26"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="33"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="43"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="turn" evidence="189">
        <location>
            <begin position="47"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="52"/>
            <end position="54"/>
        </location>
    </feature>
    <feature type="strand" evidence="190">
        <location>
            <begin position="56"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="helix" evidence="189">
        <location>
            <begin position="66"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="82"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="92"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="97"/>
            <end position="99"/>
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    </feature>
    <feature type="turn" evidence="189">
        <location>
            <begin position="100"/>
            <end position="102"/>
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    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="103"/>
            <end position="106"/>
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    </feature>
    <feature type="strand" evidence="189">
        <location>
            <begin position="110"/>
            <end position="112"/>
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    <feature type="strand" evidence="189">
        <location>
            <begin position="115"/>
            <end position="119"/>
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    <feature type="strand" evidence="179">
        <location>
            <begin position="134"/>
            <end position="139"/>
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    <feature type="helix" evidence="179">
        <location>
            <begin position="147"/>
            <end position="160"/>
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    </feature>
    <feature type="strand" evidence="179">
        <location>
            <begin position="163"/>
            <end position="174"/>
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    </feature>
    <feature type="turn" evidence="179">
        <location>
            <begin position="175"/>
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    </feature>
    <feature type="strand" evidence="179">
        <location>
            <begin position="178"/>
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    <feature type="helix" evidence="178">
        <location>
            <begin position="288"/>
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    <feature type="strand" evidence="178">
        <location>
            <begin position="299"/>
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    <feature type="strand" evidence="178">
        <location>
            <begin position="304"/>
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    <feature type="turn" evidence="178">
        <location>
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    <feature type="strand" evidence="178">
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            <begin position="315"/>
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    <feature type="strand" evidence="178">
        <location>
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    <feature type="strand" evidence="178">
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    </evidence>
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    </evidence>
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        <source>
            <dbReference type="PDB" id="7OW1"/>
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        <source>
            <dbReference type="PDB" id="7OXN"/>
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        <source>
            <dbReference type="PDB" id="8X52"/>
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    </evidence>
    <sequence length="770" mass="86943" checksum="A12EE761403740F5" modified="1991-11-01" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-03-27" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NRG9</accession>
    <accession>Q5JB47</accession>
    <accession>Q9NWI6</accession>
    <accession>Q9UG19</accession>
    <name>AAAS_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aladin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adracalin</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AAAS</name>
        <name type="synonym">ADRACALA</name>
        <name type="ORF">GL003</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>TISSUE SPECIFICITY</scope>
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                <person name="Zorrilla S.E."/>
                <person name="Nelson D."/>
                <person name="Kucherlapati R."/>
                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16541075"/>
            <dbReference type="DOI" id="10.1038/nature04569"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 210-546 (ISOFORM 1)</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2009" name="Biochem. Biophys. Res. Commun." volume="390" first="205" last="210">
            <title>The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope.</title>
            <authorList>
                <person name="Kind B."/>
                <person name="Koehler K."/>
                <person name="Lorenz M."/>
                <person name="Huebner A."/>
            </authorList>
            <dbReference type="PubMed" id="19782045"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2009.09.080"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH NDC1</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33 AND SER-495</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495; SER-511 AND SER-541</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2015" name="Mol. Biol. Cell" volume="26" first="3424" last="3438">
            <title>The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.</title>
            <authorList>
                <person name="Carvalhal S."/>
                <person name="Ribeiro S.A."/>
                <person name="Arocena M."/>
                <person name="Kasciukovic T."/>
                <person name="Temme A."/>
                <person name="Koehler K."/>
                <person name="Huebner A."/>
                <person name="Griffis E.R."/>
            </authorList>
            <dbReference type="PubMed" id="26246606"/>
            <dbReference type="DOI" id="10.1091/mbc.e15-02-0113"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH AURKA</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2016" name="Biol. Open" volume="5" first="1697" last="1705">
            <title>Identification of a novel putative interaction partner of the nucleoporin ALADIN.</title>
            <authorList>
                <person name="Juehlen R."/>
                <person name="Landgraf D."/>
                <person name="Huebner A."/>
                <person name="Koehler K."/>
            </authorList>
            <dbReference type="PubMed" id="27754849"/>
            <dbReference type="DOI" id="10.1242/bio.021162"/>
        </citation>
        <scope>INTERACTION WITH PGRMC2</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6 8">Plays a role in the normal development of the peripheral and central nervous system (PubMed:11062474, PubMed:11159947, PubMed:16022285). Required for the correct localization of aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 as well as a subset of AURKA targets which ensures proper spindle formation and timely chromosome alignment (PubMed:26246606).</text>
    </comment>
    <comment type="subunit">
        <text evidence="7 8 9">Interacts with NDC1, the interaction is required for nuclear pore localization (PubMed:19782045). Interacts with the inactive form aurora kinase AURKA (PubMed:26246606). Interacts with PGRMC2 (PubMed:27754849).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Nucleus</location>
            <location evidence="7">Nuclear pore complex</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cytoplasm</location>
            <location evidence="8">Cytoskeleton</location>
            <location evidence="8">Spindle pole</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Nucleus envelope</location>
        </subcellularLocation>
        <text evidence="8">In metaphase cells localizes within the spindle with some accumulation around spindle poles, with the highest concentration between the centrosome and metaphase plate (PubMed:26246606). The localization to the spindle is microtubule-mediated (PubMed:26246606).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NRG9-1</id>
            <name>1</name>
            <name>AAAS-v1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NRG9-2</id>
            <name>2</name>
            <name>AAAS-v2</name>
            <sequence type="described" ref="VSP_043014"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Widely expressed (PubMed:11159947, PubMed:16022285). Particularly abundant in cerebellum, corpus callosum, adrenal gland, pituitary gland, gastrointestinal structures and fetal lung (PubMed:11159947).</text>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-00018">
            <name>Achalasia-addisonianism-alacrima syndrome</name>
            <acronym>AAAS</acronym>
            <description>An autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)-resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.</description>
            <dbReference type="MIM" id="231550"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="11">Ubiquitously expressed.</text>
    </comment>
    <dbReference type="EMBL" id="AJ289857">
        <property type="protein sequence ID" value="CAC19017.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289841">
        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289842">
        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289843">
        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289844">
        <property type="protein sequence ID" value="CAC19038.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289845">
        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289846">
        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289847">
        <property type="protein sequence ID" value="CAC19038.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAC19038.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="JOINED"/>
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        <property type="protein sequence ID" value="CAC17465.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAP69911.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAF86948.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAA91394.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAP35558.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH00659.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL110160">
        <property type="protein sequence ID" value="CAB53665.2"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="Q9NRG9-2"/>
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    <dbReference type="CCDS" id="CCDS8856.1">
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    <dbReference type="RefSeq" id="NP_001166937.1">
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        <property type="nucleotide sequence ID" value="NM_001173466.2"/>
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    <dbReference type="RefSeq" id="NP_056480.1">
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        <property type="nucleotide sequence ID" value="NM_015665.6"/>
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        <property type="resolution" value="50.00 A"/>
        <property type="chains" value="40/41=1-546"/>
    </dbReference>
    <dbReference type="PDB" id="7R5K">
        <property type="method" value="EM"/>
        <property type="resolution" value="12.00 A"/>
        <property type="chains" value="40/41=1-546"/>
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    <dbReference type="PDBsum" id="7R5J"/>
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    <dbReference type="AlphaFoldDB" id="Q9NRG9"/>
    <dbReference type="EMDB" id="EMD-14321"/>
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        <property type="interactions" value="200"/>
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    <dbReference type="ComplexPortal" id="CPX-873">
        <property type="entry name" value="Nuclear pore complex"/>
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        <property type="family name" value="the nuclear pore complex (npc) family"/>
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        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NRG9"/>
    <dbReference type="PhosphoSitePlus" id="Q9NRG9"/>
    <dbReference type="SwissPalm" id="Q9NRG9"/>
    <dbReference type="BioMuta" id="AAAS"/>
    <dbReference type="DMDM" id="20137527"/>
    <dbReference type="jPOST" id="Q9NRG9"/>
    <dbReference type="MassIVE" id="Q9NRG9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000209873"/>
    <dbReference type="PeptideAtlas" id="Q9NRG9"/>
    <dbReference type="ProteomicsDB" id="82359">
        <molecule id="Q9NRG9-1"/>
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    <dbReference type="ProteomicsDB" id="82360">
        <molecule id="Q9NRG9-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9NRG9"/>
    <dbReference type="Antibodypedia" id="27006">
        <property type="antibodies" value="262 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8086"/>
    <dbReference type="Ensembl" id="ENST00000209873.9">
        <molecule id="Q9NRG9-1"/>
        <property type="protein sequence ID" value="ENSP00000209873.4"/>
        <property type="gene ID" value="ENSG00000094914.15"/>
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    <dbReference type="Ensembl" id="ENST00000394384.7">
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        <property type="protein sequence ID" value="ENSP00000377908.3"/>
        <property type="gene ID" value="ENSG00000094914.15"/>
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        <property type="protein sequence ID" value="ENSP00000517437.1"/>
        <property type="gene ID" value="ENSG00000291836.1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0853">WD repeat</keyword>
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        <location>
            <position position="1"/>
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            <begin position="529"/>
            <end position="539"/>
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            <position position="2"/>
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        <location>
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        <original>WSSCCLRVFAWHPHTNKFAVALLDDSVRVYNASS</original>
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            <begin position="149"/>
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            <position position="108"/>
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            <position position="160"/>
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            <begin position="342"/>
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    </feature>
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            <position position="479"/>
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            <dbReference type="UniProtKB" id="P58742"/>
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            <dbReference type="PubMed" id="27754849"/>
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        <source>
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        <source>
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        <source>
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        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="546" mass="59574" checksum="E0F4E7145D8C192E" modified="2000-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="250" xmlns="https://uniprot.org/uniprot">
    <accession>P01023</accession>
    <accession>Q13677</accession>
    <accession>Q59F47</accession>
    <accession>Q5QTS0</accession>
    <accession>Q68DN2</accession>
    <accession>Q6PIY3</accession>
    <accession>Q6PN97</accession>
    <name>A2MG_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-2-macroglobulin</fullName>
            <shortName>Alpha-2-M</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>C3 and PZP-like alpha-2-macroglobulin domain-containing protein 5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">A2M</name>
        <name type="synonym">CPAMD5</name>
        <name type="ORF">FWP007</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>PROTEIN SEQUENCE OF 273-286 AND 426-436</scope>
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        <interactant intactId="EBI-25829984">
            <id>Q9ULX5</id>
            <label>RNF112</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-743938">
            <id>Q96D59</id>
            <label>RNF183</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-458391">
            <id>P04271</id>
            <label>S100B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-395447">
            <id>Q16637-3</id>
            <label>SMN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-10696971">
            <id>Q7Z6I5</id>
            <label>SPATA12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-357085">
            <id>Q9UNE7</id>
            <label>STUB1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-714135">
            <id>O75558</id>
            <label>STX11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-8484990">
            <id>Q8N4C7</id>
            <label>STX19</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-25892332">
            <id>P43405-2</id>
            <label>SYK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-12151837">
            <id>P28347-2</id>
            <label>TEAD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-11525489">
            <id>Q86WT6-2</id>
            <label>TRIM69</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-1797313">
            <id>Q8WVJ9</id>
            <label>TWIST2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-594644">
            <id>P10599</id>
            <label>TXN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-473284">
            <id>Q9BVJ6</id>
            <label>UTP14A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-11141397">
            <id>Q9UBQ0-2</id>
            <label>VPS29</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-2527283">
            <id>Q96AX1</id>
            <label>VPS33A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-2813661">
            <id>Q8N895</id>
            <label>ZNF366</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-640741">
            <id>P01023</id>
        </interactant>
        <interactant intactId="EBI-6455001">
            <id>Q99KR7</id>
            <label>Ppif</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="14">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14">Secreted in plasma.</text>
    </comment>
    <comment type="developmental stage">
        <text>Unlike the rat protein, which is an acute phase protein, this protein is always in circulation at high levels.</text>
    </comment>
    <comment type="similarity">
        <text evidence="16">Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAT02228" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD92851" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Alpha_2-macroglobulin"/>
        <text>Alpha-2 macroglobulin entry</text>
    </comment>
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        <property type="protein sequence ID" value="AAA51551.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAT02228.1"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH26246.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH40071.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAA77774.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA48670.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA48670.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAA51552.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAQ13498.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="MAHU"/>
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        <property type="nucleotide sequence ID" value="NM_000014.6"/>
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        <property type="nucleotide sequence ID" value="NM_001347423.2"/>
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        <property type="method" value="NMR"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=126-227"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="4.20 A"/>
        <property type="chains" value="A/B/C/D=1-1474"/>
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        <property type="interactions" value="223"/>
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    <dbReference type="MINT" id="P01023"/>
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        <property type="generic name" value="Anacaulase"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00626">
        <property type="generic name" value="Bacitracin"/>
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        <property type="generic name" value="Becaplermin"/>
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        <property type="generic name" value="Cisplatin"/>
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        <property type="generic name" value="Copper"/>
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        <property type="generic name" value="Mangafodipir"/>
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        <property type="generic name" value="Silver"/>
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        <property type="generic name" value="Zinc"/>
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        <property type="generic name" value="Zinc acetate"/>
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        <property type="generic name" value="Zinc chloride"/>
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        <property type="generic name" value="Zinc sulfate, unspecified form"/>
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        <property type="glycosylation" value="47 N-Linked glycans (7 sites)"/>
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        <property type="glycosylation" value="14 sites, 62 glycans"/>
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        <property type="gene ID" value="ENSG00000175899.16"/>
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        <property type="protein sequence ID" value="ENSP00000323929.8"/>
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        <property type="RefSeq protein sequence ID" value="NP_000005.3"/>
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        <property type="gene designation" value="A2M"/>
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        <property type="type" value="gene"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Alpha-macroglobulin receptor domain"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Terpenoid cyclases/Protein prenyltransferases"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00477">
        <property type="entry name" value="ALPHA_2_MACROGLOBULIN"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0082">Bait region</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0646">Protease inhibitor</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0722">Serine protease inhibitor</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0882">Thioester bond</keyword>
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            <end position="23"/>
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    <feature type="chain" id="PRO_0000000055" description="Alpha-2-macroglobulin" evidence="14">
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            <end position="1474"/>
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    <feature type="region of interest" description="Inhibitory">
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            <begin position="730"/>
            <end position="735"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="7 10">
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            <position position="55"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="14">
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="7 14">
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="7 11 14">
        <location>
            <position position="396"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="7 14">
        <location>
            <position position="410"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4 7">
        <location>
            <position position="869"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2 7 11 14">
        <location>
            <position position="991"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="4 7 10 11">
        <location>
            <position position="1424"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="48"/>
            <end position="86"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="251"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="269"/>
            <end position="287"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-431)" evidence="12">
        <location>
            <position position="278"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (with C-278)" evidence="12">
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="12">
        <location>
            <begin position="470"/>
            <end position="563"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="12 14">
        <location>
            <begin position="595"/>
            <end position="771"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="642"/>
            <end position="689"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="821"/>
            <end position="849"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="847"/>
            <end position="883"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="921"/>
            <end position="1321"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="1079"/>
            <end position="1127"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14">
        <location>
            <begin position="1352"/>
            <end position="1467"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)" evidence="1">
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain with K-? in other proteins)" evidence="1">
        <location>
            <position position="694"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl cysteine thioester (Cys-Gln)" evidence="14">
        <location>
            <begin position="972"/>
            <end position="975"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026820" description="In dbSNP:rs226405." evidence="5 6 9 13 15">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="639"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000012" description="In dbSNP:rs1800434.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="704"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026821" description="In dbSNP:rs3180392.">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="815"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000013" description="Probably interferes with the activity; dbSNP:rs1800433." evidence="3">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="972"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000014" description="In dbSNP:rs669." evidence="5 6 8 9 13">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="1000"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AA sequence." evidence="16" ref="8">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAT02228." evidence="16" ref="3">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH26246." evidence="16" ref="6">
        <original>LSFV</original>
        <variation>ACCS</variation>
        <location>
            <begin position="350"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AA sequence." evidence="16" ref="8">
        <original>C</original>
        <variation>E</variation>
        <location>
            <position position="563"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD92851." evidence="16" ref="4">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="844"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; CAH18188." evidence="16" ref="5">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="872"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 13; AAA51552." evidence="16" ref="13">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1148"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 13; AAA51552." evidence="16" ref="13">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="1195"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="128"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="136"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="143"/>
            <end position="151"/>
        </location>
    </feature>
    <feature type="helix" evidence="18">
        <location>
            <begin position="153"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="161"/>
            <end position="168"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="174"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="187"/>
            <end position="193"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="201"/>
            <end position="208"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="214"/>
            <end position="221"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1341"/>
            <end position="1347"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="1355"/>
            <end position="1359"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1360"/>
            <end position="1369"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1379"/>
            <end position="1384"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1389"/>
            <end position="1391"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="1393"/>
            <end position="1400"/>
        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="1401"/>
            <end position="1403"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1407"/>
            <end position="1410"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1412"/>
            <end position="1419"/>
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    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1427"/>
            <end position="1434"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1445"/>
            <end position="1450"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1454"/>
            <end position="1456"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="1459"/>
            <end position="1463"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="12754519"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="1370808"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="14760718"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15611997"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
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        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="1707161"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="19139490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="19159218"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="2430963"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="2581245"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="6203908"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source ref="3"/>
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    <evidence type="ECO:0000305" key="16"/>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="1BV8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="2P9R"/>
        </source>
    </evidence>
    <sequence length="1474" mass="163291" checksum="0A46DF09EFD3CF40" modified="2010-10-05" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="240" xmlns="https://uniprot.org/uniprot">
    <accession>P29274</accession>
    <accession>B2R7E0</accession>
    <name>AA2AR_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenosine receptor A2a</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADORA2A</name>
        <name type="synonym">ADORA2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>INTERACTION WITH NECAB2</scope>
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        <scope>POSSIBLE INTERACTION WITH DRD4</scope>
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        <scope>INTERACTION WITH USP4</scope>
        <scope>UBIQUITINATION</scope>
        <scope>DEUBIQUITINATION BY USP4</scope>
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        <scope>VARIANT VAL-50</scope>
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    <comment type="function">
        <text evidence="1">Receptor for adenosine (By similarity). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 7 8 9">Interacts (via cytoplasmic C-terminal domain) with USP4; the interaction is direct (PubMed:16339847). May interact with DRD4 (PubMed:18832607). Interacts with NECAB2 (PubMed:17689978). Interacts (via cytoplasmic C-terminal domain) with GAS2L2; interaction enhances receptor-mediated adenylyl cyclase activity (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
            <label>ADORA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
            <label>ADORA2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-3904751">
            <id>P29275</id>
            <label>ADORA2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-749204">
            <id>O15155</id>
            <label>BET1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-2909859">
            <id>P21554</id>
            <label>CNR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-448974">
            <id>Q99418</id>
            <label>CYTH2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-15639515">
            <id>O15354</id>
            <label>GPR37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-950070">
            <id>Q7Z6G3</id>
            <label>NECAB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-12187159">
            <id>O43759-2</id>
            <label>SYNGR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-723290">
            <id>Q13107</id>
            <label>USP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
        </interactant>
        <interactant intactId="EBI-22114623">
            <id>Q5T9L3-1</id>
            <label>WLS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P29274</id>
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            <id>P31424-1</id>
            <label>Grm5</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="2">Colocalizes with GAS2L2 at neuronal processes.</text>
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    <comment type="domain">
        <text>The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface.</text>
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        <text evidence="7">Ubiquitinated. Deubiquitinated by USP4; leading to stabilization and expression at the cell surface.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
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        <location>
            <begin position="151"/>
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        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="158"/>
            <end position="160"/>
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    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="163"/>
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    <feature type="helix" evidence="17">
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    <feature type="helix" evidence="17">
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    <feature type="helix" evidence="17">
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    <feature type="helix" evidence="17">
        <location>
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    <feature type="strand" evidence="16">
        <location>
            <begin position="213"/>
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    <feature type="helix" evidence="17">
        <location>
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    <feature type="strand" evidence="14">
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            <begin position="260"/>
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    <feature type="helix" evidence="17">
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    <feature type="helix" evidence="17">
        <location>
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    <feature type="turn" evidence="15">
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    <feature type="turn" evidence="14">
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    <feature type="helix" evidence="14">
        <location>
            <begin position="312"/>
            <end position="317"/>
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    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P11617"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P30543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10391209"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16339847"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17689978"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="18832607"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="21593763"/>
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    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PDB" id="2YDO"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PDB" id="2YDV"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="2YDV"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="3QAK"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="3VGA"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="5NM4"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="8JWY"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="8WDT"/>
        </source>
    </evidence>
    <sequence length="412" mass="44707" checksum="9438E9D64A6BE61B" modified="1994-06-01" version="2">MPIMGSSVYITVELAIAVLAILGNVLVCWAVWLNSNLQNVTNYFVVSLAAADIAVGVLAIPFAITISTGFCAACHGCLFIACFVLVLTQSSIFSLLAIAIDRYIAIRIPLRYNGLVTGTRAKGIIAICWVLSFAIGLTPMLGWNNCGQPKEGKNHSQGCGEGQVACLFEDVVPMNYMVYFNFFACVLVPLLLMLGVYLRIFLAARRQLKQMESQPLPGERARSTLQKEVHAAKSLAIIVGLFALCWLPLHIINCFTFFCPDCSHAPLWLMYLAIVLSHTNSVVNPFIYAYRIREFRQTFRKIIRSHVLRQQEPFKAAGTSARVLAAHGSDGEQVSLRLNGHPPGVWANGSAPHPERRPNGYALGLVSGGSAQESQGNTGLPDVELLSHELKGVCPEPPGLDDPLAQDGAGVS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-15" modified="2026-01-28" version="176" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NS82</accession>
    <accession>B2RE84</accession>
    <name>AAA1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Asc-type amino acid transporter 1</fullName>
            <shortName>Asc-1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Solute carrier family 7 member 10</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">SLC7A10</name>
        <name type="synonym">ASC1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Neurosci. Lett." volume="287" first="231" last="235">
            <title>Cloning and characterization of a human brain Na+-independent transporter for small neutral amino acids that transports D-serine with high affinity.</title>
            <authorList>
                <person name="Nakauchi J."/>
                <person name="Matsuo H."/>
                <person name="Kim D.K."/>
                <person name="Goto A."/>
                <person name="Chairoungdua A."/>
                <person name="Cha S.H."/>
                <person name="Inatomi J."/>
                <person name="Shiokawa Y."/>
                <person name="Yamaguchi K."/>
                <person name="Saito I."/>
                <person name="Endou H."/>
                <person name="Kanai Y."/>
            </authorList>
            <dbReference type="PubMed" id="10863037"/>
            <dbReference type="DOI" id="10.1016/s0304-3940(00)01169-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Mol. Genet. Metab." volume="73" first="333" last="339">
            <title>Is the SLC7A10 gene on chromosome 19 a candidate locus for cystinuria?</title>
            <authorList>
                <person name="Leclerc D."/>
                <person name="Wu Q."/>
                <person name="Ellis J.R."/>
                <person name="Goodyer P."/>
                <person name="Rozen R."/>
            </authorList>
            <dbReference type="PubMed" id="11509015"/>
            <dbReference type="DOI" id="10.1006/mgme.2001.3209"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ASP-112</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2000-05" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Bassi M.T."/>
                <person name="Borsani G."/>
                <person name="Nunes V."/>
                <person name="Palacin M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Amygdala</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1 2 5">Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane. Preferentially mediates exchange transport, but can also operate via facilitated diffusion (By similarity) (PubMed:10863037). Acts as a major transporter for glycine, L- and D-serine in the central nervous system. At the spinal cord and brainstem regulates glycine metabolism and glycinergic inhibitory neurotransmission by providing for glycine de novo synthesis from L-serine and glycine recycling from astrocytes to glycinergic motor neurons (By similarity). At Schaffer collateral-CA1 synapses mediates D-serine and glycine release that modulates post-synaptic activation of NMDA receptors and excitatory glutamatergic transmission (By similarity). May regulate D-serine release from mesenchymal progenitors located in developing subcutaneous adipose tissue, favoring white adipocyte over thermogenic beige adipocyte lineage commitment (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-alanine(in) + glycine(out) = L-alanine(out) + glycine(in)</text>
            <dbReference type="Rhea" id="RHEA:74019"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-serine(out) + L-alanine(in) = L-serine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74023"/>
            <dbReference type="ChEBI" id="CHEBI:33384"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-threonine(out) + L-alanine(in) = L-threonine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74027"/>
            <dbReference type="ChEBI" id="CHEBI:57926"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-cysteine(out) + L-alanine(in) = L-cysteine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74031"/>
            <dbReference type="ChEBI" id="CHEBI:35235"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>2-aminoisobutanoate(out) + L-alanine(in) = 2-aminoisobutanoate(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74063"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
            <dbReference type="ChEBI" id="CHEBI:193090"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>D-serine(out) + L-alanine(in) = D-serine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74035"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>D-alanine(out) + L-alanine(in) = D-alanine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74039"/>
            <dbReference type="ChEBI" id="CHEBI:57416"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-valine(out) + L-alanine(in) = L-valine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74047"/>
            <dbReference type="ChEBI" id="CHEBI:57762"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-methionine(out) + L-alanine(in) = L-methionine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74043"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>beta-alanine(out) + L-alanine(in) = beta-alanine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74059"/>
            <dbReference type="ChEBI" id="CHEBI:57966"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>D-cysteine(out) + L-alanine(in) = D-cysteine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74055"/>
            <dbReference type="ChEBI" id="CHEBI:35236"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>D-threonine(out) + L-alanine(in) = D-threonine(in) + L-alanine(out)</text>
            <dbReference type="Rhea" id="RHEA:74051"/>
            <dbReference type="ChEBI" id="CHEBI:57757"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>D-isoleucine(out) + D-serine(in) = D-isoleucine(in) + D-serine(out)</text>
            <dbReference type="Rhea" id="RHEA:74299"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
            <dbReference type="ChEBI" id="CHEBI:193151"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:74300"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>D-serine(in) = D-serine(out)</text>
            <dbReference type="Rhea" id="RHEA:29455"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">22.8 uM for D-serine</KM>
            <KM evidence="5">9.16 uM for L-alanine</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1">Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12068238">
            <id>Q9NS82</id>
        </interactant>
        <interactant intactId="EBI-743771">
            <id>Q92624</id>
            <label>APPBP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">Colocalizes with OLIG2 in astrocytic processes. Localizes to the plasma membrane in mature adipocytes and to intracellular structures in preadipocytes.</text>
    </comment>
    <comment type="tissue specificity">
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<entry dataset="Swiss-Prot" created="1993-04-01" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
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    <organism>
        <name type="scientific">Homo sapiens</name>
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                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] LYS-170</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2016" name="Mov. Disord." volume="31" first="1004" last="1011">
            <title>Mutation in ADORA1 identified as likely cause of early-onset parkinsonism and cognitive dysfunction.</title>
            <authorList>
                <person name="Jaberi E."/>
                <person name="Rohani M."/>
                <person name="Shahidi G.A."/>
                <person name="Nafissi S."/>
                <person name="Arefian E."/>
                <person name="Soleimani M."/>
                <person name="Moghadam A."/>
                <person name="Arzenani M.K."/>
                <person name="Keramatian F."/>
                <person name="Klotzle B."/>
                <person name="Fan J.B."/>
                <person name="Turk C."/>
                <person name="Steemers F."/>
                <person name="Elahi E."/>
            </authorList>
            <dbReference type="PubMed" id="27134041"/>
            <dbReference type="DOI" id="10.1002/mds.26627"/>
        </citation>
        <scope>VARIANT SER-279</scope>
        <scope>CHARACTERIZATION OF VARIANT SER-279</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Receptor for adenosine (PubMed:29925945). The activity of this receptor is mediated by G proteins such as GNAI2 which inhibit adenylyl cyclase.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Interacts with GNAI2.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
        </interactant>
        <interactant intactId="EBI-2902702">
            <id>P29274</id>
            <label>ADORA2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
        </interactant>
        <interactant intactId="EBI-991009">
            <id>P08588</id>
            <label>ADRB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
        </interactant>
        <interactant intactId="EBI-491169">
            <id>P07550</id>
            <label>ADRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
        </interactant>
        <interactant intactId="EBI-13939599">
            <id>P16473</id>
            <label>TSHR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P30542-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P30542-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_034401 VSP_034402"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the G-protein coupled receptor 1 family.</text>
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        <property type="protein sequence ID" value="AAB23388.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAA17544.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="chains" value="A/B=2-211, A/B=228-311"/>
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        <property type="resolution" value="3.60 A"/>
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    <dbReference type="CORUM" id="P30542"/>
    <dbReference type="FunCoup" id="P30542">
        <property type="interactions" value="889"/>
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        <property type="interactions" value="12"/>
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        <property type="generic name" value="3-isobutyl-1-methyl-7H-xanthine"/>
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        <property type="generic name" value="4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol"/>
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        <property type="generic name" value="5'-S-methyl-5'-thioadenosine"/>
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        <property type="generic name" value="DPCPX"/>
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        <property type="generic name" value="GW-493838"/>
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        <property type="generic name" value="Neladenoson bialanate"/>
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        <property type="generic name" value="Oxtriphylline"/>
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        <property type="generic name" value="Pentoxifylline"/>
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        <property type="generic name" value="Peoniflorin"/>
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        <property type="generic name" value="Rolofylline"/>
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        <property type="generic name" value="Selodenoson"/>
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        <property type="generic name" value="Tecadenoson"/>
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        <property type="generic name" value="Theobromine"/>
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        <property type="generic name" value="Theophylline"/>
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        <property type="generic name" value="Tonapofylline"/>
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        <property type="generic name" value="Trabodenoson"/>
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        <property type="generic name" value="Tramadol"/>
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        <property type="family name" value="the g-protein-coupled receptor (gpcr) family"/>
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            <fullName>Adenosine receptor A2b</fullName>
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            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
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            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
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    <reference key="1">
        <citation type="journal article" date="1992" name="Biochem. Biophys. Res. Commun." volume="187" first="86" last="93">
            <title>Molecular cloning and expression of an adenosine A2b receptor from human brain.</title>
            <authorList>
                <person name="Pierce K.D."/>
                <person name="Furlong T.J."/>
                <person name="Selbie L.A."/>
                <person name="Shine J."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1995" name="Genomics" volume="27" first="374" last="376">
            <title>Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene.</title>
            <authorList>
                <person name="Jacobson M.A."/>
                <person name="Johnson R.G."/>
                <person name="Luneau C.J."/>
                <person name="Salvatore C.A."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-07" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Brain</tissue>
        </source>
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    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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            <tissue>Brain</tissue>
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    </reference>
    <comment type="function">
        <text>Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3904751">
            <id>P29275</id>
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        <interactant intactId="EBI-2902702">
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            <label>ADORA2A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
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        <text evidence="4">Belongs to the G-protein coupled receptor 1 family.</text>
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<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="181" xmlns="https://uniprot.org/uniprot">
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Mammary gland</tissue>
            <tissue>Retinoblastoma</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <scope>VARIANT VAL-118</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Kidney</tissue>
            <tissue>Testis</tissue>
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            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-672 (ISOFORM 1)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2007" name="J. Lipid Res." volume="48" first="2736" last="2750">
            <title>Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome.</title>
            <authorList>
                <person name="Watkins P.A."/>
                <person name="Maiguel D."/>
                <person name="Jia Z."/>
                <person name="Pevsner J."/>
            </authorList>
            <dbReference type="PubMed" id="17762044"/>
            <dbReference type="DOI" id="10.1194/jlr.m700378-jlr200"/>
        </citation>
        <scope>IDENTIFICATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2">Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>acetoacetate + ATP + CoA = acetoacetyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:16117"/>
            <dbReference type="ChEBI" id="CHEBI:13705"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57286"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.16"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:16118"/>
        </physiologicalReaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10259474">
            <id>Q86V21</id>
        </interactant>
        <interactant intactId="EBI-2548702">
            <id>Q96DZ9</id>
            <label>CMTM5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q86V21-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q86V21-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_030702"/>
        </isoform>
        <isoform>
            <id>Q86V21-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_030701"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Highly expressed in kidney, heart and brain, but low in liver.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAH41000" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAB14793" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.16" evidence="2"/>
    <dbReference type="EMBL" id="AB054121">
        <property type="protein sequence ID" value="BAD22560.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK022451">
        <property type="protein sequence ID" value="BAB14040.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK024036">
        <property type="protein sequence ID" value="BAB14793.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW98474.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004997">
        <property type="protein sequence ID" value="AAH04997.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC040490">
        <property type="protein sequence ID" value="AAH40490.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC040574">
        <property type="protein sequence ID" value="AAH40574.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041000">
        <property type="protein sequence ID" value="AAH41000.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051862">
        <property type="protein sequence ID" value="AAH51862.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY091468">
        <property type="protein sequence ID" value="AAM44124.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL833047">
        <property type="protein sequence ID" value="CAH56309.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9263.1">
        <molecule id="Q86V21-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001306768.1">
        <molecule id="Q86V21-2"/>
        <property type="nucleotide sequence ID" value="NM_001319839.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_076417.2">
        <molecule id="Q86V21-1"/>
        <property type="nucleotide sequence ID" value="NM_023928.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q86V21"/>
    <dbReference type="SMR" id="Q86V21"/>
    <dbReference type="BioGRID" id="122434">
        <property type="interactions" value="32"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q86V21">
        <property type="interactions" value="498"/>
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    <dbReference type="IntAct" id="Q86V21">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000324842"/>
    <dbReference type="GlyGen" id="Q86V21">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q86V21"/>
    <dbReference type="MetOSite" id="Q86V21"/>
    <dbReference type="PhosphoSitePlus" id="Q86V21"/>
    <dbReference type="SwissPalm" id="Q86V21"/>
    <dbReference type="BioMuta" id="AACS"/>
    <dbReference type="DMDM" id="74750446"/>
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    <dbReference type="MassIVE" id="Q86V21"/>
    <dbReference type="PaxDb" id="9606-ENSP00000324842"/>
    <dbReference type="PeptideAtlas" id="Q86V21"/>
    <dbReference type="ProteomicsDB" id="69950">
        <molecule id="Q86V21-1"/>
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    <dbReference type="ProteomicsDB" id="69951">
        <molecule id="Q86V21-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="69952">
        <molecule id="Q86V21-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q86V21"/>
    <dbReference type="Antibodypedia" id="31900">
        <property type="antibodies" value="141 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="65985"/>
    <dbReference type="Ensembl" id="ENST00000316519.11">
        <molecule id="Q86V21-1"/>
        <property type="protein sequence ID" value="ENSP00000324842.6"/>
        <property type="gene ID" value="ENSG00000081760.18"/>
    </dbReference>
    <dbReference type="GeneID" id="65985"/>
    <dbReference type="KEGG" id="hsa:65985"/>
    <dbReference type="MANE-Select" id="ENST00000316519.11">
        <property type="protein sequence ID" value="ENSP00000324842.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_023928.5"/>
        <property type="RefSeq protein sequence ID" value="NP_076417.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001uhc.4">
        <molecule id="Q86V21-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21298"/>
    <dbReference type="ClinPGx" id="PA134940696"/>
    <dbReference type="CTD" id="65985"/>
    <dbReference type="DisGeNET" id="65985"/>
    <dbReference type="GeneCards" id="AACS"/>
    <dbReference type="HGNC" id="HGNC:21298">
        <property type="gene designation" value="AACS"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000081760">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="614364">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000081760"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000081760"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156044"/>
    <dbReference type="HOGENOM" id="CLU_000022_3_3_1"/>
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    <dbReference type="OMA" id="MPNTWQT"/>
    <dbReference type="OrthoDB" id="10253869at2759"/>
    <dbReference type="PAN-GO" id="Q86V21">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q86V21"/>
    <dbReference type="PathwayCommons" id="Q86V21"/>
    <dbReference type="Reactome" id="R-HSA-77111">
        <property type="pathway name" value="Synthesis of Ketone Bodies"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q86V21"/>
    <dbReference type="Agora" id="ENSG00000081760"/>
    <dbReference type="BioGRID-ORCS" id="65985">
        <property type="hits" value="16 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AACS">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="65985"/>
    <dbReference type="Pharos" id="Q86V21">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q86V21"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q86V21">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000081760">
        <property type="expression patterns" value="Expressed in parotid gland and 196 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q86V21">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030729">
        <property type="term" value="F:acetoacetate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046951">
        <property type="term" value="P:ketone body biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032024">
        <property type="term" value="P:positive regulation of insulin secretion"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd05943">
        <property type="entry name" value="AACS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000036">
        <property type="entry name" value="Acetoacetyl-CoA synthetase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000037">
        <property type="entry name" value="acetoacetyl-CoA synthetase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005914">
        <property type="entry name" value="Acac_CoA_synth"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032387">
        <property type="entry name" value="ACAS_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01217">
        <property type="entry name" value="ac_ac_CoA_syn"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="NCBIfam" id="NF002937">
        <property type="entry name" value="PRK03584.1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42921">
        <property type="entry name" value="ACETOACETYL-COA SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42921:SF1">
        <property type="entry name" value="ACETOACETYL-COA SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16177">
        <property type="entry name" value="ACAS_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000315784" description="Acetoacetyl-CoA synthetase">
        <location>
            <begin position="1"/>
            <end position="672"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030701" description="In isoform 3." evidence="5">
        <location>
            <begin position="1"/>
            <end position="402"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030702" description="In isoform 2." evidence="5">
        <original>ESFEEVEDSLCVPQYNKYREERVILFLKMASGHAFQPDLVKRIRDAIRMGLSARHVPSLILETKGIPYTLNGKKVEVAVKQIIAGKAVEQGGAFSNPETLDLYRDIPELQGF</original>
        <variation>YAQRQESGSCRQTDHRWKSRGARRCFLEPRDPGSVPGHP</variation>
        <location>
            <begin position="561"/>
            <end position="672"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038303" description="In dbSNP:rs11549081." evidence="4">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060997" description="In dbSNP:rs59883951.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="470"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14793." evidence="6" ref="2">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14040." evidence="6" ref="2">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14793." evidence="6" ref="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14040." evidence="6" ref="2">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14040." evidence="6" ref="2">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH41000." evidence="6" ref="4">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="391"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9D2R0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9JMI1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="12623130"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="672" mass="75144" checksum="36006739EE4857D9" modified="2003-06-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1991-08-01" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>P22760</accession>
    <accession>A8K3L3</accession>
    <accession>D3DNJ6</accession>
    <accession>Q8N1A9</accession>
    <name>AAAD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arylacetamide deacetylase</fullName>
            <ecNumber>3.1.1.3</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AADAC</name>
        <name type="synonym">DAC</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="J. Biol. Chem." volume="269" first="21650" last="21656">
            <title>Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.</title>
            <authorList>
                <person name="Probst M.R."/>
                <person name="Beer M."/>
                <person name="Beer D."/>
                <person name="Jenoe P."/>
                <person name="Meyer U.A."/>
                <person name="Gasser R."/>
            </authorList>
            <dbReference type="PubMed" id="8063807"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(17)31855-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>VARIANT ILE-281</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
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        <scope>VARIANT ILE-281</scope>
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    <comment type="function">
        <text evidence="8 10 11 12 13">Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12044"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17855"/>
            <dbReference type="ChEBI" id="CHEBI:18035"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="EC" id="3.1.1.3"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="10 11 12 14">0.8 mM for flutamide</KM>
            <KM evidence="10 11 12 14">0.6 mM for flutamide</KM>
            <KM evidence="10 11 12 14">0.472 mM for flutamide</KM>
            <KM evidence="10 11 12 14">3.05 mM for phenacetin</KM>
            <KM evidence="10 11 12 14">1.8 mM for phenacetin</KM>
            <KM evidence="10 11 12 14">1.42 mM for phenacetin</KM>
            <KM evidence="10 11 12 14">0.2 mM for rifampicin</KM>
            <KM evidence="10 11 12 14">0.154 mM for rifampicin</KM>
            <Vmax evidence="10 11 12 14">1.1 nmol/min/mg enzyme toward flutamide</Vmax>
            <Vmax evidence="10 11 12 14">0.617 nmol/min/mg enzyme toward flutamide</Vmax>
            <Vmax evidence="10 11 12 14">1.34 nmol/min/mg enzyme toward phenacetin</Vmax>
            <Vmax evidence="10 11 12 14">6.4 nmol/min/mg enzyme toward phenacetin</Vmax>
            <Vmax evidence="10 11 12 14">1.42 nmol/min/mg enzyme toward phenacetin</Vmax>
            <Vmax evidence="10 11 12 14">0.149 nmol/min/mg enzyme toward rifampicin</Vmax>
            <Vmax evidence="10 11 12 14">0.06 nmol/min/mg enzyme toward rifampicin</Vmax>
        </kinetics>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13217105">
            <id>P22760</id>
        </interactant>
        <interactant intactId="EBI-743771">
            <id>Q92624</id>
            <label>APPBP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Endoplasmic reticulum membrane</location>
            <topology>Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Microsome membrane</location>
            <topology>Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10 11 12">Detected in liver (at protein level). Mainly expressed in liver, small intestine, colon, adrenal gland and bladder.</text>
    </comment>
    <comment type="induction">
        <text evidence="13">Down-regulated following infection with hepatis C virus which results in impaired triacylglycerol lipolysis and impaired assembly of very low density lipoproteins. This may represent a cellular adaptation to infection that is aimed at limiting viral production.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9 14">Glycosylation is required for enzyme activity.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="12">Three alleles are known: AADAC*1, AADAC*2 and AADAC*3. The sequence shown is that of AADAC*1 which is found in European American, African American, Japanese and Korean populations at allelic frequencies of 39.3 to 47.4%. The AADAC*2 allele is found in European American, African American, Korean, and Japanese populations at allelic frequencies of 52.6 to 63.5% whereas the AADAC*3 allele is found in European American (1.3%) and African American (2.0%) samples but not in Japanese or Korean samples.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Can hydrolyze a number of clinical drugs such as flutamide, an antiandrogen drug used for the treatment of prostate cancer; phenacetin, an analgesic antipyretic which has been withdrawn from the market due to its links with renal failure; and rifamycins which have been used as antituberculosis drugs.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the 'GDXG' lipolytic enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA35551" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.1.3"/>
    <dbReference type="EMBL" id="L32179">
        <property type="protein sequence ID" value="AAA35551.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290628">
        <property type="protein sequence ID" value="BAF83317.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC068647">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW78791.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW78792.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC032309">
        <property type="protein sequence ID" value="AAH32309.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33877.1"/>
    <dbReference type="PIR" id="A53856">
        <property type="entry name" value="A53856"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001077.2">
        <property type="nucleotide sequence ID" value="NM_001086.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P22760"/>
    <dbReference type="SMR" id="P22760"/>
    <dbReference type="BioGRID" id="106531">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="P22760">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="IntAct" id="P22760">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000232892"/>
    <dbReference type="BindingDB" id="P22760"/>
    <dbReference type="ChEMBL" id="CHEMBL3509584"/>
    <dbReference type="DrugBank" id="DB16349">
        <property type="generic name" value="Vicagrel"/>
    </dbReference>
    <dbReference type="ESTHER" id="human-AADAC">
        <property type="family name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.991"/>
    <dbReference type="GlyCosmos" id="P22760">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P22760">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P22760"/>
    <dbReference type="PhosphoSitePlus" id="P22760"/>
    <dbReference type="BioMuta" id="AADAC"/>
    <dbReference type="DMDM" id="317373587"/>
    <dbReference type="jPOST" id="P22760"/>
    <dbReference type="MassIVE" id="P22760"/>
    <dbReference type="PaxDb" id="9606-ENSP00000232892"/>
    <dbReference type="PeptideAtlas" id="P22760"/>
    <dbReference type="ProteomicsDB" id="54037"/>
    <dbReference type="Antibodypedia" id="1182">
        <property type="antibodies" value="197 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="13"/>
    <dbReference type="Ensembl" id="ENST00000232892.12">
        <property type="protein sequence ID" value="ENSP00000232892.6"/>
        <property type="gene ID" value="ENSG00000114771.15"/>
    </dbReference>
    <dbReference type="GeneID" id="13"/>
    <dbReference type="KEGG" id="hsa:13"/>
    <dbReference type="MANE-Select" id="ENST00000232892.12">
        <property type="protein sequence ID" value="ENSP00000232892.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001086.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001077.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003eze.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17"/>
    <dbReference type="ClinPGx" id="PA24363"/>
    <dbReference type="CTD" id="13"/>
    <dbReference type="DisGeNET" id="13"/>
    <dbReference type="GeneCards" id="AADAC"/>
    <dbReference type="HGNC" id="HGNC:17">
        <property type="gene designation" value="AADAC"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000114771">
        <property type="expression patterns" value="Tissue enhanced (adrenal gland, intestine, liver)"/>
    </dbReference>
    <dbReference type="MIM" id="600338">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000114771"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000114771"/>
    <dbReference type="eggNOG" id="KOG1515">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155975"/>
    <dbReference type="HOGENOM" id="CLU_012494_12_0_1"/>
    <dbReference type="InParanoid" id="P22760"/>
    <dbReference type="OMA" id="PKHMARW"/>
    <dbReference type="OrthoDB" id="408631at2759"/>
    <dbReference type="PAN-GO" id="P22760">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P22760"/>
    <dbReference type="PathwayCommons" id="P22760"/>
    <dbReference type="Reactome" id="R-HSA-211945">
        <property type="pathway name" value="Phase I - Functionalization of compounds"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P22760"/>
    <dbReference type="SignaLink" id="P22760"/>
    <dbReference type="Agora" id="ENSG00000114771"/>
    <dbReference type="BioGRID-ORCS" id="13">
        <property type="hits" value="6 hits in 1160 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AADAC"/>
    <dbReference type="GenomeRNAi" id="13"/>
    <dbReference type="Pharos" id="P22760">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P22760"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="P22760">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000114771">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 121 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P22760">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003824">
        <property type="term" value="F:catalytic activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019213">
        <property type="term" value="F:deacetylase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016298">
        <property type="term" value="F:lipase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017171">
        <property type="term" value="F:serine hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004806">
        <property type="term" value="F:triacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010898">
        <property type="term" value="P:positive regulation of triglyceride catabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006805">
        <property type="term" value="P:xenobiotic metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013094">
        <property type="entry name" value="AB_hydrolase_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017157">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050300">
        <property type="entry name" value="GDXG_lipolytic_enzyme"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033140">
        <property type="entry name" value="Lipase_GDXG_put_SER_AS"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081">
        <property type="entry name" value="AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081:SF28">
        <property type="entry name" value="ALPHA_BETA HYDROLASE FOLD-3 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07859">
        <property type="entry name" value="Abhydrolase_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037251">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01174">
        <property type="entry name" value="LIPASE_GDXG_SER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0492">Microsome</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000071542" description="Arylacetamide deacetylase">
        <location>
            <begin position="1"/>
            <end position="399"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="1"/>
            <end position="5"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="4">
        <location>
            <begin position="6"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="4">
        <location>
            <begin position="24"/>
            <end position="399"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole" evidence="2">
        <location>
            <begin position="111"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="active site" evidence="3 5">
        <location>
            <position position="189"/>
        </location>
    </feature>
    <feature type="active site" evidence="3">
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="active site" evidence="3">
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="9 14">
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="9 14">
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="116"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014798" description="In alleles AADAC*2 and AADAC*3; mildly decreased enzyme activity; dbSNP:rs1803155." evidence="6 7 12 15 16">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070543" description="In allele AADAC*3; decreased enzyme activity." evidence="12">
        <original>L</original>
        <variation>LQ</variation>
        <location>
            <position position="399"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes glycosylation at this site and causes moderate decrease in activity." evidence="14">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes glycosylation at this site and causes substantial decrease in activity and reduced substrate affinity." evidence="14">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AA sequence." evidence="17" ref="6">
        <original>R</original>
        <variation>M</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA35551." evidence="17" ref="1">
        <original>LHH</original>
        <variation>VHI</variation>
        <location>
            <begin position="55"/>
            <end position="57"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q5NUF3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8BLF1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10038"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12721789"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17936933"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="19159218"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="19339378"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="22207054"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="22415931"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="23542347"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="24125761"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="8063807"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <sequence length="399" mass="45734" checksum="34F9CB717DD7417A" modified="2011-01-11" version="5">MGRKSLYLLIVGILIAYYIYTPLPDNVEEPWRMMWINAHLKTIQNLATFVELLGLHHFMDSFKVVGSFDEVPPTSDENVTVTETKFNNILVRVYVPKRKSEALRRGLFYIHGGGWCVGSAALSGYDLLSRWTADRLDAVVVSTNYRLAPKYHFPIQFEDVYNALRWFLRKKVLAKYGVNPERIGISGDSAGGNLAAAVTQQLLDDPDVKIKLKIQSLIYPALQPLDVDLPSYQENSNFLFLSKSLMVRFWSEYFTTDRSLEKAMLSRQHVPVESSHLFKFVNWSSLLPERFIKGHVYNNPNYGSSELAKKYPGFLDVRAAPLLADDNKLRGLPLTYVITCQYDLLRDDGLMYVTRLRNTGVQVTHNHVEDGFHGAFSFLGLKISHRLINQYIEWLKENL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2026-01-28" version="225" xmlns="https://uniprot.org/uniprot">
    <accession>Q15758</accession>
    <accession>A8K9H5</accession>
    <accession>B4DR77</accession>
    <accession>B4DWS4</accession>
    <accession>B7ZB81</accession>
    <accession>D0EYG6</accession>
    <accession>E9PC01</accession>
    <accession>O95720</accession>
    <accession>Q96RL9</accession>
    <accession>Q9BWQ3</accession>
    <accession>Q9UNP2</accession>
    <name>AAAT_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Neutral amino acid transporter B(0)</fullName>
            <shortName>ATB(0)</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Baboon M7 virus receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>RD114/simian type D retrovirus receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Sodium-dependent neutral amino acid transporter type 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Solute carrier family 1 member 5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="24" type="primary">SLC1A5</name>
        <name evidence="25" type="synonym">ASCT2</name>
        <name type="synonym">M7V1</name>
        <name type="synonym">RDR</name>
        <name type="synonym">RDRC</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Biol. Chem." volume="271" first="18657" last="18661">
            <title>Cloning of the sodium-dependent, broad-scope, neutral amino acid transporter Bo from a human placental choriocarcinoma cell line.</title>
            <authorList>
                <person name="Kekuda R."/>
                <person name="Prasad P.D."/>
                <person name="Fei Y.-J."/>
                <person name="Torres-Zamorano V."/>
                <person name="Sinha S."/>
                <person name="Yang-Feng T.L."/>
                <person name="Leibach F.H."/>
                <person name="Ganapathy V."/>
            </authorList>
            <dbReference type="PubMed" id="8702519"/>
            <dbReference type="DOI" id="10.1074/jbc.271.31.18657"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Choriocarcinoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Proc. Natl. Acad. Sci. U.S.A." volume="96" first="2129" last="2134">
            <title>The RD114/simian type D retrovirus receptor is a neutral amino acid transporter.</title>
            <authorList>
                <person name="Rasko J.E.J."/>
                <person name="Battini J.L."/>
                <person name="Gottschalk R.J."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-535</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-493; THR-494; SER-535 AND SER-539</scope>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ERVH48-1</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
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        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 158-230</scope>
        <scope>SUBUNIT</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.85 ANGSTROMS)</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
        <scope>DOMAIN</scope>
        <scope>SUBUNIT</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.61 ANGSTROMS)</scope>
        <scope>DOMAIN</scope>
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            <dbReference type="PubMed" id="39095408"/>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH SODIUM IONS AND L-GLUTAMINE</scope>
        <scope>DOMAIN</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
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        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.31 ANGSTROMS) IN COMPLEX WITH SODIUM IONS AND L-ALANINE</scope>
        <scope>SUBUNIT</scope>
        <scope>DOMAIN</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ERVW-1 AND ERVH48-1</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6 9 11 12 13 14 15 16 18 19 20 21 22">Sodium-coupled antiporter of neutral amino acids. In a tri-substrate transport cycle, exchanges neutral amino acids between the extracellular and intracellular compartments, coupled to the inward cotransport of at least one sodium ion (PubMed:17094966, PubMed:23756778, PubMed:26492990, PubMed:29872227, PubMed:34741534, PubMed:8702519, PubMed:39095408, PubMed:27272177). The preferred substrate is the essential amino acid L-glutamine, a precursor for biosynthesis of proteins, nucleotides and amine sugars as well as an alternative fuel for mitochondrial oxidative phosphorylation. Exchanges L-glutamine with other neutral amino acids such as L-serine, L-threonine and L-asparagine in a bidirectional way. Provides L-glutamine to proliferating stem and activated cells driving the metabolic switch toward cell differentiation (PubMed:23756778, PubMed:24953180). The transport cycle is usually pH-independent, with the exception of L-glutamate. Transports extracellular L-glutamate coupled to the cotransport of one proton and one sodium ion in exchange for intracellular L-glutamine counter-ion. May provide for L-glutamate uptake in glial cells regulating glutamine/glutamate cycle in the nervous system (PubMed:32733894). Can transport D-amino acids. Mediates D-serine release from the retinal glia potentially affecting NMDA receptor function in retinal neurons (PubMed:17094966). Displays sodium- and amino acid-dependent but uncoupled channel-like anion conductance with a preference SCN(-) &gt;&gt; NO3(-) &gt; I(-) &gt; Cl(-) (By similarity). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904, PubMed:38671230).</text>
    </comment>
    <comment type="function">
        <text evidence="4 5">(Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.</text>
    </comment>
    <comment type="function">
        <text evidence="5">(Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.</text>
    </comment>
    <comment type="function">
        <text evidence="5">(Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 16 19">
            <text>L-glutamine(out) + L-serine(in) + Na(+)(out) = L-glutamine(in) + L-serine(out) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70855"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:33384"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 18">
            <text>L-glutamine(in) + L-serine(out) + Na(+)(out) = L-glutamine(out) + L-serine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70887"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:33384"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 14 16">
            <text>L-threonine(in) + L-glutamine(out) + Na(+)(out) = L-threonine(out) + L-glutamine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70863"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:57926"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14">
            <text>L-threonine(out) + L-glutamine(in) + Na(+)(out) = L-threonine(in) + L-glutamine(out) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70879"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:57926"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>L-asparagine(in) + L-glutamine(out) + Na(+)(out) = L-asparagine(out) + L-glutamine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70859"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:58048"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 16 18">
            <text>L-asparagine(out) + L-glutamine(in) + Na(+)(out) = L-asparagine(in) + L-glutamine(out) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70891"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:58048"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 16">
            <text>L-glutamine(in) + L-alanine(out) + Na(+)(out) = L-glutamine(out) + L-alanine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70867"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>L-valine(out) + L-glutamine(in) + Na(+)(out) = L-valine(in) + L-glutamine(out) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70871"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:57762"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>L-glutamine(in) + L-methionine(out) + Na(+)(out) = L-glutamine(out) + L-methionine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70875"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="18">
            <text>L-glutamine(in) + L-glutamate(out) + Na(+)(out) + H(+)(out) = L-glutamine(out) + L-glutamate(in) + Na(+)(in) + H(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:70883"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 15">
            <text>D-serine(in) + L-glutamine(out) + Na(+)(out) = D-serine(out) + L-glutamine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:75307"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>D-serine(out) + L-glutamine(in) + Na(+)(out) = D-serine(in) + L-glutamine(out) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:84327"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 15">
            <text>D-serine(in) + L-alanine(out) + Na(+)(out) = D-serine(out) + L-alanine(in) + Na(+)(in)</text>
            <dbReference type="Rhea" id="RHEA:75311"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
            <dbReference type="ChEBI" id="CHEBI:35247"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>nitrate(in) = nitrate(out)</text>
            <dbReference type="Rhea" id="RHEA:34923"/>
            <dbReference type="ChEBI" id="CHEBI:17632"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>iodide(out) = iodide(in)</text>
            <dbReference type="Rhea" id="RHEA:66324"/>
            <dbReference type="ChEBI" id="CHEBI:16382"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>thiocyanate(in) = thiocyanate(out)</text>
            <dbReference type="Rhea" id="RHEA:75347"/>
            <dbReference type="ChEBI" id="CHEBI:18022"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="14">Regulated by L-cysteine, which can either inhibit substrate influx or trigger substrate efflux without being transported itself.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="16">0.056 mM for L-glutamine(out)</KM>
            <KM evidence="12">0.097 mM for L-glutamine(out)</KM>
            <KM evidence="12">1.8 mM for L-glutamine(in)</KM>
            <KM evidence="12">32 mM for Na(+)(out)</KM>
            <KM evidence="16">16.5 mM for Na(+)(out)</KM>
            <Vmax evidence="12">13.3 nmol/min/mg enzyme toward L-glutamine(out)</Vmax>
            <Vmax evidence="12">12.0 nmol/min/mg enzyme toward L-glutamine(in)</Vmax>
            <Vmax evidence="12">11.5 nmol/min/mg enzyme toward Na(+)(out)</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="12">Optimum pH is 7.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="11 16 20 21 27">Homotrimer (Probable) (PubMed:29872227, PubMed:38671230, PubMed:39095408). Interacts with secreted ERVH48-1/suppressyn (via RBD domain); this interaction decreases SLC1A5 transport rate and may negatively regulate syncytialization (PubMed:23492904, PubMed:38671230). Interacts with ERVW-1/syncytin (via RBD domain); this interaction decreases SLC1A5 transport rate (PubMed:38671230).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-11976321">
            <id>O95236-2</id>
            <label>APOL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-12188331">
            <id>P60201-2</id>
            <label>PLP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-1047946">
            <id>P26045</id>
            <label>PTPN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-348482">
            <id>Q99942</id>
            <label>RNF5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356576">
            <id>Q15758</id>
        </interactant>
        <interactant intactId="EBI-11988865">
            <id>A5PKU2</id>
            <label>TUSC5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 22 28">Cell membrane</location>
            <topology evidence="16">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Melanosome</location>
        </subcellularLocation>
        <text>Identified by mass spectrometry in melanosome fractions from stage I to stage IV.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <event type="alternative initiation"/>
        <isoform>
            <id>Q15758-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15758-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046354"/>
        </isoform>
        <isoform>
            <id>Q15758-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046851"/>
        </isoform>
        <text evidence="7">A number of isoforms are produced by alternative initiation. Isoforms start at multiple alternative CUG and GUG codons.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="13 22">Placenta, lung, skeletal muscle, kidney, pancreas, and intestine (PubMed:8702519). Expressed in CD34-positive hematopoietic progenitors (at protein level) (PubMed:24953180).</text>
    </comment>
    <comment type="domain">
        <text evidence="17 21">The transport domain consists of four transmembrane regions 3, 6, 7 and 8 and two helical hairpins HP1 and HP2. According to the one-gate elevator transport model, substrate binding and release is controlled by HP2 which acts as a gate for the transport domain. HP2 gate opening enables substrate binding or release. The gate closes once one amino acid and up to three sodium ions bind to the transport domain, which subsequently triggers transmembrane elevator-like motion of the transporter across the plasma membrane.</text>
    </comment>
    <comment type="domain">
        <text evidence="16 20">The beta-hairpin (aa 204-224) located between the helical segments of TM4 protrudes in the extracellular space and forms a docking platform for proteins of retroviral origin.</text>
    </comment>
    <comment type="similarity">
        <text evidence="26">Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A5 subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="U53347">
        <property type="protein sequence ID" value="AAC50629.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF102826">
        <property type="protein sequence ID" value="AAD09812.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF105423">
        <property type="protein sequence ID" value="AAD27806.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="GQ919058">
        <property type="protein sequence ID" value="ACX53626.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292690">
        <property type="protein sequence ID" value="BAF85379.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299137">
        <property type="protein sequence ID" value="BAG61189.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301661">
        <property type="protein sequence ID" value="BAG63136.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK316546">
        <property type="protein sequence ID" value="BAH14917.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008622">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471126">
        <property type="protein sequence ID" value="EAW57446.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000062">
        <property type="protein sequence ID" value="AAH00062.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF334818">
        <property type="protein sequence ID" value="AAK77026.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12692.1">
        <molecule id="Q15758-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46125.1">
        <molecule id="Q15758-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46126.1">
        <molecule id="Q15758-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138616.1">
        <molecule id="Q15758-3"/>
        <property type="nucleotide sequence ID" value="NM_001145144.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138617.1">
        <molecule id="Q15758-2"/>
        <property type="nucleotide sequence ID" value="NM_001145145.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005619.1">
        <molecule id="Q15758-1"/>
        <property type="nucleotide sequence ID" value="NM_005628.3"/>
    </dbReference>
    <dbReference type="PDB" id="5LLM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="A=158-230"/>
    </dbReference>
    <dbReference type="PDB" id="5LLU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.32 A"/>
        <property type="chains" value="A=158-230"/>
    </dbReference>
    <dbReference type="PDB" id="5LM4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A=158-230"/>
    </dbReference>
    <dbReference type="PDB" id="5MJU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.71 A"/>
        <property type="chains" value="A=158-230"/>
    </dbReference>
    <dbReference type="PDB" id="6GCT">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.85 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="6MP6">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.54 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="6MPB">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.84 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="6RVX">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.61 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="6RVY">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.13 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="7BCQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.43 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="7BCS">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.43 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="7BCT">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.37 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8OUD">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.31 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8OUH">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.62 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8OUJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRO">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRP">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.74 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRR">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.78 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRS">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.86 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRU">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRV">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDB" id="8QRW">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="B=1-541"/>
    </dbReference>
    <dbReference type="PDBsum" id="5LLM"/>
    <dbReference type="PDBsum" id="5LLU"/>
    <dbReference type="PDBsum" id="5LM4"/>
    <dbReference type="PDBsum" id="5MJU"/>
    <dbReference type="PDBsum" id="6GCT"/>
    <dbReference type="PDBsum" id="6MP6"/>
    <dbReference type="PDBsum" id="6MPB"/>
    <dbReference type="PDBsum" id="6RVX"/>
    <dbReference type="PDBsum" id="6RVY"/>
    <dbReference type="PDBsum" id="7BCQ"/>
    <dbReference type="PDBsum" id="7BCS"/>
    <dbReference type="PDBsum" id="7BCT"/>
    <dbReference type="PDBsum" id="8OUD"/>
    <dbReference type="PDBsum" id="8OUH"/>
    <dbReference type="PDBsum" id="8OUJ"/>
    <dbReference type="PDBsum" id="8QRO"/>
    <dbReference type="PDBsum" id="8QRP"/>
    <dbReference type="PDBsum" id="8QRQ"/>
    <dbReference type="PDBsum" id="8QRR"/>
    <dbReference type="PDBsum" id="8QRS"/>
    <dbReference type="PDBsum" id="8QRU"/>
    <dbReference type="PDBsum" id="8QRV"/>
    <dbReference type="PDBsum" id="8QRW"/>
    <dbReference type="AlphaFoldDB" id="Q15758"/>
    <dbReference type="EMDB" id="EMD-10016"/>
    <dbReference type="EMDB" id="EMD-10018"/>
    <dbReference type="EMDB" id="EMD-12142"/>
    <dbReference type="EMDB" id="EMD-12143"/>
    <dbReference type="EMDB" id="EMD-17189"/>
    <dbReference type="EMDB" id="EMD-17192"/>
    <dbReference type="EMDB" id="EMD-17194"/>
    <dbReference type="EMDB" id="EMD-18621"/>
    <dbReference type="EMDB" id="EMD-18622"/>
    <dbReference type="EMDB" id="EMD-18623"/>
    <dbReference type="EMDB" id="EMD-18624"/>
    <dbReference type="EMDB" id="EMD-18625"/>
    <dbReference type="EMDB" id="EMD-18626"/>
    <dbReference type="EMDB" id="EMD-18627"/>
    <dbReference type="EMDB" id="EMD-18628"/>
    <dbReference type="EMDB" id="EMD-4386"/>
    <dbReference type="EMDB" id="EMD-9187"/>
    <dbReference type="EMDB" id="EMD-9188"/>
    <dbReference type="SMR" id="Q15758"/>
    <dbReference type="BioGRID" id="112401">
        <property type="interactions" value="452"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q15758">
        <property type="interactions" value="1104"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15758">
        <property type="interactions" value="180"/>
    </dbReference>
    <dbReference type="MINT" id="Q15758"/>
    <dbReference type="STRING" id="9606.ENSP00000444408"/>
    <dbReference type="BindingDB" id="Q15758"/>
    <dbReference type="ChEMBL" id="CHEMBL3562162"/>
    <dbReference type="DrugBank" id="DB00174">
        <property type="generic name" value="Asparagine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13146">
        <property type="generic name" value="Fluciclovine (18F)"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00130">
        <property type="generic name" value="L-Glutamine"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="874"/>
    <dbReference type="TCDB" id="2.A.23.3.3">
        <property type="family name" value="the dicarboxylate/amino acid:cation (na(+) or h(+)) symporter (daacs) family"/>
    </dbReference>
    <dbReference type="GlyConnect" id="1562">
        <property type="glycosylation" value="3 N-Linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q15758">
        <property type="glycosylation" value="2 sites, 3 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15758">
        <property type="glycosylation" value="2 sites, 11 N-linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15758"/>
    <dbReference type="MetOSite" id="Q15758"/>
    <dbReference type="PhosphoSitePlus" id="Q15758"/>
    <dbReference type="SwissPalm" id="Q15758"/>
    <dbReference type="BioMuta" id="SLC1A5"/>
    <dbReference type="DMDM" id="21542389"/>
    <dbReference type="CPTAC" id="CPTAC-2713"/>
    <dbReference type="CPTAC" id="CPTAC-2714"/>
    <dbReference type="jPOST" id="Q15758"/>
    <dbReference type="MassIVE" id="Q15758"/>
    <dbReference type="PaxDb" id="9606-ENSP00000444408"/>
    <dbReference type="PeptideAtlas" id="Q15758"/>
    <dbReference type="ProteomicsDB" id="19331"/>
    <dbReference type="ProteomicsDB" id="5376"/>
    <dbReference type="ProteomicsDB" id="60744">
        <molecule id="Q15758-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q15758"/>
    <dbReference type="ABCD" id="Q15758">
        <property type="antibodies" value="10 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="18149">
        <property type="antibodies" value="311 antibodies from 36 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="6510"/>
    <dbReference type="Ensembl" id="ENST00000412532.6">
        <molecule id="Q15758-3"/>
        <property type="protein sequence ID" value="ENSP00000397924.1"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000434726.6">
        <molecule id="Q15758-2"/>
        <property type="protein sequence ID" value="ENSP00000406532.1"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000542575.6">
        <molecule id="Q15758-1"/>
        <property type="protein sequence ID" value="ENSP00000444408.1"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000593713.2">
        <molecule id="Q15758-3"/>
        <property type="protein sequence ID" value="ENSP00000468890.2"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000598022.2">
        <molecule id="Q15758-3"/>
        <property type="protein sequence ID" value="ENSP00000471626.2"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000713951.1">
        <molecule id="Q15758-3"/>
        <property type="protein sequence ID" value="ENSP00000519244.1"/>
        <property type="gene ID" value="ENSG00000105281.14"/>
    </dbReference>
    <dbReference type="GeneID" id="6510"/>
    <dbReference type="KEGG" id="hsa:6510"/>
    <dbReference type="MANE-Select" id="ENST00000542575.6">
        <property type="protein sequence ID" value="ENSP00000444408.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005628.3"/>
        <property type="RefSeq protein sequence ID" value="NP_005619.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002pfr.4">
        <molecule id="Q15758-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:10943"/>
    <dbReference type="ClinPGx" id="PA35830"/>
    <dbReference type="CTD" id="6510"/>
    <dbReference type="DisGeNET" id="6510"/>
    <dbReference type="GeneCards" id="SLC1A5"/>
    <dbReference type="HGNC" id="HGNC:10943">
        <property type="gene designation" value="SLC1A5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000105281">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="SLC1A5"/>
    <dbReference type="MIM" id="109190">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000105281"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000105281"/>
    <dbReference type="eggNOG" id="KOG3787">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159485"/>
    <dbReference type="HOGENOM" id="CLU_019375_3_3_1"/>
    <dbReference type="InParanoid" id="Q15758"/>
    <dbReference type="OMA" id="VGTFYAT"/>
    <dbReference type="OrthoDB" id="5877963at2759"/>
    <dbReference type="PAN-GO" id="Q15758">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15758"/>
    <dbReference type="PathwayCommons" id="Q15758"/>
    <dbReference type="Reactome" id="R-HSA-352230">
        <property type="pathway name" value="Amino acid transport across the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9013149">
        <property type="pathway name" value="RAC1 GTPase cycle"/>
    </dbReference>
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</entry>
<entry dataset="Swiss-Prot" created="2004-04-13" modified="2026-01-28" version="184" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N5Z0</accession>
    <accession>B3KP84</accession>
    <accession>Q9UL02</accession>
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            <fullName evidence="10">Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial</fullName>
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        <alternativeName>
            <fullName>2-aminoadipate aminotransferase</fullName>
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        <alternativeName>
            <fullName>2-aminoadipate transaminase</fullName>
            <ecNumber evidence="5 8">2.6.1.39</ecNumber>
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        <alternativeName>
            <fullName>Alpha-aminoadipate aminotransferase</fullName>
            <shortName>AadAT</shortName>
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        <alternativeName>
            <fullName evidence="10">Glycine transaminase AADAT</fullName>
            <ecNumber evidence="8">2.6.1.4</ecNumber>
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        <alternativeName>
            <fullName>Kynurenine aminotransferase II</fullName>
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            <fullName evidence="10">Kynurenine--glyoxylate transaminase AADAT</fullName>
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        <alternativeName>
            <fullName>Kynurenine--oxoglutarate aminotransferase II</fullName>
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        <alternativeName>
            <fullName>Kynurenine--oxoglutarate transaminase 2</fullName>
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            <fullName>Kynurenine--oxoglutarate transaminase II</fullName>
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            <fullName evidence="10">Methionine--glyoxylate transaminase AADAT</fullName>
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        <name evidence="14" type="primary">AADAT</name>
        <name evidence="14" type="synonym">KAT2</name>
        <name evidence="14" type="synonym">KYAT2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1998-10" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human L-kynurenine/alpha-aminoadipate aminotransferase cDNA from brain tissue.</title>
            <authorList>
                <person name="Gatti S."/>
                <person name="Breton J."/>
                <person name="Mostardini M."/>
                <person name="Mosca M."/>
                <person name="Tarroni P."/>
                <person name="Schwarcz R."/>
                <person name="Speciale C."/>
                <person name="Okuno E."/>
                <person name="Toma S."/>
                <person name="Benatti L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="Mol. Genet. Metab." volume="76" first="172" last="180">
            <title>Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT).</title>
            <authorList>
                <person name="Goh D.L.M."/>
                <person name="Patel A."/>
                <person name="Thomas G.H."/>
                <person name="Salomons G.S."/>
                <person name="Schor D.S.M."/>
                <person name="Jakobs C."/>
                <person name="Geraghty M.T."/>
            </authorList>
            <dbReference type="PubMed" id="12126930"/>
            <dbReference type="DOI" id="10.1016/s1096-7192(02)00037-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2008" name="Biosci. Rep." volume="28" first="205" last="215">
            <title>Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II.</title>
            <authorList>
                <person name="Han Q."/>
                <person name="Cai T."/>
                <person name="Tagle D.A."/>
                <person name="Robinson H."/>
                <person name="Li J."/>
            </authorList>
            <dbReference type="PubMed" id="18620547"/>
            <dbReference type="DOI" id="10.1042/bsr20080085"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH 2-OXOGLUTARATE</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="3567" last="3573">
            <title>Crystal structure of human kynurenine aminotransferase II.</title>
            <authorList>
                <person name="Han Q."/>
                <person name="Robinson H."/>
                <person name="Li J."/>
            </authorList>
            <dbReference type="PubMed" id="18056995"/>
            <dbReference type="DOI" id="10.1074/jbc.m708358200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND KYRUNENINE</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="3559" last="3566">
            <title>Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia.</title>
            <authorList>
                <person name="Rossi F."/>
                <person name="Garavaglia S."/>
                <person name="Montalbano V."/>
                <person name="Walsh M.A."/>
                <person name="Rizzi M."/>
            </authorList>
            <dbReference type="PubMed" id="18056996"/>
            <dbReference type="DOI" id="10.1074/jbc.m707925200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 8">Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>glycine + 2-oxoglutarate = glyoxylate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:14089"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="EC" id="2.6.1.4"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8">
            <text>L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + H2O</text>
            <dbReference type="Rhea" id="RHEA:65560"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="EC" id="2.6.1.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12 13">
            <dbReference type="Rhea" id="RHEA:65561"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-kynurenine + glyoxylate = kynurenate + glycine + H2O</text>
            <dbReference type="Rhea" id="RHEA:65896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="EC" id="2.6.1.63"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:65897"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>3-hydroxy-L-kynurenine + glyoxylate = xanthurenate + glycine + H2O</text>
            <dbReference type="Rhea" id="RHEA:65900"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:58125"/>
            <dbReference type="ChEBI" id="CHEBI:71201"/>
            <dbReference type="EC" id="2.6.1.63"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>2-oxohexanoate + L-kynurenine = L-2-aminohexanoate + kynurenate + H2O</text>
            <dbReference type="Rhea" id="RHEA:66060"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:35177"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="ChEBI" id="CHEBI:58455"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:66061"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>3-phenylpyruvate + L-kynurenine = kynurenate + L-phenylalanine + H2O</text>
            <dbReference type="Rhea" id="RHEA:66092"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18005"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:66093"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>4-methylsulfanyl-2-oxobutanoate + L-kynurenine = kynurenate + L-methionine + H2O</text>
            <dbReference type="Rhea" id="RHEA:69096"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16723"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:69097"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>2-oxo-3-sulfanylpropanoate + L-kynurenine = kynurenate + L-cysteine + H2O</text>
            <dbReference type="Rhea" id="RHEA:69104"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:35235"/>
            <dbReference type="ChEBI" id="CHEBI:57678"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:69105"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>indole-3-pyruvate + L-kynurenine = kynurenate + L-tryptophan + H2O</text>
            <dbReference type="Rhea" id="RHEA:66052"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17640"/>
            <dbReference type="ChEBI" id="CHEBI:57912"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:66053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>2-oxopentanoate + L-kynurenine = L-2-aminopentanoate + kynurenate + H2O</text>
            <dbReference type="Rhea" id="RHEA:66076"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28644"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58441"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:66077"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>4-methyl-2-oxopentanoate + L-kynurenine = kynurenate + L-leucine + H2O</text>
            <dbReference type="Rhea" id="RHEA:66068"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17865"/>
            <dbReference type="ChEBI" id="CHEBI:57427"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:66069"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 8">
            <text>L-2-aminoadipate + 2-oxoglutarate = 2-oxoadipate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:12601"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:57499"/>
            <dbReference type="ChEBI" id="CHEBI:58672"/>
            <dbReference type="EC" id="2.6.1.39"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:12602"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>glyoxylate + L-methionine = 4-methylsulfanyl-2-oxobutanoate + glycine</text>
            <dbReference type="Rhea" id="RHEA:22884"/>
            <dbReference type="ChEBI" id="CHEBI:16723"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
            <dbReference type="EC" id="2.6.1.73"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-2-aminoadipate + glyoxylate = 2-oxoadipate + glycine</text>
            <dbReference type="Rhea" id="RHEA:69112"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57499"/>
            <dbReference type="ChEBI" id="CHEBI:58672"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:69113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-tyrosine + glyoxylate = 3-(4-hydroxyphenyl)pyruvate + glycine</text>
            <dbReference type="Rhea" id="RHEA:69116"/>
            <dbReference type="ChEBI" id="CHEBI:36242"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:58315"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>glyoxylate + L-phenylalanine = 3-phenylpyruvate + glycine</text>
            <dbReference type="Rhea" id="RHEA:69120"/>
            <dbReference type="ChEBI" id="CHEBI:18005"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-tryptophan + glyoxylate = indole-3-pyruvate + glycine</text>
            <dbReference type="Rhea" id="RHEA:69124"/>
            <dbReference type="ChEBI" id="CHEBI:17640"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57912"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-leucine + glyoxylate = 4-methyl-2-oxopentanoate + glycine</text>
            <dbReference type="Rhea" id="RHEA:69128"/>
            <dbReference type="ChEBI" id="CHEBI:17865"/>
            <dbReference type="ChEBI" id="CHEBI:36655"/>
            <dbReference type="ChEBI" id="CHEBI:57305"/>
            <dbReference type="ChEBI" id="CHEBI:57427"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>2-oxobutanoate + L-kynurenine = (2S)-2-aminobutanoate + kynurenate + H2O</text>
            <dbReference type="Rhea" id="RHEA:66044"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16763"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="ChEBI" id="CHEBI:74359"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:66045"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>2-oxoadipate + L-kynurenine = L-2-aminoadipate + kynurenate + H2O</text>
            <dbReference type="Rhea" id="RHEA:70047"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57499"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="ChEBI" id="CHEBI:58672"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:70048"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="5 6 7">
            <name>pyridoxal 5'-phosphate</name>
            <dbReference type="ChEBI" id="CHEBI:597326"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="8">Kynurenine transaminase activity is competitively inhibited by aminoadipate, asparagine, glutamate, histidine, cysteine, lysine, 3-hydroxy-kynurenine and phenylalanine.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="8">0.9 mM for aminoadipate</KM>
            <KM evidence="8">4.7 mM for kynurenine</KM>
            <KM evidence="8">1.7 mM for methionine</KM>
            <KM evidence="8">1.6 mM for glutamate</KM>
            <KM evidence="8">1.8 mM for tyrosine</KM>
            <KM evidence="8">1.2 mM for 2-oxoglutarate</KM>
            <KM evidence="8">1.5 mM for 2-oxocaproic acid</KM>
            <KM evidence="8">1.8 mM for phenylpyruvate</KM>
            <KM evidence="8">1.4 mM for ino-3-pyruvate</KM>
        </kinetics>
        <phDependence>
            <text evidence="8">Optimum pH is 7-9.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="8">Optimum temperature is 50 degrees Celsius.</text>
        </temperatureDependence>
    </comment>
    <comment type="pathway">
        <text>Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 4/6.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 7 8">Homodimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N5Z0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N5Z0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009874"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Higher expression in the liver. Also found in heart, brain, kidney, pancreas, prostate, testis and ovary.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>May be due to a competing donor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
    </comment>
    <dbReference type="EC" id="2.6.1.39" evidence="5 8"/>
    <dbReference type="EC" id="2.6.1.4" evidence="8"/>
    <dbReference type="EC" id="2.6.1.63" evidence="8"/>
    <dbReference type="EC" id="2.6.1.7" evidence="6 8"/>
    <dbReference type="EC" id="2.6.1.73" evidence="8"/>
    <dbReference type="EMBL" id="AF097994">
        <property type="protein sequence ID" value="AAF04623.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF481738">
        <property type="protein sequence ID" value="AAM09683.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK055952">
        <property type="protein sequence ID" value="BAG51596.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031068">
        <property type="protein sequence ID" value="AAH31068.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3814.1">
        <molecule id="Q8N5Z0-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS75209.1">
        <molecule id="Q8N5Z0-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273611.1">
        <molecule id="Q8N5Z0-2"/>
        <property type="nucleotide sequence ID" value="NM_001286682.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273612.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="NM_001286683.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057312.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="NM_016228.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_872603.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="NM_182662.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024309845.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="XM_024454077.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047271719.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="XM_047415763.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206124.1">
        <molecule id="Q8N5Z0-1"/>
        <property type="nucleotide sequence ID" value="XM_054350149.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206125.1">
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            <dbReference type="HGNC" id="HGNC:17929"/>
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            <dbReference type="PDB" id="4GEB"/>
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            <dbReference type="PDB" id="6T8P"/>
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    <sequence length="425" mass="47352" checksum="448CCAAB2173A7BA" modified="2004-04-13" version="2" precursor="true">MNYARFITAASAARNPSPIRTMTDILSRGPKSMISLAGGLPNPNMFPFKTAVITVENGKTIQFGEEMMKRALQYSPSAGIPELLSWLKQLQIKLHNPPTIHYPPSQGQMDLCVTSGSQQGLCKVFEMIINPGDNVLLDEPAYSGTLQSLHPLGCNIINVASDESGIVPDSLRDILSRWKPEDAKNPQKNTPKFLYTVPNGNNPTGNSLTSERKKEIYELARKYDFLIIEDDPYYFLQFNKFRVPTFLSMDVDGRVIRADSFSKIISSGLRIGFLTGPKPLIERVILHIQVSTLHPSTFNQLMISQLLHEWGEEGFMAHVDRVIDFYSNQKDAILAAADKWLTGLAEWHVPAAGMFLWIKVKGINDVKELIEEKAVKMGVLMLPGNAFYVDSSAPSPYLRASFSSASPEQMDVAFQVLAQLIKESL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="261" xmlns="https://uniprot.org/uniprot">
    <accession>P01011</accession>
    <accession>B3KVQ7</accession>
    <accession>Q13703</accession>
    <accession>Q2TU87</accession>
    <accession>Q2TU88</accession>
    <accession>Q59GP9</accession>
    <accession>Q6LBY8</accession>
    <accession>Q6LDT7</accession>
    <accession>Q6NSC9</accession>
    <accession>Q8N177</accession>
    <accession>Q96DW8</accession>
    <accession>Q9UC47</accession>
    <accession>Q9UNU9</accession>
    <name>AACT_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-1-antichymotrypsin</fullName>
            <shortName>ACT</shortName>
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        <alternativeName>
            <fullName>Cell growth-inhibiting gene 24/25 protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Serpin A3</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Alpha-1-antichymotrypsin His-Pro-less</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">SERPINA3</name>
        <name type="synonym">AACT</name>
        <name type="ORF">GIG24</name>
        <name type="ORF">GIG25</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1983" name="Biochemistry" volume="22" first="5055" last="5061">
            <title>Sequence homology between human alpha 1-antichymotrypsin, alpha 1-antitrypsin, and antithrombin III.</title>
            <authorList>
                <person name="Chandra T."/>
                <person name="Stackhouse R."/>
                <person name="Kidd V.J."/>
                <person name="Robson K.J.H."/>
                <person name="Woo S.L.C."/>
            </authorList>
            <dbReference type="PubMed" id="6606438"/>
            <dbReference type="DOI" id="10.1021/bi00291a001"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="Genomics" volume="17" first="740" last="743">
            <title>A leucine-to-proline substitution causes a defective alpha 1-antichymotrypsin allele associated with familial obstructive lung disease.</title>
            <authorList>
                <person name="Poller W."/>
                <person name="Faber J.-P."/>
                <person name="Weidinger S."/>
                <person name="Tief K."/>
                <person name="Scholz S."/>
                <person name="Fischer M."/>
                <person name="Olek K."/>
                <person name="Kirchgesser M."/>
                <person name="Heidtmann H.-H."/>
            </authorList>
            <dbReference type="PubMed" id="8244391"/>
            <dbReference type="DOI" id="10.1006/geno.1993.1396"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS PRO-78 AND ALA-252</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-12" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of a human cell growth inhibiting gene.</title>
            <authorList>
                <person name="Kim J.W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT THR-9</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT THR-9</scope>
        <source>
            <tissue>Urinary bladder</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-03" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Takeda T."/>
                <person name="Sakaki Y."/>
                <person name="Tanaka A."/>
                <person name="Yokoyama S."/>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
                <person name="Kikuno R.F."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT THR-9</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <scope>VARIANTS THR-9 AND ARG-267</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Liver</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1988" name="Cell" volume="52" first="487" last="501">
            <title>Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease.</title>
            <authorList>
                <person name="Abraham C.R."/>
                <person name="Selkoe D.J."/>
                <person name="Potter H."/>
            </authorList>
            <dbReference type="PubMed" id="3257719"/>
            <dbReference type="DOI" id="10.1016/0092-8674(88)90462-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-46</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="1821" last="1827">
            <title>Molecular studies define the primary structure of alpha1-antichymotrypsin (ACT) protease inhibitor in Alzheimer's disease brains. Comparison of act in hippocampus and liver.</title>
            <authorList>
                <person name="Hwang S.-R."/>
                <person name="Steineckert B."/>
                <person name="Kohn A."/>
                <person name="Palkovits M."/>
                <person name="Hook V.Y.H."/>
            </authorList>
            <dbReference type="PubMed" id="9880565"/>
            <dbReference type="DOI" id="10.1074/jbc.274.3.1821"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 17-423 (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="submission" date="1989-10" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Rubin H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 22-86 AND 130-423 (ISOFORM 1)</scope>
    </reference>
    <reference key="10">
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        <scope>PROTEIN SEQUENCE OF 24-34</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 36-45</scope>
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        <scope>PROTEIN SEQUENCE OF 41-60</scope>
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        <scope>PROTEIN SEQUENCE OF 48-68 (ISOFORMS 1/2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 87-129 (ISOFORMS 1/2)</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Liver</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 205-423</scope>
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            <dbReference type="PubMed" id="6556193"/>
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        <scope>REACTIVE SITE</scope>
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        </citation>
        <scope>GLYCOSYLATION AT ASN-93 AND ASN-106</scope>
    </reference>
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            <dbReference type="PubMed" id="14668352"/>
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        <scope>INTERACTION WITH DNAJC1</scope>
    </reference>
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            <dbReference type="PubMed" id="15638460"/>
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        <scope>REGION RCL</scope>
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            <dbReference type="PubMed" id="14760718"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93</scope>
        <source>
            <tissue>Plasma</tissue>
        </source>
    </reference>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-33; ASN-93; ASN-106; ASN-127; ASN-186 AND ASN-271</scope>
        <source>
            <tissue>Plasma</tissue>
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            <dbReference type="PubMed" id="19159218"/>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-93; ASN-106; ASN-127 AND ASN-271</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="23">
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            <dbReference type="PubMed" id="23234360"/>
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        <scope>GLYCOSYLATION</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 24-423</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 43-423 OF MUTANTS ARG-370 AND ARG-372</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 43-423 OF MUTANTS ARG-370; ARG-372 AND ARG-374</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 26-423</scope>
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        <scope>VARIANT VAL-401</scope>
    </reference>
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            <dbReference type="PubMed" id="1351206"/>
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        <scope>VARIANT ALA-252</scope>
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                <person name="Tachikawa H."/>
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        <scope>VARIANT VAL-401</scope>
    </reference>
    <comment type="function">
        <text evidence="12">Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts with DNAJC1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-718729">
            <id>P55212</id>
            <label>CASP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-296550">
            <id>Q96KC8</id>
            <label>DNAJC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-21591415">
            <id>P13473-2</id>
            <label>LAMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-357085">
            <id>Q9UNE7</id>
            <label>STUB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-11141397">
            <id>Q9UBQ0-2</id>
            <label>VPS29</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-2527283">
            <id>Q96AX1</id>
            <label>VPS33A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-296557">
            <id>P01011</id>
        </interactant>
        <interactant intactId="EBI-11946">
            <id>Q06389</id>
            <label>FRQ1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P01011-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P01011-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_014227 VSP_014228"/>
        </isoform>
        <isoform>
            <id>P01011-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_014225 VSP_014226"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14 16">Plasma. Synthesized in the liver. Like the related alpha-1-antitrypsin, its concentration increases in the acute phase of inflammation or infection. Found in the amyloid plaques from the hippocampus of Alzheimer disease brains.</text>
    </comment>
    <comment type="domain">
        <text>The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2 6 9 10 11">N- and O-glycosylated.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Alpha-1-antichymotrypsin can bind DNA.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the serpin family.</text>
    </comment>
    <comment type="caution">
        <text evidence="21">It is uncertain whether Met-1 or Met-4 is the initiator.</text>
    </comment>
    <comment type="sequence caution" evidence="21">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA51543" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="21">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAT08029" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="21">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAT08029" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="21">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD92297" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="21">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA48671" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Alpha_1-antichymotrypsin"/>
        <text>Alpha-1 antichymotrypsin entry</text>
    </comment>
    <dbReference type="EMBL" id="K01500">
        <property type="protein sequence ID" value="AAA51543.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="X68733">
        <property type="protein sequence ID" value="CAA48671.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X68734">
        <property type="protein sequence ID" value="CAA48671.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X68735">
        <property type="protein sequence ID" value="CAA48671.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X68736">
        <property type="protein sequence ID" value="CAA48671.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X68737">
        <property type="protein sequence ID" value="CAA48671.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY513275">
        <property type="protein sequence ID" value="AAT08028.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AY513276">
        <property type="protein sequence ID" value="AAT08029.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK123091">
        <property type="protein sequence ID" value="BAG53869.1"/>
        <property type="molecule type" value="mRNA"/>
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</entry>
<entry dataset="Swiss-Prot" created="2005-03-29" modified="2026-01-28" version="157" xmlns="https://uniprot.org/uniprot">
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    <reference key="1">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
                <person name="Wellenreuther R."/>
                <person name="Gassenhuber J."/>
                <person name="Glassl S."/>
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                <person name="Ottenwaelder B."/>
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                <person name="Poustka A."/>
            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT LEU-132</scope>
        <source>
            <tissue>Fetal kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT LEU-132</scope>
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            <tissue>Amygdala</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
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            <title>Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer.</title>
            <authorList>
                <person name="Giehl K.A."/>
                <person name="Eckstein G.N."/>
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            </authorList>
            <dbReference type="PubMed" id="23000146"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2012.08.024"/>
        </citation>
        <scope>INVOLVEMENT IN PPKP1A</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="12">
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            <title>Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma.</title>
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                <person name="Pohler E."/>
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                <person name="Saad A."/>
                <person name="Gribaa M."/>
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                <person name="Reversade B."/>
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                <person name="McLean W.H."/>
            </authorList>
            <dbReference type="PubMed" id="23064416"/>
            <dbReference type="DOI" id="10.1038/ng.2444"/>
        </citation>
        <scope>INVOLVEMENT IN PPKP1A</scope>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN AP-1 AND AP-2 COMPLEXES</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="5">May be involved in endocytic recycling of growth factor receptors such as EGFR.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5">Associated with AP-1 and AP-2 complexes.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-10185819">
            <id>O43747-2</id>
            <label>AP1G1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-3923129">
            <id>Q96PC3</id>
            <label>AP1S3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-12780485">
            <id>Q96PC3-2</id>
            <label>AP1S3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-1642835">
            <id>O94973</id>
            <label>AP2A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-297662">
            <id>P53680</id>
            <label>AP2S1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-719906">
            <id>Q6PD74</id>
        </interactant>
        <interactant intactId="EBI-10285245">
            <id>Q96ES5</id>
            <label>HEATR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 5">Cytoplasm</location>
            <location evidence="4 5">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6PD74-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6PD74-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054597"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5">Widely expressed, including in skin and keratinocytes, with highest levels in adrenal gland, rectum and thymus.</text>
    </comment>
    <comment type="disease" evidence="4 5">
        <disease id="DI-03540">
            <name>Keratoderma, palmoplantar, punctate 1A</name>
            <acronym>PPKP1A</acronym>
            <description>An autosomal dominant dermatological disorder characterized by multiple hyperkeratotic, centrally indented, papules that develop in early adolescence, or later, and are irregularly distributed on the palms and soles (other palmoplantar keratoses have mostly diffuse hyperkeratinization). In mechanically irritated areas, confluent plaques can be found. Interfamilial and intrafamilial severity shows broad variation. In some cases, PPKP1 is associated with the development of early- and late-onset malignancies, including squamous cell carcinoma.</description>
            <dbReference type="MIM" id="148600"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <dbReference type="EMBL" id="AL136715">
        <property type="protein sequence ID" value="CAB66649.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK021568">
        <property type="protein sequence ID" value="BAB13845.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK294402">
        <property type="protein sequence ID" value="BAG57655.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR533540">
        <property type="protein sequence ID" value="CAG38571.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012568">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC110292">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001975">
        <property type="protein sequence ID" value="AAH01975.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047026">
        <property type="protein sequence ID" value="AAH47026.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC058886">
        <property type="protein sequence ID" value="AAH58886.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42050.1">
        <molecule id="Q6PD74-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS61679.1">
        <molecule id="Q6PD74-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258814.1">
        <molecule id="Q6PD74-2"/>
        <property type="nucleotide sequence ID" value="NM_001271885.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258815.1">
        <molecule id="Q6PD74-2"/>
        <property type="nucleotide sequence ID" value="NM_001271886.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_078942.3">
        <molecule id="Q6PD74-1"/>
        <property type="nucleotide sequence ID" value="NM_024666.4"/>
    </dbReference>
    <dbReference type="PDB" id="7TWD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.11 A"/>
        <property type="chains" value="A/B=258-301"/>
    </dbReference>
    <dbReference type="PDB" id="9DDS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.78 A"/>
        <property type="chains" value="A/B=1-177"/>
    </dbReference>
    <dbReference type="PDB" id="9DDT">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.68 A"/>
        <property type="chains" value="A=1-177"/>
    </dbReference>
    <dbReference type="PDBsum" id="7TWD"/>
    <dbReference type="PDBsum" id="9DDS"/>
    <dbReference type="PDBsum" id="9DDT"/>
    <dbReference type="AlphaFoldDB" id="Q6PD74"/>
    <dbReference type="SMR" id="Q6PD74"/>
    <dbReference type="BioGRID" id="122835">
        <property type="interactions" value="35"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6PD74">
        <property type="interactions" value="2347"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6PD74">
        <property type="interactions" value="27"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000261880"/>
    <dbReference type="TCDB" id="8.A.203.1.1">
        <property type="family name" value="the adaptor protein 4 chaparone (aagab) family"/>
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    <dbReference type="GlyGen" id="Q6PD74">
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    <sequence length="315" mass="34594" checksum="C1C765B4F9717E0B" modified="2004-07-05" version="1">MAAGVPCALVTSCSSVFSGDQLVQHILGTEDLIVEVTSNDAVRFYPWTIDNKYYSADINLCVVPNKFLVTAEIAESVQAFVVYFDSTQKSGLDSVSSWLPLAKAWLPEVMILVCDRVSEDGINRQKAQEWCIKHGFELVELSPEELPEEDDDFPESTGVKRIVQALNANVWSNVVMKNDRNQGFSLLNSLTGTNHSIGSADPCHPEQPHLPAADSTESLSDHRGGASNTTDAQVDSIVDPMLDLDIQELASLTTGGGDVENFERLFSKLKEMKDKAATLPHEQRKVHAEKVAKAFWMAIGGDRDEIEGLSSDEEH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UGJ0</accession>
    <accession>Q53Y07</accession>
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    <accession>Q75MP4</accession>
    <accession>Q9NUZ9</accession>
    <accession>Q9UDN8</accession>
    <accession>Q9ULX8</accession>
    <name>AAKG2_HUMAN</name>
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        <recommendedName>
            <fullName>5'-AMP-activated protein kinase subunit gamma-2</fullName>
            <shortName>AMPK gamma2</shortName>
            <shortName>AMPK subunit gamma-2</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>H91620p</fullName>
        </alternativeName>
    </protein>
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        <name type="primary">PRKAG2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1999-03" db="EMBL/GenBank/DDBJ databases">
            <title>Human homolog of AMPK gamma-1 chain.</title>
            <authorList>
                <person name="Hattori A."/>
                <person name="Seki N."/>
                <person name="Hayashi A."/>
                <person name="Kozuma S."/>
                <person name="Muramatsu M."/>
                <person name="Saito T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Biochem. J." volume="346" first="659" last="669">
            <title>Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding.</title>
            <authorList>
                <person name="Cheung P.C.F."/>
                <person name="Salt I.P."/>
                <person name="Davies S.P."/>
                <person name="Hardie D.G."/>
                <person name="Carling D."/>
            </authorList>
            <dbReference type="PubMed" id="10698692"/>
            <dbReference type="DOI" id="10.1042/bj3460659"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2000" name="Genomics" volume="70" first="258" last="263">
            <title>Molecular cloning, genomic organization, and mapping of PRKAG2, a heart abundant gamma-2 subunit of 5'-AMP-activated protein kinase, to human chromosome 7q36.</title>
            <authorList>
                <person name="Lang T.M."/>
                <person name="Yu L."/>
                <person name="Qiang T."/>
                <person name="Jiang J.M."/>
                <person name="Chen Z."/>
                <person name="Xin Y.R."/>
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                <person name="Zhao S."/>
            </authorList>
            <dbReference type="PubMed" id="11112354"/>
            <dbReference type="DOI" id="10.1006/geno.2000.6376"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Takahashi M."/>
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                <person name="Yamazaki M."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
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                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
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                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
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    <comment type="function">
        <text evidence="9 13">AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:14722619, PubMed:24563466). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:14722619, PubMed:24563466). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:14722619, PubMed:24563466). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:14722619, PubMed:24563466). Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits (PubMed:14722619, PubMed:24563466). ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit (PubMed:14722619, PubMed:24563466). ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive (PubMed:14722619, PubMed:24563466).</text>
    </comment>
    <comment type="subunit">
        <text>AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2959705">
            <id>Q9UGJ0</id>
        </interactant>
        <interactant intactId="EBI-25836642">
            <id>Q8NE08</id>
            <label>COL25A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2959705">
            <id>Q9UGJ0</id>
        </interactant>
        <interactant intactId="EBI-10178578">
            <id>I6L9F6</id>
            <label>NEFL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2959705">
            <id>Q9UGJ0</id>
        </interactant>
        <interactant intactId="EBI-307104">
            <id>Q13501</id>
            <label>SQSTM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25939641">
            <id>Q9UGJ0-3</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UGJ0-1</id>
            <name>A</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UGJ0-2</id>
            <name>B</name>
            <sequence type="described" ref="VSP_000261"/>
        </isoform>
        <isoform>
            <id>Q9UGJ0-3</id>
            <name>C</name>
            <sequence type="described" ref="VSP_015589"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Isoform B is ubiquitously expressed except in liver and thymus. The highest level is detected in heart with abundant expression in placenta and testis.</text>
    </comment>
    <comment type="domain">
        <text>The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13">Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.</text>
    </comment>
    <comment type="disease" evidence="6 7 9">
        <disease id="DI-01150">
            <name>Wolff-Parkinson-White syndrome</name>
            <acronym>WPW</acronym>
            <description>A supernormal conduction disorder characterized by the presence of one or several accessory atrioventricular connections, which can lead to episodes of sporadic tachycardia.</description>
            <dbReference type="MIM" id="194200"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5 8">
        <disease id="DI-00245">
            <name>Cardiomyopathy, familial hypertrophic, 6</name>
            <acronym>CMH6</acronym>
            <description>A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen-containing cytosolic vacuoles within cardiomyocytes.</description>
            <dbReference type="MIM" id="600858"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-01676">
            <name>Glycogen storage disease of heart lethal congenital</name>
            <acronym>GSDH</acronym>
            <description>Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise.</description>
            <dbReference type="MIM" id="261740"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the 5'-AMP-activated protein kinase gamma subunit family.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH20540" version="2"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAS02032" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAA84695" version="1"/>
        </conflict>
        <text>Frameshifts are upstream of the initiating Met of isoform B.</text>
    </comment>
    <dbReference type="EMBL" id="AB025580">
        <property type="protein sequence ID" value="BAA84695.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249976">
        <property type="protein sequence ID" value="CAB65116.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF087875">
        <property type="protein sequence ID" value="AAK00413.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001887">
        <property type="protein sequence ID" value="BAA91962.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007127">
        <property type="protein sequence ID" value="AAP35791.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006358">
        <property type="protein sequence ID" value="AAS02032.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006966">
        <property type="protein sequence ID" value="AAF03528.2"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093583">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020540">
        <property type="protein sequence ID" value="AAH20540.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC068598">
        <property type="protein sequence ID" value="AAH68598.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43683.1">
        <molecule id="Q9UGJ0-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47752.1">
        <molecule id="Q9UGJ0-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5928.1">
        <molecule id="Q9UGJ0-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035723.1">
        <molecule id="Q9UGJ0-3"/>
        <property type="nucleotide sequence ID" value="NM_001040633.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001291456.1">
        <property type="nucleotide sequence ID" value="NM_001304527.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001291460.1">
        <molecule id="Q9UGJ0-2"/>
        <property type="nucleotide sequence ID" value="NM_001304531.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393953.1">
        <molecule id="Q9UGJ0-3"/>
        <property type="nucleotide sequence ID" value="NM_001407024.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057287.2">
        <molecule id="Q9UGJ0-1"/>
        <property type="nucleotide sequence ID" value="NM_016203.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_077747.1">
        <molecule id="Q9UGJ0-2"/>
        <property type="nucleotide sequence ID" value="NM_024429.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9UGJ0"/>
    <dbReference type="SMR" id="Q9UGJ0"/>
    <dbReference type="BioGRID" id="119531">
        <property type="interactions" value="69"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-5786">
        <property type="entry name" value="AMPK complex, alpha1-beta1-gamma2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-5844">
        <property type="entry name" value="AMPK complex, alpha2-beta1-gamma2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-5845">
        <property type="entry name" value="AMPK complex, alpha2-beta2-gamma2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-5846">
        <property type="entry name" value="AMPK complex, alpha1-beta2-gamma2 variant"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9UGJ0">
        <property type="interactions" value="1560"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UGJ0">
        <property type="interactions" value="52"/>
    </dbReference>
    <dbReference type="MINT" id="Q9UGJ0"/>
    <dbReference type="STRING" id="9606.ENSP00000287878"/>
    <dbReference type="BindingDB" id="Q9UGJ0"/>
    <dbReference type="ChEMBL" id="CHEMBL2453"/>
    <dbReference type="DrugBank" id="DB00945">
        <property type="generic name" value="Acetylsalicylic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00131">
        <property type="generic name" value="Adenosine phosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12010">
        <property type="generic name" value="Fostamatinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00273">
        <property type="generic name" value="Topiramate"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q9UGJ0"/>
    <dbReference type="GlyGen" id="Q9UGJ0">
        <property type="glycosylation" value="5 sites, 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UGJ0"/>
    <dbReference type="PhosphoSitePlus" id="Q9UGJ0"/>
    <dbReference type="BioMuta" id="PRKAG2"/>
    <dbReference type="DMDM" id="14285344"/>
    <dbReference type="jPOST" id="Q9UGJ0"/>
    <dbReference type="MassIVE" id="Q9UGJ0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000287878"/>
    <dbReference type="PeptideAtlas" id="Q9UGJ0"/>
    <dbReference type="ProteomicsDB" id="84222">
        <molecule id="Q9UGJ0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84223">
        <molecule id="Q9UGJ0-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84224">
        <molecule id="Q9UGJ0-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9UGJ0"/>
    <dbReference type="Antibodypedia" id="1327">
        <property type="antibodies" value="156 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51422"/>
    <dbReference type="Ensembl" id="ENST00000287878.9">
        <molecule id="Q9UGJ0-1"/>
        <property type="protein sequence ID" value="ENSP00000287878.3"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000392801.6">
        <molecule id="Q9UGJ0-3"/>
        <property type="protein sequence ID" value="ENSP00000376549.2"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000418337.6">
        <molecule id="Q9UGJ0-2"/>
        <property type="protein sequence ID" value="ENSP00000387386.2"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000476632.2">
        <molecule id="Q9UGJ0-2"/>
        <property type="protein sequence ID" value="ENSP00000419493.2"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000651378.1">
        <molecule id="Q9UGJ0-2"/>
        <property type="protein sequence ID" value="ENSP00000499103.1"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000651764.1">
        <molecule id="Q9UGJ0-3"/>
        <property type="protein sequence ID" value="ENSP00000498796.1"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000652159.1">
        <molecule id="Q9UGJ0-3"/>
        <property type="protein sequence ID" value="ENSP00000499025.1"/>
        <property type="gene ID" value="ENSG00000106617.17"/>
    </dbReference>
    <dbReference type="GeneID" id="51422"/>
    <dbReference type="KEGG" id="hsa:51422"/>
    <dbReference type="MANE-Select" id="ENST00000287878.9">
        <property type="protein sequence ID" value="ENSP00000287878.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016203.4"/>
        <property type="RefSeq protein sequence ID" value="NP_057287.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003wki.4">
        <molecule id="Q9UGJ0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:9386"/>
    <dbReference type="ClinPGx" id="PA33752"/>
    <dbReference type="CTD" id="51422"/>
    <dbReference type="DisGeNET" id="51422"/>
    <dbReference type="GeneCards" id="PRKAG2"/>
    <dbReference type="GeneReviews" id="PRKAG2"/>
    <dbReference type="HGNC" id="HGNC:9386">
        <property type="gene designation" value="PRKAG2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000106617">
        <property type="expression patterns" value="Tissue enhanced (heart)"/>
    </dbReference>
    <dbReference type="MalaCards" id="PRKAG2"/>
    <dbReference type="MIM" id="194200">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="261740">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="600858">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="602743">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000106617"/>
    <dbReference type="Orphanet" id="439854">
        <property type="disease" value="Fatal congenital hypertrophic cardiomyopathy due to glycogen storage disease"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000106617"/>
    <dbReference type="eggNOG" id="KOG1764">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183019"/>
    <dbReference type="HOGENOM" id="CLU_021740_3_0_1"/>
    <dbReference type="InParanoid" id="Q9UGJ0"/>
    <dbReference type="OMA" id="XVQIYEL"/>
    <dbReference type="OrthoDB" id="449052at2759"/>
    <dbReference type="PAN-GO" id="Q9UGJ0">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UGJ0"/>
    <dbReference type="PathwayCommons" id="Q9UGJ0"/>
    <dbReference type="Reactome" id="R-HSA-1445148">
        <property type="pathway name" value="Translocation of SLC2A4 (GLUT4) to the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-1632852">
        <property type="pathway name" value="Macroautophagy"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163680">
        <property type="pathway name" value="AMPK inhibits chREBP transcriptional activation activity"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-200425">
        <property type="pathway name" value="Carnitine shuttle"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2151209">
        <property type="pathway name" value="Activation of PPARGC1A (PGC-1alpha) by phosphorylation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-380972">
        <property type="pathway name" value="Energy dependent regulation of mTOR by LKB1-AMPK"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5628897">
        <property type="pathway name" value="TP53 Regulates Metabolic Genes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6804756">
        <property type="pathway name" value="Regulation of TP53 Activity through Phosphorylation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9613354">
        <property type="pathway name" value="Lipophagy"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9619483">
        <property type="pathway name" value="Activation of AMPK downstream of NMDARs"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UGJ0"/>
    <dbReference type="SIGNOR" id="Q9UGJ0"/>
    <dbReference type="Agora" id="ENSG00000106617"/>
    <dbReference type="BioGRID-ORCS" id="51422">
        <property type="hits" value="20 hits in 1164 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="PRKAG2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="PRKAG2"/>
    <dbReference type="GenomeRNAi" id="51422"/>
    <dbReference type="Pharos" id="Q9UGJ0">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UGJ0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
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    <dbReference type="RNAct" id="Q9UGJ0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000106617">
        <property type="expression patterns" value="Expressed in right atrium auricular region and 174 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9UGJ0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031588">
        <property type="term" value="C:nucleotide-activated protein kinase complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043531">
        <property type="term" value="F:ADP binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016208">
        <property type="term" value="F:AMP binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004679">
        <property type="term" value="F:AMP-activated protein kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004862">
        <property type="term" value="F:cAMP-dependent protein kinase inhibitor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008603">
        <property type="term" value="F:cAMP-dependent protein kinase regulator activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008607">
        <property type="term" value="F:phosphorylase kinase regulator activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030295">
        <property type="term" value="F:protein kinase activator activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019901">
        <property type="term" value="F:protein kinase binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019887">
        <property type="term" value="F:protein kinase regulator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006754">
        <property type="term" value="P:ATP biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042149">
        <property type="term" value="P:cellular response to glucose starvation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031669">
        <property type="term" value="P:cellular response to nutrient levels"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005977">
        <property type="term" value="P:glycogen metabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035556">
        <property type="term" value="P:intracellular signal transduction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045722">
        <property type="term" value="P:positive regulation of gluconeogenesis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043609">
        <property type="term" value="P:regulation of carbon utilization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051726">
        <property type="term" value="P:regulation of cell cycle"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046324">
        <property type="term" value="P:regulation of D-glucose import"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019217">
        <property type="term" value="P:regulation of fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046320">
        <property type="term" value="P:regulation of fatty acid oxidation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006110">
        <property type="term" value="P:regulation of glycolytic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0016126">
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<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="170" xmlns="https://uniprot.org/uniprot">
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            <fullName>AP2-associated protein kinase 1</fullName>
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        <name type="synonym">KIAA1048</name>
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        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>VARIANT GLN-509</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389 AND THR-606</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-637</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389; THR-441; SER-637 AND SER-731</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-234; SER-235; THR-389; THR-606; THR-620; SER-623; SER-624 AND SER-637</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; THR-354; THR-389; SER-637; SER-650; TYR-687 AND SER-731</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389; THR-606; SER-637 AND THR-653</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620; SER-623; SER-624 AND SER-637</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-606; THR-620; SER-624 AND SER-637</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] VAL-59; HIS-533; ALA-603; MET-694; THR-725; ARG-771 AND ASP-835</scope>
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    <comment type="function">
        <text evidence="8 9 10 11 14 15 16 17">Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:17494869, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124).</text>
    </comment>
    <comment type="function">
        <text evidence="17 25">(Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="23">
            <text>L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17989"/>
            <dbReference type="Rhea" id="RHEA-COMP:9863"/>
            <dbReference type="Rhea" id="RHEA-COMP:11604"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 9 10 11 14 15 18 19">
            <text>L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46608"/>
            <dbReference type="Rhea" id="RHEA-COMP:11060"/>
            <dbReference type="Rhea" id="RHEA-COMP:11605"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="11 14">Stimulated by clathrin.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 10 11 14 15 16">Interacts (via CBD domain) with clathrin (PubMed:14617351, PubMed:17494869). Interacts with AP-2 complex (PubMed:12952931, PubMed:14617351, PubMed:17494869). Interacts with NUMB (PubMed:18657069). Interacts with alpha-adaptin (By similarity). Interacts with EPS15 isoform 2 (PubMed:21464124). Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1 (PubMed:21464124). Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form (PubMed:21464124).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383433">
            <id>Q2M2I8</id>
        </interactant>
        <interactant intactId="EBI-6308763">
            <id>Q9NQ11</id>
            <label>ATP13A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="1">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Membrane</location>
            <location evidence="9">Clathrin-coated pit</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Presynapse</location>
        </subcellularLocation>
        <text evidence="2">Active when found in clathrin-coated pits at the plasma membrane. In neuronal cells, enriched at presynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q2M2I8-1</id>
            <name>1</name>
            <name evidence="22">AAK1L</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q2M2I8-2</id>
            <name>2</name>
            <name evidence="22">AAK1S</name>
            <sequence type="described" ref="VSP_039459"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14">Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14">Autophosphorylated.</text>
    </comment>
    <comment type="pharmaceutical">
        <text evidence="24 25">By regulating the entry of hepatitis C virus as well as the lifecycle of other viruses such as Ebola and Dengue, AAK1 is a potential drug target for developing antiviral therapies.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.</text>
    </comment>
    <comment type="sequence caution" evidence="23">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA83000" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
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        <property type="protein sequence ID" value="BAA83000.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC092431">
        <property type="protein sequence ID" value="AAX88861.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC079121">
        <property type="protein sequence ID" value="AAY14931.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC136007">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC104842">
        <property type="protein sequence ID" value="AAI04843.1"/>
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        <property type="resolution" value="1.95 A"/>
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        <property type="RefSeq protein sequence ID" value="NP_055726.4"/>
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    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
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    <keyword id="KW-0168">Coated pit</keyword>
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    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
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            <begin position="1"/>
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    <feature type="compositionally biased region" description="Gly residues" evidence="6">
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            <begin position="12"/>
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    <feature type="binding site" evidence="4">
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            <begin position="52"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="4">
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            <position position="74"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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            <position position="1"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="34 39">
        <location>
            <position position="14"/>
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    </feature>
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            <position position="234"/>
        </location>
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            <position position="235"/>
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            <position position="354"/>
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            <position position="653"/>
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            <position position="687"/>
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            <position position="731"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
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            <position position="938"/>
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            <position position="509"/>
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    <feature type="sequence variant" id="VAR_040350" description="In dbSNP:rs56038532." evidence="13">
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    </feature>
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            <position position="725"/>
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    </feature>
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            <begin position="777"/>
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            <begin position="70"/>
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            <begin position="106"/>
            <end position="113"/>
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            <begin position="120"/>
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            <begin position="339"/>
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    <sequence length="961" mass="103885" checksum="1FB44D0FDEF6CAD0" modified="2010-07-13" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-13" modified="2026-01-28" version="160" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H7C9</accession>
    <accession>Q96AQ4</accession>
    <accession>Q9Y6B1</accession>
    <name>AAMDC_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Mth938 domain-containing protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adipogenesis associated Mth938 domain-containing protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AAMDC</name>
        <name type="synonym">C11orf67</name>
        <name type="ORF">PTD015</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1998-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mao M."/>
                <person name="Peng Y."/>
                <person name="Dai M."/>
                <person name="Song H."/>
                <person name="Mao Y."/>
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                <person name="Huang Q."/>
                <person name="Fu G."/>
                <person name="Luo M."/>
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                <person name="Hu R."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Pituitary tumor</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
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                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
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                <person name="Nicol R."/>
                <person name="Park H.-S."/>
                <person name="Seaman C."/>
                <person name="Sougnez C."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Zody M.C."/>
                <person name="Birren B.W."/>
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                <person name="Hattori M."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Ovary</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-07" db="PDB data bank">
            <title>X-ray structure of gene product from Homo sapiens HS.95870.</title>
            <authorList>
                <consortium name="Center for eukaryotic structural genomics (CESG)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS)</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2007" name="Structure" volume="15" first="1040" last="1052">
            <title>Ensemble refinement of protein crystal structures: validation and application.</title>
            <authorList>
                <person name="Levin E.J."/>
                <person name="Kondrashov D.A."/>
                <person name="Wesenberg G.E."/>
                <person name="Phillips G.N. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="17850744"/>
            <dbReference type="DOI" id="10.1016/j.str.2007.06.019"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS)</scope>
    </reference>
    <comment type="function">
        <text evidence="1">May play a role in preadipocyte differentiation and adipogenesis.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
            <label>ACY3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-17264467">
            <id>P05067-2</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-946046">
            <id>P54252</id>
            <label>ATXN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-10968534">
            <id>P50570-2</id>
            <label>DNM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-11110431">
            <id>Q8TB36</id>
            <label>GDAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-739467">
            <id>Q9H8Y8</id>
            <label>GORASP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
        </interactant>
        <interactant intactId="EBI-9031083">
            <id>Q9Y2B5</id>
            <label>VPS9D1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">Diffuse distribution with some highly concentrated spots around the nucleus.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H7C9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H7C9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_019267 VSP_019269"/>
        </isoform>
        <isoform>
            <id>Q9H7C9-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_019266 VSP_019268"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the AAMDC family.</text>
    </comment>
    <dbReference type="EMBL" id="AF092136">
        <property type="protein sequence ID" value="AAD40378.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK024688">
        <property type="protein sequence ID" value="BAB14963.1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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            <begin position="1"/>
            <end position="122"/>
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            <begin position="6"/>
            <end position="122"/>
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    </feature>
    <feature type="splice variant" id="VSP_019267" description="In isoform 2." evidence="3">
        <original>VPSSTVEYLKKHGIDVRVLQTEQAVKEYNALVAQGVRVGGVF</original>
        <variation>APTQQLPSGVHVRAGVQFHLLQLHGTSFERCKTGAGLTSNML</variation>
        <location>
            <begin position="77"/>
            <end position="118"/>
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    </feature>
    <feature type="splice variant" id="VSP_019266" description="In isoform 3." evidence="2">
        <original>VPSSTVEYLKKH</original>
        <variation>DGIQGAQLDLNC</variation>
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            <begin position="77"/>
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        <variation>M</variation>
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            <begin position="6"/>
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    </feature>
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        <source ref="1"/>
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            <dbReference type="PDB" id="2AB1"/>
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    <sequence length="122" mass="13332" checksum="A0C88AD311E62C78" modified="2001-03-01" version="1">MTSPEIASLSWGQMKVKGSNTTYKDCKVWPGGSRTWDWRETGTEHSPGVQPADVKEVVEKGVQTLVIGRGMSEALKVPSSTVEYLKKHGIDVRVLQTEQAVKEYNALVAQGVRVGGVFHSTC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="183" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UGI9</accession>
    <accession>Q4QQG8</accession>
    <accession>Q4V779</accession>
    <accession>Q9NRL1</accession>
    <name>AAKG3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>5'-AMP-activated protein kinase subunit gamma-3</fullName>
            <shortName>AMPK gamma3</shortName>
            <shortName>AMPK subunit gamma-3</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PRKAG3</name>
        <name type="synonym">AMPKG3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Biochem. J." volume="346" first="659" last="669">
            <title>Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding.</title>
            <authorList>
                <person name="Cheung P.C.F."/>
                <person name="Salt I.P."/>
                <person name="Davies S.P."/>
                <person name="Hardie D.G."/>
                <person name="Carling D."/>
            </authorList>
            <dbReference type="PubMed" id="10698692"/>
            <dbReference type="DOI" id="10.1042/bj3460659"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Science" volume="288" first="1248" last="1251">
            <title>A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle.</title>
            <authorList>
                <person name="Milan D."/>
                <person name="Jeon J.-T."/>
                <person name="Looft C."/>
                <person name="Amarger V."/>
                <person name="Robic A."/>
                <person name="Thelander M."/>
                <person name="Rogel-Gaillard C."/>
                <person name="Paul S."/>
                <person name="Iannuccelli N."/>
                <person name="Rask L."/>
                <person name="Ronne H."/>
                <person name="Lundstroem K."/>
                <person name="Reinsch N."/>
                <person name="Gellin J."/>
                <person name="Kalm E."/>
                <person name="Le Roy P."/>
                <person name="Chardon P."/>
                <person name="Andersson L."/>
            </authorList>
            <dbReference type="PubMed" id="10818001"/>
            <dbReference type="DOI" id="10.1126/science.288.5469.1248"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-71</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="J. Clin. Invest." volume="113" first="274" last="284">
            <title>CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.</title>
            <authorList>
                <person name="Scott J.W."/>
                <person name="Hawley S.A."/>
                <person name="Green K.A."/>
                <person name="Anis M."/>
                <person name="Stewart G."/>
                <person name="Scullion G.A."/>
                <person name="Norman D.G."/>
                <person name="Hardie D.G."/>
            </authorList>
            <dbReference type="PubMed" id="14722619"/>
            <dbReference type="DOI" id="10.1172/jci19874"/>
        </citation>
        <scope>DOMAIN CBS</scope>
        <scope>AMP-BINDING</scope>
        <scope>ATP-BINDING</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2007" name="EMBO J." volume="26" first="806" last="815">
            <title>Regulation of AMP-activated protein kinase by a pseudosubstrate sequence on the gamma subunit.</title>
            <authorList>
                <person name="Scott J.W."/>
                <person name="Ross F.A."/>
                <person name="Liu J.K."/>
                <person name="Hardie D.G."/>
            </authorList>
            <dbReference type="PubMed" id="17255938"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7601542"/>
        </citation>
        <scope>DOMAIN AMPK PSEUDOSUBSTRATE</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="Circ. Res." volume="100" first="328" last="341">
            <title>AMP-activated protein kinase in metabolic control and insulin signaling.</title>
            <authorList>
                <person name="Towler M.C."/>
                <person name="Hardie D.G."/>
            </authorList>
            <dbReference type="PubMed" id="17307971"/>
            <dbReference type="DOI" id="10.1161/01.res.0000256090.42690.05"/>
        </citation>
        <scope>REVIEW ON FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2007" name="Nat. Rev. Mol. Cell Biol." volume="8" first="774" last="785">
            <title>AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.</title>
            <authorList>
                <person name="Hardie D.G."/>
            </authorList>
            <dbReference type="PubMed" id="17712357"/>
            <dbReference type="DOI" id="10.1038/nrm2249"/>
        </citation>
        <scope>REVIEW ON FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="Autophagy" volume="7" first="696" last="706">
            <title>Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop.</title>
            <authorList>
                <person name="Loffler A.S."/>
                <person name="Alers S."/>
                <person name="Dieterle A.M."/>
                <person name="Keppeler H."/>
                <person name="Franz-Wachtel M."/>
                <person name="Kundu M."/>
                <person name="Campbell D.G."/>
                <person name="Wesselborg S."/>
                <person name="Alessi D.R."/>
                <person name="Stork B."/>
            </authorList>
            <dbReference type="PubMed" id="21460634"/>
            <dbReference type="DOI" id="10.4161/auto.7.7.15451"/>
        </citation>
        <scope>PHOSPHORYLATION BY ULK1</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2014" name="J. Biol. Chem." volume="289" first="10592" last="10606">
            <title>Cross-talk between two essential nutrient-sensitive enzymes: O-GlcNAc transferase (OGT) and AMP-activated protein kinase (AMPK).</title>
            <authorList>
                <person name="Bullen J.W."/>
                <person name="Balsbaugh J.L."/>
                <person name="Chanda D."/>
                <person name="Shabanowitz J."/>
                <person name="Hunt D.F."/>
                <person name="Neumann D."/>
                <person name="Hart G.W."/>
            </authorList>
            <dbReference type="PubMed" id="24563466"/>
            <dbReference type="DOI" id="10.1074/jbc.m113.523068"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>GLYCOSYLATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2007" name="PLoS ONE" volume="2" first="E903" last="E903">
            <title>Gain-of-function R225W mutation in human AMPKgamma(3) causing increased glycogen and decreased triglyceride in skeletal muscle.</title>
            <authorList>
                <person name="Costford S.R."/>
                <person name="Kavaslar N."/>
                <person name="Ahituv N."/>
                <person name="Chaudhry S.N."/>
                <person name="Schackwitz W.S."/>
                <person name="Dent R."/>
                <person name="Pennacchio L.A."/>
                <person name="McPherson R."/>
                <person name="Harper M.E."/>
            </authorList>
            <dbReference type="PubMed" id="17878938"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0000903"/>
        </citation>
        <scope>VARIANTS ALA-71; GLN-76; GLY-103; VAL-113; VAL-153; PRO-161; SER-171; SER-180; THR-197; GLN-211; GLN-225; TRP-225; ARG-260; THR-269; CYS-307; GLN-340; TRP-340; MET-446; VAL-482 AND ASN-485</scope>
        <scope>INVOLVEMENT IN SMGMQTL</scope>
        <scope>FUNCTION</scope>
        <scope>CHARACTERIZATION OF VARIANT TRP-225</scope>
    </reference>
    <comment type="function">
        <text evidence="5 7 9">AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:14722619, PubMed:17878938, PubMed:24563466). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. AMPK also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. The AMPK gamma3 subunit is a non-catalytic subunit with a regulatory role in muscle energy metabolism (PubMed:17878938). It mediates binding to AMP, ADP and ATP, leading to AMPK activation or inhibition: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7428853">
            <id>Q9UGI9</id>
        </interactant>
        <interactant intactId="EBI-1048945">
            <id>Q3LI72</id>
            <label>KRTAP19-5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7428853">
            <id>Q9UGI9</id>
        </interactant>
        <interactant intactId="EBI-1053424">
            <id>O43741</id>
            <label>PRKAB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UGI9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UGI9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_015587"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Skeletal muscle, with weak expression in heart and pancreas.</text>
    </comment>
    <comment type="domain">
        <text>The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="8">Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9">Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="7">Genetic variation in PRKAG3 defines the skeletal muscle glycogen content and metabolism quantitative trait locus (SMGMQTL) [MIM:619030]. Muscle fibers from carriers of variant Trp-225 have approximately 90% more muscle glycogen content than controls and decreased levels of intramuscular triglyceride.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the 5'-AMP-activated protein kinase gamma subunit family.</text>
    </comment>
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        <property type="gene designation" value="PRKAG3"/>
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    <dbReference type="MalaCards" id="PRKAG3"/>
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    <proteinExistence type="evidence at protein level"/>
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            <position position="197"/>
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            <position position="485"/>
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            <position position="83"/>
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            <dbReference type="PROSITE-ProRule" id="PRU00703"/>
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            <dbReference type="SAM" id="MobiDB-lite"/>
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            <dbReference type="PubMed" id="14722619"/>
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            <dbReference type="PubMed" id="15489334"/>
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    <evidence type="ECO:0000305" key="11"/>
    <sequence length="489" mass="54258" checksum="0E93E2B5117B328D" modified="2005-09-13" version="3">MEPGLEHALRRTPSWSSLGGSEHQEMSFLEQENSSSWPSPAVTSSSERIRGKRRAKALRWTRQKSVEEGEPPGQGEGPRSRPAAESTGLEATFPKTTPLAQADPAGVGTPPTGWDCLPSDCTASAAGSSTDDVELATEFPATEAWECELEGLLEERPALCLSPQAPFPKLGWDDELRKPGAQIYMRFMQEHTCYDAMATSSKLVIFDTMLEIKKAFFALVANGVRAAPLWDSKKQSFVGMLTITDFILVLHRYYRSPLVQIYEIEQHKIETWREIYLQGCFKPLVSISPNDSLFEAVYTLIKNRIHRLPVLDPVSGNVLHILTHKRLLKFLHIFGSLLPRPSFLYRTIQDLGIGTFRDLAVVLETAPILTALDIFVDRRVSALPVVNECGQVVGLYSRFDVIHLAAQQTYNHLDMSVGEALRQRTLCLEGVLSCQPHESLGEVIDRIAREQVHRLVLVDETQHLLGVVSLSDILQALVLSPAGIDALGA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>Q13685</accession>
    <accession>Q8WUJ9</accession>
    <accession>Q96H92</accession>
    <name>AAMP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Angio-associated migratory cell protein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AAMP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="Cancer Res." volume="55" first="2140" last="2149">
            <title>Identification of a new immunoglobulin superfamily protein expressed in blood vessels with a heparin-binding consensus sequence.</title>
            <authorList>
                <person name="Beckner M.E."/>
                <person name="Krutzsch H.C."/>
                <person name="Stracke M.L."/>
                <person name="Williams S.T."/>
                <person name="Gallardo J.A."/>
                <person name="Liotta L.A."/>
            </authorList>
            <dbReference type="PubMed" id="7743515"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Ovary</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1999" name="Microvasc. Res." volume="57" first="347" last="352">
            <title>Angio-associated migratory cell protein is expressed as an extracellular protein by blood-vessel-associated mesenchymal cells.</title>
            <authorList>
                <person name="Beckner M.E."/>
                <person name="Peterson V.A."/>
                <person name="Moul D.E."/>
            </authorList>
            <dbReference type="PubMed" id="10329261"/>
            <dbReference type="DOI" id="10.1006/mvre.1999.2144"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2008" name="J. Am. Coll. Cardiol." volume="52" first="302" last="311">
            <title>Blockade of angio-associated migratory cell protein inhibits smooth muscle cell migration and neointima formation in accelerated atherosclerosis.</title>
            <authorList>
                <person name="Vogt F."/>
                <person name="Zernecke A."/>
                <person name="Beckner M."/>
                <person name="Krott N."/>
                <person name="Bosserhoff A.-K."/>
                <person name="Hoffmann R."/>
                <person name="Zandvoort M.A.M.J."/>
                <person name="Jahnke T."/>
                <person name="Kelm M."/>
                <person name="Weber C."/>
                <person name="Blindt R."/>
            </authorList>
            <dbReference type="PubMed" id="18634987"/>
            <dbReference type="DOI" id="10.1016/j.jacc.2008.03.055"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2 3">Plays a role in angiogenesis and cell migration. In smooth muscle cell migration, may act through the RhoA pathway.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727274">
            <id>Q13685</id>
        </interactant>
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
            <label>AEN</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-727274">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 4">Expressed in metastatic melanoma, liver, skin, kidney, heart, lung, lymph node, skeletal muscle and brain, and also in A2058 melanoma cells and activated T-cells (at protein level). Expressed in blood vessels. Strongly expressed in endothelial cells, cytotrophoblasts, and poorly differentiated. colon adenocarcinoma cells found in lymphatics.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA68889" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAG33036" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/533/AAMP"/>
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        <property type="protein sequence ID" value="AAH08809.2"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC020244">
        <property type="protein sequence ID" value="AAH20244.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH39866.2"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_001087.5"/>
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        <property type="interactions" value="1643"/>
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        <property type="interactions" value="35"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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    <dbReference type="Antibodypedia" id="34259">
        <property type="antibodies" value="171 antibodies from 30 providers"/>
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    <dbReference type="DNASU" id="14"/>
    <dbReference type="Ensembl" id="ENST00000248450.9">
        <property type="protein sequence ID" value="ENSP00000248450.4"/>
        <property type="gene ID" value="ENSG00000127837.11"/>
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    <dbReference type="GeneID" id="14"/>
    <dbReference type="KEGG" id="hsa:14"/>
    <dbReference type="MANE-Select" id="ENST00000248450.9">
        <property type="protein sequence ID" value="ENSP00000248450.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001087.5"/>
        <property type="RefSeq protein sequence ID" value="NP_001078.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002vhk.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18"/>
    <dbReference type="ClinPGx" id="PA24365"/>
    <dbReference type="CTD" id="14"/>
    <dbReference type="DisGeNET" id="14"/>
    <dbReference type="GeneCards" id="AAMP"/>
    <dbReference type="HGNC" id="HGNC:18">
        <property type="gene designation" value="AAMP"/>
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    <dbReference type="HPA" id="ENSG00000127837">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AAMP"/>
    <dbReference type="MIM" id="603488">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000127837"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000127837"/>
    <dbReference type="eggNOG" id="KOG0296">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00940000153648"/>
    <dbReference type="HOGENOM" id="CLU_000288_57_9_1"/>
    <dbReference type="InParanoid" id="Q13685"/>
    <dbReference type="OMA" id="GPDEVMW"/>
    <dbReference type="OrthoDB" id="10261640at2759"/>
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        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q13685"/>
    <dbReference type="PathwayCommons" id="Q13685"/>
    <dbReference type="Reactome" id="R-HSA-168638">
        <property type="pathway name" value="NOD1/2 Signaling Pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-177929">
        <property type="pathway name" value="Signaling by EGFR"/>
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    <dbReference type="Reactome" id="R-HSA-194138">
        <property type="pathway name" value="Signaling by VEGF"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-428930">
        <property type="pathway name" value="Thromboxane signalling through TP receptor"/>
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    <dbReference type="SignaLink" id="Q13685"/>
    <dbReference type="Agora" id="ENSG00000127837"/>
    <dbReference type="BioGRID-ORCS" id="14">
        <property type="hits" value="753 hits in 1174 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AAMP">
        <property type="organism name" value="human"/>
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    <dbReference type="GeneWiki" id="AAMP_(gene)"/>
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        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:Q13685"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
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    <dbReference type="RNAct" id="Q13685">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000127837">
        <property type="expression patterns" value="Expressed in body of stomach and 200 other cell types or tissues"/>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="C:cell surface"/>
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        <property type="term" value="C:microtubule cytoskeleton"/>
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        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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        <property type="term" value="F:heparin binding"/>
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        <property type="term" value="P:angiogenesis"/>
        <property type="evidence" value="ECO:0000303"/>
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        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0010595">
        <property type="term" value="P:positive regulation of endothelial cell migration"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:smooth muscle cell migration"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="CDD" id="cd00200">
        <property type="entry name" value="WD40"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.130.10.10:FF:000074">
        <property type="entry name" value="Angio-associated migratory cell protein-like protein"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.130.10.10">
        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
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    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
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        <property type="entry name" value="WD40_repeat_CS"/>
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    <dbReference type="InterPro" id="IPR036322">
        <property type="entry name" value="WD40_repeat_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001680">
        <property type="entry name" value="WD40_rpt"/>
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    <dbReference type="InterPro" id="IPR051179">
        <property type="entry name" value="WD_repeat_multifunction"/>
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    <dbReference type="PANTHER" id="PTHR19857:SF8">
        <property type="entry name" value="ANGIO-ASSOCIATED MIGRATORY CELL PROTEIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR19857">
        <property type="entry name" value="MITOCHONDRIAL DIVISION PROTEIN 1-RELATED"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00400">
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        <property type="match status" value="6"/>
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        <property type="match status" value="8"/>
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    <dbReference type="SUPFAM" id="SSF50978">
        <property type="entry name" value="WD40 repeat-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="WD_REPEATS_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50082">
        <property type="entry name" value="WD_REPEATS_2"/>
        <property type="match status" value="6"/>
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    <dbReference type="PROSITE" id="PS50294">
        <property type="entry name" value="WD_REPEATS_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0037">Angiogenesis</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0853">WD repeat</keyword>
    <feature type="chain" id="PRO_0000050832" description="Angio-associated migratory cell protein">
        <location>
            <begin position="1"/>
            <end position="434"/>
        </location>
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    <feature type="repeat" description="WD 1">
        <location>
            <begin position="89"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 2">
        <location>
            <begin position="132"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 3">
        <location>
            <begin position="173"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 4">
        <location>
            <begin position="214"/>
            <end position="254"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 5">
        <location>
            <begin position="258"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 6">
        <location>
            <begin position="315"/>
            <end position="354"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 7">
        <location>
            <begin position="356"/>
            <end position="395"/>
        </location>
    </feature>
    <feature type="repeat" description="WD 8">
        <location>
            <begin position="398"/>
            <end position="433"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="1">
        <location>
            <begin position="39"/>
            <end position="62"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="6">
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037061" description="In dbSNP:rs2305835.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="250"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="10329261"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="18634987"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="7743515"/>
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    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="434" mass="46751" checksum="A7B8314442EBAF15" modified="2005-04-26" version="2">MESESESGAAADTPPLETLSFHGDEEIIEVVELDPGPPDPDDLAQEMEDVDFEEEEEEEGNEEGWVLEPQEGVVGSMEGPDDSEVTFALHSASVFCVSLDPKTNTLAVTGGEDDKAFVWRLSDGELLFECAGHKDSVTCAGFSHDSTLVATGDMSGLLKVWQVDTKEEVWSFEAGDLEWMEWHPRAPVLLAGTADGNTWMWKVPNGDCKTFQGPNCPATCGRVLPDGKRAVVGYEDGTIRIWDLKQGSPIHVLKGTEGHQGPLTCVAANQDGSLILTGSVDCQAKLVSATTGKVVGVFRPETVASQPSLGEGEESESNSVESLGFCSVMPLAAVGYLDGTLAIYDLATQTLRHQCQHQSGIVQLLWEAGTAVVYTCSLDGIVRLWDARTGRLLTDYRGHTAEILDFALSKDASLVVTTSGDHKAKVFCVQRPDR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="222" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y478</accession>
    <accession>Q9UBV0</accession>
    <accession>Q9UE20</accession>
    <accession>Q9UEX2</accession>
    <accession>Q9Y6V8</accession>
    <name>AAKB1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>5'-AMP-activated protein kinase subunit beta-1</fullName>
            <shortName>AMPK subunit beta-1</shortName>
            <shortName>AMPKb</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PRKAB1</name>
        <name type="synonym">AMPK</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1998-02" db="EMBL/GenBank/DDBJ databases">
            <title>Non-catalytic beta and gamma subunits isoforms of the AMP-activated protein kinase.</title>
            <authorList>
                <person name="Carling D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="409" first="452" last="456">
            <title>AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location.</title>
            <authorList>
                <person name="Stapleton D."/>
                <person name="Woollatt E."/>
                <person name="Mitchelhill K."/>
                <person name="Nicholl J.K."/>
                <person name="Fernandez C.S."/>
                <person name="Michell B.J."/>
                <person name="Witters L.A."/>
                <person name="Power D.A."/>
                <person name="Sutherland G.R."/>
                <person name="Kemp B.E."/>
            </authorList>
            <dbReference type="PubMed" id="9224708"/>
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            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-96 AND SER-108</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96 AND SER-108</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6 8">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="7">Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the 5'-AMP-activated protein kinase beta subunit family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAB71326" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAC98897" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44100/PRKAB1"/>
    </comment>
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        <property type="entry name" value="5'-AMP-ACTIVATED PROTEIN KINASE , BETA SUBUNIT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10343:SF84">
        <property type="entry name" value="5'-AMP-ACTIVATED PROTEIN KINASE SUBUNIT BETA-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16561">
        <property type="entry name" value="AMPK1_CBM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04739">
        <property type="entry name" value="AMPKBI"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM01010">
        <property type="entry name" value="AMPKBI"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF160219">
        <property type="entry name" value="AMPKBI-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF81296">
        <property type="entry name" value="E set domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0275">Fatty acid biosynthesis</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0519">Myristate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000204363" description="5'-AMP-activated protein kinase subunit beta-1">
        <location>
            <begin position="2"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="region of interest" description="Glycogen-binding domain" evidence="1">
        <location>
            <begin position="68"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="21"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="10">
        <location>
            <position position="4"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="12 13">
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by autocatalysis" evidence="2">
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by autocatalysis" evidence="2">
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12 13 15 17">
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="14 17 18">
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 11 12 13 14 15 16 17 18">
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="13">
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="N-myristoyl glycine" evidence="8">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes myristoylation and AMP-enhanced phosphorylation of PRKAA1 or PRKAA2." evidence="8">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA73146 and 4; AAC98897." evidence="9" ref="2 4">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA12024." evidence="9" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA73146 and 4; AAC98897." evidence="9" ref="2 4">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAD09237/AAD00625." evidence="9" ref="3">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAD09237/AAD00625." evidence="9" ref="3">
        <original>E</original>
        <variation>Y</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="79"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="91"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="96"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="106"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="112"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="120"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="132"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="strand" evidence="20">
        <location>
            <begin position="137"/>
            <end position="139"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="141"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="145"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="149"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="157"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="162"/>
            <end position="179"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="208"/>
            <end position="211"/>
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    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="214"/>
            <end position="216"/>
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    <feature type="strand" evidence="21">
        <location>
            <begin position="221"/>
            <end position="223"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="233"/>
            <end position="235"/>
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    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="240"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="248"/>
            <end position="257"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="260"/>
            <end position="269"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P80386"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9R078"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17028174"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="18403135"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21460634"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="21680840"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="18088087"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19369195"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="4CFE"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="6C9G"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="7MYJ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="8BIK"/>
        </source>
    </evidence>
    <sequence length="270" mass="30382" checksum="F0BCAA94D5BC15FC" modified="2007-01-23" version="4">MGNTSSERAALERHGGHKTPRRDSSGGTKDGDRPKILMDSPEDADLFHSEEIKAPEKEEFLAWQHDLEVNDKAPAQARPTVFRWTGGGKEVYLSGSFNNWSKLPLTRSHNNFVAILDLPEGEHQYKFFVDGQWTHDPSEPIVTSQLGTVNNIIQVKKTDFEVFDALMVDSQKCSDVSELSSSPPGPYHQEPYVCKPEERFRAPPILPPHLLQVILNKDTGISCDPALLPEPNHVMLNHLYALSIKDGVMVLSATHRYKKKYVTTLLYKPI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="109" xmlns="https://uniprot.org/uniprot">
    <accession>Q4LEZ3</accession>
    <accession>A5PKU8</accession>
    <name>AARD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alanine- and arginine-rich domain-containing protein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AARD</name>
        <name type="synonym">C8orf85</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Novel gene containing alanine and arginine rich domain on human chromosome 8.</title>
            <authorList>
                <person name="Ishikawa S.K."/>
                <person name="Shimizu A."/>
                <person name="Yamazaki S."/>
                <person name="Asakawa S."/>
                <person name="Shimizu N."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ARG-96</scope>
    </reference>
    <comment type="interaction">
        <interactant intactId="EBI-5463075">
            <id>Q4LEZ3</id>
        </interactant>
        <interactant intactId="EBI-2350265">
            <id>Q7L2Z9</id>
            <label>CENPQ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5463075">
            <id>Q4LEZ3</id>
        </interactant>
        <interactant intactId="EBI-11752486">
            <id>Q86XR8-3</id>
            <label>CEP57</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q4LEZ3</id>
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        <interactant intactId="EBI-717919">
            <id>Q4V328</id>
            <label>GRIPAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5463075">
            <id>Q4LEZ3</id>
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        <interactant intactId="EBI-2805604">
            <id>Q2KHM9</id>
            <label>KIAA0753</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5463075">
            <id>Q4LEZ3</id>
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        <interactant intactId="EBI-2952736">
            <id>Q2M2I5</id>
            <label>KRT24</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5463075">
            <id>Q4LEZ3</id>
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        <interactant intactId="EBI-3044087">
            <id>Q7Z3Y8</id>
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    </comment>
    <comment type="interaction">
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            <id>Q4LEZ3</id>
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        <interactant intactId="EBI-2798728">
            <id>P61968</id>
            <label>LMO4</label>
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    <comment type="interaction">
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        <interactant intactId="EBI-751857">
            <id>O15481</id>
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2559305">
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            <label>VPS37C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <dbReference type="EMBL" id="AB181519">
        <property type="protein sequence ID" value="BAE03184.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC142621">
        <property type="protein sequence ID" value="AAI42622.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS34935.1"/>
    <dbReference type="RefSeq" id="NP_001020528.1">
        <property type="nucleotide sequence ID" value="NM_001025357.3"/>
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    <dbReference type="BioGRID" id="137412">
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    <dbReference type="FunCoup" id="Q4LEZ3">
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    <dbReference type="IntAct" id="Q4LEZ3">
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    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000367528"/>
    <dbReference type="GlyGen" id="Q4LEZ3">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="BioMuta" id="AARD"/>
    <dbReference type="DMDM" id="121944377"/>
    <dbReference type="jPOST" id="Q4LEZ3"/>
    <dbReference type="MassIVE" id="Q4LEZ3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000367528"/>
    <dbReference type="PeptideAtlas" id="Q4LEZ3"/>
    <dbReference type="ProteomicsDB" id="62246"/>
    <dbReference type="Antibodypedia" id="74104">
        <property type="antibodies" value="1 antibodies from 1 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="441376"/>
    <dbReference type="Ensembl" id="ENST00000378279.4">
        <property type="protein sequence ID" value="ENSP00000367528.3"/>
        <property type="gene ID" value="ENSG00000205002.4"/>
    </dbReference>
    <dbReference type="GeneID" id="441376"/>
    <dbReference type="KEGG" id="hsa:441376"/>
    <dbReference type="MANE-Select" id="ENST00000378279.4">
        <property type="protein sequence ID" value="ENSP00000367528.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001025357.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001020528.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003yof.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:33842"/>
    <dbReference type="ClinPGx" id="PA164717502"/>
    <dbReference type="CTD" id="441376"/>
    <dbReference type="DisGeNET" id="441376"/>
    <dbReference type="GeneCards" id="AARD"/>
    <dbReference type="HGNC" id="HGNC:33842">
        <property type="gene designation" value="AARD"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000205002">
        <property type="expression patterns" value="Tissue enhanced (testis, urinary bladder)"/>
    </dbReference>
    <dbReference type="MIM" id="621042">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000205002"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000205002"/>
    <dbReference type="eggNOG" id="ENOG502SG9F">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000007815"/>
    <dbReference type="HOGENOM" id="CLU_142929_0_0_1"/>
    <dbReference type="InParanoid" id="Q4LEZ3"/>
    <dbReference type="OMA" id="ELEMAWE"/>
    <dbReference type="OrthoDB" id="9948935at2759"/>
    <dbReference type="PAN-GO" id="Q4LEZ3">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q4LEZ3"/>
    <dbReference type="PathwayCommons" id="Q4LEZ3"/>
    <dbReference type="SignaLink" id="Q4LEZ3"/>
    <dbReference type="Agora" id="ENSG00000205002"/>
    <dbReference type="BioGRID-ORCS" id="441376">
        <property type="hits" value="14 hits in 1137 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="441376"/>
    <dbReference type="Pharos" id="Q4LEZ3">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q4LEZ3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q4LEZ3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000205002">
        <property type="expression patterns" value="Expressed in left testis and 90 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033574">
        <property type="term" value="P:response to testosterone"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051771">
        <property type="entry name" value="FAM167_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR32289:SF2">
        <property type="entry name" value="ALANINE AND ARGININE-RICH DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR32289">
        <property type="entry name" value="PROTEIN FAM167A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000337036" description="Alanine- and arginine-rich domain-containing protein">
        <location>
            <begin position="1"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043570" description="In dbSNP:rs16889283." evidence="1">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <sequence length="155" mass="17575" checksum="4D991ECA38D29531" modified="2005-08-02" version="1">MGPGDFRRCRERISQGLQGLPGRAELWFPPRPACDFFGDGRSTDIQEEALAASPLLEDLRRRLTRAFQWAVQRAISRRVQEAAAAAAAREEQSWTGVEATLARLRAELVEMHFQNHQLARTLLDLNMKVQQLKKEYELEITSDSQSPKDDAANPE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-04-13" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UDR5</accession>
    <accession>O95462</accession>
    <name>AASS_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10 11">Alpha-aminoadipic semialdehyde synthase, mitochondrial</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="10">LKR/SDH</fullName>
        </alternativeName>
        <domain>
            <recommendedName>
                <fullName evidence="10">Lysine ketoglutarate reductase</fullName>
                <shortName evidence="8">LKR</shortName>
                <shortName>LOR</shortName>
                <ecNumber evidence="4 6">1.5.1.8</ecNumber>
            </recommendedName>
        </domain>
        <domain>
            <recommendedName>
                <fullName evidence="10">Saccharopine dehydrogenase</fullName>
                <shortName evidence="8">SDH</shortName>
                <ecNumber evidence="4 6">1.5.1.9</ecNumber>
            </recommendedName>
        </domain>
    </protein>
    <gene>
        <name evidence="12" type="primary">AASS</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Am. J. Hum. Genet." volume="66" first="1736" last="1743">
            <title>Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia.</title>
            <authorList>
                <person name="Sacksteder K.A."/>
                <person name="Biery B.J."/>
                <person name="Morrell J.C."/>
                <person name="Goodman B.K."/>
                <person name="Geisbrecht B.V."/>
                <person name="Cox R.P."/>
                <person name="Gould S.J."/>
                <person name="Geraghty M.T."/>
            </authorList>
            <dbReference type="PubMed" id="10775527"/>
            <dbReference type="DOI" id="10.1086/302919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>INVOLVEMENT IN HYPLYS1</scope>
        <scope>DOMAIN</scope>
        <scope>REGION</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="1999-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and expression analysis of the LKR/SDH gene in human tissues.</title>
            <authorList>
                <person name="Papes F."/>
                <person name="Kemper E.L."/>
                <person name="Cord-Neto G."/>
                <person name="Langone F."/>
                <person name="Arruda P."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Graves T.A."/>
                <person name="Pepin K.H."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Maas J."/>
                <person name="Jaeger S."/>
                <person name="Walker R."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="O'Laughlin M.D."/>
                <person name="Schaller M.E."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Cordes M."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Edwards J."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Andrews S."/>
                <person name="Isak A."/>
                <person name="Vanbrunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Lamar B."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Bielicki L."/>
                <person name="Scott K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Harris A."/>
                <person name="Strong C.M."/>
                <person name="Hou S."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Leonard S."/>
                <person name="Rohlfing T."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Abbott A."/>
                <person name="Minx P."/>
                <person name="Maupin R."/>
                <person name="Strowmatt C."/>
                <person name="Latreille P."/>
                <person name="Miller N."/>
                <person name="Johnson D."/>
                <person name="Murray J."/>
                <person name="Woessner J.P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Schultz B.R."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Nelson J.O."/>
                <person name="Berkowicz N."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Bedell J.A."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Chissoe S.L."/>
                <person name="Marra M.A."/>
                <person name="Raymond C."/>
                <person name="Haugen E."/>
                <person name="Gillett W."/>
                <person name="Zhou Y."/>
                <person name="James R."/>
                <person name="Phelps K."/>
                <person name="Iadanoto S."/>
                <person name="Bubb K."/>
                <person name="Simms E."/>
                <person name="Levy R."/>
                <person name="Clendenning J."/>
                <person name="Kaul R."/>
                <person name="Kent W.J."/>
                <person name="Furey T.S."/>
                <person name="Baertsch R.A."/>
                <person name="Brent M.R."/>
                <person name="Keibler E."/>
                <person name="Flicek P."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Bailey J.A."/>
                <person name="Portnoy M.E."/>
                <person name="Torrents D."/>
                <person name="Chinwalla A.T."/>
                <person name="Gish W.R."/>
                <person name="Eddy S.R."/>
                <person name="McPherson J.D."/>
                <person name="Olson M.V."/>
                <person name="Eichler E.E."/>
                <person name="Green E.D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1979" name="Am. J. Hum. Genet." volume="31" first="290" last="299">
            <title>Familial hyperlysinemia: enzyme studies, diagnostic methods, comments on terminology.</title>
            <authorList>
                <person name="Dancis J."/>
                <person name="Hutzler J."/>
                <person name="Cox R.P."/>
            </authorList>
            <dbReference type="PubMed" id="463877"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INVOLVEMENT IN HYPLYS1</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="Hum. Mol. Genet." volume="23" first="5009" last="5016">
            <title>Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.</title>
            <authorList>
                <person name="Houten S.M."/>
                <person name="Denis S."/>
                <person name="Te Brinke H."/>
                <person name="Jongejan A."/>
                <person name="van Kampen A.H."/>
                <person name="Bradley E.J."/>
                <person name="Baas F."/>
                <person name="Hennekam R.C."/>
                <person name="Millington D.S."/>
                <person name="Young S.P."/>
                <person name="Frazier D.M."/>
                <person name="Gucsavas-Calikoglu M."/>
                <person name="Wanders R.J."/>
            </authorList>
            <dbReference type="PubMed" id="24847004"/>
            <dbReference type="DOI" id="10.1093/hmg/ddu218"/>
        </citation>
        <scope>INVOLVEMENT IN DECRD</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference evidence="13" key="8">
        <citation type="submission" date="2016-06" db="PDB data bank">
            <title>Crystal structure of human aminoadipate semialdehyde synthase, saccharopine dehydrogenase domain (in NAD+ bound form).</title>
            <authorList>
                <person name="Kopec J."/>
                <person name="Yue W.W."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 455-926 IN COMPLEX WITH NAD</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6">Bifunctional enzyme that catalyzes the first two steps in lysine degradation.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6">
            <text>L-saccharopine + NADP(+) + H2O = L-lysine + 2-oxoglutarate + NADPH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19373"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:32551"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:57951"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="EC" id="1.5.1.8"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="4">
            <dbReference type="Rhea" id="RHEA:19375"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6">
            <text>L-saccharopine + NAD(+) + H2O = (S)-2-amino-6-oxohexanoate + L-glutamate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:24520"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:57951"/>
            <dbReference type="ChEBI" id="CHEBI:58321"/>
            <dbReference type="EC" id="1.5.1.9"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:24521"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="4">Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 1/6.</text>
    </comment>
    <comment type="pathway">
        <text evidence="4">Amino-acid degradation; L-lysine degradation via saccharopine pathway; glutaryl-CoA from L-lysine: step 2/6.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Homotetramer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in all 16 tissues examined with highest expression in the liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="1">Induced by starvation.</text>
    </comment>
    <comment type="domain">
        <text evidence="8">The N-terminal and the C-terminal domains contain respectively the lysine ketoglutarate reductase and saccharopine dehydrogenase activity.</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-01773">
            <name>Hyperlysinemia, 1</name>
            <acronym>HYPLYS1</acronym>
            <description>An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.</description>
            <dbReference type="MIM" id="238700"/>
        </disease>
        <text evidence="11">The disease is caused by variants affecting the gene represented in this entry. In hyperlysinemia 1, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine. Some individuals, however, retain significant amounts of lysine-ketoglutarate reductase and present with saccharopinuria, a metabolic condition with few, if any, clinical manifestations.</text>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-04240">
            <name>2,4-dienoyl-CoA reductase deficiency</name>
            <acronym>DECRD</acronym>
            <description>A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia.</description>
            <dbReference type="MIM" id="616034"/>
        </disease>
        <text evidence="5">The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">In the N-terminal section; belongs to the AlaDH/PNT family.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">In the C-terminal section; belongs to the saccharopine dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.5.1.8" evidence="4 6"/>
    <dbReference type="EC" id="1.5.1.9" evidence="4 6"/>
    <dbReference type="EMBL" id="AF229180">
        <property type="protein sequence ID" value="AAF44328.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007714">
        <property type="protein sequence ID" value="CAA07619.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006020">
        <property type="protein sequence ID" value="AAF03526.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5783.1"/>
    <dbReference type="RefSeq" id="NP_005754.2">
        <property type="nucleotide sequence ID" value="NM_005763.3"/>
    </dbReference>
    <dbReference type="PDB" id="5L76">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.57 A"/>
        <property type="chains" value="A=455-926"/>
    </dbReference>
    <dbReference type="PDB" id="5L78">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.68 A"/>
        <property type="chains" value="A/B=455-926"/>
    </dbReference>
    <dbReference type="PDB" id="5O1N">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.28 A"/>
        <property type="chains" value="A=455-926"/>
    </dbReference>
    <dbReference type="PDB" id="5O1O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.48 A"/>
        <property type="chains" value="A/B=455-926"/>
    </dbReference>
    <dbReference type="PDB" id="5O1P">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A=455-926"/>
    </dbReference>
    <dbReference type="PDB" id="8DDA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C/D=1-476"/>
    </dbReference>
    <dbReference type="PDB" id="8E8T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.18 A"/>
        <property type="chains" value="A/B=21-452"/>
    </dbReference>
    <dbReference type="PDB" id="8E8U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.65 A"/>
        <property type="chains" value="A/B/C/D=21-470"/>
    </dbReference>
    <dbReference type="PDB" id="8E8V">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.45 A"/>
        <property type="chains" value="A/B/C/D=21-452"/>
    </dbReference>
    <dbReference type="PDBsum" id="5L76"/>
    <dbReference type="PDBsum" id="5L78"/>
    <dbReference type="PDBsum" id="5O1N"/>
    <dbReference type="PDBsum" id="5O1O"/>
    <dbReference type="PDBsum" id="5O1P"/>
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    <dbReference type="PDBsum" id="8E8T"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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    <reference key="2">
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                <person name="Wiemann S."/>
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            <dbReference type="PubMed" id="11230166"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
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            <dbReference type="PubMed" id="11780052"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lung</tissue>
            <tissue>Skin</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 228-384</scope>
        <source>
            <tissue>Fetal liver</tissue>
        </source>
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            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="8">
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                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
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            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
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            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <authorList>
                <person name="Santos K."/>
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                <person name="Weber G."/>
            </authorList>
            <dbReference type="PubMed" id="26527271"/>
            <dbReference type="DOI" id="10.1107/s2053230x15019202"/>
        </citation>
        <scope>CRYSTALLIZATION</scope>
        <scope>INTERACTION WITH PRPF8</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">Interacts with PRPF8 (via RNase H homology domain) (PubMed:26527271). Component of a U5 snRNP complex that contains PRPF8 (By similarity).</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the AAR2 family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAF29578" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AF132957">
        <property type="protein sequence ID" value="AAD27732.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL117419">
        <property type="protein sequence ID" value="CAB55913.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121895">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW76141.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW76142.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW76143.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001751">
        <property type="protein sequence ID" value="AAH01751.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC019311">
        <property type="protein sequence ID" value="AAH19311.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF113672">
        <property type="protein sequence ID" value="AAF29578.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13273.1"/>
    <dbReference type="PIR" id="T17223">
        <property type="entry name" value="T17223"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001258803.1">
        <property type="nucleotide sequence ID" value="NM_001271874.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056326.2">
        <property type="nucleotide sequence ID" value="NM_015511.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006723833.1">
        <property type="nucleotide sequence ID" value="XM_006723770.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011527064.1">
        <property type="nucleotide sequence ID" value="XM_011528762.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011527065.1">
        <property type="nucleotide sequence ID" value="XM_011528763.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047296038.1">
        <property type="nucleotide sequence ID" value="XM_047440082.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179291.1">
        <property type="nucleotide sequence ID" value="XM_054323316.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179292.1">
        <property type="nucleotide sequence ID" value="XM_054323317.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179293.1">
        <property type="nucleotide sequence ID" value="XM_054323318.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179294.1">
        <property type="nucleotide sequence ID" value="XM_054323319.1"/>
    </dbReference>
    <dbReference type="PDB" id="7PJH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.35 A"/>
        <property type="chains" value="A=1-384"/>
    </dbReference>
    <dbReference type="PDBsum" id="7PJH"/>
    <dbReference type="AlphaFoldDB" id="Q9Y312"/>
    <dbReference type="SMR" id="Q9Y312"/>
    <dbReference type="BioGRID" id="117464">
        <property type="interactions" value="688"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26552">
        <property type="entry name" value="U5 small nuclear ribonucleoprotein complex, AAR2 variant"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y312">
        <property type="interactions" value="1781"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y312"/>
    <dbReference type="STRING" id="9606.ENSP00000363043"/>
    <dbReference type="GlyGen" id="Q9Y312">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y312"/>
    <dbReference type="MetOSite" id="Q9Y312"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y312"/>
    <dbReference type="BioMuta" id="AAR2"/>
    <dbReference type="DMDM" id="24211603"/>
    <dbReference type="jPOST" id="Q9Y312"/>
    <dbReference type="MassIVE" id="Q9Y312"/>
    <dbReference type="PaxDb" id="9606-ENSP00000363043"/>
    <dbReference type="PeptideAtlas" id="Q9Y312"/>
    <dbReference type="ProteomicsDB" id="85957"/>
    <dbReference type="Pumba" id="Q9Y312"/>
    <dbReference type="Antibodypedia" id="26501">
        <property type="antibodies" value="81 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="25980"/>
    <dbReference type="Ensembl" id="ENST00000320849.9">
        <property type="protein sequence ID" value="ENSP00000313674.4"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000373932.3">
        <property type="protein sequence ID" value="ENSP00000363043.3"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000679667.1">
        <property type="protein sequence ID" value="ENSP00000506354.1"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000680247.1">
        <property type="protein sequence ID" value="ENSP00000505295.1"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
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    <dbReference type="Ensembl" id="ENST00000680639.1">
        <property type="protein sequence ID" value="ENSP00000505405.1"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
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    <dbReference type="Ensembl" id="ENST00000680811.1">
        <property type="protein sequence ID" value="ENSP00000506185.1"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
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    <dbReference type="Ensembl" id="ENST00000680933.1">
        <property type="protein sequence ID" value="ENSP00000505061.1"/>
        <property type="gene ID" value="ENSG00000131043.14"/>
    </dbReference>
    <dbReference type="GeneID" id="25980"/>
    <dbReference type="KEGG" id="hsa:25980"/>
    <dbReference type="MANE-Select" id="ENST00000320849.9">
        <property type="protein sequence ID" value="ENSP00000313674.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001271874.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001258803.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002xfc.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15886"/>
    <dbReference type="ClinPGx" id="PA25753"/>
    <dbReference type="CTD" id="25980"/>
    <dbReference type="DisGeNET" id="25980"/>
    <dbReference type="GeneCards" id="AAR2"/>
    <dbReference type="HGNC" id="HGNC:15886">
        <property type="gene designation" value="AAR2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000131043">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="617365">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000131043"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000131043"/>
    <dbReference type="eggNOG" id="KOG3937">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000007796"/>
    <dbReference type="HOGENOM" id="CLU_036039_0_0_1"/>
    <dbReference type="InParanoid" id="Q9Y312"/>
    <dbReference type="OMA" id="VWQSGGL"/>
    <dbReference type="OrthoDB" id="201752at2759"/>
    <dbReference type="PAN-GO" id="Q9Y312">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y312"/>
    <dbReference type="PathwayCommons" id="Q9Y312"/>
    <dbReference type="SignaLink" id="Q9Y312"/>
    <dbReference type="Agora" id="ENSG00000131043"/>
    <dbReference type="BioGRID-ORCS" id="25980">
        <property type="hits" value="30 hits in 1166 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AAR2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="25980"/>
    <dbReference type="Pharos" id="Q9Y312">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y312"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y312">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000131043">
        <property type="expression patterns" value="Expressed in lower esophagus muscularis layer and 188 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y312">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005681">
        <property type="term" value="C:spliceosomal complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005682">
        <property type="term" value="C:U5 snRNP"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000244">
        <property type="term" value="P:spliceosomal tri-snRNP complex assembly"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="CDD" id="cd13778">
        <property type="entry name" value="Aar2_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13777">
        <property type="entry name" value="Aar2_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.550:FF:000001">
        <property type="entry name" value="AAR2 splicing factor homolog"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.34.20:FF:000001">
        <property type="entry name" value="protein AAR2 homolog"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.34.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.550">
        <property type="entry name" value="Aar2, C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007946">
        <property type="entry name" value="AAR2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033648">
        <property type="entry name" value="AAR2_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038514">
        <property type="entry name" value="AAR2_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033647">
        <property type="entry name" value="Aar2_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038516">
        <property type="entry name" value="AAR2_N_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12689">
        <property type="entry name" value="A1 CISTRON SPLICING FACTOR AAR2-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12689:SF4">
        <property type="entry name" value="PROTEIN AAR2 HOMOLOG"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF05282">
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<entry dataset="Swiss-Prot" created="1998-07-15" modified="2026-01-28" version="246" xmlns="https://uniprot.org/uniprot">
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    <accession>Q86VS1</accession>
    <accession>Q9UNQ4</accession>
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            <fullName>5'-AMP-activated protein kinase catalytic subunit alpha-1</fullName>
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            <fullName>Acetyl-CoA carboxylase kinase</fullName>
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        <alternativeName>
            <fullName>Hydroxymethylglutaryl-CoA reductase kinase</fullName>
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        <alternativeName>
            <fullName>Tau-protein kinase PRKAA1</fullName>
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            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <tissue>Intestine</tissue>
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    <comment type="function">
        <text evidence="1 2 6 7 9 10 13 19 20 21 23 25 26 27 30 31 32 33 35 36 37 38 39 40 43 44">Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:31492851, PubMed:37821951, PubMed:40233740). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). Phosphorylates ALDH7A1 in response to cellular stress, such as hypoxia or ferroptotic stress, promoting ALDH7A1 recruitment to membranes (PubMed:31492851, PubMed:40233740).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="32 33 37 38 40">
            <text>L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17989"/>
            <dbReference type="Rhea" id="RHEA-COMP:9863"/>
            <dbReference type="Rhea" id="RHEA-COMP:11604"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="30">
            <text>L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46608"/>
            <dbReference type="Rhea" id="RHEA-COMP:11060"/>
            <dbReference type="Rhea" id="RHEA-COMP:11605"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-seryl-[acetyl-CoA carboxylase] + ATP = O-phospho-L-seryl-[acetyl-CoA carboxylase] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20333"/>
            <dbReference type="Rhea" id="RHEA-COMP:13722"/>
            <dbReference type="Rhea" id="RHEA-COMP:13723"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ATP = O-phospho-L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:23172"/>
            <dbReference type="Rhea" id="RHEA-COMP:13692"/>
            <dbReference type="Rhea" id="RHEA-COMP:13693"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.31"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12801"/>
            <dbReference type="Rhea" id="RHEA-COMP:13701"/>
            <dbReference type="Rhea" id="RHEA-COMP:13702"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.26"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:53904"/>
            <dbReference type="Rhea" id="RHEA-COMP:13703"/>
            <dbReference type="Rhea" id="RHEA-COMP:13704"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.26"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="2 8 11 14 15 29">Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Inhibited by modified adenosine monophosphate (AMP) N(6)-methyl-AMP (m6AMP), N(6),N(6)-dimethyl-AMP (m6,6AMP) and N(6)-isopentenyl-AMP (i6AMP) (By similarity). AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol.</text>
    </comment>
    <comment type="subunit">
        <text evidence="17 22 24 29 34">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3) (PubMed:21680840). Interacts with FNIP1 and FNIP2 (PubMed:17028174, PubMed:18403135, PubMed:18663353). Interacts with LACC1; this interaction may regulate macrophage autophagic flux.</text>
    </comment>
    <comment type="subunit">
        <text evidence="39">(Microbial infection) Interacts with Dengue type 2 virus non-structural protein 1; this interaction promotes the AMPK/ERK/mTOR signaling pathway to induce autophagy.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-711810">
            <id>O14503</id>
            <label>BHLHE40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10181162">
            <id>O14627</id>
            <label>CDX4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10171858">
            <id>Q13363-2</id>
            <label>CTBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-1059030">
            <id>O95073</id>
            <label>FSBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-618309">
            <id>Q08379</id>
            <label>GOLGA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-2549423">
            <id>Q6NT76</id>
            <label>HMBOX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10172004">
            <id>Q8IX15-3</id>
            <label>HOMEZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-352572">
            <id>P08238</id>
            <label>HSP90AB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-747204">
            <id>Q9UKT9</id>
            <label>IKZF3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-769401">
            <id>Q8NBZ0</id>
            <label>INO80E</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10171697">
            <id>Q6A162</id>
            <label>KRT40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-2686809">
            <id>Q96JM7</id>
            <label>L3MBTL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-742948">
            <id>Q5JR59</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-713786">
            <id>Q8IXK0</id>
            <label>PHC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10171633">
            <id>Q96PV4</id>
            <label>PNMA5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-719769">
            <id>Q9Y478</id>
            <label>PRKAB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-1053424">
            <id>O43741</id>
            <label>PRKAB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>21</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
            <label>PRKAG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>18</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-740322">
            <id>Q93062</id>
            <label>RBPMS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-746118">
            <id>Q8HWS3</id>
            <label>RFX6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-10182375">
            <id>Q9UFD9</id>
            <label>RIMBP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-1378139">
            <id>Q9HAT0</id>
            <label>ROPN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-2212028">
            <id>Q9Y2D8</id>
            <label>SSX2IP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-741515">
            <id>Q9NVV9</id>
            <label>THAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-717810">
            <id>Q08117</id>
            <label>TLE5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-719493">
            <id>P14373</id>
            <label>TRIM27</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-742327">
            <id>Q15654</id>
            <label>TRIP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-739485">
            <id>Q9Y3Q8</id>
            <label>TSC22D4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-746004">
            <id>Q5T124</id>
            <label>UBXN11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-4400866">
            <id>Q9H9H4</id>
            <label>VPS37B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-2799833">
            <id>Q8N1B4</id>
            <label>VPS52</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-1044059">
            <id>P46937</id>
            <label>YAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
        </interactant>
        <interactant intactId="EBI-740037">
            <id>O96006</id>
            <label>ZBED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 39">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Nucleus</location>
        </subcellularLocation>
        <text evidence="13">In response to stress, recruited by p53/TP53 to specific promoters.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q13131-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13131-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_035431"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="18 41">The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Ubiquitinated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11 14 15 28">Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B.</text>
    </comment>
    <comment type="PTM">
        <text evidence="30">Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.</text>
    </comment>
    <comment type="similarity">
        <text evidence="45">Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA64850" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAD43027" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH37303" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA36547" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAG35788" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="2.7.11.1" evidence="33 37 38 40"/>
    <dbReference type="EC" id="2.7.11.31" evidence="1"/>
    <dbReference type="EC" id="2.7.11.26" evidence="1"/>
    <dbReference type="EMBL" id="AC008810">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC048980">
        <property type="protein sequence ID" value="AAH48980.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB022017">
        <property type="protein sequence ID" value="BAA36547.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312947">
        <property type="protein sequence ID" value="BAG35788.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC037303">
        <property type="protein sequence ID" value="AAH37303.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF100763">
        <property type="protein sequence ID" value="AAD43027.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U22456">
        <property type="protein sequence ID" value="AAA64850.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y12856">
        <property type="protein sequence ID" value="CAA73361.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="entry name" value="Pkinase"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0153">Cholesterol metabolism</keyword>
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    <keyword id="KW-0325">Glycoprotein</keyword>
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    <keyword id="KW-0418">Kinase</keyword>
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    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <keyword id="KW-0753">Steroid metabolism</keyword>
    <keyword id="KW-0756">Sterol biosynthesis</keyword>
    <keyword id="KW-1207">Sterol metabolism</keyword>
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    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0808">Transferase</keyword>
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    <keyword id="KW-0879">Wnt signaling pathway</keyword>
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            <end position="559"/>
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    <feature type="region of interest" description="AIS">
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            <end position="381"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
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            <end position="536"/>
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    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
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            <end position="505"/>
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    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
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            <begin position="516"/>
            <end position="535"/>
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    </feature>
    <feature type="active site" description="Proton acceptor" evidence="3 4">
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    <feature type="binding site" evidence="3">
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            <begin position="33"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="3">
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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            <position position="32"/>
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            <position position="269"/>
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    <feature type="modified residue" description="Phosphothreonine" evidence="52">
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="48">
        <location>
            <position position="356"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine; by ULK1" evidence="1">
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            <position position="360"/>
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    </feature>
    <feature type="modified residue" description="Phosphothreonine; by ULK1" evidence="1">
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            <position position="368"/>
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    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="47 50 51">
        <location>
            <position position="382"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="397"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="49">
        <location>
            <position position="467"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="48 51">
        <location>
            <position position="486"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="488"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="48 51">
        <location>
            <position position="490"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="48 51 52">
        <location>
            <position position="496"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="52">
        <location>
            <position position="508"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="52">
        <location>
            <position position="524"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="52">
        <location>
            <position position="527"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035431" description="In isoform 2." evidence="42">
        <original>R</original>
        <variation>RKSDVPGVVKTGSTKE</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058401" description="In dbSNP:rs17855679." evidence="12">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035622" description="In a breast cancer sample; somatic mutation; dbSNP:rs928784854." evidence="16">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Activates the kinase activity." evidence="18">
        <original>V</original>
        <variation>G</variation>
        <variation>Q</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAG35788." evidence="45" ref="4">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAD43027." evidence="45" ref="5">
        <original>K</original>
        <variation>S</variation>
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA64850." evidence="45" ref="6">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA64850." evidence="45" ref="6">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA64850." evidence="45" ref="6">
        <original>I</original>
        <variation>L</variation>
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            <title>Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle.</title>
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        <citation type="journal article" date="2002" name="Mol. Cell. Probes" volume="16" first="421" last="427">
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            <dbReference type="DOI" id="10.1006/mcpr.2002.0439"/>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Carmena D."/>
                <person name="Jing C."/>
                <person name="Walker P.A."/>
                <person name="Eccleston J.F."/>
                <person name="Haire L.F."/>
                <person name="Saiu P."/>
                <person name="Howell S.A."/>
                <person name="Aasland R."/>
                <person name="Martin S.R."/>
                <person name="Carling D."/>
                <person name="Gamblin S.J."/>
            </authorList>
            <dbReference type="PubMed" id="21399626"/>
            <dbReference type="DOI" id="10.1038/nature09932"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 187-272 IN COMPLEX WITH PRKAA1 AND PRKAG1</scope>
        <scope>MUTAGENESIS OF HIS-235</scope>
    </reference>
    <comment type="function">
        <text>Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3).</text>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0276">Fatty acid metabolism</keyword>
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    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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            <begin position="1"/>
            <end position="272"/>
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            <begin position="1"/>
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        <original>MGNTTSDRVSGERHGAKAARSEGAG</original>
        <variation>MPRGRSTRSWWGVRTTPACSASLTP</variation>
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            <begin position="1"/>
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    <evidence type="ECO:0000250" key="1">
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            <dbReference type="PubMed" id="24275569"/>
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        <source>
            <dbReference type="PDB" id="2F15"/>
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            <dbReference type="PDB" id="2V8Q"/>
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        <source>
            <dbReference type="PDB" id="2V92"/>
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    </evidence>
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        <source>
            <dbReference type="PDB" id="4CFH"/>
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        <source>
            <dbReference type="PDB" id="4EAI"/>
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    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="7JHG"/>
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    <sequence length="272" mass="30302" checksum="42B23BD70B92519C" modified="1998-06-01" version="1">MGNTTSDRVSGERHGAKAARSEGAGGHAPGKEHKIMVGSTDDPSVFSLPDSKLPGDKEFVSWQQDLEDSVKPTQQARPTVIRWSEGGKEVFISGSFNNWSTKIPLIKSHNDFVAILDLPEGEHQYKFFVDGQWVHDPSEPVVTSQLGTINNLIHVKKSDFEVFDALKLDSMESSETSCRDLSSSPPGPYGQEMYAFRSEERFKSPPILPPHLLQVILNKDTNISCDPALLPEPNHVMLNHLYALSIKDSVMVLSATHRYKKKYVTTLLYKPI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2010-02-09" modified="2026-01-28" version="53" xmlns="https://uniprot.org/uniprot">
    <accession>P86434</accession>
    <name>AAS1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative uncharacterized protein ADORA2A-AS1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ADORA2A antisense RNA 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ADORA2A antisense gene protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADORA2A-AS1</name>
        <name type="synonym">C22orf45</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="3" key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
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                <person name="Hosoiri T."/>
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                <person name="Kondo H."/>
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                <person name="Tanai H."/>
                <person name="Kimata M."/>
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                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
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                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
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                <person name="Imose N."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
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                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
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                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
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                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
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                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue evidence="2">Kidney</tissue>
        </source>
    </reference>
    <reference key="2">
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            <dbReference type="DOI" id="10.1038/990031"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="3" key="3">
        <citation type="journal article" date="2009" name="Genome Res." volume="19" first="1752" last="1759">
            <title>Recent de novo origin of human protein-coding genes.</title>
            <authorList>
                <person name="Knowles D.G."/>
                <person name="McLysaght A."/>
            </authorList>
            <dbReference type="PubMed" id="19726446"/>
            <dbReference type="DOI" id="10.1101/gr.095026.109"/>
        </citation>
        <scope>IDENTIFICATION</scope>
    </reference>
    <comment type="miscellaneous">
        <text>This protein has no orthologs in other species and appears to be the product of a protein-coding gene which has arisen since divergence from chimp.</text>
    </comment>
    <comment type="caution">
        <text evidence="3">Product of a dubious CDS prediction.</text>
    </comment>
    <dbReference type="EMBL" id="AK091970">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP000355">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P86434"/>
    <dbReference type="GlyGen" id="P86434">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="BioMuta" id="HGNC:37122"/>
    <dbReference type="jPOST" id="P86434"/>
    <dbReference type="MassIVE" id="P86434"/>
    <dbReference type="PeptideAtlas" id="P86434"/>
    <dbReference type="AGR" id="HGNC:37122"/>
    <dbReference type="GeneCards" id="ADORA2A-AS1"/>
    <dbReference type="HGNC" id="HGNC:37122">
        <property type="gene designation" value="ADORA2A-AS1"/>
    </dbReference>
    <dbReference type="InParanoid" id="P86434"/>
    <dbReference type="PAN-GO" id="P86434">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P86434"/>
    <dbReference type="ChiTaRS" id="ADORA2A-AS1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="P86434">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P86434"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="P86434">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000391464" description="Putative uncharacterized protein ADORA2A-AS1">
        <location>
            <begin position="1"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="91"/>
            <end position="110"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="159" mass="17238" checksum="C554549DBC6B15E2" modified="2010-02-09" version="1">MEQDWQPGEEVTPGPEPCSKGQAPLYPIVHVTELKHTDPNFPSNSNAVGTSSGWNRIGTGCSHTWDWRFSCTQQALLPLLGAWEWSIDTEAGGGRREQSQKPCSNGGPAAAGEGRVLPSPCFPWSTCQAAIHKVCRWQGCTRPALLAPSLATLKEHSYP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-02-06" modified="2026-01-28" version="184" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BTE6</accession>
    <accession>B4DI73</accession>
    <name>AASD1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alanyl-tRNA editing protein Aarsd1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Alanyl-tRNA synthetase domain-containing protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AARSD1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="2">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="6">
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            <title>Initial characterization of the human central proteome.</title>
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                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
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                <person name="Zhou H."/>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="5">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="5">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-11957452">
            <id>Q4LE39-3</id>
            <label>ARID4B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-1176455">
            <id>P63172</id>
            <label>DYNLT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-10226932">
            <id>Q0VG06-3</id>
            <label>FAAP100</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-721328">
            <id>P58340</id>
            <label>MLF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-12037215">
            <id>Q5MJ09</id>
            <label>SPANXN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-11993364">
            <id>Q9H8W5-2</id>
            <label>TRIM45</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-746595">
            <id>Q96E35</id>
            <label>ZMYND19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-6874731">
            <id>O15231</id>
            <label>ZNF185</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9357295">
            <id>Q9BTE6-2</id>
        </interactant>
        <interactant intactId="EBI-9356686">
            <id>Q96BE0</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BTE6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BTE6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_023014"/>
        </isoform>
        <isoform>
            <id>Q9BTE6-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043142"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="5">Based on a readthrough transcript which may produce a PTGES3L-AARSD1 fusion protein.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="5">Based on a readthrough transcript which may produce a PTGES3L-AARSD1 fusion protein.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AK295447">
        <property type="protein sequence ID" value="BAG58385.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR608238">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC055866">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471152">
        <property type="protein sequence ID" value="EAW60903.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004172">
        <property type="protein sequence ID" value="AAH04172.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC019324">
        <property type="protein sequence ID" value="AAH19324.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58552.1">
        <molecule id="Q9BTE6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001129514.2">
        <molecule id="Q9BTE6-3"/>
        <property type="nucleotide sequence ID" value="NM_001136042.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001248363.1">
        <molecule id="Q9BTE6-1"/>
        <property type="nucleotide sequence ID" value="NM_001261434.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_079543.1">
        <molecule id="Q9BTE6-2"/>
        <property type="nucleotide sequence ID" value="NM_025267.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BTE6"/>
    <dbReference type="SMR" id="Q9BTE6"/>
    <dbReference type="BioGRID" id="123290">
        <property type="interactions" value="146"/>
    </dbReference>
    <dbReference type="BioGRID" id="3190353">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BTE6">
        <property type="interactions" value="2205"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BTE6">
        <property type="interactions" value="191"/>
    </dbReference>
    <dbReference type="MINT" id="Q9BTE6"/>
    <dbReference type="STRING" id="9606.ENSP00000400870"/>
    <dbReference type="GlyGen" id="Q9BTE6">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9BTE6"/>
    <dbReference type="PhosphoSitePlus" id="Q9BTE6"/>
    <dbReference type="BioMuta" id="AARSD1"/>
    <dbReference type="DMDM" id="125987702"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00827636"/>
    <dbReference type="jPOST" id="Q9BTE6"/>
    <dbReference type="MassIVE" id="Q9BTE6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000400870"/>
    <dbReference type="PeptideAtlas" id="Q9BTE6"/>
    <dbReference type="ProteomicsDB" id="78985">
        <molecule id="Q9BTE6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="78986">
        <molecule id="Q9BTE6-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="78987">
        <molecule id="Q9BTE6-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9BTE6"/>
    <dbReference type="Antibodypedia" id="17173">
        <property type="antibodies" value="82 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="67174">
        <property type="antibodies" value="180 antibodies from 15 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="80755"/>
    <dbReference type="Ensembl" id="ENST00000360221.8">
        <molecule id="Q9BTE6-2"/>
        <property type="protein sequence ID" value="ENSP00000353355.4"/>
        <property type="gene ID" value="ENSG00000108825.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000427569.7">
        <molecule id="Q9BTE6-1"/>
        <property type="protein sequence ID" value="ENSP00000400870.1"/>
        <property type="gene ID" value="ENSG00000266967.8"/>
    </dbReference>
    <dbReference type="GeneID" id="80755"/>
    <dbReference type="KEGG" id="hsa:100885850"/>
    <dbReference type="KEGG" id="hsa:80755"/>
    <dbReference type="MANE-Select" id="ENST00000427569.7">
        <property type="protein sequence ID" value="ENSP00000400870.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001261434.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001248363.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002icd.3">
        <molecule id="Q9BTE6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28417"/>
    <dbReference type="AGR" id="HGNC:43946"/>
    <dbReference type="ClinPGx" id="PA142670464"/>
    <dbReference type="CTD" id="80755"/>
    <dbReference type="GeneCards" id="AARSD1"/>
    <dbReference type="GeneCards" id="PTGES3L-AARSD1"/>
    <dbReference type="HGNC" id="HGNC:28417">
        <property type="gene designation" value="AARSD1"/>
    </dbReference>
    <dbReference type="HGNC" id="HGNC:43946">
        <property type="gene designation" value="PTGES3L-AARSD1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000108825">
        <property type="expression patterns" value="Tissue enhanced (skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000266967">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="613212">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000108825"/>
    <dbReference type="OpenTargets" id="ENSG00000266967"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000108825"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000266967"/>
    <dbReference type="eggNOG" id="KOG2105">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156241"/>
    <dbReference type="HOGENOM" id="CLU_004485_7_0_1"/>
    <dbReference type="InParanoid" id="Q9BTE6"/>
    <dbReference type="OMA" id="KYDTTSW"/>
    <dbReference type="OrthoDB" id="288942at2759"/>
    <dbReference type="PAN-GO" id="Q9BTE6">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BTE6"/>
    <dbReference type="PathwayCommons" id="Q9BTE6"/>
    <dbReference type="SignaLink" id="Q9BTE6"/>
    <dbReference type="Agora" id="ENSG00000108825"/>
    <dbReference type="Agora" id="ENSG00000266967"/>
    <dbReference type="BioGRID-ORCS" id="100885850">
        <property type="hits" value="23 hits in 1066 CRISPR screens"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="80755">
        <property type="hits" value="16 hits in 1113 CRISPR screens"/>
    </dbReference>
    <dbReference type="Pharos" id="Q9BTE6">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BTE6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BTE6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000108825">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 103 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9BTE6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004813">
        <property type="term" value="F:alanine-tRNA ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003676">
        <property type="term" value="F:nucleic acid binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002196">
        <property type="term" value="F:Ser-tRNA(Ala) deacylase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006419">
        <property type="term" value="P:alanyl-tRNA aminoacylation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006450">
        <property type="term" value="P:regulation of translational fidelity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.980.10:FF:000007">
        <property type="entry name" value="alanyl-tRNA editing protein Aarsd1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.30.130:FF:000012">
        <property type="entry name" value="Predicted gene, 27029"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.30.130">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.980.10">
        <property type="entry name" value="Threonyl-trna Synthetase, Chain A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018165">
        <property type="entry name" value="Ala-tRNA-synth_IIc_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051335">
        <property type="entry name" value="Alanyl-tRNA_Editing_Enzymes"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018163">
        <property type="entry name" value="Thr/Ala-tRNA-synth_IIc_edit"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009000">
        <property type="entry name" value="Transl_B-barrel_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012947">
        <property type="entry name" value="tRNA_SAD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43462">
        <property type="entry name" value="ALANYL-TRNA EDITING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43462:SF1">
        <property type="entry name" value="ALANYL-TRNA EDITING PROTEIN AARSD1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07973">
        <property type="entry name" value="tRNA_SAD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00863">
        <property type="entry name" value="tRNA_SAD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55186">
        <property type="entry name" value="ThrRS/AlaRS common domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50447">
        <property type="entry name" value="Translation proteins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50860">
        <property type="entry name" value="AA_TRNA_LIGASE_II_ALA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0648">Protein biosynthesis</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000277465" description="Alanyl-tRNA editing protein Aarsd1">
        <location>
            <begin position="1"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="109"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="113"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="209"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="213"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="6">
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023014" description="In isoform 2." evidence="4">
        <original>MAFWCQRDSYARE</original>
        <variation>MEFCVEDSTDVHVLIEDHRIVFSCKNADGVELYNEIEFYAKVNSKDSQDKRSSRSITCFVRKWKEKVAWPRLTKEDIKPVWLSVDFDNWRDWEGDEEMELAHVEHYAELLKKVSTKRPPPAMDDLD</variation>
        <location>
            <begin position="1"/>
            <end position="13"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043142" description="In isoform 3." evidence="3">
        <original>MAFWCQRDSYARE</original>
        <variation>MFSLPLNCSPDHIRRGSCWGRPQDLKIAAPAWNSKCHPGAGAAMARQHARTLWYDRPRYVFMEFCVEDSTDVHVLIEDHRIVFSCKNADGVELYNEIEFYAKVNSKDSQDKRSSRSITCFVRKWKEKVAWPRLTKEDIKPVWLSVDFDNWRDWEGDEEMELAHVEHYAELLKKVSTKRPPPAMDDLD</variation>
        <location>
            <begin position="1"/>
            <end position="13"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="412" mass="45480" checksum="2E14B6274C6EF897" modified="2007-02-06" version="2">MAFWCQRDSYAREFTTTVVSCCPAELQTEGSNGKKEVLSGFQVVLEDTVLFPEGGGQPDDRGTINDISVLRVTRRGEQADHFTQTPLDPGSQVLVRVDWERRFDHMQQHSGQHLITAVADHLFKLKTTSWELGRFRSAIELDTPSMTAEQVAAIEQSVNEKIRDRLPVNVRELSLDDPEVEQVSGRGLPDDHAGPIRVVNIEGVDSNMCCGTHVSNLSDLQVIKILGTEKGKKNRTNLIFLSGNRVLKWMERSHGTEKALTALLKCGAEDHVEAVKKLQNSTKILQKNNLNLLRDLAVHIAHSLRNSPDWGGVVILHRKEGDSEFMNIIANEIGSEETLLFLTVGDEKGGGLFLLAGPPASVETLGPRVAEVLEGKGAGKKGRFQGKATKMSRRMEAQALLQDYISTQSAKE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="215" xmlns="https://uniprot.org/uniprot">
    <accession>P54619</accession>
    <accession>B4DDT7</accession>
    <accession>Q8N7V9</accession>
    <name>AAKG1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>5'-AMP-activated protein kinase subunit gamma-1</fullName>
            <shortName>AMPK gamma1</shortName>
            <shortName>AMPK subunit gamma-1</shortName>
            <shortName>AMPKg</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">PRKAG1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Glial tumor</tissue>
            <tissue>Testis</tissue>
        </source>
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    <comment type="function">
        <text evidence="8 10">AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:21680840, PubMed:24563466). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:21680840, PubMed:24563466). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:21680840, PubMed:24563466). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:21680840, PubMed:24563466). Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits (PubMed:21680840, PubMed:24563466). ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit (PubMed:21680840, PubMed:24563466). ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive (PubMed:21680840, PubMed:24563466).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 6 8">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.</text>
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        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
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        <interactant intactId="EBI-16439278">
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    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-747278">
            <id>P26367</id>
            <label>PAX6</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-1181405">
            <id>Q13131</id>
            <label>PRKAA1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
            <label>PRKAA2</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-719769">
            <id>Q9Y478</id>
            <label>PRKAB1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
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        <interactant intactId="EBI-1053424">
            <id>O43741</id>
            <label>PRKAB2</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P54619</id>
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            <id>O75400-2</id>
            <label>PRPF40A</label>
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    <comment type="interaction">
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            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-10180409">
            <id>Q969V4</id>
            <label>TEKT1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-2505861">
            <id>Q13829</id>
            <label>TNFAIP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-1181439">
            <id>P54619</id>
        </interactant>
        <interactant intactId="EBI-17516">
            <id>P06782</id>
            <label>SNF1</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P54619-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P54619-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046711"/>
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        <isoform>
            <id>P54619-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046712"/>
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    </comment>
    <comment type="domain">
        <text>The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.</text>
    </comment>
    <comment type="domain">
        <text evidence="5 9 11">The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="7">Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10">Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="13">May be due to competing acceptor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the 5'-AMP-activated protein kinase gamma subunit family.</text>
    </comment>
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            <dbReference type="PDB" id="8BIK"/>
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    <sequence length="331" mass="37579" checksum="0F22B9CA1DBD87AE" modified="1996-10-01" version="1">METVISSDSSPAVENEHPQETPESNNSVYTSFMKSHRCYDLIPTSSKLVVFDTSLQVKKAFFALVTNGVRAAPLWDSKKQSFVGMLTITDFINILHRYYKSALVQIYELEEHKIETWREVYLQDSFKPLVCISPNASLFDAVSSLIRNKIHRLPVIDPESGNTLYILTHKRILKFLKLFITEFPKPEFMSKSLEELQIGTYANIAMVRTTTPVYVALGIFVQHRVSALPVVDEKGRVVDIYSKFDVINLAAEKTYNNLDVSVTKALQHRSHYFEGVLKCYLHETLETIINRLVEAEVHRLVVVDENDVVKGIVSLSDILQALVLTGGEKKP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>P54646</accession>
    <accession>Q9H1E8</accession>
    <accession>Q9UD43</accession>
    <name>AAPK2_HUMAN</name>
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        <recommendedName>
            <fullName>5'-AMP-activated protein kinase catalytic subunit alpha-2</fullName>
            <shortName>AMPK subunit alpha-2</shortName>
            <ecNumber evidence="27 29 33 34">2.7.11.1</ecNumber>
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        <alternativeName>
            <fullName>Acetyl-CoA carboxylase kinase</fullName>
            <shortName>ACACA kinase</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Hydroxymethylglutaryl-CoA reductase kinase</fullName>
            <shortName>HMGCR kinase</shortName>
            <ecNumber evidence="1">2.7.11.31</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="40" type="primary">PRKAA2</name>
        <name type="synonym">AMPK</name>
        <name type="synonym">AMPK2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Gene" volume="149" first="345" last="350">
            <title>Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals.</title>
            <authorList>
                <person name="Aguan K."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Heart</tissue>
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    </reference>
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                <person name="Beri R.K."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <tissue>Skeletal muscle</tissue>
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                <person name="Shownkeen R."/>
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                <person name="Skuce C.D."/>
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                <person name="Tracey A."/>
                <person name="Tromans A."/>
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                <person name="Coulson A."/>
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                <person name="Wooster R."/>
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            <dbReference type="PubMed" id="16710414"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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    <reference key="5">
        <citation type="journal article" date="2001" name="Biochem. Biophys. Res. Commun." volume="287" first="562" last="567">
            <title>Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line.</title>
            <authorList>
                <person name="Imamura K."/>
                <person name="Ogura T."/>
                <person name="Kishimoto A."/>
                <person name="Kaminishi M."/>
                <person name="Esumi H."/>
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            <dbReference type="PubMed" id="11554766"/>
            <dbReference type="DOI" id="10.1006/bbrc.2001.5627"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
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            <title>Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors.</title>
            <authorList>
                <person name="Yang W."/>
                <person name="Hong Y.H."/>
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            <dbReference type="PubMed" id="11518699"/>
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        <scope>FUNCTION IN PHOSPHORYLATION OF EP300</scope>
    </reference>
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                <person name="Zhou G."/>
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            <dbReference type="PubMed" id="11602624"/>
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        <scope>ACTIVITY REGULATION</scope>
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        <scope>FUNCTION IN PHOSPHORYLATION OF CFTR</scope>
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            <dbReference type="PubMed" id="36367943"/>
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        </citation>
        <scope>FUNCTION</scope>
    </reference>
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            <title>A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.</title>
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                <person name="Littler D.R."/>
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            </authorList>
            <dbReference type="PubMed" id="20124709"/>
            <dbReference type="DOI" id="10.1107/s1744309109052543"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-279</scope>
    </reference>
    <reference key="39">
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            <title>Structural basis for compound C inhibition of the human AMP-activated protein kinase alpha2 subunit kinase domain.</title>
            <authorList>
                <person name="Handa N."/>
                <person name="Takagi T."/>
                <person name="Saijo S."/>
                <person name="Kishishita S."/>
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                <person name="Toyama M."/>
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            </authorList>
            <dbReference type="PubMed" id="21543851"/>
            <dbReference type="DOI" id="10.1107/s0907444911010201"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 6-279 OF MUTANT THR-172 IN COMPLEX WITH COMPOUND C</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF THR-172</scope>
    </reference>
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            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
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            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLY-523</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="17344846"/>
            <dbReference type="DOI" id="10.1038/nature05610"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLN-407</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 7 8 10 11 12 16 17 18 19 20 21 26 27 28 29 30 31 32 33 34 35 36 37">Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration (PubMed:36017701). Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation (PubMed:28552616). Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="27 29 33 34">
            <text>L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17989"/>
            <dbReference type="Rhea" id="RHEA-COMP:9863"/>
            <dbReference type="Rhea" id="RHEA-COMP:11604"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
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            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46608"/>
            <dbReference type="Rhea" id="RHEA-COMP:11060"/>
            <dbReference type="Rhea" id="RHEA-COMP:11605"/>
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            <dbReference type="ChEBI" id="CHEBI:30013"/>
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            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-seryl-[acetyl-CoA carboxylase] + ATP = O-phospho-L-seryl-[acetyl-CoA carboxylase] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20333"/>
            <dbReference type="Rhea" id="RHEA-COMP:13722"/>
            <dbReference type="Rhea" id="RHEA-COMP:13723"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
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            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ATP = O-phospho-L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:23172"/>
            <dbReference type="Rhea" id="RHEA-COMP:13692"/>
            <dbReference type="Rhea" id="RHEA-COMP:13693"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.31"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="38">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="9 13 23 24">Activated by phosphorylation on Thr-172 (PubMed:15980064). Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172 (PubMed:15980064). AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172 (PubMed:15980064). ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK (PubMed:15980064). ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive (PubMed:15980064). Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="23 26 27 31">AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3) (PubMed:21543851). Interacts with FNIP1 and FNIP2. Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; PRKAA2/AMPK2 together with ATIC and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571). Interacts with ARF6 (PubMed:36017701). The phosphorylated form at Thr-172 mediated by CamKK2 interacts with ACSS2 (PubMed:28552616).</text>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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            <id>Q15831</id>
            <label>STK11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-533224">
            <id>P15884</id>
            <label>TCF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-740711">
            <id>Q96CG3</id>
            <label>TIFA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-717810">
            <id>Q08117</id>
            <label>TLE5</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-11741437">
            <id>Q08117-2</id>
            <label>TLE5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-358993">
            <id>Q15645</id>
            <label>TRIP13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-742327">
            <id>Q15654</id>
            <label>TRIP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-739485">
            <id>Q9Y3Q8</id>
            <label>TSC22D4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-908831">
            <id>O75385</id>
            <label>ULK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-11523636">
            <id>Q9Y6N9-4</id>
            <label>USH1C</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-8601749">
            <id>Q495M9</id>
            <label>USH1G</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P54646</id>
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        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P54646</id>
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        <interactant intactId="EBI-12146727">
            <id>Q9UK41-2</id>
            <label>VPS28</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        <interactant intactId="EBI-4400866">
            <id>Q9H9H4</id>
            <label>VPS37B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2799833">
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            <label>VPS52</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P54646</id>
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        <interactant intactId="EBI-720609">
            <id>O76024</id>
            <label>WFS1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-743923">
            <id>O00308</id>
            <label>WWP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-742740">
            <id>Q96BR9</id>
            <label>ZBTB8A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-12030590">
            <id>Q9H0C1</id>
            <label>ZMYND12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-1640204">
            <id>Q9UDV6</id>
            <label>ZNF212</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-10213894">
            <id>Q8NF99</id>
            <label>ZNF397</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-5667532">
            <id>Q3MJ62</id>
            <label>ZSCAN23</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
        </interactant>
        <interactant intactId="EBI-8627450">
            <id>Q9WTK7</id>
            <label>Stk11</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Nucleus</location>
        </subcellularLocation>
        <text evidence="12">In response to stress, recruited by p53/TP53 to specific promoters.</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Ubiquitinated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13 22">Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1).</text>
    </comment>
    <comment type="similarity">
        <text evidence="38">Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA64745.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC069680">
        <property type="protein sequence ID" value="AAH69680.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC069740">
        <property type="protein sequence ID" value="AAH69740.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH69823.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="S51025"/>
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        <property type="nucleotide sequence ID" value="NM_006252.3"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A=6-279"/>
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        <property type="method" value="NMR"/>
        <property type="chains" value="A=282-339"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.02 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.08 A"/>
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        <property type="resolution" value="2.99 A"/>
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    <dbReference type="ComplexPortal" id="CPX-5787">
        <property type="entry name" value="AMPK complex, alpha2-beta1-gamma1 variant"/>
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    <dbReference type="ComplexPortal" id="CPX-5790">
        <property type="entry name" value="AMPK complex, alpha2-beta2-gamma1 variant"/>
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        <property type="entry name" value="AMPK complex, alpha2-beta2-gamma3 variant"/>
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        <property type="entry name" value="AMPK complex, alpha2-beta1-gamma3 variant"/>
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        <property type="entry name" value="AMPK complex, alpha2-beta1-gamma2 variant"/>
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        <property type="entry name" value="AMPK complex, alpha2-beta2-gamma2 variant"/>
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        <property type="generic name" value="Acetylsalicylic acid"/>
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    <dbReference type="DrugBank" id="DB00131">
        <property type="generic name" value="Adenosine phosphate"/>
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    <dbReference type="DrugBank" id="DB12010">
        <property type="generic name" value="Fostamatinib"/>
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        <property type="generic name" value="Topiramate"/>
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        <property type="family name" value="the 5'-amp-activated protein kinase (ampk) family"/>
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        <property type="glycosylation" value="2 N-Linked glycans (1 site)"/>
    </dbReference>
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        <property type="glycosylation" value="1 site, 3 glycans"/>
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        <property type="glycosylation" value="2 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site)"/>
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        <property type="entry name" value="Pkinase"/>
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        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF103243">
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    <dbReference type="SUPFAM" id="SSF56112">
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0072">Autophagy</keyword>
    <keyword id="KW-0090">Biological rhythms</keyword>
    <keyword id="KW-0152">Cholesterol biosynthesis</keyword>
    <keyword id="KW-0153">Cholesterol metabolism</keyword>
    <keyword id="KW-0156">Chromatin regulator</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0275">Fatty acid biosynthesis</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0752">Steroid biosynthesis</keyword>
    <keyword id="KW-0753">Steroid metabolism</keyword>
    <keyword id="KW-0756">Sterol biosynthesis</keyword>
    <keyword id="KW-1207">Sterol metabolism</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0879">Wnt signaling pathway</keyword>
    <feature type="chain" id="PRO_0000085594" description="5'-AMP-activated protein kinase catalytic subunit alpha-2">
        <location>
            <begin position="1"/>
            <end position="552"/>
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    <feature type="domain" description="Protein kinase" evidence="4">
        <location>
            <begin position="16"/>
            <end position="268"/>
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    </feature>
    <feature type="region of interest" description="AIS" evidence="2">
        <location>
            <begin position="291"/>
            <end position="376"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="477"/>
            <end position="521"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="480"/>
            <end position="490"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="501"/>
            <end position="510"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="511"/>
            <end position="521"/>
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    </feature>
    <feature type="active site" description="Proton acceptor" evidence="4 5">
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="22"/>
            <end position="30"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="45"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by LKB1 and CaMKK2" evidence="13 25 27">
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="41 42 43">
        <location>
            <position position="377"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="491"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035623" description="In breast cancer samples; infiltrating ductal carcinoma; somatic mutation." evidence="14 15">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_040355" description="In a gastric adenocarcinoma sample; somatic mutation." evidence="15">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035624" description="In a breast cancer sample; somatic mutation." evidence="14">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="523"/>
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            <fullName>Putative aspartate aminotransferase, cytoplasmic 2</fullName>
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            <fullName>Glutamate oxaloacetate transaminase 1-like protein 1</fullName>
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        <alternativeName>
            <fullName>Transaminase A-like protein 1</fullName>
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        <name type="primary">GOT1L1</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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    <reference key="1">
        <citation type="journal article" date="2006" name="Nature" volume="439" first="331" last="335">
            <title>DNA sequence and analysis of human chromosome 8.</title>
            <authorList>
                <person name="Nusbaum C."/>
                <person name="Mikkelsen T.S."/>
                <person name="Zody M.C."/>
                <person name="Asakawa S."/>
                <person name="Taudien S."/>
                <person name="Garber M."/>
                <person name="Kodira C.D."/>
                <person name="Schueler M.G."/>
                <person name="Shimizu A."/>
                <person name="Whittaker C.A."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Yang X."/>
                <person name="Allen N.R."/>
                <person name="Anderson S."/>
                <person name="Asakawa T."/>
                <person name="Blechschmidt K."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Butler J."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="DeArellano K."/>
                <person name="DeCaprio D."/>
                <person name="Dooley K.T."/>
                <person name="Dorris L. III"/>
                <person name="Engels R."/>
                <person name="Gloeckner G."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hall J.L."/>
                <person name="Ishikawa S.K."/>
                <person name="Jaffe D.B."/>
                <person name="Kamat A."/>
                <person name="Kudoh J."/>
                <person name="Lehmann R."/>
                <person name="Lokitsang T."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews C.D."/>
                <person name="Mauceli E."/>
                <person name="Menzel U."/>
                <person name="Mihalev A.H."/>
                <person name="Minoshima S."/>
                <person name="Murayama Y."/>
                <person name="Naylor J.W."/>
                <person name="Nicol R."/>
                <person name="Nguyen C."/>
                <person name="O'Leary S.B."/>
                <person name="O'Neill K."/>
                <person name="Parker S.C.J."/>
                <person name="Polley A."/>
                <person name="Raymond C.K."/>
                <person name="Reichwald K."/>
                <person name="Rodriguez J."/>
                <person name="Sasaki T."/>
                <person name="Schilhabel M."/>
                <person name="Siddiqui R."/>
                <person name="Smith C.L."/>
                <person name="Sneddon T.P."/>
                <person name="Talamas J.A."/>
                <person name="Tenzin P."/>
                <person name="Topham K."/>
                <person name="Venkataraman V."/>
                <person name="Wen G."/>
                <person name="Yamazaki S."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Rosenthal A."/>
                <person name="Birren B.W."/>
                <person name="Platzer M."/>
                <person name="Shimizu N."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16421571"/>
            <dbReference type="DOI" id="10.1038/nature04406"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
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            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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            <text>L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate</text>
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            <name>pyridoxal 5'-phosphate</name>
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    <comment type="subunit">
        <text evidence="1">Homodimer.</text>
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            <id>Q8NHS2</id>
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        <interactant intactId="EBI-349819">
            <id>Q5T2W1</id>
            <label>PDZK1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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            <location evidence="1">Cytoplasm</location>
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    </comment>
    <comment type="miscellaneous">
        <text>In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.</text>
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    <comment type="similarity">
        <text evidence="2">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
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        <text evidence="2">The residues that bind the substrate in other aspartate aminotransferases are not conserved.</text>
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    <dbReference type="GeneCards" id="GOT1L1"/>
    <dbReference type="HGNC" id="HGNC:28487">
        <property type="gene designation" value="GOT1L1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000169154">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000169154"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000169154"/>
    <dbReference type="eggNOG" id="KOG1412">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183082"/>
    <dbReference type="HOGENOM" id="CLU_032440_1_2_1"/>
    <dbReference type="InParanoid" id="Q8NHS2"/>
    <dbReference type="OMA" id="MSMIKSK"/>
    <dbReference type="OrthoDB" id="6752799at2759"/>
    <dbReference type="PAN-GO" id="Q8NHS2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NHS2"/>
    <dbReference type="BRENDA" id="2.6.1.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q8NHS2"/>
    <dbReference type="SignaLink" id="Q8NHS2"/>
    <dbReference type="BioGRID-ORCS" id="137362">
        <property type="hits" value="11 hits in 1137 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="137362"/>
    <dbReference type="Pharos" id="Q8NHS2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NHS2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NHS2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000169154">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 36 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8NHS2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004069">
        <property type="term" value="F:L-aspartate:2-oxoglutarate aminotransferase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030170">
        <property type="term" value="F:pyridoxal phosphate binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006532">
        <property type="term" value="P:aspartate biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd00609">
        <property type="entry name" value="AAT_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.640.10:FF:000098">
        <property type="entry name" value="Glutamic-oxaloacetic transaminase 1 like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.1150.10:FF:000306">
        <property type="entry name" value="Glutamic-oxaloacetic transaminase 1-like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.1150.10">
        <property type="entry name" value="Aspartate Aminotransferase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.640.10">
        <property type="entry name" value="Type I PLP-dependent aspartate aminotransferase-like (Major domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004839">
        <property type="entry name" value="Aminotransferase_I/II_large"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000796">
        <property type="entry name" value="Asp_trans"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015424">
        <property type="entry name" value="PyrdxlP-dep_Trfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015421">
        <property type="entry name" value="PyrdxlP-dep_Trfase_major"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015422">
        <property type="entry name" value="PyrdxlP-dep_Trfase_small"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11879">
        <property type="entry name" value="ASPARTATE AMINOTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11879:SF6">
        <property type="entry name" value="ASPARTATE AMINOTRANSFERASE, CYTOPLASMIC 2-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00155">
        <property type="entry name" value="Aminotran_1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00799">
        <property type="entry name" value="TRANSAMINASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53383">
        <property type="entry name" value="PLP-dependent transferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0032">Aminotransferase</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0663">Pyridoxal phosphate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="chain" id="PRO_0000332999" description="Putative aspartate aminotransferase, cytoplasmic 2">
        <location>
            <begin position="1"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-(pyridoxal phosphate)lysine" evidence="1">
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAH29504." evidence="2" ref="2">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="223"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="421" mass="47305" checksum="020AB902540E5B90" modified="2009-11-24" version="2">MPTLSVFMDVPLAHKLEGSLLKTYKQDDYPNKIFLAYRVCMTNEGHPWVSLVVQKTRLQISQDPSLNYEYLPTMGLKSFIQASLALLFGKHSQAIVENRVGGVHTVGDSGAFQLGVQFLRAWHKDARIVYIISSQKELHGLVFQDMGFTVYEYSVWDPKKLCMDPDILLNVVEQIPHGCVLVMGNIIDCKLTPSGWAKLMSMIKSKQIFPFFDIPCQGLYTSDLEEDTRILQYFVSQGFEFFCSQSLSKNFGIYDEGVGMLVVVAVNNQQLLCVLSQLEGLAQALWLNPPNTGARVITSILCNPALLGEWKQSLKEVVENIMLTKEKVKEKLQLLGTPGSWGHITEQSGTHGYLGLNSQQVEYLVRKKHIYIPKNGQINFSCINANNINYITEGINEAVLLTESSEMCLPKEKKTLIGIKL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-08-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P17174</accession>
    <accession>B2R6R7</accession>
    <accession>B7Z7E9</accession>
    <accession>Q5VW80</accession>
    <name>AATC_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10">Aspartate aminotransferase, cytoplasmic</fullName>
            <shortName>cAspAT</shortName>
            <ecNumber evidence="5">2.6.1.1</ecNumber>
            <ecNumber evidence="2">2.6.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Cysteine aminotransferase, cytoplasmic</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Cysteine transaminase, cytoplasmic</fullName>
            <shortName>cCAT</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Glutamate oxaloacetate transaminase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Transaminase A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">GOT1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1990" name="Biochem. J." volume="270" first="651" last="657">
            <title>The amino acid sequence of cytosolic aspartate aminotransferase from human liver.</title>
            <authorList>
                <person name="Doyle J.M."/>
                <person name="Schinina M.E."/>
                <person name="Bossa F."/>
                <person name="Doonan S."/>
            </authorList>
            <dbReference type="PubMed" id="2241899"/>
            <dbReference type="DOI" id="10.1042/bj2700651"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-413</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2005" name="Neurosci. Lett." volume="388" first="49" last="53">
            <title>Amino acids and transaminases activity in ventricular CSF and in brain of normal and Alzheimer patients.</title>
            <authorList>
                <person name="D'Aniello A."/>
                <person name="Fisher G."/>
                <person name="Migliaccio N."/>
                <person name="Cammisa G."/>
                <person name="D'Aniello E."/>
                <person name="Spinelli P."/>
            </authorList>
            <dbReference type="PubMed" id="16039064"/>
            <dbReference type="DOI" id="10.1016/j.neulet.2005.06.030"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="J. Hum. Genet." volume="56" first="801" last="805">
            <title>Genome-wide association study identifies genetic variants in GOT1 determining serum aspartate aminotransferase levels.</title>
            <authorList>
                <person name="Shen H."/>
                <person name="Damcott C."/>
                <person name="Shuldiner S.R."/>
                <person name="Chai S."/>
                <person name="Yang R."/>
                <person name="Hu H."/>
                <person name="Gibson Q."/>
                <person name="Ryan K.A."/>
                <person name="Mitchell B.D."/>
                <person name="Gong D.W."/>
            </authorList>
            <dbReference type="PubMed" id="21900944"/>
            <dbReference type="DOI" id="10.1038/jhg.2011.105"/>
        </citation>
        <scope>INVOLVEMENT IN ASTQTL1</scope>
        <scope>VARIANT ASN-389 DEL</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION OF VARIANT ASN-389 DEL</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2012" name="Early Hum. Dev." volume="88" first="773" last="778">
            <title>Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.</title>
            <authorList>
                <person name="Zlotnik A."/>
                <person name="Tsesis S."/>
                <person name="Gruenbaum B.F."/>
                <person name="Ohayon S."/>
                <person name="Gruenbaum S.E."/>
                <person name="Boyko M."/>
                <person name="Sheiner E."/>
                <person name="Brotfain E."/>
                <person name="Shapira Y."/>
                <person name="Teichberg V.I."/>
            </authorList>
            <dbReference type="PubMed" id="22633534"/>
            <dbReference type="DOI" id="10.1016/j.earlhumdev.2012.05.001"/>
        </citation>
        <scope>FETAL BLOOD LEVELS</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2016" name="Sci. Rep." volume="6" first="36749" last="36749">
            <title>2-Aminobutyric acid modulates glutathione homeostasis in the myocardium.</title>
            <authorList>
                <person name="Irino Y."/>
                <person name="Toh R."/>
                <person name="Nagao M."/>
                <person name="Mori T."/>
                <person name="Honjo T."/>
                <person name="Shinohara M."/>
                <person name="Tsuda S."/>
                <person name="Nakajima H."/>
                <person name="Satomi-Kobayashi S."/>
                <person name="Shinke T."/>
                <person name="Tanaka H."/>
                <person name="Ishida T."/>
                <person name="Miyata O."/>
                <person name="Hirata K.I."/>
            </authorList>
            <dbReference type="PubMed" id="27827456"/>
            <dbReference type="DOI" id="10.1038/srep36749"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="17">
        <citation type="submission" date="2009-08" db="PDB data bank">
            <title>Crystal structure of human glutamate oxaloacetate transaminase 1 (GOT1).</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-412 IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND TARTARIC ACID</scope>
        <scope>SUBUNIT</scope>
        <scope>PYRIDOXAL PHOSPHATE AT LYS-259</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5 7">Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway (PubMed:27827456).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:21824"/>
            <dbReference type="ChEBI" id="CHEBI:16452"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:29991"/>
            <dbReference type="EC" id="2.6.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:21825"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>L-cysteine + 2-oxoglutarate = 2-oxo-3-sulfanylpropanoate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:17441"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:35235"/>
            <dbReference type="ChEBI" id="CHEBI:57678"/>
            <dbReference type="EC" id="2.6.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:17442"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:70223"/>
            <dbReference type="ChEBI" id="CHEBI:16763"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:74359"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="7">
            <dbReference type="Rhea" id="RHEA:70225"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>3-sulfino-L-alanine + 2-oxoglutarate = 3-sulfinopyruvate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:70295"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:61085"/>
            <dbReference type="ChEBI" id="CHEBI:140699"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="2">
            <dbReference type="Rhea" id="RHEA:70297"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>pyridoxal 5'-phosphate</name>
            <dbReference type="ChEBI" id="CHEBI:597326"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="8">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727329">
            <id>P17174</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727329">
            <id>P17174</id>
        </interactant>
        <interactant intactId="EBI-297353">
            <id>P00533</id>
            <label>EGFR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P17174-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P17174-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055799"/>
        </isoform>
    </comment>
    <comment type="polymorphism">
        <text evidence="5">Genetic variations in GOT1 are associated with low serum aspartate aminotransferase and define the aspartate aminotransferase serum level quantitative trait locus 1 (ASTQTL1) [MIM:614419].</text>
    </comment>
    <comment type="miscellaneous">
        <text>In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="11 12">Aspartate aminotransferase activity found to be increased in cerebral spinal fluid (CSF) of patients with Alzheimer disease (PubMed:16039064). Fetal serum levels of the enzyme in the umbilical artery and vein are found to be significantly higher than maternal serum levels (PubMed:22633534).</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
    </comment>
    <dbReference type="EC" id="2.6.1.1" evidence="5"/>
    <dbReference type="EC" id="2.6.1.3" evidence="2"/>
    <dbReference type="EMBL" id="M37400">
        <property type="protein sequence ID" value="AAA35563.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF080467">
        <property type="protein sequence ID" value="AAC32851.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF080459">
        <property type="protein sequence ID" value="AAC32851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAC32851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF052153">
        <property type="protein sequence ID" value="AAC28622.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK301916">
        <property type="protein sequence ID" value="BAH13585.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK312684">
        <property type="protein sequence ID" value="BAG35564.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL391684">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49869.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC000498">
        <property type="protein sequence ID" value="AAH00498.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="P17174-1"/>
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    <dbReference type="PIR" id="S13035">
        <property type="entry name" value="S13035"/>
    </dbReference>
    <dbReference type="PIR" id="S29027">
        <property type="entry name" value="S29027"/>
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    <dbReference type="RefSeq" id="NP_002070.1">
        <molecule id="P17174-1"/>
        <property type="nucleotide sequence ID" value="NM_002079.3"/>
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    <dbReference type="PDB" id="3II0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="A/B/C/D=14-412"/>
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    <dbReference type="PDB" id="3WZF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.99 A"/>
        <property type="chains" value="A=2-413"/>
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    <dbReference type="PDB" id="6DNA">
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        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D/E/F=6-410"/>
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    <dbReference type="PDB" id="6DNB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
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    <dbReference type="PDB" id="6DND">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=3-413"/>
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    <dbReference type="PDB" id="6LIG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.62 A"/>
        <property type="chains" value="A/B=3-413"/>
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    <dbReference type="PDB" id="8Z0E">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.82 A"/>
        <property type="chains" value="A/B=1-413"/>
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    <dbReference type="PDBsum" id="3II0"/>
    <dbReference type="PDBsum" id="3WZF"/>
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    <dbReference type="PDBsum" id="6DND"/>
    <dbReference type="PDBsum" id="6LIG"/>
    <dbReference type="PDBsum" id="8Z0E"/>
    <dbReference type="AlphaFoldDB" id="P17174"/>
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    <dbReference type="FunCoup" id="P17174">
        <property type="interactions" value="2117"/>
    </dbReference>
    <dbReference type="IntAct" id="P17174">
        <property type="interactions" value="194"/>
    </dbReference>
    <dbReference type="MINT" id="P17174"/>
    <dbReference type="STRING" id="9606.ENSP00000359539"/>
    <dbReference type="BindingDB" id="P17174"/>
    <dbReference type="ChEMBL" id="CHEMBL2189139"/>
    <dbReference type="DrugBank" id="DB00210">
        <property type="generic name" value="Adapalene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00128">
        <property type="generic name" value="Aspartic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09130">
        <property type="generic name" value="Copper"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00151">
        <property type="generic name" value="Cysteine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00142">
        <property type="generic name" value="Glutamic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04299">
        <property type="generic name" value="Maleic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00114">
        <property type="generic name" value="Pyridoxal phosphate"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P17174"/>
    <dbReference type="GlyGen" id="P17174">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
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    <feature type="strand" evidence="17">
        <location>
            <begin position="359"/>
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        <location>
            <begin position="368"/>
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        <location>
            <begin position="384"/>
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    <feature type="strand" evidence="17">
        <location>
            <begin position="387"/>
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            <begin position="395"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="398"/>
            <end position="411"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P13221"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="16039064"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="1974457"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="21900944"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="2241899"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="27827456"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source ref="17"/>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
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            <dbReference type="PubMed" id="16039064"/>
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    <evidence type="ECO:0000305" key="12">
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            <dbReference type="PubMed" id="22633534"/>
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    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:4432"/>
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    <evidence type="ECO:0007744" key="14">
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            <dbReference type="PubMed" id="22223895"/>
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    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="3WZF"/>
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    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="6DNA"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="6DNB"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="6LIG"/>
        </source>
    </evidence>
    <sequence length="413" mass="46248" checksum="69FE68BF0C045219" modified="2007-01-23" version="3">MAPPSVFAEVPQAQPVLVFKLTADFREDPDPRKVNLGVGAYRTDDCHPWVLPVVKKVEQKIANDNSLNHEYLPILGLAEFRSCASRLALGDDSPALKEKRVGGVQSLGGTGALRIGADFLARWYNGTNNKNTPVYVSSPTWENHNAVFSAAGFKDIRSYRYWDAEKRGLDLQGFLNDLENAPEFSIVVLHACAHNPTGIDPTPEQWKQIASVMKHRFLFPFFDSAYQGFASGNLERDAWAIRYFVSEGFEFFCAQSFSKNFGLYNERVGNLTVVGKEPESILQVLSQMEKIVRITWSNPPAQGARIVASTLSNPELFEEWTGNVKTMADRILTMRSELRARLEALKTPGTWNHITDQIGMFSFTGLNPKQVEYLVNEKHIYLLPSGRINVSGLTTKNLDYVATSIHEAVTKIQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-07-19" modified="2026-01-28" version="192" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NY61</accession>
    <accession>A6NCJ6</accession>
    <accession>B3KQ26</accession>
    <accession>Q9P0A4</accession>
    <accession>Q9UNX5</accession>
    <name>AATF_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Protein AATF</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Apoptosis-antagonizing transcription factor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Rb-binding protein Che-1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">AATF</name>
        <name type="synonym">CHE1</name>
        <name type="synonym">DED</name>
        <name type="ORF">HSPC277</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Biochem. Biophys. Res. Commun." volume="276" first="660" last="666">
            <title>Identification of novel transcription factor-like gene from human intestinal cells.</title>
            <authorList>
                <person name="Lindfors K."/>
                <person name="Halttunen T."/>
                <person name="Huotari P."/>
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                <person name="Vihinen M."/>
                <person name="Visakorpi T."/>
                <person name="Maki M."/>
                <person name="Kainulainen H."/>
            </authorList>
            <dbReference type="PubMed" id="11027528"/>
            <dbReference type="DOI" id="10.1006/bbrc.2000.3480"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
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                <person name="Fanciulli M."/>
                <person name="Bruno T."/>
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                <person name="Passananti C."/>
            </authorList>
            <dbReference type="PubMed" id="10783144"/>
            <dbReference type="DOI" id="10.1096/fasebj.14.7.904"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>INTERACTION WITH POLR2J AND RB1</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
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                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
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                <person name="Saito K."/>
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                <person name="Iwayanagi T."/>
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                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Takahashi M."/>
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                <person name="Furuya T."/>
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                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
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                <person name="Ono Y."/>
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                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
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                <person name="Sharpe T."/>
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                <person name="Lupski J.R."/>
                <person name="Nicholson C."/>
                <person name="Searle S.M."/>
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                <person name="Young S.K."/>
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                <person name="Bi W."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Bugalter B.E."/>
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                <person name="Cook A."/>
                <person name="Corum B."/>
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                <person name="Dewar K."/>
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                <person name="Gilbert J."/>
                <person name="Gibson R."/>
                <person name="Gnerre S."/>
                <person name="Goldstein S."/>
                <person name="Grafham D.V."/>
                <person name="Grocock R."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
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                <person name="Norman C.H."/>
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                <person name="Kamal M."/>
                <person name="Khodiyar V.K."/>
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                <person name="Laird G."/>
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                <person name="Lokyitsang T."/>
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                <person name="Lui A."/>
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                <person name="Matthews L."/>
                <person name="Mauceli E."/>
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            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <person name="Florea L."/>
                <person name="Halpern A.L."/>
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                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
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                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
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                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
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                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
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                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="submission" date="1999-05" db="EMBL/GenBank/DDBJ databases">
            <title>Human partial CDS from CD34+ stem cells.</title>
            <authorList>
                <person name="Ye M."/>
                <person name="Zhang Q.-H."/>
                <person name="Zhou J."/>
                <person name="Shen Y."/>
                <person name="Wu X.-Y."/>
                <person name="Guan Z.Q."/>
                <person name="Wang L."/>
                <person name="Fan H.-Y."/>
                <person name="Mao Y.-F."/>
                <person name="Dai M."/>
                <person name="Huang Q.-H."/>
                <person name="Chen S.-J."/>
                <person name="Chen Z."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 361-560</scope>
        <source>
            <tissue>Umbilical cord blood</tissue>
        </source>
    </reference>
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            <title>Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb.</title>
            <authorList>
                <person name="Bruno T."/>
                <person name="De Angelis R."/>
                <person name="De Nicola F."/>
                <person name="Barbato C."/>
                <person name="Di Padova M."/>
                <person name="Corbi N."/>
                <person name="Libri V."/>
                <person name="Benassi B."/>
                <person name="Mattei E."/>
                <person name="Chersi A."/>
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                <person name="Passananti C."/>
                <person name="Fanciulli M."/>
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            <dbReference type="PubMed" id="12450794"/>
            <dbReference type="DOI" id="10.1016/s1535-6108(02)00182-4"/>
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        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT THE G1/S TRANSITION</scope>
        <scope>INTERACTION WITH RB1; RBL1 AND RBL2</scope>
    </reference>
    <reference key="9">
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            <authorList>
                <person name="Scherl A."/>
                <person name="Coute Y."/>
                <person name="Deon C."/>
                <person name="Calle A."/>
                <person name="Kindbeiter K."/>
                <person name="Sanchez J.-C."/>
                <person name="Greco A."/>
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            </authorList>
            <dbReference type="PubMed" id="12429849"/>
            <dbReference type="DOI" id="10.1091/mbc.e02-05-0271"/>
        </citation>
        <scope>SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter.</title>
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                <person name="Di Padova M."/>
                <person name="Bruno T."/>
                <person name="De Nicola F."/>
                <person name="Iezzi S."/>
                <person name="D'Angelo C."/>
                <person name="Gallo R."/>
                <person name="Nicosia D."/>
                <person name="Corbi N."/>
                <person name="Biroccio A."/>
                <person name="Floridi A."/>
                <person name="Passananti C."/>
                <person name="Fanciulli M."/>
            </authorList>
            <dbReference type="PubMed" id="12847090"/>
            <dbReference type="DOI" id="10.1074/jbc.m306694200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH SP1</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2003" name="Mol. Cell. Neurosci." volume="24" first="1038" last="1050">
            <title>Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons. Modulation during neuronal apoptosis.</title>
            <authorList>
                <person name="Barbato C."/>
                <person name="Corbi N."/>
                <person name="Canu N."/>
                <person name="Fanciulli M."/>
                <person name="Serafino A."/>
                <person name="Ciotti M."/>
                <person name="Libri V."/>
                <person name="Bruno T."/>
                <person name="Amadoro G."/>
                <person name="De Angelis R."/>
                <person name="Calissano P."/>
                <person name="Passananti C."/>
            </authorList>
            <dbReference type="PubMed" id="14697667"/>
            <dbReference type="DOI" id="10.1016/j.mcn.2003.08.002"/>
        </citation>
        <scope>INTERACTION WITH MAPT</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="4596" last="4603">
            <title>AATF inhibits aberrant production of amyloid beta peptide 1-42 by interacting directly with Par-4.</title>
            <authorList>
                <person name="Guo Q."/>
                <person name="Xie J."/>
            </authorList>
            <dbReference type="PubMed" id="14627703"/>
            <dbReference type="DOI" id="10.1074/jbc.m309811200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PAWR</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2004" name="Neurobiol. Dis." volume="16" first="150" last="157">
            <title>AATF protects neural cells against oxidative damage induced by amyloid beta-peptide.</title>
            <authorList>
                <person name="Xie J."/>
                <person name="Guo Q."/>
            </authorList>
            <dbReference type="PubMed" id="15207272"/>
            <dbReference type="DOI" id="10.1016/j.nbd.2004.02.003"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316; SER-320 AND SER-321</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
            <authorList>
                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316; SER-320 AND SER-321</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-316; SER-320 AND SER-321</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-316; SER-320 AND SER-321</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61; SER-63; SER-150; SER-155; SER-203 AND SER-273</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference evidence="13 14" key="20">
        <citation type="journal article" date="2021" name="Science" volume="373" first="eabj5338" last="eabj5338">
            <title>Nucleolar maturation of the human small subunit processome.</title>
            <authorList>
                <person name="Singh S."/>
                <person name="Vanden Broeck A."/>
                <person name="Miller L."/>
                <person name="Chaker-Margot M."/>
                <person name="Klinge S."/>
            </authorList>
            <dbReference type="PubMed" id="34516797"/>
            <dbReference type="DOI" id="10.1126/science.abj5338"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 9 10">Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 5 6 7 8 10">Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Interacts with POLR2J, RB1/RB, RBL1/P107 and RBL2/P130 (PubMed:10783144, PubMed:12450794). Interacts with PAWR and SP1 (PubMed:12847090, PubMed:14627703). May also bind MAPT (PubMed:14697667).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-495465">
            <id>Q13315</id>
            <label>ATM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-1180783">
            <id>O96017</id>
            <label>CHEK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-477622">
            <id>Q92830</id>
            <label>KAT2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-743811">
            <id>Q8NEH6</id>
            <label>MNS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-9995414">
            <id>Q8NEJ9</id>
            <label>NGDN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-9090282">
            <id>P27986-2</id>
            <label>PIK3R1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-394753">
            <id>P52435</id>
            <label>POLR2J</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-413628">
            <id>P63000</id>
            <label>RAC1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-745715">
            <id>Q99708</id>
            <label>RBBP8</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-73886">
            <id>Q04206</id>
            <label>RELA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
        </interactant>
        <interactant intactId="EBI-298336">
            <id>P08047</id>
            <label>SP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-742268">
            <id>O75478</id>
            <label>TADA2A</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-2512219">
            <id>Q86TJ2</id>
            <label>TADA2B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-473249">
            <id>O75528</id>
            <label>TADA3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-372428">
            <id>Q9NY61</id>
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        <interactant intactId="EBI-8034418">
            <id>Q6ZWQ9</id>
            <label>Myl12a</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 10">Nucleus</location>
            <location evidence="4 10">Nucleolus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 3">Ubiquitously expressed. Expressed at high levels in brain, heart, kidney, placenta and thymus.</text>
    </comment>
    <comment type="PTM">
        <text>Hyperphosphorylated during the G1/S phase transition.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the AATF family.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAD52016" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/534/AATF"/>
    </comment>
    <dbReference type="EMBL" id="AJ249940">
        <property type="protein sequence ID" value="CAB57451.2"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAG51888.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC003103">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471199">
        <property type="protein sequence ID" value="EAW57575.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC000591">
        <property type="protein sequence ID" value="AAH00591.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAF28955.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_012138.4"/>
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    <dbReference type="PDB" id="5W6A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.74 A"/>
        <property type="chains" value="E/F=539-547"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="NN=1-560"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.87 A"/>
        <property type="chains" value="NN=1-560"/>
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        <property type="glycosylation" value="4 sites, 1 O-linked glycan (4 sites)"/>
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        <property type="antibodies" value="347 antibodies from 37 providers"/>
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        <property type="gene ID" value="ENSG00000275700.7"/>
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        <property type="gene ID" value="ENSG00000276072.2"/>
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        <property type="RefSeq protein sequence ID" value="NP_036270.1"/>
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        <property type="gene designation" value="AATF"/>
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            <fullName evidence="7">Alpha/beta hydrolase domain-containing protein 17B</fullName>
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        <name evidence="8" type="primary">ABHD17B</name>
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            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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                <person name="Keenan S."/>
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                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
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                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
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                <person name="Tracey A."/>
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                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT LYS-169</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Elife" volume="4" first="E11306" last="E11306">
            <title>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</title>
            <authorList>
                <person name="Lin D.T."/>
                <person name="Conibear E."/>
            </authorList>
            <dbReference type="PubMed" id="26701913"/>
            <dbReference type="DOI" id="10.7554/elife.11306"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2 5">Hydrolyzes fatty acids from S-acylated cysteine residues in proteins (PubMed:26701913). Has depalmitoylating activity towards DLG4/PSD95 (PubMed:26701913). Has depalmitoylating activity towards GAP43 (By similarity). Has depalmitoylating activity towards MAP6 (By similarity). Has depalmitoylating activity towards NRAS (PubMed:26701913).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19233"/>
            <dbReference type="Rhea" id="RHEA-COMP:10131"/>
            <dbReference type="Rhea" id="RHEA-COMP:11032"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29950"/>
            <dbReference type="ChEBI" id="CHEBI:74151"/>
            <dbReference type="EC" id="3.1.2.22"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="5">Inhibited by palmostatin-B.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cell membrane</location>
            <topology evidence="2">Lipid-anchor</topology>
            <orientation evidence="2">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Recycling endosome membrane</location>
            <topology evidence="2">Lipid-anchor</topology>
            <orientation evidence="2">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Dendritic spine</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Postsynaptic density membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5VST6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5VST6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_023975"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="2">Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization. Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily. ABHD17 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.22" evidence="5"/>
    <dbReference type="EMBL" id="AF151825">
        <property type="protein sequence ID" value="AAD34062.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293060">
        <property type="protein sequence ID" value="BAF85749.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138751">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL671309">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471089">
        <property type="protein sequence ID" value="EAW62521.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC038390">
        <property type="protein sequence ID" value="AAH38390.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC044576">
        <property type="protein sequence ID" value="AAH44576.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS35042.1">
        <molecule id="Q5VST6-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS35043.1">
        <molecule id="Q5VST6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001020951.1">
        <molecule id="Q5VST6-1"/>
        <property type="nucleotide sequence ID" value="NM_001025780.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057098.2">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="NM_016014.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006717197.2">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_006717134.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016870276.1">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_017014787.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016870277.1">
        <molecule id="Q5VST6-1"/>
        <property type="nucleotide sequence ID" value="XM_017014788.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016870278.1">
        <molecule id="Q5VST6-1"/>
        <property type="nucleotide sequence ID" value="XM_017014789.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047279402.1">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_047423446.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054219026.1">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_054363051.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054219027.1">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_054363052.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054219028.1">
        <molecule id="Q5VST6-2"/>
        <property type="nucleotide sequence ID" value="XM_054363053.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054219029.1">
        <molecule id="Q5VST6-1"/>
        <property type="nucleotide sequence ID" value="XM_054363054.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054219030.1">
        <molecule id="Q5VST6-1"/>
        <property type="nucleotide sequence ID" value="XM_054363055.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VST6"/>
    <dbReference type="SMR" id="Q5VST6"/>
    <dbReference type="BioGRID" id="119293">
        <property type="interactions" value="63"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5VST6">
        <property type="interactions" value="1807"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5VST6">
        <property type="interactions" value="57"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000366240"/>
    <dbReference type="ChEMBL" id="CHEMBL2189132"/>
    <dbReference type="ESTHER" id="human-ABHD17B">
        <property type="family name" value="ABHD17-depalmitoylase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.055"/>
    <dbReference type="iPTMnet" id="Q5VST6"/>
    <dbReference type="PhosphoSitePlus" id="Q5VST6"/>
    <dbReference type="SwissPalm" id="Q5VST6"/>
    <dbReference type="BioMuta" id="ABHD17B"/>
    <dbReference type="DMDM" id="74746845"/>
    <dbReference type="jPOST" id="Q5VST6"/>
    <dbReference type="MassIVE" id="Q5VST6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000366240"/>
    <dbReference type="PeptideAtlas" id="Q5VST6"/>
    <dbReference type="ProteomicsDB" id="65278">
        <molecule id="Q5VST6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65279">
        <molecule id="Q5VST6-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q5VST6"/>
    <dbReference type="Antibodypedia" id="26944">
        <property type="antibodies" value="32 antibodies from 13 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51104"/>
    <dbReference type="Ensembl" id="ENST00000333421.7">
        <molecule id="Q5VST6-1"/>
        <property type="protein sequence ID" value="ENSP00000330222.6"/>
        <property type="gene ID" value="ENSG00000107362.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377041.6">
        <molecule id="Q5VST6-2"/>
        <property type="protein sequence ID" value="ENSP00000366240.2"/>
        <property type="gene ID" value="ENSG00000107362.15"/>
    </dbReference>
    <dbReference type="GeneID" id="51104"/>
    <dbReference type="KEGG" id="hsa:51104"/>
    <dbReference type="MANE-Select" id="ENST00000333421.7">
        <property type="protein sequence ID" value="ENSP00000330222.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001025780.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001020951.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004ail.4">
        <molecule id="Q5VST6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24278"/>
    <dbReference type="ClinPGx" id="PA162385624"/>
    <dbReference type="CTD" id="51104"/>
    <dbReference type="GeneCards" id="ABHD17B"/>
    <dbReference type="HGNC" id="HGNC:24278">
        <property type="gene designation" value="ABHD17B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000107362">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="617943">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000107362"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000107362"/>
    <dbReference type="eggNOG" id="KOG1552">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157611"/>
    <dbReference type="HOGENOM" id="CLU_029375_5_4_1"/>
    <dbReference type="InParanoid" id="Q5VST6"/>
    <dbReference type="OMA" id="GENIYML"/>
    <dbReference type="OrthoDB" id="446723at2759"/>
    <dbReference type="PAN-GO" id="Q5VST6">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VST6"/>
    <dbReference type="PathwayCommons" id="Q5VST6"/>
    <dbReference type="Reactome" id="R-HSA-9648002">
        <property type="pathway name" value="RAS processing"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q5VST6"/>
    <dbReference type="Agora" id="ENSG00000107362"/>
    <dbReference type="BioGRID-ORCS" id="51104">
        <property type="hits" value="18 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD17B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="51104"/>
    <dbReference type="Pharos" id="Q5VST6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VST6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VST6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000107362">
        <property type="expression patterns" value="Expressed in endothelial cell and 183 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5VST6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043197">
        <property type="term" value="C:dendritic spine"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010008">
        <property type="term" value="C:endosome membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098839">
        <property type="term" value="C:postsynaptic density membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098944">
        <property type="term" value="C:postsynaptic recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055038">
        <property type="term" value="C:recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902817">
        <property type="term" value="P:negative regulation of protein localization to microtubule"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905668">
        <property type="term" value="P:positive regulation of protein localization to endosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002084">
        <property type="term" value="P:protein depalmitoylation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902950">
        <property type="term" value="P:regulation of dendritic spine maintenance"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099175">
        <property type="term" value="P:regulation of postsynapse organization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902473">
        <property type="term" value="P:regulation of protein localization to synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000008">
        <property type="entry name" value="Alpha/beta hydrolase domain-containing protein 17B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR022742">
        <property type="entry name" value="Hydrolase_4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF48">
        <property type="entry name" value="ALPHA_BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12146">
        <property type="entry name" value="Hydrolase_4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <feature type="chain" id="PRO_0000281111" description="Alpha/beta hydrolase domain-containing protein 17B">
        <location>
            <begin position="1"/>
            <end position="288"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="3">
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023975" description="In isoform 2." evidence="6">
        <original>NL</original>
        <variation>QKHKEGK</variation>
        <location>
            <begin position="287"/>
            <end position="288"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054080" description="In dbSNP:rs12380380.">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031230" description="In dbSNP:rs17854317." evidence="4">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD34062." evidence="7" ref="1">
        <original>CPGK</original>
        <variation>LSGE</variation>
        <location>
            <begin position="18"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD34062." evidence="7" ref="1">
        <original>GS</original>
        <variation>RT</variation>
        <location>
            <begin position="43"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD34062." evidence="7" ref="1">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O75608"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q7M759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q96GS6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="26701913"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="10810093"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:24278"/>
        </source>
    </evidence>
    <sequence length="288" mass="32215" checksum="F315AF711AF532BD" modified="2004-12-07" version="1">MNNLSFSELCCLFCCPPCPGKIASKLAFLPPDPTYTLMCDESGSRWTLHLSERADWQYSSREKDAIECFMTRTSKGNRIACMFVRCSPNAKYTLLFSHGNAVDLGQMSSFYIGLGSRINCNIFSYDYSGYGASSGKPTEKNLYADIEAAWLALRTRYGIRPENVIIYGQSIGTVPSVDLAARYESAAVILHSPLTSGMRVAFPDTKKTYCFDAFPNIDKISKITSPVLIIHGTEDEVIDFSHGLALFERCQRPVEPLWVEGAGHNDVELYGQYLERLKQFVSQELVNL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-08-21" modified="2026-01-28" version="148" xmlns="https://uniprot.org/uniprot">
    <accession>Q6PCB6</accession>
    <accession>Q1RMD6</accession>
    <accession>Q9NPM1</accession>
    <name>AB17C_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">Alpha/beta hydrolase domain-containing protein 17C</fullName>
            <shortName evidence="9">Abhydrolase domain-containing protein 17C</shortName>
            <ecNumber evidence="6">3.1.2.22</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ABHD17C</name>
        <name type="synonym">FAM108C1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Embryonic stem cell</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2000-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="The European IMAGE consortium"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-329</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2015" name="Elife" volume="4" first="E11306" last="E11306">
            <title>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</title>
            <authorList>
                <person name="Lin D.T."/>
                <person name="Conibear E."/>
            </authorList>
            <dbReference type="PubMed" id="26701913"/>
            <dbReference type="DOI" id="10.7554/elife.11306"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards NRAS and DLG4/PSD95.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19233"/>
            <dbReference type="Rhea" id="RHEA-COMP:10131"/>
            <dbReference type="Rhea" id="RHEA-COMP:11032"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29950"/>
            <dbReference type="ChEBI" id="CHEBI:74151"/>
            <dbReference type="EC" id="3.1.2.22"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="6">Inhibited by palmostatin-B.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-640741">
            <id>P01023</id>
            <label>A2M</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-21535880">
            <id>Q92870-2</id>
            <label>APBB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-946046">
            <id>P54252</id>
            <label>ATXN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-10968534">
            <id>P50570-2</id>
            <label>DNM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>21</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-1189067">
            <id>P51608</id>
            <label>MECP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-748974">
            <id>Q96CV9</id>
            <label>OPTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-752057">
            <id>Q7Z412</id>
            <label>PEX26</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-721853">
            <id>O14832</id>
            <label>PHYH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-50433196">
            <id>A0A6Q8PF08</id>
            <label>PMP22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-395421">
            <id>Q16637</id>
            <label>SMN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-985879">
            <id>P37840</id>
            <label>SNCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-524257">
            <id>O14656</id>
            <label>TOR1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-22011868">
            <id>Q6PCB6</id>
        </interactant>
        <interactant intactId="EBI-25847109">
            <id>O14656-2</id>
            <label>TOR1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Recycling endosome membrane</location>
            <topology evidence="1">Lipid-anchor</topology>
            <orientation evidence="1">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Dendritic spine</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Postsynaptic density membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6PCB6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6PCB6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_027273"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="3">Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization. Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the AB hydrolase superfamily. ABHD17 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.22" evidence="6"/>
    <dbReference type="EMBL" id="BC059401">
        <property type="protein sequence ID" value="AAH59401.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC115003">
        <property type="protein sequence ID" value="AAI15004.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390079">
        <property type="protein sequence ID" value="CAB98203.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45323.1">
        <molecule id="Q6PCB6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_067037.1">
        <molecule id="Q6PCB6-1"/>
        <property type="nucleotide sequence ID" value="NM_021214.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6PCB6"/>
    <dbReference type="SMR" id="Q6PCB6"/>
    <dbReference type="BioGRID" id="121819">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6PCB6">
        <property type="interactions" value="159"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6PCB6">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000258884"/>
    <dbReference type="ESTHER" id="human-ABHD17C">
        <property type="family name" value="ABHD17-depalmitoylase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.053"/>
    <dbReference type="iPTMnet" id="Q6PCB6"/>
    <dbReference type="PhosphoSitePlus" id="Q6PCB6"/>
    <dbReference type="SwissPalm" id="Q6PCB6"/>
    <dbReference type="BioMuta" id="ABHD17C"/>
    <dbReference type="DMDM" id="156630444"/>
    <dbReference type="jPOST" id="Q6PCB6"/>
    <dbReference type="MassIVE" id="Q6PCB6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000258884"/>
    <dbReference type="PeptideAtlas" id="Q6PCB6"/>
    <dbReference type="ProteomicsDB" id="67058">
        <molecule id="Q6PCB6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="67059">
        <molecule id="Q6PCB6-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q6PCB6"/>
    <dbReference type="Antibodypedia" id="63038">
        <property type="antibodies" value="56 antibodies from 14 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="58489"/>
    <dbReference type="Ensembl" id="ENST00000258884.5">
        <molecule id="Q6PCB6-1"/>
        <property type="protein sequence ID" value="ENSP00000258884.4"/>
        <property type="gene ID" value="ENSG00000136379.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000558464.1">
        <molecule id="Q6PCB6-2"/>
        <property type="protein sequence ID" value="ENSP00000452778.1"/>
        <property type="gene ID" value="ENSG00000136379.13"/>
    </dbReference>
    <dbReference type="GeneID" id="58489"/>
    <dbReference type="KEGG" id="hsa:58489"/>
    <dbReference type="MANE-Select" id="ENST00000258884.5">
        <property type="protein sequence ID" value="ENSP00000258884.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_021214.2"/>
        <property type="RefSeq protein sequence ID" value="NP_067037.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002bfu.4">
        <molecule id="Q6PCB6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:26925"/>
    <dbReference type="ClinPGx" id="PA162385639"/>
    <dbReference type="CTD" id="58489"/>
    <dbReference type="DisGeNET" id="58489"/>
    <dbReference type="GeneCards" id="ABHD17C"/>
    <dbReference type="HGNC" id="HGNC:26925">
        <property type="gene designation" value="ABHD17C"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000136379">
        <property type="expression patterns" value="Tissue enhanced (intestine)"/>
    </dbReference>
    <dbReference type="MIM" id="617944">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000136379"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000136379"/>
    <dbReference type="eggNOG" id="KOG1552">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159424"/>
    <dbReference type="HOGENOM" id="CLU_029375_5_4_1"/>
    <dbReference type="InParanoid" id="Q6PCB6"/>
    <dbReference type="OMA" id="YSEREKX"/>
    <dbReference type="OrthoDB" id="446723at2759"/>
    <dbReference type="PAN-GO" id="Q6PCB6">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6PCB6"/>
    <dbReference type="PathwayCommons" id="Q6PCB6"/>
    <dbReference type="Reactome" id="R-HSA-9648002">
        <property type="pathway name" value="RAS processing"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6PCB6"/>
    <dbReference type="Agora" id="ENSG00000136379"/>
    <dbReference type="BioGRID-ORCS" id="58489">
        <property type="hits" value="11 hits in 1144 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD17C">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="58489"/>
    <dbReference type="Pharos" id="Q6PCB6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6PCB6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6PCB6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000136379">
        <property type="expression patterns" value="Expressed in ileal mucosa and 145 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6PCB6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043197">
        <property type="term" value="C:dendritic spine"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010008">
        <property type="term" value="C:endosome membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098839">
        <property type="term" value="C:postsynaptic density membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055038">
        <property type="term" value="C:recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902817">
        <property type="term" value="P:negative regulation of protein localization to microtubule"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905668">
        <property type="term" value="P:positive regulation of protein localization to endosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002084">
        <property type="term" value="P:protein depalmitoylation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099175">
        <property type="term" value="P:regulation of postsynapse organization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000008">
        <property type="entry name" value="Alpha/beta hydrolase domain-containing protein 17B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR022742">
        <property type="entry name" value="Hydrolase_4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF55">
        <property type="entry name" value="ALPHA_BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12146">
        <property type="entry name" value="Hydrolase_4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <feature type="chain" id="PRO_0000297513" description="Alpha/beta hydrolase domain-containing protein 17C">
        <location>
            <begin position="1"/>
            <end position="329"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="53"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="53"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="4">
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="2">
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="2">
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027273" description="In isoform 2." evidence="7">
        <location>
            <begin position="223"/>
            <end position="256"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="B5DFK7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="O75608"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q7M759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q96GS6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="26701913"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:26925"/>
        </source>
    </evidence>
    <sequence length="329" mass="35831" checksum="A5EE8ED4291EC49F" modified="2007-05-15" version="2">MPEPGPRMNGFSLGELCWLFCCPPCPSRIAAKLAFLPPEPTYTVLAPEQRGAGASAPAPAQATAAAAAAQPAPQQPEEGAGAGPGACSLHLSERADWQYSQRELDAVEVFFSRTARDNRLGCMFVRCAPSSRYTLLFSHGNAVDLGQMCSFYIGLGSRINCNIFSYDYSGYGVSSGKPSEKNLYADIDAAWQALRTRYGVSPENIILYGQSIGTVPTVDLASRYECAAVILHSPLMSGLRVAFPDTRKTYCFDAFPSIDKISKVTSPVLVIHGTEDEVIDFSHGLAMYERCPRAVEPLWVEGAGHNDIELYAQYLERLKQFISHELPNS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="241" xmlns="https://uniprot.org/uniprot">
    <accession>P00505</accession>
    <accession>B4DJA6</accession>
    <accession>E7ERW2</accession>
    <accession>Q53FL3</accession>
    <accession>Q9BWA3</accession>
    <name>AATM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aspartate aminotransferase, mitochondrial</fullName>
            <shortName>mAspAT</shortName>
            <ecNumber evidence="7 8">2.6.1.1</ecNumber>
            <ecNumber evidence="2">2.6.1.7</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Fatty acid-binding protein</fullName>
            <shortName>FABP-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Glutamate oxaloacetate transaminase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Kynurenine aminotransferase 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Kynurenine aminotransferase IV</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Kynurenine--oxoglutarate transaminase 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Kynurenine--oxoglutarate transaminase IV</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Plasma membrane-associated fatty acid-binding protein</fullName>
            <shortName>FABPpm</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Transaminase A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">GOT2</name>
        <name evidence="14" type="synonym">KYAT4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Nucleotide sequence and tissue distribution of the human mitochondrial aspartate aminotransferase mRNA.</title>
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                <person name="Pol S."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT GLY-346</scope>
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                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
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                <person name="Wakebe H."/>
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                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
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                <person name="Kumagai A."/>
                <person name="Itakura S."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
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                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Isogai T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT GLY-346</scope>
        <source>
            <tissue>Subthalamic nucleus</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
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        </source>
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                <person name="Rubin E.M."/>
                <person name="Pennacchio L.A."/>
            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-428</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1985" name="Biochim. Biophys. Acta" volume="832" first="46" last="51">
            <title>The primary structure of mitochondrial aspartate aminotransferase from human heart.</title>
            <authorList>
                <person name="Martini F."/>
                <person name="Angelaccio S."/>
                <person name="Barra D."/>
                <person name="Pascarella S."/>
                <person name="Maras B."/>
                <person name="Doonan S."/>
                <person name="Bossa F."/>
            </authorList>
            <dbReference type="PubMed" id="4052435"/>
            <dbReference type="DOI" id="10.1016/0167-4838(85)90172-4"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 30-430</scope>
        <scope>VARIANT GLY-346</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1998" name="Hepatology" volume="27" first="1064" last="1074">
            <title>Ethanol up-regulates fatty acid uptake and plasma membrane expression and export of mitochondrial aspartate aminotransferase in HepG2 cells.</title>
            <authorList>
                <person name="Zhou S.L."/>
                <person name="Gordon R.E."/>
                <person name="Bradbury M."/>
                <person name="Stump D."/>
                <person name="Kiang C.L."/>
                <person name="Berk P.D."/>
            </authorList>
            <dbReference type="PubMed" id="9537447"/>
            <dbReference type="DOI" id="10.1002/hep.510270423"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-73; LYS-90; LYS-159; LYS-234; LYS-296; LYS-396 AND LYS-404</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143 AND THR-333</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-48; TYR-96; SER-143 AND THR-333</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER ALA-29</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2019" name="Am. J. Hum. Genet." volume="105" first="534" last="548">
            <title>Bi-allelic GOT2 mutations cause a treatable malate-aspartate shuttle-related encephalopathy.</title>
            <authorList>
                <person name="van Karnebeek C.D.M."/>
                <person name="Ramos R.J."/>
                <person name="Wen X.Y."/>
                <person name="Tarailo-Graovac M."/>
                <person name="Gleeson J.G."/>
                <person name="Skrypnyk C."/>
                <person name="Brand-Arzamendi K."/>
                <person name="Karbassi F."/>
                <person name="Issa M.Y."/>
                <person name="van der Lee R."/>
                <person name="Droegemoeller B.I."/>
                <person name="Koster J."/>
                <person name="Rousseau J."/>
                <person name="Campeau P.M."/>
                <person name="Wang Y."/>
                <person name="Cao F."/>
                <person name="Li M."/>
                <person name="Ruiter J."/>
                <person name="Ciapaite J."/>
                <person name="Kluijtmans L.A.J."/>
                <person name="Willemsen M.A.A.P."/>
                <person name="Jans J.J."/>
                <person name="Ross C.J."/>
                <person name="Wintjes L.T."/>
                <person name="Rodenburg R.J."/>
                <person name="Huigen M.C.D.G."/>
                <person name="Jia Z."/>
                <person name="Waterham H.R."/>
                <person name="Wasserman W.W."/>
                <person name="Wanders R.J.A."/>
                <person name="Verhoeven-Duif N.M."/>
                <person name="Zaki M.S."/>
                <person name="Wevers R.A."/>
            </authorList>
            <dbReference type="PubMed" id="31422819"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2019.07.015"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INVOLVEMENT IN DEE82</scope>
        <scope>VARIANTS DEE82 LEU-209 DEL; GLY-262; GLY-337 AND VAL-366</scope>
        <scope>CHARACTERIZATION OF VARIANTS DEE82 GLY-262 AND VAL-366</scope>
    </reference>
    <reference evidence="15" key="14">
        <citation type="journal article" date="2016" name="Biosci. Trends" volume="10" first="79" last="84">
            <title>Recombinant expression, purification and crystallographic studies of the mature form of human mitochondrial aspartate aminotransferase.</title>
            <authorList>
                <person name="Jiang X."/>
                <person name="Wang J."/>
                <person name="Chang H."/>
                <person name="Zhou Y."/>
            </authorList>
            <dbReference type="PubMed" id="26902786"/>
            <dbReference type="DOI" id="10.5582/bst.2015.01150"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.99 ANGSTROMS) OF 30-430</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="8 11">Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate</text>
            <dbReference type="Rhea" id="RHEA:21824"/>
            <dbReference type="ChEBI" id="CHEBI:16452"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:29991"/>
            <dbReference type="EC" id="2.6.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + H2O</text>
            <dbReference type="Rhea" id="RHEA:65560"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16810"/>
            <dbReference type="ChEBI" id="CHEBI:29985"/>
            <dbReference type="ChEBI" id="CHEBI:57959"/>
            <dbReference type="ChEBI" id="CHEBI:58454"/>
            <dbReference type="EC" id="2.6.1.7"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>pyridoxal 5'-phosphate</name>
            <dbReference type="ChEBI" id="CHEBI:597326"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <phDependence>
            <text evidence="7">Optimum pH is 8.5.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="7">Optimum temperature is 47.5 degrees Celsius.</text>
        </temperatureDependence>
    </comment>
    <comment type="subunit">
        <text>Homodimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Mitochondrion matrix</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11">Cell membrane</location>
        </subcellularLocation>
        <text evidence="11">Exposure to alcohol promotes translocation to the cell membrane.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P00505-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P00505-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054848"/>
        </isoform>
    </comment>
    <comment type="induction">
        <text evidence="11">Up-regulated by long-time exposure to alcohol.</text>
    </comment>
    <comment type="disease" evidence="8">
        <disease id="DI-05722">
            <name>Developmental and epileptic encephalopathy 82</name>
            <acronym>DEE82</acronym>
            <description>A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE82 is an autosomal recessive metabolic encephalopathy characterized by epilepsy from the first year of life, global developmental delay, hypotonia and feeding difficulties apparent soon after birth, and intellectual and motor disabilities. Other features include poor overall growth, progressive microcephaly and biochemical abnormalities, including increased serum lactate and ammonia.</description>
            <dbReference type="MIM" id="618721"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.</text>
    </comment>
    <dbReference type="EC" id="2.6.1.1" evidence="7 8"/>
    <dbReference type="EC" id="2.6.1.7" evidence="2"/>
    <dbReference type="EMBL" id="M22632">
        <property type="protein sequence ID" value="AAA35568.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK295993">
        <property type="protein sequence ID" value="BAG58768.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223271">
        <property type="protein sequence ID" value="BAD96991.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012183">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000525">
        <property type="protein sequence ID" value="AAH00525.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10801.1">
        <molecule id="P00505-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS67045.1">
        <molecule id="P00505-2"/>
    </dbReference>
    <dbReference type="PIR" id="A31873">
        <property type="entry name" value="XNHUDM"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273149.1">
        <molecule id="P00505-2"/>
        <property type="nucleotide sequence ID" value="NM_001286220.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002071.2">
        <molecule id="P00505-1"/>
        <property type="nucleotide sequence ID" value="NM_002080.4"/>
    </dbReference>
    <dbReference type="PDB" id="5AX8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.99 A"/>
        <property type="chains" value="A/B/C/D=30-430"/>
    </dbReference>
    <dbReference type="PDB" id="8SKR">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.99 A"/>
        <property type="chains" value="A/C=1-430"/>
    </dbReference>
    <dbReference type="PDBsum" id="5AX8"/>
    <dbReference type="PDBsum" id="8SKR"/>
    <dbReference type="AlphaFoldDB" id="P00505"/>
    <dbReference type="EMDB" id="EMD-40565"/>
    <dbReference type="SMR" id="P00505"/>
    <dbReference type="BioGRID" id="109068">
        <property type="interactions" value="127"/>
    </dbReference>
    <dbReference type="FunCoup" id="P00505">
        <property type="interactions" value="1960"/>
    </dbReference>
    <dbReference type="IntAct" id="P00505">
        <property type="interactions" value="58"/>
    </dbReference>
    <dbReference type="MINT" id="P00505"/>
    <dbReference type="STRING" id="9606.ENSP00000245206"/>
    <dbReference type="BindingDB" id="P00505"/>
    <dbReference type="ChEMBL" id="CHEMBL4524033"/>
    <dbReference type="DrugBank" id="DB02783">
        <property type="generic name" value="4'-Deoxy-4'-Acetylyamino-Pyridoxal-5'-Phosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00128">
        <property type="generic name" value="Aspartic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00151">
        <property type="generic name" value="Cysteine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00142">
        <property type="generic name" value="Glutamic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00114">
        <property type="generic name" value="Pyridoxal phosphate"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P00505"/>
    <dbReference type="TCDB" id="9.A.70.1.1">
        <property type="family name" value="the aspartate amino transferase (aat) family"/>
    </dbReference>
    <dbReference type="GlyGen" id="P00505">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P00505"/>
    <dbReference type="MetOSite" id="P00505"/>
    <dbReference type="PhosphoSitePlus" id="P00505"/>
    <dbReference type="SwissPalm" id="P00505"/>
    <dbReference type="BioMuta" id="GOT2"/>
    <dbReference type="DMDM" id="308153643"/>
    <dbReference type="CPTAC" id="CPTAC-518"/>
    <dbReference type="CPTAC" id="CPTAC-519"/>
    <dbReference type="jPOST" id="P00505"/>
    <dbReference type="MassIVE" id="P00505"/>
    <dbReference type="PaxDb" id="9606-ENSP00000245206"/>
    <dbReference type="PeptideAtlas" id="P00505"/>
    <dbReference type="ProteomicsDB" id="17864"/>
    <dbReference type="ProteomicsDB" id="51258">
        <molecule id="P00505-1"/>
    </dbReference>
    <dbReference type="Pumba" id="P00505"/>
    <dbReference type="TopDownProteomics" id="P00505-1">
        <molecule id="P00505-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="15396">
        <property type="antibodies" value="648 antibodies from 40 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2806"/>
    <dbReference type="Ensembl" id="ENST00000245206.10">
        <molecule id="P00505-1"/>
        <property type="protein sequence ID" value="ENSP00000245206.5"/>
        <property type="gene ID" value="ENSG00000125166.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000434819.2">
        <molecule id="P00505-2"/>
        <property type="protein sequence ID" value="ENSP00000394100.2"/>
        <property type="gene ID" value="ENSG00000125166.14"/>
    </dbReference>
    <dbReference type="GeneID" id="2806"/>
    <dbReference type="KEGG" id="hsa:2806"/>
    <dbReference type="MANE-Select" id="ENST00000245206.10">
        <property type="protein sequence ID" value="ENSP00000245206.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_002080.4"/>
        <property type="RefSeq protein sequence ID" value="NP_002071.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002eof.2">
        <molecule id="P00505-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:4433"/>
    <dbReference type="ClinPGx" id="PA28818"/>
    <dbReference type="CTD" id="2806"/>
    <dbReference type="DisGeNET" id="2806"/>
    <dbReference type="GeneCards" id="GOT2"/>
    <dbReference type="HGNC" id="HGNC:4433">
        <property type="gene designation" value="GOT2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000125166">
        <property type="expression patterns" value="Group enriched (choroid plexus, heart muscle, liver, skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MalaCards" id="GOT2"/>
    <dbReference type="MIM" id="138150">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="618721">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000125166"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000125166"/>
    <dbReference type="eggNOG" id="KOG1411">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183082"/>
    <dbReference type="HOGENOM" id="CLU_032440_1_2_1"/>
    <dbReference type="InParanoid" id="P00505"/>
    <dbReference type="OMA" id="VGACTIV"/>
    <dbReference type="OrthoDB" id="6752799at2759"/>
    <dbReference type="PAN-GO" id="P00505">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P00505"/>
    <dbReference type="BioCyc" id="MetaCyc:HS04858-MONOMER"/>
    <dbReference type="BRENDA" id="2.6.1.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P00505"/>
    <dbReference type="Reactome" id="R-HSA-1614558">
        <property type="pathway name" value="Degradation of cysteine and homocysteine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389661">
        <property type="pathway name" value="Glyoxylate metabolism and glycine degradation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8963693">
        <property type="pathway name" value="Aspartate and asparagine metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8964539">
        <property type="pathway name" value="Glutamate and glutamine metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9856872">
        <property type="pathway name" value="Malate-aspartate shuttle"/>
    </dbReference>
    <dbReference type="SignaLink" id="P00505"/>
    <dbReference type="SIGNOR" id="P00505"/>
    <dbReference type="Agora" id="ENSG00000125166"/>
    <dbReference type="BioGRID-ORCS" id="2806">
        <property type="hits" value="155 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="GOT2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="GOT2"/>
    <dbReference type="GenomeRNAi" id="2806"/>
    <dbReference type="Pharos" id="P00505">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P00505"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
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    <keyword id="KW-0032">Aminotransferase</keyword>
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    <keyword id="KW-0663">Pyridoxal phosphate</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <keyword id="KW-0809">Transit peptide</keyword>
    <keyword id="KW-0813">Transport</keyword>
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        <ligand>
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            <position position="96"/>
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            <position position="143"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="16">
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    <feature type="modified residue" description="N6-(pyridoxal phosphate)lysine; alternate" evidence="1">
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            <position position="279"/>
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        <location>
            <position position="279"/>
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    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="16">
        <location>
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            <position position="296"/>
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            <position position="313"/>
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        <location>
            <position position="333"/>
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            <position position="345"/>
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            <position position="396"/>
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        <location>
            <position position="404"/>
        </location>
    </feature>
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        <location>
            <position position="404"/>
        </location>
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            <begin position="83"/>
            <end position="125"/>
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    </feature>
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        <variation>S</variation>
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            <position position="2"/>
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    <feature type="sequence variant" id="VAR_031710" description="In dbSNP:rs11076256.">
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        <location>
            <position position="188"/>
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            <position position="209"/>
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    <feature type="sequence variant" id="VAR_083489" description="In DEE82; decreased glutamate oxaloacetate transferase activity; dbSNP:rs752927520." evidence="8">
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            <position position="262"/>
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            <position position="337"/>
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            <position position="346"/>
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            <position position="366"/>
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            <position position="428"/>
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            <begin position="110"/>
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    <feature type="sequence conflict" description="In Ref. 6; AA sequence." evidence="13" ref="6">
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            <position position="258"/>
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            <begin position="32"/>
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        </location>
    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="388"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="strand" evidence="20">
        <location>
            <begin position="406"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="410"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="415"/>
            <end position="428"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P00507"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P05202"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P12344"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="26902786"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="31422819"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="3207426"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="4052435"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="9537447"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="HGNC" id="HGNC:4433"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PDB" id="5AX8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="5AX8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="8SKR"/>
        </source>
    </evidence>
    <sequence length="430" mass="47518" checksum="F559567ABF2DB346" modified="2010-10-05" version="3" precursor="true">MALLHSGRVLPGIAAAFHPGLAAAASARASSWWTHVEMGPPDPILGVTEAFKRDTNSKKMNLGVGAYRDDNGKPYVLPSVRKAEAQIAAKNLDKEYLPIGGLAEFCKASAELALGENSEVLKSGRFVTVQTISGTGALRIGASFLQRFFKFSRDVFLPKPTWGNHTPIFRDAGMQLQGYRYYDPKTCGFDFTGAVEDISKIPEQSVLLLHACAHNPTGVDPRPEQWKEIATVVKKRNLFAFFDMAYQGFASGDGDKDAWAVRHFIEQGINVCLCQSYAKNMGLYGERVGAFTMVCKDADEAKRVESQLKILIRPMYSNPPLNGARIAAAILNTPDLRKQWLQEVKVMADRIIGMRTQLVSNLKKEGSTHNWQHITDQIGMFCFTGLKPEQVERLIKEFSIYMTKDGRISVAGVTSSNVGYLAHAIHQVTK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-05" modified="2026-01-28" version="158" xmlns="https://uniprot.org/uniprot">
    <accession>Q7Z5M8</accession>
    <accession>Q3KNR9</accession>
    <accession>Q3KNS0</accession>
    <accession>Q7Z5M6</accession>
    <accession>Q7Z5M7</accession>
    <accession>Q8N4D2</accession>
    <name>AB12B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">Protein ABHD12B</fullName>
            <ecNumber>3.-.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Abhydrolase domain-containing protein 12B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Alpha/beta hydrolase domain-containing protein 12B</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="7" type="primary">ABHD12B</name>
        <name type="synonym">C14orf29</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2003-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and characterization of C14orf29.</title>
            <authorList>
                <person name="Schulz H.L."/>
                <person name="Weber B.H.F."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
                <person name="Pepin K."/>
                <person name="Artiguenave F."/>
                <person name="Robert C."/>
                <person name="Cruaud C."/>
                <person name="Bruels T."/>
                <person name="Jaillon O."/>
                <person name="Friedlander L."/>
                <person name="Samson G."/>
                <person name="Brottier P."/>
                <person name="Cure S."/>
                <person name="Segurens B."/>
                <person name="Aniere F."/>
                <person name="Samain S."/>
                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
                <person name="Dubois I."/>
                <person name="Friedman C."/>
                <person name="Gouyvenoux M."/>
                <person name="James R."/>
                <person name="Madan A."/>
                <person name="Mairey-Estrada B."/>
                <person name="Mangenot S."/>
                <person name="Martins N."/>
                <person name="Menard M."/>
                <person name="Oztas S."/>
                <person name="Ratcliffe A."/>
                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
                <person name="Magdelenat G."/>
                <person name="Pateau E."/>
                <person name="Petit E."/>
                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
                <person name="Vega-Czarny N."/>
                <person name="Bataille E."/>
                <person name="Bluet E."/>
                <person name="Bordelais I."/>
                <person name="Dubois M."/>
                <person name="Dumont C."/>
                <person name="Guerin T."/>
                <person name="Haffray S."/>
                <person name="Hammadi R."/>
                <person name="Muanga J."/>
                <person name="Pellouin V."/>
                <person name="Robert D."/>
                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
                <person name="Roy A."/>
                <person name="Sainte-Marthe L."/>
                <person name="Verdier J."/>
                <person name="Verdier-Discala C."/>
                <person name="Hillier L.W."/>
                <person name="Fulton L."/>
                <person name="McPherson J."/>
                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
                <person name="Waterston R."/>
                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-362 (ISOFORM 1)</scope>
        <scope>VARIANT LEU-334</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] VAL-282</scope>
    </reference>
    <comment type="interaction">
        <interactant intactId="EBI-21854797">
            <id>Q7Z5M8-2</id>
        </interactant>
        <interactant intactId="EBI-21591415">
            <id>P13473-2</id>
            <label>LAMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21854797">
            <id>Q7Z5M8-2</id>
        </interactant>
        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q7Z5M8-1</id>
            <name>1</name>
            <name>Variant 1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q7Z5M8-2</id>
            <name>2</name>
            <name>Variant 3</name>
            <sequence type="described" ref="VSP_010687"/>
        </isoform>
        <isoform>
            <id>Q7Z5M8-4</id>
            <name>4</name>
            <name>Variant 4</name>
            <sequence type="described" ref="VSP_041149 VSP_041150"/>
        </isoform>
        <isoform>
            <id>Q7Z5M8-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_010687 VSP_010688 VSP_010689"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 4</molecule>
        <text evidence="6">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the serine esterase family.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH34603" version="3"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAP78477" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAP78479" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <dbReference type="EC" id="3.-.-.-"/>
    <dbReference type="EMBL" id="AY311396">
        <property type="protein sequence ID" value="AAP78476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY311397">
        <property type="protein sequence ID" value="AAP78477.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY311398">
        <property type="protein sequence ID" value="AAP78478.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY311399">
        <property type="protein sequence ID" value="AAP78479.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK128464">
        <property type="protein sequence ID" value="BAC87452.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL358334">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034603">
        <property type="protein sequence ID" value="AAH34603.3"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC107141">
        <property type="protein sequence ID" value="AAI07142.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC107142">
        <property type="protein sequence ID" value="AAI07143.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS55916.1">
        <molecule id="Q7Z5M8-1"/>
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    <dbReference type="CCDS" id="CCDS9702.1">
        <molecule id="Q7Z5M8-2"/>
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    <dbReference type="RefSeq" id="NP_001193602.1">
        <molecule id="Q7Z5M8-1"/>
        <property type="nucleotide sequence ID" value="NM_001206673.2"/>
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    <dbReference type="RefSeq" id="NP_853511.2">
        <property type="nucleotide sequence ID" value="NM_181533.3"/>
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    <dbReference type="RefSeq" id="NP_861535.1">
        <molecule id="Q7Z5M8-2"/>
        <property type="nucleotide sequence ID" value="NM_181814.2"/>
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    <dbReference type="AlphaFoldDB" id="Q7Z5M8"/>
    <dbReference type="SMR" id="Q7Z5M8"/>
    <dbReference type="BioGRID" id="126913">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q7Z5M8">
        <property type="interactions" value="248"/>
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    <dbReference type="IntAct" id="Q7Z5M8">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000336693"/>
    <dbReference type="ESTHER" id="human-ABHD12B">
        <property type="family name" value="ABHD12-PHARC"/>
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    <dbReference type="MEROPS" id="S09.061"/>
    <dbReference type="GlyCosmos" id="Q7Z5M8">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q7Z5M8">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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    <dbReference type="iPTMnet" id="Q7Z5M8"/>
    <dbReference type="PhosphoSitePlus" id="Q7Z5M8"/>
    <dbReference type="BioMuta" id="ABHD12B"/>
    <dbReference type="DMDM" id="50401854"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000336693"/>
    <dbReference type="PeptideAtlas" id="Q7Z5M8"/>
    <dbReference type="Antibodypedia" id="130">
        <property type="antibodies" value="87 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="145447"/>
    <dbReference type="Ensembl" id="ENST00000337334.7">
        <molecule id="Q7Z5M8-1"/>
        <property type="protein sequence ID" value="ENSP00000336693.2"/>
        <property type="gene ID" value="ENSG00000131969.16"/>
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    <dbReference type="Ensembl" id="ENST00000353130.5">
        <molecule id="Q7Z5M8-2"/>
        <property type="protein sequence ID" value="ENSP00000343951.1"/>
        <property type="gene ID" value="ENSG00000131969.16"/>
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    <dbReference type="Ensembl" id="ENST00000382029.7">
        <molecule id="Q7Z5M8-4"/>
        <property type="protein sequence ID" value="ENSP00000371460.3"/>
        <property type="gene ID" value="ENSG00000131969.16"/>
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    <dbReference type="Ensembl" id="ENST00000557345.5">
        <molecule id="Q7Z5M8-4"/>
        <property type="protein sequence ID" value="ENSP00000450643.1"/>
        <property type="gene ID" value="ENSG00000131969.16"/>
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    <dbReference type="GeneID" id="145447"/>
    <dbReference type="KEGG" id="hsa:145447"/>
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        <property type="protein sequence ID" value="ENSP00000336693.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001206673.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001193602.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001wyq.4">
        <molecule id="Q7Z5M8-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:19837"/>
    <dbReference type="ClinPGx" id="PA162375213"/>
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    <dbReference type="GeneCards" id="ABHD12B"/>
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        <property type="gene designation" value="ABHD12B"/>
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    <dbReference type="HPA" id="ENSG00000131969">
        <property type="expression patterns" value="Group enriched (brain, retina, skin)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000131969"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000131969"/>
    <dbReference type="eggNOG" id="KOG1552">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00940000161597"/>
    <dbReference type="HOGENOM" id="CLU_029375_1_1_1"/>
    <dbReference type="InParanoid" id="Q7Z5M8"/>
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    <dbReference type="OrthoDB" id="10249433at2759"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7Z5M8"/>
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    <dbReference type="Agora" id="ENSG00000131969"/>
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        <property type="hits" value="7 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD12B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="145447"/>
    <dbReference type="Pharos" id="Q7Z5M8">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7Z5M8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7Z5M8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000131969">
        <property type="expression patterns" value="Expressed in upper arm skin and 117 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004622">
        <property type="term" value="F:phosphatidylcholine lysophospholipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052651">
        <property type="term" value="P:monoacylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
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    <dbReference type="GO" id="GO:0006660">
        <property type="term" value="P:phosphatidylserine catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR022742">
        <property type="entry name" value="Hydrolase_4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF69">
        <property type="entry name" value="PROTEIN ABHD12B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12146">
        <property type="entry name" value="Hydrolase_4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089887" description="Protein ABHD12B">
        <location>
            <begin position="1"/>
            <end position="362"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010687" description="In isoform 2 and isoform 5." evidence="3 4 5">
        <location>
            <begin position="36"/>
            <end position="112"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041149" description="In isoform 4." evidence="5">
        <original>YFPHSCSMLGRKIAALYDSFTSKSL</original>
        <variation>QSPISCGFKETRVKDSSHSELLPES</variation>
        <location>
            <begin position="36"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041150" description="In isoform 4." evidence="5">
        <location>
            <begin position="61"/>
            <end position="362"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010688" description="In isoform 5." evidence="3">
        <original>IYRNIPGFLRTLMDALRKDKIIFPNDENVKFLSSPLLILHGEDDRTVPLEYG</original>
        <variation>SLALSSRLECSGVISAHCKLRFPGSRHSPASASRVAGTTGARHHAWLIFLCF</variation>
        <location>
            <begin position="261"/>
            <end position="312"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010689" description="In isoform 5." evidence="3">
        <location>
            <begin position="313"/>
            <end position="362"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035676" description="In a breast cancer sample; somatic mutation; dbSNP:rs28564871." evidence="2">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019100" description="In dbSNP:rs7154732." evidence="1">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="334"/>
        </location>
    </feature>
    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:19837"/>
        </source>
    </evidence>
    <sequence length="362" mass="40776" checksum="D6BD2858CE7C04AA" modified="2003-10-01" version="1">MDAQDCQAAASPEPPGPPARSCVAAWWDMVDRNLRYFPHSCSMLGRKIAALYDSFTSKSLKEHVFLPLIDMLIYFNFFKAPFLVDLKKPELKIPHTVNFYLRVEPGVMLGIWHTVPSCRGEDAKGKDCCWYEAALRDGNPIIVYLHGSAEHRAASHRLKLVKVLSDGGFHVLSVDYRGFGDSTGKPTEEGLTTDAICVYEWTKARSGITPVCLWGHSLGTGVATNAAKVLEEKGCPVDAIVLEAPFTNMWVASINYPLLKIYRNIPGFLRTLMDALRKDKIIFPNDENVKFLSSPLLILHGEDDRTVPLEYGKKLYEIARNAYRNKERVKMVIFPPGFQHNLLCKSPTLLITVRDFLSKQWS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-07-24" modified="2026-01-28" version="180" xmlns="https://uniprot.org/uniprot">
    <accession>Q96GS6</accession>
    <accession>A8K0G8</accession>
    <accession>D6W5Z9</accession>
    <accession>Q6PJU2</accession>
    <accession>Q8WUH9</accession>
    <accession>Q9BWL0</accession>
    <accession>Q9H7Q9</accession>
    <name>AB17A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Alpha/beta hydrolase domain-containing protein 17A</fullName>
            <shortName evidence="9">Abhydrolase domain-containing protein 17A</shortName>
            <ecNumber evidence="4">3.1.2.22</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ABHD17A</name>
        <name type="synonym">C19orf27</name>
        <name type="synonym">FAM108A1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2005" name="DNA Res." volume="12" first="117" last="126">
            <title>Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.</title>
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                <person name="Otsuki T."/>
                <person name="Ota T."/>
                <person name="Nishikawa T."/>
                <person name="Hayashi K."/>
                <person name="Suzuki Y."/>
                <person name="Yamamoto J."/>
                <person name="Wakamatsu A."/>
                <person name="Kimura K."/>
                <person name="Sakamoto K."/>
                <person name="Hatano N."/>
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                <person name="Ishii S."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Embryo</tissue>
        </source>
    </reference>
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        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
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                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Cervix</tissue>
            <tissue>Colon</tissue>
            <tissue>Muscle</tissue>
            <tissue>Ovary</tissue>
            <tissue>Prostate</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Elife" volume="4" first="E11306" last="E11306">
            <title>ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization.</title>
            <authorList>
                <person name="Lin D.T."/>
                <person name="Conibear E."/>
            </authorList>
            <dbReference type="PubMed" id="26701913"/>
            <dbReference type="DOI" id="10.7554/elife.11306"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MOTIF</scope>
        <scope>PALMITOYLATION</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF 1-MET--PRO-19 AND SER-190</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">Hydrolyzes fatty acids from S-acylated cysteine residues in proteins (PubMed:26701913). Has depalmitoylating activity towards NRAS (PubMed:26701913). Has depalmitoylating activity towards DLG4/PSD95 (PubMed:26701913). May have depalmitoylating activity towards MAP6 (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19233"/>
            <dbReference type="Rhea" id="RHEA-COMP:10131"/>
            <dbReference type="Rhea" id="RHEA-COMP:11032"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29950"/>
            <dbReference type="ChEBI" id="CHEBI:74151"/>
            <dbReference type="EC" id="3.1.2.22"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">Inhibited by palmostatin-B.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2870273">
            <id>Q96GS6</id>
        </interactant>
        <interactant intactId="EBI-10187349">
            <id>O60760</id>
            <label>HPGDS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2870273">
            <id>Q96GS6</id>
        </interactant>
        <interactant intactId="EBI-3957603">
            <id>P09022</id>
            <label>Hoxa1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cell membrane</location>
            <topology evidence="4">Lipid-anchor</topology>
            <orientation evidence="4">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Endosome membrane</location>
            <topology evidence="4">Lipid-anchor</topology>
            <orientation evidence="4">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Dendritic spine</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Postsynaptic density membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96GS6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96GS6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_027268"/>
        </isoform>
        <isoform>
            <id>Q96GS6-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_027269 VSP_027270"/>
        </isoform>
        <isoform>
            <id>Q96GS6-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_027271"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="3 8">Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization (PubMed:26701913). Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95 (By similarity).</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily. ABHD17 family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB15709" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB84869" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC03419" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.2.22" evidence="4"/>
    <dbReference type="EMBL" id="AK024419">
        <property type="protein sequence ID" value="BAB15709.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074043">
        <property type="protein sequence ID" value="BAB84869.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK289533">
        <property type="protein sequence ID" value="BAF82222.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK090438">
        <property type="protein sequence ID" value="BAC03419.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074548">
        <property type="protein sequence ID" value="BAC11052.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471139">
        <property type="protein sequence ID" value="EAW69441.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471139">
        <property type="protein sequence ID" value="EAW69444.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471139">
        <property type="protein sequence ID" value="EAW69446.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000158">
        <property type="protein sequence ID" value="AAH00158.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009256">
        <property type="protein sequence ID" value="AAH09256.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011667">
        <property type="protein sequence ID" value="AAH11667.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020512">
        <property type="protein sequence ID" value="AAH20512.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033749">
        <property type="protein sequence ID" value="AAH33749.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035961">
        <property type="protein sequence ID" value="AAH35961.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC071644">
        <property type="protein sequence ID" value="AAH71644.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC071876">
        <property type="protein sequence ID" value="AAH71876.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC094816">
        <property type="protein sequence ID" value="AAH94816.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32867.1">
        <molecule id="Q96GS6-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45902.1">
        <molecule id="Q96GS6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001123583.1">
        <molecule id="Q96GS6-1"/>
        <property type="nucleotide sequence ID" value="NM_001130111.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_112490.3">
        <molecule id="Q96GS6-2"/>
        <property type="nucleotide sequence ID" value="NM_031213.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011526640.1">
        <molecule id="Q96GS6-2"/>
        <property type="nucleotide sequence ID" value="XM_011528338.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047295443.1">
        <molecule id="Q96GS6-1"/>
        <property type="nucleotide sequence ID" value="XM_047439487.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054178245.1">
        <molecule id="Q96GS6-1"/>
        <property type="nucleotide sequence ID" value="XM_054322270.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054178247.1">
        <molecule id="Q96GS6-2"/>
        <property type="nucleotide sequence ID" value="XM_054322272.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96GS6"/>
    <dbReference type="SMR" id="Q96GS6"/>
    <dbReference type="BioGRID" id="123627">
        <property type="interactions" value="47"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96GS6">
        <property type="interactions" value="1111"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96GS6">
        <property type="interactions" value="39"/>
    </dbReference>
    <dbReference type="MINT" id="Q96GS6"/>
    <dbReference type="STRING" id="9606.ENSP00000250974"/>
    <dbReference type="ESTHER" id="human-ABHD17A">
        <property type="family name" value="ABHD17-depalmitoylase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.052"/>
    <dbReference type="TCDB" id="4.C.3.2.1">
        <property type="family name" value="the acyl-coa thioesterase (acoa-t) family"/>
    </dbReference>
    <dbReference type="TCDB" id="8.A.161.1.1">
        <property type="family name" value="the acyl protein thioesterase (apte) family"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96GS6"/>
    <dbReference type="PhosphoSitePlus" id="Q96GS6"/>
    <dbReference type="SwissPalm" id="Q96GS6"/>
    <dbReference type="BioMuta" id="ABHD17A"/>
    <dbReference type="DMDM" id="74751891"/>
    <dbReference type="jPOST" id="Q96GS6"/>
    <dbReference type="MassIVE" id="Q96GS6"/>
    <dbReference type="PeptideAtlas" id="Q96GS6"/>
    <dbReference type="ProteomicsDB" id="76661">
        <molecule id="Q96GS6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76662">
        <molecule id="Q96GS6-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76663">
        <molecule id="Q96GS6-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76664">
        <molecule id="Q96GS6-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q96GS6"/>
    <dbReference type="Antibodypedia" id="53691">
        <property type="antibodies" value="46 antibodies from 14 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="81926"/>
    <dbReference type="Ensembl" id="ENST00000250974.9">
        <molecule id="Q96GS6-2"/>
        <property type="protein sequence ID" value="ENSP00000250974.9"/>
        <property type="gene ID" value="ENSG00000129968.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000292577.12">
        <molecule id="Q96GS6-1"/>
        <property type="protein sequence ID" value="ENSP00000292577.6"/>
        <property type="gene ID" value="ENSG00000129968.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000676686.1">
        <molecule id="Q96GS6-1"/>
        <property type="protein sequence ID" value="ENSP00000504042.1"/>
        <property type="gene ID" value="ENSG00000129968.18"/>
    </dbReference>
    <dbReference type="GeneID" id="81926"/>
    <dbReference type="KEGG" id="hsa:81926"/>
    <dbReference type="MANE-Select" id="ENST00000292577.12">
        <property type="protein sequence ID" value="ENSP00000292577.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001130111.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001123583.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002luf.4">
        <molecule id="Q96GS6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28756"/>
    <dbReference type="ClinPGx" id="PA134947443"/>
    <dbReference type="CTD" id="81926"/>
    <dbReference type="GeneCards" id="ABHD17A"/>
    <dbReference type="HGNC" id="HGNC:28756">
        <property type="gene designation" value="ABHD17A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000129968">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="617942">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000129968"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000129968"/>
    <dbReference type="GeneTree" id="ENSGT00940000155854"/>
    <dbReference type="HOGENOM" id="CLU_029375_5_4_1"/>
    <dbReference type="InParanoid" id="Q96GS6"/>
    <dbReference type="OMA" id="YIRCVPG"/>
    <dbReference type="OrthoDB" id="446723at2759"/>
    <dbReference type="PAN-GO" id="Q96GS6">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96GS6"/>
    <dbReference type="PathwayCommons" id="Q96GS6"/>
    <dbReference type="Reactome" id="R-HSA-9648002">
        <property type="pathway name" value="RAS processing"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q96GS6"/>
    <dbReference type="Agora" id="ENSG00000129968"/>
    <dbReference type="BioGRID-ORCS" id="81926">
        <property type="hits" value="135 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD17A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="81926"/>
    <dbReference type="Pharos" id="Q96GS6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96GS6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96GS6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000129968">
        <property type="expression patterns" value="Expressed in granulocyte and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96GS6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043197">
        <property type="term" value="C:dendritic spine"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010008">
        <property type="term" value="C:endosome membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016607">
        <property type="term" value="C:nuclear speck"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098839">
        <property type="term" value="C:postsynaptic density membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098944">
        <property type="term" value="C:postsynaptic recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055038">
        <property type="term" value="C:recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:1900226">
        <property type="term" value="P:negative regulation of NLRP3 inflammasome complex assembly"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902817">
        <property type="term" value="P:negative regulation of protein localization to microtubule"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905668">
        <property type="term" value="P:positive regulation of protein localization to endosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002084">
        <property type="term" value="P:protein depalmitoylation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072657">
        <property type="term" value="P:protein localization to membrane"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099175">
        <property type="term" value="P:regulation of postsynapse organization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000008">
        <property type="entry name" value="Alpha/beta hydrolase domain-containing protein 17B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR022742">
        <property type="entry name" value="Hydrolase_4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF52">
        <property type="entry name" value="ALPHA_BETA HYDROLASE DOMAIN-CONTAINING PROTEIN 17A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12146">
        <property type="entry name" value="Hydrolase_4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <feature type="chain" id="PRO_0000297509" description="Alpha/beta hydrolase domain-containing protein 17A">
        <location>
            <begin position="1"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="190"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="255"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027268" description="In isoform 2." evidence="6">
        <original>G</original>
        <variation>GARQGHQAQGGHPQLAWVGRLGDSNNPAPGGCLLGKSWGTGAALACGYIHLL</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027271" description="In isoform 4." evidence="5">
        <location>
            <begin position="177"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027269" description="In isoform 3." evidence="6">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027270" description="In isoform 3." evidence="6">
        <location>
            <begin position="237"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces catalytic activity. Loss of membrane localization. No effect on NRAS plasma membrane localization." evidence="4">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of catalytic activity. No effect on its localization. No effect on NRAS plasma membrane localization." evidence="4">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="190"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH00158/AAH11667." evidence="7" ref="4">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH20512." evidence="7" ref="4">
        <original>K</original>
        <variation>E</variation>
        <location sequence="Q96GS6-2">
            <position position="144"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O75608"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q5XIJ5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q7M759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="26701913"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="26701913"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:28756"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <sequence length="310" mass="33990" checksum="35FC521C6C245BA0" modified="2001-12-01" version="1">MNGLSLSELCCLFCCPPCPGRIAAKLAFLPPEATYSLVPEPEPGPGGAGAAPLGTLRASSGAPGRWKLHLTERADFQYSQRELDTIEVFPTKSARGNRVSCMYVRCVPGARYTVLFSHGNAVDLGQMSSFYIGLGSRLHCNIFSYDYSGYGASSGRPSERNLYADIDAAWQALRTRYGISPDSIILYGQSIGTVPTVDLASRYECAAVVLHSPLTSGMRVAFPDTKKTYCFDAFPNIEKVSKITSPVLIIHGTEDEVIDFSHGLALYERCPKAVEPLWVEGAGHNDIELYSQYLERLRRFISQELPSQRA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-11-22" modified="2026-01-28" version="173" xmlns="https://uniprot.org/uniprot">
    <accession>Q7Z5R6</accession>
    <accession>Q8IWS8</accession>
    <accession>Q8IYL7</accession>
    <accession>Q8IZZ7</accession>
    <name>AB1IP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Amyloid beta A4 precursor protein-binding family B member 1-interacting protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>APBB1-interacting protein 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Proline-rich EVH1 ligand 1</fullName>
            <shortName>PREL-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Proline-rich protein 73</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Rap1-GTP-interacting adapter molecule</fullName>
            <shortName>RIAM</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Retinoic acid-responsive proline-rich protein 1</fullName>
            <shortName>RARP-1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">APBB1IP</name>
        <name type="synonym">PREL1</name>
        <name type="synonym">RARP1</name>
        <name type="synonym">RIAM</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="51685" last="51692">
            <title>The retinoic acid-responsive proline-rich protein is identified in promyeloleukemic HL-60 cells.</title>
            <authorList>
                <person name="Inagaki T."/>
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            </authorList>
            <dbReference type="PubMed" id="14530287"/>
            <dbReference type="DOI" id="10.1074/jbc.m308016200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Thymus</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Dev. Cell" volume="7" first="585" last="595">
            <title>RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion.</title>
            <authorList>
                <person name="Lafuente E.M."/>
                <person name="van Puijenbroek A.A."/>
                <person name="Krause M."/>
                <person name="Carman C.V."/>
                <person name="Freeman G.J."/>
                <person name="Berezovskaya A."/>
                <person name="Constantine E."/>
                <person name="Springer T.A."/>
                <person name="Gertler F.B."/>
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            </authorList>
            <dbReference type="PubMed" id="15469846"/>
            <dbReference type="DOI" id="10.1016/j.devcel.2004.07.021"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INTERACTION WITH RAP1A; PFN1; VASP AND ENAH</scope>
        <source>
            <tissue>T-cell</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2005" name="FEBS Lett." volume="579" first="455" last="463">
            <title>PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins.</title>
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                <person name="Jenzora A."/>
                <person name="Behrendt B."/>
                <person name="Small J.V."/>
                <person name="Wehland J."/>
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            </authorList>
            <dbReference type="PubMed" id="15642358"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2004.10.110"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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                <person name="Nickerson T."/>
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                <person name="Overton-Larty E."/>
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                <person name="Pearce A.V."/>
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                <person name="Pelan S."/>
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                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
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                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
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                <person name="Weinstock K."/>
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                <person name="Whitehead S.L."/>
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                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
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                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
    <reference key="7">
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                <person name="Carrascal M."/>
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            <dbReference type="PubMed" id="19367720"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>T-cell</tissue>
        </source>
    </reference>
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                <person name="Mayya V."/>
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            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-55 AND SER-526</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
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                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
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            <dbReference type="PubMed" id="21269460"/>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Bian Y."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-526</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2013" name="J. Biol. Chem." volume="288" first="8238" last="8249">
            <title>RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover.</title>
            <authorList>
                <person name="Goult B.T."/>
                <person name="Zacharchenko T."/>
                <person name="Bate N."/>
                <person name="Tsang R."/>
                <person name="Hey F."/>
                <person name="Gingras A.R."/>
                <person name="Elliott P.R."/>
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            </authorList>
            <dbReference type="PubMed" id="23389036"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.438119"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-31 IN COMPLEX WITH VCL</scope>
        <scope>INTERACTION WITH VCL AND TLN1</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7">Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling. Suppresses insulin-induced promoter activities through AP1 and SRE. Mediates Rap1-induced adhesion.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7 8">Interacts, through the N-terminal Pro-rich region, with the WW domain of APBB1. Interacts with RAP1A, PFN1, TLN1, VASP, VCL and ENAH.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818084">
            <id>Q7Z5R6</id>
        </interactant>
        <interactant intactId="EBI-524753">
            <id>Q8IUH5</id>
            <label>ZDHHC17</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12059807">
            <id>Q7Z5R6-2</id>
        </interactant>
        <interactant intactId="EBI-10988864">
            <id>P46379-2</id>
            <label>BAG6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12059807">
            <id>Q7Z5R6-2</id>
        </interactant>
        <interactant intactId="EBI-3939165">
            <id>O43711</id>
            <label>TLX3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="1">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Lamellipodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell junction</location>
            <location evidence="1">Focal adhesion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <text evidence="1">Colocalizes with ENA/VASP proteins at lamellipodia tips and focal adhesions, and F-actin at the leading edge. At the membrane surface, associates, via the PH domain, preferentially with the inositol phosphates, PtdIns(5)P and PtdIns(3)P. This binding appears to be necessary for the efficient interaction of the RA domain to Ras-GTPases (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q7Z5R6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q7Z5R6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056542 VSP_056543"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 7">Widely expressed with high expression in thymus, spleen, lymph node, bone marrow and peripheral leukocytes.</text>
    </comment>
    <comment type="induction">
        <text>By all-trans-retinoic acid (ATRA).</text>
    </comment>
    <comment type="domain">
        <text>The two Pro-rich regions are required for the suppression of AP1 transcription activity.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the MRL family.</text>
    </comment>
    <dbReference type="EMBL" id="AB085852">
        <property type="protein sequence ID" value="BAC41256.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY152730">
        <property type="protein sequence ID" value="AAN75525.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL160287">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL355798">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86097.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035636">
        <property type="protein sequence ID" value="AAH35636.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC054516">
        <property type="protein sequence ID" value="AAH54516.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31167.1">
        <molecule id="Q7Z5R6-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_061916.3">
        <molecule id="Q7Z5R6-1"/>
        <property type="nucleotide sequence ID" value="NM_019043.3"/>
    </dbReference>
    <dbReference type="PDB" id="2MWN">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=7-30"/>
    </dbReference>
    <dbReference type="PDB" id="3ZDL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="B=1-31"/>
    </dbReference>
    <dbReference type="PDBsum" id="2MWN"/>
    <dbReference type="PDBsum" id="3ZDL"/>
    <dbReference type="AlphaFoldDB" id="Q7Z5R6"/>
    <dbReference type="BMRB" id="Q7Z5R6"/>
    <dbReference type="SMR" id="Q7Z5R6"/>
    <dbReference type="BioGRID" id="120012">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="CORUM" id="Q7Z5R6"/>
    <dbReference type="FunCoup" id="Q7Z5R6">
        <property type="interactions" value="1338"/>
    </dbReference>
    <dbReference type="IntAct" id="Q7Z5R6">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="MINT" id="Q7Z5R6"/>
    <dbReference type="STRING" id="9606.ENSP00000365411"/>
    <dbReference type="iPTMnet" id="Q7Z5R6"/>
    <dbReference type="PhosphoSitePlus" id="Q7Z5R6"/>
    <dbReference type="BioMuta" id="APBB1IP"/>
    <dbReference type="DMDM" id="74750143"/>
    <dbReference type="jPOST" id="Q7Z5R6"/>
    <dbReference type="MassIVE" id="Q7Z5R6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000365411"/>
    <dbReference type="PeptideAtlas" id="Q7Z5R6"/>
    <dbReference type="ProteomicsDB" id="69350">
        <molecule id="Q7Z5R6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71199"/>
    <dbReference type="Antibodypedia" id="38122">
        <property type="antibodies" value="248 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="54518"/>
    <dbReference type="Ensembl" id="ENST00000356785.4">
        <molecule id="Q7Z5R6-2"/>
        <property type="protein sequence ID" value="ENSP00000349237.4"/>
        <property type="gene ID" value="ENSG00000077420.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000376236.9">
        <molecule id="Q7Z5R6-1"/>
        <property type="protein sequence ID" value="ENSP00000365411.4"/>
        <property type="gene ID" value="ENSG00000077420.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000718302.1">
        <molecule id="Q7Z5R6-1"/>
        <property type="protein sequence ID" value="ENSP00000520735.1"/>
        <property type="gene ID" value="ENSG00000077420.18"/>
    </dbReference>
    <dbReference type="GeneID" id="54518"/>
    <dbReference type="KEGG" id="hsa:54518"/>
    <dbReference type="MANE-Select" id="ENST00000376236.9">
        <property type="protein sequence ID" value="ENSP00000365411.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_019043.4"/>
        <property type="RefSeq protein sequence ID" value="NP_061916.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001isr.4">
        <molecule id="Q7Z5R6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17379"/>
    <dbReference type="ClinPGx" id="PA134933955"/>
    <dbReference type="CTD" id="54518"/>
    <dbReference type="DisGeNET" id="54518"/>
    <dbReference type="GeneCards" id="APBB1IP"/>
    <dbReference type="HGNC" id="HGNC:17379">
        <property type="gene designation" value="APBB1IP"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000077420">
        <property type="expression patterns" value="Tissue enhanced (lymphoid)"/>
    </dbReference>
    <dbReference type="MIM" id="609036">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000077420"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000077420"/>
    <dbReference type="eggNOG" id="KOG3751">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156105"/>
    <dbReference type="HOGENOM" id="CLU_023207_2_0_1"/>
    <dbReference type="InParanoid" id="Q7Z5R6"/>
    <dbReference type="OMA" id="CCDDQAT"/>
    <dbReference type="OrthoDB" id="6235964at2759"/>
    <dbReference type="PAN-GO" id="Q7Z5R6">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7Z5R6"/>
    <dbReference type="PathwayCommons" id="Q7Z5R6"/>
    <dbReference type="Reactome" id="R-HSA-354192">
        <property type="pathway name" value="Integrin signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-354194">
        <property type="pathway name" value="GRB2:SOS provides linkage to MAPK signaling for Integrins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-372708">
        <property type="pathway name" value="p130Cas linkage to MAPK signaling for integrins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5674135">
        <property type="pathway name" value="MAP2K and MAPK activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6802946">
        <property type="pathway name" value="Signaling by moderate kinase activity BRAF mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6802948">
        <property type="pathway name" value="Signaling by high-kinase activity BRAF mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6802952">
        <property type="pathway name" value="Signaling by BRAF and RAF1 fusions"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6802955">
        <property type="pathway name" value="Paradoxical activation of RAF signaling by kinase inactive BRAF"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9649948">
        <property type="pathway name" value="Signaling downstream of RAS mutants"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9656223">
        <property type="pathway name" value="Signaling by RAF1 mutants"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q7Z5R6"/>
    <dbReference type="Agora" id="ENSG00000077420"/>
    <dbReference type="BioGRID-ORCS" id="54518">
        <property type="hits" value="18 hits in 1143 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APBB1IP">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q7Z5R6"/>
    <dbReference type="GeneWiki" id="APBB1IP"/>
    <dbReference type="GenomeRNAi" id="54518"/>
    <dbReference type="Pharos" id="Q7Z5R6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7Z5R6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7Z5R6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000077420">
        <property type="expression patterns" value="Expressed in blood and 173 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005856">
        <property type="term" value="C:cytoskeleton"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005925">
        <property type="term" value="C:focal adhesion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030027">
        <property type="term" value="C:lamellipodium"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042101">
        <property type="term" value="C:T cell receptor complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045785">
        <property type="term" value="P:positive regulation of cell adhesion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002291">
        <property type="term" value="P:T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd01259">
        <property type="entry name" value="PH_APBB1IP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd16137">
        <property type="entry name" value="RA_MRL_RIAM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.20.90:FF:000124">
        <property type="entry name" value="amyloid beta A4 precursor protein-binding family B member 1-interacting protein-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000048">
        <property type="entry name" value="Ras association (RalGDS/AF-6) and pleckstrin homology domains 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.10.20.90">
        <property type="entry name" value="Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="IDEAL" id="IID00572"/>
    <dbReference type="InterPro" id="IPR039664">
        <property type="entry name" value="GRB/APBB1IP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039665">
        <property type="entry name" value="PH_APBB1IP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000159">
        <property type="entry name" value="RA_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029071">
        <property type="entry name" value="Ubiquitin-like_domsf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11243:SF14">
        <property type="entry name" value="AMYLOID BETA A4 PRECURSOR PROTEIN-BINDING FAMILY B MEMBER 1-INTERACTING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11243">
        <property type="entry name" value="GROWTH FACTOR RECEPTOR-BOUND PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF21989">
        <property type="entry name" value="RA_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00314">
        <property type="entry name" value="RA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54236">
        <property type="entry name" value="Ubiquitin-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50200">
        <property type="entry name" value="RA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000181347" description="Amyloid beta A4 precursor protein-binding family B member 1-interacting protein">
        <location>
            <begin position="1"/>
            <end position="666"/>
        </location>
    </feature>
    <feature type="domain" description="Ras-associating" evidence="4">
        <location>
            <begin position="176"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="3">
        <location>
            <begin position="310"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="122"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="448"/>
            <end position="666"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="129"/>
            <end position="148"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="453"/>
            <end position="478"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="483"/>
            <end position="504"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="547"/>
            <end position="589"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="5">
        <location>
            <begin position="598"/>
            <end position="631"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12">
        <location>
            <position position="526"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="528"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="531"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056542" description="In isoform 2." evidence="9">
        <original>EEEEAQAKADKIKLALEKLKE</original>
        <variation>VSMWDQRWQDHQPLLPITDVP</variation>
        <location>
            <begin position="152"/>
            <end position="172"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056543" description="In isoform 2." evidence="9">
        <location>
            <begin position="173"/>
            <end position="666"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050098" description="In dbSNP:rs34081356.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059447" description="In dbSNP:rs7903226.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="617"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC41256." evidence="10" ref="1">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="423"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAN75525." evidence="10" ref="2">
        <location>
            <position position="599"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="8"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="turn" evidence="13">
        <location>
            <begin position="26"/>
            <end position="31"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8R5A3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00166"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="14530287"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15469846"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="23389036"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="3ZDL"/>
        </source>
    </evidence>
    <sequence length="666" mass="73183" checksum="525C906C490D8D97" modified="2003-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-03-29" modified="2026-01-28" version="162" xmlns="https://uniprot.org/uniprot">
    <accession>Q96AK3</accession>
    <accession>Q5JZ91</accession>
    <accession>Q7Z2N2</accession>
    <accession>Q7Z2N5</accession>
    <accession>Q7Z2N6</accession>
    <name>ABC3D_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>DNA dC-&gt;dU-editing enzyme APOBEC-3D</fullName>
            <shortName>A3D</shortName>
            <shortName evidence="14">A3DE</shortName>
            <ecNumber>3.5.4.38</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="16" type="primary">APOBEC3D</name>
        <name evidence="16" type="synonym">APOBEC3DE</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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    </reference>
    <comment type="function">
        <text evidence="3 4 5 7 8 10 11">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:16920826, PubMed:20062055, PubMed:21835787). Exhibits antiviral activity against HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA (PubMed:16920826). The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Also inhibits the mobility of LTR and non-LTR retrotransposons (PubMed:27428332).</text>
    </comment>
    <comment type="function">
        <text evidence="12">(Microbial infection) Enhances hepatitis B virus/HBV replication by excluding restriction factors APOBEC3F and APOBEC3G from HBV capsids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="7">(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 12 13">Can form homo- and heterodimers with APOBEC3F and APOBEC3G (PubMed:16920826, PubMed:27289067). Interacts with L1RE1; this interaction inhibits LINE-1 retrotransposition (PubMed:27428332).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 9">(Microbial infection) Interacts with HIV-1 Vif (PubMed:16920826, PubMed:23001005). This interaction triggers APOBEC3D polyubiquitylation and degradation by the 26S proteasome (PubMed:16920826).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12 13">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>P-body</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung.</text>
    </comment>
    <comment type="domain">
        <text>The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.</text>
    </comment>
    <comment type="miscellaneous">
        <text>It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.38"/>
    <dbReference type="EMBL" id="AL022318">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46709.1"/>
    <dbReference type="RefSeq" id="NP_689639.2">
        <property type="nucleotide sequence ID" value="NM_152426.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96AK3"/>
    <dbReference type="SMR" id="Q96AK3"/>
    <dbReference type="FunCoup" id="Q96AK3">
        <property type="interactions" value="262"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96AK3">
        <property type="interactions" value="59"/>
    </dbReference>
    <dbReference type="MINT" id="Q96AK3"/>
    <dbReference type="STRING" id="9606.ENSP00000216099"/>
    <dbReference type="iPTMnet" id="Q96AK3"/>
    <dbReference type="PhosphoSitePlus" id="Q96AK3"/>
    <dbReference type="SwissPalm" id="Q96AK3"/>
    <dbReference type="BioMuta" id="APOBEC3D"/>
    <dbReference type="DMDM" id="48474596"/>
    <dbReference type="jPOST" id="Q96AK3"/>
    <dbReference type="MassIVE" id="Q96AK3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000216099"/>
    <dbReference type="PeptideAtlas" id="Q96AK3"/>
    <dbReference type="ProteomicsDB" id="75971"/>
    <dbReference type="Pumba" id="Q96AK3"/>
    <dbReference type="Antibodypedia" id="35025">
        <property type="antibodies" value="156 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="140564"/>
    <dbReference type="Ensembl" id="ENST00000216099.13">
        <property type="protein sequence ID" value="ENSP00000216099.7"/>
        <property type="gene ID" value="ENSG00000243811.13"/>
    </dbReference>
    <dbReference type="GeneID" id="140564"/>
    <dbReference type="KEGG" id="hsa:140564"/>
    <dbReference type="MANE-Select" id="ENST00000216099.13">
        <property type="protein sequence ID" value="ENSP00000216099.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_152426.4"/>
        <property type="RefSeq protein sequence ID" value="NP_689639.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003awt.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17354"/>
    <dbReference type="ClinPGx" id="PA24894"/>
    <dbReference type="CTD" id="140564"/>
    <dbReference type="GeneCards" id="APOBEC3D"/>
    <dbReference type="HGNC" id="HGNC:17354">
        <property type="gene designation" value="APOBEC3D"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000243811">
        <property type="expression patterns" value="Tissue enhanced (lymphoid)"/>
    </dbReference>
    <dbReference type="MIM" id="609900">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000243811"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000243811"/>
    <dbReference type="eggNOG" id="KOG4075">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162695"/>
    <dbReference type="HOGENOM" id="CLU_047918_0_0_1"/>
    <dbReference type="InParanoid" id="Q96AK3"/>
    <dbReference type="OMA" id="HTELCIL"/>
    <dbReference type="OrthoDB" id="9445293at2759"/>
    <dbReference type="PAN-GO" id="Q96AK3">
        <property type="GO annotations" value="12 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96AK3"/>
    <dbReference type="BRENDA" id="3.5.4.38">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q96AK3"/>
    <dbReference type="SignaLink" id="Q96AK3"/>
    <dbReference type="SIGNOR" id="Q96AK3"/>
    <dbReference type="Agora" id="ENSG00000243811"/>
    <dbReference type="Pharos" id="Q96AK3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96AK3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96AK3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000243811">
        <property type="expression patterns" value="Expressed in granulocyte and 99 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96AK3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000932">
        <property type="term" value="C:P-body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044355">
        <property type="term" value="P:clearance of foreign intracellular DNA"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070383">
        <property type="term" value="P:DNA cytosine deamination"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045087">
        <property type="term" value="P:innate immune response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045869">
        <property type="term" value="P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000044">
        <property type="entry name" value="Apolipoprotein B mRNA editing enzyme catalytic subunit 3B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000029">
        <property type="entry name" value="DNA dC-&gt;dU-editing enzyme APOBEC-3G"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF24">
        <property type="entry name" value="DNA DC-DU-EDITING ENZYME APOBEC-3D"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18782">
        <property type="entry name" value="NAD2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0391">Immunity</keyword>
    <keyword id="KW-0399">Innate immunity</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171756" description="DNA dC-&gt;dU-editing enzyme APOBEC-3D">
        <location>
            <begin position="1"/>
            <end position="386"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase 1" evidence="2">
        <location>
            <begin position="29"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase 2" evidence="2">
        <location>
            <begin position="187"/>
            <end position="334"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="2">
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="78"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="109"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="112"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="262"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="293"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="296"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="mutagenesis site" description="About two-third loss of anti HIV-1 activity." evidence="4">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on Vif binding." evidence="9">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>L</original>
        <variation>D</variation>
        <location>
            <position position="268"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="9">
        <original>C</original>
        <variation>K</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>IL</original>
        <variation>AA</variation>
        <location>
            <begin position="275"/>
            <end position="276"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="9">
        <original>S</original>
        <variation>D</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="302"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>F</original>
        <variation>K</variation>
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="9">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="9">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="12859895"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16920826"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="20062055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="20308164"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21835787"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="22807680"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="23001005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="23097438"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="23152537"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="27289067"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="27428332"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="23001005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:17354"/>
        </source>
    </evidence>
    <sequence length="386" mass="46598" checksum="94C7253BDCC85B22" modified="2001-12-01" version="1">MNPQIRNPMERMYRDTFYDNFENEPILYGRSYTWLCYEVKIKRGRSNLLWDTGVFRGPVLPKRQSNHRQEVYFRFENHAEMCFLSWFCGNRLPANRRFQITWFVSWNPCLPCVVKVTKFLAEHPNVTLTISAARLYYYRDRDWRWVLLRLHKAGARVKIMDYEDFAYCWENFVCNEGQPFMPWYKFDDNYASLHRTLKEILRNPMEAMYPHIFYFHFKNLLKACGRNESWLCFTMEVTKHHSAVFRKRGVFRNQVDPETHCHAERCFLSWFCDDILSPNTNYEVTWYTSWSPCPECAGEVAEFLARHSNVNLTIFTARLCYFWDTDYQEGLCSLSQEGASVKIMGYKDFVSCWKNFVYSDDEPFKPWKGLQTNFRLLKRRLREILQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-03-29" modified="2026-01-28" version="184" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IUX4</accession>
    <accession>B0QYD4</accession>
    <accession>Q45F03</accession>
    <accession>Q6ICH3</accession>
    <accession>Q7Z2N2</accession>
    <accession>Q7Z2N5</accession>
    <name>ABC3F_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="32">DNA dC-&gt;dU-editing enzyme APOBEC-3F</fullName>
            <ecNumber evidence="10">3.5.4.38</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3F</fullName>
            <shortName evidence="31">A3F</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="28 34" type="primary">APOBEC3F</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
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                <person name="Stenglein M.D."/>
                <person name="Burns M.B."/>
                <person name="Li M."/>
                <person name="Lengyel J."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20062055"/>
            <dbReference type="DOI" id="10.1038/nsmb.1744"/>
        </citation>
        <scope>FUNCTION IN RETROTRANSPOSITION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2010" name="Nucleic Acids Res." volume="38" first="4274" last="4284">
            <title>Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction.</title>
            <authorList>
                <person name="Refsland E.W."/>
                <person name="Stenglein M.D."/>
                <person name="Shindo K."/>
                <person name="Albin J.S."/>
                <person name="Brown W.L."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20308164"/>
            <dbReference type="DOI" id="10.1093/nar/gkq174"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2011" name="Cell" volume="145" first="423" last="434">
            <title>Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.</title>
            <authorList>
                <person name="Guo J.U."/>
                <person name="Su Y."/>
                <person name="Zhong C."/>
                <person name="Ming G.L."/>
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            </authorList>
            <dbReference type="PubMed" id="21496894"/>
            <dbReference type="DOI" id="10.1016/j.cell.2011.03.022"/>
        </citation>
        <scope>FUNCTION IN DNA DEMETHYLATION</scope>
    </reference>
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            <title>Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.</title>
            <authorList>
                <person name="Hultquist J.F."/>
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                <person name="Refsland E.W."/>
                <person name="LaRue R.S."/>
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                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="21835787"/>
            <dbReference type="DOI" id="10.1128/jvi.05238-11"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2011" name="Nature" volume="481" first="371" last="375">
            <title>Vif hijacks CBF-beta to degrade APOBEC3G and promote HIV-1 infection.</title>
            <authorList>
                <person name="Jaeger S."/>
                <person name="Kim D.Y."/>
                <person name="Hultquist J.F."/>
                <person name="Shindo K."/>
                <person name="LaRue R.S."/>
                <person name="Kwon E."/>
                <person name="Li M."/>
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            </authorList>
            <dbReference type="PubMed" id="22190037"/>
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        </citation>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2012" name="Front. Microbiol." volume="3" first="275" last="275">
            <title>Retroelements versus APOBEC3 family members: No great escape from the magnificent seven.</title>
            <authorList>
                <person name="Arias J.F."/>
                <person name="Koyama T."/>
                <person name="Kinomoto M."/>
                <person name="Tokunaga K."/>
            </authorList>
            <dbReference type="PubMed" id="22912627"/>
            <dbReference type="DOI" id="10.3389/fmicb.2012.00275"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="26">
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            <title>HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.</title>
            <authorList>
                <person name="Phalora P.K."/>
                <person name="Sherer N.M."/>
                <person name="Wolinsky S.M."/>
                <person name="Swanson C.M."/>
                <person name="Malim M.H."/>
            </authorList>
            <dbReference type="PubMed" id="22915799"/>
            <dbReference type="DOI" id="10.1128/jvi.00595-12"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH AGO1; AGO2 AND AGO3</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2012" name="Nat. Struct. Mol. Biol." volume="19" first="1005" last="1010">
            <title>The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.</title>
            <authorList>
                <person name="Kitamura S."/>
                <person name="Ode H."/>
                <person name="Nakashima M."/>
                <person name="Imahashi M."/>
                <person name="Naganawa Y."/>
                <person name="Kurosawa T."/>
                <person name="Yokomaku Y."/>
                <person name="Yamane T."/>
                <person name="Watanabe N."/>
                <person name="Suzuki A."/>
                <person name="Sugiura W."/>
                <person name="Iwatani Y."/>
            </authorList>
            <dbReference type="PubMed" id="23001005"/>
            <dbReference type="DOI" id="10.1038/nsmb.2378"/>
        </citation>
        <scope>FUNCTION IN HIV-1 INFECTIVITY</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF GLU-251; LEU-255; PHE-258; CYS-259; 262-ILE-LEU-263; SER-264; TYR-269; GLU-289; PHE-290; HIS-294 AND GLU-324</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2012" name="PLoS Pathog." volume="8" first="E1002800" last="E1002800">
            <title>Endogenous origins of HIV-1 G-to-A hypermutation and restriction in the nonpermissive T cell line CEM2n.</title>
            <authorList>
                <person name="Refsland E.W."/>
                <person name="Hultquist J.F."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="22807680"/>
            <dbReference type="DOI" id="10.1371/journal.ppat.1002800"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2012" name="Semin. Cell Dev. Biol." volume="23" first="258" last="268">
            <title>Functions and regulation of the APOBEC family of proteins.</title>
            <authorList>
                <person name="Smith H.C."/>
                <person name="Bennett R.P."/>
                <person name="Kizilyer A."/>
                <person name="McDougall W.M."/>
                <person name="Prohaska K.M."/>
            </authorList>
            <dbReference type="PubMed" id="22001110"/>
            <dbReference type="DOI" id="10.1016/j.semcdb.2011.10.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2013" name="J. Mol. Biol." volume="425" first="1172" last="1182">
            <title>Dispersed sites of HIV Vif-dependent polyubiquitination in the DNA deaminase APOBEC3F.</title>
            <authorList>
                <person name="Albin J.S."/>
                <person name="Anderson J.S."/>
                <person name="Johnson J.R."/>
                <person name="Harjes E."/>
                <person name="Matsuo H."/>
                <person name="Krogan N.J."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="23318957"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2013.01.010"/>
        </citation>
        <scope>UBIQUITINATION AT LYS-52; LYS-234; LYS-334; LYS-352; LYS-355 AND LYS-358 (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="2013" name="J. Virol." volume="87" first="444" last="453">
            <title>APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE in human primary CD4+ t cells and macrophages.</title>
            <authorList>
                <person name="Chaipan C."/>
                <person name="Smith J.L."/>
                <person name="Hu W.S."/>
                <person name="Pathak V.K."/>
            </authorList>
            <dbReference type="PubMed" id="23097438"/>
            <dbReference type="DOI" id="10.1128/jvi.00676-12"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="2013" name="J. Virol." volume="87" first="1508" last="1517">
            <title>The suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4+ T cells is associated with the inhibition of processive reverse transcription as well as excessive cytidine deamination.</title>
            <authorList>
                <person name="Gillick K."/>
                <person name="Pollpeter D."/>
                <person name="Phalora P."/>
                <person name="Kim E.Y."/>
                <person name="Wolinsky S.M."/>
                <person name="Malim M.H."/>
            </authorList>
            <dbReference type="PubMed" id="23152537"/>
            <dbReference type="DOI" id="10.1128/jvi.02587-12"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
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    <reference key="33">
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            <title>Differential Activity of APOBEC3F, APOBEC3G, and APOBEC3H in the Restriction of HIV-2.</title>
            <authorList>
                <person name="Meissner M.E."/>
                <person name="Willkomm N.A."/>
                <person name="Lucas J."/>
                <person name="Arndt W.G."/>
                <person name="Aitken S.F."/>
                <person name="Julik E.J."/>
                <person name="Baliga S."/>
                <person name="Mansky L.M."/>
            </authorList>
            <dbReference type="PubMed" id="34774569"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2021.167355"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference evidence="35 36" key="34">
        <citation type="journal article" date="2016" name="J. Mol. Biol." volume="428" first="2307" last="2316">
            <title>1.92 Angstrom Zinc-Free APOBEC3F Catalytic Domain Crystal Structure.</title>
            <authorList>
                <person name="Shaban N.M."/>
                <person name="Shi K."/>
                <person name="Li M."/>
                <person name="Aihara H."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="27139641"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2016.04.026"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 185-373 IN COMPLEX WITH ZINC</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="37" key="35">
        <citation type="journal article" date="2019" name="Nat. Struct. Mol. Biol." volume="26" first="1176" last="1183">
            <title>Structural basis of antagonism of human APOBEC3F by HIV-1 Vif.</title>
            <authorList>
                <person name="Hu Y."/>
                <person name="Desimmie B.A."/>
                <person name="Nguyen H.C."/>
                <person name="Ziegler S.J."/>
                <person name="Cheng T.C."/>
                <person name="Chen J."/>
                <person name="Wang J."/>
                <person name="Wang H."/>
                <person name="Zhang K."/>
                <person name="Pathak V.K."/>
                <person name="Xiong Y."/>
            </authorList>
            <dbReference type="PubMed" id="31792451"/>
            <dbReference type="DOI" id="10.1038/s41594-019-0343-6"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 185-373 IN COMPLEX WITH CBFB; HIV-1 VIF AND ZINC</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVE SITE</scope>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH APOBEC3G</scope>
        <scope>MUTAGENESIS OF 260-ASP-ASP-261; PRO-265; GLU-289; ARG-293; GLU-324 AND ASP-347</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 6 7 11 12 13 15 16 17 19 20 21 22 23 26">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:15141007, PubMed:20062055, PubMed:22915799, PubMed:34774569). Exhibits antiviral activity against viruse such as HIV-1 or HIV-2 (PubMed:15141007, PubMed:15152192, PubMed:20219927, PubMed:21835787, PubMed:22807680, PubMed:23001005, PubMed:23097438, PubMed:23152537, PubMed:34774569). After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA (PubMed:15141007). The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells (PubMed:15141007). Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA (PubMed:15141007). Exhibits antiviral activity also against hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV) and may inhibit the mobility of LTR and non-LTR retrotransposons (PubMed:16378963, PubMed:16527742, PubMed:19458006, PubMed:20062055, PubMed:20335265). May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation (PubMed:21496894).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="24 25">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="17 18 25">(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 20 24 25">Homodimer (PubMed:27139641). Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599, PubMed:31792451). Interacts with AGO1, AGO2 and AGO3 (PubMed:22915799).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 17 18 21 25">(Microbial infection) Interacts with HIV-1 Vif, leading to its ubiquitination and degradation by the proteasome (PubMed:15152192, PubMed:22190037, PubMed:23001005, PubMed:31792451). In the absence of Vif protein, specifically packaged into HIV-1 virions (PubMed:15152192).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11306991">
            <id>Q8IUX4</id>
        </interactant>
        <interactant intactId="EBI-11306991">
            <id>Q8IUX4</id>
            <label>APOBEC3F</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 8 17">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8 20">Cytoplasm</location>
            <location evidence="8 20">P-body</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IUX4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IUX4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009803 VSP_009804"/>
        </isoform>
        <isoform>
            <id>Q8IUX4-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_042754 VSP_042755"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 4 14">Widely expressed. Highly expressed in ovary.</text>
    </comment>
    <comment type="domain">
        <text evidence="9">The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18 25">(Microbial infection) Following infection by HIV-1, ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="2">It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="32">May be due to a competing donor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="32">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.38" evidence="10"/>
    <dbReference type="EMBL" id="CR456395">
        <property type="protein sequence ID" value="CAG30281.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ146365">
        <property type="protein sequence ID" value="AAZ38720.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL022318">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471095">
        <property type="protein sequence ID" value="EAW60288.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471095">
        <property type="protein sequence ID" value="EAW60289.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC038808">
        <property type="protein sequence ID" value="AAH38808.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC061914">
        <property type="protein sequence ID" value="AAH61914.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33648.1">
        <molecule id="Q8IUX4-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33649.1">
        <molecule id="Q8IUX4-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001006667.1">
        <molecule id="Q8IUX4-3"/>
        <property type="nucleotide sequence ID" value="NM_001006666.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_660341.2">
        <molecule id="Q8IUX4-1"/>
        <property type="nucleotide sequence ID" value="NM_145298.5"/>
    </dbReference>
    <dbReference type="PDB" id="3WUS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.54 A"/>
        <property type="chains" value="A/B=187-373"/>
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    <dbReference type="PDB" id="4IOU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.75 A"/>
        <property type="chains" value="A/B/C/D=185-373"/>
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    <dbReference type="PDB" id="4J4J">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B=218-373"/>
    </dbReference>
    <dbReference type="PDB" id="5HX4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="A/B=185-373"/>
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    <dbReference type="PDB" id="5HX5">
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        <property type="resolution" value="2.33 A"/>
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    </dbReference>
    <dbReference type="PDB" id="5W2M">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="A/B/C/D/J/K/L/M=190-373"/>
    </dbReference>
    <dbReference type="PDB" id="5ZVA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=220-373"/>
    </dbReference>
    <dbReference type="PDB" id="5ZVB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=220-373"/>
    </dbReference>
    <dbReference type="PDB" id="6NIL">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="A/D/G/J=185-373"/>
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    <dbReference type="PDB" id="8VUD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B=1-190"/>
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    <dbReference type="PDBsum" id="3WUS"/>
    <dbReference type="PDBsum" id="4IOU"/>
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    <dbReference type="AlphaFoldDB" id="Q8IUX4"/>
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        <property type="interactions" value="151"/>
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    </dbReference>
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    <dbReference type="ProteomicsDB" id="70623">
        <molecule id="Q8IUX4-1"/>
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    <dbReference type="ProteomicsDB" id="70624">
        <molecule id="Q8IUX4-2"/>
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        <molecule id="Q8IUX4-3"/>
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    <dbReference type="Pumba" id="Q8IUX4"/>
    <dbReference type="Antibodypedia" id="34783">
        <property type="antibodies" value="200 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="200316"/>
    <dbReference type="Ensembl" id="ENST00000308521.10">
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        <property type="protein sequence ID" value="ENSP00000309749.5"/>
        <property type="gene ID" value="ENSG00000128394.18"/>
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    <dbReference type="Ensembl" id="ENST00000381565.2">
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        <property type="protein sequence ID" value="ENSP00000370977.2"/>
        <property type="gene ID" value="ENSG00000128394.18"/>
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    <dbReference type="GeneID" id="200316"/>
    <dbReference type="KEGG" id="hsa:200316"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_145298.6"/>
        <property type="RefSeq protein sequence ID" value="NP_660341.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003awv.4">
        <molecule id="Q8IUX4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
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        <property type="gene designation" value="APOBEC3F"/>
    </dbReference>
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        <property type="expression patterns" value="Low tissue specificity"/>
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="12 GO annotations based on evolutionary models"/>
    </dbReference>
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        <property type="hits" value="17 hits in 1105 CRISPR screens"/>
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    </dbReference>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 22"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000128394">
        <property type="expression patterns" value="Expressed in granulocyte and 104 other cell types or tissues"/>
    </dbReference>
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        <property type="term" value="C:apolipoprotein B mRNA editing enzyme complex"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="HGNC-UCL"/>
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        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0042802">
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        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0016553">
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        <property type="project" value="HGNC-UCL"/>
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        <property type="term" value="P:clearance of foreign intracellular DNA"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0051607">
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0070383">
        <property type="term" value="P:DNA cytosine deamination"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045869">
        <property type="term" value="P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0045071">
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002230">
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        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0044029">
        <property type="term" value="P:positive regulation of gene expression via chromosomal CpG island demethylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010526">
        <property type="term" value="P:transposable element silencing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000044">
        <property type="entry name" value="Apolipoprotein B mRNA editing enzyme catalytic subunit 3B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000029">
        <property type="entry name" value="DNA dC-&gt;dU-editing enzyme APOBEC-3G"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
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    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF45">
        <property type="entry name" value="DNA DC-DU-EDITING ENZYME APOBEC-3F"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18782">
        <property type="entry name" value="NAD2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="2"/>
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    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0391">Immunity</keyword>
    <keyword id="KW-0399">Innate immunity</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171757" description="DNA dC-&gt;dU-editing enzyme APOBEC-3F">
        <location>
            <begin position="1"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase 1" evidence="1">
        <location>
            <begin position="29"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase 2" evidence="1">
        <location>
            <begin position="174"/>
            <end position="321"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="1 25 37">
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="65"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="96"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="99"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 24 25 37">
        <location>
            <position position="249"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 24 25 37">
        <location>
            <position position="280"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 24 25 37">
        <location>
            <position position="283"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="disulfide bond" evidence="24 35">
        <location>
            <begin position="280"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="334"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="352"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="33">
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009803" description="In isoform 2." evidence="30">
        <original>VYSQPEHHAEMCFLSWFCGNQL</original>
        <variation>VPPGLQSLCRQELSQLGKQTTH</variation>
        <location>
            <begin position="58"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_042754" description="In isoform 3." evidence="29">
        <original>YSQPEHHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLAEHPNV</original>
        <variation>PRSFIRAPFQVLSSPFGQCAPPHGTAQVQWPPQLTAGREQGRP</variation>
        <location>
            <begin position="59"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009804" description="In isoform 2." evidence="30">
        <location>
            <begin position="80"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_042755" description="In isoform 3." evidence="29">
        <location>
            <begin position="114"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038355" description="In dbSNP:rs35053197." evidence="5">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018145" description="In dbSNP:rs2076109.">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="61"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018146" description="In dbSNP:rs201939303.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018147" description="In dbSNP:rs2020390." evidence="5">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025058" description="In dbSNP:rs34182094." evidence="27">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018148" description="In dbSNP:rs2076101." evidence="27">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025059" description="In dbSNP:rs12157816." evidence="27">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity." evidence="10">
        <original>H</original>
        <variation>C</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Nearly abolished antiviral activity; when associated with R-249." evidence="10">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decrease in cytidine deaminase and antiviral activity; when associated with A-251." evidence="9">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cytidine deaminase and antiviral activity." evidence="9">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity. Nearly abolished antiviral activity; when associated with Q-251." evidence="10">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity. Nearly abolished antiviral activity; when associated with Q-280." evidence="10">
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activityy. Nearly abolished antiviral activity; when associated with S-283." evidence="10">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity." evidence="10">
        <original>H</original>
        <variation>C</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Nearly abolished antiviral activity; when associated with R-65." evidence="10">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decrease in cytidine deaminase and antiviral activity." evidence="9">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decrease in cytidine deaminase and antiviral activity; when associated with A-67." evidence="9">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains able to bind Vif." evidence="21">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity. Nearly abolished antiviral activity; when associated with Q-67." evidence="10">
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>L</original>
        <variation>D</variation>
        <location>
            <position position="255"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>C</original>
        <variation>K</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with APOBEC3G." evidence="25">
        <original>DD</original>
        <variation>RR</variation>
        <location>
            <begin position="260"/>
            <end position="261"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>IL</original>
        <variation>AA</variation>
        <location>
            <begin position="262"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>S</original>
        <variation>D</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired interaction with HIV-1 Vif protein." evidence="25">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="269"/>
        </location>
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    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity. Nearly abolished antiviral activity; when associated with Q-96." evidence="10">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="280"/>
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    <feature type="mutagenesis site" description="Reduced but not abolished antiviral activity. Nearly abolished antiviral activity; when associated with S-99." evidence="10">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="283"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with HIV-1 Vif protein. Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21 25">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding but is still efficiently incorporated into the virion." evidence="21">
        <original>F</original>
        <variation>K</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with HIV-1 Vif protein." evidence="25">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="293"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif, reduces Vif binding and abolishes incorporation into the virion." evidence="21">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="21">
        <original>E</original>
        <variation>K</variation>
        <variation>A</variation>
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished interaction with HIV-1 Vif protein." evidence="25">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with HIV-1 Vif protein." evidence="25">
        <original>D</original>
        <variation>R</variation>
        <location>
            <position position="347"/>
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    <feature type="helix" evidence="38">
        <location>
            <begin position="197"/>
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    <feature type="helix" evidence="38">
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            <begin position="208"/>
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        <location>
            <begin position="217"/>
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    <feature type="strand" evidence="38">
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            <begin position="232"/>
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            <begin position="244"/>
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            <begin position="250"/>
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            <begin position="267"/>
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            <begin position="281"/>
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            <begin position="297"/>
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            <begin position="307"/>
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        <location>
            <begin position="312"/>
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        <location>
            <begin position="327"/>
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        <location>
            <begin position="333"/>
            <end position="343"/>
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    <feature type="helix" evidence="38">
        <location>
            <begin position="357"/>
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<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="163" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WWZ7</accession>
    <accession>Q8IVJ2</accession>
    <accession>Q96LJ1</accession>
    <accession>Q96MS4</accession>
    <accession>Q96PZ9</accession>
    <accession>Q9NY14</accession>
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            <fullName evidence="15">Cholesterol transporter ABCA5</fullName>
            <ecNumber evidence="16">7.6.2.-</ecNumber>
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            <fullName evidence="15">ATP-binding cassette sub-family A member 5</fullName>
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        <name evidence="17" type="primary">ABCA5</name>
        <name type="synonym">KIAA1888</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="GeneScreen" volume="1" first="157" last="164">
            <title>Identifying and characterizing a five-gene cluster of ATP-binding cassette transporters mapping to human chromosome 17q24: a new subgroup within the ABCA subfamily.</title>
            <authorList>
                <person name="Arnould I."/>
                <person name="Schriml L.M."/>
                <person name="Prades C."/>
                <person name="Lachtermacher-Triunfol M."/>
                <person name="Schneider T."/>
                <person name="Maintoux C."/>
                <person name="Lemoine C."/>
                <person name="Debono D."/>
                <person name="Devaud C."/>
                <person name="Naudin L."/>
                <person name="Bauche S."/>
                <person name="Annat M."/>
                <person name="Annilo T."/>
                <person name="Allikmets R."/>
                <person name="Gold B."/>
                <person name="Denefle P."/>
                <person name="Rosier M."/>
                <person name="Dean M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-832</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Biochem. Biophys. Res. Commun." volume="300" first="343" last="350">
            <title>Cloning of human and rat ABCA5/Abca5 and detection of a human splice variant.</title>
            <authorList>
                <person name="Petry F."/>
                <person name="Kotthaus A."/>
                <person name="Hirsch-Ernst K.I."/>
            </authorList>
            <dbReference type="PubMed" id="12504089"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(02)02827-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS THR-178; ARG-484 AND SER-832</scope>
        <source>
            <tissue>Hepatoma</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1187-1642 (ISOFORM 1)</scope>
        <scope>VARIANT SER-832</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="DNA Res." volume="8" first="179" last="187">
            <title>Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="11572484"/>
            <dbReference type="DOI" id="10.1093/dnares/8.4.179"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 906-1642 (ISOFORM 1)</scope>
        <scope>VARIANT VAL-960</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="PLoS Genet." volume="10" first="e1004333" last="e1004333">
            <title>Mutations in the cholesterol transporter gene ABCA5 are associated with excessive hair overgrowth.</title>
            <authorList>
                <person name="DeStefano G.M."/>
                <person name="Kurban M."/>
                <person name="Anyane-Yeboa K."/>
                <person name="Dall'Armi C."/>
                <person name="Di Paolo G."/>
                <person name="Feenstra H."/>
                <person name="Silverberg N."/>
                <person name="Rohena L."/>
                <person name="Lopez-Cepeda L.D."/>
                <person name="Jobanputra V."/>
                <person name="Fantauzzo K.A."/>
                <person name="Kiuru M."/>
                <person name="Tadin-Strapps M."/>
                <person name="Sobrino A."/>
                <person name="Vitebsky A."/>
                <person name="Warburton D."/>
                <person name="Levy B."/>
                <person name="Salas-Alanis J.C."/>
                <person name="Christiano A.M."/>
            </authorList>
            <dbReference type="PubMed" id="24831815"/>
            <dbReference type="DOI" id="10.1371/journal.pgen.1004333"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="J. Alzheimers Dis." volume="43" first="857" last="869">
            <title>ABCA5 regulates amyloid-beta peptide production and is associated with Alzheimer's disease neuropathology.</title>
            <authorList>
                <person name="Fu Y."/>
                <person name="Hsiao J.H."/>
                <person name="Paxinos G."/>
                <person name="Halliday G.M."/>
                <person name="Kim W.S."/>
            </authorList>
            <dbReference type="PubMed" id="25125465"/>
            <dbReference type="DOI" id="10.3233/jad-141320"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="3 11">Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport (PubMed:25125465). May play a role in the processing of autolysosomes (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Golgi apparatus membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Lysosome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Late endosome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cell membrane</location>
        </subcellularLocation>
        <text evidence="3">Localized at cell membrane under high cholesterol levels.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WWZ7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WWZ7-2</id>
            <name>2</name>
            <name>V20+16</name>
            <sequence type="described" ref="VSP_020691 VSP_020692"/>
        </isoform>
        <isoform>
            <id>Q8WWZ7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_020690"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8 10 11 12">Ubiquitously expressed. Highly expressed in testis, skeletal muscle, kidney, liver and placenta. Expressed in both the epithelial and mesenchymal compartments, present within the outer root sheath (ORS) of the hair follicle as well as dermal sheath (PubMed:24831815). Expressed in multiple regions of the brain, including the hippocampus, superior frontal and inferior temporal cortices (PubMed:25125465). Strongly expressed in neurons and moderately in microglia, with only weak expression in astrocytes and oligodendrocytes (PubMed:25125465).</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="12">Expressed in fetal liver, kidney and brain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">N-glycosylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="15">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB71700" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="16"/>
    <dbReference type="EMBL" id="AY028897">
        <property type="protein sequence ID" value="AAK30022.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ275973">
        <property type="protein sequence ID" value="CAB93535.3"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ512612">
        <property type="protein sequence ID" value="CAD54757.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK056533">
        <property type="protein sequence ID" value="BAB71208.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK058170">
        <property type="protein sequence ID" value="BAB71700.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB067475">
        <property type="protein sequence ID" value="BAB67781.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11685.1">
        <molecule id="Q8WWZ7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_061142.2">
        <molecule id="Q8WWZ7-1"/>
        <property type="nucleotide sequence ID" value="NM_018672.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_758424.1">
        <molecule id="Q8WWZ7-1"/>
        <property type="nucleotide sequence ID" value="NM_172232.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8WWZ7"/>
    <dbReference type="SMR" id="Q8WWZ7"/>
    <dbReference type="BioGRID" id="117024">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8WWZ7">
        <property type="interactions" value="434"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WWZ7">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000376443"/>
    <dbReference type="DrugBank" id="DB00864">
        <property type="generic name" value="Tacrolimus"/>
    </dbReference>
    <dbReference type="TCDB" id="3.A.1.211.9">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q8WWZ7">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8WWZ7">
        <property type="glycosylation" value="3 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8WWZ7"/>
    <dbReference type="PhosphoSitePlus" id="Q8WWZ7"/>
    <dbReference type="BioMuta" id="ABCA5"/>
    <dbReference type="DMDM" id="115503762"/>
    <dbReference type="jPOST" id="Q8WWZ7"/>
    <dbReference type="MassIVE" id="Q8WWZ7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000376443"/>
    <dbReference type="PeptideAtlas" id="Q8WWZ7"/>
    <dbReference type="ProteomicsDB" id="74970">
        <molecule id="Q8WWZ7-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74971">
        <molecule id="Q8WWZ7-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74972">
        <molecule id="Q8WWZ7-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="19335">
        <property type="antibodies" value="174 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23461"/>
    <dbReference type="Ensembl" id="ENST00000392676.8">
        <molecule id="Q8WWZ7-1"/>
        <property type="protein sequence ID" value="ENSP00000376443.2"/>
        <property type="gene ID" value="ENSG00000154265.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000588877.5">
        <molecule id="Q8WWZ7-1"/>
        <property type="protein sequence ID" value="ENSP00000467882.1"/>
        <property type="gene ID" value="ENSG00000154265.17"/>
    </dbReference>
    <dbReference type="GeneID" id="23461"/>
    <dbReference type="KEGG" id="hsa:23461"/>
    <dbReference type="MANE-Select" id="ENST00000392676.8">
        <property type="protein sequence ID" value="ENSP00000376443.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_172232.4"/>
        <property type="RefSeq protein sequence ID" value="NP_758424.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002jif.3">
        <molecule id="Q8WWZ7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:35"/>
    <dbReference type="ClinPGx" id="PA24380"/>
    <dbReference type="CTD" id="23461"/>
    <dbReference type="DisGeNET" id="23461"/>
    <dbReference type="GeneCards" id="ABCA5"/>
    <dbReference type="HGNC" id="HGNC:35">
        <property type="gene designation" value="ABCA5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000154265">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCA5"/>
    <dbReference type="MIM" id="612503">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000154265"/>
    <dbReference type="Orphanet" id="2026">
        <property type="disease" value="Gingival fibromatosis-hypertrichosis syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000154265"/>
    <dbReference type="eggNOG" id="KOG0059">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158172"/>
    <dbReference type="InParanoid" id="Q8WWZ7"/>
    <dbReference type="OMA" id="MNPLWPD"/>
    <dbReference type="OrthoDB" id="8061355at2759"/>
    <dbReference type="PAN-GO" id="Q8WWZ7">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WWZ7"/>
    <dbReference type="PathwayCommons" id="Q8WWZ7"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8WWZ7"/>
    <dbReference type="Agora" id="ENSG00000154265"/>
    <dbReference type="BioGRID-ORCS" id="23461">
        <property type="hits" value="13 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCA5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="23461"/>
    <dbReference type="Pharos" id="Q8WWZ7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WWZ7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WWZ7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000154265">
        <property type="expression patterns" value="Expressed in adrenal tissue and 204 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WWZ7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000139">
        <property type="term" value="C:Golgi membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005770">
        <property type="term" value="C:late endosome"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031902">
        <property type="term" value="C:late endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005765">
        <property type="term" value="C:lysosomal membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005764">
        <property type="term" value="C:lysosome"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042626">
        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005319">
        <property type="term" value="F:lipid transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033344">
        <property type="term" value="P:cholesterol efflux"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042632">
        <property type="term" value="P:cholesterol homeostasis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008203">
        <property type="term" value="P:cholesterol metabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034375">
        <property type="term" value="P:high-density lipoprotein particle remodeling"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006869">
        <property type="term" value="P:lipid transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010745">
        <property type="term" value="P:negative regulation of macrophage derived foam cell differentiation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:1903064">
        <property type="term" value="P:positive regulation of reverse cholesterol transport"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010874">
        <property type="term" value="P:regulation of cholesterol efflux"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043691">
        <property type="term" value="P:reverse cholesterol transport"/>
        <property type="evidence" value="ECO:0000305"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd03263">
        <property type="entry name" value="ABC_subfamily_A"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000335">
        <property type="entry name" value="ATP binding cassette subfamily A member 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000729">
        <property type="entry name" value="ATP-binding cassette, sub-family A (ABC1), member 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026082">
        <property type="entry name" value="ABCA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR056264">
        <property type="entry name" value="R2_ABCA1-4-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229">
        <property type="entry name" value="ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229:SF100">
        <property type="entry name" value="CHOLESTEROL TRANSPORTER ABCA5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12698">
        <property type="entry name" value="ABC2_membrane_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF23321">
        <property type="entry name" value="R1_ABCA1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000250669" description="Cholesterol transporter ABCA5">
        <location>
            <begin position="1"/>
            <end position="1642"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="32"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="220"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="264"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="297"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="328"/>
            <end position="348"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="355"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="396"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="866"/>
            <end position="886"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="967"/>
            <end position="987"/>
        </location>
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    <feature type="transmembrane region" description="Helical" evidence="4">
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            <begin position="1021"/>
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    <feature type="transmembrane region" description="Helical" evidence="4">
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    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
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    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="1207"/>
            <end position="1227"/>
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    <feature type="domain" description="ABC transporter 1" evidence="5">
        <location>
            <begin position="478"/>
            <end position="713"/>
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    <feature type="domain" description="ABC transporter 2" evidence="5">
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            <begin position="1290"/>
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    <feature type="region of interest" description="Disordered" evidence="6">
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            <begin position="1249"/>
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    <feature type="compositionally biased region" description="Acidic residues" evidence="6">
        <location>
            <begin position="1259"/>
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    <feature type="binding site" evidence="5">
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        <ligand>
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    <feature type="binding site" evidence="5">
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        <ligand>
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            <position position="86"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
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            <begin position="922"/>
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            <position position="93"/>
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            <position position="832"/>
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            <position position="960"/>
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            <position position="1260"/>
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        <variation>H</variation>
        <location>
            <position position="1215"/>
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    <feature type="sequence conflict" description="In Ref. 2; CAB93535." evidence="15" ref="2">
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            <position position="1357"/>
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    <feature type="sequence conflict" description="In Ref. 2; CAB93535." evidence="15" ref="2">
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            <position position="1366"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAB71208." evidence="15" ref="3">
        <original>D</original>
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            <position position="1371"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAB71208." evidence="15" ref="3">
        <original>A</original>
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        <source>
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    <evidence type="ECO:0000305" key="16">
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        <source>
            <dbReference type="HGNC" id="HGNC:35"/>
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    <accession>Q96JT3</accession>
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            <fullName evidence="27">Glucosylceramide transporter ABCA12</fullName>
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            <fullName>ATP-binding cassette sub-family A member 12</fullName>
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        <alternativeName>
            <fullName>ATP-binding cassette transporter 12</fullName>
            <shortName>ATP-binding cassette 12</shortName>
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        <name type="synonym">ABC12</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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            <dbReference type="PubMed" id="15815621"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <citation type="journal article" date="2009" name="J. Biol. Chem." volume="284" first="18942" last="18952">
            <title>Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes.</title>
            <authorList>
                <person name="Jiang Y.J."/>
                <person name="Uchida Y."/>
                <person name="Lu B."/>
                <person name="Kim P."/>
                <person name="Mao C."/>
                <person name="Akiyama M."/>
                <person name="Elias P.M."/>
                <person name="Holleran W.M."/>
                <person name="Grunfeld C."/>
                <person name="Feingold K.R."/>
            </authorList>
            <dbReference type="PubMed" id="19429679"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.006973"/>
        </citation>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="J. Dermatol. Sci." volume="60" first="128" last="129">
            <title>ABCA12 dysfunction causes a disorder in glucosylceramide accumulation during keratinocyte differentiation.</title>
            <authorList>
                <person name="Mitsutake S."/>
                <person name="Suzuki C."/>
                <person name="Akiyama M."/>
                <person name="Tsuji K."/>
                <person name="Yanagi T."/>
                <person name="Shimizu H."/>
                <person name="Igarashi Y."/>
            </authorList>
            <dbReference type="PubMed" id="20869849"/>
            <dbReference type="DOI" id="10.1016/j.jdermsci.2010.08.012"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2020" name="EMBO Rep." volume="21" first="e48692" last="e48692">
            <title>ABCA12 regulates insulin secretion from beta-cells.</title>
            <authorList>
                <person name="Ursino G.M."/>
                <person name="Fu Y."/>
                <person name="Cottle D.L."/>
                <person name="Mukhamedova N."/>
                <person name="Jones L.K."/>
                <person name="Low H."/>
                <person name="Tham M.S."/>
                <person name="Gan W.J."/>
                <person name="Mellett N.A."/>
                <person name="Das P.P."/>
                <person name="Weir J.M."/>
                <person name="Ditiatkovski M."/>
                <person name="Fynch S."/>
                <person name="Thorn P."/>
                <person name="Thomas H.E."/>
                <person name="Meikle P.J."/>
                <person name="Parkington H.C."/>
                <person name="Smyth I.M."/>
                <person name="Sviridov D."/>
            </authorList>
            <dbReference type="PubMed" id="32072744"/>
            <dbReference type="DOI" id="10.15252/embr.201948692"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2010" name="Hum. Mutat." volume="31" first="1090" last="1096">
            <title>ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.</title>
            <authorList>
                <person name="Akiyama M."/>
            </authorList>
            <dbReference type="PubMed" id="20672373"/>
            <dbReference type="DOI" id="10.1002/humu.21326"/>
        </citation>
        <scope>REVIEW ON VARIANTS</scope>
        <scope>INVOLVEMENT IN ARCI</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2003" name="Hum. Mol. Genet." volume="12" first="2369" last="2378">
            <title>Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2.</title>
            <authorList>
                <person name="Lefevre C."/>
                <person name="Audebert S."/>
                <person name="Jobard F."/>
                <person name="Bouadjar B."/>
                <person name="Lakhdar H."/>
                <person name="Boughdene-Stambouli O."/>
                <person name="Blanchet-Bardon C."/>
                <person name="Heilig R."/>
                <person name="Foglio M."/>
                <person name="Weissenbach J."/>
                <person name="Lathrop M."/>
                <person name="Prud'homme J.F."/>
                <person name="Fischer J."/>
            </authorList>
            <dbReference type="PubMed" id="12915478"/>
            <dbReference type="DOI" id="10.1093/hmg/ddg235"/>
        </citation>
        <scope>VARIANTS ARCI4A SER-1380; GLU-1381; HIS-1514; LYS-1539 AND SER-1651</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2005" name="Am. J. Hum. Genet." volume="76" first="794" last="803">
            <title>Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.</title>
            <authorList>
                <person name="Kelsell D.P."/>
                <person name="Norgett E.E."/>
                <person name="Unsworth H."/>
                <person name="Teh M.-T."/>
                <person name="Cullup T."/>
                <person name="Mein C.A."/>
                <person name="Dopping-Hepenstal P.J."/>
                <person name="Dale B.A."/>
                <person name="Tadini G."/>
                <person name="Fleckman P."/>
                <person name="Stephens K.G."/>
                <person name="Sybert V.P."/>
                <person name="Mallory S.B."/>
                <person name="North B.V."/>
                <person name="Witt D.R."/>
                <person name="Sprecher E."/>
                <person name="Taylor A.E.M."/>
                <person name="Ilchyshyn A."/>
                <person name="Kennedy C.T."/>
                <person name="Goodyear H."/>
                <person name="Moss C."/>
                <person name="Paige D."/>
                <person name="Harper J.I."/>
                <person name="Young B.D."/>
                <person name="Leigh I.M."/>
                <person name="Eady R.A.J."/>
                <person name="O'Toole E.A."/>
            </authorList>
            <dbReference type="PubMed" id="15756637"/>
            <dbReference type="DOI" id="10.1086/429844"/>
        </citation>
        <scope>VARIANT ASN-2365</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2006" name="J. Invest. Dermatol." volume="126" first="1518" last="1523">
            <title>Compound heterozygous mutations including a de novo missense mutation in ABCA12 led to a case of harlequin ichthyosis with moderate clinical severity.</title>
            <authorList>
                <person name="Akiyama M."/>
                <person name="Sakai K."/>
                <person name="Sugiyama-Nakagiri Y."/>
                <person name="Yamanaka Y."/>
                <person name="McMillan J.R."/>
                <person name="Sawamura D."/>
                <person name="Niizeki H."/>
                <person name="Miyagawa S."/>
                <person name="Shimizu H."/>
            </authorList>
            <dbReference type="PubMed" id="16675967"/>
            <dbReference type="DOI" id="10.1038/sj.jid.5700295"/>
        </citation>
        <scope>VARIANT ARCI4B ASN-387</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2006" name="J. Invest. Dermatol." volume="126" first="2408" last="2413">
            <title>ABCA12 is the major harlequin ichthyosis gene.</title>
            <authorList>
                <person name="Thomas A.C."/>
                <person name="Cullup T."/>
                <person name="Norgett E.E."/>
                <person name="Hill T."/>
                <person name="Barton S."/>
                <person name="Dale B.A."/>
                <person name="Sprecher E."/>
                <person name="Sheridan E."/>
                <person name="Taylor A.E."/>
                <person name="Wilroy R.S."/>
                <person name="DeLozier C."/>
                <person name="Burrows N."/>
                <person name="Goodyear H."/>
                <person name="Fleckman P."/>
                <person name="Stephens K.G."/>
                <person name="Mehta L."/>
                <person name="Watson R.M."/>
                <person name="Graham R."/>
                <person name="Wolf R."/>
                <person name="Slavotinek A."/>
                <person name="Martin M."/>
                <person name="Bourn D."/>
                <person name="Mein C.A."/>
                <person name="O'Toole E.A."/>
                <person name="Kelsell D.P."/>
            </authorList>
            <dbReference type="PubMed" id="16902423"/>
            <dbReference type="DOI" id="10.1038/sj.jid.5700455"/>
        </citation>
        <scope>VARIANT ARCI4B ARG-1179</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2007" name="J. Invest. Dermatol." volume="127" first="2669" last="2673">
            <title>Novel ABCA12 mutations identified in two cases of non-bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia.</title>
            <authorList>
                <person name="Natsuga K."/>
                <person name="Akiyama M."/>
                <person name="Kato N."/>
                <person name="Sakai K."/>
                <person name="Sugiyama-Nakagiri Y."/>
                <person name="Nishimura M."/>
                <person name="Hata H."/>
                <person name="Abe M."/>
                <person name="Arita K."/>
                <person name="Tsuji-Abe Y."/>
                <person name="Onozuka T."/>
                <person name="Aoyagi S."/>
                <person name="Kodama K."/>
                <person name="Ujiie H."/>
                <person name="Tomita Y."/>
                <person name="Shimizu H."/>
            </authorList>
            <dbReference type="PubMed" id="17508018"/>
            <dbReference type="DOI" id="10.1038/sj.jid.5700885"/>
        </citation>
        <scope>VARIANTS ARCI4A PRO-345 AND THR-1494</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2008" name="Br. J. Dermatol." volume="158" first="864" last="867">
            <title>Novel compound heterozygous nonsense and missense ABCA12 mutations lead to nonbullous congenital ichthyosiform erythroderma.</title>
            <authorList>
                <person name="Akiyama M."/>
                <person name="Sakai K."/>
                <person name="Hatamochi A."/>
                <person name="Yamazaki S."/>
                <person name="McMillan J.R."/>
                <person name="Shimizu H."/>
            </authorList>
            <dbReference type="PubMed" id="18284401"/>
            <dbReference type="DOI" id="10.1111/j.1365-2133.2008.08439.x"/>
        </citation>
        <scope>VARIANT ARCI4A ASP-1136</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
                <person name="Kern S.E."/>
                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] VAL-476</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2009" name="J. Invest. Dermatol." volume="129" first="2306" last="2309">
            <title>ABCA12 is a major causative gene for non-bullous congenital ichthyosiform erythroderma.</title>
            <authorList>
                <person name="Sakai K."/>
                <person name="Akiyama M."/>
                <person name="Yanagi T."/>
                <person name="McMillan J.R."/>
                <person name="Suzuki T."/>
                <person name="Tsukamoto K."/>
                <person name="Sugiyama H."/>
                <person name="Hatano Y."/>
                <person name="Hayashitani M."/>
                <person name="Takamori K."/>
                <person name="Nakashima K."/>
                <person name="Shimizu H."/>
            </authorList>
            <dbReference type="PubMed" id="19262603"/>
            <dbReference type="DOI" id="10.1038/jid.2009.23"/>
        </citation>
        <scope>VARIANTS ARCI4A SER-1235; HIS-1514; LEU-1798 AND LYS-1980</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2012" name="Eur. J. Dermatol." volume="22" first="178" last="181">
            <title>Non-bullous congenital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12.</title>
            <authorList>
                <person name="Nawaz S."/>
                <person name="Tariq M."/>
                <person name="Ahmad I."/>
                <person name="Malik N.A."/>
                <person name="Baig S.M."/>
                <person name="Dahl N."/>
                <person name="Klar J."/>
            </authorList>
            <dbReference type="PubMed" id="22257947"/>
            <dbReference type="DOI" id="10.1684/ejd.2011.1638"/>
        </citation>
        <scope>VARIANT ARCI4A VAL-1559</scope>
    </reference>
    <comment type="function">
        <text evidence="2 9 18 21">Transports lipids such as glucosylceramides from the outer to the inner leaflet of lamellar granules (LGs) membrane, whereby the lipids are finally transported to the keratinocyte periphery via the trans-Golgi network and LGs and released to the apical surface of the granular keratinocytes to form lipid lamellae in the stratum corneum of the epidermis, which is essential for skin barrier function (PubMed:16007253, PubMed:20869849). In the meantime, participates in the transport of the lamellar granules-associated proteolytic enzymes, in turn regulates desquamation and keratinocyte differentiation (PubMed:19179616). Furthermore, is essential for the regulation of cellular cholesterol homeostasis by regulating ABCA1-dependent cholesterol efflux from macrophages through interaction with NR1H2 and ABCA1 (By similarity). Plays pleiotropic roles in regulating glucose stimulated insulin secretion from beta cells, regulating the morphology and fusion of insulin granules, lipid raft abundance and the actin cytoskeleton (By similarity). Also involved in lung surfactant biogenesis (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 21">
            <text>ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.</text>
            <dbReference type="EC" id="7.6.2.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 21">
            <text>a beta-D-glucosylceramide(in) + ATP + H2O = a beta-D-glucosylceramide(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66660"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:83264"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="28 30">
            <dbReference type="Rhea" id="RHEA:66661"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts with NR1H2 and ABCA1; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9541582">
            <id>Q86UK0</id>
        </interactant>
        <interactant intactId="EBI-784112">
            <id>O95477</id>
            <label>ABCA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 15">Cytoplasmic vesicle</location>
            <location evidence="9 15">Secretory vesicle membrane</location>
            <topology evidence="27">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15">Golgi apparatus membrane</location>
        </subcellularLocation>
        <text evidence="9 15">Localizes in the limiting membrane of the lamellar granules (LGs) (PubMed:17927575). Trafficks from the Golgi apparatus to the lamellar granules (LGs) at the cell periphery in the uppermost granular layer keratinocytes where ABCA12-positive LGs fuse with the keratinocyte-cell membrane to secrete their lipid content to the extracellular space of the stratum corneum (PubMed:16007253, PubMed:17927575). Co-localizes through the Golgi apparatus to the cell periphery with glucosylceramide (PubMed:17927575).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q86UK0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q86UK0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011283 VSP_011284"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 9 13 15 18 23">Mainly expressed in the stomach, placenta, testis and fetal brain (PubMed:12697999). Expressed in the upper epidermal layers, mainly the granular layers, of skin (PubMed:16007253, PubMed:17591952, PubMed:17927575). Expressed throughout the normal interfollicular epidermis with prominent expression in the stratum granulosum (PubMed:19179616). Expressed in alpha and beta cells of pancreatic islets (PubMed:32072744).</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="13">At about 6 to 9 weeks estimated gestational age (EGA), expressed in the periderm during the early period when the two-layered epidermis form. At 10 to 13 weeks EGA, expressed in the entire epidermis with high expression in periderm until to 14 to 22 weeks EGA.</text>
    </comment>
    <comment type="induction">
        <text evidence="9 13 14 20 29">Up-regulated during keratinization (PubMed:16007253). Up-regulated after 15 weeks estimated gestational age (EGA) (PubMed:17591952). Highly up-regulated by PPARG activators such as ciglitazone, troglitazone, and the PPARD activator GW 0742 in time- and dose-dependent manner but independently of keratinocyte differentiation. In addition, modestly up-regulated by the NR1H3 and NR1H2 activator TO901317 in an keratinocyte differentiation-independent manner (PubMed:17611579). Up-regulated by N-(hexanoyl)sphing-4-enine in a time- and dose-dependent manner or by glucosyltransferase inhibitors, ceramidase inhibitors and sphingomyelin synthase inhibitors that increase endogenous ceramide levels and induce ABCA12 expression via the PPARD signaling pathway (PubMed:19429679). Up-regulated by N-acetylsphingosine in a time- and dose-dependent manner via the PPARD signaling pathway (Probable).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.</text>
    </comment>
    <comment type="disease" evidence="7 12 16 19 22">
        <disease id="DI-00588">
            <name>Ichthyosis, congenital, autosomal recessive 4A</name>
            <acronym>ARCI4A</acronym>
            <description>A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.</description>
            <dbReference type="MIM" id="601277"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 10 11">
        <disease id="DI-00584">
            <name>Ichthyosis, congenital, autosomal recessive 4B</name>
            <acronym>ARCI4B</acronym>
            <description>A rare, very severe form of congenital ichthyosis, in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period. Babies who survive into infancy and beyond develop skin changes resembling severe non-bullous congenital ichthyosiform erythroderma.</description>
            <dbReference type="MIM" id="242500"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="27">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="27">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAN40735" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.1" evidence="9 21"/>
    <dbReference type="EMBL" id="AY219711">
        <property type="protein sequence ID" value="AAP21093.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY033486">
        <property type="protein sequence ID" value="AAK54355.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC072062">
        <property type="protein sequence ID" value="AAY24276.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC114780">
        <property type="protein sequence ID" value="AAY24230.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF418105">
        <property type="protein sequence ID" value="AAN40735.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL080207">
        <property type="protein sequence ID" value="CAB45776.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33372.1">
        <molecule id="Q86UK0-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33373.1">
        <molecule id="Q86UK0-2"/>
    </dbReference>
    <dbReference type="PIR" id="T12512">
        <property type="entry name" value="T12512"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056472.2">
        <molecule id="Q86UK0-2"/>
        <property type="nucleotide sequence ID" value="NM_015657.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_775099.2">
        <molecule id="Q86UK0-1"/>
        <property type="nucleotide sequence ID" value="NM_173076.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q86UK0"/>
    <dbReference type="SMR" id="Q86UK0"/>
    <dbReference type="BioGRID" id="117585">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="CORUM" id="Q86UK0"/>
    <dbReference type="FunCoup" id="Q86UK0">
        <property type="interactions" value="78"/>
    </dbReference>
    <dbReference type="IntAct" id="Q86UK0">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="MINT" id="Q86UK0"/>
    <dbReference type="STRING" id="9606.ENSP00000272895"/>
    <dbReference type="TCDB" id="3.A.1.211.13">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q86UK0">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="435"/>
        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="528"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="543"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="577"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="608"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="623"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="648"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="752"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="826"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="920"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="963"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1170"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1524"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1663"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1704"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1769"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1819"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1835"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1876"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1921"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="1952"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2178"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2208"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2223"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2318"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2542"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="2547"/>
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    <feature type="splice variant" id="VSP_011283" description="In isoform 2." evidence="26">
        <location>
            <begin position="1"/>
            <end position="318"/>
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    <feature type="splice variant" id="VSP_011284" description="In isoform 2." evidence="26">
        <original>LLYTLDSPAQ</original>
        <variation>MFTYIKIITS</variation>
        <location>
            <begin position="319"/>
            <end position="328"/>
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    </feature>
    <feature type="sequence variant" id="VAR_055473" description="In dbSNP:rs16853238.">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="199"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055474" description="In dbSNP:rs11890512.">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055475" description="In dbSNP:rs11890468.">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055476" description="In dbSNP:rs11891778.">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067075" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs1295935868." evidence="12">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067076" description="In ARCI4B; dbSNP:rs746315995." evidence="10">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="387"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084428" description="In ARCI4B." evidence="9">
        <location>
            <begin position="434"/>
            <end position="2595"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019597" description="In dbSNP:rs113112835.">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="459"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062663" description="In a pancreatic ductal adenocarcinoma sample; somatic mutation; dbSNP:rs370640837." evidence="17">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="476"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027444" description="In dbSNP:rs16853149.">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="550"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027445" description="In dbSNP:rs7560008." evidence="6 24 25">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="777"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067077" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma." evidence="16">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1136"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067078" description="In ARCI4B; dbSNP:rs267606622." evidence="11">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067079" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs2105975227." evidence="19">
        <original>W</original>
        <variation>S</variation>
        <location>
            <position position="1235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027446" description="In dbSNP:rs13414448.">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1251"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019598" description="In ARCI4A; dbSNP:rs28940269." evidence="7">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="1380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019599" description="In ARCI4A; dbSNP:rs28940268." evidence="7">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1381"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084429" description="In ARCI4B; uncertain significance." evidence="9">
        <location>
            <position position="1385"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067080" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs1263698595." evidence="12">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1494"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019600" description="In ARCI4A; dbSNP:rs28940270." evidence="7 19">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1514"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019601" description="In ARCI4A; dbSNP:rs28940271." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1539"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027447" description="In dbSNP:rs13401480.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1546"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067081" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs1457513156." evidence="22">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1559"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019602" description="In ARCI4A; dbSNP:rs28940568." evidence="7">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="1651"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067082" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs181314573." evidence="19">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1798"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084430" description="In ARCI4B; uncertain significance." evidence="9">
        <location>
            <begin position="1950"/>
            <end position="2595"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067083" description="In ARCI4A; skin phenotype consistent with non-bullous congenital ichthyosiform erythroderma; dbSNP:rs763858530." evidence="19">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="1980"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027448" description="In dbSNP:rs1213011.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="2064"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027449" description="In dbSNP:rs726070." evidence="8">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="2365"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP21093." evidence="27" ref="1">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="651"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP21093." evidence="27" ref="1">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="811"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAK54355." evidence="27" ref="2">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="826"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP21093." evidence="27" ref="1">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="2079"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="E9Q876"/>
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    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
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    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12697999"/>
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="12915478"/>
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    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15756637"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16007253"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="16675967"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="16902423"/>
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    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="17508018"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="17591952"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="17611579"/>
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="17927575"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="18284401"/>
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    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="18772397"/>
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    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="19179616"/>
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    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="19262603"/>
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    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="19429679"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="20869849"/>
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    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="22257947"/>
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    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="32072744"/>
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    </evidence>
    <evidence type="ECO:0000269" key="24">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000269" key="25">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="26">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="27"/>
    <evidence type="ECO:0000305" key="28">
        <source>
            <dbReference type="PubMed" id="16007253"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="29">
        <source>
            <dbReference type="PubMed" id="19429679"/>
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    </evidence>
    <evidence type="ECO:0000305" key="30">
        <source>
            <dbReference type="PubMed" id="20869849"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="31">
        <source>
            <dbReference type="HGNC" id="HGNC:14637"/>
        </source>
    </evidence>
    <sequence length="2595" mass="293237" checksum="5B71359B642BBAE6" modified="2009-11-24" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="202" xmlns="https://uniprot.org/uniprot">
    <accession>P31941</accession>
    <accession>A0AVM1</accession>
    <accession>Q12807</accession>
    <accession>Q5JZ93</accession>
    <accession>Q9UH18</accession>
    <name>ABC3A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>DNA dC-&gt;dU-editing enzyme APOBEC-3A</fullName>
            <shortName>A3A</shortName>
            <ecNumber evidence="6 8 10 11">3.5.4.38</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Phorbolin-1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">APOBEC3A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1.</title>
            <authorList>
                <person name="Madsen P.P."/>
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            <dbReference type="PubMed" id="10469298"/>
            <dbReference type="DOI" id="10.1046/j.1523-1747.1999.00682.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 19-27; 31-35; 53-60; 112-123; 129-137 AND 192-198</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R84.1" last="R84.11">
            <title>A genome annotation-driven approach to cloning the human ORFeome.</title>
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                <person name="Collins J.E."/>
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                <person name="Davis M.P."/>
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            </authorList>
            <dbReference type="PubMed" id="15461802"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-10-r84"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="Nature" volume="402" first="489" last="495">
            <title>The DNA sequence of human chromosome 22.</title>
            <authorList>
                <person name="Dunham I."/>
                <person name="Hunt A.R."/>
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    </reference>
    <reference key="26">
        <citation type="journal article" date="2012" name="Semin. Cell Dev. Biol." volume="23" first="258" last="268">
            <title>Functions and regulation of the APOBEC family of proteins.</title>
            <authorList>
                <person name="Smith H.C."/>
                <person name="Bennett R.P."/>
                <person name="Kizilyer A."/>
                <person name="McDougall W.M."/>
                <person name="Prohaska K.M."/>
            </authorList>
            <dbReference type="PubMed" id="22001110"/>
            <dbReference type="DOI" id="10.1016/j.semcdb.2011.10.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5 6 7 8 10 11 12 13 14 15 16">DNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno-associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8 10 11">
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="17 18">Interacts with AGO2. Interacts with TRIB3 (via N-terminus).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13050366">
            <id>P31941</id>
        </interactant>
        <interactant intactId="EBI-17557678">
            <id>Q16775-2</id>
            <label>HAGH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13050366">
            <id>P31941</id>
        </interactant>
        <interactant intactId="EBI-396676">
            <id>O95630</id>
            <label>STAMBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13050366">
            <id>P31941</id>
        </interactant>
        <interactant intactId="EBI-11666471">
            <id>Q784Z8</id>
            <label>C</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>P31941-1</id>
            <name>1</name>
            <name>Phorbolin-1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P31941-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041723"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 6 8 9">Expressed in peripheral leukocytes with higher expression in CD14-positive phagocytic cells. Highly expressed in keratinocytes and in periphery blood monocytes. Also detected in non-lymphoid tissues including lung and adipose tissues. Found at high levels in colorectal adenocarcinoma, Burkitt's lymphoma and chronic myelogenous leukemia.</text>
    </comment>
    <comment type="induction">
        <text evidence="8 10">Up-regulated by interferon and CpG single-stranded DNA (at protein level).</text>
    </comment>
    <comment type="miscellaneous">
        <text>It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>Enzymatically active.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="19">Enzymatically active.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.38" evidence="6 8 10 11"/>
    <dbReference type="EMBL" id="U03891">
        <property type="protein sequence ID" value="AAA03706.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456393">
        <property type="protein sequence ID" value="CAG30279.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL022318">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126416">
        <property type="protein sequence ID" value="AAI26417.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13981.1">
        <molecule id="P31941-1"/>
    </dbReference>
    <dbReference type="PIR" id="G01233">
        <property type="entry name" value="G01233"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001180218.1">
        <molecule id="P31941-1"/>
        <property type="nucleotide sequence ID" value="NM_001193289.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_663745.1">
        <molecule id="P31941-1"/>
        <property type="nucleotide sequence ID" value="NM_145699.4"/>
    </dbReference>
    <dbReference type="PDB" id="2M65">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="4XXO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.84 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="5KEG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="5SWW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.15 A"/>
        <property type="chains" value="A/B/C/D=1-196"/>
    </dbReference>
    <dbReference type="PDB" id="7D3V">
        <property type="method" value="NMR"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="7D3W">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="7D3X">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="8FII">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.94 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="8FIJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="8FIK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.91 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="8FIL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.01 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDB" id="8FIM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.22 A"/>
        <property type="chains" value="A/B=1-199"/>
    </dbReference>
    <dbReference type="PDBsum" id="2M65"/>
    <dbReference type="PDBsum" id="4XXO"/>
    <dbReference type="PDBsum" id="5KEG"/>
    <dbReference type="PDBsum" id="5SWW"/>
    <dbReference type="PDBsum" id="7D3V"/>
    <dbReference type="PDBsum" id="7D3W"/>
    <dbReference type="PDBsum" id="7D3X"/>
    <dbReference type="PDBsum" id="8FII"/>
    <dbReference type="PDBsum" id="8FIJ"/>
    <dbReference type="PDBsum" id="8FIK"/>
    <dbReference type="PDBsum" id="8FIL"/>
    <dbReference type="PDBsum" id="8FIM"/>
    <dbReference type="AlphaFoldDB" id="P31941"/>
    <dbReference type="BMRB" id="P31941"/>
    <dbReference type="SMR" id="P31941"/>
    <dbReference type="BioGRID" id="128318">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-61365N"/>
    <dbReference type="FunCoup" id="P31941">
        <property type="interactions" value="135"/>
    </dbReference>
    <dbReference type="IntAct" id="P31941">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000384359"/>
    <dbReference type="BindingDB" id="P31941"/>
    <dbReference type="ChEMBL" id="CHEMBL1741179"/>
    <dbReference type="iPTMnet" id="P31941"/>
    <dbReference type="PhosphoSitePlus" id="P31941"/>
    <dbReference type="BioMuta" id="APOBEC3A"/>
    <dbReference type="DMDM" id="12644206"/>
    <dbReference type="jPOST" id="P31941"/>
    <dbReference type="MassIVE" id="P31941"/>
    <dbReference type="PaxDb" id="9606-ENSP00000384359"/>
    <dbReference type="PeptideAtlas" id="P31941"/>
    <dbReference type="ProteomicsDB" id="54806">
        <molecule id="P31941-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="54807">
        <molecule id="P31941-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P31941"/>
    <dbReference type="ABCD" id="P31941">
        <property type="antibodies" value="1 sequenced antibody"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="26513">
        <property type="antibodies" value="247 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="200315"/>
    <dbReference type="Ensembl" id="ENST00000249116.7">
        <molecule id="P31941-1"/>
        <property type="protein sequence ID" value="ENSP00000249116.2"/>
        <property type="gene ID" value="ENSG00000128383.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000402255.5">
        <molecule id="P31941-1"/>
        <property type="protein sequence ID" value="ENSP00000384359.1"/>
        <property type="gene ID" value="ENSG00000128383.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000570508.3">
        <molecule id="P31941-1"/>
        <property type="protein sequence ID" value="ENSP00000461288.1"/>
        <property type="gene ID" value="ENSG00000262156.6"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000623492.3">
        <molecule id="P31941-1"/>
        <property type="protein sequence ID" value="ENSP00000485234.1"/>
        <property type="gene ID" value="ENSG00000262156.6"/>
    </dbReference>
    <dbReference type="GeneID" id="100913187"/>
    <dbReference type="GeneID" id="200315"/>
    <dbReference type="KEGG" id="hsa:100913187"/>
    <dbReference type="KEGG" id="hsa:200315"/>
    <dbReference type="MANE-Select" id="ENST00000249116.7">
        <property type="protein sequence ID" value="ENSP00000249116.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_145699.4"/>
        <property type="RefSeq protein sequence ID" value="NP_663745.1"/>
    </dbReference>
    <dbReference type="MANE-Select" id="ENST00000570508.3">
        <property type="protein sequence ID" value="ENSP00000461288.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001193289.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001180218.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003awn.2">
        <molecule id="P31941-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17343"/>
    <dbReference type="AGR" id="HGNC:44196"/>
    <dbReference type="ClinPGx" id="PA24891"/>
    <dbReference type="CTD" id="100913187"/>
    <dbReference type="CTD" id="200315"/>
    <dbReference type="DisGeNET" id="100913187"/>
    <dbReference type="DisGeNET" id="200315"/>
    <dbReference type="GeneCards" id="APOBEC3A"/>
    <dbReference type="HGNC" id="HGNC:17343">
        <property type="gene designation" value="APOBEC3A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000128383">
        <property type="expression patterns" value="Group enriched (bone marrow, lymphoid tissue, urinary bladder)"/>
    </dbReference>
    <dbReference type="MIM" id="607109">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000128383"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000128383"/>
    <dbReference type="eggNOG" id="KOG4075">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000164701"/>
    <dbReference type="HOGENOM" id="CLU_080056_2_0_1"/>
    <dbReference type="InParanoid" id="P31941"/>
    <dbReference type="OMA" id="GNRWMIL"/>
    <dbReference type="OrthoDB" id="5956704at2759"/>
    <dbReference type="PAN-GO" id="P31941">
        <property type="GO annotations" value="12 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P31941"/>
    <dbReference type="BRENDA" id="3.5.4.38">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P31941"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="P31941"/>
    <dbReference type="SIGNOR" id="P31941"/>
    <dbReference type="Agora" id="ENSG00000128383"/>
    <dbReference type="BioGRID-ORCS" id="100913187">
        <property type="hits" value="2 hits in 89 CRISPR screens"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="200315">
        <property type="hits" value="13 hits in 1139 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APOBEC3A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P31941"/>
    <dbReference type="Pharos" id="P31941">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P31941"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="P31941">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000128383">
        <property type="expression patterns" value="Expressed in monocyte and 136 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P31941">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000932">
        <property type="term" value="C:P-body"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044355">
        <property type="term" value="P:clearance of foreign intracellular DNA"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070383">
        <property type="term" value="P:DNA cytosine deamination"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045087">
        <property type="term" value="P:innate immune response"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045869">
        <property type="term" value="P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045071">
        <property type="term" value="P:negative regulation of viral genome replication"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044029">
        <property type="term" value="P:positive regulation of gene expression via chromosomal CpG island demethylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010526">
        <property type="term" value="P:transposable element silencing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000047">
        <property type="entry name" value="Apolipoprotein B editing enzyme catalytic polypeptide-like 3H"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF39">
        <property type="entry name" value="DNA DC-DU-EDITING ENZYME APOBEC-3A-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18782">
        <property type="entry name" value="NAD2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0391">Immunity</keyword>
    <keyword id="KW-0399">Innate immunity</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171752" description="DNA dC-&gt;dU-editing enzyme APOBEC-3A">
        <location>
            <begin position="1"/>
            <end position="199"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="2">
        <location>
            <begin position="27"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="1">
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="70"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="101"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="106"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_041723" description="In isoform 2." evidence="19">
        <location>
            <begin position="1"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048721" description="In dbSNP:rs17000556.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on deaminase activity despite an altered restriction activity towards genetic invaders." evidence="11">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="28"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>K</original>
        <variation>F</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity." evidence="6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="6 11">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>W</original>
        <variation>L</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity." evidence="6">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on deaminase activity despite an altered restriction activity towards genetic invaders." evidence="11">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Altered deaminase activity and restriction activity towards genetic invaders." evidence="11">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="6"/>
            <end position="8"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="15"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="24"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="strand" evidence="20">
        <location>
            <begin position="27"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="32"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="41"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="45"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="62"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="71"/>
            <end position="82"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="88"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="turn" evidence="24">
        <location>
            <begin position="102"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="106"/>
            <end position="116"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="120"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="136"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="149"/>
            <end position="152"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="155"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="helix" evidence="23">
        <location>
            <begin position="179"/>
            <end position="195"/>
        </location>
    </feature>
    <feature type="turn" evidence="21">
        <location>
            <begin position="196"/>
            <end position="198"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10469298"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11863358"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12859895"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16527742"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="19461882"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="20062055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="20308164"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="20615867"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="21123384"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="21368204"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="21460793"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="21496894"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22457529"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="22896697"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="22915799"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="22977230"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="19"/>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="2M65"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="7D3V"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="7D3W"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="23">
        <source>
            <dbReference type="PDB" id="8FIK"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="8FIL"/>
        </source>
    </evidence>
    <sequence length="199" mass="23012" checksum="42E99E0D7DF7AA14" modified="2001-01-11" version="3">MEASPASGPRHLMDPHIFTSNFNNGIGRHKTYLCYEVERLDNGTSVKMDQHRGFLHNQAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFISWSPCFSWGCAGEVRAFLQENTHVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIMTYDEFKHCWDTFVDHQGCPFQPWDGLDEHSQALSGRLRAILQNQGN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-03-01" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>Q9HC16</accession>
    <accession>B2RDR9</accession>
    <accession>Q45F02</accession>
    <accession>Q5TF77</accession>
    <accession>Q7Z2N1</accession>
    <accession>Q7Z2N4</accession>
    <accession>Q9H9H8</accession>
    <name>ABC3G_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="57">DNA dC-&gt;dU-editing enzyme APOBEC-3G</fullName>
            <ecNumber evidence="4 21 25 26 46">3.5.4.38</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>APOBEC-related cytidine deaminase</fullName>
            <shortName>APOBEC-related protein</shortName>
            <shortName>ARCD</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>APOBEC-related protein 9</fullName>
            <shortName>ARP-9</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="53">CEM-15</fullName>
            <shortName evidence="53">CEM15</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Deoxycytidine deaminase</fullName>
            <shortName evidence="56">A3G</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="53 61" type="primary">APOBEC3G</name>
        <name type="ORF">MDS019</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Tashiro H."/>
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                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
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                <person name="Ikema Y."/>
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                <person name="Okitani R."/>
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                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Synovium</tissue>
            <tissue>Teratocarcinoma</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS ARG-186 AND GLU-275</scope>
    </reference>
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        <scope>INDUCTION</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH APOBEC3F; AGO2; EIF4E; EIF4ENIF1; DCP2 AND DDX6</scope>
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        <scope>SUBUNIT</scope>
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        <scope>INTERACTION WITH PRKACA</scope>
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        <scope>UBIQUITINATION AT LYS- 297; LYS-301; LYS-303 AND LYS-334 (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF 297-LYS--LYS-303 AND LYS-334</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF THR-218</scope>
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        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
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        <scope>MUTAGENESIS OF GLU-217 AND PRO-247</scope>
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        <scope>INTERACTION WITH MOV10</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH AGO1; AGO2 AND AGO3</scope>
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        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
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        <scope>UBIQUITINATION AT LYS-42; LYS-52; LYS-63; LYS-150; LYS-163; LYS-249; LYS-270; LYS-297; LYS-303 AND LYS-334 (MICROBIAL INFECTION)</scope>
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        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
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        <scope>UBIQUITINATION AT LYS--63; LYS-249; LYS-297; LYS-303 AND LYS-334 (MICROBIAL INFECTION)</scope>
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        <scope>INTERACTION WITH APOBEC3F</scope>
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        <scope>STRUCTURE BY NMR OF 198-384 IN COMPLEX WITH ZINC</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF ARG-213; ARG-215; GLU-259; TRP-285; ARG-313 AND ARG-320</scope>
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            <dbReference type="PubMed" id="18849968"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 197-380 IN COMPLEX WITH ZINC</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVE SITE</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF ARG-213; ARG-215; ASN-244; TRP-285 AND TYR-315</scope>
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            <dbReference type="PubMed" id="19153609"/>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVE SITE</scope>
        <scope>COFACTOR</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 191-380</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 193-384 IN COMPLEX WITH ZINC</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVE SITE</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF PRO-210; GLN-245; HIS-248; HIS-250; ARG-256; ASP-264; PHE-268; ASP-370; ARG-374; ARG-376 AND GLN-380</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) IN COMPLEX WITH ZINC; CBFB; CUL5; ELOB; ELOC AND HIV-1 VIF</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVE SITE</scope>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.50 ANGSTROMS) OF 11-384 IN COMPLEX WITH ZINC; CBFB AND HIV-1 VIF</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF ASP-128; 297-LYS--LYS-303 AND LYS-334</scope>
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    <comment type="function">
        <text evidence="3 4 5 6 7 8 10 12 13 15 17 20 21 25 26 27 29 31 33 36 39 40 41 43 44 46 48 55">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:12808465, PubMed:16527742, PubMed:17121840, PubMed:18288108, PubMed:18849968, PubMed:19153609, PubMed:21123384, PubMed:22791714, PubMed:25542899). Exhibits potent antiviral activity against Vif-deficient HIV-1 (PubMed:12167863, PubMed:12859895, PubMed:14557625, PubMed:20219927, PubMed:21835787, PubMed:22807680, PubMed:22915799, PubMed:23097438, PubMed:23152537, PubMed:31397674). After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA (PubMed:12808465, PubMed:12808466, PubMed:12809610, PubMed:12970355, PubMed:14528300, PubMed:22807680). The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells (PubMed:12808465, PubMed:12808466, PubMed:12809610, PubMed:12970355, PubMed:14528300). Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA (PubMed:12808465, PubMed:12809610, PubMed:12970355, PubMed:14528300). Exhibits antiviral activity also against simian immunodeficiency viruses (SIVs), hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV) (PubMed:15031497, PubMed:16378963, PubMed:18448976, PubMed:19458006, PubMed:20335265). May inhibit the mobility of LTR and non-LTR retrotransposons (PubMed:16527742).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 21 25 26 46">
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4 21 25 26 46 50 51">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="36 37 50 51">(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome (PubMed:21835787, PubMed:22190037, PubMed:36754086, PubMed:37419875). Can also be neutralized by simian immunodeficiency virus sooty mangabey monkey virus (SIV-sm) and chimpanzee immunodeficiency virus (SIV-cpz) Vif (PubMed:21835787).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="46">20.42 uM for 2'-deoxycytidine in single-stranded DNA</KM>
            <text evidence="46">kcat is 0.11 min(-1) with 2'-deoxycytidine in single-stranded DNA as substrate.</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="2 18 19 23 24 39 41 46 49">Homodimer (PubMed:11863358, PubMed:17020885, PubMed:18842592, PubMed:25542899). Homooligomer (PubMed:11863358, PubMed:17020885, PubMed:18842592). Can bind RNA to form ribonucleoprotein complexes of high-molecular-mass (HMM) or low-molecular-mass (LMM) (PubMed:11863358, PubMed:17020885, PubMed:18842592). HMM is inactive and heterogeneous in protein composition because of binding nonselectively to cellular RNAs, which in turn are associated with variety of cellular proteins (PubMed:11863358, PubMed:17020885, PubMed:18842592). The LMM form which is enzymatically active has few or no RNAs associated (PubMed:11863358, PubMed:17020885, PubMed:18842592). Its ability to form homooligomer is distinct from its ability to assemble into HMM (PubMed:11863358, PubMed:17020885, PubMed:18842592). Interacts with APOBEC3B, APOBEC3F, MOV10, AGO2, EIF4E, EIF4ENIF1, DCP2 and DDX6 in an RNA-dependent manner (PubMed:16699599, PubMed:22791714, PubMed:31792451). Interacts with AGO1, AGO3 and PKA/PRKACA (PubMed:18836454, PubMed:22915799).</text>
    </comment>
    <comment type="subunit">
        <text evidence="7 9 11 37 42 50 51">(Microbial infection) Interacts with HIV-1 Vif; promoting its ubiquitination by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif.</text>
    </comment>
    <comment type="subunit">
        <text evidence="38">(Microbial infection) Interacts with HIV-1 reverse transcriptase/ribonuclease H.</text>
    </comment>
    <comment type="subunit">
        <text evidence="32">(Microbial infection) Interacts with hepatitis B virus capsid protein.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717839">
            <id>Q9HC16</id>
        </interactant>
        <interactant intactId="EBI-717839">
            <id>Q9HC16</id>
            <label>APOBEC3G</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717839">
            <id>Q9HC16</id>
        </interactant>
        <interactant intactId="EBI-476586">
            <id>P17612</id>
            <label>PRKACA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717839">
            <id>Q9HC16</id>
        </interactant>
        <interactant intactId="EBI-15528966">
            <id>P69723</id>
            <label>vif</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717839">
            <id>Q9HC16</id>
        </interactant>
        <interactant intactId="EBI-15731903">
            <id>Q77YG0</id>
            <label>vif</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 17 18 22 35 36">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="22">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18 41">Cytoplasm</location>
            <location evidence="18 41">P-body</location>
        </subcellularLocation>
        <text evidence="7 17 18 22 36">Mainly cytoplasmic (PubMed:16527742, PubMed:16699599, PubMed:21835787). Small amount are found in the nucleus (PubMed:18667511). During HIV-1 infection, virion-encapsidated in absence of HIV-1 Vif (PubMed:12859895).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9HC16-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9HC16-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_009588 VSP_009589"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 3 30">Expressed in spleen, testes, ovary and peripheral blood leukocytes and CD4+ lymphocytes. Also expressed in non-permissive peripheral blood mononuclear cells, and several tumor cell lines; no expression detected in permissive lymphoid and non-lymphoid cell lines. Exists only in the LMM form in peripheral blood-derived resting CD4 T-cells and monocytes, both of which are refractory to HIV-1 infection. LMM is converted to a HMM complex when resting CD4 T-cells are activated or when monocytes are induced to differentiate into macrophages. This change correlates with increased susceptibility of these cells to HIV-1 infection.</text>
    </comment>
    <comment type="induction">
        <text evidence="16">Up-regulated by IFN-alpha.</text>
    </comment>
    <comment type="domain">
        <text evidence="19 34">The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10 11 28 37 45 47 48 50 51">(Microbial infection) Following infection by HIV-1, ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation (PubMed:14528300, PubMed:14528301, PubMed:19887642, PubMed:22190037, PubMed:23300442, PubMed:31253590, PubMed:36754086, PubMed:37419875). Deubiquitinated by USP49; leading to stabilization (PubMed:31397674).</text>
    </comment>
    <comment type="PTM">
        <text evidence="23 35">Phosphorylation at Thr-32 reduces its binding to HIV-1 Vif and subsequent ubiquitination and degradation thus promoting its antiviral activity.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="4 40">Accumulation of APOBEC3G induced non-lethal hypermutation could contribute to the genetic variation of primate lentiviral populations.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="2">It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="57">May be due to a competing donor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="57">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/045"/>
        <text>Protein wars - Issue 45 of April 2004</text>
    </comment>
    <dbReference type="EC" id="3.5.4.38" evidence="4 21 25 26 46"/>
    <dbReference type="EMBL" id="AK022802">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
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            <end position="336"/>
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            <position position="259"/>
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        <location>
            <position position="65"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
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    </feature>
    <feature type="binding site" evidence="1 50 51 64 65 67 68">
        <location>
            <position position="97"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 50 51 64 65 67 68">
        <location>
            <position position="100"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21 25 26 46 50 51 62 63 64 65 67 68">
        <location>
            <position position="257"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21 25 26 46 50 51 62 63 64 65 67 68">
        <location>
            <position position="288"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21 25 26 46 50 51 62 63 64 65 67 68">
        <location>
            <position position="291"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="site" description="Interaction with DNA" evidence="57">
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by PKA" evidence="23 35">
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by PKA and CAMK2" evidence="35">
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59">
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59 60">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59">
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59">
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59 60">
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="59">
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="58 59 60">
        <location>
            <position position="297"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="58">
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="58 59 60">
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="58 59 60">
        <location>
            <position position="334"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009588" description="In isoform 3." evidence="54">
        <original>VYSELKYHPEMRFFHWFSKWRK</original>
        <variation>VPPGLQSLCRQELSQLGKQTTH</variation>
        <location>
            <begin position="58"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009589" description="In isoform 3." evidence="54">
        <location>
            <begin position="80"/>
            <end position="384"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017837" description="In dbSNP:rs8177832." evidence="52">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048723" description="In dbSNP:rs17000736.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="256"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025060" description="In dbSNP:rs17496046." evidence="52">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="275"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of cytidine deaminase activity and significant decrease in antiviral activity; when associated with A-259." evidence="5 8 19">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on cytidine deaminase and antiviral activity." evidence="5 8 19">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="5 8 19">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains sensitive to HIV-1 Vif and able to bind Vif." evidence="42">
        <original>F</original>
        <variation>W</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains sensitive to HIV-1 Vif and able to bind Vif." evidence="42">
        <original>L</original>
        <variation>D</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not decrease cytidine deaminase activity." evidence="5">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="85"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains sensitive to HIV-1 Vif and able to bind Vif." evidence="42">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5 8">
        <original>C</original>
        <variation>A</variation>
        <variation>S</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains sensitive to HIV-1 Vif and able to bind Vif." evidence="42">
        <original>F</original>
        <variation>K</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif with complete loss of Vif-induced ubiquitination and degradation and Vif binding." evidence="14 42 51">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Nearly abolished catalytic efficiency of cytidine deaminase activity." evidence="46">
        <original>P</original>
        <variation>A</variation>
        <variation>G</variation>
        <location>
            <position position="210"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly reduces enzyme activity." evidence="21 25">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="213"/>
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    <feature type="mutagenesis site" description="Reduces enzyme activity." evidence="21 25">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="213"/>
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    <feature type="mutagenesis site" description="Abolishes enzyme activity." evidence="21 25">
        <original>R</original>
        <variation>A</variation>
        <variation>E</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Modifies the spectrum of action against mobile genetic elements; when associated with K-247." evidence="33">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="217"/>
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    <feature type="mutagenesis site" description="Loss of phosphorylation. No effect on cytidine deaminase activity or HIV-1 restriction activity." evidence="35">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Phosphomimetic mutant which shows loss of cytidine deaminase activity and HIV-1 restriction activity." evidence="35">
        <original>T</original>
        <variation>E</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not decrease cytidine deaminase activity." evidence="5">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="221"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes enzyme activity." evidence="25">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="244"/>
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    </feature>
    <feature type="mutagenesis site" description="Nearly abolished cytidine deaminase activity." evidence="46">
        <original>Q</original>
        <variation>A</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Modifies the spectrum of action against mobile genetic elements; when associated with K-217." evidence="33">
        <original>P</original>
        <variation>K</variation>
        <location>
            <position position="247"/>
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    </feature>
    <feature type="mutagenesis site" description="Improved catalytic efficiency of cytidine deaminase activity." evidence="46">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="248"/>
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    </feature>
    <feature type="mutagenesis site" description="Improved catalytic efficiency of cytidine deaminase activity." evidence="46">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="250"/>
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    </feature>
    <feature type="mutagenesis site" description="Strongly reduced cytidine deaminase activity." evidence="46">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="256"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="257"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of cytidine deaminase activity and significant decrease in antiviral activity." evidence="5 8 19 21">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="259"/>
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    <feature type="mutagenesis site" description="Loss of cytidine deaminase activity and significant decrease in antiviral activity; when associated with A-67." evidence="5 8 19 21">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="259"/>
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    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity and antiviral activity." evidence="5 8 19 21">
        <original>E</original>
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        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Nearly abolished cytidine deaminase activity." evidence="46">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="264"/>
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    </feature>
    <feature type="mutagenesis site" description="Strongly reduced cytidine deaminase activity." evidence="46">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="268"/>
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    <feature type="mutagenesis site" description="Abolishes enzyme activity." evidence="21 25">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="285"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="288"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreases cytidine deaminase activity." evidence="4 5 8">
        <original>C</original>
        <variation>A</variation>
        <variation>S</variation>
        <location>
            <position position="291"/>
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    </feature>
    <feature type="mutagenesis site" description="In 4KR mutant; decreased ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif; when associated with R-334." evidence="28 51">
        <original>KFISKNK</original>
        <variation>RFISRNR</variation>
        <location>
            <begin position="297"/>
            <end position="303"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes enzyme activity." evidence="21">
        <original>R</original>
        <variation>A</variation>
        <variation>E</variation>
        <location>
            <position position="313"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes enzyme activity." evidence="25">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="315"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly reduces enzyme activity." evidence="21">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces enzyme activity." evidence="21">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not decrease cytidine deaminase activity." evidence="5">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In 4KR mutant; decreased ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif; when associated with R-297--R-303." evidence="28">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="334"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduced catalytic efficiency of cytidine deaminase activity." evidence="46">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="370"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced cytidine deaminase activity." evidence="46">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="374"/>
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    </feature>
    <feature type="mutagenesis site" description="Strongly reduced cytidine deaminase activity." evidence="46">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly reduced cytidine deaminase activity." evidence="46">
        <original>Q</original>
        <variation>A</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; no nucleotide entry." evidence="57" ref="1">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; no nucleotide entry." evidence="57" ref="1">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="370"/>
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    </feature>
    <feature type="strand" evidence="76">
        <location>
            <begin position="10"/>
            <end position="12"/>
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    </feature>
    <feature type="helix" evidence="78">
        <location>
            <begin position="14"/>
            <end position="20"/>
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    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="35"/>
            <end position="42"/>
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    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="45"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="50"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="56"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="helix" evidence="75">
        <location>
            <begin position="62"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="helix" evidence="78">
        <location>
            <begin position="66"/>
            <end position="77"/>
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    </feature>
    <feature type="helix" evidence="75">
        <location>
            <begin position="78"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="86"/>
            <end position="94"/>
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    </feature>
    <feature type="helix" evidence="78">
        <location>
            <begin position="98"/>
            <end position="110"/>
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    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="114"/>
            <end position="122"/>
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    </feature>
    <feature type="turn" evidence="78">
        <location>
            <begin position="124"/>
            <end position="127"/>
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    <feature type="helix" evidence="78">
        <location>
            <begin position="129"/>
            <end position="140"/>
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    </feature>
    <feature type="strand" evidence="77">
        <location>
            <begin position="142"/>
            <end position="144"/>
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    </feature>
    <feature type="strand" evidence="78">
        <location>
            <begin position="148"/>
            <end position="151"/>
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    <feature type="helix" evidence="78">
        <location>
            <begin position="154"/>
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    <feature type="helix" evidence="78">
        <location>
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    <feature type="strand" evidence="72">
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    <sequence length="384" mass="46408" checksum="60525DC3B7D903D6" modified="2001-03-01" version="1">MKPHFRNTVERMYRDTFSYNFYNRPILSRRNTVWLCYEVKTKGPSRPPLDAKIFRGQVYSELKYHPEMRFFHWFSKWRKLHRDQEYEVTWYISWSPCTKCTRDMATFLAEDPKVTLTIFVARLYYFWDPDYQEALRSLCQKRDGPRATMKIMNYDEFQHCWSKFVYSQRELFEPWNNLPKYYILLHIMLGEILRHSMDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGFLEGRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIYDDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGRLRAILQNQEN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-17" modified="2026-01-28" version="159" xmlns="https://uniprot.org/uniprot">
    <accession>Q86UQ4</accession>
    <accession>A0A0A0MT16</accession>
    <accession>K9LC76</accession>
    <accession>K9LC79</accession>
    <accession>K9LCX7</accession>
    <accession>K9LDK8</accession>
    <accession>K9LDY4</accession>
    <accession>Q6ZTT7</accession>
    <accession>Q86WI2</accession>
    <accession>Q8N248</accession>
    <name>ABCAD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">ATP-binding cassette sub-family A member 13</fullName>
            <ecNumber evidence="1">7.6.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="12" type="primary">ABCA13</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>The human ATP binding cassette gene ABCA13, located on chromosome 7p12.3, encodes a 5058 amino acid protein with an extracellular domain encoded in part by a 4.8-kb conserved exon.</title>
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                <person name="Prades C."/>
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            <dbReference type="PubMed" id="12697998"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2013" name="Gene" volume="515" first="298" last="307">
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                <person name="Maess M.B."/>
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            </authorList>
            <dbReference type="PubMed" id="23266639"/>
            <dbReference type="DOI" id="10.1016/j.gene.2012.11.072"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6 AND 7)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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                <person name="Fujii Y."/>
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                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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                <person name="Senba T."/>
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                <person name="Morinaga M."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4659-5058 (ISOFORM 1)</scope>
        <source>
            <tissue>Thymus</tissue>
            <tissue>Tongue</tissue>
        </source>
    </reference>
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                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Leonard S."/>
                <person name="Rohlfing T."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Abbott A."/>
                <person name="Minx P."/>
                <person name="Maupin R."/>
                <person name="Strowmatt C."/>
                <person name="Latreille P."/>
                <person name="Miller N."/>
                <person name="Johnson D."/>
                <person name="Murray J."/>
                <person name="Woessner J.P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Schultz B.R."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Nelson J.O."/>
                <person name="Berkowicz N."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Bedell J.A."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Chissoe S.L."/>
                <person name="Marra M.A."/>
                <person name="Raymond C."/>
                <person name="Haugen E."/>
                <person name="Gillett W."/>
                <person name="Zhou Y."/>
                <person name="James R."/>
                <person name="Phelps K."/>
                <person name="Iadanoto S."/>
                <person name="Bubb K."/>
                <person name="Simms E."/>
                <person name="Levy R."/>
                <person name="Clendenning J."/>
                <person name="Kaul R."/>
                <person name="Kent W.J."/>
                <person name="Furey T.S."/>
                <person name="Baertsch R.A."/>
                <person name="Brent M.R."/>
                <person name="Keibler E."/>
                <person name="Flicek P."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Bailey J.A."/>
                <person name="Portnoy M.E."/>
                <person name="Torrents D."/>
                <person name="Chinwalla A.T."/>
                <person name="Gish W.R."/>
                <person name="Eddy S.R."/>
                <person name="McPherson J.D."/>
                <person name="Olson M.V."/>
                <person name="Eichler E.E."/>
                <person name="Green E.D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of two novel ABC transporters, ABCA12 and ABCA13, tentatively involved in lipid homeostasis.</title>
            <authorList>
                <person name="Schaap F.G."/>
                <person name="van Wijland M.J.A."/>
                <person name="Groen A.K."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 2933-5058 (ISOFORM 4)</scope>
        <scope>VARIANT PHE-3851</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2021" name="J. Biol. Chem." volume="296" first="100166" last="100177">
            <title>ABCA13 dysfunction associated with psychiatric disorders causes impaired cholesterol trafficking.</title>
            <authorList>
                <person name="Nakato M."/>
                <person name="Shiranaga N."/>
                <person name="Tomioka M."/>
                <person name="Watanabe H."/>
                <person name="Kurisu J."/>
                <person name="Kengaku M."/>
                <person name="Komura N."/>
                <person name="Ando H."/>
                <person name="Kimura Y."/>
                <person name="Kioka N."/>
                <person name="Ueda K."/>
            </authorList>
            <dbReference type="PubMed" id="33478937"/>
            <dbReference type="DOI" id="10.1074/jbc.ra120.015997"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="6">May mediate the cholesterol and gangliosides transport from the plasma membrane to intracellular vesicles in an ATP hydrolysis dependent manner, thus playing a role in their internalization by endocytic retrograde transport and may also participate in the endocytosis of synaptic vesicle in cortical neurons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasmic vesicle membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q86UQ4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_021069 VSP_021070"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_021068"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_054634"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_054633 VSP_054634"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_054633 VSP_054634 VSP_054636"/>
        </isoform>
        <isoform>
            <id>Q86UQ4-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_054633 VSP_054634 VSP_054635"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5">Significantly expressed in the bone marrow, trachea, testis, thyroid and lung as well as in skin fibroblasts.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="11">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ABC transporter superfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC03623" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAC86492" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAC86492" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="1"/>
    <dbReference type="EMBL" id="AY204751">
        <property type="protein sequence ID" value="AAP13576.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JF913488">
        <property type="protein sequence ID" value="AFH89038.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JF913489">
        <property type="protein sequence ID" value="AFH89039.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JF913490">
        <property type="protein sequence ID" value="AFH89040.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JF913491">
        <property type="protein sequence ID" value="AFH89041.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="JF913492">
        <property type="protein sequence ID" value="AFH89042.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK091270">
        <property type="protein sequence ID" value="BAC03623.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK126220">
        <property type="protein sequence ID" value="BAC86492.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073424">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073927">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091770">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC095039">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC232300">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC232312">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="FJ770081">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF458461">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF511036">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF501281">
        <property type="protein sequence ID" value="AAO59914.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47584.1">
        <molecule id="Q86UQ4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_689914.3">
        <molecule id="Q86UQ4-1"/>
        <property type="nucleotide sequence ID" value="NM_152701.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011513432.1">
        <molecule id="Q86UQ4-4"/>
        <property type="nucleotide sequence ID" value="XM_011515130.3"/>
    </dbReference>
    <dbReference type="SMR" id="Q86UQ4"/>
    <dbReference type="BioGRID" id="127551">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q86UQ4">
        <property type="interactions" value="94"/>
    </dbReference>
    <dbReference type="IntAct" id="Q86UQ4">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="MINT" id="Q86UQ4"/>
    <dbReference type="STRING" id="9606.ENSP00000411096"/>
    <dbReference type="TCDB" id="3.A.1.211.18">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="CarbonylDB" id="Q86UQ4"/>
    <dbReference type="GlyCosmos" id="Q86UQ4">
        <property type="glycosylation" value="4 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q86UQ4">
        <property type="glycosylation" value="6 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (4 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q86UQ4"/>
    <dbReference type="PhosphoSitePlus" id="Q86UQ4"/>
    <dbReference type="BioMuta" id="ABCA13"/>
    <dbReference type="DMDM" id="327478592"/>
    <dbReference type="jPOST" id="Q86UQ4"/>
    <dbReference type="MassIVE" id="Q86UQ4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000411096"/>
    <dbReference type="PeptideAtlas" id="Q86UQ4"/>
    <dbReference type="ProteomicsDB" id="69861">
        <molecule id="Q86UQ4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="69862">
        <molecule id="Q86UQ4-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="69863">
        <molecule id="Q86UQ4-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="51819">
        <property type="antibodies" value="68 antibodies from 14 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="154664"/>
    <dbReference type="Ensembl" id="ENST00000417403.5">
        <molecule id="Q86UQ4-2"/>
        <property type="protein sequence ID" value="ENSP00000409268.1"/>
        <property type="gene ID" value="ENSG00000179869.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000435803.6">
        <molecule id="Q86UQ4-1"/>
        <property type="protein sequence ID" value="ENSP00000411096.1"/>
        <property type="gene ID" value="ENSG00000179869.15"/>
    </dbReference>
    <dbReference type="GeneID" id="154664"/>
    <dbReference type="KEGG" id="hsa:154664"/>
    <dbReference type="MANE-Select" id="ENST00000435803.6">
        <property type="protein sequence ID" value="ENSP00000411096.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_152701.5"/>
        <property type="RefSeq protein sequence ID" value="NP_689914.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc064dot.1">
        <molecule id="Q86UQ4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:14638"/>
    <dbReference type="ClinPGx" id="PA134925234"/>
    <dbReference type="CTD" id="154664"/>
    <dbReference type="DisGeNET" id="154664"/>
    <dbReference type="GeneCards" id="ABCA13"/>
    <dbReference type="HGNC" id="HGNC:14638">
        <property type="gene designation" value="ABCA13"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCA13"/>
    <dbReference type="MIM" id="607807">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000179869"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000179869"/>
    <dbReference type="eggNOG" id="KOG0059">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161703"/>
    <dbReference type="HOGENOM" id="CLU_076113_0_0_1"/>
    <dbReference type="InParanoid" id="Q86UQ4"/>
    <dbReference type="OMA" id="PNQFQNI"/>
    <dbReference type="OrthoDB" id="9833608at2759"/>
    <dbReference type="PAN-GO" id="Q86UQ4">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q86UQ4"/>
    <dbReference type="PathwayCommons" id="Q86UQ4"/>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q86UQ4"/>
    <dbReference type="SIGNOR" id="Q86UQ4"/>
    <dbReference type="Agora" id="ENSG00000179869"/>
    <dbReference type="BioGRID-ORCS" id="154664">
        <property type="hits" value="15 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCA13">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCA13"/>
    <dbReference type="GenomeRNAi" id="154664"/>
    <dbReference type="Pharos" id="Q86UQ4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q86UQ4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q86UQ4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000179869">
        <property type="expression patterns" value="Expressed in bronchial epithelial cell and 93 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q86UQ4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035577">
        <property type="term" value="C:azurophil granule membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097708">
        <property type="term" value="C:intracellular vesicle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030667">
        <property type="term" value="C:secretory granule membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042626">
        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005319">
        <property type="term" value="F:lipid transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035627">
        <property type="term" value="P:ceramide transport"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006869">
        <property type="term" value="P:lipid transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032376">
        <property type="term" value="P:positive regulation of cholesterol transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1900244">
        <property type="term" value="P:positive regulation of synaptic vesicle endocytosis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd03263">
        <property type="entry name" value="ABC_subfamily_A"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000689">
        <property type="entry name" value="ATP binding cassette subfamily A member 12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000298">
        <property type="entry name" value="ATP-binding cassette sub-family A member 12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026082">
        <property type="entry name" value="ABCA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR056264">
        <property type="entry name" value="R2_ABCA1-4-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229:SF113">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY A MEMBER 13"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229">
        <property type="entry name" value="ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12698">
        <property type="entry name" value="ABC2_membrane_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF23321">
        <property type="entry name" value="R1_ABCA1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000253573" description="ATP-binding cassette sub-family A member 13">
        <location>
            <begin position="1"/>
            <end position="5058"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="23"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3568"/>
            <end position="3588"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3607"/>
            <end position="3627"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3648"/>
            <end position="3668"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3679"/>
            <end position="3699"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3709"/>
            <end position="3729"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="3752"/>
            <end position="3772"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4226"/>
            <end position="4246"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4458"/>
            <end position="4478"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4504"/>
            <end position="4524"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4536"/>
            <end position="4556"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4568"/>
            <end position="4588"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4607"/>
            <end position="4627"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="4651"/>
            <end position="4671"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="3">
        <location>
            <begin position="3842"/>
            <end position="4074"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="3">
        <location>
            <begin position="4718"/>
            <end position="4956"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="3875"/>
            <end position="3882"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="4754"/>
            <end position="4761"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_054633" description="In isoform 5, isoform 6 and isoform 7." evidence="9">
        <location>
            <begin position="1"/>
            <end position="2736"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021068" description="In isoform 3." evidence="11">
        <location>
            <begin position="1"/>
            <end position="2298"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021069" description="In isoform 2." evidence="8">
        <original>IPTDTSLEKMVCSVLSST</original>
        <variation>VHMLDCFSHRWAFPGDWI</variation>
        <location>
            <begin position="300"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021070" description="In isoform 2." evidence="8">
        <location>
            <begin position="318"/>
            <end position="5058"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054634" description="In isoform 4, isoform 5, isoform 6 and isoform 7." evidence="9 10">
        <original>F</original>
        <variation>FS</variation>
        <location>
            <position position="4271"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054635" description="In isoform 7." evidence="9">
        <location>
            <begin position="4478"/>
            <end position="4508"/>
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    </feature>
    <feature type="splice variant" id="VSP_054636" description="In isoform 6." evidence="9">
        <original>FGDGYTVKVWLCKEANQHCTVSDHLKLYFPGIQFKGQHLNLLEYHVPKRWGCLADLFKVIENNKTFLNIKHYSINQTTLEQVFINFASEQQQTLQSTLDPSTDSHHTHHLPI</original>
        <variation>KLNKTN</variation>
        <location>
            <begin position="4947"/>
            <end position="5058"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059087" description="In dbSNP:rs1880738.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="506"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059088" description="In dbSNP:rs2361519.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="555"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059089" description="In dbSNP:rs17712293.">
        <original>I</original>
        <variation>S</variation>
        <location>
            <position position="767"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059090" description="In dbSNP:rs17547816.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="799"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059091" description="In dbSNP:rs17132195.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="1434"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055470" description="In dbSNP:rs6583483.">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="1508"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059092" description="In dbSNP:rs17712299.">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="1540"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059093" description="In dbSNP:rs17132197.">
        <original>I</original>
        <variation>K</variation>
        <location>
            <position position="1889"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059094" description="In dbSNP:rs17661364.">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="2033"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059095" description="In dbSNP:rs17092911.">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="2154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059096" description="In dbSNP:rs1880736.">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="2178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059097" description="In dbSNP:rs17132198.">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="2212"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059098" description="In dbSNP:rs17132206.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="2436"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059099" description="In dbSNP:rs17132208.">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="2537"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059100" description="In dbSNP:rs2222648.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="2674"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059101" description="In dbSNP:rs3931814.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="3142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059102" description="In dbSNP:rs17132289." evidence="7">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="3851"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059103" description="In dbSNP:rs4917152.">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="4277"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059104" description="In dbSNP:rs4917153.">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="4302"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059105" description="In dbSNP:rs17132370.">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="4335"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP13576." evidence="11" ref="1">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="1416"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP13576." evidence="11" ref="1">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="2718"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP13576." evidence="11" ref="1">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="2831"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP13576." evidence="11" ref="1">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="2870"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAO59914." evidence="11" ref="5">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="3057"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AFH89038/AFH89039/AFH89041/AFH89042." evidence="11" ref="2">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="4446"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP13576." evidence="11" ref="1">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="4584"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5SSE9"/>
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    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12697998"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="23266639"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="33478937"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="5"/>
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    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="23266639"/>
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    <evidence type="ECO:0000303" key="10">
        <source ref="5"/>
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    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:14638"/>
        </source>
    </evidence>
    <sequence length="5058" mass="576160" checksum="912B52FAB669A40B" modified="2025-06-18" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-12-15" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>O75027</accession>
    <accession>G3XAC4</accession>
    <accession>O75345</accession>
    <accession>Q5VWY7</accession>
    <accession>Q5VWY8</accession>
    <accession>Q9BRE1</accession>
    <accession>Q9UND1</accession>
    <accession>Q9UP01</accession>
    <name>ABCB7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="20">Iron-sulfur clusters transporter ABCB7, mitochondrial</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20">ATP-binding cassette sub-family B member 7, mitochondrial</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 7</fullName>
            <shortName>ABC transporter 7 protein</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ABCB7</name>
        <name type="synonym">ABC7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS GLY-315 AND ILE-346</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>VARIANT SCAX6 MET-400</scope>
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    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="11050011"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT SCAX6 LYS-433</scope>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Umbilical cord blood</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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        <scope>INTERACTION WITH C10ORF88</scope>
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        <scope>FUNCTION</scope>
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        <scope>SUBUNIT</scope>
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        <scope>VARIANT SCAX6 LEU-411</scope>
        <scope>VARIANTS GLY-315 AND ILE-346</scope>
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        <scope>VARIANT SCAX6 ASP-208</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4 9 12 15 16">Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and participates in iron homeostasis (PubMed:10196363, PubMed:17192393, PubMed:33157103). Moreover, through a functional complex formed of ABCB7, FECH and ABCB10, also plays a role in the cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). In cardiomyocytes, regulates cellular iron homeostasis and cellular reactive oxygen species (ROS) levels through its interaction with COX4I1 (By similarity). May also play a role in hematopoiesis (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>(glutathione)4[2Fe(III)-2S] cluster(in) + ATP + H2O = (glutathione)4[2Fe(III)-2S] cluster(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67028"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167627"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:67029"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="16">ATPase activity is stimulated by glutathione.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="16">5.3 mM for Mg-ATP</KM>
            <KM evidence="16">0.54 mM for Mg-ATP (in the presence of the [2Fe-2S](GS)4 cluster)</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="4 14 15">Homodimer or heterodimer (PubMed:30765471). Interacts with C10orf88/PAAT (PubMed:25063848). Forms a complex with ABCB10 and FECH, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with FECH (PubMed:30765471). Interacts with ATP5F1A (By similarity). Interacts with COX4I1; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1236950">
            <id>O75027</id>
        </interactant>
        <interactant intactId="EBI-1236950">
            <id>O75027</id>
            <label>ABCB7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1236950">
            <id>O75027</id>
        </interactant>
        <interactant intactId="EBI-1390356">
            <id>P22830</id>
            <label>FECH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion inner membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O75027-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O75027-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_014635"/>
        </isoform>
        <isoform>
            <id>O75027-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_054700"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="9 10 11 13 16">
        <disease id="DI-02459">
            <name>Spinocerebellar ataxia, X-linked 6, with or without sideroblastic anemia</name>
            <acronym>SCAX6</acronym>
            <description>An X-linked recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar ataxia and mild anemia, with hypochromia and microcytosis.</description>
            <dbReference type="MIM" id="301310"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EMBL" id="AB005289">
        <property type="protein sequence ID" value="BAA28861.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF133659">
        <property type="protein sequence ID" value="AAD33045.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF241887">
        <property type="protein sequence ID" value="AAK20173.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF241872">
        <property type="protein sequence ID" value="AAK20173.1"/>
        <property type="status" value="JOINED"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="315"/>
            <end position="319"/>
        </location>
        <ligand>
            <name>glutathione</name>
            <dbReference type="ChEBI" id="CHEBI:57925"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="378"/>
            <end position="381"/>
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        <ligand>
            <name>glutathione</name>
            <dbReference type="ChEBI" id="CHEBI:57925"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="428"/>
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        <ligand>
            <name>glutathione</name>
            <dbReference type="ChEBI" id="CHEBI:57925"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="481"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
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    <feature type="binding site" evidence="7">
        <location>
            <begin position="505"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="23">
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="23">
        <location>
            <position position="251"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="4">
        <location>
            <position position="336"/>
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    <feature type="modified residue" description="Phosphotyrosine" evidence="4">
        <location>
            <position position="340"/>
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    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="4">
        <location>
            <position position="342"/>
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    </feature>
    <feature type="splice variant" id="VSP_014635" description="In isoform 2." evidence="18 19">
        <original>Q</original>
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        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054700" description="In isoform 3." evidence="20">
        <location>
            <begin position="112"/>
            <end position="151"/>
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    </feature>
    <feature type="sequence variant" id="VAR_067354" description="In SCAX6; dbSNP:rs515726147." evidence="13">
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        <location>
            <position position="208"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022872" evidence="11 17">
        <original>R</original>
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            <position position="315"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022873" evidence="11 17">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="346"/>
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    <feature type="sequence variant" id="VAR_009156" description="In SCAX6; dbSNP:rs72554634." evidence="9">
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        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022874" description="In SCAX6; dbSNP:rs80356713." evidence="11">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="411"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012640" description="In SCAX6; impaired maturation of cytosolic Fe/S proteins; loss of the ability to couple MgATP binding with stimulation of ATPase activity at the nucleotide binding domain; loss of [2Fe-2S]-(GS)4 cluster transport; loss of ATPase activity stimulation by [2Fe-2S]-(GS)4 cluster stimulation; dbSNP:rs80356714." evidence="10 16">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="433"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055471" description="In dbSNP:rs1340989.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="580"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037972" description="In dbSNP:rs1340989.">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="581"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly increases ATPase activity by [2Fe-2S]-(GS)4 cluster stimulation. Increases affinity for Mg-ATP. Does not affect affinity for Mg-ATP in the presence of the in the presence of [2Fe-2S]-(GS)4 cluster. Does not affect [2Fe-2S]-(GS)4 cluster transport." evidence="16">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="433"/>
        </location>
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    <feature type="mutagenesis site" description="Loss of ATPase activity stimulation by [2Fe-2S]-(GS)4 cluster stimulation. Loss of the ability to couple MgATP binding with stimulation of ATPase activity at the nucleotide binding domain. Loss of [2Fe-2S]-(GS)4 cluster transport." evidence="16">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="433"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA28861." evidence="20" ref="1">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>LLPIMF</original>
        <variation>PLPNHV</variation>
        <location>
            <begin position="271"/>
            <end position="276"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>L</original>
        <variation>LL</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>FALVT</original>
        <variation>LLGN</variation>
        <location>
            <begin position="293"/>
            <end position="297"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAC39865." evidence="20" ref="4">
        <original>IEMNK</original>
        <variation>LEIDQ</variation>
        <location>
            <begin position="320"/>
            <end position="324"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAD47141." evidence="20" ref="9">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="542"/>
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        <location>
            <begin position="134"/>
            <end position="170"/>
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    <feature type="helix" evidence="24">
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            <begin position="186"/>
            <end position="233"/>
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    <feature type="helix" evidence="24">
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    <feature type="helix" evidence="24">
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            <begin position="248"/>
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    <feature type="helix" evidence="24">
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            <end position="345"/>
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    <feature type="helix" evidence="24">
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            <begin position="350"/>
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            <begin position="410"/>
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    <feature type="helix" evidence="24">
        <location>
            <begin position="424"/>
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    <feature type="helix" evidence="24">
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            <begin position="450"/>
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            <begin position="487"/>
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    <feature type="strand" evidence="24">
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            <begin position="500"/>
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        <source>
            <dbReference type="PubMed" id="25063848"/>
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            <dbReference type="PubMed" id="9621516"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <source ref="5"/>
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    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="33157103"/>
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    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:48"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="19608861"/>
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    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="7VGF"/>
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    <sequence length="752" mass="82641" checksum="B1FFA57ABD24FB90" modified="2000-12-01" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="167" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N139</accession>
    <accession>Q6NSH9</accession>
    <accession>Q8N856</accession>
    <accession>Q8WWZ6</accession>
    <name>ABCA6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10">ATP-binding cassette sub-family A member 6</fullName>
            <ecNumber evidence="11">7.6.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ABCA6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Biochem. Biophys. Res. Commun." volume="285" first="1295" last="1301">
            <title>ABCA6, a novel A subclass ABC transporter.</title>
            <authorList>
                <person name="Kaminski W.E."/>
                <person name="Wenzel J.J."/>
                <person name="Piehler A."/>
                <person name="Langmann T."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="11478798"/>
            <dbReference type="DOI" id="10.1006/bbrc.2001.5326"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Macrophage</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="GeneScreen" volume="1" first="157" last="164">
            <title>Identifying and characterizing a five-gene cluster of ATP-binding cassette transporters mapping to human chromosome 17q24: a new subgroup within the ABCA subfamily.</title>
            <authorList>
                <person name="Arnould I."/>
                <person name="Schriml L.M."/>
                <person name="Prades C."/>
                <person name="Lachtermacher-Triunfol M."/>
                <person name="Schneider T."/>
                <person name="Maintoux C."/>
                <person name="Lemoine C."/>
                <person name="Debono D."/>
                <person name="Devaud C."/>
                <person name="Naudin L."/>
                <person name="Bauche S."/>
                <person name="Annat M."/>
                <person name="Annilo T."/>
                <person name="Allikmets R."/>
                <person name="Gold B."/>
                <person name="Denefle P."/>
                <person name="Rosier M."/>
                <person name="Dean M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS ILE-282; ILE-875 AND SER-1322</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 801-1617 (ISOFORM 1)</scope>
        <scope>VARIANT SER-1322</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2000" name="Proc. Natl. Acad. Sci. U.S.A." volume="97" first="817" last="822">
            <title>ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport.</title>
            <authorList>
                <person name="Klucken J."/>
                <person name="Buechler C."/>
                <person name="Orso E."/>
                <person name="Kaminski W.E."/>
                <person name="Porsch-Oezcueruemez M."/>
                <person name="Liebisch G."/>
                <person name="Kapinsky M."/>
                <person name="Diederich W."/>
                <person name="Drobnik W."/>
                <person name="Dean M."/>
                <person name="Allikmets R."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="10639163"/>
            <dbReference type="DOI" id="10.1073/pnas.97.2.817"/>
        </citation>
        <scope>INDUCTION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2009" name="J. Proteome Res." volume="8" first="651" last="661">
            <title>Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.</title>
            <authorList>
                <person name="Chen R."/>
                <person name="Jiang X."/>
                <person name="Sun D."/>
                <person name="Han G."/>
                <person name="Wang F."/>
                <person name="Ye M."/>
                <person name="Wang L."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="19159218"/>
            <dbReference type="DOI" id="10.1021/pr8008012"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-940</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2013" name="Int. J. Biochem. Cell Biol." volume="45" first="2651" last="2659">
            <title>FoxO regulates expression of ABCA6, an intracellular ATP-binding-cassette transporter responsive to cholesterol.</title>
            <authorList>
                <person name="Gai J."/>
                <person name="Ji M."/>
                <person name="Shi C."/>
                <person name="Li W."/>
                <person name="Chen S."/>
                <person name="Wang Y."/>
                <person name="Li H."/>
            </authorList>
            <dbReference type="PubMed" id="24028821"/>
            <dbReference type="DOI" id="10.1016/j.biocel.2013.08.020"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="11">Probable transporter which may play a role in macrophage lipid transport and homeostasis.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Golgi apparatus membrane</location>
            <topology evidence="10">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N139-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N139-2</id>
            <name>2</name>
            <name>ABCA6delta-139</name>
            <sequence type="described" ref="VSP_020697 VSP_020698"/>
        </isoform>
        <isoform>
            <id>Q8N139-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_020695 VSP_020696"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 8">Widely expressed with higher expression in liver.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="8">Expressed in fetal kidney, lung and liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="3 7">Up-regulated during monocyte differentiation into macrophages (PubMed:10639163). Down-regulated by cholesterol loading of macrophages (PubMed:10639163, PubMed:24028821).</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAM77557" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAM77558" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC04994" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="11"/>
    <dbReference type="EMBL" id="AF373290">
        <property type="protein sequence ID" value="AAM77557.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373328">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373291">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373292">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373293">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373294">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373295">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373296">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373297">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373298">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373299">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373300">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373301">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373302">
        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373303">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373304">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373305">
        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373306">
        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF373307">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373308">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373309">
        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373310">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373311">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373312">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373317">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373318">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373320">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF373327">
        <property type="protein sequence ID" value="AAM77558.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028898">
        <property type="protein sequence ID" value="AAK30023.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC070125">
        <property type="protein sequence ID" value="AAH70125.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK097296">
        <property type="protein sequence ID" value="BAC04994.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11683.1">
        <molecule id="Q8N139-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_525023.2">
        <molecule id="Q8N139-1"/>
        <property type="nucleotide sequence ID" value="NM_080284.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8N139"/>
    <dbReference type="SMR" id="Q8N139"/>
    <dbReference type="BioGRID" id="117023">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8N139">
        <property type="interactions" value="115"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N139">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000284425"/>
    <dbReference type="TCDB" id="3.A.1.211.15">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q8N139">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8N139">
        <property type="glycosylation" value="5 sites, 4 N-linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8N139"/>
    <dbReference type="PhosphoSitePlus" id="Q8N139"/>
    <dbReference type="SwissPalm" id="Q8N139"/>
    <dbReference type="BioMuta" id="ABCA6"/>
    <dbReference type="DMDM" id="115503764"/>
    <dbReference type="jPOST" id="Q8N139"/>
    <dbReference type="MassIVE" id="Q8N139"/>
    <dbReference type="PaxDb" id="9606-ENSP00000284425"/>
    <dbReference type="PeptideAtlas" id="Q8N139"/>
    <dbReference type="ProteomicsDB" id="71545">
        <molecule id="Q8N139-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71546">
        <molecule id="Q8N139-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71547">
        <molecule id="Q8N139-3"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="Q8N139-3">
        <molecule id="Q8N139-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="31832">
        <property type="antibodies" value="166 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23460"/>
    <dbReference type="Ensembl" id="ENST00000284425.7">
        <molecule id="Q8N139-1"/>
        <property type="protein sequence ID" value="ENSP00000284425.1"/>
        <property type="gene ID" value="ENSG00000154262.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000590645.1">
        <molecule id="Q8N139-3"/>
        <property type="protein sequence ID" value="ENSP00000466862.1"/>
        <property type="gene ID" value="ENSG00000154262.14"/>
    </dbReference>
    <dbReference type="GeneID" id="23460"/>
    <dbReference type="KEGG" id="hsa:23460"/>
    <dbReference type="MANE-Select" id="ENST00000284425.7">
        <property type="protein sequence ID" value="ENSP00000284425.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_080284.3"/>
        <property type="RefSeq protein sequence ID" value="NP_525023.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002jhw.2">
        <molecule id="Q8N139-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:36"/>
    <dbReference type="ClinPGx" id="PA24381"/>
    <dbReference type="CTD" id="23460"/>
    <dbReference type="DisGeNET" id="23460"/>
    <dbReference type="GeneCards" id="ABCA6"/>
    <dbReference type="HGNC" id="HGNC:36">
        <property type="gene designation" value="ABCA6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000154262">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="612504">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000154262"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000154262"/>
    <dbReference type="eggNOG" id="KOG0059">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162244"/>
    <dbReference type="HOGENOM" id="CLU_000604_19_1_1"/>
    <dbReference type="InParanoid" id="Q8N139"/>
    <dbReference type="OMA" id="ITSQIVF"/>
    <dbReference type="OrthoDB" id="8061355at2759"/>
    <dbReference type="PAN-GO" id="Q8N139">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N139"/>
    <dbReference type="PathwayCommons" id="Q8N139"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9615017">
        <property type="pathway name" value="FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8N139"/>
    <dbReference type="Agora" id="ENSG00000154262"/>
    <dbReference type="BioGRID-ORCS" id="23460">
        <property type="hits" value="26 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCA6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="23460"/>
    <dbReference type="Pharos" id="Q8N139">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8N139"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
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        <property type="term" value="F:ABC-type transporter activity"/>
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        <property type="term" value="F:ATP hydrolysis activity"/>
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        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
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        <property type="term" value="F:lipid transporter activity"/>
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        <property type="entry name" value="ATP binding cassette subfamily A member 5"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-1185">Reference proteome</keyword>
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            <begin position="1"/>
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            <begin position="31"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="355"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="397"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="854"/>
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            <begin position="1007"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="1062"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="1094"/>
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    <feature type="transmembrane region" description="Helical" evidence="1">
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            <begin position="1127"/>
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            <begin position="1150"/>
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            <begin position="1194"/>
            <end position="1214"/>
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            <begin position="478"/>
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            <begin position="1288"/>
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    <feature type="splice variant" id="VSP_020697" description="In isoform 2." evidence="10">
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            <begin position="636"/>
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    <feature type="splice variant" id="VSP_020698" description="In isoform 2." evidence="10">
        <location>
            <begin position="638"/>
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    </feature>
    <feature type="sequence variant" id="VAR_027576" description="In dbSNP:rs4968839." evidence="8">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="282"/>
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    </feature>
    <feature type="sequence variant" id="VAR_027577" description="In dbSNP:rs9282554.">
        <original>N</original>
        <variation>Y</variation>
        <location>
            <position position="610"/>
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    </feature>
    <feature type="sequence variant" id="VAR_027578" description="In dbSNP:rs9282553.">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="698"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027579" description="In dbSNP:rs7212506." evidence="8">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="875"/>
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    </feature>
    <feature type="sequence variant" id="VAR_027580" description="In dbSNP:rs2302134." evidence="5 8">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="1322"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH70125." evidence="10" ref="3">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH70125." evidence="10" ref="3">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAC04994." evidence="10" ref="4">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="812"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAC04994." evidence="10" ref="4">
        <original>MY</original>
        <variation>IH</variation>
        <location>
            <begin position="875"/>
            <end position="876"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10639163"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11478798"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="19159218"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24028821"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="10639163"/>
        </source>
    </evidence>
    <sequence length="1617" mass="184286" checksum="73940D8050B0A3CA" modified="2006-10-03" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="200" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NE71</accession>
    <accession>A2BF75</accession>
    <accession>O14897</accession>
    <accession>Q69YP6</accession>
    <name>ABCF1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family F member 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette 50</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>TNF-alpha-stimulated ABC protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABCF1</name>
        <name type="synonym">ABC50</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Genomics" volume="53" first="137" last="145">
            <title>ABC50, a novel human ATP-binding cassette protein found in tumor necrosis factor-alpha-stimulated synoviocytes.</title>
            <authorList>
                <person name="Richard M."/>
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                <person name="Beaulieu A.D."/>
            </authorList>
            <dbReference type="PubMed" id="9790762"/>
            <dbReference type="DOI" id="10.1006/geno.1998.5480"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="1999-09" db="EMBL/GenBank/DDBJ databases">
            <title>Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.</title>
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                <person name="Shiina S."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-07" db="EMBL/GenBank/DDBJ databases">
            <title>Genome diversity in HLA: a new strategy for detection of genetic polymorphisms in expressed genes within the HLA class III and class I regions.</title>
            <authorList>
                <person name="Shiina T."/>
                <person name="Ota M."/>
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                <person name="Inoko H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <title>The DNA sequence and analysis of human chromosome 6.</title>
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            <dbReference type="PubMed" id="14574404"/>
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        <scope>INTERACTION WITH EIF2S1</scope>
        <scope>ASSOCIATION WITH RIBOSOMES</scope>
        <scope>PHOSPHORYLATION AT SER-109 AND SER-140</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-228</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>ATP-BINDING</scope>
        <scope>ASSOCIATION WITH RIBOSOMES</scope>
        <scope>MUTAGENESIS OF LYS-342; GLN-367; GLY-454; GLU-477; HIS-506; LYS-664; GLN-695; GLY-745; GLU-768 AND HIS-797</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-108; SER-109; SER-140 AND SER-228</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Leukemic T-cell</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; SER-105; THR-108; SER-109; SER-140 AND SER-228</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-108; SER-109; SER-140; SER-166 AND SER-228</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; SER-105; THR-108; SER-109; SER-140; SER-166; SER-228 AND SER-595</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-105 AND THR-108</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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    <comment type="function">
        <text evidence="4">Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Isoform 2 interacts (via N-terminus) with EIF2S1; the interaction is independent of its phosphorylated status. Isoform 2 associates (via both ABC transporter domains) with the ribosomes.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Nucleus</location>
            <location evidence="4">Nucleoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Nucleus envelope</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NE71-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NE71-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012078"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Ubiquitous.</text>
    </comment>
    <comment type="induction">
        <text>By TNF in cultured synoviocytes.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Isoform 2 is phosphorylated at phosphoserine and phosphothreonine. Isoform 2 phosphorylation on Ser-109 and Ser-140 by CK2 inhibits association of EIF2 with ribosomes.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EMBL" id="AF027302">
        <property type="protein sequence ID" value="AAC70891.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BA000025">
        <property type="protein sequence ID" value="BAB63325.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB088096">
        <property type="protein sequence ID" value="BAC54928.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL662800">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL662825">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX000357">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX119957">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX248518">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR753328">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR388372">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX927220">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR759778">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR847863">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034488">
        <property type="protein sequence ID" value="AAH34488.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC112923">
        <property type="protein sequence ID" value="AAI12924.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832430">
        <property type="protein sequence ID" value="CAH10648.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34380.1">
        <molecule id="Q8NE71-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34381.1">
        <molecule id="Q8NE71-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001020262.1">
        <molecule id="Q8NE71-1"/>
        <property type="nucleotide sequence ID" value="NM_001025091.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001081.1">
        <molecule id="Q8NE71-2"/>
        <property type="nucleotide sequence ID" value="NM_001090.3"/>
    </dbReference>
    <dbReference type="PDB" id="5ZXD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.29 A"/>
        <property type="chains" value="A/B=300-841"/>
    </dbReference>
    <dbReference type="PDBsum" id="5ZXD"/>
    <dbReference type="AlphaFoldDB" id="Q8NE71"/>
    <dbReference type="SMR" id="Q8NE71"/>
    <dbReference type="BioGRID" id="106541">
        <property type="interactions" value="220"/>
    </dbReference>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000093318" description="ATP-binding cassette sub-family F member 1">
        <location>
            <begin position="1"/>
            <end position="845"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="1">
        <location>
            <begin position="304"/>
            <end position="548"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="1">
        <location>
            <begin position="625"/>
            <end position="840"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="261"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="559"/>
            <end position="602"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="2">
        <location>
            <begin position="29"/>
            <end position="39"/>
        </location>
    </feature>
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        <location>
            <begin position="47"/>
            <end position="64"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="2">
        <location>
            <begin position="73"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="147"/>
            <end position="160"/>
        </location>
    </feature>
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            <end position="226"/>
        </location>
    </feature>
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        <location>
            <begin position="227"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="559"/>
            <end position="580"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="336"/>
            <end position="343"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="658"/>
            <end position="665"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
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        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="24"/>
        </location>
    </feature>
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        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="9 13 14 15 16 17">
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CK2" evidence="3 9 13 14 15 16">
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by CK2" evidence="3 9 13 14 15 16">
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15 16">
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="8 9 11 12 13 14 15 16">
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 16">
        <location>
            <position position="595"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012078" description="In isoform 2." evidence="6">
        <location>
            <begin position="226"/>
            <end position="263"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048136" description="In dbSNP:rs6902544.">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces phosphorylation. Inhibits strongly phosphorylation by CK2; when associated with S-140. Does not inhibit interaction with EIF2; when associated with S-140. Does not inhibit association with ribosomes; when associated with S-140. Reduces EIF2 interaction with ribosomes; when associated with S-140. Does not inhibit protein synthesis; when associated with A-140." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces phosphorylation. Inhibits strongly phosphorylation by CK2; when associated with S-109. Does not inhibits interaction with EIF2; when associated with S-109. Does not inhibit association with ribosomes; when associated with S-109. Reduces EIF2 interaction with ribosomes; when associated with S-109. Does not inhibit protein synthesis; when associated with A-109." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding. Reduces ATP-binding. Inhibits ATP-binding and reduces protein synthesis; when associated with M-664. Shows an enhanced association with polyribosomes; when associated with M-664. Does not inhibit IRES-mediated protein synthesis; when associated with M-664." evidence="4">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="367"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="454"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding. Reduces protein synthesis; when associated with Q-768." evidence="4">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="477"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="506"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding. Reduces ATP-binding. Inhibits ATP-binding and reduces protein synthesis; when associated with M-342. Shows a reduced association with polyribosomes; when associated with M-664. Does not inhibit IRES-mediated protein synthesis; when associated with M-664." evidence="4">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="664"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="695"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="745"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding. Reduces protein synthesis; when associated with Q-477." evidence="4">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="768"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not inhibit ribosome binding." evidence="4">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="797"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH34488." evidence="7" ref="5">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT LYS-146</scope>
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            <dbReference type="PubMed" id="16060832"/>
            <dbReference type="DOI" id="10.1089/aid.2005.21.611"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT LYS-146</scope>
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            <dbReference type="PubMed" id="11863358"/>
            <dbReference type="DOI" id="10.1006/geno.2002.6718"/>
        </citation>
        <scope>GENE FAMILY ORGANIZATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>RNA-BINDING</scope>
        <scope>ZINC-BINDING</scope>
        <scope>INTERACTION WITH APOBEC3G</scope>
    </reference>
    <reference key="7">
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            <title>Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business.</title>
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            </authorList>
            <dbReference type="PubMed" id="12683974"/>
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        </citation>
        <scope>REVIEW ON APOBEC FAMILIES</scope>
    </reference>
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            <title>Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.</title>
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        </citation>
        <scope>FUNCTION IN HIV-1 INFECTIVITY</scope>
    </reference>
    <reference key="9">
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            </authorList>
            <dbReference type="PubMed" id="15466872"/>
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        </citation>
        <scope>FUNCTION IN SIV RESTRICTION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="16527742"/>
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        </citation>
        <scope>FUNCTION IN RETROTRANSPOSITION</scope>
    </reference>
    <reference key="11">
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            </authorList>
            <dbReference type="PubMed" id="17020885"/>
            <dbReference type="DOI" id="10.1074/jbc.m604980200"/>
        </citation>
        <scope>DOMAIN CMP/DCMP DEAMINASE</scope>
    </reference>
    <reference key="12">
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            <title>Human retroviral host restriction factors APOBEC3G and APOBEC3F localize to mRNA processing bodies.</title>
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                <person name="Wichroski M.J."/>
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            </authorList>
            <dbReference type="PubMed" id="16699599"/>
            <dbReference type="DOI" id="10.1371/journal.ppat.0020041"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="13">
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                <person name="Greene W.C."/>
            </authorList>
            <dbReference type="PubMed" id="18304004"/>
            <dbReference type="DOI" id="10.1146/annurev.immunol.26.021607.090350"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="14">
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            <title>Hepatitis B: modern concepts in pathogenesis--APOBEC3 cytidine deaminases as effectors in innate immunity against the hepatitis B virus.</title>
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                <person name="Bonvin M."/>
                <person name="Greeve J."/>
            </authorList>
            <dbReference type="PubMed" id="18448976"/>
            <dbReference type="DOI" id="10.1097/qco.0b013e3282fe1bb2"/>
        </citation>
        <scope>REVIEW ON FUNCTION IN HBV RESTRICTION</scope>
    </reference>
    <reference key="15">
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            <title>Two regions within the amino-terminal half of APOBEC3G cooperate to determine cytoplasmic localization.</title>
            <authorList>
                <person name="Stenglein M.D."/>
                <person name="Matsuo H."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="18667511"/>
            <dbReference type="DOI" id="10.1128/jvi.02471-07"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="16">
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            <title>Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction.</title>
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                <person name="Refsland E.W."/>
                <person name="Stenglein M.D."/>
                <person name="Shindo K."/>
                <person name="Albin J.S."/>
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                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20308164"/>
            <dbReference type="DOI" id="10.1093/nar/gkq174"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="17">
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            <title>APOBEC3 proteins mediate the clearance of foreign DNA from human cells.</title>
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                <person name="Stenglein M.D."/>
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                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20062055"/>
            <dbReference type="DOI" id="10.1038/nsmb.1744"/>
        </citation>
        <scope>FUNCTION IN RETROTRANSPOSITION</scope>
    </reference>
    <reference key="18">
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            <title>Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.</title>
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                <person name="Hultquist J.F."/>
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                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="21835787"/>
            <dbReference type="DOI" id="10.1128/jvi.05238-11"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="19">
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            <title>Retroelements versus APOBEC3 family members: No great escape from the magnificent seven.</title>
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            </authorList>
            <dbReference type="PubMed" id="22912627"/>
            <dbReference type="DOI" id="10.3389/fmicb.2012.00275"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="20">
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            <title>APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1.</title>
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                <person name="Ooms M."/>
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        <scope>FUNCTION IN HTLV-1 RESTRICTION</scope>
    </reference>
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            <title>HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.</title>
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            <dbReference type="PubMed" id="22915799"/>
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        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="22">
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            <title>Functions and regulation of the APOBEC family of proteins.</title>
            <authorList>
                <person name="Smith H.C."/>
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            </authorList>
            <dbReference type="PubMed" id="22001110"/>
            <dbReference type="DOI" id="10.1016/j.semcdb.2011.10.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="6 8 10 11 15 18">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="5">Homodimer. Interacts with APOBEC3G. Does not interact with APOBEC1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2967317">
            <id>Q9UH17</id>
        </interactant>
        <interactant intactId="EBI-295644">
            <id>P11802</id>
            <label>CDK4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17624977">
            <id>Q9UH17-2</id>
        </interactant>
        <interactant intactId="EBI-712648">
            <id>O95994</id>
            <label>AGR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17624977">
            <id>Q9UH17-2</id>
        </interactant>
        <interactant intactId="EBI-752094">
            <id>Q12982</id>
            <label>BNIP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12 14 17 19">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UH17-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UH17-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009802"/>
        </isoform>
        <isoform>
            <id>Q9UH17-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_044900"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 16">Expressed at high and moderate levels in peripheral blood leukocytes, spleen, testes, heart, thymus, prostate and ovary. Also expressed at low levels in several other tissues.</text>
    </comment>
    <comment type="induction">
        <text evidence="4">Phorbol 12-myristate 13-acetate (PMA) induces overexpression in keratinocytes. Up-regulated by IFN-alpha.</text>
    </comment>
    <comment type="domain">
        <text evidence="13">The CMP/dCMP deaminase domain 1 mediates RNA binding, RNA-dependent oligomerization and virion incorporation whereas the CMP/dCMP deaminase domain 2 confers deoxycytidine deaminase activity and substrate sequence specificity.</text>
    </comment>
    <comment type="miscellaneous">
        <text>It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="22">May be due to a competing donor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="22">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <comment type="sequence caution" evidence="22">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAD00089" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="22">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAD00090" version="1"/>
        </conflict>
        <text>Frameshifts result in two separate ORFs termed phorbolins 2 and 3.</text>
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        <property type="protein sequence ID" value="AAD00089.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="U61084">
        <property type="protein sequence ID" value="AAD00090.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AY743217">
        <property type="protein sequence ID" value="AAW31743.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CT841510">
        <property type="protein sequence ID" value="CAJ86440.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL022318">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC053859">
        <property type="protein sequence ID" value="AAH53859.1"/>
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        <property type="nucleotide sequence ID" value="NM_001270411.2"/>
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        <property type="antibodies" value="1 sequenced antibody"/>
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        <property type="antibodies" value="168 antibodies from 29 providers"/>
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            <position position="62"/>
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            <position position="146"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD00090." evidence="22" ref="1">
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            <begin position="103"/>
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            <begin position="227"/>
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            <begin position="14"/>
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            <begin position="114"/>
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            <begin position="128"/>
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            <begin position="134"/>
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    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="7RW6"/>
        </source>
    </evidence>
    <sequence length="382" mass="45924" checksum="DA6EDD23E8856240" modified="2000-05-01" version="1">MNPQIRNPMERMYRDTFYDNFENEPILYGRSYTWLCYEVKIKRGRSNLLWDTGVFRGQVYFKPQYHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLSEHPNVTLTISAARLYYYWERDYRRALCRLSQAGARVTIMDYEEFAYCWENFVYNEGQQFMPWYKFDENYAFLHRTLKEILRYLMDPDTFTFNFNNDPLVLRRRQTYLCYEVERLDNGTWVLMDQHMGFLCNEAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFISWSPCFSWGCAGEVRAFLQENTHVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIMTYDEFEYCWDTFVYRQGCPFQPWDGLEEHSQALSGRLRAILQNQGN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="172" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IZY2</accession>
    <accession>Q96S58</accession>
    <accession>Q9BZC4</accession>
    <accession>Q9NR73</accession>
    <accession>Q9UKP8</accession>
    <name>ABCA7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="24">Phospholipid-transporting ATPase ABCA7</fullName>
            <ecNumber evidence="15">7.6.2.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="22">ABCA-SSN</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="24">ATP-binding cassette sub-family A member 7</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="23">Autoantigen SS-N</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="21">Macrophage ABC transporter</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="26" type="primary">ABCA7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS GLN-1349; ALA-1527 AND SER-2045</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ALA-1527</scope>
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        <scope>TISSUE SPECIFICITY</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <dbReference type="PubMed" id="12925201"/>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>FUNCTION</scope>
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        <scope>FUNCTION</scope>
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            <dbReference type="PubMed" id="26141617"/>
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        <scope>INVOLVEMENT IN AD9</scope>
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        <scope>INVOLVEMENT IN AD9</scope>
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        <scope>TISSUE SPECIFICITY</scope>
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        <scope>VARIANTS GLY-188; ALA-319; ARG-395; HIS-463; THR-718; GLN-1349; ARG-1686 AND SER-2045</scope>
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        <scope>VARIANT AD9 GLN-880</scope>
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    <comment type="function">
        <text evidence="2 11 12 13 14 15 18">Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:12917409, PubMed:12925201, PubMed:14570867, PubMed:14592415). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.</text>
            <dbReference type="EC" id="7.6.2.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38583"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57643"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:38584"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38567"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57262"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:38568"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="15">ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylserine, phosphatidylcholine and sphingomyelin, but phosphatidylserine is more effective.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838910">
            <id>Q8IZY2</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11 14">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Golgi apparatus membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Early endosome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Ruffle membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Phagocytic cup</location>
        </subcellularLocation>
        <text evidence="2">Localizes to cell membrane ruffles and phagocytic cups of macrophages stimulated with C1q or apoptotic cells. Localizes to the cytoplasm of resting macrophages, probably in Golgi and endosomes. Localizes to the apical brush border of cells in the proximal tubules of kidney (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="14">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="14">Endoplasmic reticulum</location>
        </subcellularLocation>
        <text evidence="14">May localize to the endoplasmic reticulum.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IZY2-1</id>
            <name>1</name>
            <name>Type 1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IZY2-2</id>
            <name>2</name>
            <name>Type 2</name>
            <sequence type="described" ref="VSP_020701 VSP_020702"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 9 14 19">Expressed in leukocytes (at protein level) (PubMed:10873640). Widely expressed (PubMed:10873640). Highly expressed in myelo-lymphatic tissues including peripheral leukocytes, thymus, spleen and bone marrow (PubMed:10873640, PubMed:11435699). Expressed in the hippocampus and the cerebellum (PubMed:27472885). Isoform 2: Abundant in lymph node, spleen, thymus and trachea (PubMed:14592415). Isoform 1: Strongly expressed in brain and bone marrow (PubMed:14592415).</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="6 9">Expressed in fetal tissues. Strongly expressed in fetal liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="6 12">Up-regulated in macrophages upon cholesterol uptake and inversely regulated upon cholesterol deloading from the cells (at protein level). Up-regulated in keratinocytes during terminal differentiation.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">N-glycosylated.</text>
    </comment>
    <comment type="disease" evidence="16 17 20">
        <disease id="DI-04711">
            <name>Alzheimer disease 9</name>
            <acronym>AD9</acronym>
            <description>A familial, late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.</description>
            <dbReference type="MIM" id="608907"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="24">Inactive for apoA-I-mediated lipid release.</text>
    </comment>
    <comment type="similarity">
        <text evidence="24">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="caution">
        <text evidence="2 11 19">There are conflicting results concerning the role of ABCA7 in lipid transport. ABCA7 was described to play a role in apolipoprotein-mediated phospholipid and cholesterol efflux when expressed in HEK293 cells (PubMed:12917409, PubMed:27472885). However, another report shows that ABCA7 deficiency does not influence cholesterol and phospholipid efflux in mouse primary macrophages, but leads to lower serum HDL cholesterol levels and a reduction in fat mass in female mice (By similarity).</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.1" evidence="15"/>
    <dbReference type="EMBL" id="AF250238">
        <property type="protein sequence ID" value="AAF85794.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311102">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311058">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311059">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311060">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311061">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311062">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311063">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311064">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311065">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311066">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311067">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311068">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311057">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311069">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311070">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311071">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311072">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311073">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311074">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311075">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311076">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311077">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311078">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311079">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311080">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311081">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311082">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311083">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311084">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311085">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311086">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311087">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311088">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311089">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311090">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311091">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311092">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311093">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311094">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311095">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311096">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311097">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311098">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311099">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311100">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311101">
        <property type="protein sequence ID" value="AAN04657.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB055390">
        <property type="protein sequence ID" value="BAB62294.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF328787">
        <property type="protein sequence ID" value="AAK00959.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011558">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF140342">
        <property type="protein sequence ID" value="AAF06727.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12055.1">
        <molecule id="Q8IZY2-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_061985.2">
        <molecule id="Q8IZY2-1"/>
        <property type="nucleotide sequence ID" value="NM_019112.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047294000.1">
        <molecule id="Q8IZY2-1"/>
        <property type="nucleotide sequence ID" value="XM_047438044.1"/>
    </dbReference>
    <dbReference type="PDB" id="8EDW">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDB" id="8EE6">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.00 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDB" id="8EEB">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDB" id="8EOP">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDB" id="8Y1O">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.92 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDB" id="8Y1P">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.45 A"/>
        <property type="chains" value="A=1-2146"/>
    </dbReference>
    <dbReference type="PDBsum" id="8EDW"/>
    <dbReference type="PDBsum" id="8EE6"/>
    <dbReference type="PDBsum" id="8EEB"/>
    <dbReference type="PDBsum" id="8EOP"/>
    <dbReference type="PDBsum" id="8Y1O"/>
    <dbReference type="PDBsum" id="8Y1P"/>
    <dbReference type="AlphaFoldDB" id="Q8IZY2"/>
    <dbReference type="EMDB" id="EMD-28041"/>
    <dbReference type="EMDB" id="EMD-28047"/>
    <dbReference type="EMDB" id="EMD-28050"/>
    <dbReference type="EMDB" id="EMD-28451"/>
    <dbReference type="EMDB" id="EMD-38841"/>
    <dbReference type="EMDB" id="EMD-38842"/>
    <dbReference type="SMR" id="Q8IZY2"/>
    <dbReference type="BioGRID" id="115629">
        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8IZY2">
        <property type="interactions" value="325"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8IZY2">
        <property type="interactions" value="47"/>
    </dbReference>
    <dbReference type="MINT" id="Q8IZY2"/>
    <dbReference type="STRING" id="9606.ENSP00000263094"/>
    <dbReference type="SwissLipids" id="SLP:000000346"/>
    <dbReference type="TCDB" id="3.A.1.211.10">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyConnect" id="1022">
        <property type="glycosylation" value="1 N-Linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q8IZY2">
        <property type="glycosylation" value="3 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8IZY2">
        <property type="glycosylation" value="10 sites, 4 N-linked glycans (6 sites), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8IZY2"/>
    <dbReference type="PhosphoSitePlus" id="Q8IZY2"/>
    <dbReference type="SwissPalm" id="Q8IZY2"/>
    <dbReference type="BioMuta" id="ABCA7"/>
    <dbReference type="DMDM" id="161784300"/>
    <dbReference type="jPOST" id="Q8IZY2"/>
    <dbReference type="MassIVE" id="Q8IZY2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000263094"/>
    <dbReference type="PeptideAtlas" id="Q8IZY2"/>
    <dbReference type="ProteomicsDB" id="71441">
        <molecule id="Q8IZY2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71442">
        <molecule id="Q8IZY2-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="22516">
        <property type="antibodies" value="184 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10347"/>
    <dbReference type="Ensembl" id="ENST00000263094.11">
        <molecule id="Q8IZY2-1"/>
        <property type="protein sequence ID" value="ENSP00000263094.6"/>
        <property type="gene ID" value="ENSG00000064687.13"/>
    </dbReference>
    <dbReference type="GeneID" id="10347"/>
    <dbReference type="KEGG" id="hsa:10347"/>
    <dbReference type="MANE-Select" id="ENST00000263094.11">
        <property type="protein sequence ID" value="ENSP00000263094.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_019112.4"/>
        <property type="RefSeq protein sequence ID" value="NP_061985.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002lqw.5">
        <molecule id="Q8IZY2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:37"/>
    <dbReference type="ClinPGx" id="PA24382"/>
    <dbReference type="CTD" id="10347"/>
    <dbReference type="DisGeNET" id="10347"/>
    <dbReference type="GeneCards" id="ABCA7"/>
    <dbReference type="HGNC" id="HGNC:37">
        <property type="gene designation" value="ABCA7"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000064687">
        <property type="expression patterns" value="Tissue enhanced (pituitary)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCA7"/>
    <dbReference type="MIM" id="605414">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="608907">
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        <source>
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    <sequence length="2146" mass="234350" checksum="6EA624088E74FEE6" modified="2007-12-04" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="253" xmlns="https://uniprot.org/uniprot">
    <accession>P33897</accession>
    <accession>Q6GTZ2</accession>
    <name>ABCD1_HUMAN</name>
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        <recommendedName>
            <fullName evidence="62">ATP-binding cassette sub-family D member 1</fullName>
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            <ecNumber evidence="15 35 36 56 59">7.6.2.-</ecNumber>
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        <alternativeName>
            <fullName evidence="51">Adrenoleukodystrophy protein</fullName>
            <shortName evidence="52 53">ALDP</shortName>
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    </protein>
    <gene>
        <name evidence="62" type="primary">ABCD1</name>
        <name type="synonym">ALD</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION OF VARIANTS ALD SER-512 AND LEU-606</scope>
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            <title>Human adrenoleukodystrophy protein and related peroxisomal ABC transporters interact with the peroxisomal assembly protein PEX19p.</title>
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        <scope>INTERACTION WITH PEX19</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>REGION</scope>
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        <scope>INTERACTION WITH PEX19</scope>
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            <dbReference type="PubMed" id="16213491"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2005.09.014"/>
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        <scope>INDUCTION</scope>
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        <scope>REGION</scope>
        <scope>MUTAGENESIS OF MET-67; ASN-68; ARG-69; VAL-70; PHE-71; LEU-72; GLN-73; ARG-74; LEU-75; LEU-76; TRP-77; LEU-78; LEU-79; ARG-80; LEU-81; LEU-82 AND PHE-83</scope>
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                <person name="Guimaraes C.P."/>
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            <dbReference type="PubMed" id="15682271"/>
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        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
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            <title>ATP-binding and -hydrolysis activities of ALDP (ABCD1) and ALDRP (ABCD2), human peroxisomal ABC proteins, overexpressed in Sf21 cells.</title>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>INTERACTION WITH ABCD3</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>REGION</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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                <person name="van Roermund C.W."/>
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                <person name="Wiesinger C."/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-733</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-733</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF LYS-513</scope>
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        <scope>VARIANT ALD LYS-291</scope>
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        <scope>VARIANTS ALD SER-148; ASP-174; ARG-266; GLN-401; TRP-418 AND PHE-515</scope>
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        <scope>VARIANTS ALD TRP-518; LEU-606; CYS-617 AND HIS-617</scope>
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        <scope>VARIANTS ALD CYS-104; ASN-149; PRO-152; HIS-163; HIS-194; PRO-220; ARG-266; HIS-389; GLY-609; LYS-609; CYS-617 AND TRP-660</scope>
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        <scope>VARIANTS ALD HIS-104; GLU-178; GLY-528 DEL AND LEU-560</scope>
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        <scope>VARIANTS ALD GLU-276; ASP-291; GLU-291 DEL; PRO-342; HIS-389; GLN-401; GLN-591; LEU-606; HIS-617; THR-626; HIS-629 AND TRP-660</scope>
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        <scope>VARIANTS ALD CYS-104; THR-141; PRO-182; TRP-277; HIS-389; SER-512; LYS-566; LEU-606; HIS-617 AND TRP-660</scope>
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            <dbReference type="PubMed" id="9452087"/>
            <dbReference type="DOI" id="10.1002/humu.1380110166"/>
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        <scope>VARIANT ALD ARG-679</scope>
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        <scope>REVIEW</scope>
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        <scope>VARIANTS ALD SER-148; ASN-200; ASP-214; ARG-266; LYS-271; CYS-296; TRP-401; VAL-507; GLN-518; SER-540; ARG-544; TRP-591; LEU-606 AND TRP-660</scope>
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        <scope>VARIANTS ALD PRO-105; SER-143; SER-148; PRO-190; ASP-298; ARG-339; SER-529 AND TYR-638</scope>
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        <scope>VARIANTS ALD LEU-108 AND SER-143</scope>
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        <scope>VARIANTS ALD ARG-103; ARG-116; SER-152; CYS-174; TRP-189; THR-218; PRO-229; ASP-298; GLN-401; TRP-401; TRP-418; LEU-543; HIS-554; VAL-616; ARG-633 AND PRO-646</scope>
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        <scope>VARIANTS ALD GLN-401; TRP-418; LEU-543 AND ARG-556</scope>
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        <scope>VARIANTS ALD LEU-98; ASP-99; GLU-217; GLN-518; ASP-608; ILE-633 AND PRO-660</scope>
        <scope>VARIANT THR-13</scope>
        <scope>CHARACTERIZATION OF VARIANT ALD GLU-217</scope>
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        <scope>VARIANTS ALD GLN-401; PRO-516; LEU-560; PRO-606 AND GLN-660</scope>
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        <scope>VARIANTS ALD LEU-139 DEL; ARG-198; ARG-266; GLU-266; TRP-401; GLN-518; PHE-523; CYS-540; LEU-560; PRO-606; HIS-617; THR-626; PRO-632; ARG-633; LYS-640 AND ASP-677</scope>
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    <comment type="function">
        <text evidence="2 15 20 23 25 27 32 35 36">ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed:15682271, PubMed:16946495, PubMed:18757502, PubMed:21145416, PubMed:23671276, PubMed:29397936, PubMed:33500543). Coupled to the ATP-dependent transporter activity also has a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process (PubMed:29397936, PubMed:33500543). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:21145416, PubMed:23671276). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Also controls the cellular response to oxidative stress by regulating mitochondrial functions such as mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="35 36">
            <text>a very long-chain fatty acyl-CoA + H2O = a very long-chain fatty acid + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67072"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
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    <comment type="catalytic activity">
        <reaction evidence="15 35 36 56 58 59">
            <text>a very long-chain fatty acid(in) + ATP + H2O = a very long-chain fatty acid(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
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            <dbReference type="Rhea" id="RHEA:67081"/>
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    </comment>
    <comment type="catalytic activity">
        <reaction evidence="36">
            <text>tetracosanoyl-CoA + H2O = tetracosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40787"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
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        <physiologicalReaction direction="left-to-right" evidence="60">
            <dbReference type="Rhea" id="RHEA:40788"/>
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    <comment type="catalytic activity">
        <reaction evidence="58">
            <text>tetracosanoate(in) + ATP + H2O = tetracosanoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67088"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
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        <physiologicalReaction direction="left-to-right" evidence="60">
            <dbReference type="Rhea" id="RHEA:67089"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="36">
            <text>hexacosanoyl-CoA + H2O = hexacosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40791"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:31013"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:64868"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="60">
            <dbReference type="Rhea" id="RHEA:40792"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="58 59">
            <text>hexacosanoate(in) + ATP + H2O = hexacosanoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67084"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:31013"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="58">
            <dbReference type="Rhea" id="RHEA:67085"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="36">
            <text>docosanoyl-CoA + H2O = docosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40783"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:23858"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65059"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="60">
            <dbReference type="Rhea" id="RHEA:40784"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="59">
            <text>docosanoate(in) + ATP + H2O = docosanoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67092"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:23858"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="59">
            <dbReference type="Rhea" id="RHEA:67093"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="36">The cysteine-reactive reagent p-chloromercuribenzoic acid (pCMB) strongly decreased the ACOT activity. The serine esterase inhibitors phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP) and bis-(4-nitrophenyl)phosphate (BNPP) moderately reduced the ACOT activity. The histidine-reacting reagent diethyl pyrocarbonate (DEPC) has no effect on the ACOT activity.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 10 11 13 24 57">Can form homodimers and heterodimers with ABCD2 and ABCD3. Dimerization is necessary to form an active transporter (Probable) (PubMed:10551832, PubMed:17609205). The minimal functional unit is a homodimer but the major oligomeric form in peroxisomal membrane is a homotetramer (By similarity). Forms heterotramers with ABCD2 (By similarity). Interacts with PEX19; facilitates ABCD1 insertion into the peroxisome membrane (PubMed:10704444, PubMed:10777694).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-81045">
            <id>P33897</id>
        </interactant>
        <interactant intactId="EBI-81045">
            <id>P33897</id>
            <label>ABCD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-81045">
            <id>P33897</id>
        </interactant>
        <interactant intactId="EBI-80992">
            <id>P28288</id>
            <label>ABCD3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-81045">
            <id>P33897</id>
        </interactant>
        <interactant intactId="EBI-594747">
            <id>P40855</id>
            <label>PEX19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-81045">
            <id>P33897</id>
        </interactant>
        <interactant intactId="EBI-81118">
            <id>P48410</id>
            <label>Abcd1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 23 24 25 35">Peroxisome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="23">Mitochondrion membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="23">Lysosome membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="23">Endoplasmic reticulum membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="induction">
        <text evidence="22">Up-regulated by degradation or export of cholesterol.</text>
    </comment>
    <comment type="domain">
        <text evidence="20">The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Tyrosine-phosphorylated.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 9 10 12 14 15 16 17 18 26 28 29 30 31 33 34 37 38 39 40 41 42 43 44 45 46 47 48 49 50">
        <disease id="DI-00050">
            <name>Adrenoleukodystrophy</name>
            <acronym>ALD</acronym>
            <description>A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype.</description>
            <dbReference type="MIM" id="300100"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text evidence="19">The promoter region of ABCD1 is deleted in the chromosome Xq28 deletion syndrome which involves ABCD1 and the neighboring gene BCAP31.</text>
    </comment>
    <comment type="similarity">
        <text evidence="54">Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="55 61">Variants Trp-88, Cys-152, Cys-181, Ser-343, Pro-503, Arg-514 and His-554 have original been associated with ALD. However this paper was retracted due to inconsistencies in a confirmation immunoblot that could not be validated from the originally published data.</text>
    </comment>
    <comment type="online information" name="X-ALD gene mutation database">
        <link uri="https://adrenoleukodystrophy.info/"/>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="35 36"/>
    <dbReference type="EC" id="7.6.2.-" evidence="15 35 36 56 59"/>
    <dbReference type="EMBL" id="Z21876">
        <property type="protein sequence ID" value="CAA79922.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31348">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31006">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31007">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31008">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31009">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z31010">
        <property type="protein sequence ID" value="CAA83230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U52111">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015541">
        <property type="protein sequence ID" value="AAH15541.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC025358">
        <property type="protein sequence ID" value="AAH25358.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14728.1"/>
    <dbReference type="PIR" id="G02500">
        <property type="entry name" value="G02500"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000024.2">
        <property type="nucleotide sequence ID" value="NM_000033.3"/>
    </dbReference>
    <dbReference type="PDB" id="7RR9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7RRA">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.40 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7SHM">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.14 A"/>
        <property type="chains" value="A/B=2-745"/>
    </dbReference>
    <dbReference type="PDB" id="7SHN">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B=2-686"/>
    </dbReference>
    <dbReference type="PDB" id="7VR1">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7VWC">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.53 A"/>
        <property type="chains" value="A/B=65-745"/>
    </dbReference>
    <dbReference type="PDB" id="7VX8">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=65-745"/>
    </dbReference>
    <dbReference type="PDB" id="7VZB">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.59 A"/>
        <property type="chains" value="A/B=65-745"/>
    </dbReference>
    <dbReference type="PDB" id="7X07">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.78 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7X0T">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7X0Z">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.96 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7X1W">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7XEC">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.34 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDB" id="7YRQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.35 A"/>
        <property type="chains" value="A/B=1-745"/>
    </dbReference>
    <dbReference type="PDBsum" id="7RR9"/>
    <dbReference type="PDBsum" id="7RRA"/>
    <dbReference type="PDBsum" id="7SHM"/>
    <dbReference type="PDBsum" id="7SHN"/>
    <dbReference type="PDBsum" id="7VR1"/>
    <dbReference type="PDBsum" id="7VWC"/>
    <dbReference type="PDBsum" id="7VX8"/>
    <dbReference type="PDBsum" id="7VZB"/>
    <dbReference type="PDBsum" id="7X07"/>
    <dbReference type="PDBsum" id="7X0T"/>
    <dbReference type="PDBsum" id="7X0Z"/>
    <dbReference type="PDBsum" id="7X1W"/>
    <dbReference type="PDBsum" id="7XEC"/>
    <dbReference type="PDBsum" id="7YRQ"/>
    <dbReference type="AlphaFoldDB" id="P33897"/>
    <dbReference type="EMDB" id="EMD-24656"/>
    <dbReference type="EMDB" id="EMD-24657"/>
    <dbReference type="EMDB" id="EMD-25130"/>
    <dbReference type="EMDB" id="EMD-25131"/>
    <dbReference type="EMDB" id="EMD-32096"/>
    <dbReference type="EMDB" id="EMD-32152"/>
    <dbReference type="EMDB" id="EMD-32171"/>
    <dbReference type="EMDB" id="EMD-32224"/>
    <dbReference type="EMDB" id="EMD-32919"/>
    <dbReference type="EMDB" id="EMD-32924"/>
    <dbReference type="EMDB" id="EMD-32930"/>
    <dbReference type="EMDB" id="EMD-32951"/>
    <dbReference type="EMDB" id="EMD-33155"/>
    <dbReference type="EMDB" id="EMD-34064"/>
    <dbReference type="SMR" id="P33897"/>
    <dbReference type="BioGRID" id="106717">
        <property type="interactions" value="86"/>
    </dbReference>
    <dbReference type="FunCoup" id="P33897">
        <property type="interactions" value="1414"/>
    </dbReference>
    <dbReference type="IntAct" id="P33897">
        <property type="interactions" value="58"/>
    </dbReference>
    <dbReference type="MINT" id="P33897"/>
    <dbReference type="STRING" id="9606.ENSP00000218104"/>
    <dbReference type="SwissLipids" id="SLP:000000458"/>
    <dbReference type="TCDB" id="3.A.1.203.3">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P33897">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P33897">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P33897"/>
    <dbReference type="PhosphoSitePlus" id="P33897"/>
    <dbReference type="SwissPalm" id="P33897"/>
    <dbReference type="BioMuta" id="ABCD1"/>
    <dbReference type="DMDM" id="67476960"/>
    <dbReference type="jPOST" id="P33897"/>
    <dbReference type="MassIVE" id="P33897"/>
    <dbReference type="PaxDb" id="9606-ENSP00000218104"/>
    <dbReference type="PeptideAtlas" id="P33897"/>
    <dbReference type="ProteomicsDB" id="54928"/>
    <dbReference type="Pumba" id="P33897"/>
    <dbReference type="Antibodypedia" id="30940">
        <property type="antibodies" value="446 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="215"/>
    <dbReference type="Ensembl" id="ENST00000218104.6">
        <property type="protein sequence ID" value="ENSP00000218104.3"/>
        <property type="gene ID" value="ENSG00000101986.13"/>
    </dbReference>
    <dbReference type="GeneID" id="215"/>
    <dbReference type="KEGG" id="hsa:215"/>
    <dbReference type="MANE-Select" id="ENST00000218104.6">
        <property type="protein sequence ID" value="ENSP00000218104.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000033.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000024.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004fif.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:61"/>
    <dbReference type="ClinPGx" id="PA24396"/>
    <dbReference type="CTD" id="215"/>
    <dbReference type="DisGeNET" id="215"/>
    <dbReference type="GeneCards" id="ABCD1"/>
    <dbReference type="GeneReviews" id="ABCD1"/>
    <dbReference type="HGNC" id="HGNC:61">
        <property type="gene designation" value="ABCD1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000101986">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCD1"/>
    <dbReference type="MIM" id="300100">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="300371">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000101986"/>
    <dbReference type="Orphanet" id="139399">
        <property type="disease" value="Adrenomyeloneuropathy"/>
    </dbReference>
    <dbReference type="Orphanet" id="369942">
        <property type="disease" value="CADDS"/>
    </dbReference>
    <dbReference type="Orphanet" id="388">
        <property type="disease" value="Hirschsprung disease"/>
    </dbReference>
    <dbReference type="Orphanet" id="139396">
        <property type="disease" value="X-linked cerebral adrenoleukodystrophy"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000101986"/>
    <dbReference type="eggNOG" id="KOG0064">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182955"/>
    <dbReference type="HOGENOM" id="CLU_007587_1_1_1"/>
    <dbReference type="InParanoid" id="P33897"/>
    <dbReference type="OMA" id="CHRTSLW"/>
    <dbReference type="OrthoDB" id="422637at2759"/>
    <dbReference type="PAN-GO" id="P33897">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P33897"/>
    <dbReference type="BRENDA" id="7.6.2.4">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P33897"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2046105">
        <property type="pathway name" value="Linoleic acid (LA) metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2046106">
        <property type="pathway name" value="alpha-linolenic acid (ALA) metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-390247">
        <property type="pathway name" value="Beta-oxidation of very long chain fatty acids"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5684045">
        <property type="pathway name" value="Defective ABCD1 causes ALD"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9603798">
        <property type="pathway name" value="Class I peroxisomal membrane protein import"/>
    </dbReference>
    <dbReference type="SignaLink" id="P33897"/>
    <dbReference type="Agora" id="ENSG00000101986"/>
    <dbReference type="BioGRID-ORCS" id="215">
        <property type="hits" value="23 hits in 782 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCD1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCD1"/>
    <dbReference type="GenomeRNAi" id="215"/>
    <dbReference type="Pharos" id="P33897">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P33897"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="RNAct" id="P33897">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000101986">
        <property type="expression patterns" value="Expressed in ileal mucosa and 130 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P33897">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005765">
        <property type="term" value="C:lysosomal membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048471">
        <property type="term" value="C:perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005778">
        <property type="term" value="C:peroxisomal membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015607">
        <property type="term" value="F:ABC-type fatty-acyl-CoA transporter activity"/>
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        <property type="entry name" value="FA_transporter"/>
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    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
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    <dbReference type="PANTHER" id="PTHR11384:SF21">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY D MEMBER 1"/>
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    <dbReference type="PANTHER" id="PTHR11384">
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    <dbReference type="Pfam" id="PF06472">
        <property type="entry name" value="ABC_membrane_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90123">
        <property type="entry name" value="ABC transporter transmembrane region"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ABC_TM1F"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00211">
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093304" description="ATP-binding cassette sub-family D member 1">
        <location>
            <begin position="1"/>
            <end position="745"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="92"/>
            <end position="112"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="131"/>
            <end position="151"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="238"/>
            <end position="258"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="333"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="473"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1" evidence="5">
        <location>
            <begin position="94"/>
            <end position="386"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="4">
        <location>
            <begin position="474"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with PEX19" evidence="13">
        <location>
            <begin position="67"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="region of interest" description="PEX19 binding site and required for peroxisomal targeting" evidence="21">
        <location>
            <begin position="67"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for homodimerization" evidence="24">
        <location>
            <begin position="658"/>
            <end position="745"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="507"/>
            <end position="514"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63 64">
        <location>
            <position position="733"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013340" description="Does not affect fatty acid beta-oxidation; dbSNP:rs183021839." evidence="16">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009349" description="In ALD." evidence="17">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075284" description="In ALD." evidence="31">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000024" description="In ALD; CALD type; dbSNP:rs1557052294." evidence="16 47">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013341" description="In ALD; AMN-type." evidence="16">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009350" description="In ALD." evidence="12">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="103"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000025" description="In ALD; dbSNP:rs2148388971." evidence="38 41">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000026" description="In ALD; ADO-type; dbSNP:rs1557052302." evidence="40">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000027" description="In ALD; ADO-type; dbSNP:rs2148388980." evidence="47">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009351" description="In ALD." evidence="9">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000028" description="In ALD; ALD/AMN/ADO-types and asymptomatic; dbSNP:rs1569540688." evidence="46">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009352" description="In ALD; dbSNP:rs2091705631." evidence="8 26">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000029" description="In ALD; CALD and AMN-types." evidence="47">
        <original>S</original>
        <variation>W</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009353" description="In ALD; dbSNP:rs1557052306." evidence="17">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013342" description="In ALD." evidence="17">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000030" description="In ALD; CALD-type; dbSNP:rs398123110." evidence="12 47">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000032" description="In ALD; ALD-type; dbSNP:rs1557052351." evidence="7">
        <location>
            <begin position="138"/>
            <end position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067239" description="In ALD; dbSNP:rs1557052351." evidence="28">
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000033" description="In ALD; dbSNP:rs193922097." evidence="38">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009354" description="In ALD." evidence="8 9">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000034" description="In ALD; ADO-type; dbSNP:rs128624216." evidence="6 9 26 42 47">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000035" description="In ALD." evidence="41">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009355" description="In ALD." evidence="17">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000037" description="In ALD; dbSNP:rs1557052367." evidence="41">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009356" description="In ALD; dbSNP:rs1569540693." evidence="12">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009357" description="In ALD; dbSNP:rs2148389260." evidence="17">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000038" description="In ALD; dbSNP:rs1057517954." evidence="41">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009358" description="In ALD; dbSNP:rs1057517954." evidence="17">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009359" description="In ALD; dbSNP:rs1557052390." evidence="12">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000039" description="In ALD; ALD-type; dbSNP:rs128624217." evidence="42 46">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000040" description="In ALD; CALD-type and AMN-type; dbSNP:rs1557052390." evidence="34 43">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000041" description="In ALD; AMN-type." evidence="40">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000043" description="In ALD." evidence="38">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009360" description="In ALD; dbSNP:rs1131691916." evidence="12">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="189"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009361" description="In ALD." evidence="9">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="190"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000044" description="In ALD." evidence="41">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="194"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009362" description="In ALD." evidence="17">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067240" description="In ALD." evidence="28">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009363" description="In ALD; dbSNP:rs2091708688." evidence="6">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000045" description="In ALD; CALD-type." evidence="47">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013343" description="In ALD." evidence="17">
        <original>S</original>
        <variation>SAAS</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000046" description="In ALD." evidence="46">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009364" description="In ALD." evidence="49">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009365" description="In ALD." evidence="6 26">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013344" description="In ALD; not able to restore defective beta-oxidation in fibroblast from patients with ALD." evidence="16">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009366" description="In ALD." evidence="12">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000047" description="In ALD; dbSNP:rs2091709142." evidence="41">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="220"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000048" description="In ALD; CALD and AMN-types." evidence="47">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="221"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013345" description="In ALD." evidence="17">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009367" description="In ALD." evidence="12">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000049" description="In ALD; AMN-type; dbSNP:rs1131691743." evidence="46">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000050" description="In ALD; AMN-type." evidence="26">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000051" description="In ALD; CALD, AMN and AD-types." evidence="47">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="263"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067241" description="In ALD; dbSNP:rs2091711094." evidence="28">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000052" description="In ALD; dbSNP:rs128624218." evidence="6 26 28 30 41 42">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009368" description="In ALD." evidence="6 26">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013346" description="In ALD; uncertain significance; dbSNP:rs782760033." evidence="17">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000053" description="In ALD; CALD-type." evidence="39">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000055" description="In ALD; ADO-type." evidence="7">
        <original>G</original>
        <variation>GN</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000054" description="In ALD; AMN-type; dbSNP:rs1603232195." evidence="26 46">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000056" description="In ALD; dbSNP:rs1603232195." evidence="38">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013347" description="In ALD; dbSNP:rs193922098." evidence="17">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009369" description="In ALD." evidence="17">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000057" description="In ALD; ACALD and CALD-types; dbSNP:rs2148389975." evidence="39">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000058" description="In ALD; dbSNP:rs128624213." evidence="44">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000059" description="In ALD; ALD-type." evidence="39">
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000060" description="In ALD; AMN-type; dbSNP:rs1131691954." evidence="47">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009370" description="In ALD; dbSNP:rs797044610." evidence="6">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009371" description="In ALD." evidence="9 12">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013348" description="In ALD." evidence="18">
        <original>E</original>
        <variation>EVGQ</variation>
        <location>
            <position position="300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009372" description="In ALD." evidence="30">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="302"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075285" description="In ALD." evidence="33">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009373" description="In ALD; dbSNP:rs2148391974." evidence="50">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009374" description="In ALD." evidence="17">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013349" description="In ALD; dbSNP:rs1603233120." evidence="9">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="339"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000061" description="In ALD; AMN-type." evidence="39">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013350" description="In ALD; dbSNP:rs2091726809." evidence="17">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000062" description="In ALD; AMN-type; dbSNP:rs128624215." evidence="46">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000063" description="In ALD; does not affect protein stability, homo- and heterodimerization with ABCD2 and ABCD3; dbSNP:rs886044777." evidence="10 38 39 41">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000064" description="In ALD; ALD and AMN-types; does not affect protein stability, homo- and heterodimerization with ABCD2 and ABCD3; dbSNP:rs128624219." evidence="10 12 14 29 30 39 42 46">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="401"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009375" description="In ALD; dbSNP:rs727503786." evidence="6 12 26 28">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="401"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000065" description="In ALD; AMN-type; dbSNP:rs128624220." evidence="12 14 42 46">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013351" description="In ALD." evidence="17">
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000066" description="In ALD; CALD, AMN and ADO-types; significantly decreases homodimerization and abolishes heterodimerization with ABCD2 and ABCD3; dbSNP:rs128624214." evidence="10">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="484"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000067" description="In ALD; CALD-types." evidence="6">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="507"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000068" description="In ALD; CALD and AS-types; reduced ATPase activity; dbSNP:rs1569541088." evidence="15 37 38 47">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="512"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000069" description="In ALD; dbSNP:rs128624223." evidence="42">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="515"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067328" description="In ALD." evidence="29">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="516"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000070" description="In ALD; CALD-type; dbSNP:rs398123102." evidence="6 16 26 28">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000071" description="In ALD; CALD-type; dbSNP:rs128624224." evidence="26 45 47">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000072" description="In ALD; AD-type." evidence="47">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="522"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067242" description="In ALD; dbSNP:rs1159943880." evidence="28">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="523"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000073" description="In ALD; CALD-type." evidence="40">
        <location>
            <position position="528"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009376" description="In ALD; dbSNP:rs2148397619." evidence="9">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000074" description="In ALD." evidence="37">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="534"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067243" description="In ALD." evidence="28">
        <original>F</original>
        <variation>C</variation>
        <location>
            <position position="540"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009377" description="In ALD." evidence="6 26">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="540"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009378" description="In ALD; dbSNP:rs1557054776." evidence="12 14">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="543"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009379" description="In ALD; dbSNP:rs2091763089." evidence="6 26">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009380" description="In ALD." evidence="7">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="552"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009381" description="In ALD; dbSNP:rs201568579." evidence="12">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013352" description="In ALD; ACALD type." evidence="14">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="556"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000075" description="In ALD; CALD-type; dbSNP:rs398123105." evidence="26 28 29 40">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="560"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000076" description="In ALD; AMN and ALMD-types; dbSNP:rs398123105." evidence="47">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="560"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013353" description="In ALD." evidence="17">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="560"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000077" description="In ALD." evidence="38">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="566"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013354" description="In ALD." evidence="17">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="591"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000078" description="In ALD; AMN-type; significantly decreases homodimerization and abolishes heterodimerization with ABCD2 and ABCD3; dbSNP:rs1557054873." evidence="10 39">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="591"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009382" description="In ALD; dbSNP:rs398123106." evidence="6 30">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="591"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000079" description="In ALD; decreased ATP-binding affinity; dbSNP:rs128624225." evidence="6 15 38 39 45">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="606"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000080" description="In ALD; uncertain significance; CALD, AMN and ALMD-types; dbSNP:rs201774661." evidence="28 29 30 47">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="606"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013355" description="In ALD; uncertain significance; CALD-type; dbSNP:rs78993751." evidence="16">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="608"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000081" description="In ALD; dbSNP:rs1557055260." evidence="41">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="609"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000082" description="In ALD; AMN-type; dbSNP:rs150346282." evidence="26 30 41 46">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="609"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009383" description="In ALD." evidence="12">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="616"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000083" description="In ALD; ALD-type and asymptomatic; dbSNP:rs4010613." evidence="41 45 46">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="617"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000084" description="In ALD; ADO and AMN-types with cerebral involvement; dbSNP:rs4010613." evidence="46">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="617"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000085" description="In ALD; dbSNP:rs11146842." evidence="28 38 39 45">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="617"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013356" description="In ALD." evidence="17">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="626"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000086" description="In ALD; CALD and AMN-types; dbSNP:rs1557055316." evidence="28 39">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="626"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000087" description="In ALD." evidence="39">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="629"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009384" description="In ALD." evidence="17">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="630"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009385" description="In ALD; dbSNP:rs2091773525." evidence="17">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="631"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013357" description="In ALD; dbSNP:rs1064793877." evidence="17">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="632"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067244" description="In ALD." evidence="28">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="632"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013358" description="In ALD; asymptomatic." evidence="16">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="633"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009386" description="In ALD; dbSNP:rs202125585." evidence="12 28">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="633"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013359" description="In ALD; dbSNP:rs201427153." evidence="17">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="635"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009387" description="In ALD; dbSNP:rs2091773697." evidence="49">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="636"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009388" description="In ALD." evidence="9">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067245" description="In ALD." evidence="28">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="640"/>
        </location>
    </feature>
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    </evidence>
    <evidence type="ECO:0000269" key="46">
        <source>
            <dbReference type="PubMed" id="8566952"/>
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    </evidence>
    <evidence type="ECO:0000269" key="47">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="48">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="49">
        <source>
            <dbReference type="PubMed" id="9553942"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="50">
        <source>
            <dbReference type="PubMed" id="9584268"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="51">
        <source>
            <dbReference type="PubMed" id="10777694"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="52">
        <source>
            <dbReference type="PubMed" id="16946495"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="53">
        <source>
            <dbReference type="PubMed" id="18757502"/>
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    </evidence>
    <evidence type="ECO:0000305" key="54"/>
    <evidence type="ECO:0000305" key="55">
        <source>
            <dbReference type="PubMed" id="15643618"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="56">
        <source>
            <dbReference type="PubMed" id="16946495"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="57">
        <source>
            <dbReference type="PubMed" id="18757502"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="58">
        <source>
            <dbReference type="PubMed" id="21145416"/>
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    </evidence>
    <evidence type="ECO:0000305" key="59">
        <source>
            <dbReference type="PubMed" id="23671276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="60">
        <source>
            <dbReference type="PubMed" id="33500543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="61">
        <source>
            <dbReference type="PubMed" id="34337821"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="62">
        <source>
            <dbReference type="HGNC" id="HGNC:61"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="63">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="64">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="65">
        <source>
            <dbReference type="PDB" id="7RR9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="66">
        <source>
            <dbReference type="PDB" id="7SHM"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="67">
        <source>
            <dbReference type="PDB" id="7SHN"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="68">
        <source>
            <dbReference type="PDB" id="7VR1"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="69">
        <source>
            <dbReference type="PDB" id="7VX8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="70">
        <source>
            <dbReference type="PDB" id="7X0T"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="71">
        <source>
            <dbReference type="PDB" id="7X0Z"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="72">
        <source>
            <dbReference type="PDB" id="7X1W"/>
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    </evidence>
    <evidence type="ECO:0007829" key="73">
        <source>
            <dbReference type="PDB" id="7XEC"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="74">
        <source>
            <dbReference type="PDB" id="7YRQ"/>
        </source>
    </evidence>
    <sequence length="745" mass="82937" checksum="82F90905F71FFDC8" modified="2005-06-07" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-01-24" modified="2026-01-28" version="202" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UG63</accession>
    <accession>O60864</accession>
    <accession>Q75MJ0</accession>
    <accession>Q75MJ1</accession>
    <accession>Q96TE8</accession>
    <name>ABCF2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family F member 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Iron-inhibited ABC transporter 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABCF2</name>
        <name type="ORF">HUSSY-18</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs.</title>
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            <dbReference type="PubMed" id="10944468"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="17974005"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
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        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
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                <person name="Baertsch R.A."/>
                <person name="Brent M.R."/>
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                <person name="Flicek P."/>
                <person name="Bork P."/>
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                <person name="Bailey J.A."/>
                <person name="Portnoy M.E."/>
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                <person name="Chinwalla A.T."/>
                <person name="Gish W.R."/>
                <person name="Eddy S.R."/>
                <person name="McPherson J.D."/>
                <person name="Olson M.V."/>
                <person name="Eichler E.E."/>
                <person name="Green E.D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Sutton G."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2001" name="Yeast" volume="18" first="69" last="80">
            <title>Characterization of 16 novel human genes showing high similarity to yeast sequences.</title>
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                <person name="Stanchi F."/>
                <person name="Bertocco E."/>
                <person name="Toppo S."/>
                <person name="Dioguardi R."/>
                <person name="Simionati B."/>
                <person name="Cannata N."/>
                <person name="Zimbello R."/>
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                <person name="Valle G."/>
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            <dbReference type="PubMed" id="11124703"/>
            <dbReference type="DOI" id="10.1002/1097-0061(200101)18:1&lt;69::aid-yea647&gt;3.0.co;2-h"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 74-623</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
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                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
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            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
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                <person name="Burkard T.R."/>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
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                <person name="Aldabe R."/>
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            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
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            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-218 AND SER-512</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UG63-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UG63-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054715"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">Lacks transmembrane domains and is probably not involved in transport.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EMBL" id="AF261091">
        <property type="protein sequence ID" value="AAG13902.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF261092">
        <property type="protein sequence ID" value="AAG13903.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007451">
        <property type="protein sequence ID" value="AAP36119.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL050291">
        <property type="protein sequence ID" value="CAB43392.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC021097">
        <property type="protein sequence ID" value="AAS00378.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC021097">
        <property type="protein sequence ID" value="AAS00379.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471173">
        <property type="protein sequence ID" value="EAW54014.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471173">
        <property type="protein sequence ID" value="EAW54016.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471173">
        <property type="protein sequence ID" value="EAW54017.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001661">
        <property type="protein sequence ID" value="AAH01661.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ005016">
        <property type="protein sequence ID" value="CAA06290.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5923.1">
        <molecule id="Q9UG63-1"/>
    </dbReference>
    <dbReference type="PIR" id="T08810">
        <property type="entry name" value="T08810"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005683.2">
        <molecule id="Q9UG63-2"/>
        <property type="nucleotide sequence ID" value="NM_005692.4"/>
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    <reference evidence="19" key="24">
        <citation type="journal article" date="2012" name="Nat. Struct. Mol. Biol." volume="19" first="1005" last="1010">
            <title>The APOBEC3C crystal structure and the interface for HIV-1 Vif binding.</title>
            <authorList>
                <person name="Kitamura S."/>
                <person name="Ode H."/>
                <person name="Nakashima M."/>
                <person name="Imahashi M."/>
                <person name="Naganawa Y."/>
                <person name="Kurosawa T."/>
                <person name="Yokomaku Y."/>
                <person name="Yamane T."/>
                <person name="Watanabe N."/>
                <person name="Suzuki A."/>
                <person name="Sugiura W."/>
                <person name="Iwatani Y."/>
            </authorList>
            <dbReference type="PubMed" id="23001005"/>
            <dbReference type="DOI" id="10.1038/nsmb.2378"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH ZINC</scope>
        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF LEU-72; PHE-75; CYS-76; ILE-79; LEU-80; SER-81; TYR-86; GLU-106; PHE-107; ALA-109; HIS-111; PRO-129 AND GLU-141</scope>
    </reference>
    <reference evidence="18" key="25">
        <citation type="submission" date="2011-12" db="PDB data bank">
            <title>Crystal structure of the human APOBEC3C having HIV-1 Vif-binding interface.</title>
            <authorList>
                <person name="Kitamura S."/>
                <person name="Ode H."/>
                <person name="Nakashima M."/>
                <person name="Imahashi M."/>
                <person name="Naganawa Y."/>
                <person name="Ibe S."/>
                <person name="Yokomaku Y."/>
                <person name="Watanabe N."/>
                <person name="Suzuki A."/>
                <person name="Sugiura W."/>
                <person name="Iwatani Y."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH ZINC</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 9 11 12">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against simian immunodeficiency virus (SIV), hepatitis B virus (HBV), herpes simplex virus 1 (HHV-1) and Epstein-Barr virus (EBV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">(Microbial infection) Antiviral activity is neutralized by the HIV-1 virion infectivity factor (Vif), that prevents its incorporation into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.</text>
    </comment>
    <comment type="subunit">
        <text evidence="14 15 16">Homodimer (PubMed:22977230, PubMed:23001005). Interacts with TRIB3 (PubMed:22977230). Interacts with AGO2 (PubMed:22915799).</text>
    </comment>
    <comment type="subunit">
        <text evidence="8">(Microbial infection) Interacts with human foamy virus protein Bet; this interaction does not induce APOBEC3C degradation but prevents its dimerization and incorporation into the virion by binding of Bet close to or within the APOBEC3C dimerization site.</text>
    </comment>
    <comment type="subunit">
        <text evidence="16">(Microbial infection) Interacts with HIV-1 Vif.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-11984237">
            <id>Q9Y3Y2-3</id>
            <label>CHTOP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-747421">
            <id>Q03014</id>
            <label>HHEX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-7060731">
            <id>P61978-2</id>
            <label>HNRNPK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-2803328">
            <id>P79522</id>
            <label>PRR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-743526">
            <id>P38159</id>
            <label>RBMX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-8638511">
            <id>P0DJD3</id>
            <label>RBMY1A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-8642021">
            <id>Q15415</id>
            <label>RBMY1J</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-492476">
            <id>Q96RU7</id>
            <label>TRIB3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-10177272">
            <id>P15622-3</id>
            <label>ZNF250</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-347633">
            <id>Q9H9D4</id>
            <label>ZNF408</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-12006434">
            <id>Q96MX3</id>
            <label>ZNF48</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1044593">
            <id>Q9NRW3</id>
        </interactant>
        <interactant intactId="EBI-745520">
            <id>Q9P0T4</id>
            <label>ZNF581</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 15">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13 15">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 10">Expressed in spleen, testes, peripherical blood lymphocytes, heart, thymus, prostate and ovary.</text>
    </comment>
    <comment type="induction">
        <text>Up-regulated by IFN-alpha.</text>
    </comment>
    <comment type="miscellaneous">
        <text>It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAF86650" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.5.4.38"/>
    <dbReference type="EMBL" id="AF165520">
        <property type="protein sequence ID" value="AAF86650.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456394">
        <property type="protein sequence ID" value="CAG30280.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313272">
        <property type="protein sequence ID" value="BAG36081.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL022318">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471095">
        <property type="protein sequence ID" value="EAW60284.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011739">
        <property type="protein sequence ID" value="AAH11739.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC021080">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13983.1"/>
    <dbReference type="RefSeq" id="NP_055323.2">
        <property type="nucleotide sequence ID" value="NM_014508.2"/>
    </dbReference>
    <dbReference type="PDB" id="3VM8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=1-190"/>
    </dbReference>
    <dbReference type="PDB" id="3VOW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="A/B=1-190"/>
    </dbReference>
    <dbReference type="PDBsum" id="3VM8"/>
    <dbReference type="PDBsum" id="3VOW"/>
    <dbReference type="AlphaFoldDB" id="Q9NRW3"/>
    <dbReference type="SMR" id="Q9NRW3"/>
    <dbReference type="BioGRID" id="118162">
        <property type="interactions" value="205"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-48919N"/>
    <dbReference type="FunCoup" id="Q9NRW3">
        <property type="interactions" value="262"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NRW3">
        <property type="interactions" value="245"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NRW3"/>
    <dbReference type="STRING" id="9606.ENSP00000355340"/>
    <dbReference type="GlyGen" id="Q9NRW3">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NRW3"/>
    <dbReference type="PhosphoSitePlus" id="Q9NRW3"/>
    <dbReference type="SwissPalm" id="Q9NRW3"/>
    <dbReference type="BioMuta" id="APOBEC3C"/>
    <dbReference type="DMDM" id="48474983"/>
    <dbReference type="jPOST" id="Q9NRW3"/>
    <dbReference type="MassIVE" id="Q9NRW3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000355340"/>
    <dbReference type="PeptideAtlas" id="Q9NRW3"/>
    <dbReference type="ProteomicsDB" id="82428"/>
    <dbReference type="Pumba" id="Q9NRW3"/>
    <dbReference type="Antibodypedia" id="35026">
        <property type="antibodies" value="258 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="27350"/>
    <dbReference type="Ensembl" id="ENST00000361441.5">
        <property type="protein sequence ID" value="ENSP00000355340.3"/>
        <property type="gene ID" value="ENSG00000244509.5"/>
    </dbReference>
    <dbReference type="GeneID" id="27350"/>
    <dbReference type="KEGG" id="hsa:27350"/>
    <dbReference type="MANE-Select" id="ENST00000361441.5">
        <property type="protein sequence ID" value="ENSP00000355340.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014508.3"/>
        <property type="RefSeq protein sequence ID" value="NP_055323.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003awr.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17353"/>
    <dbReference type="ClinPGx" id="PA24893"/>
    <dbReference type="CTD" id="27350"/>
    <dbReference type="DisGeNET" id="27350"/>
    <dbReference type="GeneCards" id="APOBEC3C"/>
    <dbReference type="HGNC" id="HGNC:17353">
        <property type="gene designation" value="APOBEC3C"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000244509">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="607750">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000244509"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000244509"/>
    <dbReference type="eggNOG" id="KOG4075">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162695"/>
    <dbReference type="HOGENOM" id="CLU_080056_2_0_1"/>
    <dbReference type="InParanoid" id="Q9NRW3"/>
    <dbReference type="OMA" id="DLETHCH"/>
    <dbReference type="OrthoDB" id="9445293at2759"/>
    <dbReference type="PAN-GO" id="Q9NRW3">
        <property type="GO annotations" value="12 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NRW3"/>
    <dbReference type="BRENDA" id="3.5.4.38">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NRW3"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NRW3"/>
    <dbReference type="SIGNOR" id="Q9NRW3"/>
    <dbReference type="Agora" id="ENSG00000244509"/>
    <dbReference type="BioGRID-ORCS" id="27350">
        <property type="hits" value="20 hits in 1130 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APOBEC3C">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NRW3"/>
    <dbReference type="GeneWiki" id="APOBEC3C"/>
    <dbReference type="GenomeRNAi" id="27350"/>
    <dbReference type="Pharos" id="Q9NRW3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NRW3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NRW3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000244509">
        <property type="expression patterns" value="Expressed in leukocyte and 186 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NRW3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000932">
        <property type="term" value="C:P-body"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044355">
        <property type="term" value="P:clearance of foreign intracellular DNA"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070383">
        <property type="term" value="P:DNA cytosine deamination"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045087">
        <property type="term" value="P:innate immune response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045869">
        <property type="term" value="P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045071">
        <property type="term" value="P:negative regulation of viral genome replication"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044029">
        <property type="term" value="P:positive regulation of gene expression via chromosomal CpG island demethylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010526">
        <property type="term" value="P:transposable element silencing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000029">
        <property type="entry name" value="DNA dC-&gt;dU-editing enzyme APOBEC-3G"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF46">
        <property type="entry name" value="DNA DC-DU-EDITING ENZYME APOBEC-3C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18782">
        <property type="entry name" value="NAD2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0391">Immunity</keyword>
    <keyword id="KW-0399">Innate immunity</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171755" description="DNA dC-&gt;dU-editing enzyme APOBEC-3C">
        <location>
            <begin position="1"/>
            <end position="190"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="3">
        <location>
            <begin position="29"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="region of interest" description="(Microbial infection) Required for interaction with human foamy virus protein Bet" evidence="8">
        <location>
            <begin position="40"/>
            <end position="86"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="3">
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="binding site" evidence="18 19">
        <location>
            <position position="66"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="18 19">
        <location>
            <position position="97"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="18 19">
        <location>
            <position position="100"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="16">
        <original>L</original>
        <variation>D</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>F</original>
        <variation>W</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>C</original>
        <variation>K</variation>
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>I</original>
        <variation>A</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="16">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and abolishes Vif binding." evidence="16">
        <original>F</original>
        <variation>D</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif." evidence="16">
        <original>A</original>
        <variation>K</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistant to HIV-1 Vif and reduces Vif binding." evidence="16">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on Vif binding." evidence="16">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Remains sensitive to HIV-1 Vif but abolishes Vif binding." evidence="16">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH11739." evidence="17" ref="6">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="14"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="turn" evidence="20">
        <location>
            <begin position="27"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="32"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="46"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="63"/>
            <end position="65"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="67"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="84"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="98"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="114"/>
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        </location>
    </feature>
    <feature type="turn" evidence="21">
        <location>
            <begin position="124"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="129"/>
            <end position="141"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="144"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="150"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="174"/>
            <end position="189"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q96AK3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11863358"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12859895"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15466872"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16527742"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="19074429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="20062055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="20308164"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="21496894"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="21632763"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="21835787"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="22915799"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22977230"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="23001005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PDB" id="3VM8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PDB" id="3VOW"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="3VM8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="3VOW"/>
        </source>
    </evidence>
    <sequence length="190" mass="22826" checksum="BE49E80F95C71214" modified="2004-03-29" version="2">MNPQIRNPMKAMYPGTFYFQFKNLWEANDRNETWLCFTVEGIKRRSVVSWKTGVFRNQVDSETHCHAERCFLSWFCDDILSPNTKYQVTWYTSWSPCPDCAGEVAEFLARHSNVNLTIFTARLYYFQYPCYQEGLRSLSQEGVAVEIMDYEDFKYCWENFVYNDNEPFKPWKGLKTNFRLLKRRLRESLQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-06-26" modified="2026-01-28" version="154" xmlns="https://uniprot.org/uniprot">
    <accession>Q6NTF7</accession>
    <accession>B0QYP0</accession>
    <accession>B0QYP1</accession>
    <accession>B7TQM5</accession>
    <accession>E9PF38</accession>
    <accession>M4W6S4</accession>
    <accession>Q5JYL9</accession>
    <accession>Q6IC87</accession>
    <name>ABC3H_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>DNA dC-&gt;dU-editing enzyme APOBEC-3H</fullName>
            <ecNumber evidence="4 17">3.5.4.38</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>APOBEC-related protein 10</fullName>
            <shortName>ARP-10</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H</fullName>
            <shortName>A3H</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22 24" type="primary">APOBEC3H</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H.</title>
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                <person name="Harari A."/>
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            </authorList>
            <dbReference type="PubMed" id="18945781"/>
            <dbReference type="DOI" id="10.1128/jvi.01665-08"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>POLYMORPHISM</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R84.1" last="R84.11">
            <title>A genome annotation-driven approach to cloning the human ORFeome.</title>
            <authorList>
                <person name="Collins J.E."/>
                <person name="Wright C.L."/>
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                <person name="Davis M.P."/>
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            </authorList>
            <dbReference type="PubMed" id="15461802"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-10-r84"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANTS ASN-15 DEL; LEU-18; ARG-105 AND ASP-178</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2012-12" db="EMBL/GenBank/DDBJ databases">
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            <authorList>
                <person name="Dad R."/>
                <person name="Sawal H.A."/>
                <person name="Rehman Z."/>
                <person name="Fahim A."/>
                <person name="Sadia H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
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            <title>The DNA sequence of human chromosome 22.</title>
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                <person name="Lane L."/>
                <person name="Tilahun Y."/>
                <person name="Wright H."/>
            </authorList>
            <dbReference type="PubMed" id="10591208"/>
            <dbReference type="DOI" id="10.1038/990031"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Astrocyte</tissue>
        </source>
    </reference>
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            <title>Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business.</title>
            <authorList>
                <person name="Wedekind J.E."/>
                <person name="Dance G.S.C."/>
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                <person name="Smith H.C."/>
            </authorList>
            <dbReference type="PubMed" id="12683974"/>
            <dbReference type="DOI" id="10.1016/s0168-9525(03)00054-4"/>
        </citation>
        <scope>REVIEW ON APOBEC FAMILY</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="J. Virol." volume="80" first="3853" last="3862">
            <title>Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H.</title>
            <authorList>
                <person name="OhAinle M."/>
                <person name="Kerns J.A."/>
                <person name="Malik H.S."/>
                <person name="Emerman M."/>
            </authorList>
            <dbReference type="PubMed" id="16571802"/>
            <dbReference type="DOI" id="10.1128/jvi.80.8.3853-3862.2006"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2006" name="J. Virol." volume="80" first="10522" last="10533">
            <title>Identification of APOBEC3DE as another antiretroviral factor from the human APOBEC family.</title>
            <authorList>
                <person name="Dang Y."/>
                <person name="Wang X."/>
                <person name="Esselman W.J."/>
                <person name="Zheng Y.-H."/>
            </authorList>
            <dbReference type="PubMed" id="16920826"/>
            <dbReference type="DOI" id="10.1128/jvi.01123-06"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="9">
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            <title>The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements.</title>
            <authorList>
                <person name="Chiu Y.L."/>
                <person name="Greene W.C."/>
            </authorList>
            <dbReference type="PubMed" id="18304004"/>
            <dbReference type="DOI" id="10.1146/annurev.immunol.26.021607.090350"/>
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        <scope>REVIEW</scope>
    </reference>
    <reference key="10">
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            <title>Antiretroelement activity of APOBEC3H was lost twice in recent human evolution.</title>
            <authorList>
                <person name="OhAinle M."/>
                <person name="Kerns J.A."/>
                <person name="Li M.M."/>
                <person name="Malik H.S."/>
                <person name="Emerman M."/>
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            <dbReference type="PubMed" id="18779051"/>
            <dbReference type="DOI" id="10.1016/j.chom.2008.07.005"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>POLYMORPHISM</scope>
        <scope>CHARACTERIZATION OF VARIANTS ASN-15 DEL AND ARG-105</scope>
    </reference>
    <reference key="11">
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            <title>Human cytidine deaminase APOBEC3H restricts HIV-1 replication.</title>
            <authorList>
                <person name="Dang Y."/>
                <person name="Siew L.M."/>
                <person name="Wang X."/>
                <person name="Han Y."/>
                <person name="Lampen R."/>
                <person name="Zheng Y.H."/>
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            <dbReference type="PubMed" id="18299330"/>
            <dbReference type="DOI" id="10.1074/jbc.m707586200"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
    </reference>
    <reference key="12">
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            <title>Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1.</title>
            <authorList>
                <person name="Tan L."/>
                <person name="Sarkis P.T."/>
                <person name="Wang T."/>
                <person name="Tian C."/>
                <person name="Yu X.F."/>
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            <dbReference type="PubMed" id="18827027"/>
            <dbReference type="DOI" id="10.1096/fj.07-088781"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CHARACTERIZATION OF ALLELE A3H-VAR</scope>
        <scope>MUTAGENESIS OF GLU-56</scope>
    </reference>
    <reference key="13">
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            <title>Quantitative profiling of the full APOBEC3 mRNA repertoire in lymphocytes and tissues: implications for HIV-1 restriction.</title>
            <authorList>
                <person name="Refsland E.W."/>
                <person name="Stenglein M.D."/>
                <person name="Shindo K."/>
                <person name="Albin J.S."/>
                <person name="Brown W.L."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20308164"/>
            <dbReference type="DOI" id="10.1093/nar/gkq174"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2010" name="Nat. Struct. Mol. Biol." volume="17" first="222" last="229">
            <title>APOBEC3 proteins mediate the clearance of foreign DNA from human cells.</title>
            <authorList>
                <person name="Stenglein M.D."/>
                <person name="Burns M.B."/>
                <person name="Li M."/>
                <person name="Lengyel J."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="20062055"/>
            <dbReference type="DOI" id="10.1038/nsmb.1744"/>
        </citation>
        <scope>FUNCTION IN RETROTRANSPOSITION</scope>
    </reference>
    <reference key="15">
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            <title>Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity.</title>
            <authorList>
                <person name="Li M.M."/>
                <person name="Emerman M."/>
            </authorList>
            <dbReference type="PubMed" id="21653666"/>
            <dbReference type="DOI" id="10.1128/jvi.00624-11"/>
        </citation>
        <scope>CHARACTERIZATION OF ALLELE A3H-VAR</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2011" name="J. Virol." volume="85" first="11220" last="11234">
            <title>Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1.</title>
            <authorList>
                <person name="Hultquist J.F."/>
                <person name="Lengyel J.A."/>
                <person name="Refsland E.W."/>
                <person name="LaRue R.S."/>
                <person name="Lackey L."/>
                <person name="Brown W.L."/>
                <person name="Harris R.S."/>
            </authorList>
            <dbReference type="PubMed" id="21835787"/>
            <dbReference type="DOI" id="10.1128/jvi.05238-11"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ACTIVITY REGULATION (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2011" name="Student Perspec. Contemp. Virol." volume="0" first="0" last="0">
            <title>Cytosine deaminases APOBEC3A, APOBEC3C, and APOBEC3H: Current understanding of their functional roles.</title>
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                <person name="Love R."/>
            </authorList>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="18">
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            <title>Retroelements versus APOBEC3 family members: No great escape from the magnificent seven.</title>
            <authorList>
                <person name="Arias J.F."/>
                <person name="Koyama T."/>
                <person name="Kinomoto M."/>
                <person name="Tokunaga K."/>
            </authorList>
            <dbReference type="PubMed" id="22912627"/>
            <dbReference type="DOI" id="10.3389/fmicb.2012.00275"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2012" name="J. Virol." volume="86" first="6097" last="6108">
            <title>APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1.</title>
            <authorList>
                <person name="Ooms M."/>
                <person name="Krikoni A."/>
                <person name="Kress A.K."/>
                <person name="Simon V."/>
                <person name="Muenk C."/>
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            <dbReference type="PubMed" id="22457529"/>
            <dbReference type="DOI" id="10.1128/jvi.06570-11"/>
        </citation>
        <scope>FUNCTION IN HTLV-1 RESTRICTION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2012" name="J. Virol." volume="86" first="11712" last="11724">
            <title>HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.</title>
            <authorList>
                <person name="Phalora P.K."/>
                <person name="Sherer N.M."/>
                <person name="Wolinsky S.M."/>
                <person name="Swanson C.M."/>
                <person name="Malim M.H."/>
            </authorList>
            <dbReference type="PubMed" id="22915799"/>
            <dbReference type="DOI" id="10.1128/jvi.00595-12"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH AGO1; AGO2 AND AGO3</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2012" name="Semin. Cell Dev. Biol." volume="23" first="258" last="268">
            <title>Functions and regulation of the APOBEC family of proteins.</title>
            <authorList>
                <person name="Smith H.C."/>
                <person name="Bennett R.P."/>
                <person name="Kizilyer A."/>
                <person name="McDougall W.M."/>
                <person name="Prohaska K.M."/>
            </authorList>
            <dbReference type="PubMed" id="22001110"/>
            <dbReference type="DOI" id="10.1016/j.semcdb.2011.10.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2013" name="J. Virol." volume="87" first="444" last="453">
            <title>APOBEC3G restricts HIV-1 to a greater extent than APOBEC3F and APOBEC3DE in human primary CD4+ t cells and macrophages.</title>
            <authorList>
                <person name="Chaipan C."/>
                <person name="Smith J.L."/>
                <person name="Hu W.S."/>
                <person name="Pathak V.K."/>
            </authorList>
            <dbReference type="PubMed" id="23097438"/>
            <dbReference type="DOI" id="10.1128/jvi.00676-12"/>
        </citation>
        <scope>FUNCTION IN HIV-1 RESTRICTION</scope>
    </reference>
    <reference evidence="25 26" key="23">
        <citation type="journal article" date="2018" name="Mol. Cell" volume="69" first="75" last="86">
            <title>The antiviral and cancer genomic DNA deaminase APOBEC3H is regulated by an RNA-mediated dimerization mechanism.</title>
            <authorList>
                <person name="Shaban N.M."/>
                <person name="Shi K."/>
                <person name="Lauer K.V."/>
                <person name="Carpenter M.A."/>
                <person name="Richards C.M."/>
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                <person name="Wang J."/>
                <person name="Lopresti M.W."/>
                <person name="Banerjee S."/>
                <person name="Levin-Klein R."/>
                <person name="Brown W.L."/>
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            </authorList>
            <dbReference type="PubMed" id="29290613"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2017.12.010"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.28 ANGSTROMS) OF 1-181 IN COMPLEX WITH RNA AND ZINC</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVE SITE</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ARG-18; ARG-20; ARG-21; PRO-22; TYR-23; TYR-24; PRO-25; ARG-26; LYS-50; LYS-51; LYS-52; GLU-56; ARG-110; LEU-111; TYR-112; TYR-113; HIS-114; TRP-115; ARG-171; ALA-172; ILE-173; ARG-175; ARG-176 AND ARG-179</scope>
    </reference>
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            <title>Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.</title>
            <authorList>
                <person name="Ito F."/>
                <person name="Alvarez-Cabrera A.L."/>
                <person name="Kim K."/>
                <person name="Zhou Z.H."/>
                <person name="Chen X.S."/>
            </authorList>
            <dbReference type="PubMed" id="37640699"/>
            <dbReference type="DOI" id="10.1038/s41467-023-40955-x"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.24 ANGSTROMS) OF 1-181 IN COMPLEX WITH ELOB; ELOC; CBFB AND HIV-1 VIF</scope>
        <scope>UBIQUITINATION (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF 50-LYS-LYS-51; GLU-70; TRP-90; ASP-94; LYS-97; LEU-125 AND SER-129</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6 7 8 10 13 14 15 16 17">DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms (PubMed:16571802, PubMed:16920826, PubMed:18779051, PubMed:18827027, PubMed:20062055, PubMed:22915799, PubMed:29290613). The A3H-var/haplotype 2 exhibits antiviral activity against vif-deficient HIV-1 (PubMed:18299330, PubMed:21835787, PubMed:23097438, PubMed:29290613). After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA (PubMed:18299330). The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells (PubMed:18299330). Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA (PubMed:20062055). Exhibits antiviral activity also against T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons (PubMed:20062055, PubMed:22457529).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 17">
            <text>a 2'-deoxycytidine in single-stranded DNA + H2O + H(+) = a 2'-deoxyuridine in single-stranded DNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50948"/>
            <dbReference type="Rhea" id="RHEA-COMP:12846"/>
            <dbReference type="Rhea" id="RHEA-COMP:12847"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:85452"/>
            <dbReference type="ChEBI" id="CHEBI:133902"/>
            <dbReference type="EC" id="3.5.4.38"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="17">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="17">APOBEC3H activity is regulated by RNA (PubMed:29290613). While RNA-binding inhibits the DNA deaminase activity, double-stranded RNA is required for HIV-1 restriction by promoting APOBEC3H homodimerization and packaging into retroviral nucleocapsids (PubMed:29290613).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="13 18">(Microbial infection) Antiviral activity is inhibited to some extent by the HIV-1 virion infectivity factor (VIF), that prevents its incorporation into progeny virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome.</text>
    </comment>
    <comment type="subunit">
        <text evidence="15 17">Homodimer (PubMed:29290613). Interacts with AGO1, AGO2 and AGO3 (PubMed:22915799).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12 13 17">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7 12">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15">Cytoplasm</location>
            <location evidence="15">P-body</location>
        </subcellularLocation>
        <text evidence="12">Haplotype 1 is distributed in both the nucleus and cytoplasm, whereas haplotype 2 is predominantly cytoplasmic.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6NTF7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6NTF7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_035034"/>
        </isoform>
        <isoform>
            <id>Q6NTF7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_039975"/>
        </isoform>
        <isoform>
            <id>Q6NTF7-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_047044"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 11">Expressed in lymphoid organs. Also detected in non-lymphoid tissues including lung, testis, ovary, fetal liver and skin.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18">(Microbial infection) Following infection by some HIV-1 strains, such as isolate BRU/LAI, can be ubiquitinated by a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, leading to its degradation (PubMed:37640699). Ubiquitination by the ECS complex is however less efficent compared to APOBEC3G or APOBEC3G (PubMed:37640699).</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="7 9">There are at least 4 different haplotypes in the human population (PubMed:18779051, PubMed:18945781). The allele A3H-var/haplotype 2 encodes a more stable protein which is able to block HIV-1 replication (PubMed:18779051, PubMed:18945781). The displayed allele (haplotype 1) is unstable and inefficient to block HIV-1 replication (PubMed:18779051, PubMed:18945781).</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="4">APOBEC3H from old world monkeys has retained its antiviral activity, while it is lost in other primates.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="19">It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22.</text>
    </comment>
    <comment type="similarity">
        <text evidence="23">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.38" evidence="4 17"/>
    <dbReference type="EMBL" id="FJ376613">
        <property type="protein sequence ID" value="ACK77774.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456481">
        <property type="protein sequence ID" value="CAG30367.3"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KC329529">
        <property type="protein sequence ID" value="AGI04217.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL031846">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF457460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC069023">
        <property type="protein sequence ID" value="AAH69023.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BQ052182">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13985.1">
        <molecule id="Q6NTF7-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54530.1">
        <molecule id="Q6NTF7-1"/>
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    <dbReference type="CCDS" id="CCDS54531.1">
        <molecule id="Q6NTF7-2"/>
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    <dbReference type="CCDS" id="CCDS54532.1">
        <molecule id="Q6NTF7-4"/>
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    <dbReference type="RefSeq" id="NP_001159474.2">
        <molecule id="Q6NTF7-2"/>
        <property type="nucleotide sequence ID" value="NM_001166002.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159475.2">
        <molecule id="Q6NTF7-1"/>
        <property type="nucleotide sequence ID" value="NM_001166003.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159476.2">
        <property type="nucleotide sequence ID" value="NM_001166004.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_861438.3">
        <molecule id="Q6NTF7-3"/>
        <property type="nucleotide sequence ID" value="NM_181773.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011528294.1">
        <molecule id="Q6NTF7-1"/>
        <property type="nucleotide sequence ID" value="XM_011529992.4"/>
    </dbReference>
    <dbReference type="PDB" id="5W45">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.49 A"/>
        <property type="chains" value="A/B=2-177"/>
    </dbReference>
    <dbReference type="PDB" id="6B0B">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.28 A"/>
        <property type="chains" value="A/E=1-181"/>
    </dbReference>
    <dbReference type="PDB" id="6BBO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.43 A"/>
        <property type="chains" value="A/E=3-181"/>
    </dbReference>
    <dbReference type="PDB" id="8FVI">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.24 A"/>
        <property type="chains" value="A=1-181"/>
    </dbReference>
    <dbReference type="PDBsum" id="5W45"/>
    <dbReference type="PDBsum" id="6B0B"/>
    <dbReference type="PDBsum" id="6BBO"/>
    <dbReference type="PDBsum" id="8FVI"/>
    <dbReference type="AlphaFoldDB" id="Q6NTF7"/>
    <dbReference type="EMDB" id="EMD-29488"/>
    <dbReference type="EMDB" id="EMD-29490"/>
    <dbReference type="SMR" id="Q6NTF7"/>
    <dbReference type="BioGRID" id="127899">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6NTF7">
        <property type="interactions" value="36"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000385741"/>
    <dbReference type="iPTMnet" id="Q6NTF7"/>
    <dbReference type="PhosphoSitePlus" id="Q6NTF7"/>
    <dbReference type="BioMuta" id="APOBEC3H"/>
    <dbReference type="DMDM" id="205371798"/>
    <dbReference type="MassIVE" id="Q6NTF7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000385741"/>
    <dbReference type="PeptideAtlas" id="Q6NTF7"/>
    <dbReference type="ProteomicsDB" id="66670">
        <molecule id="Q6NTF7-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="26556">
        <property type="antibodies" value="48 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="164668"/>
    <dbReference type="Ensembl" id="ENST00000348946.8">
        <molecule id="Q6NTF7-2"/>
        <property type="protein sequence ID" value="ENSP00000216123.5"/>
        <property type="gene ID" value="ENSG00000100298.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000401756.5">
        <molecule id="Q6NTF7-1"/>
        <property type="protein sequence ID" value="ENSP00000385741.1"/>
        <property type="gene ID" value="ENSG00000100298.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000442487.8">
        <molecule id="Q6NTF7-3"/>
        <property type="protein sequence ID" value="ENSP00000411754.3"/>
        <property type="gene ID" value="ENSG00000100298.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000613677.4">
        <molecule id="Q6NTF7-1"/>
        <property type="protein sequence ID" value="ENSP00000483689.1"/>
        <property type="gene ID" value="ENSG00000100298.16"/>
    </dbReference>
    <dbReference type="GeneID" id="164668"/>
    <dbReference type="KEGG" id="hsa:164668"/>
    <dbReference type="MANE-Select" id="ENST00000442487.8">
        <molecule id="Q6NTF7-3"/>
        <property type="protein sequence ID" value="ENSP00000411754.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_181773.5"/>
        <property type="RefSeq protein sequence ID" value="NP_861438.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc021wps.2">
        <molecule id="Q6NTF7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="UCSC" id="uc062ejr.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24100"/>
    <dbReference type="ClinPGx" id="PA162376694"/>
    <dbReference type="CTD" id="164668"/>
    <dbReference type="DisGeNET" id="164668"/>
    <dbReference type="GeneCards" id="APOBEC3H"/>
    <dbReference type="HGNC" id="HGNC:24100">
        <property type="gene designation" value="APOBEC3H"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100298">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="610976">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000100298"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000100298"/>
    <dbReference type="eggNOG" id="ENOG502TFVZ">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162772"/>
    <dbReference type="HOGENOM" id="CLU_080056_4_0_1"/>
    <dbReference type="InParanoid" id="Q6NTF7"/>
    <dbReference type="OMA" id="HVQGCYI"/>
    <dbReference type="OrthoDB" id="9445293at2759"/>
    <dbReference type="PAN-GO" id="Q6NTF7">
        <property type="GO annotations" value="12 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6NTF7"/>
    <dbReference type="BRENDA" id="3.5.4.38">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q6NTF7"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6NTF7"/>
    <dbReference type="SIGNOR" id="Q6NTF7"/>
    <dbReference type="Agora" id="ENSG00000100298"/>
    <dbReference type="BioGRID-ORCS" id="164668">
        <property type="hits" value="6 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="APOBEC3H"/>
    <dbReference type="GenomeRNAi" id="164668"/>
    <dbReference type="Pharos" id="Q6NTF7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6NTF7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6NTF7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000100298">
        <property type="expression patterns" value="Expressed in granulocyte and 91 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6NTF7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000932">
        <property type="term" value="C:P-body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044355">
        <property type="term" value="P:clearance of foreign intracellular DNA"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070383">
        <property type="term" value="P:DNA cytosine deamination"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044828">
        <property type="term" value="P:host-mediated suppression of viral genome replication"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045087">
        <property type="term" value="P:innate immune response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045869">
        <property type="term" value="P:negative regulation of single stranded viral RNA replication via double stranded DNA intermediate"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010526">
        <property type="term" value="P:transposable element silencing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000047">
        <property type="entry name" value="Apolipoprotein B editing enzyme catalytic polypeptide-like 3H"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041512">
        <property type="entry name" value="APOBEC3H"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF43">
        <property type="entry name" value="DNA DC-DU-EDITING ENZYME APOBEC-3H"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18771">
        <property type="entry name" value="APOBEC3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0391">Immunity</keyword>
    <keyword id="KW-0399">Innate immunity</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000291663" description="DNA dC-&gt;dU-editing enzyme APOBEC-3H">
        <location>
            <begin position="1"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="2">
        <location>
            <begin position="4"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="160"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="17 25 26">
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="binding site" evidence="17 25 26">
        <location>
            <position position="54"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="17 25 26">
        <location>
            <position position="85"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="17 25 26">
        <location>
            <position position="88"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_047044" description="In isoform 4." evidence="23">
        <original>EFADCWENFVDHEKPLSFNPYKMLEELDKNSRAIKRRLERIKIPGVRAQGRYMDILCDAEV</original>
        <variation>NSRGTCAGSLHGYIV</variation>
        <location>
            <begin position="140"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035034" description="In isoform 2." evidence="20 21">
        <original>IPGVRAQGRYMDILCDAEV</original>
        <variation>S</variation>
        <location>
            <begin position="182"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039975" description="In isoform 3." evidence="21">
        <original>IPGVRAQGRYMDILCDAEV</original>
        <variation>QS</variation>
        <location>
            <begin position="182"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_065622" description="Decreases protein stability." evidence="3 7">
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032835" description="In dbSNP:rs139293." evidence="3">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032836" description="In allele A3H-Var; haplotype 2; allele presenting a higher expression and which is more effective in retrotransposons and HIV-1 restriction; increases protein stability; dbSNP:rs139297." evidence="3 7">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032837" description="In allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction; dbSNP:rs139298.">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032838" description="In dbSNP:rs139299.">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067444" description="In dbSNP:rs139300.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032839" description="In allele A3H-Var; haplotype 2; allele presenting a higher expression and more effective in retrotransposons and HIV-1 restriction; dbSNP:rs139302." evidence="3">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased DNA deaminase activity." evidence="17">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased DNA deaminase activity." evidence="17">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect the DNA deaminase activity." evidence="17">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ubiquitination by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>KK</original>
        <variation>RR</variation>
        <location>
            <begin position="50"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect the DNA deaminase activity." evidence="17">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect the DNA deaminase activity." evidence="17">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect the DNA deaminase activity." evidence="17">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished DNA deaminase activity." evidence="17">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces the ability to inhibit the retrotransposition of LINE-1 elements." evidence="8">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Partial resistance to ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistance to ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistance to ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>R</original>
        <variation>E</variation>
        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased DNA deaminase activity." evidence="17">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased DNA deaminase activity." evidence="17">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased DNA deaminase activity." evidence="17">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistance to ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Resistance to ubiquitination and degradation by an ECS complex hijacked by HIV-1 Vif." evidence="18">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased DNA deaminase activity." evidence="17">
        <original>R</original>
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</entry>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
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    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
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                <person name="Iwayanagi T."/>
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                <person name="Hosoiri T."/>
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                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
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                <person name="Katsuta N."/>
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                <person name="Yamazaki M."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Takahashi-Fujii A."/>
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                <person name="Nomura Y."/>
                <person name="Togiya S."/>
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                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT LEU-503</scope>
        <source>
            <tissue>Placenta</tissue>
            <tissue>Subthalamic nucleus</tissue>
            <tissue>Vascular smooth muscle</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Cervix</tissue>
            <tissue>Muscle</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-283</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-83; SER-155; SER-157; SER-161 AND SER-283</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B.</text>
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    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="6">Lacks transmembrane domains and is probably not involved in transport.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB14989" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK002060">
        <property type="protein sequence ID" value="BAA92063.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK024758">
        <property type="protein sequence ID" value="BAB14989.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092415">
        <property type="protein sequence ID" value="BAC03881.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290106">
        <property type="protein sequence ID" value="BAF82795.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009253">
        <property type="protein sequence ID" value="AAH09253.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051754">
        <property type="protein sequence ID" value="AAH51754.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051884">
        <property type="protein sequence ID" value="AAH51884.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3254.1">
        <molecule id="Q9NUQ8-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS87173.1">
        <molecule id="Q9NUQ8-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001338227.1">
        <molecule id="Q9NUQ8-2"/>
        <property type="nucleotide sequence ID" value="NM_001351298.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060828.2">
        <molecule id="Q9NUQ8-1"/>
        <property type="nucleotide sequence ID" value="NM_018358.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NUQ8"/>
    <dbReference type="SMR" id="Q9NUQ8"/>
    <dbReference type="BioGRID" id="120605">
        <property type="interactions" value="154"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NUQ8">
        <property type="interactions" value="1358"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NUQ8">
        <property type="interactions" value="116"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NUQ8"/>
    <dbReference type="STRING" id="9606.ENSP00000411471"/>
    <dbReference type="TCDB" id="3.A.1.121.9">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NUQ8">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NUQ8"/>
    <dbReference type="PhosphoSitePlus" id="Q9NUQ8"/>
    <dbReference type="BioMuta" id="ABCF3"/>
    <dbReference type="DMDM" id="114149223"/>
    <dbReference type="jPOST" id="Q9NUQ8"/>
    <dbReference type="MassIVE" id="Q9NUQ8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000411471"/>
    <dbReference type="PeptideAtlas" id="Q9NUQ8"/>
    <dbReference type="ProteomicsDB" id="82712">
        <molecule id="Q9NUQ8-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82713">
        <molecule id="Q9NUQ8-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9NUQ8"/>
    <dbReference type="Antibodypedia" id="33796">
        <property type="antibodies" value="193 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55324"/>
    <dbReference type="Ensembl" id="ENST00000292808.5">
        <molecule id="Q9NUQ8-2"/>
        <property type="protein sequence ID" value="ENSP00000292808.4"/>
        <property type="gene ID" value="ENSG00000161204.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000429586.7">
        <molecule id="Q9NUQ8-1"/>
        <property type="protein sequence ID" value="ENSP00000411471.2"/>
        <property type="gene ID" value="ENSG00000161204.13"/>
    </dbReference>
    <dbReference type="GeneID" id="55324"/>
    <dbReference type="KEGG" id="hsa:55324"/>
    <dbReference type="MANE-Select" id="ENST00000429586.7">
        <property type="protein sequence ID" value="ENSP00000411471.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018358.3"/>
        <property type="RefSeq protein sequence ID" value="NP_060828.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003fmz.3">
        <molecule id="Q9NUQ8-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:72"/>
    <dbReference type="ClinPGx" id="PA24407"/>
    <dbReference type="CTD" id="55324"/>
    <dbReference type="DisGeNET" id="55324"/>
    <dbReference type="GeneCards" id="ABCF3"/>
    <dbReference type="HGNC" id="HGNC:72">
        <property type="gene designation" value="ABCF3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000161204">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCF3"/>
    <dbReference type="MIM" id="618967">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000161204"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000161204"/>
    <dbReference type="eggNOG" id="KOG0062">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155604"/>
    <dbReference type="HOGENOM" id="CLU_000604_36_6_1"/>
    <dbReference type="InParanoid" id="Q9NUQ8"/>
    <dbReference type="OMA" id="CTHIADI"/>
    <dbReference type="OrthoDB" id="2110130at2759"/>
    <dbReference type="PAN-GO" id="Q9NUQ8">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NUQ8"/>
    <dbReference type="PathwayCommons" id="Q9NUQ8"/>
    <dbReference type="SignaLink" id="Q9NUQ8"/>
    <dbReference type="Agora" id="ENSG00000161204"/>
    <dbReference type="BioGRID-ORCS" id="55324">
        <property type="hits" value="9 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCF3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="55324"/>
    <dbReference type="Pharos" id="Q9NUQ8">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NUQ8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NUQ8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000161204">
        <property type="expression patterns" value="Expressed in right adrenal gland cortex and 170 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NUQ8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045296">
        <property type="term" value="F:cadherin binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051607">
        <property type="term" value="P:defense response to virus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd03221">
        <property type="entry name" value="ABCF_EF-3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000104">
        <property type="entry name" value="ATP-binding cassette sub-family F member 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000688">
        <property type="entry name" value="ATP-binding cassette sub-family F member 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032781">
        <property type="entry name" value="ABC_tran_Xtn"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050611">
        <property type="entry name" value="ABCF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR058770">
        <property type="entry name" value="PWI_ABCF3"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19211:SF117">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY F MEMBER 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19211">
        <property type="entry name" value="ATP-BINDING TRANSPORT PROTEIN-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12848">
        <property type="entry name" value="ABC_tran_Xtn"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF26051">
        <property type="entry name" value="PWI_ABCF3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0051">Antiviral defense</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="initiator methionine" description="Removed" evidence="8 9">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000248042" description="ATP-binding cassette sub-family F member 3">
        <location>
            <begin position="2"/>
            <end position="709"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="2">
        <location>
            <begin position="178"/>
            <end position="424"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="2">
        <location>
            <begin position="492"/>
            <end position="707"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="129"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="129"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="161"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="210"/>
            <end position="217"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="525"/>
            <end position="532"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="8 9">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="83"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="157"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 10">
        <location>
            <position position="283"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_020142" description="In isoform 2." evidence="5">
        <location>
            <begin position="69"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027247" description="In dbSNP:rs11706273." evidence="4">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="503"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027248" description="In dbSNP:rs9811715.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="510"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC03881." evidence="6" ref="1">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB14989." evidence="6" ref="1">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA92063." evidence="6" ref="1">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="468"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="709" mass="79745" checksum="E7E0FDB6426F3F60" modified="2006-09-05" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-08-02" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NP78</accession>
    <accession>B4E2J0</accession>
    <accession>Q5W9G7</accession>
    <accession>Q769F3</accession>
    <accession>Q769F4</accession>
    <accession>Q96AB1</accession>
    <accession>Q9P208</accession>
    <name>ABCB9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ABC-type oligopeptide transporter ABCB9</fullName>
            <ecNumber evidence="7 9 11 15">7.4.2.6</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette sub-family B member 9</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 9</fullName>
            <shortName>ABC transporter 9 protein</shortName>
            <shortName>hABCB9</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22">TAP-like protein</fullName>
            <shortName evidence="22">TAPL</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="27" type="primary">ABCB9</name>
        <name evidence="21" type="synonym">KIAA1520</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="J. Biochem." volume="128" first="711" last="718">
            <title>A half-type ABC transporter TAPL is highly conserved between rodent and man, and the human gene is not responsive to interferon-gamma in contrast to TAP1 and TAP2.</title>
            <authorList>
                <person name="Kobayashi A."/>
                <person name="Kasano M."/>
                <person name="Maeda T."/>
                <person name="Hori S."/>
                <person name="Motojima K."/>
                <person name="Suzuki M."/>
                <person name="Fujiwara T."/>
                <person name="Takahashi E."/>
                <person name="Yabe T."/>
                <person name="Tanaka K."/>
                <person name="Kasahara M."/>
                <person name="Yamaguchi Y."/>
                <person name="Maeda M."/>
            </authorList>
            <dbReference type="PubMed" id="11011155"/>
            <dbReference type="DOI" id="10.1093/oxfordjournals.jbchem.a022805"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>INDUCTION</scope>
        <source>
            <tissue>Embryonic kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="23287" last="23294">
            <title>Characterization of ABCB9, an ATP binding cassette protein associated with lysosomes.</title>
            <authorList>
                <person name="Zhang F."/>
                <person name="Zhang W."/>
                <person name="Liu L."/>
                <person name="Fisher C.L."/>
                <person name="Hui D."/>
                <person name="Childs S."/>
                <person name="Dorovini-Zis K."/>
                <person name="Ling V."/>
            </authorList>
            <dbReference type="PubMed" id="10748049"/>
            <dbReference type="DOI" id="10.1074/jbc.m001819200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Lymphoblast</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Biochem. Biophys. Res. Commun." volume="309" first="815" last="822">
            <title>Gene organization of human transporter associated with antigen processing-like (TAPL, ABCB9): analysis of alternative splicing variants and promoter activity.</title>
            <authorList>
                <person name="Kobayashi A."/>
                <person name="Hori S."/>
                <person name="Suita N."/>
                <person name="Maeda M."/>
            </authorList>
            <dbReference type="PubMed" id="13679046"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2003.08.081"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5)</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Embryonic kidney</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="J. Mol. Biol." volume="343" first="1207" last="1220">
            <title>Alternative splice variants encoding unstable protein domains exist in the human brain.</title>
            <authorList>
                <person name="Homma K."/>
                <person name="Kikuno R.F."/>
                <person name="Nagase T."/>
                <person name="Ohara O."/>
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            </authorList>
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            </authorList>
            <dbReference type="PubMed" id="21212514"/>
            <dbReference type="DOI" id="10.1248/bpb.34.36"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2012" name="J. Cell Sci." volume="125" first="4230" last="4240">
            <title>The lysosomal polypeptide transporter TAPL is stabilized by interaction with LAMP-1 and LAMP-2.</title>
            <authorList>
                <person name="Demirel O."/>
                <person name="Jan I."/>
                <person name="Wolters D."/>
                <person name="Blanz J."/>
                <person name="Saftig P."/>
                <person name="Tampe R."/>
                <person name="Abele R."/>
            </authorList>
            <dbReference type="PubMed" id="22641697"/>
            <dbReference type="DOI" id="10.1242/jcs.087346"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH LAMP1 AND LAMP2 (ISOFORM LAMP-2B)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>DOMAIN</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2015" name="Proc. Natl. Acad. Sci. U.S.A." volume="112" first="2046" last="2051">
            <title>Single liposome analysis of peptide translocation by the ABC transporter TAPL.</title>
            <authorList>
                <person name="Zollmann T."/>
                <person name="Moiset G."/>
                <person name="Tumulka F."/>
                <person name="Tampe R."/>
                <person name="Poolman B."/>
                <person name="Abele R."/>
            </authorList>
            <dbReference type="PubMed" id="25646430"/>
            <dbReference type="DOI" id="10.1073/pnas.1418100112"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2018" name="Sci. Rep." volume="8" first="15662" last="15662">
            <title>Structural and functional insights into the interaction and targeting hub TMD0 of the polypeptide transporter TAPL.</title>
            <authorList>
                <person name="Bock C."/>
                <person name="Loehr F."/>
                <person name="Tumulka F."/>
                <person name="Reichel K."/>
                <person name="Wuerz J."/>
                <person name="Hummer G."/>
                <person name="Schaefer L."/>
                <person name="Tampe R."/>
                <person name="Joseph B."/>
                <person name="Bernhard F."/>
                <person name="Doetsch V."/>
                <person name="Abele R."/>
            </authorList>
            <dbReference type="PubMed" id="30353140"/>
            <dbReference type="DOI" id="10.1038/s41598-018-33841-w"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2019" name="J. Biol. Chem." volume="294" first="7308" last="7323">
            <title>Lysosomal targeting of the ABC transporter TAPL is determined by membrane-localized charged residues.</title>
            <authorList>
                <person name="Graab P."/>
                <person name="Bock C."/>
                <person name="Weiss K."/>
                <person name="Hirth A."/>
                <person name="Koller N."/>
                <person name="Braner M."/>
                <person name="Jung J."/>
                <person name="Loehr F."/>
                <person name="Tampe R."/>
                <person name="Behrends C."/>
                <person name="Abele R."/>
            </authorList>
            <dbReference type="PubMed" id="30877195"/>
            <dbReference type="DOI" id="10.1074/jbc.ra118.007071"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ASP-17; ASP-45; ASP-49; ARG-57 AND LYS-100</scope>
        <scope>INTERACTION WITH YIF1B</scope>
        <scope>DOMAIN</scope>
        <scope>SITE</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2019" name="Sci. Rep." volume="9" first="11884" last="11884">
            <title>Peptide translocation by the lysosomal ABC transporter TAPL is regulated by coupling efficiency and activation energy.</title>
            <authorList>
                <person name="Bock C."/>
                <person name="Zollmann T."/>
                <person name="Lindt K.A."/>
                <person name="Tampe R."/>
                <person name="Abele R."/>
            </authorList>
            <dbReference type="PubMed" id="31417173"/>
            <dbReference type="DOI" id="10.1038/s41598-019-48343-6"/>
        </citation>
        <scope>MUTAGENESIS OF LYS-545 AND HIS-699</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2002" name="J. Hum. Genet." volume="47" first="38" last="50">
            <title>Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population.</title>
            <authorList>
                <person name="Saito S."/>
                <person name="Iida A."/>
                <person name="Sekine A."/>
                <person name="Miura Y."/>
                <person name="Ogawa C."/>
                <person name="Kawauchi S."/>
                <person name="Higuchi S."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="11829140"/>
            <dbReference type="DOI" id="10.1007/s10038-002-8653-6"/>
        </citation>
        <scope>VARIANT MET-121</scope>
    </reference>
    <comment type="function">
        <text evidence="7 9 11 15 16 17 18 19">ATP-dependent low-affinity peptide transporter which translocates a broad spectrum of peptides from the cytosol to the lysosomal lumen for degradation (PubMed:15863492, PubMed:17977821, PubMed:18434309, PubMed:22641697, PubMed:25646430, PubMed:30353140, PubMed:30877195, PubMed:31417173). Displays a broad peptide length specificity from 6-mer up to at least 59-mer peptides with an optimum of 23-mers (PubMed:15863492, PubMed:25646430). Binds and transports smaller and larger peptides with the same affinity (PubMed:31417173). Favors positively charged, aromatic or hydrophobic residues in the N- and C-terminal positions whereas negatively charged residues as well as asparagine and methionine are not favored (PubMed:15863492, PubMed:17977821, PubMed:18434309).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 9 11 15 17 18 19">
            <text>a [oligopeptide](in) + ATP + H2O = a [oligopeptide](out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:14429"/>
            <dbReference type="Rhea" id="RHEA-COMP:10531"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:83228"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="7.4.2.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7 9 11 15 17 18 19">
            <dbReference type="Rhea" id="RHEA:14430"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="16 19">Transport activity is limited by threshold levels of luminal peptide (PubMed:25646430). ATP hydrolysis is reduced in the presence of the spatial challenging 18-mer peptide by 50% and the branched 16-mer peptide by 75% (PubMed:31417173). Transport rate of the longer peptides is strongly reduced (PubMed:31417173).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="7">6.8 uM for a 9-mer oligopeptide</KM>
            <KM evidence="16">2.8 uM for a 9-mer oligopeptide (with a macroscopic filter assay)</KM>
            <KM evidence="16">0.9 uM for a 9-mer oligopeptide (with a dual-color fluorescenceburst analysis (DCFBA))</KM>
            <KM evidence="19">15 uM for a 9-mer oligopeptide</KM>
            <KM evidence="19">8 uM for a branched 16-mer oligopeptide</KM>
            <KM evidence="19">7 uM for a spatial challenging 18-mer oligopeptide</KM>
            <KM evidence="19">4.4 uM for a 9-mer oligopeptide (in presence of mM GTP)</KM>
            <KM evidence="19">97 uM for ATP</KM>
            <KM evidence="19">87 uM for GTP</KM>
        </kinetics>
        <phDependence>
            <text evidence="7">Optimum pH is 7.0.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="7">Optimum temperature is 37 degrees Celsius.</text>
        </temperatureDependence>
    </comment>
    <comment type="subunit">
        <text evidence="7 15 17 18">Homodimer (PubMed:15863492, PubMed:30353140). Interacts (via TMD0 region) with LAMP1; this interaction strongly stabilizes ABCB9 and protects ABCB9 against lysosomal degradation (PubMed:22641697). Interacts (via TMD0 region) with LAMP2 (isoform LAMP-2B) (PubMed:22641697). Interacts (via TMD0) with YIF1B; this interaction allows (but is not essential) the ER-to-Golgi trafficking and strongly depends on a salt bridge within TMD0 (PubMed:30877195).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3 6 8 9 10 12 13 14 15 18">Lysosome membrane</location>
            <topology evidence="2 3 6 8 9 10 12 13 14">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="18">May be located in membrane rafts. Takes an intracellular route from the endoplasmic reticulum (ER), via Golgi and early endosomes to late endosomal and lysosomal compartments (PubMed:30877195).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NP78-1</id>
            <name>1</name>
            <name>12A</name>
            <name>c1-l</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NP78-2</id>
            <name>2</name>
            <name>c1-s</name>
            <sequence type="described" ref="VSP_000027"/>
        </isoform>
        <isoform>
            <id>Q9NP78-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_000029 VSP_000030"/>
        </isoform>
        <isoform>
            <id>Q9NP78-5</id>
            <name>4</name>
            <name>12B</name>
            <sequence type="described" ref="VSP_041884 VSP_041886"/>
        </isoform>
        <isoform>
            <id>Q9NP78-6</id>
            <name>5</name>
            <name>12C</name>
            <sequence type="described" ref="VSP_041885"/>
        </isoform>
        <isoform>
            <id>Q9NP78-7</id>
            <name>6</name>
            <sequence type="described" ref="VSP_044884"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 9">Highly expressed in testis, and at moderate levels in brain, spinal cord, and thyroid. Not expressed in monocytes but strongly expressed during differentiation of monocytes to dendritic cells and macrophages.</text>
    </comment>
    <comment type="induction">
        <text evidence="4">Not induced by interferon-gamma.</text>
    </comment>
    <comment type="domain">
        <text evidence="6 10 12 13 15 18">Divided into an N-terminal domain (TMD0) comprising four transmembrane helices and the following core domain (coreABCB9) (PubMed:18952056). TMD0 is required for lysosomal localization and LAMP1, LAMP2 and YIF1B interaction (PubMed:15577206, PubMed:18175933, PubMed:20377823, PubMed:22641697, PubMed:30877195). The core domain is required for homodimerization and peptide transport activity (PubMed:18952056, PubMed:20377823).</text>
    </comment>
    <comment type="similarity">
        <text evidence="25">Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="26">Has also been detected in the endoplasmic reticulum but appears to be a lysosomal protein in vivo.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA96044" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD66830" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.4.2.6" evidence="7 9 11 15"/>
    <dbReference type="EMBL" id="AB045381">
        <property type="protein sequence ID" value="BAA97989.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF216494">
        <property type="protein sequence ID" value="AAF89993.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB112582">
        <property type="protein sequence ID" value="BAC98409.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB112583">
        <property type="protein sequence ID" value="BAC98410.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB177852">
        <property type="protein sequence ID" value="BAD66830.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB040953">
        <property type="protein sequence ID" value="BAA96044.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK304295">
        <property type="protein sequence ID" value="BAG65152.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026362">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC027290">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017348">
        <property type="protein sequence ID" value="AAH17348.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58286.1">
        <molecule id="Q9NP78-7"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58287.1">
        <molecule id="Q9NP78-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58288.1">
        <molecule id="Q9NP78-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9241.1">
        <molecule id="Q9NP78-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001229942.1">
        <molecule id="Q9NP78-7"/>
        <property type="nucleotide sequence ID" value="NM_001243013.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001229943.1">
        <molecule id="Q9NP78-6"/>
        <property type="nucleotide sequence ID" value="NM_001243014.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424772.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="NM_001437843.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001425327.1">
        <molecule id="Q9NP78-2"/>
        <property type="nucleotide sequence ID" value="NM_001438398.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_062570.1">
        <molecule id="Q9NP78-2"/>
        <property type="nucleotide sequence ID" value="NM_019624.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_062571.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="NM_019625.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_982269.2">
        <molecule id="Q9NP78-5"/>
        <property type="nucleotide sequence ID" value="NM_203444.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011536398.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_011538096.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016874592.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_017019103.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227568.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371593.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227570.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371595.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227571.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371596.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227572.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371597.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227573.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371598.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227574.1">
        <molecule id="Q9NP78-1"/>
        <property type="nucleotide sequence ID" value="XM_054371599.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227575.1">
        <molecule id="Q9NP78-2"/>
        <property type="nucleotide sequence ID" value="XM_054371600.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054227577.1">
        <molecule id="Q9NP78-7"/>
        <property type="nucleotide sequence ID" value="XM_054371602.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NP78"/>
    <dbReference type="SMR" id="Q9NP78"/>
    <dbReference type="BioGRID" id="117021">
        <property type="interactions" value="43"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NP78">
        <property type="interactions" value="506"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NP78">
        <property type="interactions" value="31"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000440288"/>
    <dbReference type="ChEMBL" id="CHEMBL1293189"/>
    <dbReference type="TCDB" id="3.A.1.209.2">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NP78">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NP78"/>
    <dbReference type="PhosphoSitePlus" id="Q9NP78"/>
    <dbReference type="BioMuta" id="ABCB9"/>
    <dbReference type="DMDM" id="22095458"/>
    <dbReference type="jPOST" id="Q9NP78"/>
    <dbReference type="MassIVE" id="Q9NP78"/>
    <dbReference type="PaxDb" id="9606-ENSP00000440288"/>
    <dbReference type="PeptideAtlas" id="Q9NP78"/>
    <dbReference type="ProteomicsDB" id="5823"/>
    <dbReference type="ProteomicsDB" id="81917">
        <molecule id="Q9NP78-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81918">
        <molecule id="Q9NP78-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81919">
        <molecule id="Q9NP78-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81920">
        <molecule id="Q9NP78-5"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81921">
        <molecule id="Q9NP78-6"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="31719">
        <property type="antibodies" value="245 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23457"/>
    <dbReference type="Ensembl" id="ENST00000280560.13">
        <molecule id="Q9NP78-1"/>
        <property type="protein sequence ID" value="ENSP00000280560.8"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000344275.11">
        <molecule id="Q9NP78-6"/>
        <property type="protein sequence ID" value="ENSP00000456813.1"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000346530.9">
        <molecule id="Q9NP78-2"/>
        <property type="protein sequence ID" value="ENSP00000280559.7"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000392439.7">
        <molecule id="Q9NP78-1"/>
        <property type="protein sequence ID" value="ENSP00000376234.3"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000442833.6">
        <molecule id="Q9NP78-5"/>
        <property type="protein sequence ID" value="ENSP00000456375.1"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000540285.5">
        <molecule id="Q9NP78-7"/>
        <property type="protein sequence ID" value="ENSP00000441734.1"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000542678.5">
        <molecule id="Q9NP78-1"/>
        <property type="protein sequence ID" value="ENSP00000440288.1"/>
        <property type="gene ID" value="ENSG00000150967.20"/>
    </dbReference>
    <dbReference type="GeneID" id="23457"/>
    <dbReference type="KEGG" id="hsa:23457"/>
    <dbReference type="MANE-Select" id="ENST00000280560.13">
        <property type="protein sequence ID" value="ENSP00000280560.8"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_019625.4"/>
        <property type="RefSeq protein sequence ID" value="NP_062571.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001udm.5">
        <molecule id="Q9NP78-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:50"/>
    <dbReference type="ClinPGx" id="PA24391"/>
    <dbReference type="CTD" id="23457"/>
    <dbReference type="DisGeNET" id="23457"/>
    <dbReference type="GeneCards" id="ABCB9"/>
    <dbReference type="HGNC" id="HGNC:50">
        <property type="gene designation" value="ABCB9"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000150967">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="605453">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000150967"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000150967"/>
    <dbReference type="eggNOG" id="KOG0058">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155431"/>
    <dbReference type="InParanoid" id="Q9NP78"/>
    <dbReference type="OrthoDB" id="6500128at2759"/>
    <dbReference type="PAN-GO" id="Q9NP78">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NP78"/>
    <dbReference type="BRENDA" id="7.4.2.5">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NP78"/>
    <dbReference type="Reactome" id="R-HSA-382556">
        <property type="pathway name" value="ABC-family proteins mediated transport"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9NP78"/>
    <dbReference type="SignaLink" id="Q9NP78"/>
    <dbReference type="Agora" id="ENSG00000150967"/>
    <dbReference type="BioGRID-ORCS" id="23457">
        <property type="hits" value="15 hits in 1160 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCB9">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCB9"/>
    <dbReference type="GenomeRNAi" id="23457"/>
    <dbReference type="Pharos" id="Q9NP78">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NP78"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NP78">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000150967">
        <property type="expression patterns" value="Expressed in buccal mucosa cell and 171 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NP78">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005765">
        <property type="term" value="C:lysosomal membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005764">
        <property type="term" value="C:lysosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015421">
        <property type="term" value="F:ABC-type oligopeptide transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015440">
        <property type="term" value="F:ABC-type peptide transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022857">
        <property type="term" value="F:transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006518">
        <property type="term" value="P:peptide metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015833">
        <property type="term" value="P:peptide transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015031">
        <property type="term" value="P:protein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055085">
        <property type="term" value="P:transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd18784">
        <property type="entry name" value="ABC_6TM_ABCB9_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd03248">
        <property type="entry name" value="ABCC_TAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1560.10:FF:000031">
        <property type="entry name" value="ATP-binding cassette sub-family B member 9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000140">
        <property type="entry name" value="Lipid A export ATP-binding/permease protein MsbA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1560.10">
        <property type="entry name" value="ABC transporter type 1, transmembrane domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011527">
        <property type="entry name" value="ABC1_TM_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036640">
        <property type="entry name" value="ABC1_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR030254">
        <property type="entry name" value="ABCB9_6-TMD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039421">
        <property type="entry name" value="Type_1_exporter"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43394:SF21">
        <property type="entry name" value="ATP BINDING CASSETTE SUBFAMILY B MEMBER 9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43394">
        <property type="entry name" value="ATP-DEPENDENT PERMEASE MDL1, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00664">
        <property type="entry name" value="ABC_membrane"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF002773">
        <property type="entry name" value="ABC_prm/ATPase_B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90123">
        <property type="entry name" value="ABC transporter transmembrane region"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50929">
        <property type="entry name" value="ABC_TM1F"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0571">Peptide transport</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000000252" description="ABC-type oligopeptide transporter ABCB9">
        <location>
            <begin position="1"/>
            <end position="766"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="7"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="47"/>
            <end position="67"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="84"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="116"/>
            <end position="136"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="185"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="225"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="319"/>
            <end position="339"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="416"/>
            <end position="436"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1" evidence="2">
        <location>
            <begin position="188"/>
            <end position="471"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="1">
        <location>
            <begin position="504"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="539"/>
            <end position="546"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="site" description="Intramolecular salt bridge with Arg-57. Essential for the release from the ER" evidence="18">
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="site" description="Important for the second trafficking step from the Golgi to the endosomal and lysosomal compartments" evidence="18">
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="site" description="Important for the second trafficking step from the Golgi to the endosomal and lysosomal compartments" evidence="18">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="site" description="Intramolecular salt bridge with Asp-17. Essential for the release from the ER" evidence="18">
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000027" description="In isoform 2." evidence="20">
        <location>
            <begin position="418"/>
            <end position="460"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044884" description="In isoform 6." evidence="25">
        <location>
            <begin position="461"/>
            <end position="523"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000029" description="In isoform 3." evidence="24">
        <original>ISLVSQEPVLFARSI</original>
        <variation>VCARAWATLLRPFCI</variation>
        <location>
            <begin position="582"/>
            <end position="596"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000030" description="In isoform 3." evidence="24">
        <location>
            <begin position="597"/>
            <end position="766"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041884" description="In isoform 4." evidence="23">
        <original>IQQ</original>
        <variation>CAG</variation>
        <location>
            <begin position="681"/>
            <end position="683"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041885" description="In isoform 5." evidence="23">
        <location>
            <begin position="682"/>
            <end position="766"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041886" description="In isoform 4." evidence="23">
        <location>
            <begin position="684"/>
            <end position="766"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013701" description="In dbSNP:rs3803002." evidence="5">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lysosomal localization. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect dimerization. Does not affect peptide transport activity. Decreases interaction with YIF1B." evidence="18">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lysosomal localization. Does not affect lysosomal localization; when associated with D-57. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with D-57. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with D-100." evidence="18">
        <original>D</original>
        <variation>R</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lysosomal localization; when assosiated with K-49. Loss of lysosomal localization; when assosiated with K-49 and D-100. Does not affect peptide transport activity; when assosiated with K-49 and D-100." evidence="18">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases lysosomal localization; when associated with N-49." evidence="18">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lysosomal localization; when assosiated with K-45. Loss of lysosomal localization; when assosiated with K-45 and D-100. Does not affect peptide transport activity; when assosiated with K-45 and D-100." evidence="18">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases lysosomal localization; when associated with N-45." evidence="18">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases lysosomal localization. Loss of lysosomal localization; when associated with A-100." evidence="18">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lysosomal localization. Does not affect lysosomal localization; when associated with R-17. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with R-17." evidence="18">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases lysosomal localization. Loss of lysosomal localization; when associated with A-57." evidence="18">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases lysosomal localization. Loss of lysosomal localization; when assosiated with R-17. Loss of lysosomal localization; when assosiated with K-45 and K-49. Does not affect peptide transport activity; when assosiated with K-45 and K-49. Does not affect interaction between coreABCB9 and TMD0 domains. Does not affect interaction between coreABCB9 and TMD0 domains; when associated with R-17." evidence="18">
        <original>K</original>
        <variation>D</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on lysosomal localization." evidence="13">
        <original>LL</original>
        <variation>AA</variation>
        <location>
            <begin position="136"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of peptide transport activity; whena ssociated with A-699." evidence="19">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="545"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of peptide transport activity; whena ssociated with A-545." evidence="19">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="699"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00441"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10748049"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11011155"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11829140"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15577206"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15863492"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17897319"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17977821"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18175933"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18434309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="18952056"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="20377823"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="21212514"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22641697"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="25646430"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="30353140"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="30877195"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="31417173"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="10748049"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="10819331"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="11011155"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="13679046"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="25"/>
    <evidence type="ECO:0000305" key="26">
        <source>
            <dbReference type="PubMed" id="11011155"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="27">
        <source>
            <dbReference type="HGNC" id="HGNC:50"/>
        </source>
    </evidence>
    <sequence length="766" mass="84475" checksum="C83FA62C929EC792" modified="2000-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-01-24" modified="2026-01-28" version="229" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UNQ0</accession>
    <accession>A0A1W3</accession>
    <accession>A8K1T5</accession>
    <accession>O95374</accession>
    <accession>Q4W5I3</accession>
    <accession>Q53ZQ1</accession>
    <accession>Q569L4</accession>
    <accession>Q5YLG4</accession>
    <accession>Q86V64</accession>
    <accession>Q8IX16</accession>
    <accession>Q96LD6</accession>
    <accession>Q96TA8</accession>
    <accession>Q9BY73</accession>
    <accession>Q9NUS0</accession>
    <name>ABCG2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="45">Broad substrate specificity ATP-binding cassette transporter ABCG2</fullName>
            <ecNumber evidence="4 35">7.6.2.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette sub-family G member 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Breast cancer resistance protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>CDw338</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Mitoxantrone resistance-associated protein</fullName>
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        <alternativeName>
            <fullName>Placenta-specific ATP-binding cassette transporter</fullName>
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        <alternativeName>
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        <cdAntigenName>CD338</cdAntigenName>
    </protein>
    <gene>
        <name evidence="52" type="primary">ABCG2</name>
        <name type="synonym">ABCP</name>
        <name type="synonym">BCRP</name>
        <name type="synonym">BCRP1</name>
        <name type="synonym">MXR</name>
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    <organism>
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        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>GLYCOSYLATION AT ASN-596</scope>
        <scope>LACK OF GLYCOSYLATION AT ASN-418 AND ASN-557</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>HOMODIMERIZATION</scope>
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        <scope>DISULFIDE BONDS</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>PHOSPHORYLATION AT THR-362</scope>
        <scope>MUTAGENESIS OF THR-362</scope>
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        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN UAQTL1</scope>
        <scope>ASSOCIATION OF VARIANT LYS-141 WITH GOUT</scope>
        <scope>CHARACTERIZATION OF VARIANT LYS-141</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>POLYMORPHISM</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>CAUTION</scope>
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        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF HIS-583; CYS-603 AND TYR-605</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN JR</scope>
        <scope>VARIANT MET-12</scope>
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        <scope>INVOLVEMENT IN JR</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>GLYCOSYLATION</scope>
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        <scope>CAUTION</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANT LYS-141; TRP-147; MET-153; LYS-360 DEL; CYS-373; MET-434 AND PRO-476</scope>
        <scope>MUTAGENESIS OF MET-71; LYS-86 AND ARG-383</scope>
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        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>DISULFIDE BOND</scope>
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                <person name="Sugiyama Y."/>
                <person name="Ozawa S."/>
                <person name="Sawada J."/>
            </authorList>
            <dbReference type="PubMed" id="15618737"/>
            <dbReference type="DOI" id="10.2133/dmpk.18.212"/>
        </citation>
        <scope>VARIANTS LEU-431 AND LEU-489</scope>
    </reference>
    <reference key="44">
        <citation type="journal article" date="2003" name="Pharmacogenetics" volume="13" first="19" last="28">
            <title>Natural allelic variants of breast cancer resistance protein (BCRP) and their relationship to BCRP expression in human intestine.</title>
            <authorList>
                <person name="Zamber C.P."/>
                <person name="Lamba J.K."/>
                <person name="Yasuda K."/>
                <person name="Farnum J."/>
                <person name="Thummel K."/>
                <person name="Schuetz J.D."/>
                <person name="Schuetz E.G."/>
            </authorList>
            <dbReference type="PubMed" id="12544509"/>
            <dbReference type="DOI" id="10.1097/00008571-200301000-00004"/>
        </citation>
        <scope>VARIANTS MET-12; LYS-141; LEU-206 AND TYR-590</scope>
    </reference>
    <reference key="45">
        <citation type="journal article" date="2005" name="Cancer Chemother. Pharmacol." volume="56" first="161" last="172">
            <title>Single nucleotide polymorphisms modify the transporter activity of ABCG2.</title>
            <authorList>
                <person name="Morisaki K."/>
                <person name="Robey R.W."/>
                <person name="Oezvegy-Laczka C."/>
                <person name="Honjo Y."/>
                <person name="Polgar O."/>
                <person name="Steadman K."/>
                <person name="Sarkadi B."/>
                <person name="Bates S.E."/>
            </authorList>
            <dbReference type="PubMed" id="15838659"/>
            <dbReference type="DOI" id="10.1007/s00280-004-0931-x"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS MET-12; LYS-141 AND ASN-620</scope>
    </reference>
    <reference key="46">
        <citation type="journal article" date="2006" name="Drug Metab. Pharmacokinet." volume="21" first="109" last="121">
            <title>Genetic variation and haplotype structure of the ABC transporter gene ABCG2 in a Japanese population.</title>
            <authorList>
                <person name="Maekawa K."/>
                <person name="Itoda M."/>
                <person name="Sai K."/>
                <person name="Saito Y."/>
                <person name="Kaniwa N."/>
                <person name="Shirao K."/>
                <person name="Hamaguchi T."/>
                <person name="Kunitoh H."/>
                <person name="Yamamoto N."/>
                <person name="Tamura T."/>
                <person name="Minami H."/>
                <person name="Kubota K."/>
                <person name="Ohtsu A."/>
                <person name="Yoshida T."/>
                <person name="Saijo N."/>
                <person name="Kamatani N."/>
                <person name="Ozawa S."/>
                <person name="Sawada J."/>
            </authorList>
            <dbReference type="PubMed" id="16702730"/>
            <dbReference type="DOI" id="10.2133/dmpk.21.109"/>
        </citation>
        <scope>VARIANTS MET-12; LEU-13; LYS-141; GLN-160; ARG-354; LEU-431; ASN-441 AND LEU-489</scope>
    </reference>
    <reference key="47">
        <citation type="journal article" date="2019" name="Cells" volume="8" first="0" last="0">
            <title>Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort.</title>
            <authorList>
                <person name="Toyoda Y."/>
                <person name="Mancikova A."/>
                <person name="Krylov V."/>
                <person name="Morimoto K."/>
                <person name="Pavelcova K."/>
                <person name="Bohata J."/>
                <person name="Pavelka K."/>
                <person name="Pavlikova M."/>
                <person name="Suzuki H."/>
                <person name="Matsuo H."/>
                <person name="Takada T."/>
                <person name="Stiburkova B."/>
            </authorList>
            <dbReference type="PubMed" id="31003562"/>
            <dbReference type="DOI" id="10.3390/cells8040363"/>
        </citation>
        <scope>VARIANTS TRP-147; MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476; ARG-572 AND ASN-620</scope>
        <scope>CHARACTERIZATION OF VARIANTS LYS-141; TRP-147; MET-153; LYS-360 DEL; CYS-373; ALA-421; MET-434; PRO-476; ARG-572 AND ASN-620</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 6 8 9 13 19 21 22 24 25 26 29 31 33 34 35 37 38 46">Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the vitamins riboflavin and biotin into milk (By similarity). Involved in the excretion of the riboflavin-derived compound lumichrome into the intestinal lumen and in its secretion into milk (PubMed:39337371). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity). In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6 9 35">
            <text>ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.</text>
            <dbReference type="EC" id="7.6.2.2"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="36 47 48 49 50">
            <text>urate(in) + ATP + H2O = urate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16461"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17775"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:16462"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>indoxyl sulfate(in) + ATP + H2O = indoxyl sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61332"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:144643"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:61333"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="22">
            <text>sphing-4-enine 1-phosphate(in) + ATP + H2O = sphing-4-enine 1-phosphate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38951"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60119"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:38952"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 31 33">
            <text>estrone 3-sulfate(in) + ATP + H2O = estrone 3-sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61348"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60050"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61349"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>dehydroepiandrosterone 3-sulfate(in) + ATP + H2O = dehydroepiandrosterone 3-sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61364"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57905"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61365"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>4-methylumbelliferone sulfate(in) + ATP + H2O = 4-methylumbelliferone sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61368"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:144581"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61369"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl beta-D-glucuronate(in) + ATP + H2O = 5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl beta-D-glucuronate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61384"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:144584"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61385"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>4-methylumbelliferone beta-D-glucuronate(in) + ATP + H2O = 4-methylumbelliferone beta-D-glucuronate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61372"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:144582"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61373"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl sulfate(in) + ATP + H2O = 5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)-1,3-benzothiazol-6-yl sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61376"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:144583"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61377"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60128"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:82961"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:60129"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>methotrexate(in) + ATP + H2O = methotrexate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61356"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:50681"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:61357"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>riboflavin(in) + ATP + H2O = riboflavin(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61352"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57986"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:61353"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>pheophorbide a(in) + ATP + H2O = pheophorbide a(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61360"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58687"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:61361"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="36">
            <text>itaconate(in) + ATP + H2O = itaconate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:82291"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17240"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="36">
            <dbReference type="Rhea" id="RHEA:82292"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="38">
            <text>lumichrome(in) + ATP + H2O = lumichrome(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86403"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17781"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="51">
            <dbReference type="Rhea" id="RHEA:86404"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="6">Specifically inhibited by the fungal toxin fumitremorgin C and Ko143.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="8">16.6 uM for estrone 3-sulfate</KM>
            <KM evidence="8">1.23 mM for ATP</KM>
            <KM evidence="8">12.9 uM for 4-methylumbelliferone sulfate</KM>
            <KM evidence="8">26.9 uM for 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl)benzothiazole sulfate</KM>
            <KM evidence="26">8.24 mM for urate</KM>
            <Vmax evidence="8">2.34 nmol/min/mg enzyme for estrone 3-sulfate transport</Vmax>
            <Vmax evidence="26">6.96 nmol/min/mg enzyme for urate transport</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="10 18 19 31">Homodimer; disulfide-linked (PubMed:15001581, PubMed:17686774, PubMed:18056989, PubMed:28554189). The minimal functional unit is a homodimer, but the major oligomeric form in plasma membrane is a homotetramer with possibility of higher order oligomerization up to homododecamers (PubMed:15001581).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1569435">
            <id>Q9UNQ0</id>
        </interactant>
        <interactant intactId="EBI-1569435">
            <id>Q9UNQ0</id>
            <label>ABCG2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1569435">
            <id>Q9UNQ0</id>
        </interactant>
        <interactant intactId="EBI-3197846">
            <id>P22413</id>
            <label>ENPP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1569435">
            <id>Q9UNQ0</id>
        </interactant>
        <interactant intactId="EBI-1018633">
            <id>P11309-2</id>
            <label>PIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1569435">
            <id>Q9UNQ0</id>
        </interactant>
        <interactant intactId="EBI-3390054">
            <id>P0CG48</id>
            <label>UBC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-20717342">
            <id>Q9UNQ0-1</id>
        </interactant>
        <interactant intactId="EBI-20717342">
            <id>Q9UNQ0-1</id>
            <label>ABCG2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10 14 15 19 34 35">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="21">Apical cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="29">Mitochondrion membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="32">Enriched in membrane lipid rafts.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UNQ0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UNQ0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_014232 VSP_014233"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 39 40">Highly expressed in placenta (PubMed:9850061). Low expression in small intestine, liver and colon (PubMed:9861027). Expressed in brain (at protein level) (PubMed:12958161).</text>
    </comment>
    <comment type="domain">
        <text evidence="25">The extracellular loop 3 (ECL3) is involved in binding porphyrins and transfer them to other carriers, probably albumin.</text>
    </comment>
    <comment type="PTM">
        <text evidence="15 29">N-glycosylated (PubMed:15807535, PubMed:23189181). Glycosylation-deficient ABCG2 is normally expressed and functional.</text>
    </comment>
    <comment type="PTM">
        <text evidence="19">Phosphorylated. Phosphorylation at Thr-362 by PIM1 is induced by drugs like mitoxantrone and is associated with cells increased drug resistance. It regulates the localization to the plasma membrane, the homooligomerization and therefore, the activity of the transporter.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="27 28">Genetic variations in ABCG2 define the blood group Junior system (JR) [MIM:614490]. Individuals with Jr(a-) blood group lack the Jr(a) antigen on their red blood cells. These individuals may have anti-Jr(a) antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. Although the clinical significance of the Jr(a-) blood group has been controversial, severe fatal hemolytic disease of the newborn has been reported. The Jr(a-) phenotype has a higher frequency in individuals of Asian descent, compared to those of European descent. The Jr(a-) phenotype is inherited as an autosomal recessive trait.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="20 21 24">Genetic variations in ABCG2 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 1 (UAQTL1) [MIM:138900]. Excess serum accumulation of uric acid can lead to the development of gout, a common disorder characterized by tissue deposition of monosodium urate crystals as a consequence of hyperuricemia (PubMed:18834626, PubMed:19506252, PubMed:20368174).</text>
    </comment>
    <comment type="similarity">
        <text evidence="45">Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="23 30">Was originally proposed to function as a glutathione transporter (PubMed:20332504). However, some evidences suggest it is not the case (PubMed:24312054).</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="AF093771"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="AF093772"/>
        </conflict>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/222/"/>
        <text>The unwalkable disease - Issue 222 of February 2020</text>
    </comment>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="33 55 56">
        <location>
            <position position="211"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="33 55 56">
        <location>
            <position position="243"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="site" description="Not glycosylated" evidence="15">
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="site" description="Not glycosylated" evidence="15">
        <location>
            <position position="557"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by PIM1" evidence="19">
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="15 31 53 54">
        <location>
            <position position="596"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 31 53 54">
        <location>
            <begin position="592"/>
            <end position="608"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain" evidence="18 31 53 54">
        <location>
            <position position="603"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_014232" description="In isoform 2." evidence="44">
        <original>IFSGLLVNLTTIASWLSWLQYFSIPRYGFTALQHNEFLGQNFCPGLNATGNNPCNYATCTGE</original>
        <variation>VCWSISQPLHLGCHGFSTSAFHDMDLRLCSIMNFWDKTSAQDSMQQETILVTMQHVLAKNIW</variation>
        <location>
            <begin position="550"/>
            <end position="611"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_014233" description="In isoform 2." evidence="44">
        <location>
            <begin position="612"/>
            <end position="655"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020779" description="Found in Jr(a-) blood group phenotype; dbSNP:rs2231137." evidence="5 7 16 17 28 41">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067363" description="In dbSNP:rs1319203095." evidence="17">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020780" description="Associated with high serum levels of uric acid and increased risk of gout; results in lower urate transport rates compared to wild-type; decreased protein abundance; dbSNP:rs2231142." evidence="5 7 11 16 17 21 34 35 41 42">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082302" description="Loss of protein expression; loss of localization to the plasma membrane; dbSNP:rs372192400." evidence="34 35">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082303" description="Decreased protein abundance; no effect on localization to the plasma membrane; no effect on substrate transmembrane transport; decreased ATPase activity; no effect on ATPase-coupled transmembrane transporter activity; dbSNP:rs753759474." evidence="34 35">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067364" description="In dbSNP:rs528655917." evidence="17">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022704" description="In dbSNP:rs1061017." evidence="9 39">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022705" description="In dbSNP:rs12721643." evidence="7">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022706" description="In dbSNP:rs1061018." evidence="9 39">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="208"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022707" description="In dbSNP:rs3116448.">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030357" description="In dbSNP:rs41282401." evidence="41">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022443" evidence="43">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067365" description="In dbSNP:rs138606116." evidence="17">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="354"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082304" description="No effect on protein abundance; no effect on localization to the plasma membrane; no effect on ATPase activity; no effect on substrate transmembrane transport." evidence="34 35">
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082305" description="Decreased protein abundance; decreased localization to the plasma membrane; no effect on ATPase-coupled transmembrane transporter activity; dbSNP:rs752626614." evidence="34 35">
        <original>F</original>
        <variation>C</variation>
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082306" description="No effect on protein abundance; no effect on substrate transmembrane transport; dbSNP:rs199854112." evidence="34">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="421"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018349" evidence="12 17">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082307" description="No effect on protein abundance; no effect on localization to the plasma membrane; increased ATPase activity; decreased ATPase-coupled transmembrane transporter activity; dbSNP:rs769734146." evidence="34 35">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="434"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067366" description="In dbSNP:rs1354553769." evidence="17">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="441"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082308" description="No effect on protein abundance; no effect on localization to the plasma membrane; no effect on ATPase activity; decreased ATPase-coupled transmembrane transporter activity; dbSNP:rs1274428653." evidence="34 35">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="476"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018350" description="In dbSNP:rs192169063." evidence="12 17">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="489"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030358" description="In dbSNP:rs45605536." evidence="41">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="528"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022708" description="In dbSNP:rs9282571.">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="571"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082309" description="Decreased protein abundance; loss of localization to the plasma membrane; dbSNP:rs200894058." evidence="34">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="572"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035355" description="In dbSNP:rs34264773." evidence="7">
        <original>N</original>
        <variation>Y</variation>
        <location>
            <position position="590"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022709" description="No effect on protein abundance; no effect on substrate transmembrane transport; dbSNP:rs34783571." evidence="16 34">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="620"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased protein abundance. No effect on substrate transmembrane transport." evidence="35">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased protein abundance. Decreased localization to the plasma membrane and retained intracellularly. Loss of ATPase-coupled transmembrane transporter activity." evidence="14 35">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Loss of ATP-dependent itaconate export resulting in itaconate cytosolic accumulation." evidence="31 33 37">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of phosphorylation by PIM1. Decreased localization to the plasma membrane. Decreased homooligomerization. Loss of function in resistance to drug treatment." evidence="19">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of phosphorylation by PIM1. Constitutive drug resistance independent of PIM1." evidence="19">
        <original>T</original>
        <variation>D</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of protein expression." evidence="35">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect." evidence="15">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Increased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased substrate-induced ATP hydrolysis. Increased substrate transport." evidence="33">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="435"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Decreased substrate transport." evidence="33">
        <original>T</original>
        <variation>F</variation>
        <location>
            <position position="435"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Decreased substrate transport." evidence="33">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="436"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Decreased substrate-induced ATP hydrolysis. Decreased substrate transport." evidence="33">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="439"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases ATPase activity." evidence="13">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases ATPase activity." evidence="13">
        <original>R</original>
        <variation>G</variation>
        <variation>N</variation>
        <variation>S</variation>
        <variation>T</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No change in ATPase activity." evidence="13">
        <original>R</original>
        <variation>K</variation>
        <variation>I</variation>
        <variation>M</variation>
        <variation>Y</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases transport activity." evidence="13">
        <original>R</original>
        <variation>T</variation>
        <variation>Y</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. No effect on estrone-3 sulfate ATPase-coupled transmembrane transporter activity. No effect on substrate-induced ATP hydrolysis. No effect on substrate transport." evidence="33">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Decreased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased basal and substrate-induced ATP hydrolysis. Decreased substrate transport." evidence="33">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. No effect on estrone-3 sulfate ATPase-coupled transmembrane transporter activity. No effect on substrate-induced ATP hydrolysis. No effect on substrate transport." evidence="33">
        <original>M</original>
        <variation>A</variation>
        <location>
            <position position="549"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on stability. Increased estrone-3 sulfate ATPase-coupled transmembrane transporter activity. Increased basal and substrate-induced ATP hydrolysis. Increased substrate transport." evidence="33">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of protein expression." evidence="33">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="555"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect." evidence="15">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="557"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly reduced binding to hemin but not to PPIX." evidence="25">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of glycosylation." evidence="15">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="596"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly reduced binding to hemin but not to PPIX." evidence="25">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="603"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hemin binding." evidence="25">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="605"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD09188 and 7; AAP44087." evidence="45" ref="1 7">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 10; BAA92050." evidence="45" ref="10">
        <location>
            <begin position="315"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 13; AAH92408." evidence="45" ref="13">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="390"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 14; AF093771/AF093772." evidence="45" ref="14">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAC97367." evidence="45" ref="2">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 14; AF093772." evidence="45" ref="14">
        <original>LP</original>
        <variation>FT</variation>
        <location>
            <begin position="484"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAG52982." evidence="45" ref="6">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="501"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="37"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="62"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="73"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="turn" evidence="62">
        <location>
            <begin position="82"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="86"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="turn" evidence="62">
        <location>
            <begin position="99"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="104"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="117"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="121"/>
            <end position="124"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="132"/>
            <end position="135"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="136"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="150"/>
            <end position="152"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="154"/>
            <end position="168"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="171"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="174"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="181"/>
            <end position="183"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="188"/>
            <end position="200"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="205"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="turn" evidence="62">
        <location>
            <begin position="212"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="218"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="237"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="247"/>
            <end position="250"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="254"/>
            <end position="260"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="263"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="270"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="273"/>
            <end position="280"/>
        </location>
    </feature>
    <feature type="strand" evidence="59">
        <location>
            <begin position="286"/>
            <end position="288"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="290"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="helix" evidence="57">
        <location>
            <begin position="303"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="329"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="340"/>
            <end position="352"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="373"/>
            <end position="390"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="393"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="turn" evidence="60">
        <location>
            <begin position="413"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="strand" evidence="58">
        <location>
            <begin position="418"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="422"/>
            <end position="439"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="440"/>
            <end position="445"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="446"/>
            <end position="449"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="452"/>
            <end position="460"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="466"/>
            <end position="476"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="478"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="484"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="503"/>
            <end position="528"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="535"/>
            <end position="550"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="552"/>
            <end position="556"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="558"/>
            <end position="560"/>
        </location>
    </feature>
    <feature type="helix" evidence="62">
        <location>
            <begin position="563"/>
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</entry>
<entry dataset="Swiss-Prot" created="2001-12-05" modified="2026-01-28" version="212" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H221</accession>
    <accession>Q53QN8</accession>
    <name>ABCG8_HUMAN</name>
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        <recommendedName>
            <fullName evidence="16">ATP-binding cassette sub-family G member 8</fullName>
            <ecNumber evidence="1">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="15">Sterolin-2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="18" type="primary">ABCG8</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>VARIANT CYS-54</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS STSL1 HIS-184; THR-231; LYS-238; GLN-263; HIS-405; PRO-501; SER-543; PHE-570 DEL; PRO-572; ARG-574; GLU-574 AND ARG-596</scope>
        <scope>VARIANTS HIS-19; CYS-54; VAL-259; LYS-400; ARG-575 AND ALA-632</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
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            <dbReference type="DOI" id="10.1038/nature03466"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>REVIEW</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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            <dbReference type="DOI" id="10.1021/bi0608055"/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>GLYCOSYLATION</scope>
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                <person name="Johnson B.J."/>
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            </authorList>
            <dbReference type="PubMed" id="20210363"/>
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        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBUNIT</scope>
        <scope>GLYCOSYLATION</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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                <person name="Xie X.S."/>
                <person name="Grishin N.V."/>
                <person name="Cohen J.C."/>
                <person name="Otwinowski Z."/>
                <person name="Hobbs H.H."/>
                <person name="Rosenbaum D.M."/>
            </authorList>
            <dbReference type="PubMed" id="27144356"/>
            <dbReference type="DOI" id="10.1038/nature17666"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) IN COMPLEX WITH ABCG5</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF GLY-216</scope>
        <scope>SUBUNIT</scope>
        <scope>TOPOLOGY</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2001" name="Hum. Mutat." volume="18" first="359" last="360">
            <title>Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia.</title>
            <authorList>
                <person name="Hubacek J.A."/>
                <person name="Berge K.E."/>
                <person name="Cohen J.C."/>
                <person name="Hobbs H.H."/>
            </authorList>
            <dbReference type="PubMed" id="11668628"/>
            <dbReference type="DOI" id="10.1002/humu.1206"/>
        </citation>
        <scope>VARIANTS HIS-19; CYS-54; LYS-400; ALA-632 AND PHE-641</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2002" name="J. Hum. Genet." volume="47" first="285" last="310">
            <title>Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.</title>
            <authorList>
                <person name="Iida A."/>
                <person name="Saito S."/>
                <person name="Sekine A."/>
                <person name="Mishima C."/>
                <person name="Kitamura Y."/>
                <person name="Kondo K."/>
                <person name="Harigae S."/>
                <person name="Osawa S."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="12111378"/>
            <dbReference type="DOI" id="10.1007/s100380200041"/>
        </citation>
        <scope>VARIANTS CYS-54 AND LYS-400</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="24881" last="24888">
            <title>Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking.</title>
            <authorList>
                <person name="Graf G.A."/>
                <person name="Cohen J.C."/>
                <person name="Hobbs H.H."/>
            </authorList>
            <dbReference type="PubMed" id="15054092"/>
            <dbReference type="DOI" id="10.1074/jbc.m402634200"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS STSL1 HIS-184; THR-231; GLN-263; PRO-501; SER-543; GLU-574 AND ARG-596</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2007" name="Nat. Genet." volume="39" first="995" last="999">
            <title>A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.</title>
            <authorList>
                <person name="Buch S."/>
                <person name="Schafmayer C."/>
                <person name="Voelzke H."/>
                <person name="Becker C."/>
                <person name="Franke A."/>
                <person name="von Eller-Eberstein H."/>
                <person name="Kluck C."/>
                <person name="Baessmann I."/>
                <person name="Brosch M."/>
                <person name="Lammert F."/>
                <person name="Miquel J.F."/>
                <person name="Nervi F."/>
                <person name="Wittig M."/>
                <person name="Rosskopf D."/>
                <person name="Timm B."/>
                <person name="Hoell C."/>
                <person name="Seeger M."/>
                <person name="ElSharawy A."/>
                <person name="Lu T."/>
                <person name="Egberts J."/>
                <person name="Faendrich F."/>
                <person name="Foelsch U.R."/>
                <person name="Krawczak M."/>
                <person name="Schreiber S."/>
                <person name="Nuernberg P."/>
                <person name="Tepel J."/>
                <person name="Hampe J."/>
            </authorList>
            <dbReference type="PubMed" id="17632509"/>
            <dbReference type="DOI" id="10.1038/ng2101"/>
        </citation>
        <scope>VARIANT HIS-19</scope>
        <scope>INVOLVEMENT IN GBD4</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 10 11 14">ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane. Plays an essential role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:11099417, PubMed:11452359, PubMed:15054092, PubMed:27144356). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11452359, PubMed:15054092). The heterodimer with ABCG5 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>sitosterol(in) + ATP + H2O = sitosterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39103"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27693"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:39104"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="13 14">The ATPase activity of the heterodimer is stimulated by cholate. Taurocholate, glycocholate, taurochenodeoxycholate, glycochenodeoxycholate and taurodeoxycholate also stimulate ATPase activity, but to a lower degree. Glycodeoxycholate has no significant effect on ATPase activity. ATPase activity is inhibited by vanadate and by berillium fluoride.</text>
    </comment>
    <comment type="subunit">
        <text evidence="11 13 14">Heterodimer with ABCG8.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3908684">
            <id>Q9H221</id>
        </interactant>
        <interactant intactId="EBI-1761423">
            <id>Q9H222</id>
            <label>ABCG5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3908684">
            <id>Q9H221</id>
        </interactant>
        <interactant intactId="EBI-6165891">
            <id>Q14696</id>
            <label>MESD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16205990">
            <id>Q9H221-1</id>
        </interactant>
        <interactant intactId="EBI-16205983">
            <id>Q9H222-1</id>
            <label>ABCG5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="17">Cell membrane</location>
            <topology evidence="14">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Apical cell membrane</location>
            <topology evidence="14">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H221-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H221-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_000052"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Predominantly expressed in the liver (PubMed:11099417, PubMed:11452359). Low expression levels in the small intestine and colon (PubMed:11099417). Very low levels in other tissues, including brain, heart and spleen (PubMed:11452359).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">A functional Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. The essential Lys in this region is not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for transport activity mediated by the heterodimer with ABCG5.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11 13">N-glycosylated.</text>
    </comment>
    <comment type="disease" evidence="12">
        <disease id="DI-02886">
            <name>Gallbladder disease 4</name>
            <acronym>GBD4</acronym>
            <description>One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes.</description>
            <dbReference type="MIM" id="611465"/>
        </disease>
        <text>Disease susceptibility may be associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5 6 10">
        <disease id="DI-02308">
            <name>Sitosterolemia 1</name>
            <acronym>STSL1</acronym>
            <description>A form of sitosterolemia, an autosomal recessive metabolic disorder characterized by unregulated intestinal absorption of cholesterol, phytosterols and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.</description>
            <dbReference type="MIM" id="210250"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="16">Minor form detected in approximately 10% of the cDNA clones.</text>
    </comment>
    <comment type="similarity">
        <text evidence="16">Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="16">Seems to have a defective ATP-binding region.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="1"/>
    <dbReference type="EMBL" id="AF320294">
        <property type="protein sequence ID" value="AAG40004.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF324494">
        <property type="protein sequence ID" value="AAK84078.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351824">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351812">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351813">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351814">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351815">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351816">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351817">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351818">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351819">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351820">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351821">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351822">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF351823">
        <property type="protein sequence ID" value="AAK84663.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC108476">
        <property type="protein sequence ID" value="AAY24011.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1815.1">
        <molecule id="Q9H221-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001344250.1">
        <molecule id="Q9H221-2"/>
        <property type="nucleotide sequence ID" value="NM_001357321.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_071882.1">
        <molecule id="Q9H221-1"/>
        <property type="nucleotide sequence ID" value="NM_022437.3"/>
    </dbReference>
    <dbReference type="PDB" id="5DO7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.93 A"/>
        <property type="chains" value="B/D=2-673"/>
    </dbReference>
    <dbReference type="PDB" id="7JR7">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="7R87">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="7R88">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="7R89">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="7R8A">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="7R8B">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="B=1-673"/>
    </dbReference>
    <dbReference type="PDB" id="8CUB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="4.05 A"/>
        <property type="chains" value="B/D=2-673"/>
    </dbReference>
    <dbReference type="PDBsum" id="5DO7"/>
    <dbReference type="PDBsum" id="7JR7"/>
    <dbReference type="PDBsum" id="7R87"/>
    <dbReference type="PDBsum" id="7R88"/>
    <dbReference type="PDBsum" id="7R89"/>
    <dbReference type="PDBsum" id="7R8A"/>
    <dbReference type="PDBsum" id="7R8B"/>
    <dbReference type="PDBsum" id="8CUB"/>
    <dbReference type="AlphaFoldDB" id="Q9H221"/>
    <dbReference type="EMDB" id="EMD-22443"/>
    <dbReference type="EMDB" id="EMD-24310"/>
    <dbReference type="EMDB" id="EMD-24311"/>
    <dbReference type="EMDB" id="EMD-24312"/>
    <dbReference type="EMDB" id="EMD-24313"/>
    <dbReference type="EMDB" id="EMD-24314"/>
    <dbReference type="SMR" id="Q9H221"/>
    <dbReference type="BioGRID" id="122125">
        <property type="interactions" value="20"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9H221"/>
    <dbReference type="DIP" id="DIP-42631N"/>
    <dbReference type="FunCoup" id="Q9H221">
        <property type="interactions" value="92"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H221">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H221"/>
    <dbReference type="STRING" id="9606.ENSP00000272286"/>
    <dbReference type="DrugBank" id="DB08834">
        <property type="generic name" value="Tauroursodeoxycholic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11635">
        <property type="generic name" value="Tocofersolan"/>
    </dbReference>
    <dbReference type="TCDB" id="3.A.1.204.5">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9H221">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H221">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H221"/>
    <dbReference type="PhosphoSitePlus" id="Q9H221"/>
    <dbReference type="BioMuta" id="ABCG8"/>
    <dbReference type="DMDM" id="17432916"/>
    <dbReference type="MassIVE" id="Q9H221"/>
    <dbReference type="PaxDb" id="9606-ENSP00000272286"/>
    <dbReference type="PeptideAtlas" id="Q9H221"/>
    <dbReference type="ProteomicsDB" id="80473">
        <molecule id="Q9H221-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="80474">
        <molecule id="Q9H221-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="14910">
        <property type="antibodies" value="311 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="64241"/>
    <dbReference type="Ensembl" id="ENST00000272286.4">
        <molecule id="Q9H221-1"/>
        <property type="protein sequence ID" value="ENSP00000272286.2"/>
        <property type="gene ID" value="ENSG00000143921.10"/>
    </dbReference>
    <dbReference type="GeneID" id="64241"/>
    <dbReference type="KEGG" id="hsa:64241"/>
    <dbReference type="MANE-Select" id="ENST00000272286.4">
        <property type="protein sequence ID" value="ENSP00000272286.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_022437.3"/>
        <property type="RefSeq protein sequence ID" value="NP_071882.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002rtq.3">
        <molecule id="Q9H221-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:13887"/>
    <dbReference type="ClinPGx" id="PA24412"/>
    <dbReference type="CTD" id="64241"/>
    <dbReference type="DisGeNET" id="64241"/>
    <dbReference type="GeneCards" id="ABCG8"/>
    <dbReference type="GeneReviews" id="ABCG8"/>
    <dbReference type="HGNC" id="HGNC:13887">
        <property type="gene designation" value="ABCG8"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000143921">
        <property type="expression patterns" value="Group enriched (intestine, liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCG8"/>
    <dbReference type="MIM" id="210250">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="605460">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="611465">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000143921"/>
    <dbReference type="Orphanet" id="391665">
        <property type="disease" value="Homozygous familial hypercholesterolemia"/>
    </dbReference>
    <dbReference type="Orphanet" id="2882">
        <property type="disease" value="Sitosterolemia"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000143921"/>
    <dbReference type="eggNOG" id="KOG0061">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159739"/>
    <dbReference type="HOGENOM" id="CLU_000604_57_9_1"/>
    <dbReference type="InParanoid" id="Q9H221"/>
    <dbReference type="OMA" id="WLAWEDY"/>
    <dbReference type="OrthoDB" id="66620at2759"/>
    <dbReference type="PAN-GO" id="Q9H221">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H221"/>
    <dbReference type="PathwayCommons" id="Q9H221"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5679090">
        <property type="pathway name" value="Defective ABCG8 causes GBD4 and sitosterolemia"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5679096">
        <property type="pathway name" value="Defective ABCG5 causes sitosterolemia"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9029569">
        <property type="pathway name" value="NR1H3 &amp; NR1H2 regulate gene expression linked to cholesterol transport and efflux"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9H221"/>
    <dbReference type="SIGNOR" id="Q9H221"/>
    <dbReference type="Agora" id="ENSG00000143921"/>
    <dbReference type="BioGRID-ORCS" id="64241">
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    <keyword id="KW-0460">Magnesium</keyword>
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    <keyword id="KW-0479">Metal-binding</keyword>
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    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
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            <end position="673"/>
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            <end position="416"/>
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            <end position="497"/>
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            <end position="548"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="14">
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            <end position="555"/>
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    <feature type="transmembrane region" description="Helical; Name=5" evidence="14">
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            <end position="576"/>
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    <feature type="topological domain" description="Extracellular" evidence="14">
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    <feature type="transmembrane region" description="Helical; Name=6" evidence="14">
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            <end position="660"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="14">
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            <begin position="661"/>
            <end position="673"/>
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    <feature type="domain" description="ABC transporter" evidence="3">
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            <begin position="47"/>
            <end position="313"/>
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    <feature type="domain" description="ABC transmembrane type-2">
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            <end position="665"/>
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            <end position="25"/>
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            <end position="11"/>
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    <feature type="sequence variant" id="VAR_012250" description="Associated significantly with GBD4; dbSNP:rs11887534." evidence="6 7 12">
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            <position position="19"/>
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    <feature type="sequence variant" id="VAR_012251" description="In dbSNP:rs4148211." evidence="5 6 7 8">
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        <variation>C</variation>
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            <position position="54"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012252" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs766212636." evidence="6 10">
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        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022074" description="In dbSNP:rs9282574.">
        <original>V</original>
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            <position position="210"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012253" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs137852993." evidence="5 6 10">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012254" description="In STSL1; uncertain significance; dbSNP:rs34754243." evidence="6">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="238"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012255" description="In dbSNP:rs35518570." evidence="6">
        <original>A</original>
        <variation>V</variation>
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            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012256" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs137852990." evidence="5 6 10">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="263"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012257" description="In dbSNP:rs4148217." evidence="6 7 8">
        <original>T</original>
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            <position position="400"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012258" description="In STSL1; dbSNP:rs1177309800." evidence="6">
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            <position position="405"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012259" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs1233989408." evidence="6 10">
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        <location>
            <position position="501"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012260" description="In STSL1; decreased maturation of glycan chains; dbSNP:rs201690654." evidence="6 10">
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        <variation>S</variation>
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            <position position="543"/>
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        <location>
            <position position="570"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012262" description="In STSL1; dbSNP:rs769576789." evidence="6">
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            <position position="572"/>
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    <feature type="sequence variant" id="VAR_012263" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs1325979386." evidence="6 10">
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        <variation>E</variation>
        <location>
            <position position="574"/>
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    <feature type="sequence variant" id="VAR_012264" description="In STSL1; decreased maturation of glycan chains; dbSNP:rs137852988." evidence="5 6 10">
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        <location>
            <position position="574"/>
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            <position position="575"/>
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    <feature type="sequence variant" id="VAR_012266" description="In STSL1; strongly decreased maturation of glycan chains; dbSNP:rs137852992." evidence="5 6 10">
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            <position position="596"/>
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            <position position="655"/>
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            <begin position="88"/>
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            <begin position="100"/>
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            <begin position="110"/>
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            <end position="119"/>
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    <feature type="strand" evidence="22">
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            <begin position="130"/>
            <end position="134"/>
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            <begin position="141"/>
            <end position="147"/>
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    <feature type="strand" evidence="22">
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            <begin position="148"/>
            <end position="151"/>
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            <end position="174"/>
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    <feature type="helix" evidence="22">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
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    <reference key="2">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
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        <scope>VARIANT SER-1369</scope>
        <source>
            <tissue>Pancreatic islet</tissue>
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    <reference key="3">
        <citation type="submission" date="1996-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Thomas P.T."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-1369</scope>
        <scope>VARIANT PNDM3 PRO-225</scope>
        <source>
            <tissue>Brain</tissue>
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    <reference key="4">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-1369</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
    <reference key="5">
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            </authorList>
            <dbReference type="PubMed" id="16554811"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="6">
        <citation type="journal article" date="1995" name="Science" volume="268" first="426" last="429">
            <title>Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.</title>
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                <person name="Thomas P.M."/>
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                <person name="Wohllk N."/>
                <person name="Haddad B."/>
                <person name="Mathew P.M."/>
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            <dbReference type="DOI" id="10.1126/science.7716548"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1187-1581</scope>
        <scope>VARIANT SER-1369</scope>
        <source>
            <tissue>Pancreatic islet</tissue>
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    <reference key="7">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="29122" last="29129">
            <title>Membrane topology of the amino-terminal region of the sulfonylurea receptor.</title>
            <authorList>
                <person name="Raab-Graham K.F."/>
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                <person name="Boettcher A.A."/>
                <person name="Radeke C.M."/>
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    <reference evidence="49 50" key="8">
        <citation type="journal article" date="2017" name="Elife" volume="6" first="e32481" last="e32481">
            <title>Molecular structure of human KATP in complex with ATP and ADP.</title>
            <authorList>
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            <dbReference type="PubMed" id="29286281"/>
            <dbReference type="DOI" id="10.7554/elife.32481"/>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH ATP; ADP AND MG(2+)</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>TOPOLOGY</scope>
    </reference>
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        <citation type="journal article" date="2021" name="Proc. Natl. Acad. Sci. U.S.A." volume="118" first="e2112267118" last="e2112267118">
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                <person name="MacKinnon R."/>
            </authorList>
            <dbReference type="PubMed" id="34815345"/>
            <dbReference type="DOI" id="10.1073/pnas.2112267118"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 2-1581</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <dbReference type="PubMed" id="10338089"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(1999)13:5&lt;351::aid-humu3&gt;3.0.co;2-r"/>
        </citation>
        <scope>REVIEW ON VARIANTS</scope>
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    <reference key="11">
        <citation type="journal article" date="1996" name="Am. J. Hum. Genet." volume="59" first="510" last="518">
            <title>Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.</title>
            <authorList>
                <person name="Thomas P.M."/>
                <person name="Wohllk N."/>
                <person name="Huang E."/>
                <person name="Kuhnle U."/>
                <person name="Rabl W."/>
                <person name="Gagel R.F."/>
                <person name="Cote G.J."/>
            </authorList>
            <dbReference type="PubMed" id="8751851"/>
        </citation>
        <scope>VARIANT HHF1 VAL-716</scope>
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    <reference key="12">
        <citation type="journal article" date="1996" name="Diabetes" volume="45" first="825" last="831">
            <title>Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.</title>
            <authorList>
                <person name="Inoue H."/>
                <person name="Ferrer J."/>
                <person name="Welling C.M."/>
                <person name="Elbein S.C."/>
                <person name="Hoffman M."/>
                <person name="Mayorga R."/>
                <person name="Warren-Perry M."/>
                <person name="Zhang Y."/>
                <person name="Millns H."/>
                <person name="Turner R."/>
                <person name="Province M."/>
                <person name="Bryan J."/>
                <person name="Permutt M.A."/>
                <person name="Aguilar-Bryan L."/>
            </authorList>
            <dbReference type="PubMed" id="8635661"/>
            <dbReference type="DOI" id="10.2337/diab.45.6.825"/>
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        <scope>VARIANT SER-1369</scope>
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    <reference key="13">
        <citation type="journal article" date="1996" name="Hum. Mol. Genet." volume="5" first="1813" last="1822">
            <title>Mutations in the sulfonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.</title>
            <authorList>
                <person name="Nestorowicz A."/>
                <person name="Wilson B.A."/>
                <person name="Schoor K.P."/>
                <person name="Inoue H."/>
                <person name="Glaser B."/>
                <person name="Landau H."/>
                <person name="Stanley C.A."/>
                <person name="Thornton P.S."/>
                <person name="Clement J.P. IV"/>
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                <person name="Aguilar-Bryan L."/>
                <person name="Permutt M.A."/>
            </authorList>
            <dbReference type="PubMed" id="8923011"/>
            <dbReference type="DOI" id="10.1093/hmg/5.11.1813"/>
        </citation>
        <scope>VARIANT HHF1 PHE-1387 DEL</scope>
        <scope>VARIANTS GLY-1360; SER-1369 AND ILE-1572</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1996" name="Science" volume="272" first="1785" last="1787">
            <title>Adenosine diphosphate as an intracellular regulator of insulin secretion.</title>
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                <person name="Nichols C.G."/>
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                <person name="Glaser B."/>
                <person name="Clement J.P. IV"/>
                <person name="Gonzalez G."/>
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            </authorList>
            <dbReference type="PubMed" id="8650576"/>
            <dbReference type="DOI" id="10.1126/science.272.5269.1785"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT HHF1 ARG-1478</scope>
    </reference>
    <reference key="15">
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            <title>Identification and functional analysis of sulfonylurea receptor 1 variants in Japanese patients with NIDDM.</title>
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                <person name="Ohta Y."/>
                <person name="Tanizawa Y."/>
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                <person name="Hosaka T."/>
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                <person name="Oka Y."/>
            </authorList>
            <dbReference type="PubMed" id="9519757"/>
            <dbReference type="DOI" id="10.2337/diabetes.47.3.476"/>
        </citation>
        <scope>VARIANTS GLN-275; MET-560; ASN-810; CYS-834 AND SER-1369</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1998" name="Diabetes" volume="47" first="598" last="605">
            <title>Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene.</title>
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                <person name="Hansen T."/>
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                <person name="Hansen L."/>
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                <person name="Inoue H."/>
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                <person name="Pedersen O."/>
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            <dbReference type="PubMed" id="9568693"/>
            <dbReference type="DOI" id="10.2337/diabetes.47.4.598"/>
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        <scope>VARIANTS ASN-673 AND SER-1369</scope>
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        <citation type="journal article" date="1998" name="Diabetes" volume="47" first="1145" last="1151">
            <title>Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy.</title>
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                <person name="Shyng S.-L."/>
                <person name="Ferrigni T."/>
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        <scope>CHARACTERIZATION OF VARIANTS HHF1 GLN-125; SER-188; LEU-591; MET-1138; GLN-1214; SER-1381; PHE-1387 DEL AND HIS-1393</scope>
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            <dbReference type="DOI" id="10.1093/hmg/7.7.1119"/>
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        <scope>VARIANTS HHF1 GLN-74; GLN-125; SER-188; ASP-406; LEU-591; MET-1138; GLN-1214; ARG-1378; SER-1381; PHE-1387 DEL AND HIS-1393</scope>
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        <scope>VARIANTS HHF1 PRO-1352; CYS-1420 AND TRP-1493</scope>
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                <person name="Huang E."/>
                <person name="Komulainen J."/>
                <person name="Ashcroft F.M."/>
                <person name="Dunne M.J."/>
                <person name="Kere J."/>
                <person name="Thomas P.M."/>
            </authorList>
            <dbReference type="PubMed" id="10334322"/>
            <dbReference type="DOI" id="10.2337/diabetes.48.2.408"/>
        </citation>
        <scope>VARIANT HHF1 ASP-187</scope>
    </reference>
    <reference key="21">
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            <title>Molecular biology of adenosine triphosphate-sensitive potassium channels.</title>
            <authorList>
                <person name="Aguilar-Bryan L."/>
                <person name="Bryan J."/>
            </authorList>
            <dbReference type="PubMed" id="10204114"/>
            <dbReference type="DOI" id="10.1210/edrv.20.2.0361"/>
        </citation>
        <scope>VARIANTS HHF1 PRO-116; ARG-418; PRO-508; CYS-620; PHE-956 AND MET-1360</scope>
    </reference>
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            <title>Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.</title>
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                <person name="Glaser B."/>
                <person name="Furth J."/>
                <person name="Stanley C.A."/>
                <person name="Baker L."/>
                <person name="Thornton P.S."/>
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            <dbReference type="PubMed" id="10447255"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(1999)14:1&lt;23::aid-humu3&gt;3.0.co;2-#"/>
        </citation>
        <scope>VARIANTS SER-1369 AND ILE-1572</scope>
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            <title>Clinical features of 52 neonates with hyperinsulinism.</title>
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                <person name="de Lonlay-Debeney P."/>
                <person name="Poggi-Travert F."/>
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                <person name="Sempoux C."/>
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                <person name="Nihoul-Fekete C."/>
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            </authorList>
            <dbReference type="PubMed" id="10202168"/>
            <dbReference type="DOI" id="10.1056/nejm199904153401505"/>
        </citation>
        <scope>VARIANTS HHF1 GLY-841; CYS-1420 AND TRP-1493</scope>
    </reference>
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            <title>Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1.</title>
            <authorList>
                <person name="Tanizawa Y."/>
                <person name="Matsuda K."/>
                <person name="Matsuo M."/>
                <person name="Ohta Y."/>
                <person name="Ochi N."/>
                <person name="Adachi M."/>
                <person name="Koga M."/>
                <person name="Mizuno S."/>
                <person name="Kajita M."/>
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                <person name="Inoue H."/>
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                <person name="Amachi T."/>
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            </authorList>
            <dbReference type="PubMed" id="10615958"/>
            <dbReference type="DOI" id="10.2337/diabetes.49.1.114"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS HHF1 CYS-1420 AND GLN-1436</scope>
        <scope>VARIANT SER-1369</scope>
    </reference>
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            <authorList>
                <person name="Huopio H."/>
                <person name="Reimann F."/>
                <person name="Ashfield R."/>
                <person name="Komulainen J."/>
                <person name="Lenko H.-L."/>
                <person name="Rahier J."/>
                <person name="Vauhkonen I."/>
                <person name="Kere J."/>
                <person name="Laakso M."/>
                <person name="Ashcroft F."/>
                <person name="Otonkoski T."/>
            </authorList>
            <dbReference type="PubMed" id="11018078"/>
            <dbReference type="DOI" id="10.1172/jci9804"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT HHF1 LYS-1506</scope>
    </reference>
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            <title>Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy.</title>
            <authorList>
                <person name="Cartier E.A."/>
                <person name="Conti L.R."/>
                <person name="Vandenberg C.A."/>
                <person name="Shyng S.-L."/>
            </authorList>
            <dbReference type="PubMed" id="11226335"/>
            <dbReference type="DOI" id="10.1073/pnas.051499698"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT HHF1 PHE-1387 DEL</scope>
    </reference>
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            <title>Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels.</title>
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                <person name="Taschenberger G."/>
                <person name="Mougey A."/>
                <person name="Shen S."/>
                <person name="Lester L.B."/>
                <person name="LaFranchi S."/>
                <person name="Shyng S.-L."/>
            </authorList>
            <dbReference type="PubMed" id="11867634"/>
            <dbReference type="DOI" id="10.1074/jbc.m200363200"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT HHF1 PRO-1543</scope>
    </reference>
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            <title>Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism.</title>
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                <person name="Huopio H."/>
                <person name="Jaeaeskelaeinen J."/>
                <person name="Komulainen J."/>
                <person name="Miettinen R."/>
                <person name="Kaerkkaeinen P."/>
                <person name="Laakso M."/>
                <person name="Tapanainen P."/>
                <person name="Voutilainen R."/>
                <person name="Otonkoski T."/>
            </authorList>
            <dbReference type="PubMed" id="12364426"/>
            <dbReference type="DOI" id="10.1210/jc.2002-020378"/>
        </citation>
        <scope>VARIANTS HHF1 ASP-187; THR-1457; LYS-1506; ASP-1550 AND VAL-1551</scope>
    </reference>
    <reference key="29">
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            <title>Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.</title>
            <authorList>
                <person name="Thornton P.S."/>
                <person name="MacMullen C."/>
                <person name="Ganguly A."/>
                <person name="Ruchelli E."/>
                <person name="Steinkrauss L."/>
                <person name="Crane A."/>
                <person name="Aguilar-Bryan L."/>
                <person name="Stanley C.A."/>
            </authorList>
            <dbReference type="PubMed" id="12941782"/>
            <dbReference type="DOI" id="10.2337/diabetes.52.9.2403"/>
        </citation>
        <scope>VARIANT HHF1 SER-1385 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT HHF1 SER-1385 DEL</scope>
    </reference>
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            <title>Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.</title>
            <authorList>
                <person name="Magge S.N."/>
                <person name="Shyng S.-L."/>
                <person name="MacMullen C."/>
                <person name="Steinkrauss L."/>
                <person name="Ganguly A."/>
                <person name="Katz L.E.L."/>
                <person name="Stanley C.A."/>
            </authorList>
            <dbReference type="PubMed" id="15356046"/>
            <dbReference type="DOI" id="10.1210/jc.2004-0441"/>
        </citation>
        <scope>VARIANT LIH HIS-1352</scope>
        <scope>CHARACTERIZATION OF VARIANT LIH HIS-1352</scope>
    </reference>
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            <authorList>
                <person name="Tornovsky S."/>
                <person name="Crane A."/>
                <person name="Cosgrove K.E."/>
                <person name="Hussain K."/>
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                <person name="Heyman M."/>
                <person name="Nesher Y."/>
                <person name="Kuchinski N."/>
                <person name="Ben-Shushan E."/>
                <person name="Shatz O."/>
                <person name="Nahari E."/>
                <person name="Potikha T."/>
                <person name="Zangen D."/>
                <person name="Tenenbaum-Rakover Y."/>
                <person name="de Vries L."/>
                <person name="Argente J."/>
                <person name="Gracia R."/>
                <person name="Landau H."/>
                <person name="Eliakim A."/>
                <person name="Lindley K."/>
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                <person name="Aguilar-Bryan L."/>
                <person name="Glaser B."/>
            </authorList>
            <dbReference type="PubMed" id="15579781"/>
            <dbReference type="DOI" id="10.1210/jc.2004-1233"/>
        </citation>
        <scope>VARIANTS HHF1 GLU-70; ARG-111; GLU-1342; HIS-1418 AND TRP-1493</scope>
        <scope>CHARACTERIZATION OF VARIANTS HHF1 GLU-70; ARG-111; GLU-1342; HIS-1418 AND TRP-1493</scope>
    </reference>
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                <person name="Ohkubo K."/>
                <person name="Nagashima M."/>
                <person name="Naito Y."/>
                <person name="Taguchi T."/>
                <person name="Suita S."/>
                <person name="Okamoto N."/>
                <person name="Fujinaga H."/>
                <person name="Tsumura K."/>
                <person name="Kikuchi K."/>
                <person name="Ono J."/>
            </authorList>
            <dbReference type="PubMed" id="15807877"/>
            <dbReference type="DOI" id="10.1111/j.1365-2265.2005.02242.x"/>
        </citation>
        <scope>VARIANTS HHF1 GLN-1384 AND LYS-1486</scope>
        <scope>VARIANT SER-1369</scope>
    </reference>
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            <title>Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.</title>
            <authorList>
                <person name="Henwood M.J."/>
                <person name="Kelly A."/>
                <person name="MacMullen C."/>
                <person name="Bhatia P."/>
                <person name="Ganguly A."/>
                <person name="Thornton P.S."/>
                <person name="Stanley C.A."/>
            </authorList>
            <dbReference type="PubMed" id="15562009"/>
            <dbReference type="DOI" id="10.1210/jc.2004-1604"/>
        </citation>
        <scope>VARIANTS HHF1 SER-27; TRP-74; SER-188; GLN-495; LYS-501; SER-686; TRP-1214; GLN-1214; ASN-1336; PHE-1387 DEL; HIS-1471 AND ASN-1471</scope>
    </reference>
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            <title>A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.</title>
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                <person name="Proks P."/>
                <person name="Arnold A.L."/>
                <person name="Bruining J."/>
                <person name="Girard C."/>
                <person name="Flanagan S.E."/>
                <person name="Larkin B."/>
                <person name="Colclough K."/>
                <person name="Hattersley A.T."/>
                <person name="Ashcroft F.M."/>
                <person name="Ellard S."/>
            </authorList>
            <dbReference type="PubMed" id="16613899"/>
            <dbReference type="DOI" id="10.1093/hmg/ddl101"/>
        </citation>
        <scope>VARIANT PNDM3 LEU-132</scope>
        <scope>CHARACTERIZATION OF VARIANT PNDM3 LEU-132</scope>
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                <person name="Salas A."/>
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            <dbReference type="PubMed" id="16429405"/>
            <dbReference type="DOI" id="10.1002/humu.9401"/>
        </citation>
        <scope>VARIANTS HHF1 TRP-74; ARG-111; SER-188; ARG-233; ASN-310; ARG-551; THR-719; PRO-1130; ARG-1147; LYS-1295 AND PRO-1450</scope>
        <scope>VARIANTS SER-1369 AND ILE-1572</scope>
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                <person name="Suchi M."/>
                <person name="MacMullen C.M."/>
                <person name="Thornton P.S."/>
                <person name="Adzick N.S."/>
                <person name="Ganguly A."/>
                <person name="Ruchelli E.D."/>
                <person name="Stanley C.A."/>
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            <dbReference type="PubMed" id="16357843"/>
            <dbReference type="DOI" id="10.1038/modpathol.3800497"/>
        </citation>
        <scope>VARIANTS HHF1 ARG-7; ASP-21; SER-27; TRP-74; LYS-501; PRO-503; SER-686; TRP-1214; TRP-1214; GLN-1349; ARG-1378; PHE-1387 DEL; ARG-1400 AND GLN-1493</scope>
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            <title>Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.</title>
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                <person name="Babenko A.P."/>
                <person name="Polak M."/>
                <person name="Cave H."/>
                <person name="Busiah K."/>
                <person name="Czernichow P."/>
                <person name="Scharfmann R."/>
                <person name="Bryan J."/>
                <person name="Aguilar-Bryan L."/>
                <person name="Vaxillaire M."/>
                <person name="Froguel P."/>
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            <dbReference type="PubMed" id="16885549"/>
            <dbReference type="DOI" id="10.1056/nejmoa055068"/>
        </citation>
        <scope>VARIANTS PNDM3 ARG-213 AND VAL-1424</scope>
        <scope>VARIANTS TNDM2 ARG-435; VAL-582; TYR-1023; GLN-1182 AND CYS-1379</scope>
        <scope>CHARACTERIZATION OF VARIANT PNDM3 VAL-1424</scope>
        <scope>CHARACTERIZATION OF VARIANT TNDM2 TYR-1023</scope>
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                <person name="Ellard S."/>
                <person name="Flanagan S.E."/>
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            <dbReference type="DOI" id="10.1086/519174"/>
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        <scope>VARIANTS PNDM3 LEU-45; SER-72; ALA-86; GLY-86; LEU-132; VAL-132; SER-207; LYS-208; GLU-209; LYS-211; PRO-225; ILE-229; ASP-263; LYS-382; GLU-1184; LYS-1326; ARG-1400; ALA-1522 AND LEU-1522</scope>
        <scope>CHARACTERIZATION OF VARIANTS PNDM3 LEU-132; SER-207; ILE-229; GLU-1184 AND LEU-1522</scope>
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                <person name="Gasperikova D."/>
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                <person name="Flanagan S.E."/>
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        <scope>VARIANT PNDM3 ALA-86</scope>
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                <person name="Batra C.M."/>
                <person name="Gupta N."/>
                <person name="Atwal G."/>
                <person name="Gupta V."/>
            </authorList>
            <dbReference type="PubMed" id="20092027"/>
            <dbReference type="DOI" id="10.1007/s12098-009-0222-y"/>
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        <scope>VARIANT TNDM2 TRP-1182</scope>
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        <scope>VARIANT TNDM2 TRP-1182</scope>
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            <dbReference type="DOI" id="10.1007/s00125-011-2319-x"/>
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        <scope>VARIANTS MODY12 ARG-214; MET-222; ARG-485; ASP-1244 AND HIS-1379</scope>
        <scope>VARIANT LYS-100</scope>
        <scope>INVOLVEMENT IN MODY12</scope>
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            <dbReference type="DOI" id="10.1111/cge.12428"/>
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        <scope>VARIANTS HHF1 MET-511; ASP-716; LYS-824; THR-889; PRO-890; PRO-1352; SER-1378; PHE-1386; TYR-1388; PRO-1389; VAL-1457; ILE-1480; GLU-1505 AND SER-1511</scope>
        <scope>CHARACTERIZATION OF VARIANTS HHF1 MET-511; LYS-824; THR-889; PRO-890; SER-1378; VAL-1457; ILE-1480; GLU-1505 AND SER-1511</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>VARIANT HHF1 HIS-1418</scope>
        <scope>CHARACTERIZATION OF VARIANT HHF1 HIS-1418</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="45">
        <citation type="journal article" date="2021" name="Diabetes Metab. Res. Rev." volume="37" first="e3459" last="e3459">
            <title>ABCC8 variants in MODY12: Review of the literature and report of a case with severe complications.</title>
            <authorList>
                <person name="Timmers M."/>
                <person name="Dirinck E."/>
                <person name="Lauwers P."/>
                <person name="Wuyts W."/>
                <person name="De Block C."/>
            </authorList>
            <dbReference type="PubMed" id="34014594"/>
            <dbReference type="DOI" id="10.1002/dmrr.3459"/>
        </citation>
        <scope>VARIANT MODY12 TRP-1182</scope>
    </reference>
    <comment type="function">
        <text evidence="28 29 30 32">Regulator subunit of pancreatic ATP-sensitive potassium channel (KATP), playing a major role in the regulation of insulin release. In pancreatic cells, it forms KATP channels with KCNJ11; KCNJ11 forms the channel pore while ABCC8 is required for activation and regulation.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="30 32">KATP channels are regulated by cytoplasmic ATP/ADP ratios; ATP inhibits the channel by closing the pore, while ADP activates the channel (PubMed:29286281, PubMed:34815345). Activated by phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2) (PubMed:34815345).</text>
    </comment>
    <comment type="subunit">
        <text evidence="30 32">Forms an heterooctamer with KCNJ11; four ABCC8/SUR1 molecules interact with one KCNJ11 homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15807650">
            <id>Q09428-1</id>
        </interactant>
        <interactant intactId="EBI-2866553">
            <id>Q14654</id>
            <label>KCNJ11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="28">Cell membrane</location>
            <topology evidence="30 32">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q09428-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q09428-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_000055"/>
        </isoform>
        <isoform>
            <id>Q09428-3</id>
            <name>3</name>
            <name>SUR1Delta2</name>
            <sequence type="described" ref="VSP_044090"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="15">
        <disease id="DI-01896">
            <name>Leucine-induced hypoglycemia</name>
            <acronym>LIH</acronym>
            <description>Rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine.</description>
            <dbReference type="MIM" id="240800"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5 6 7 9 10 11 12 13 14 16 17 18 19 20 28 29 35 36 37 40 41 42">
        <disease id="DI-01579">
            <name>Hyperinsulinemic hypoglycemia, familial, 1</name>
            <acronym>HHF1</acronym>
            <description>A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF1 is the most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF1 inheritance can be autosomal dominant or autosomal recessive.</description>
            <dbReference type="MIM" id="256450"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="21 22 23 24 27 31">
        <disease id="DI-05824">
            <name>Diabetes mellitus, permanent neonatal, 3</name>
            <acronym>PNDM3</acronym>
            <description>A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Some PNDM3 patients may also have developmental delay, muscle weakness, and epilepsy. PNDM3 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance.</description>
            <dbReference type="MIM" id="618857"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="22 25 26">
        <disease id="DI-02381">
            <name>Transient neonatal diabetes mellitus 2</name>
            <acronym>TNDM2</acronym>
            <description>Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence.</description>
            <dbReference type="MIM" id="610374"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="27 31">
        <disease id="DI-07037">
            <name>Maturity-onset diabetes of the young 12</name>
            <acronym>MODY12</acronym>
            <description>A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.</description>
            <dbReference type="MIM" id="621196"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="47">Abundant isoform with prodiabetic properties, predominant in heart.</text>
    </comment>
    <comment type="similarity">
        <text evidence="47">Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
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            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="30 49 50">
        <location>
            <position position="1482"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="1049"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="49 50">
        <location>
            <begin position="6"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044090" description="In isoform 3." evidence="46">
        <location>
            <begin position="51"/>
            <end position="1581"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000055" description="In isoform 2." evidence="47">
        <original>S</original>
        <variation>SS</variation>
        <location>
            <position position="740"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031349" description="In HHF1; dbSNP:rs781059815." evidence="19">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031350" description="In HHF1; dbSNP:rs200670692." evidence="19">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031351" description="In HHF1." evidence="16 19">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072928" description="In PNDM3; likely pathogenic; dbSNP:rs267606623." evidence="24">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031352" description="In HHF1; altered intracellular trafficking." evidence="17">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072929" description="In PNDM3; uncertain significance; dbSNP:rs80356634." evidence="24">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008639" description="In HHF1; dbSNP:rs72559734." evidence="40">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031353" description="In HHF1; dbSNP:rs201682634." evidence="16 19 20">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031354" description="In PNDM3; likely pathogenic; dbSNP:rs193929360." evidence="23 24">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072930" description="In PNDM3; likely pathogenic; dbSNP:rs193929360." evidence="24">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090794" description="Found in a patient with clinical features of diabetes; uncertain significance." evidence="27">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029777" description="In dbSNP:rs10400391.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031355" description="In HHF1; altered intracellular trafficking; dbSNP:rs761749884." evidence="17 20">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031356" description="In HHF1; dbSNP:rs72559731." evidence="6">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008640" description="In HHF1; mild; dbSNP:rs60637558." evidence="40 41">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029778" description="In PNDM3; pathogenic; reduces the sensitivity of the K(ATP) channel to inhibition by MgATP; increases whole-cell K(ATP) current; dbSNP:rs80356637." evidence="21 24">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072931" description="In PNDM3; likely pathogenic; dbSNP:rs80356637." evidence="24">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008641" description="In HHF1; severe; high prevalence in Finland; loss of channel activity; dbSNP:rs137852672." evidence="7 13">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008642" description="In HHF1; severe; dbSNP:rs797045213." evidence="16 20 40 41">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="188"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072932" description="In PNDM3; likely pathogenic; reduced inhibition by ATP." evidence="24">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072933" description="In PNDM3; dbSNP:rs2133680513." evidence="24">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="208"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072934" description="In PNDM3; likely pathogenic; dbSNP:rs80356640." evidence="24">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072935" description="In PNDM3; likely pathogenic; dbSNP:rs193929366." evidence="24">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029779" description="In PNDM3; dbSNP:rs80356642." evidence="22">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090795" description="In MODY12; uncertain significance." evidence="27">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090796" description="In MODY12; uncertain significance." evidence="27">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072936" description="In PNDM3; likely pathogenic; dbSNP:rs1048095." evidence="24">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="225"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072937" description="In PNDM3; uncertain significance; affects channel function resulting in increased potassium currents at physiological MgATP concentrations; dbSNP:rs768017509." evidence="24">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031357" description="In HHF1." evidence="20">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072938" description="In PNDM3; dbSNP:rs778892038." evidence="24">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="263"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008643" description="In dbSNP:rs185040406." evidence="38">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="275"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031358" description="In HHF1; dbSNP:rs769569410." evidence="20">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="310"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072939" description="In PNDM3; uncertain significance; dbSNP:rs80356651." evidence="24">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="382"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008644" description="In HHF1; dbSNP:rs72559728." evidence="40">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="406"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031359" description="In HHF1; dbSNP:rs67254669." evidence="6">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029780" description="In TNDM2." evidence="22">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="435"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090797" description="In MODY12; likely pathogenic." evidence="27">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="485"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031360" description="In HHF1; dbSNP:rs1420601296." evidence="16">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="495"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031361" description="In HHF1; dbSNP:rs372307320." evidence="16 19">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="501"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031362" description="In HHF1; dbSNP:rs1554933168." evidence="19">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="503"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031363" description="In HHF1; dbSNP:rs72559727." evidence="6">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="508"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072940" description="In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide." evidence="28">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031364" description="In HHF1; dbSNP:rs1955881024." evidence="20">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="551"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008645" description="In dbSNP:rs4148619." evidence="38">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="560"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029781" description="In TNDM2; dbSNP:rs137852674." evidence="22">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="582"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008646" description="In HHF1; dbSNP:rs72559726." evidence="40 41">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="591"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031365" description="In HHF1; dbSNP:rs58241708." evidence="6">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="620"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015006" description="In dbSNP:rs777986828." evidence="39">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="673"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031366" description="In HHF1; dbSNP:rs1159625966." evidence="16 19">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="686"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072941" description="In HHF1; dbSNP:rs72559723." evidence="28">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="716"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000100" description="In HHF1; dbSNP:rs72559723." evidence="36">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="716"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031367" description="In HHF1." evidence="20">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="719"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008647" description="In dbSNP:rs767572066." evidence="38">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="810"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072942" description="In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide." evidence="28">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="824"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008648" description="In dbSNP:rs140068774." evidence="38">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="834"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031368" description="In HHF1; dbSNP:rs1484689392." evidence="5">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="841"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031369" description="In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; reduced potassium channel response to activators such as MgADP or to diazoxide; dbSNP:rs761862121." evidence="28">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="889"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072943" description="In HHF1; no effect on cell membrane expression; no effect on traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide." evidence="28">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="890"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031370" description="In HHF1; dbSNP:rs72559721." evidence="6">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="956"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029782" description="In TNDM2; overactive channel." evidence="22">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="1023"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031371" description="In HHF1." evidence="20">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="1130"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008649" description="In HHF1; dbSNP:rs201351976." evidence="40 41">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1138"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031372" description="In HHF1; dbSNP:rs1262517518." evidence="20">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="1147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029783" description="In TNDM2; dbSNP:rs193922400." evidence="22">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090798" description="In MODY12 and TNDM2; likely pathogenic." evidence="25 26 31">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072944" description="In PNDM3; uncertain significance; slightly reduced inhibition by ATP; dbSNP:rs137852675." evidence="24">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="1184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008650" description="In HHF1; severe; dbSNP:rs367850779." evidence="16 40 41">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031373" description="In HHF1; dbSNP:rs139964066." evidence="16 19">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090799" description="In MODY12; uncertain significance." evidence="27">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="1244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031374" description="In HHF1; dbSNP:rs542157938." evidence="20">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="1295"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072945" description="In PNDM3; associated in cis with A-1522; uncertain significance; dbSNP:rs200563930." evidence="24">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1326"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031375" description="In HHF1; dbSNP:rs67767715." evidence="16">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="1336"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031376" description="In HHF1; altered intracellular trafficking." evidence="17">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1342"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031377" description="In HHF1." evidence="19">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="1349"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029784" description="In LIH; partially impairs ATP-dependent potassium channel function; dbSNP:rs28936370." evidence="15">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1352"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008537" description="In HHF1; dbSNP:rs28936370." evidence="28 42">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="1352"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008651" evidence="37">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="1360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015007" description="In HHF1; dbSNP:rs1953962707." evidence="6">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="1360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008652" description="In dbSNP:rs757110." evidence="8 9 18 20 33 34 37 38 39 43 44 45">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="1369"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008653" description="In HHF1; dbSNP:rs925231098." evidence="19 40">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072946" description="In HHF1; highly decreases cell membrane expression; highly reduced traffic efficiency; dramatically reduced potassium channel response to activators such as MgADP or to diazoxide; dbSNP:rs925231098." evidence="28">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="1378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029785" description="In TNDM2; likely pathogenic; dbSNP:rs137852673." evidence="22">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090800" description="In MODY12; likely pathogenic." evidence="27">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008654" description="In HHF1; dbSNP:rs773448052." evidence="40 41">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="1381"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031378" description="In HHF1." evidence="18">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="1384"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029786" description="In HHF1; does not alter surface expression but channels are not functional; dbSNP:rs387906408." evidence="14">
        <location>
            <position position="1385"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031379" description="In HHF1; dbSNP:rs72559718." evidence="28">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="1386"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008538" description="In HHF1; severe; high frequency in Ashkenazi Jewish patients; defective trafficking and lack of surface expression." evidence="11 16 19 37 40 41">
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            <position position="1387"/>
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            <position position="1393"/>
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            <position position="1400"/>
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            <position position="1424"/>
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            <position position="1457"/>
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            <position position="1478"/>
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            <position position="1480"/>
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            <position position="1486"/>
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            <position position="1493"/>
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            <position position="1505"/>
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            <position position="1506"/>
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            <position position="1522"/>
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            <position position="1522"/>
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            <position position="1543"/>
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            <position position="1550"/>
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            <position position="1551"/>
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            <position position="1572"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAB02278/AAB02417/AAB02418." evidence="47" ref="2">
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    <feature type="sequence conflict" description="In Ref. 2; AAB02278/AAB02417/AAB02418." evidence="47" ref="2">
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    <feature type="sequence conflict" description="In Ref. 3; AAB36699/AAB36700." evidence="47" ref="3">
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    <feature type="sequence conflict" description="In Ref. 2; AAB02278/AAB02417/AAB02418." evidence="47" ref="2">
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    <feature type="sequence conflict" description="In Ref. 2; AAB02278/AAB02417/AAB02418." evidence="47" ref="2">
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    <feature type="sequence conflict" description="In Ref. 3; AAB36699/AAB36700." evidence="47" ref="3">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT LYS-970</scope>
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            <tissue>Melanocyte</tissue>
            <tissue>Melanoma</tissue>
        </source>
    </reference>
    <reference key="2">
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                <person name="Chen K.G."/>
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            <dbReference type="PubMed" id="15760339"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANTS GLU-560 AND LYS-970</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Melanoma</tissue>
        </source>
    </reference>
    <reference key="3">
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                <person name="Wilson B.J."/>
                <person name="Schatton T."/>
                <person name="Zhan Q."/>
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            </authorList>
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            <dbReference type="DOI" id="10.1158/0008-5472.can-11-0221"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Colon adenocarcinoma</tissue>
        </source>
    </reference>
    <reference key="4">
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                <person name="Kawanobe T."/>
                <person name="Kogure S."/>
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            </authorList>
            <dbReference type="PubMed" id="22306008"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2012.01.090"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <scope>FUNCTION</scope>
        <scope>VARIANT LYS-970</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <source>
            <tissue>Prostate</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
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            <authorList>
                <person name="Meij I.C."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <scope>VARIANT LYS-970</scope>
    </reference>
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        <text evidence="1 6 7 9 13">Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present in limbal stem cells, where it plays a key role in corneal development and repair (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13">
            <text>daunorubicin(in) + ATP + H2O = daunorubicin(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:33147"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:64677"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="7.6.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:33148"/>
        </physiologicalReaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cell membrane</location>
            <topology evidence="4 6">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q2M3G0-4</id>
            <name>4</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q2M3G0-2</id>
            <name>2</name>
            <name>ABCB5alpha</name>
            <sequence type="described" ref="VSP_056752 VSP_056753 VSP_056756"/>
        </isoform>
        <isoform>
            <id>Q2M3G0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_056752 VSP_056754 VSP_056755"/>
        </isoform>
        <isoform>
            <id>Q2M3G0-1</id>
            <name>1</name>
            <name>ABCB5beta</name>
            <sequence type="described" ref="VSP_056752"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 8 12 14 15 16 17 18">Expressed by CD133-expressing progenitor cells among epidermal melanocytes (at protein level). Widely expressed with specific expression in pigment cells. Highly expressed in several malignant tissues: highly expressed in clinical melanomas, with low expression in normal skin. In melanoma, marks malignant melanoma-initiating cells (MMIC), in which clinical virulence resides as a consequence of unlimited self-renewal capacity, resulting in inexorable tumor progression and metastasis. Also highly expressed in a number of leukemia cells. Expressed in basal limbal epithelium.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="26 27 28 29 30">Acts as a marker of stem-like cells (CSC) in a number of malignancies (PubMed:24934811). Associated with clinical drug resistance, tumor progression and disease recurrence in malignant melanoma and acute leukemias. Responsible for the resistance to doxorubicin of a subset of malignant melanomas. ABCB5-expressing cells selectively survive when exposed to dacarbazine drug, the reference treatment of metastatic melanoma, vemurafenib and other various chemotherapeutic drugs, suggesting that anti-melanoma chemotherapy participates in the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5 (PubMed:22044138, PubMed:22675422, PubMed:22784549, PubMed:23770371, PubMed:24934811). Present in melanoma-initiating cells that acts as an enhancer of tumor growth by promoting CSC maintenance and tumor growth by controlling IL-1beta (IL1B) secretion to maintain slow-cycling, chemoresistant cells through an IL-1beta (IL1B)/IL8/CXCR1 cytokine signaling circuit (PubMed:24934811).</text>
    </comment>
    <comment type="similarity">
        <text evidence="25">Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="25">Was named ABCB1 by some authors.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAN76500" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAQ03033" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44305/ABCB5"/>
    </comment>
    <dbReference type="EC" id="7.6.2.2" evidence="13"/>
    <dbReference type="EMBL" id="AF319622">
        <property type="protein sequence ID" value="AAN76500.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF399931">
        <property type="protein sequence ID" value="AAQ03033.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY090613">
        <property type="protein sequence ID" value="AAM09027.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY234788">
        <property type="protein sequence ID" value="AAO73470.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY851364">
        <property type="protein sequence ID" value="AAW31629.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY851365">
        <property type="protein sequence ID" value="AAW31630.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="GU437216">
        <property type="protein sequence ID" value="ADV32636.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="GU437217">
        <property type="protein sequence ID" value="ADV32637.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB353947">
        <property type="protein sequence ID" value="BAF75364.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY230001">
        <property type="protein sequence ID" value="AAP55848.1"/>
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            <end position="350"/>
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            <end position="622"/>
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            <end position="428"/>
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            <position position="1104"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1188"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056752" description="In isoform 1, isoform 2 and isoform 3." evidence="21 22 23 24">
        <location>
            <begin position="1"/>
            <end position="445"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056753" description="In isoform 2." evidence="23">
        <original>ASKGRTT</original>
        <variation>DTPRYSF</variation>
        <location>
            <begin position="570"/>
            <end position="576"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056754" description="In isoform 3." evidence="22">
        <original>AS</original>
        <variation>KK</variation>
        <location>
            <begin position="570"/>
            <end position="571"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056755" description="In isoform 3." evidence="22">
        <location>
            <begin position="572"/>
            <end position="1257"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056756" description="In isoform 2." evidence="23">
        <location>
            <begin position="577"/>
            <end position="1257"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028387" description="In dbSNP:rs2301641." evidence="8">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="560"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028388" description="In dbSNP:rs13222448.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="669"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035731" description="In a colorectal cancer sample; somatic mutation." evidence="10">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="675"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062662" description="In a pancreatic ductal adenocarcinoma sample; somatic mutation; dbSNP:rs1187237313." evidence="11">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="880"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033456" description="In dbSNP:rs35885925.">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="905"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028389" description="In dbSNP:rs17143304.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="915"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028390" description="In dbSNP:rs6461515." evidence="6 8 13 19 20">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="970"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAN76500." evidence="25" ref="1">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="577"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAW31630." evidence="25" ref="2">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1141"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; ADV32637." evidence="25" ref="3">
        <original>L</original>
        <variation>I</variation>
        <location>
            <position position="1186"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="B5X0E4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00441"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12960149"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15205344"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15760339"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15899824"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18772397"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="22044138"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="22306008"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="22675422"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22784549"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="23770371"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="24934811"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="25030174"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source ref="5"/>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="12960149"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="15760339"/>
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    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="21652540"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="25"/>
    <evidence type="ECO:0000305" key="26">
        <source>
            <dbReference type="PubMed" id="22044138"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="27">
        <source>
            <dbReference type="PubMed" id="22675422"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="28">
        <source>
            <dbReference type="PubMed" id="22784549"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="29">
        <source>
            <dbReference type="PubMed" id="23770371"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="30">
        <source>
            <dbReference type="PubMed" id="24934811"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="31">
        <source>
            <dbReference type="HGNC" id="HGNC:46"/>
        </source>
    </evidence>
    <sequence length="1257" mass="138641" checksum="A4521B83E0D234CF" modified="2014-10-01" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>O94911</accession>
    <accession>A1L3U3</accession>
    <accession>C9JQE6</accession>
    <accession>Q86WW0</accession>
    <name>ABCA8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ABC-type organic anion transporter ABCA8</fullName>
            <ecNumber evidence="5">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="11">ATP-binding cassette sub-family A member 8</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">ABCA8</name>
        <name evidence="10" type="synonym">KIAA0822</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>SEQUENCE REVISION</scope>
    </reference>
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            <dbReference type="PubMed" id="16625196"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <scope>VARIANT VAL-416</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
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                <person name="Tsuruoka S."/>
                <person name="Ishibashi K."/>
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                <person name="Wakaumi M."/>
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            </authorList>
            <dbReference type="PubMed" id="12379217"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(02)02389-6"/>
        </citation>
        <scope>FUNCTION (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES (ISOFORM 1)</scope>
        <scope>ACTIVITY REGULATION (ISOFORM 1)</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="19159218"/>
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        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-84</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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                <person name="Kim W.S."/>
                <person name="Hsiao J.H."/>
                <person name="Bhatia S."/>
                <person name="Glaros E.N."/>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>FUNCTION (ISOFORM 1)</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION (ISOFORM 3)</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORM 3)</scope>
        <scope>ACTIVITY REGULATION (ISOFORM 3)</scope>
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                <person name="Iida A."/>
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            <dbReference type="PubMed" id="12111378"/>
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        <scope>VARIANT SER-331</scope>
    </reference>
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            <title>ABCA8 Regulates Cholesterol Efflux and High-Density Lipoprotein Cholesterol Levels.</title>
            <authorList>
                <person name="Trigueros-Motos L."/>
                <person name="van Capelleveen J.C."/>
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            </authorList>
            <dbReference type="PubMed" id="28882873"/>
            <dbReference type="DOI" id="10.1161/atvbaha.117.309574"/>
        </citation>
        <scope>VARIANTS ARG-649 AND 781-THR--PRO-1621 DEL</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION (ISOFORM 3)</scope>
        <scope>CHARACTERIZATION OF VARIANTS ARG-649 AND 781-THR--PRO-1621 DEL</scope>
        <scope>INTERACTION WITH ABCA1 (ISOFORM 3)</scope>
    </reference>
    <comment type="function">
        <molecule>Isoform 1</molecule>
        <text evidence="5 7">Catalyzes ATP-dependent import of organic anions such as taurocholate and estrone sulfate (PubMed:12379217). In vitro, also imports ochratoxin A (PubMed:12379217). Also mediates cholesterol efflux independent of apolipoprotein, and plays a role in sphingomyelin production in oligodendrocytes (PubMed:23560799).</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 3</molecule>
        <text evidence="8 9">Catalyzes ATP-dependent efflux of cholesterol and taurocholate (PubMed:29300488). Interaction with ABCA1 potentiates cholesterol efflux to lipid-free APOA1, which regulates high-density lipoprotein cholesterol levels (PubMed:28882873).</text>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 3</molecule>
        <reaction evidence="13">
            <text>taurocholate(in) + ATP + H2O = taurocholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50052"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:36257"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:50053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 9">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8 9">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="5">
            <text>estrone 3-sulfate(out) + ATP + H2O = estrone 3-sulfate(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:65956"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60050"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:65957"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="5">
            <text>leukotriene C4(out) + ATP + H2O = leukotriene C4(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:65960"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57973"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:65961"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="5">
            <text>taurocholate(out) + ATP + H2O = taurocholate(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:65964"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:36257"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:65965"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="5">
            <text>17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:65968"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:82961"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:65969"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <molecule>Isoform 1</molecule>
        <text evidence="5">Dofequidar (MS-209) and ochratoxin A inhibited the 17beta-estradiol 17-O-(beta-D-glucuronate) influx.</text>
    </comment>
    <comment type="activity regulation">
        <molecule>Isoform 3</molecule>
        <text evidence="9">Cholesterol efflux is increased by extracellularly applied taurocholate.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 1</molecule>
        <kinetics>
            <KM evidence="5">30.4 uM for estradiol-beta-glucuronide</KM>
            <KM evidence="5">0.1 uM for LTC4</KM>
            <KM evidence="5">10.3 uM for taurochlorate</KM>
            <KM evidence="5">5 uM for PAH</KM>
            <KM evidence="5">0.5 uM for estrone sulfate</KM>
            <KM evidence="5">0.4 uM for ochratoxin A</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <molecule>Isoform 3</molecule>
        <text evidence="8">Interacts with ABCA1; this interaction potentiates cholesterol efflux.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8 9">Cell membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Basolateral cell membrane</location>
        </subcellularLocation>
        <text evidence="1">Predominantly expressed on the sinusoidal plasma membrane.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O94911-3</id>
            <name>3</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O94911-1</id>
            <name>1</name>
            <sequence type="described" ref="VSP_060912"/>
        </isoform>
        <isoform>
            <id>O94911-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_060911"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 8 9">Widely expressed with higher expression in heart, skeletal muscle and liver (PubMed:12379217, PubMed:28882873, PubMed:29300488). Highly expressed in the superior frontal white matter and inferior temporal white matter (PubMed:12379217).</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA74845" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="5"/>
    <dbReference type="EMBL" id="AB020629">
        <property type="protein sequence ID" value="BAA74845.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005922">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC015844">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC024003">
        <property type="protein sequence ID" value="AAH24003.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047765">
        <property type="protein sequence ID" value="AAH47765.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC094689">
        <property type="protein sequence ID" value="AAH94689.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC130280">
        <property type="protein sequence ID" value="AAI30281.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11680.1">
        <molecule id="O94911-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS74139.1">
        <molecule id="O94911-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001275914.1">
        <molecule id="O94911-3"/>
        <property type="nucleotide sequence ID" value="NM_001288985.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001275915.1">
        <property type="nucleotide sequence ID" value="NM_001288986.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_009099.1">
        <molecule id="O94911-1"/>
        <property type="nucleotide sequence ID" value="NM_007168.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047291064.1">
        <molecule id="O94911-3"/>
        <property type="nucleotide sequence ID" value="XM_047435108.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054170659.1">
        <molecule id="O94911-3"/>
        <property type="nucleotide sequence ID" value="XM_054314684.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O94911"/>
    <dbReference type="SMR" id="O94911"/>
    <dbReference type="BioGRID" id="115632">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="CORUM" id="O94911"/>
    <dbReference type="FunCoup" id="O94911">
        <property type="interactions" value="78"/>
    </dbReference>
    <dbReference type="IntAct" id="O94911">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000467271"/>
    <dbReference type="TCDB" id="3.A.1.211.6">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O94911">
        <property type="glycosylation" value="16 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O94911">
        <property type="glycosylation" value="16 sites, 3 N-linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O94911"/>
    <dbReference type="PhosphoSitePlus" id="O94911"/>
    <dbReference type="SwissPalm" id="O94911"/>
    <dbReference type="BioMuta" id="ABCA8"/>
    <dbReference type="jPOST" id="O94911"/>
    <dbReference type="MassIVE" id="O94911"/>
    <dbReference type="PaxDb" id="9606-ENSP00000467271"/>
    <dbReference type="PeptideAtlas" id="O94911"/>
    <dbReference type="ProteomicsDB" id="11233"/>
    <dbReference type="ProteomicsDB" id="50546">
        <molecule id="O94911-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="50547">
        <molecule id="O94911-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="31802">
        <property type="antibodies" value="141 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10351"/>
    <dbReference type="Ensembl" id="ENST00000269080.6">
        <molecule id="O94911-1"/>
        <property type="protein sequence ID" value="ENSP00000269080.1"/>
        <property type="gene ID" value="ENSG00000141338.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000586539.6">
        <molecule id="O94911-3"/>
        <property type="protein sequence ID" value="ENSP00000467271.1"/>
        <property type="gene ID" value="ENSG00000141338.16"/>
    </dbReference>
    <dbReference type="GeneID" id="10351"/>
    <dbReference type="KEGG" id="hsa:10351"/>
    <dbReference type="MANE-Select" id="ENST00000586539.6">
        <property type="protein sequence ID" value="ENSP00000467271.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001288985.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001275914.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002jhp.5">
        <molecule id="O94911-3"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:38"/>
    <dbReference type="ClinPGx" id="PA24383"/>
    <dbReference type="CTD" id="10351"/>
    <dbReference type="DisGeNET" id="10351"/>
    <dbReference type="GeneCards" id="ABCA8"/>
    <dbReference type="HGNC" id="HGNC:38">
        <property type="gene designation" value="ABCA8"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000141338">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="612505">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000141338"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000141338"/>
    <dbReference type="eggNOG" id="KOG0059">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162012"/>
    <dbReference type="HOGENOM" id="CLU_000604_19_1_1"/>
    <dbReference type="InParanoid" id="O94911"/>
    <dbReference type="OMA" id="GVCYHMP"/>
    <dbReference type="OrthoDB" id="8061355at2759"/>
    <dbReference type="PAN-GO" id="O94911">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O94911"/>
    <dbReference type="PathwayCommons" id="O94911"/>
    <dbReference type="Reactome" id="R-HSA-382556">
        <property type="pathway name" value="ABC-family proteins mediated transport"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="O94911"/>
    <dbReference type="SignaLink" id="O94911"/>
    <dbReference type="Agora" id="ENSG00000141338">
        <property type="nominated target" value="Agora Nominated Target for Alzheimer's Disease"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="10351">
        <property type="hits" value="13 hits in 1162 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCA8">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCA8"/>
    <dbReference type="GenomeRNAi" id="10351"/>
    <dbReference type="Pharos" id="O94911">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O94911"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="O94911">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000141338">
        <property type="expression patterns" value="Expressed in dorsal root ganglion and 192 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O94911">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016323">
        <property type="term" value="C:basolateral plasma membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008559">
        <property type="term" value="F:ABC-type xenobiotic transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042626">
        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005319">
        <property type="term" value="F:lipid transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033344">
        <property type="term" value="P:cholesterol efflux"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030301">
        <property type="term" value="P:cholesterol transport"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006869">
        <property type="term" value="P:lipid transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010875">
        <property type="term" value="P:positive regulation of cholesterol efflux"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010874">
        <property type="term" value="P:regulation of cholesterol efflux"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006686">
        <property type="term" value="P:sphingomyelin biosynthetic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055085">
        <property type="term" value="P:transmembrane transport"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006855">
        <property type="term" value="P:xenobiotic transmembrane transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042908">
        <property type="term" value="P:xenobiotic transport"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd03263">
        <property type="entry name" value="ABC_subfamily_A"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000335">
        <property type="entry name" value="ATP binding cassette subfamily A member 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000436">
        <property type="entry name" value="ATP binding cassette subfamily A member 9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026082">
        <property type="entry name" value="ABCA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR056264">
        <property type="entry name" value="R2_ABCA1-4-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229:SF274">
        <property type="entry name" value="ABC-TYPE ORGANIC ANION TRANSPORTER ABCA8"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229">
        <property type="entry name" value="ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12698">
        <property type="entry name" value="ABC2_membrane_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF23321">
        <property type="entry name" value="R1_ABCA1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
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            <taxon>Vertebrata</taxon>
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            <taxon>Eutheria</taxon>
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            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
        <scope>VARIANT ARG-1587</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ARG-1587</scope>
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                <person name="Milne S."/>
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                <person name="Nisbett J."/>
                <person name="Nordsiek G."/>
                <person name="Pearce A.V."/>
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                <person name="Pelan S."/>
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                <person name="Tromans A."/>
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                <person name="Hubbard T."/>
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                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
                <person name="Langmann T."/>
                <person name="Klucken J."/>
                <person name="Reil M."/>
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            <dbReference type="PubMed" id="10092505"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 21-2261</scope>
        <scope>VARIANTS THR-1555; ARG-1587; PRO-1648 AND PRO-2168</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 21-2261</scope>
        <scope>VARIANTS THR-1555; ARG-1587; PRO-1648 AND PRO-2168</scope>
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        <scope>PHOSPHORYLATION AT SER-1042 AND SER-2054</scope>
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        <scope>REPRESSION BY ZNF202</scope>
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        <scope>INDUCTION BY LPS</scope>
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        <scope>INTERACTION WITH MEGF10</scope>
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        <scope>INTERACTION WITH ABCA12 AND NR1H2</scope>
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        <scope>REVIEW ON VARIANTS</scope>
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        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN HDLCQ13</scope>
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        <scope>PALMITOYLATION AT CYS-3; CYS-23; CYS-1110 AND CYS-1111</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF CYS-3; CYS-23; CYS-1110 AND CYS-1111</scope>
        <scope>CHARACTERIZATION OF VARIANT FHA1 THR-1091</scope>
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        <scope>DISULFIDE BONDS</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98 AND ASN-244</scope>
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            <tissue>Liver</tissue>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF SER-100; PHE-593; LYS-939; THR-1512 AND LYS-1952</scope>
        <scope>FUNCTION</scope>
        <scope>VARIANTS TGD SER-590; ILE-929; SER-935; ARG-1477 AND TRP-2081</scope>
        <scope>CHARACTERIZATION OF VARIANTS TGD SER-590; ILE-929; SER-935; ARG-1477 AND TRP-2081</scope>
        <scope>VARIANT FHA1 LEU-2150</scope>
        <scope>CHARACTERIZATION OF VARIANT FHA1 LEU-2150</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH APOE</scope>
        <scope>CHARACTERIZATION OF VARIANT TGD ARG-1477</scope>
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        <scope>INTERACTION WITH ABCA8</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>REGION GATEWAY DOMAIN</scope>
        <scope>REGION ANNULUS DOMAINS</scope>
        <scope>MUTAGENESIS OF ILE-74; VAL-304; VAL-308; ILE-371; LEU-375; LYS-568; TYR-573; ASP-581; PHE-583; GLU-584; ASP-585 AND TRP-590</scope>
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        <scope>VARIANTS FHA1 THR-1091 AND 1893-GLU-ASP-1894 DEL</scope>
        <scope>FUNCTION</scope>
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        <scope>VARIANTS TGD ARG-597 AND ARG-1477</scope>
        <scope>VARIANT FHA1 LEU-693 DEL</scope>
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        <scope>VARIANTS TGD SER-590; SER-935 AND VAL-937</scope>
        <scope>VARIANTS ALA-399 AND MET-883</scope>
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        <scope>VARIANTS TGD ARG-597; ILE-929 AND ARG-1477</scope>
        <scope>VARIANTS FHA1 LEU-693 DEL; THR-1091; 1893-GLU-ASP-1894 DEL AND LEU-2150</scope>
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        <scope>VARIANTS TGD ASN-1289 AND HIS-1800</scope>
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        <scope>VARIANT TGD ASP-1046</scope>
        <scope>VARIANTS LYS-219; CYS-230; ILE-825; MET-883 AND ARG-1587</scope>
        <scope>INVOLVEMENT IN HDLCQ13</scope>
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        <scope>VARIANT TGD TRP-587</scope>
        <scope>VARIANT PRO-2168</scope>
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                <person name="Brousseau M.E."/>
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            <dbReference type="PubMed" id="11257261"/>
            <dbReference type="DOI" id="10.1016/s0021-9150(00)00722-x"/>
        </citation>
        <scope>VARIANTS LYS-219; MET-883 AND ASP-1172</scope>
    </reference>
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            <title>Homogeneous assay based on 52 primer sets to scan for mutations of the ABCA1 gene and its application in genetic analysis of a new patient with familial high-density lipoprotein deficiency syndrome.</title>
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                <person name="Lapicka-Bodzioch K."/>
                <person name="Bodzioch M."/>
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            <dbReference type="PubMed" id="11476961"/>
            <dbReference type="DOI" id="10.1016/s0925-4439(01)00053-9"/>
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        <scope>VARIANT TGD LEU-1506</scope>
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            <title>Novel mutations in ABCA1 gene in Japanese patients with Tangier disease and familial high density lipoprotein deficiency with coronary heart disease.</title>
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                <person name="Huang W."/>
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            <dbReference type="DOI" id="10.1016/s0925-4439(01)00058-8"/>
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        <scope>VARIANTS TGD ASN-1289 AND TRP-2081</scope>
        <scope>VARIANT LYS-219</scope>
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            <dbReference type="PubMed" id="11238261"/>
            <dbReference type="DOI" id="10.1161/01.cir.103.9.1198"/>
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        <scope>VARIANTS LYS-219; ALA-399; MET-771; PRO-774; ASN-776; ILE-825; MET-883; ASP-1172; ARG-1587 AND CYS-1731</scope>
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                <person name="Hong S.H."/>
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            <dbReference type="PubMed" id="12204794"/>
            <dbReference type="DOI" id="10.1016/s0021-9150(02)00106-5"/>
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        <scope>VARIANT FHA1 LEU-85</scope>
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                <person name="Hong S.H."/>
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            <dbReference type="PubMed" id="12009425"/>
            <dbReference type="DOI" id="10.1016/s0925-4439(02)00066-2"/>
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        <scope>VARIANTS FHA1 TYR-1099 AND SER-2009</scope>
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            <dbReference type="PubMed" id="11785958"/>
            <dbReference type="DOI" id="10.1006/bbrc.2001.6219"/>
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        <scope>VARIANT TGD THR-255</scope>
        <scope>VARIANT FHA1 ASP-1611</scope>
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                <person name="Hong S.H."/>
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        <scope>VARIANT TGD LEU-590</scope>
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            <dbReference type="PubMed" id="12111381"/>
            <dbReference type="DOI" id="10.1007/s100380200044"/>
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        <scope>VARIANTS TGD HIS-935 AND SER-935</scope>
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            <title>Clinical variant of Tangier disease in Japan: mutation of the ABCA1 gene in hypoalphalipoproteinemia with corneal lipidosis.</title>
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            <dbReference type="PubMed" id="12111371"/>
            <dbReference type="DOI" id="10.1007/s100380200051"/>
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        <scope>VARIANT TGD TRP-1680</scope>
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                <person name="Hong S.H."/>
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        <scope>VARIANT TGD GLN-1851</scope>
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        <scope>VARIANTS ILE-825 AND MET-883</scope>
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            <dbReference type="DOI" id="10.1093/hmg/ddg314"/>
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        <scope>VARIANTS LYS-219; MET-771; ILE-825; MET-883; ASP-1172; PHE-1181 AND ARG-1587</scope>
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            <dbReference type="PubMed" id="12624133"/>
            <dbReference type="DOI" id="10.1136/jmg.40.3.163"/>
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        <scope>VARIANT LYS-219</scope>
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            <dbReference type="PubMed" id="15262183"/>
            <dbReference type="DOI" id="10.1016/j.atherosclerosis.2004.02.019"/>
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        <scope>VARIANTS TGD LEU-590; ARG-840 AND CYS-1068</scope>
        <scope>VARIANTS MET-771; SER-2163 AND ILE-2244</scope>
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            <dbReference type="PubMed" id="15019541"/>
            <dbReference type="DOI" id="10.1016/j.atherosclerosis.2003.11.009"/>
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        <scope>VARIANTS TGD LYS-284; CYS-482; HIS-1800; SER-1901 AND HIS-2196</scope>
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            <dbReference type="PubMed" id="15158913"/>
            <dbReference type="DOI" id="10.1016/j.bbadis.2004.01.007"/>
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        <scope>VARIANTS TGD PHE-1379 AND ASP-1704</scope>
        <scope>CHARACTERIZATION OF VARIANTS TGD PHE-1379 AND ASP-1704</scope>
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            <dbReference type="DOI" id="10.1172/jci20361"/>
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        <scope>VARIANT TGD HIS-1800</scope>
        <scope>VARIANTS LYS-219; CYS-364; MET-771; PRO-774; ASN-776; ILE-825; MET-883; SER-1065; ASP-1172; VAL-1216 AND ARG-1587</scope>
        <scope>INVOLVEMENT IN HDLCQ13</scope>
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            <dbReference type="DOI" id="10.1126/science.1099870"/>
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        <scope>VARIANT TGD HIS-1800</scope>
        <scope>VARIANTS ALA-248; GLN-401; TRP-496; SER-590; GLN-638; SER-774; GLY-815; PHE-1181; THR-1341; GLY-1376; GLN-1615; THR-1670; GLN-1680 AND GLU-2243</scope>
        <scope>INVOLVEMENT IN HDLCQ13</scope>
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            <dbReference type="DOI" id="10.1182/blood-2004-05-2056"/>
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        <scope>VARIANT SCOTT SYNDROME GLN-1925</scope>
        <scope>CHARACTERIZATION OF VARIANT SCOTT SYNDROME GLN-1925</scope>
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        <scope>VARIANT ASN-776</scope>
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        <scope>VARIANT FHA1 TRP-1897</scope>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] ASP-210; TYR-917; THR-1407 AND THR-2109</scope>
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        <scope>VARIANT TGD ARG-1517</scope>
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                <person name="Poplin R."/>
                <person name="Rivas M.A."/>
                <person name="Ruano-Rubio V."/>
                <person name="Rose S.A."/>
                <person name="Ruderfer D.M."/>
                <person name="Shakir K."/>
                <person name="Stenson P.D."/>
                <person name="Stevens C."/>
                <person name="Thomas B.P."/>
                <person name="Tiao G."/>
                <person name="Tusie-Luna M.T."/>
                <person name="Weisburd B."/>
                <person name="Won H.H."/>
                <person name="Yu D."/>
                <person name="Altshuler D.M."/>
                <person name="Ardissino D."/>
                <person name="Boehnke M."/>
                <person name="Danesh J."/>
                <person name="Donnelly S."/>
                <person name="Elosua R."/>
                <person name="Florez J.C."/>
                <person name="Gabriel S.B."/>
                <person name="Getz G."/>
                <person name="Glatt S.J."/>
                <person name="Hultman C.M."/>
                <person name="Kathiresan S."/>
                <person name="Laakso M."/>
                <person name="McCarroll S."/>
                <person name="McCarthy M.I."/>
                <person name="McGovern D."/>
                <person name="McPherson R."/>
                <person name="Neale B.M."/>
                <person name="Palotie A."/>
                <person name="Purcell S.M."/>
                <person name="Saleheen D."/>
                <person name="Scharf J.M."/>
                <person name="Sklar P."/>
                <person name="Sullivan P.F."/>
                <person name="Tuomilehto J."/>
                <person name="Tsuang M.T."/>
                <person name="Watkins H.C."/>
                <person name="Wilson J.G."/>
                <person name="Daly M.J."/>
                <person name="MacArthur D.G."/>
            </authorList>
            <dbReference type="PubMed" id="27535533"/>
            <dbReference type="DOI" id="10.1038/nature19057"/>
        </citation>
        <scope>VARIANT CYS-230</scope>
    </reference>
    <comment type="function">
        <text evidence="9 33 50 53">Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs (PubMed:14754908). Transports preferentially phosphatidylcholine over phosphatidylserine (PubMed:24097981). May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908, PubMed:24097981, PubMed:35974019). Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain (PubMed:35974019).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="50">
            <text>ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.</text>
            <dbReference type="EC" id="7.6.2.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="50 53">
            <text>a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38583"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57643"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="58">
            <dbReference type="Rhea" id="RHEA:38585"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="50">
            <text>a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38567"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57262"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="58">
            <dbReference type="Rhea" id="RHEA:38569"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="50">
            <text>a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38903"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17636"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="50">
            <dbReference type="Rhea" id="RHEA:38904"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="53 56 57 58">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="56 57 58">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="50">ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylcholine and to a lesser degree by phosphatidylserine and sphingomyelin. Phospholipid translocase activity is highly reduced by berylium fluoride and aluminum flouride and reduced by N-ethylmaleimide.</text>
    </comment>
    <comment type="subunit">
        <text evidence="33 43 49 52">Interacts with MEGF10 (PubMed:17205124). May interact with APOE1; functionally associated with APOE1 in the biogenesis of HDLs (PubMed:14754908). Interacts with ABCA8; this interaction potentiates cholesterol efflux (PubMed:28882873). Interacts with ABCA12 and NR1H2; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability (PubMed:23931754).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-9541582">
            <id>Q86UK0</id>
            <label>ABCA12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-701692">
            <id>P02647</id>
            <label>APOA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-311099">
            <id>O15085</id>
            <label>ARHGEF11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-355947">
            <id>P27824</id>
            <label>CANX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-81752">
            <id>P60953</id>
            <label>CDC42</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-357481">
            <id>Q12959</id>
            <label>DLG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-80426">
            <id>Q15700</id>
            <label>DLG2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-80440">
            <id>Q92796</id>
            <label>DLG3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-80389">
            <id>P78352</id>
            <label>DLG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-821335">
            <id>Q9HAP6</id>
            <label>LIN7B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-311035">
            <id>Q86UL8</id>
            <label>MAGI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-821405">
            <id>O75970</id>
            <label>MPDZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-724390">
            <id>Q8NI35</id>
            <label>PATJ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-717191">
            <id>Q13424</id>
            <label>SNTA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-295843">
            <id>Q13884</id>
            <label>SNTB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-80411">
            <id>Q13425</id>
            <label>SNTB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-784112">
            <id>O95477</id>
        </interactant>
        <interactant intactId="EBI-2691717">
            <id>Q86Y82</id>
            <label>STX12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="47 48 50 53">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="50">Endosome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed, but most abundant in macrophages.</text>
    </comment>
    <comment type="induction">
        <text evidence="17 23">By bacterial lipopolysaccharides (LPS). LPS regulates expression through a liver X receptor (LXR) -independent mechanism. Repressed by ZNF202.</text>
    </comment>
    <comment type="domain">
        <text>Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="26">Phosphorylation on Ser-2054 regulates phospholipid efflux.</text>
    </comment>
    <comment type="PTM">
        <text evidence="48">Palmitoylated by ZDHHC8 (PubMed:19556522). Palmitoylation is essential for localization to the plasma membrane (PubMed:19556522).</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="12 37 38 44">Genetic variations in ABCA1 define the high density lipoprotein cholesterol level quantitative trait locus 13 (HDLCQ13) [MIM:600046].</text>
    </comment>
    <comment type="disease" evidence="6 7 10 12 13 15 19 20 21 24 25 28 32 33 34 35 36 37 38 45 50">
        <disease id="DI-01742">
            <name>Tangier disease</name>
            <acronym>TGD</acronym>
            <description>An autosomal recessive disorder characterized by near absence of plasma high density lipoproteins, low serum HDL cholesterol, and massive tissue deposition of cholesterol esters. Clinical features include large yellow-orange tonsils, hepatomegaly, splenomegaly, enlarged lymph nodes, and often sensory polyneuropathy.</description>
            <dbReference type="MIM" id="205400"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="6 9 13 21 22 27 39 48 50">
        <disease id="DI-01743">
            <name>Hypoalphalipoproteinemia, primary, 1</name>
            <acronym>FHA1</acronym>
            <description>An autosomal dominant disorder characterized by decreased plasma high density lipoproteins, moderately low HDL cholesterol, a reduction in cellular cholesterol efflux, and susceptibility to premature coronary artery disease.</description>
            <dbReference type="MIM" id="604091"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="55">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="55">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAD49849" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="55">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA10005" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.1" evidence="50"/>
    <dbReference type="EMBL" id="AF275948">
        <property type="protein sequence ID" value="AAF86276.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL353685">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359846">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF285167">
        <property type="protein sequence ID" value="AAF98175.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF287262">
        <property type="protein sequence ID" value="AAK43526.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB055982">
        <property type="protein sequence ID" value="BAB63210.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ012376">
        <property type="protein sequence ID" value="CAA10005.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165281">
        <property type="protein sequence ID" value="AAD49849.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165286">
        <property type="protein sequence ID" value="AAD49851.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165282">
        <property type="protein sequence ID" value="AAD49851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165283">
        <property type="protein sequence ID" value="AAD49851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165284">
        <property type="protein sequence ID" value="AAD49851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165285">
        <property type="protein sequence ID" value="AAD49851.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165306">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165287">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165288">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165289">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165290">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165291">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165292">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165293">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165294">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165295">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165296">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165297">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165298">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165299">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165300">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165301">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165302">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165303">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165304">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165305">
        <property type="protein sequence ID" value="AAD49852.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF165309">
        <property type="protein sequence ID" value="AAD49854.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="46">
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        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
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        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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            <end position="309"/>
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    <feature type="disulfide bond" evidence="47">
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            <begin position="1463"/>
            <end position="1477"/>
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    </feature>
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            <position position="219"/>
        </location>
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            <position position="230"/>
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            <position position="248"/>
        </location>
    </feature>
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        <location>
            <position position="255"/>
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    </feature>
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        <location>
            <position position="284"/>
        </location>
    </feature>
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            <position position="364"/>
        </location>
    </feature>
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            <position position="399"/>
        </location>
    </feature>
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            <position position="401"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062485" description="In TGD." evidence="34">
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            <position position="482"/>
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    </feature>
    <feature type="sequence variant" id="VAR_062486" description="In dbSNP:rs147675550." evidence="37">
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            <position position="496"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009146" description="In TGD; dbSNP:rs2853574." evidence="15">
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        <variation>W</variation>
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062487" description="In TGD; dbSNP:rs137854496." evidence="28 36">
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        <variation>L</variation>
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            <position position="590"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009147" description="In TGD; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; dbSNP:rs137854496." evidence="7 37 50">
        <original>W</original>
        <variation>S</variation>
        <location>
            <position position="590"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009148" description="In TGD; dbSNP:rs2853578." evidence="6 13">
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        <location>
            <position position="597"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062488" description="In dbSNP:rs374190304." evidence="37">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="638"/>
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    </feature>
    <feature type="sequence variant" id="VAR_009149" description="In FHA1." evidence="6 13">
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012621" description="In dbSNP:rs2066718." evidence="14 31 36 38">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="771"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012622" description="In dbSNP:rs35819696." evidence="14 38">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="774"/>
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    </feature>
    <feature type="sequence variant" id="VAR_062489" evidence="37">
        <original>T</original>
        <variation>S</variation>
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            <position position="774"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012623" description="In dbSNP:rs138880920." evidence="14 38 41">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="776"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062490" description="In dbSNP:rs145582736." evidence="37">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="815"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012624" description="In dbSNP:rs2066715." evidence="12 14 30 31 38">
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        <variation>I</variation>
        <location>
            <position position="825"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062491" description="In TGD; dbSNP:rs1322998567." evidence="36">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="840"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012625" description="In dbSNP:rs2066714." evidence="7 12 14 16 30 31 38">
        <original>I</original>
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        <location>
            <position position="883"/>
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    </feature>
    <feature type="sequence variant" id="VAR_035725" description="In a colorectal cancer sample; somatic mutation." evidence="42">
        <original>D</original>
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        <location>
            <position position="917"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012626" description="In TGD; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; loss protein subcellular localization to the plasma membrane; dbSNP:rs1832457117." evidence="13 50">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="929"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037968" description="In TGD; dbSNP:rs28937314." evidence="25">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="935"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009150" description="In TGD; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; dbSNP:rs28937313." evidence="7 25 50">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="935"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009151" description="In TGD; dbSNP:rs137854495." evidence="7">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="937"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012627" description="In TGD; dbSNP:rs141021096." evidence="12">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1046"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037969" description="In dbSNP:rs13306072.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="1054"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062492" evidence="38">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="1065"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062493" description="In TGD; dbSNP:rs745593394." evidence="36">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1068"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012628" description="In FHA1; loss of localization to plasma membrane; decreased cholesterol efflux; decreased phospholipid efflux." evidence="9 13 48">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="1091"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017530" description="In FHA1; dbSNP:rs28933692." evidence="22">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="1099"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012629" description="In dbSNP:rs33918808." evidence="14 16 31 38">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="1172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017016" description="In dbSNP:rs76881554." evidence="31 37">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="1181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062494" description="In dbSNP:rs562403512." evidence="38">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009152" description="In TGD; dbSNP:rs137854500." evidence="10 20">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="1289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062495" description="In dbSNP:rs147743782." evidence="37">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="1341"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062496" description="In dbSNP:rs145689805." evidence="37">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="1376"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062497" description="In TGD; the mutant protein is retained in the endoplasmic reticulum while the wild-type protein is located at the plasma membrane; dbSNP:rs1831213945." evidence="35">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="1379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035726" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs189206655." evidence="42">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="1407"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009153" description="In TGD; loss of interaction with APOE; unable to generate APOE-containing high density lipoproteins; moderately decreased protein abundance; moderately decreased ATPase activity; moderately decreased phospholipid translocase activity; dbSNP:rs137854494." evidence="6 13 33 50">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="1477"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012630" description="In TGD; dbSNP:rs137854497." evidence="19">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="1506"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009154" description="In TGD." evidence="45">
        <original>I</original>
        <variation>R</variation>
        <location>
            <position position="1517"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012638" description="In dbSNP:rs1997618." evidence="5 8">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1555"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012631" description="In dbSNP:rs2230808." evidence="5 8 11 12 14 18 31 38 54">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="1587"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012632" description="In FHA1; deficient cellular cholesterol efflux." evidence="21">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="1611"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062498" description="In dbSNP:rs1251839800." evidence="37">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1615"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012639" description="In dbSNP:rs1883024." evidence="5 8">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1648"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062499" description="In dbSNP:rs1203589782." evidence="37">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="1670"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062500" description="In dbSNP:rs150125857." evidence="37">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1680"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037970" description="In TGD; dbSNP:rs137854498." evidence="24">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1680"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062501" description="In TGD; the mutant protein is retained in the endoplasmic reticulum while the wild-type protein is located at the plasma membrane." evidence="35">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="1704"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012633" description="In dbSNP:rs760507032." evidence="14">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="1731"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009155" description="In TGD; dbSNP:rs146292819." evidence="10 34 37 38">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="1800"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062502" description="In TGD; dbSNP:rs1055285452." evidence="32">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1851"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012634" description="In FHA1." evidence="9 13">
        <location>
            <begin position="1893"/>
            <end position="1894"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062503" description="In FHA1; uncertain significance; dbSNP:rs760768125." evidence="39">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1897"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062504" description="In TGD." evidence="34">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="1901"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062505" description="In Scott syndrome; shows impaired trafficking of the mutant protein to the plasma membrane; dbSNP:rs142688906." evidence="40">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1925"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037971" description="In FHA1; dbSNP:rs137854499." evidence="22">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="2009"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012635" description="In TGD; highly decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; loss protein subcellular localization to the plasma membrane; dbSNP:rs137854501." evidence="20 50">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="2081"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035727" description="In a colorectal cancer sample; somatic mutation." evidence="42">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="2109"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012636" description="In FHA1; moderately decreased protein abundance; does not affect ATPase activity; moderately decreased phospholipid translocase activity; dbSNP:rs369098049." evidence="13 50">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="2150"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062506" evidence="36">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="2163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012637" description="In dbSNP:rs2853577." evidence="5 8 15">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="2168"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062507" description="In TGD; dbSNP:rs564764153." evidence="34">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="2196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062508" description="In dbSNP:rs34879708." evidence="37">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="2243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062509" description="In dbSNP:rs144588452." evidence="36">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="2244"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Mild decrease of palmitoylation. Loss of localization to plasma membrane. Decreased cholesterol efflux. Decreased phospholipid efflux. Decreased palmitoylation; when associated with S-23, S-1110 and S-1111." evidence="48">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Mild decrease of palmitoylation. Loss of localization to plasma membrane. Decreased palmitoylation; when associated with S-3, S-1110 and S-1111." evidence="48">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with C-371." evidence="53">
        <original>I</original>
        <variation>C</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with E-371." evidence="53">
        <original>I</original>
        <variation>K</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Highly decreased protein abundance. Highly decreased ATPase activity. Highly decreased phospholipid translocase activity." evidence="50">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with C-308." evidence="53">
        <original>V</original>
        <variation>C</variation>
        <location>
            <position position="304"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on phospholipid and cholesterol efflux or localization to cell membrane; when associated with C-304." evidence="53">
        <original>V</original>
        <variation>C</variation>
        <location>
            <position position="308"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on phospholipid and cholesterol efflux or localization to cell membrane. 85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with C-74 or C-375." evidence="53">
        <original>I</original>
        <variation>C</variation>
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-74." evidence="53">
        <original>I</original>
        <variation>E</variation>
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="85-90% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with C-371." evidence="53">
        <original>L</original>
        <variation>C</variation>
        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="60-65% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane." evidence="53">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="568"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on phospholipid and cholesterol efflux and on localization to cell membrane." evidence="53">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="573"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-584 and K-585." evidence="53">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="581"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with E-590." evidence="53">
        <original>F</original>
        <variation>K</variation>
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-581 and K-585." evidence="53">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="584"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="80-85% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-581 and K-584." evidence="53">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="585"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="90-95% reduction in phospholipid and cholesterol efflux but no effect on localization to cell membrane; when associated with K-583." evidence="53">
        <original>W</original>
        <variation>E</variation>
        <location>
            <position position="590"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Moderately decreased protein abundance. Highly decreased ATPase activity. Highly decreased phospholipid translocase activity." evidence="50">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="593"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibits ATPase activity; when associated with M-1952. Decreases translocase activity; when associated with M-1952. Does not affect protein subcellular localization in plasma membrane and endosome; when associated with M-1952." evidence="50">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="939"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased palmitoylation; when associated with S-3, S-23 and S-1111." evidence="48">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="1110"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased palmitoylation; when associated with S-3, S-23 and S-1110." evidence="48">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="1111"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Moderately decreased protein abundance. Does not affect ATPase activity. Moderately decreased phospholipid translocase activity." evidence="50">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1512"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibits ATPase activity; when associated with M-939. Decreases translocase activity; when associated with M-939. Does not affect protein subcellular localization in plasma membrane and endosome; when associated with M-939." evidence="50">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="1952"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAK43526." evidence="55" ref="3">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="793"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAK43526." evidence="55" ref="3">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="831"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAK43526." evidence="55" ref="3">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1005"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAD49852." evidence="55" ref="7">
        <location>
            <begin position="1745"/>
            <end position="1746"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="4"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="22"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="58"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="62"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="66"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="87"/>
            <end position="89"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="90"/>
            <end position="92"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="98"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="101"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="121"/>
            <end position="135"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="200"/>
            <end position="209"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="212"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="216"/>
            <end position="226"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="230"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="236"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="turn" evidence="61">
        <location>
            <begin position="240"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="253"/>
            <end position="274"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="278"/>
            <end position="288"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="299"/>
            <end position="308"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="353"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="369"/>
            <end position="379"/>
        </location>
    </feature>
    <feature type="strand" evidence="62">
        <location>
            <begin position="384"/>
            <end position="386"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="390"/>
            <end position="404"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="405"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="412"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="419"/>
            <end position="426"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="431"/>
            <end position="440"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="441"/>
            <end position="444"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="445"/>
            <end position="453"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="460"/>
            <end position="467"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="484"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="516"/>
            <end position="528"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="535"/>
            <end position="537"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="541"/>
            <end position="545"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="550"/>
            <end position="557"/>
        </location>
    </feature>
    <feature type="turn" evidence="61">
        <location>
            <begin position="560"/>
            <end position="562"/>
        </location>
    </feature>
    <feature type="turn" evidence="61">
        <location>
            <begin position="582"/>
            <end position="585"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="587"/>
            <end position="590"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
            <begin position="593"/>
            <end position="608"/>
        </location>
    </feature>
    <feature type="strand" evidence="61">
        <location>
            <begin position="616"/>
            <end position="621"/>
        </location>
    </feature>
    <feature type="helix" evidence="61">
        <location>
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    </evidence>
    <evidence type="ECO:0000269" key="34">
        <source>
            <dbReference type="PubMed" id="15019541"/>
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    </evidence>
    <evidence type="ECO:0000269" key="35">
        <source>
            <dbReference type="PubMed" id="15158913"/>
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    </evidence>
    <evidence type="ECO:0000269" key="36">
        <source>
            <dbReference type="PubMed" id="15262183"/>
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    </evidence>
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        <source>
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    <evidence type="ECO:0000269" key="38">
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    </evidence>
    <evidence type="ECO:0000269" key="39">
        <source>
            <dbReference type="PubMed" id="15722566"/>
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    </evidence>
    <evidence type="ECO:0000269" key="40">
        <source>
            <dbReference type="PubMed" id="15790791"/>
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    </evidence>
    <evidence type="ECO:0000269" key="41">
        <source>
            <dbReference type="PubMed" id="16226177"/>
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    </evidence>
    <evidence type="ECO:0000269" key="42">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="43">
        <source>
            <dbReference type="PubMed" id="17205124"/>
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    </evidence>
    <evidence type="ECO:0000269" key="44">
        <source>
            <dbReference type="PubMed" id="18354102"/>
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    </evidence>
    <evidence type="ECO:0000269" key="45">
        <source>
            <dbReference type="PubMed" id="18776170"/>
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    </evidence>
    <evidence type="ECO:0000269" key="46">
        <source>
            <dbReference type="PubMed" id="19159218"/>
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    </evidence>
    <evidence type="ECO:0000269" key="47">
        <source>
            <dbReference type="PubMed" id="19258317"/>
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    </evidence>
    <evidence type="ECO:0000269" key="48">
        <source>
            <dbReference type="PubMed" id="19556522"/>
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    </evidence>
    <evidence type="ECO:0000269" key="49">
        <source>
            <dbReference type="PubMed" id="23931754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="50">
        <source>
            <dbReference type="PubMed" id="24097981"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="51">
        <source>
            <dbReference type="PubMed" id="27535533"/>
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    </evidence>
    <evidence type="ECO:0000269" key="52">
        <source>
            <dbReference type="PubMed" id="28882873"/>
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    </evidence>
    <evidence type="ECO:0000269" key="53">
        <source>
            <dbReference type="PubMed" id="35974019"/>
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    </evidence>
    <evidence type="ECO:0000269" key="54">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="55"/>
    <evidence type="ECO:0000305" key="56">
        <source>
            <dbReference type="PubMed" id="10533863"/>
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    </evidence>
    <evidence type="ECO:0000305" key="57">
        <source>
            <dbReference type="PubMed" id="14754908"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="58">
        <source>
            <dbReference type="PubMed" id="24097981"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="59">
        <source>
            <dbReference type="PubMed" id="35974019"/>
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    </evidence>
    <evidence type="ECO:0000312" key="60">
        <source>
            <dbReference type="HGNC" id="HGNC:29"/>
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    </evidence>
    <evidence type="ECO:0007829" key="61">
        <source>
            <dbReference type="PDB" id="7TBW"/>
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    </evidence>
    <evidence type="ECO:0007829" key="62">
        <source>
            <dbReference type="PDB" id="7TC0"/>
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    </evidence>
    <sequence length="2261" mass="254302" checksum="21A2CF8F3F518D6D" modified="2010-10-05" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-08-02" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NRK6</accession>
    <accession>Q13040</accession>
    <accession>Q6P1Q8</accession>
    <accession>Q9H3V0</accession>
    <name>ABCBA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">ATP-binding cassette sub-family B member 10, mitochondrial</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">ABC-mitochondrial erythroid protein</fullName>
            <shortName evidence="1">ABC-me protein</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 10</fullName>
            <shortName>ABC transporter 10 protein</shortName>
            <ecNumber evidence="14 15">7.6.2.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="17">Mitochondrial ATP-binding cassette 2</fullName>
            <shortName evidence="17">M-ABC2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ABCB10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Whitman J.C."/>
                <person name="Musso G."/>
                <person name="Wallace J.A."/>
                <person name="Bradley T."/>
                <person name="Bergonia H.A."/>
                <person name="Kafina M.D."/>
                <person name="Matsumoto M."/>
                <person name="Igarashi K."/>
                <person name="Phillips J.D."/>
                <person name="Paw B.H."/>
                <person name="Kaplan J."/>
                <person name="Ward D.M."/>
            </authorList>
            <dbReference type="PubMed" id="28808058"/>
            <dbReference type="DOI" id="10.1074/jbc.m117.797415"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF LYS-533; SER-635; GLN-638; ASP-658 AND GLU-659</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2019" name="Haematologica" volume="104" first="1756" last="1767">
            <title>Dimeric ferrochelatase bridges ABCB7 and ABCB10 homodimers in an architecturally defined molecular complex required for heme biosynthesis.</title>
            <authorList>
                <person name="Maio N."/>
                <person name="Kim K.S."/>
                <person name="Holmes-Hampton G."/>
                <person name="Singh A."/>
                <person name="Rouault T.A."/>
            </authorList>
            <dbReference type="PubMed" id="30765471"/>
            <dbReference type="DOI" id="10.3324/haematol.2018.214320"/>
        </citation>
        <scope>INTERACTION WITH FECH</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2020" name="PLoS ONE" volume="15" first="e0238754" last="e0238754">
            <title>Stimulation of the human mitochondrial transporter ABCB10 by zinc-mesoporphrin.</title>
            <authorList>
                <person name="Martinez M."/>
                <person name="Fendley G.A."/>
                <person name="Saxberg A.D."/>
                <person name="Zoghbi M.E."/>
            </authorList>
            <dbReference type="PubMed" id="33253225"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0238754"/>
        </citation>
        <scope>MUTAGENESIS OF CYS-215; CYS-224 AND CYS-582</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2025" name="J. Cell Sci." volume="138" first="0" last="0">
            <title>Definition of the human mitochondrial TOM interactome reveals TRABD as a new interacting protein.</title>
            <authorList>
                <person name="Oezdemir M."/>
                <person name="Oeljeklaus S."/>
                <person name="Schendzielorz A."/>
                <person name="Morgenstern M."/>
                <person name="Valpadashi A."/>
                <person name="Yousefi R."/>
                <person name="Warscheid B."/>
                <person name="Dennerlein S."/>
            </authorList>
            <dbReference type="PubMed" id="40105103"/>
            <dbReference type="DOI" id="10.1242/jcs.263576"/>
        </citation>
        <scope>INTERACTION WITH MUL1</scope>
    </reference>
    <reference evidence="23 24 25 26" key="18">
        <citation type="journal article" date="2013" name="Proc. Natl. Acad. Sci. U.S.A." volume="110" first="9710" last="9715">
            <title>Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states.</title>
            <authorList>
                <person name="Shintre C.A."/>
                <person name="Pike A.C."/>
                <person name="Li Q."/>
                <person name="Kim J.I."/>
                <person name="Barr A.J."/>
                <person name="Goubin S."/>
                <person name="Shrestha L."/>
                <person name="Yang J."/>
                <person name="Berridge G."/>
                <person name="Ross J."/>
                <person name="Stansfeld P.J."/>
                <person name="Sansom M.S."/>
                <person name="Edwards A.M."/>
                <person name="Bountra C."/>
                <person name="Marsden B.D."/>
                <person name="von Delft F."/>
                <person name="Bullock A.N."/>
                <person name="Gileadi O."/>
                <person name="Burgess-Brown N.A."/>
                <person name="Carpenter E.P."/>
            </authorList>
            <dbReference type="PubMed" id="23716676"/>
            <dbReference type="DOI" id="10.1073/pnas.1217042110"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 152-738 ALONE AND IN COMPLEX WITH ATP ANALOGS</scope>
        <scope>ATP-BINDING REGION</scope>
        <scope>SUBUNIT</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2002" name="J. Hum. Genet." volume="47" first="38" last="50">
            <title>Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population.</title>
            <authorList>
                <person name="Saito S."/>
                <person name="Iida A."/>
                <person name="Sekine A."/>
                <person name="Miura Y."/>
                <person name="Ogawa C."/>
                <person name="Kawauchi S."/>
                <person name="Higuchi S."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="11829140"/>
            <dbReference type="DOI" id="10.1007/s10038-002-8653-6"/>
        </citation>
        <scope>VARIANT SER-150</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] THR-471</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2021" name="Sci. Transl. Med." volume="13" first="0" last="0">
            <title>ABCB10 exports mitochondrial biliverdin, driving metabolic maladaptation in obesity.</title>
            <authorList>
                <person name="Shum M."/>
                <person name="Shintre C.A."/>
                <person name="Althoff T."/>
                <person name="Gutierrez V."/>
                <person name="Segawa M."/>
                <person name="Saxberg A.D."/>
                <person name="Martinez M."/>
                <person name="Adamson R."/>
                <person name="Young M.R."/>
                <person name="Faust B."/>
                <person name="Gharakhanian R."/>
                <person name="Su S."/>
                <person name="Chella Krishnan K."/>
                <person name="Mahdaviani K."/>
                <person name="Veliova M."/>
                <person name="Wolf D.M."/>
                <person name="Ngo J."/>
                <person name="Nocito L."/>
                <person name="Stiles L."/>
                <person name="Abramson J."/>
                <person name="Lusis A.J."/>
                <person name="Hevener A.L."/>
                <person name="Zoghbi M.E."/>
                <person name="Carpenter E.P."/>
                <person name="Liesa M."/>
            </authorList>
            <dbReference type="PubMed" id="34011630"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.abd1869"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference evidence="27 28" key="22">
        <citation type="journal article" date="2023" name="Nat. Commun." volume="14" first="2030" last="2030">
            <title>Cryo-EM structures of mitochondrial ABC transporter ABCB10 in apo and biliverdin-bound form.</title>
            <authorList>
                <person name="Cao S."/>
                <person name="Yang Y."/>
                <person name="He L."/>
                <person name="Hang Y."/>
                <person name="Yan X."/>
                <person name="Shi H."/>
                <person name="Wu J."/>
                <person name="Ouyang Z."/>
            </authorList>
            <dbReference type="PubMed" id="37041204"/>
            <dbReference type="DOI" id="10.1038/s41467-023-37851-9"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.85 ANGSTROMS) OF 152-738</scope>
        <scope>MUTAGENESIS OF ASN-229; PHE-398 AND ASN-407</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 7 10 11 14 15">ATP-dependent transporter located in the mitochondrial inner membrane that catalyzes the export of biliverdin from the mitochondrial matrix, and plays a crucial role in hemoglobin synthesis and antioxidative stress (PubMed:22085049, PubMed:28315685, PubMed:28808058, PubMed:34011630, PubMed:37041204). Participates in the early step of the heme biosynthetic process during insertion of iron into protoporphyrin IX (PPIX) (PubMed:22085049, PubMed:28808058). Involved in the stabilization of the iron transporter mitoferrin-1/SLC25A37 (By similarity). In addition may be involved in mitochondrial unfolded protein response (UPRmt) signaling pathway, although ABCB10 probably does not participate in peptide export from mitochondria (PubMed:28315685).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14 15">
            <text>biliverdin IXalpha(in) + ATP + H2O = biliverdin IXalpha(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:82359"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57991"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20 21">
            <dbReference type="Rhea" id="RHEA:82360"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="15">Cholesterol promotes the ATPase activity of ABCB10 in a dose-dependent manner.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="8">0.18 mM for ATP (from ABCB10 purified in cholesteryl-hemisuccinate, without reconstitution into liposomes)</KM>
            <KM evidence="8">0.3 mM for ATP (from ABCB10 purified in cholesteryl-hemisuccinate, with reconstitution into liposomes)</KM>
            <KM evidence="8">0.5 mM for ATP (from ABCB10 purified in mitochondrial lipid cardiolipin, without reconstitution into liposomes)</KM>
            <KM evidence="8">0.19 mM for ATP (from ABCB10 purified in mitochondrial lipid cardiolipin, with reconstitution into liposomes)</KM>
            <Vmax evidence="8">51.0 nmol/min/mg enzyme toward ATP (from ABCB10 purified in cholesteryl-hemisuccinate, without reconstitution into liposomes)</Vmax>
            <Vmax evidence="8">319.0 nmol/min/mg enzyme toward ATP (from ABCB10 purified in cholesteryl-hemisuccinate, with reconstitution into liposomes)</Vmax>
            <Vmax evidence="8">106.0 nmol/min/mg enzyme toward ATP (from ABCB10 purified in mitochondrial lipid cardiolipin, without reconstitution into liposomes)</Vmax>
            <Vmax evidence="8">181.0 nmol/min/mg enzyme toward ATP (from ABCB10 purified in mitochondrial lipid cardiolipin, with reconstitution into liposomes)</Vmax>
            <Vmax evidence="14">323.0 nmol/min/mg enzyme toward ATP (from nanodisc-reconstituted ABCB10 in the presence of biliverdin)</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1 8 9 12 16">Homodimer or homooligomer (PubMed:23716676, PubMed:30765471). Interacts with PAAT; this interaction regulates ABCB10 (PubMed:25063848). Interacts with SLC25A37; this interaction stabilizes SLC25A37 and enhances the function of SLC25A37 to import mitochondrial iron during erythroid differentiation (By similarity). Interacts with FECH; this interaction may allow the formation of an oligomeric complex with SLC25A37 (By similarity). Forms a complex with ABCB7 and FECH, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with MUL1/MAPL (PubMed:40105103).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6164528">
            <id>Q9NRK6</id>
        </interactant>
        <interactant intactId="EBI-1390356">
            <id>P22830</id>
            <label>FECH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion inner membrane</location>
            <topology evidence="8">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Ubiquitous. Highly expressed in bone marrow, expressed at intermediate to high levels in skeletal muscle, small intestine, thyroid, heart, brain, placenta, liver, pancreas, prostate, testis, ovary, leukocyte, stomach, spinal cord, lymph node, trachea and adrenal gland, and low levels are found in lung, kidney, spleen, thymus and colon.</text>
    </comment>
    <comment type="similarity">
        <text evidence="18">Belongs to the ABC transporter superfamily. ABCB family. Mitochondrial peptide exporter (TC 3.A.1.212) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="14 15"/>
    <dbReference type="EMBL" id="AF216833">
        <property type="protein sequence ID" value="AAF78198.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB013380">
        <property type="protein sequence ID" value="BAB20265.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121990">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471098">
        <property type="protein sequence ID" value="EAW69901.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064930">
        <property type="protein sequence ID" value="AAH64930.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U18237">
        <property type="protein sequence ID" value="AAA84438.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1580.1"/>
    <dbReference type="RefSeq" id="NP_036221.2">
        <property type="nucleotide sequence ID" value="NM_012089.3"/>
    </dbReference>
    <dbReference type="PDB" id="3ZDQ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A=152-738"/>
    </dbReference>
    <dbReference type="PDB" id="4AYT">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A=152-738"/>
    </dbReference>
    <dbReference type="PDB" id="4AYW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=1-738"/>
    </dbReference>
    <dbReference type="PDB" id="4AYX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=152-738"/>
    </dbReference>
    <dbReference type="PDB" id="7Y48">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="B=152-738"/>
    </dbReference>
    <dbReference type="PDB" id="7Y49">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.67 A"/>
        <property type="chains" value="A=152-738"/>
    </dbReference>
    <dbReference type="PDBsum" id="3ZDQ"/>
    <dbReference type="PDBsum" id="4AYT"/>
    <dbReference type="PDBsum" id="4AYW"/>
    <dbReference type="PDBsum" id="4AYX"/>
    <dbReference type="PDBsum" id="7Y48"/>
    <dbReference type="PDBsum" id="7Y49"/>
    <dbReference type="AlphaFoldDB" id="Q9NRK6"/>
    <dbReference type="EMDB" id="EMD-33603"/>
    <dbReference type="EMDB" id="EMD-33604"/>
    <dbReference type="SMR" id="Q9NRK6"/>
    <dbReference type="BioGRID" id="117020">
        <property type="interactions" value="89"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-8302">
        <property type="entry name" value="ABCB10-ABCB7-FECH ABC transporter"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NRK6">
        <property type="interactions" value="2019"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NRK6">
        <property type="interactions" value="63"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000355637"/>
    <dbReference type="TCDB" id="3.A.1.201.17">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9NRK6">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NRK6">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NRK6"/>
    <dbReference type="MetOSite" id="Q9NRK6"/>
    <dbReference type="PhosphoSitePlus" id="Q9NRK6"/>
    <dbReference type="SwissPalm" id="Q9NRK6"/>
    <dbReference type="BioMuta" id="ABCB10"/>
    <dbReference type="DMDM" id="143811359"/>
    <dbReference type="jPOST" id="Q9NRK6"/>
    <dbReference type="MassIVE" id="Q9NRK6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000355637"/>
    <dbReference type="PeptideAtlas" id="Q9NRK6"/>
    <dbReference type="ProteomicsDB" id="82382"/>
    <dbReference type="Pumba" id="Q9NRK6"/>
    <dbReference type="Antibodypedia" id="34677">
        <property type="antibodies" value="224 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23456"/>
    <dbReference type="Ensembl" id="ENST00000344517.5">
        <property type="protein sequence ID" value="ENSP00000355637.3"/>
        <property type="gene ID" value="ENSG00000135776.6"/>
    </dbReference>
    <dbReference type="GeneID" id="23456"/>
    <dbReference type="KEGG" id="hsa:23456"/>
    <dbReference type="MANE-Select" id="ENST00000344517.5">
        <property type="protein sequence ID" value="ENSP00000355637.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_012089.3"/>
        <property type="RefSeq protein sequence ID" value="NP_036221.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001htp.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:41"/>
    <dbReference type="ClinPGx" id="PA24385"/>
    <dbReference type="CTD" id="23456"/>
    <dbReference type="DisGeNET" id="23456"/>
    <dbReference type="GeneCards" id="ABCB10"/>
    <dbReference type="HGNC" id="HGNC:41">
        <property type="gene designation" value="ABCB10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000135776">
        <property type="expression patterns" value="Tissue enhanced (bone)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCB10"/>
    <dbReference type="MIM" id="605454">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000135776"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000135776"/>
    <dbReference type="eggNOG" id="KOG0058">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157680"/>
    <dbReference type="HOGENOM" id="CLU_000604_84_3_1"/>
    <dbReference type="InParanoid" id="Q9NRK6"/>
    <dbReference type="OMA" id="MYTGHTL"/>
    <dbReference type="OrthoDB" id="6500128at2759"/>
    <dbReference type="PAN-GO" id="Q9NRK6">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NRK6"/>
    <dbReference type="BRENDA" id="7.4.2.5">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NRK6"/>
    <dbReference type="Reactome" id="R-HSA-1369007">
        <property type="pathway name" value="Mitochondrial ABC transporters"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9NRK6"/>
    <dbReference type="SignaLink" id="Q9NRK6"/>
    <dbReference type="Agora" id="ENSG00000135776"/>
    <dbReference type="BioGRID-ORCS" id="23456">
        <property type="hits" value="69 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCB10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NRK6"/>
    <dbReference type="GenomeRNAi" id="23456"/>
    <dbReference type="Pharos" id="Q9NRK6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NRK6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NRK6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000135776">
        <property type="expression patterns" value="Expressed in trabecular bone tissue and 185 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048821">
        <property type="term" value="P:erythrocyte development"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0170037">
        <property type="term" value="P:export from the mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006783">
        <property type="term" value="P:heme biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006839">
        <property type="term" value="P:mitochondrial transport"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034514">
        <property type="term" value="P:mitochondrial unfolded protein response"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045648">
        <property type="term" value="P:positive regulation of erythrocyte differentiation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070455">
        <property type="term" value="P:positive regulation of heme biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046985">
        <property type="term" value="P:positive regulation of hemoglobin biosynthetic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd18573">
        <property type="entry name" value="ABC_6TM_ABCB10_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd03249">
        <property type="entry name" value="ABC_MTABC3_MDL1_MDL2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1560.10:FF:000048">
        <property type="entry name" value="ATP-binding cassette sub-family B member 10, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000403">
        <property type="entry name" value="ATP-binding cassette sub-family B member 8, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1560.10">
        <property type="entry name" value="ABC transporter type 1, transmembrane domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011527">
        <property type="entry name" value="ABC1_TM_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036640">
        <property type="entry name" value="ABC1_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039421">
        <property type="entry name" value="Type_1_exporter"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43394:SF1">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY B MEMBER 10, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43394">
        <property type="entry name" value="ATP-DEPENDENT PERMEASE MDL1, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00664">
        <property type="entry name" value="ABC_membrane"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90123">
        <property type="entry name" value="ABC transporter transmembrane region"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50929">
        <property type="entry name" value="ABC_TM1F"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0318">Glutathionylation</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0999">Mitochondrion inner membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000255" description="ATP-binding cassette sub-family B member 10, mitochondrial">
        <location>
            <begin position="106"/>
            <end position="738"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="18">
        <location>
            <begin position="106"/>
            <end position="168"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="169"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="18">
        <location>
            <begin position="193"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="214"/>
            <end position="236"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="18">
        <location>
            <begin position="237"/>
            <end position="287"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="288"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="18">
        <location>
            <begin position="311"/>
            <end position="313"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="314"/>
            <end position="333"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="18">
        <location>
            <begin position="334"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="393"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="18">
        <location>
            <begin position="417"/>
            <end position="430"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="8 24">
        <location>
            <begin position="431"/>
            <end position="452"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="18">
        <location>
            <begin position="453"/>
            <end position="738"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1" evidence="3">
        <location>
            <begin position="171"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="2">
        <location>
            <begin position="492"/>
            <end position="731"/>
        </location>
    </feature>
    <feature type="binding site" evidence="15 27">
        <location>
            <position position="402"/>
        </location>
        <ligand>
            <name>biliverdin IXalpha</name>
            <dbReference type="ChEBI" id="CHEBI:57991"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 24 26">
        <location>
            <position position="530"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 24 25 26">
        <location>
            <position position="532"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 24 25">
        <location>
            <position position="533"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 24 25 26">
        <location>
            <position position="534"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 24 26">
        <location>
            <position position="534"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 24 25 26">
        <location>
            <position position="535"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 24 26">
        <location>
            <position position="658"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="29">
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="modified residue" description="S-glutathionyl cysteine" evidence="1">
        <location>
            <position position="582"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013702" description="In dbSNP:rs4148756." evidence="5">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048133" description="In dbSNP:rs17584642.">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035735" description="In a breast cancer sample; somatic mutation." evidence="6">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031435" description="In dbSNP:rs35698797." evidence="4">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="545"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase activity; when associated with L-224 and G-582. Activated by Zn (II) mesoporphyrin; when associated with L-224 and G-582." evidence="13">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase activity; when associated with S-215 and G-582. Activated by Zn (II) mesoporphyrin; when associated with S-215 and G-582." evidence="13">
        <original>C</original>
        <variation>L</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase activity in the absence or presence of biliverdin. No increased ATPase activity in the presence of biliverdin; when associated with A-398. Increased ATPase activity in the absence of biliverdin compared to WT; when associated with A-407. No increased ATPase activity in the presence of biliverdin; when associated with A-407. No increased ATPase activity in the presence of biliverdin; when associated with A-398 and A-407." evidence="15">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No increased ATPase activity in the presence of biliverdin. No increased ATPase activity in the presence of biliverdin; when associated with A-229. No increased ATPase activity in the presence of biliverdin; when associated with A-407. No increased ATPase activity in the presence of biliverdin; when associated with A-229 and A-407." evidence="15">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased ATPase activity in the absence of biliverdin compared to WT. No increased ATPase activity in the presence of biliverdin. Increased ATPase activity in the absence of biliverdin compared to WT; when associated with A-229. No increased ATPase activity in the presence of biliverdin; when associated with A-229. No increased ATPase activity in the presence of biliverdin; when associated with A-398. No increased ATPase activity in the presence of biliverdin; when associated with A-229 and A-398." evidence="15">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases hemoglobin biosynthetic process." evidence="11">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="533"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase activity; when associated with S-215 and L-224. Activated by Zn (II) mesoporphyrin; when associated with S-215 and L-224." evidence="13">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="582"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not rescue hemoglobin and heme biosynthetic process." evidence="11">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="635"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not rescue hemoglobin and heme biosynthetic process." evidence="11">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not rescue hemoglobin and heme biosynthetic process." evidence="11">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="658"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not rescue hemoglobin and heme biosynthetic process." evidence="11">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="659"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF78198." evidence="18" ref="1">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="393"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA84438." evidence="18" ref="6">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA84438." evidence="18" ref="6">
        <original>IRQLNP</original>
        <variation>NPSAKPS</variation>
        <location>
            <begin position="558"/>
            <end position="563"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB20265." evidence="18" ref="2">
        <original>VAEVAN</original>
        <variation>GLKGQ</variation>
        <location>
            <begin position="606"/>
            <end position="611"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA84438." evidence="18" ref="6">
        <original>FIRNFPQG</original>
        <variation>SPEFPPR</variation>
        <location>
            <begin position="615"/>
            <end position="622"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAA84438." evidence="18" ref="6">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="691"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="154"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="165"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="168"/>
            <end position="185"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="188"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="208"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="260"/>
            <end position="265"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="268"/>
            <end position="285"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="288"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="312"/>
            <end position="359"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="361"/>
            <end position="366"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="370"/>
            <end position="422"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="428"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="turn" evidence="30">
        <location>
            <begin position="485"/>
            <end position="487"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="492"/>
            <end position="499"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="502"/>
            <end position="504"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="509"/>
            <end position="517"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="522"/>
            <end position="526"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="530"/>
            <end position="540"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="547"/>
            <end position="553"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="558"/>
            <end position="560"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="563"/>
            <end position="568"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="569"/>
            <end position="573"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="581"/>
            <end position="583"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="584"/>
            <end position="589"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="592"/>
            <end position="594"/>
        </location>
    </feature>
    <feature type="turn" evidence="30">
        <location>
            <begin position="595"/>
            <end position="597"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="600"/>
            <end position="609"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="613"/>
            <end position="617"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="619"/>
            <end position="621"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="622"/>
            <end position="624"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="628"/>
            <end position="631"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="636"/>
            <end position="650"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="653"/>
            <end position="658"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="666"/>
            <end position="680"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="683"/>
            <end position="688"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="692"/>
            <end position="697"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="698"/>
            <end position="704"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="706"/>
            <end position="713"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="715"/>
            <end position="719"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9JI39"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00441"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10922475"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11829140"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22085049"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="23716676"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="25063848"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="28315685"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="28808058"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="30765471"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="33253225"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="34011630"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="37041204"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="40105103"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="10922475"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="18"/>
    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="23716676"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20">
        <source>
            <dbReference type="PubMed" id="34011630"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="37041204"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:41"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PDB" id="3ZDQ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PDB" id="4AYT"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PDB" id="4AYW"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="4AYX"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PDB" id="7Y48"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PDB" id="7Y49"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="30">
        <source>
            <dbReference type="PDB" id="3ZDQ"/>
        </source>
    </evidence>
    <sequence length="738" mass="79148" checksum="C68B4FAC0F8B7E43" modified="2007-04-03" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="161" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IUA7</accession>
    <accession>Q6P655</accession>
    <accession>Q8N2S4</accession>
    <accession>Q8WWZ5</accession>
    <accession>Q96MD8</accession>
    <name>ABCA9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">ATP-binding cassette sub-family A member 9</fullName>
            <ecNumber evidence="9">7.6.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ABCA9</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="GeneScreen" volume="1" first="157" last="164">
            <title>Identifying and characterizing a five-gene cluster of ATP-binding cassette transporters mapping to human chromosome 17q24: a new subgroup within the ABCA subfamily.</title>
            <authorList>
                <person name="Arnould I."/>
                <person name="Schriml L.M."/>
                <person name="Prades C."/>
                <person name="Lachtermacher-Triunfol M."/>
                <person name="Schneider T."/>
                <person name="Maintoux C."/>
                <person name="Lemoine C."/>
                <person name="Debono D."/>
                <person name="Devaud C."/>
                <person name="Naudin L."/>
                <person name="Bauche S."/>
                <person name="Annat M."/>
                <person name="Annilo T."/>
                <person name="Allikmets R."/>
                <person name="Gold B."/>
                <person name="Denefle P."/>
                <person name="Rosier M."/>
                <person name="Dean M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS HIS-353 AND THR-1306</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="Biochem. Biophys. Res. Commun." volume="295" first="408" last="416">
            <title>Molecular structure of a novel cholesterol-responsive A subclass ABC transporter, ABCA9.</title>
            <authorList>
                <person name="Piehler A."/>
                <person name="Kaminski W.E."/>
                <person name="Wenzel J.J."/>
                <person name="Langmann T."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="12150964"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(02)00659-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORMS 2; 3 AND 4)</scope>
        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <source>
            <tissue>Macrophage</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-856 (ISOFORM 1)</scope>
        <scope>VARIANT HIS-353</scope>
        <source>
            <tissue>Embryo</tissue>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="J. Proteome Res." volume="8" first="651" last="661">
            <title>Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.</title>
            <authorList>
                <person name="Chen R."/>
                <person name="Jiang X."/>
                <person name="Sun D."/>
                <person name="Han G."/>
                <person name="Wang F."/>
                <person name="Ye M."/>
                <person name="Wang L."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="19159218"/>
            <dbReference type="DOI" id="10.1021/pr8008012"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-949</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="9">Transporter that may play a role in monocyte differentiation and lipid transport and homeostasis.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Membrane</location>
            <topology evidence="8">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IUA7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IUA7-2</id>
            <name>2</name>
            <name>ABCA9delta+55</name>
            <sequence type="described" ref="VSP_020705"/>
        </isoform>
        <isoform>
            <id>Q8IUA7-3</id>
            <name>3</name>
            <name>ABCA9delta+73</name>
            <sequence type="described" ref="VSP_020707 VSP_020709"/>
        </isoform>
        <isoform>
            <id>Q8IUA7-4</id>
            <name>4</name>
            <name>ABCA9delta-95</name>
            <sequence type="described" ref="VSP_020708 VSP_020709"/>
        </isoform>
        <isoform>
            <id>Q8IUA7-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_020706"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Widely expressed with higher expression in heart.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="3">Expressed in fetal tissues with higher expression in fetal heart and kidney.</text>
    </comment>
    <comment type="induction">
        <text evidence="3">Up-regulated during monocyte differentiation into macrophages. Down-regulated by cholesterol loading of macrophages.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH62472" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC11021" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="9"/>
    <dbReference type="EMBL" id="AY028899">
        <property type="protein sequence ID" value="AAK30024.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423307">
        <property type="protein sequence ID" value="AAN32751.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423346">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423308">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423309">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423310">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423311">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423312">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423313">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF423314">
        <property type="protein sequence ID" value="AAN32752.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF423315">
        <property type="protein sequence ID" value="AAN32752.1"/>
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    <dbReference type="EMBL" id="AF423316">
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF423317">
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF423320">
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF423321">
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF423323">
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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            <position position="120"/>
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            <end position="1624"/>
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            <end position="1624"/>
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            <position position="1429"/>
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            <position position="353"/>
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            <position position="785"/>
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            <position position="1356"/>
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        <source>
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        <source>
            <dbReference type="PubMed" id="19159218"/>
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    <evidence type="ECO:0000269" key="6">
        <source ref="1"/>
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        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
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</entry>
<entry dataset="Swiss-Prot" created="2001-01-24" modified="2026-01-28" version="199" xmlns="https://uniprot.org/uniprot">
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    <accession>B2RAM3</accession>
    <accession>Q13210</accession>
    <accession>Q2M3H9</accession>
    <name>ABCD2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family D member 2</fullName>
            <ecNumber evidence="12">3.1.2.-</ecNumber>
            <ecNumber evidence="12 18">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Adrenoleukodystrophy-like 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adrenoleukodystrophy-related protein</fullName>
            <shortName>hALDR</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="20" type="primary">ABCD2</name>
        <name type="synonym">ALD1</name>
        <name type="synonym">ALDL1</name>
        <name evidence="15" type="synonym">ALDR</name>
        <name evidence="14 16" type="synonym">ALDRP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH ABCD3</scope>
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        <scope>INTERACTION WITH PEX19</scope>
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            <tissue>Brain</tissue>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>INTERACTION WITH ABCD1</scope>
        <scope>SUBUNIT</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
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        <scope>FUNCTION</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] LYS-244</scope>
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    <comment type="function">
        <text evidence="11 12 18">ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:21145416, PubMed:29397936). Like ABCD1 seems to have fatty acyl-CoA thioesterase (ACOT) and ATPase activities, according to this model, VLCFA-CoA as free VLCFA is transpoted in an ATP-dependent manner into peroxisomes after the hydrolysis of VLCFA-CoA mediated by the ACOT activity of ABCD2 (Probable) (PubMed:29397936). Shows overlapping substrate specificities with ABCD1 toward saturated fatty acids (FA) and monounsaturated FA (MUFA) but has a distinct substrate preference for shorter VLCFA (C22:0) and polyunsaturated fatty acid (PUFA) such as C22:6-CoA and C24:6-CoA (in vitro) (PubMed:21145416). Thus, may play a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:21145416).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>a very long-chain fatty acyl-CoA + H2O = a very long-chain fatty acid + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67072"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58950"/>
            <dbReference type="ChEBI" id="CHEBI:138261"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:67073"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 18">
            <text>a very long-chain fatty acid(in) + ATP + H2O = a very long-chain fatty acid(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58950"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:67081"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="1 6 7 8 9">Homodimers (By similarity). Homotetramers (By similarity). The minimal functional unit is a homodimer but the major oligomeric form in peroxisomal membrane is a homotetramer (By similarity). Forms heterodimers with ABCD1 (PubMed:17609205). Forms heterodimers with ABCD3 (PubMed:10551832). In addition to tetramers, some larger molecular assemblies are also found but represented only a minor fraction (By similarity). Interacts with PEX19; facilitates ABCD2 insertion into the peroxisome membrane (PubMed:10704444, PubMed:10777694).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 11 12">Peroxisome membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="13">Predominantly expressed in brain and heart.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
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</entry>
<entry dataset="Swiss-Prot" created="2001-09-26" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>O60706</accession>
    <accession>O60707</accession>
    <name>ABCC9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family C member 9</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Sulfonylurea receptor 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABCC9</name>
        <name evidence="14" type="synonym">SUR2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="DOI" id="10.1016/j.ajhg.2019.06.007"/>
        </citation>
        <scope>VARIANT ARG-1160</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2019" name="Nat. Commun." volume="10" first="4457" last="4457">
            <title>ABCC9-related Intellectual disability Myopathy Syndrome is a KATP channelopathy with loss-of-function mutations in ABCC9.</title>
            <authorList>
                <person name="Smeland M.F."/>
                <person name="McClenaghan C."/>
                <person name="Roessler H.I."/>
                <person name="Savelberg S."/>
                <person name="Hansen G.A.M."/>
                <person name="Hjellnes H."/>
                <person name="Arntzen K.A."/>
                <person name="Mueller K.I."/>
                <person name="Dybesland A.R."/>
                <person name="Harter T."/>
                <person name="Sala-Rabanal M."/>
                <person name="Emfinger C.H."/>
                <person name="Huang Y."/>
                <person name="Singareddy S.S."/>
                <person name="Gunn J."/>
                <person name="Wozniak D.F."/>
                <person name="Kovacs A."/>
                <person name="Massink M."/>
                <person name="Tessadori F."/>
                <person name="Kamel S.M."/>
                <person name="Bakkers J."/>
                <person name="Remedi M.S."/>
                <person name="Van Ghelue M."/>
                <person name="Nichols C.G."/>
                <person name="van Haaften G."/>
            </authorList>
            <dbReference type="PubMed" id="31575858"/>
            <dbReference type="DOI" id="10.1038/s41467-019-12428-7"/>
        </citation>
        <scope>INVOLVEMENT IN IDMYS</scope>
    </reference>
    <comment type="function">
        <text evidence="1 13">Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (PubMed:9831708). Can form a sulfonylurea-sensitive but ATP-insensitive potassium channel with KCNJ8 (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 13">Interacts with KCNJ11 (PubMed:9831708). Interacts with KCNJ8 (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O60706-1</id>
            <name>SUR2A</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O60706-2</id>
            <name>SUR2B</name>
            <sequence type="described" ref="VSP_000058"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-00221">
            <name>Cardiomyopathy, dilated, 1O</name>
            <acronym>CMD1O</acronym>
            <description>A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.</description>
            <dbReference type="MIM" id="608569"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="7">
        <disease id="DI-03143">
            <name>Atrial fibrillation, familial, 12</name>
            <acronym>ATFB12</acronym>
            <description>A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.</description>
            <dbReference type="MIM" id="614050"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="8 9 10">
        <disease id="DI-03485">
            <name>Hypertrichotic osteochondrodysplasia</name>
            <acronym>HTOCD</acronym>
            <description>A rare disorder characterized by congenital hypertrichosis, neonatal macrosomia, a distinct osteochondrodysplasia, and cardiomegaly. The hypertrichosis leads to thick scalp hair, which extends onto the forehead, and a general increase in body hair. In addition, macrocephaly and coarse facial features, including a broad nasal bridge, epicanthal folds, a wide mouth, and full lips, can be suggestive of a storage disorder. About half of affected individuals are macrosomic and edematous at birth, whereas in childhood they usually have a muscular appearance with little subcutaneous fat. Thickened calvarium, narrow thorax, wide ribs, flattened or ovoid vertebral bodies, coxa valga, osteopenia, enlarged medullary canals, and metaphyseal widening of long bones have been reported. Cardiac manifestations such as patent ductus arteriosus, ventricular hypertrophy, pulmonary hypertension, and pericardial effusions are present in approximately 80% of cases. Motor development is usually delayed due to hypotonia. Most patients have a mild speech delay, and a small percentage have learning difficulties or intellectual disability.</description>
            <dbReference type="MIM" id="239850"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="12">
        <disease id="DI-06322">
            <name>Intellectual disability and myopathy syndrome</name>
            <acronym>IDMYS</acronym>
            <description>An autosomal recessive disorder characterized by global developmental delay, mildly impaired intellectual development, hypotonia, muscle weakness and fatigue, and white matter abnormalities on brain imaging. Variable additional features may include sensorineural hearing loss, dysmorphic facies, and progressive heart disease.</description>
            <dbReference type="MIM" id="619719"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="16">May contribute to the regulation of sleep duration. An intronic variant of this gene may account for about 5% of the variation of sleep duration between individuals (PubMed:22105623). Sleep duration is influenced both by environmental and genetic factors, with an estimated heritability of about 40%. Numerous genes are expected to contribute to the regulation of sleep duration.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/139"/>
        <text>On The Other Side - Issue 139 of June 2012</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
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        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050173">
        <property type="entry name" value="ABC_transporter_C-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000388">
        <property type="entry name" value="ABCC8/9"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001475">
        <property type="entry name" value="ABCC9"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR047080">
        <property type="entry name" value="ABCC9_ATP-bd_dom1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24223">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24223:SF173">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY C MEMBER 9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00664">
        <property type="entry name" value="ABC_membrane"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01094">
        <property type="entry name" value="SULFNYLUR2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01092">
        <property type="entry name" value="SULFNYLUREAR"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90123">
        <property type="entry name" value="ABC transporter transmembrane region"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50929">
        <property type="entry name" value="ABC_TM1F"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1020">Atrial fibrillation</keyword>
    <keyword id="KW-0122">Cardiomyopathy</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093402" description="ATP-binding cassette sub-family C member 9">
        <location>
            <begin position="1"/>
            <end position="1549"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="1"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="4">
        <location>
            <begin position="31"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="52"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="4">
        <location>
            <begin position="73"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="94"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="4">
        <location>
            <begin position="102"/>
            <end position="122"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="123"/>
            <end position="132"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="4">
        <location>
            <begin position="133"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="154"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="4">
        <location>
            <begin position="168"/>
            <end position="188"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="189"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="4">
        <location>
            <begin position="302"/>
            <end position="322"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="323"/>
            <end position="350"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="4">
        <location>
            <begin position="351"/>
            <end position="371"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="372"/>
            <end position="423"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=8" evidence="4">
        <location>
            <begin position="424"/>
            <end position="444"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="445"/>
            <end position="455"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=9" evidence="4">
        <location>
            <begin position="456"/>
            <end position="476"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="477"/>
            <end position="531"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=10" evidence="4">
        <location>
            <begin position="532"/>
            <end position="552"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="553"/>
            <end position="571"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=11" evidence="4">
        <location>
            <begin position="572"/>
            <end position="592"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="593"/>
            <end position="990"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=12" evidence="4">
        <location>
            <begin position="991"/>
            <end position="1011"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="1012"/>
            <end position="1034"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=13" evidence="4">
        <location>
            <begin position="1035"/>
            <end position="1055"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="1056"/>
            <end position="1127"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=14" evidence="4">
        <location>
            <begin position="1128"/>
            <end position="1148"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="1149"/>
            <end position="1245"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=15" evidence="4">
        <location>
            <begin position="1246"/>
            <end position="1266"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="1267"/>
            <end position="1549"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1 1" evidence="4">
        <location>
            <begin position="297"/>
            <end position="597"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="3">
        <location>
            <begin position="672"/>
            <end position="912"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1 2" evidence="4">
        <location>
            <begin position="994"/>
            <end position="1274"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="3">
        <location>
            <begin position="1312"/>
            <end position="1546"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="944"/>
            <end position="967"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="5">
        <location>
            <begin position="951"/>
            <end position="966"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="705"/>
            <end position="712"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="1346"/>
            <end position="1353"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="334"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000058" description="In isoform SUR2B." evidence="15">
        <original>SSIMDAGLVLVFSEGILVECDTVPNLLAHKNGLFSTLVMTNK</original>
        <variation>HTILTADLVIVMKRGNILEYDTPESLLAQENGVFASFVRADM</variation>
        <location>
            <begin position="1508"/>
            <end position="1549"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068485" description="In HTOCD; dbSNP:rs387907230." evidence="9">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068486" description="In HTOCD; dbSNP:rs2137921501." evidence="9">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068487" description="In HTOCD; dbSNP:rs1165205076." evidence="9">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068488" description="In HTOCD; mutant channels show reduced ATP sensitivity; rat ABCC9 construct containing this mutation shows gain of function." evidence="9 10">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068489" description="In HTOCD; rat ABCC9 construct containing this mutation shows gain of function; dbSNP:rs387907211." evidence="8 10">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="478"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068490" description="In HTOCD; dbSNP:rs387907229." evidence="9">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1020"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068491" description="In HTOCD." evidence="9">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="1039"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068492" description="In HTOCD; rat ABCC9 construct containing this mutation shows gain of function; dbSNP:rs387907210." evidence="8 10">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="1043"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068493" description="In HTOCD." evidence="9">
        <original>S</original>
        <variation>Y</variation>
        <location>
            <position position="1054"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048143" description="In dbSNP:rs35404804.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="1108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068494" description="In HTOCD; dbSNP:rs387907228." evidence="9">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068495" description="In HTOCD; mutant channels show reduced ATP sensitivity; dbSNP:rs387907227." evidence="9">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068496" description="In HTOCD; mutant channels show reduced ATP sensitivity; dbSNP:rs387907209." evidence="8 9">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068497" description="In HTOCD; dbSNP:rs387907208." evidence="8 9">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083082" description="In dbSNP:rs780799175." evidence="11">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="1160"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_018483" description="In CMD1O; dbSNP:rs72559751." evidence="6">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="1513"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066210" description="In ATFB12; compromises adenine nucleotide-dependent induction of KATP current; mutant ABCC9 that is coexpressed with KCNJ11 pore generates an aberrant channel that retains ATP-induced inhibition of potassium current, but shows a blunted response to ADP; dbSNP:rs387906805." evidence="7">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="1547"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC16057/AAC16058." evidence="15" ref="1">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="586"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC16057/AAC16058." evidence="15" ref="1">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="589"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC16057/AAC16058." evidence="15" ref="1">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="1503"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P70170"/>
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    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00441"/>
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    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15034580"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="17245405"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="22608503"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22610116"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="26621776"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="31303265"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="31575858"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="9831708"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="31575858"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="22105623"/>
        </source>
    </evidence>
    <sequence length="1549" mass="174223" checksum="55508C9343AB1218" modified="2008-11-25" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-17" modified="2026-01-28" version="162" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WWZ4</accession>
    <accession>C9JZH2</accession>
    <accession>C9K035</accession>
    <accession>Q6PIQ6</accession>
    <accession>Q7Z2I9</accession>
    <accession>Q7Z7P7</accession>
    <accession>Q86TD2</accession>
    <name>ABCAA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">ATP-binding cassette sub-family A member 10</fullName>
            <ecNumber evidence="9">7.6.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ABCA10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="GeneScreen" volume="1" first="157" last="164">
            <title>Identifying and characterizing a five-gene cluster of ATP-binding cassette transporters mapping to human chromosome 17q24: a new subgroup within the ABCA subfamily.</title>
            <authorList>
                <person name="Arnould I."/>
                <person name="Schriml L.M."/>
                <person name="Prades C."/>
                <person name="Lachtermacher-Triunfol M."/>
                <person name="Schneider T."/>
                <person name="Maintoux C."/>
                <person name="Lemoine C."/>
                <person name="Debono D."/>
                <person name="Devaud C."/>
                <person name="Naudin L."/>
                <person name="Bauche S."/>
                <person name="Annat M."/>
                <person name="Annilo T."/>
                <person name="Allikmets R."/>
                <person name="Gold B."/>
                <person name="Denefle P."/>
                <person name="Rosier M."/>
                <person name="Dean M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS SER-203; VAL-287 AND THR-916</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Biochem. Biophys. Res. Commun." volume="306" first="1089" last="1098">
            <title>ABCA10, a novel cholesterol-regulated ABCA6-like ABC transporter.</title>
            <authorList>
                <person name="Wenzel J.J."/>
                <person name="Kaminski W.E."/>
                <person name="Piehler A."/>
                <person name="Heimerl S."/>
                <person name="Langmann T."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="12821155"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(03)01097-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS SER-203 AND VAL-287</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORMS 2; 3 AND 4)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Macrophage</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)</scope>
        <scope>VARIANTS SER-203 AND VAL-287</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
            <authorList>
                <person name="Zody M.C."/>
                <person name="Garber M."/>
                <person name="Adams D.J."/>
                <person name="Sharpe T."/>
                <person name="Harrow J."/>
                <person name="Lupski J.R."/>
                <person name="Nicholson C."/>
                <person name="Searle S.M."/>
                <person name="Wilming L."/>
                <person name="Young S.K."/>
                <person name="Abouelleil A."/>
                <person name="Allen N.R."/>
                <person name="Bi W."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Bugalter B.E."/>
                <person name="Butler J."/>
                <person name="Chang J.L."/>
                <person name="Chen C.-K."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="Cuomo C.A."/>
                <person name="de Jong P.J."/>
                <person name="DeCaprio D."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M."/>
                <person name="Gilbert J."/>
                <person name="Gibson R."/>
                <person name="Gnerre S."/>
                <person name="Goldstein S."/>
                <person name="Grafham D.V."/>
                <person name="Grocock R."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hart E."/>
                <person name="Norman C.H."/>
                <person name="Humphray S."/>
                <person name="Jaffe D.B."/>
                <person name="Jones M."/>
                <person name="Kamal M."/>
                <person name="Khodiyar V.K."/>
                <person name="LaButti K."/>
                <person name="Laird G."/>
                <person name="Lehoczky J."/>
                <person name="Liu X."/>
                <person name="Lokyitsang T."/>
                <person name="Loveland J."/>
                <person name="Lui A."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews L."/>
                <person name="Mauceli E."/>
                <person name="McCarroll S.A."/>
                <person name="Mihalev A.H."/>
                <person name="Mudge J."/>
                <person name="Nguyen C."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Osoegawa K."/>
                <person name="Schwartz D.C."/>
                <person name="Shaw-Smith C."/>
                <person name="Stankiewicz P."/>
                <person name="Steward C."/>
                <person name="Swarbreck D."/>
                <person name="Venkataraman V."/>
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                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
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                <person name="Hubbard T."/>
                <person name="Birren B.W."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1125-1543 (ISOFORMS 1/2)</scope>
        <source>
            <tissue>Liver</tissue>
            <tissue>Pancreatic carcinoma</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="9">Probable transporter which may play a role in macrophage lipid transport and homeostasis.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Membrane</location>
            <topology evidence="8">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WWZ4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WWZ4-2</id>
            <name>2</name>
            <name>ABCA10delta+82</name>
            <sequence type="described" ref="VSP_021061"/>
        </isoform>
        <isoform>
            <id>Q8WWZ4-3</id>
            <name>3</name>
            <name>ABCA10delta-104</name>
            <sequence type="described" ref="VSP_021062 VSP_021063"/>
        </isoform>
        <isoform>
            <id>Q8WWZ4-4</id>
            <name>4</name>
            <name>ABCA10delta-176</name>
            <sequence type="described" ref="VSP_021065 VSP_021066"/>
        </isoform>
        <isoform>
            <id>Q8WWZ4-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_021064 VSP_021067"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 6">Widely expressed. Highly expressed in skeletal muscle, heart, brain and gastrointestinal tract.</text>
    </comment>
    <comment type="induction">
        <text evidence="4">Down-regulated by cholesterol loading of macrophages.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="9"/>
    <dbReference type="EMBL" id="AY028900">
        <property type="protein sequence ID" value="AAK30025.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247065">
        <property type="protein sequence ID" value="AAO72161.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247105">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247069">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247070">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247071">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247072">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247073">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247074">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247075">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247076">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247077">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247078">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247079">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247080">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247081">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247082">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247083">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247084">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247085">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247086">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247087">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247088">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247089">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247090">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247091">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247092">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247093">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247094">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247095">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247096">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247097">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247098">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247099">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247100">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247101">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247102">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY247103">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY247104">
        <property type="protein sequence ID" value="AAO72160.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832004">
        <property type="protein sequence ID" value="CAD89903.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005495">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031026">
        <property type="protein sequence ID" value="AAH31026.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051320">
        <property type="protein sequence ID" value="AAH51320.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11684.1">
        <molecule id="Q8WWZ4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001364250.1">
        <molecule id="Q8WWZ4-1"/>
        <property type="nucleotide sequence ID" value="NM_001377321.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_525021.3">
        <molecule id="Q8WWZ4-1"/>
        <property type="nucleotide sequence ID" value="NM_080282.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8WWZ4"/>
    <dbReference type="SMR" id="Q8WWZ4"/>
    <dbReference type="BioGRID" id="115630">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8WWZ4">
        <property type="interactions" value="152"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WWZ4">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000269081"/>
    <dbReference type="TCDB" id="3.A.1.211.17">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8WWZ4">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8WWZ4"/>
    <dbReference type="PhosphoSitePlus" id="Q8WWZ4"/>
    <dbReference type="BioMuta" id="ABCA10"/>
    <dbReference type="DMDM" id="296439455"/>
    <dbReference type="jPOST" id="Q8WWZ4"/>
    <dbReference type="MassIVE" id="Q8WWZ4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000269081"/>
    <dbReference type="PeptideAtlas" id="Q8WWZ4"/>
    <dbReference type="ProteomicsDB" id="74965">
        <molecule id="Q8WWZ4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74966">
        <molecule id="Q8WWZ4-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2899">
        <property type="antibodies" value="50 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10349"/>
    <dbReference type="Ensembl" id="ENST00000269081.8">
        <molecule id="Q8WWZ4-1"/>
        <property type="protein sequence ID" value="ENSP00000269081.4"/>
        <property type="gene ID" value="ENSG00000154263.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000522406.5">
        <molecule id="Q8WWZ4-5"/>
        <property type="protein sequence ID" value="ENSP00000429853.1"/>
        <property type="gene ID" value="ENSG00000154263.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000523512.5">
        <molecule id="Q8WWZ4-3"/>
        <property type="protein sequence ID" value="ENSP00000429945.1"/>
        <property type="gene ID" value="ENSG00000154263.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000690296.1">
        <molecule id="Q8WWZ4-1"/>
        <property type="protein sequence ID" value="ENSP00000509702.1"/>
        <property type="gene ID" value="ENSG00000154263.18"/>
    </dbReference>
    <dbReference type="GeneID" id="10349"/>
    <dbReference type="KEGG" id="hsa:10349"/>
    <dbReference type="MANE-Select" id="ENST00000690296.1">
        <property type="protein sequence ID" value="ENSP00000509702.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001377321.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001364250.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010dfa.2">
        <molecule id="Q8WWZ4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30"/>
    <dbReference type="ClinPGx" id="PA24374"/>
    <dbReference type="CTD" id="10349"/>
    <dbReference type="DisGeNET" id="10349"/>
    <dbReference type="GeneCards" id="ABCA10"/>
    <dbReference type="HGNC" id="HGNC:30">
        <property type="gene designation" value="ABCA10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000154263">
        <property type="expression patterns" value="Tissue enhanced (ovary)"/>
    </dbReference>
    <dbReference type="MIM" id="612508">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000154263"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000154263"/>
    <dbReference type="eggNOG" id="KOG0059">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162673"/>
    <dbReference type="HOGENOM" id="CLU_000604_19_1_1"/>
    <dbReference type="InParanoid" id="Q8WWZ4"/>
    <dbReference type="OMA" id="LCKEQEM"/>
    <dbReference type="OrthoDB" id="8061355at2759"/>
    <dbReference type="PAN-GO" id="Q8WWZ4">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WWZ4"/>
    <dbReference type="PathwayCommons" id="Q8WWZ4"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8WWZ4"/>
    <dbReference type="Agora" id="ENSG00000154263"/>
    <dbReference type="BioGRID-ORCS" id="10349">
        <property type="hits" value="12 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCA10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="10349"/>
    <dbReference type="Pharos" id="Q8WWZ4">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WWZ4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WWZ4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000154263">
        <property type="expression patterns" value="Expressed in tibial nerve and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WWZ4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-ARBA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042626">
        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005319">
        <property type="term" value="F:lipid transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006869">
        <property type="term" value="P:lipid transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd03263">
        <property type="entry name" value="ABC_subfamily_A"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000335">
        <property type="entry name" value="ATP binding cassette subfamily A member 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000436">
        <property type="entry name" value="ATP binding cassette subfamily A member 9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
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    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
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    <dbReference type="InterPro" id="IPR026082">
        <property type="entry name" value="ABCA"/>
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    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
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    <dbReference type="InterPro" id="IPR056264">
        <property type="entry name" value="R2_ABCA1-4-like"/>
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    <dbReference type="PANTHER" id="PTHR19229:SF269">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY A MEMBER 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR19229">
        <property type="entry name" value="ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12698">
        <property type="entry name" value="ABC2_membrane_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
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    <dbReference type="Pfam" id="PF23321">
        <property type="entry name" value="R1_ABCA1"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
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    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
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    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000253572" description="ATP-binding cassette sub-family A member 10">
        <location>
            <begin position="1"/>
            <end position="1543"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="83"/>
            <end position="103"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="135"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="185"/>
            <end position="205"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="210"/>
            <end position="230"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="240"/>
            <end position="260"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="264"/>
            <end position="284"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="310"/>
            <end position="330"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="774"/>
            <end position="794"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="890"/>
            <end position="910"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="926"/>
            <end position="946"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="985"/>
            <end position="1005"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="1014"/>
            <end position="1034"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="1046"/>
            <end position="1066"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="1073"/>
            <end position="1093"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="1113"/>
            <end position="1133"/>
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    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="2">
        <location>
            <begin position="391"/>
            <end position="626"/>
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    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="2">
        <location>
            <begin position="1206"/>
            <end position="1440"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1153"/>
            <end position="1177"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="1153"/>
            <end position="1164"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="3">
        <location>
            <begin position="1165"/>
            <end position="1174"/>
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    <feature type="binding site" evidence="2">
        <location>
            <begin position="427"/>
            <end position="434"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="1239"/>
            <end position="1246"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="splice variant" id="VSP_021061" description="In isoform 2." evidence="8">
        <location>
            <begin position="1"/>
            <end position="23"/>
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    </feature>
    <feature type="splice variant" id="VSP_021062" description="In isoform 3." evidence="8">
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        <variation>GHNKSFCNGGVDISYWNKYEDTTFHF</variation>
        <location>
            <position position="67"/>
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    <feature type="splice variant" id="VSP_021063" description="In isoform 3." evidence="8">
        <location>
            <begin position="68"/>
            <end position="1543"/>
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    </feature>
    <feature type="splice variant" id="VSP_021064" description="In isoform 5." evidence="7">
        <original>IFFDIYEGQITAILGHNGAGKSTLLNILSGLSVSTEGSAT</original>
        <variation>SEERLCPAAHRLRCGERLCPAAHHLGCEERPCPAATPSGN</variation>
        <location>
            <begin position="413"/>
            <end position="452"/>
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    </feature>
    <feature type="splice variant" id="VSP_021065" description="In isoform 4." evidence="8">
        <original>S</original>
        <variation>KKNYNGIRHAKHSRHYC</variation>
        <location>
            <position position="450"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021066" description="In isoform 4." evidence="8">
        <location>
            <begin position="451"/>
            <end position="1543"/>
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    <feature type="splice variant" id="VSP_021067" description="In isoform 5." evidence="7">
        <location>
            <begin position="453"/>
            <end position="1543"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028384" description="In dbSNP:rs9909216." evidence="4 5 6">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028385" description="In dbSNP:rs11657804." evidence="4 5 6">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028386" description="In dbSNP:rs4968849." evidence="6">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="916"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055469" description="In dbSNP:rs10491178.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1322"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAD89903." evidence="8" ref="3">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAD89903." evidence="8" ref="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAD89903." evidence="8" ref="3">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAD89903." evidence="8" ref="3">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAD89903." evidence="8" ref="3">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAO72160/AAO72161 and 4; AAH51320." evidence="8" ref="2 4">
        <original>R</original>
        <variation>I</variation>
        <location>
            <position position="1216"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12821155"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="12821155"/>
        </source>
    </evidence>
    <sequence length="1543" mass="175790" checksum="47E932434314B538" modified="2010-05-18" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-07-11" modified="2026-01-28" version="192" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BZC7</accession>
    <accession>A6NED5</accession>
    <accession>Q5SPY5</accession>
    <accession>Q5W9G5</accession>
    <accession>Q76MW7</accession>
    <accession>Q9HC28</accession>
    <name>ABCA2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">ATP-binding cassette sub-family A member 2</fullName>
            <ecNumber evidence="21">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 2</fullName>
            <shortName>ATP-binding cassette 2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ABCA2</name>
        <name type="synonym">ABC2</name>
        <name type="synonym">KIAA1062</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Complete coding sequence, promoter region, and genomic structure of the human ABCA2 gene and evidence for sterol-dependent regulation in macrophages.</title>
            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="11178988"/>
            <dbReference type="DOI" id="10.1006/bbrc.2001.4305"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Cancer Res." volume="61" first="3339" last="3347">
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            <authorList>
                <person name="Vulevic B."/>
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            </authorList>
            <dbReference type="PubMed" id="11309290"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15164053"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 651-2435 (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 665-2435 (ISOFORM 1)</scope>
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            <tissue>Brain</tissue>
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        <scope>SEQUENCE REVISION</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-22 (ISOFORMS 3 AND 4)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <dbReference type="PubMed" id="15238223"/>
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        <scope>INDUCTION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
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        <scope>FUNCTION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1327 AND SER-1331</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2412</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <dbReference type="PubMed" id="21810484"/>
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        <scope>FUNCTION</scope>
    </reference>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1238</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="14">
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                <person name="Davis W. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="24201375"/>
            <dbReference type="DOI" id="10.1016/j.bbalip.2013.10.019"/>
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        <scope>FUNCTION</scope>
    </reference>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1331</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="16">
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            <title>The ATP-Binding Cassette Transporter-2 (ABCA2) Overexpression Modulates Sphingosine Levels and Transcription of the Amyloid Precursor Protein (APP) Gene.</title>
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                <person name="Davis W. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="26510981"/>
            <dbReference type="DOI" id="10.2174/156720501209151019105834"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="17">
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            <title>Substrate specificity of the HEMK2 protein glutamine methyltransferase and identification of novel substrates.</title>
            <authorList>
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                <person name="Jeltsch A."/>
            </authorList>
            <dbReference type="PubMed" id="26797129"/>
            <dbReference type="DOI" id="10.1074/jbc.m115.711952"/>
        </citation>
        <scope>METHYLATION AT GLN-271</scope>
        <scope>MUTAGENESIS OF GLN-271</scope>
    </reference>
    <reference key="18">
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            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="29302074"/>
            <dbReference type="DOI" id="10.1038/s41380-017-0012-2"/>
        </citation>
        <scope>INVOLVEMENT IN IDPOGSA</scope>
    </reference>
    <reference key="19">
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            <title>Autozygome and high throughput confirmation of disease genes candidacy.</title>
            <authorList>
                <person name="Maddirevula S."/>
                <person name="Alzahrani F."/>
                <person name="Al-Owain M."/>
                <person name="Al Muhaizea M.A."/>
                <person name="Kayyali H.R."/>
                <person name="AlHashem A."/>
                <person name="Rahbeeni Z."/>
                <person name="Al-Otaibi M."/>
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                <person name="Goljan E."/>
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                <person name="Hashem M."/>
                <person name="Shaheen R."/>
                <person name="AlShahwan S."/>
                <person name="Alfadhel M."/>
                <person name="Ben-Omran T."/>
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                <person name="Alkuraya F.S."/>
            </authorList>
            <dbReference type="PubMed" id="30237576"/>
            <dbReference type="DOI" id="10.1038/s41436-018-0138-x"/>
        </citation>
        <scope>VARIANT IDPOGSA 343-ALA--CYS-2435 DEL</scope>
        <scope>INVOLVEMENT IN IDPOGSA</scope>
    </reference>
    <comment type="function">
        <text evidence="1 7 8 9 10 11 21">Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis (Probable) (PubMed:15238223, PubMed:21810484, PubMed:24201375). May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes (PubMed:24201375). In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP (PubMed:22086926, PubMed:26510981). May play a role in myelin formation (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6">Endosome membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 6">Lysosome membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="5">Forms discrete, punctate intracellular vesicles.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BZC7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BZC7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_035283 VSP_035284"/>
        </isoform>
        <isoform>
            <id>Q9BZC7-3</id>
            <name>3</name>
            <name evidence="18">1A form</name>
            <sequence type="described" ref="VSP_040937"/>
        </isoform>
        <isoform>
            <id>Q9BZC7-4</id>
            <name evidence="18">4</name>
            <name evidence="18">1B form</name>
            <sequence type="described" ref="VSP_060910 VSP_040937"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 3</molecule>
        <text evidence="5 6">Highly expressed in the brain,peripheral blood leukocytes and ovary, whereas lower levels of expression is observed in kidney and liver.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 4</molecule>
        <text evidence="6">Weakly expressed in brain and highly in peripheral blood leukocytes.</text>
    </comment>
    <comment type="induction">
        <text evidence="7">Increased under sterol-deprived conditions and decreased by the addition of exogenous sterols.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Methylated at Gln-271 by N6AMT1.</text>
    </comment>
    <comment type="disease" evidence="13 14">
        <disease id="DI-05788">
            <name>Intellectual developmental disorder with poor growth and with or without seizures or ataxia</name>
            <acronym>IDPOGSA</acronym>
            <description>An autosomal recessive disorder characterized by global developmental delay apparent from infancy, impaired intellectual development, hypotonia, and poor overall growth with microcephaly. Additional variable features include dysmorphic features, cataracts, ataxia and seizures.</description>
            <dbReference type="MIM" id="618808"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="21"/>
    <dbReference type="EMBL" id="AF327657">
        <property type="protein sequence ID" value="AAK14334.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327705">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327658">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327659">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327660">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327661">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF327662">
        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF327663">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF327664">
        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF327672">
        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK14335.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="evidence" value="ECO:0000314"/>
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        <property type="evidence" value="ECO:0000270"/>
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        <property type="term" value="P:transmembrane transport"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="entry name" value="ABC_subfamily_A"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ATP-binding cassette, sub-family A (ABC1), member 2"/>
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        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
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    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
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        <property type="entry name" value="ABC2_TM"/>
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    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
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        <property type="entry name" value="ABC_transporter-like_CS"/>
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        <property type="entry name" value="ABCA"/>
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        <property type="entry name" value="P-loop_NTPase"/>
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        <property type="entry name" value="R2_ABCA1-4-like"/>
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    <dbReference type="PANTHER" id="PTHR19229:SF36">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY A MEMBER 2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ATP-BINDING CASSETTE TRANSPORTER SUBFAMILY A ABCA"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF12698">
        <property type="entry name" value="ABC2_membrane_3"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
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    <dbReference type="Pfam" id="PF23321">
        <property type="entry name" value="R1_ABCA1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
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    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="2"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0967">Endosome</keyword>
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    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
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    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093290" description="ATP-binding cassette sub-family A member 2">
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            <begin position="1"/>
            <end position="2435"/>
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            <begin position="22"/>
            <end position="42"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
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            <begin position="54"/>
            <end position="74"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
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            <begin position="699"/>
            <end position="719"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="750"/>
            <end position="770"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="782"/>
            <end position="802"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="813"/>
            <end position="833"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="857"/>
            <end position="877"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="893"/>
            <end position="913"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1456"/>
            <end position="1476"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1792"/>
            <end position="1812"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1841"/>
            <end position="1861"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1872"/>
            <end position="1892"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1905"/>
            <end position="1925"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="1991"/>
            <end position="2011"/>
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        <location>
            <begin position="990"/>
            <end position="1221"/>
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    <feature type="domain" description="ABC transporter 2" evidence="3">
        <location>
            <begin position="2050"/>
            <end position="2285"/>
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            <begin position="1223"/>
            <end position="1243"/>
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    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1325"/>
            <end position="1357"/>
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    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1586"/>
            <end position="1610"/>
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="1333"/>
            <end position="1342"/>
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    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="4">
        <location>
            <begin position="1589"/>
            <end position="1598"/>
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    <feature type="binding site" evidence="3">
        <location>
            <begin position="1024"/>
            <end position="1031"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
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    <feature type="binding site" evidence="3">
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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            <position position="271"/>
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        <location>
            <position position="1238"/>
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    </feature>
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            <position position="1327"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="23 26">
        <location>
            <position position="1331"/>
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            <position position="2412"/>
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        <location>
            <position position="14"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="89"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="168"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="173"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="305"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="368"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="379"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="420"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="476"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="484"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="494"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="530"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="590"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="600"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="628"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1408"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1557"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1612"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1677"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="1775"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="2054"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_060910" description="In isoform 4." evidence="18">
        <original>MGFLHQLQLLLWKNVTLKRRSP</original>
        <variation>MGRKTSRVQQGPPRSPACSAHGERSWGLEFPPFRWLLGIAGRTHLAALPPFQ</variation>
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_040937" description="In isoform 3 and isoform 4." evidence="16 17 20">
        <original>EA</original>
        <variation>EVS</variation>
        <location>
            <begin position="53"/>
            <end position="54"/>
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    </feature>
    <feature type="splice variant" id="VSP_035283" description="In isoform 2." evidence="15">
        <original>YKSRKIGRILAVDRLCLGVRPGECFGLLGVNG</original>
        <variation>GSGHVGWGLGGVGQGQGGGAPAVEVEPGWAGP</variation>
        <location>
            <begin position="2059"/>
            <end position="2090"/>
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    </feature>
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        <location>
            <begin position="2091"/>
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    <feature type="sequence variant" id="VAR_082138" description="In IDPOGSA; dbSNP:rs1588524458." evidence="14">
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            <begin position="343"/>
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    <feature type="sequence variant" id="VAR_044526" description="In dbSNP:rs908828.">
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            <position position="583"/>
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    </feature>
    <feature type="sequence variant" id="VAR_044527" description="In dbSNP:rs2090625.">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="674"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes methylation by N6AMT1." evidence="12">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="271"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAK14335." evidence="19" ref="1">
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        <location>
            <position position="2079"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAK14334/AAK14335 and 2; AAG09372." evidence="19" ref="1 2">
        <original>S</original>
        <variation>P</variation>
        <location sequence="Q9BZC7-3">
            <position position="55"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P41234"/>
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    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
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    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11309290"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15093135"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15238223"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="21810484"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22086926"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="24201375"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="26510981"/>
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    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="26797129"/>
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    <evidence type="ECO:0000269" key="13">
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            <dbReference type="PubMed" id="29302074"/>
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    <evidence type="ECO:0000269" key="14">
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            <dbReference type="PubMed" id="10470851"/>
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            <dbReference type="PubMed" id="11309290"/>
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    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="15999530"/>
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        <source>
            <dbReference type="HGNC" id="HGNC:32"/>
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    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="17081983"/>
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    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PubMed" id="24275569"/>
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    <sequence length="2435" mass="269833" checksum="D707CC83F30BE2BF" modified="2018-09-12" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="230" xmlns="https://uniprot.org/uniprot">
    <accession>P45844</accession>
    <accession>Q86SU8</accession>
    <accession>Q96L76</accession>
    <accession>Q9BXK6</accession>
    <accession>Q9BXK7</accession>
    <accession>Q9BXK8</accession>
    <accession>Q9BXK9</accession>
    <accession>Q9BXL0</accession>
    <accession>Q9BXL1</accession>
    <accession>Q9BXL2</accession>
    <accession>Q9BXL3</accession>
    <accession>Q9BXL4</accession>
    <name>ABCG1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">ATP-binding cassette sub-family G member 1</fullName>
            <ecNumber evidence="9">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 8</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>White protein homolog</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="20" type="primary">ABCG1</name>
        <name type="synonym">ABC8</name>
        <name type="synonym">WHT1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
        <scope>SUBUNIT</scope>
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        <scope>ACTIVITY REGULATION</scope>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF LYS-124</scope>
        <scope>INDUCTION</scope>
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            <dbReference type="PubMed" id="22042635"/>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PALMITOYLATION AT CYS-30; CYS-154; CYS-315; CYS-394 AND CYS-406</scope>
        <scope>MUTAGENESIS OF CYS-30; CYS-154; CYS-315; CYS-394 AND CYS-406</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INTERACTION WITH CAV1</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF TYR-491; TYR-493; TYR-498 AND TYR-499</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>SUBUNIT</scope>
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        <scope>MUTAGENESIS OF LYS-124</scope>
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    <comment type="function">
        <text evidence="9 10 13">Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP (PubMed:17408620, PubMed:24576892). The lipid efflux is ALB-dependent (PubMed:16702602). Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol (PubMed:17408620).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>7beta-hydroxycholesterol(in) + ATP + H2O = 7beta-hydroxycholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39795"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:42989"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:39796"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 13">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>an N-(acyl)-sphingosylphosphocholine(in) + ATP + H2O = an N-(acyl)-sphingosylphosphocholine(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46468"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:64583"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:46469"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>a sphingomyelin(in) + ATP + H2O = a sphingomyelin(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38903"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17636"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:38904"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="9">The cholesterol efflux is enhanced by APOA1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 13 14">Homodimer; disulfide-linked (PubMed:16702602). Homooligomer (PubMed:16702602). May form heterodimers with several heterologous partners of the ABCG subfamily. Forms heterodimers with ABCG4 (PubMed:27228027). Interacts with CAV1; this interaction regulates ABCG1-mediated cholesterol efflux (PubMed:24576892).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584087">
            <id>P45844-4</id>
        </interactant>
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
            <label>ABCG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584087">
            <id>P45844-4</id>
        </interactant>
        <interactant intactId="EBI-13059134">
            <id>Q13520</id>
            <label>AQP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25873349">
            <id>P45844-6</id>
        </interactant>
        <interactant intactId="EBI-21591415">
            <id>P13473-2</id>
            <label>LAMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25873349">
            <id>P45844-6</id>
        </interactant>
        <interactant intactId="EBI-5280197">
            <id>O75400-2</id>
            <label>PRPF40A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25873349">
            <id>P45844-6</id>
        </interactant>
        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Endoplasmic reticulum membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11">Golgi apparatus membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 13">Cell membrane</location>
        </subcellularLocation>
        <text>Predominantly localized in the intracellular compartments mainly associated with the endoplasmic reticulum (ER) and Golgi membranes.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P45844-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P45844-2</id>
            <name>2</name>
            <name>J</name>
            <sequence type="described" ref="VSP_000047 VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-3</id>
            <name>3</name>
            <name>ABDE</name>
            <sequence type="described" ref="VSP_000048 VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-4</id>
            <name>4</name>
            <name>G</name>
            <sequence type="described" ref="VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-5</id>
            <name>5</name>
            <name>F</name>
            <sequence type="described" ref="VSP_000049 VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-6</id>
            <name>6</name>
            <name>HI</name>
            <sequence type="described" ref="VSP_000046 VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-7</id>
            <name>7</name>
            <name>C</name>
            <sequence type="described" ref="VSP_000050 VSP_000051"/>
        </isoform>
        <isoform>
            <id>P45844-8</id>
            <name>8</name>
            <sequence type="described" ref="VSP_010718"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed in several tissues. Expressed in macrophages; expression is increased in macrophages from patients with Tangier disease.</text>
    </comment>
    <comment type="induction">
        <text evidence="3 4 5 8 9 10">Strongly induced in monocyte-derived macrophages during cholesterol influx. Conversely, mRNA and protein expression are suppressed by lipid efflux. Induction is mediated by the liver X receptor/retinoid X receptor (LXR/RXR) pathway. Not induced by bacterial lipopolysaccharides (LPS). Repressed by ZNF202.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Palmitoylation at Cys-315 seems important for trafficking from the endoplasmic reticulum.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC51098" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAK28841" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA95530" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB13728" version="2"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA62631" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="19">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAC00730" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="9"/>
    <dbReference type="EMBL" id="X91249">
        <property type="protein sequence ID" value="CAA62631.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB038161">
        <property type="protein sequence ID" value="BAB13728.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289137">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289138">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289139">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289140">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289141">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289142">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289143">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289144">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289145">
        <property type="protein sequence ID" value="CAC00730.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAC00730.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAC00730.1"/>
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        <property type="protein sequence ID" value="CAC00730.1"/>
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        <property type="protein sequence ID" value="CAC00730.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ289151">
        <property type="protein sequence ID" value="CAC00730.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF323658">
        <property type="protein sequence ID" value="AAK28836.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAK28836.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK28836.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAK28836.1"/>
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        <property type="protein sequence ID" value="AAK28842.1"/>
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        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0043691">
        <property type="term" value="P:reverse cholesterol transport"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0055085">
        <property type="term" value="P:transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:1990961">
        <property type="term" value="P:xenobiotic detoxification by transmembrane export across the plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd03213">
        <property type="entry name" value="ABCG_EPDR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000267">
        <property type="entry name" value="ATP-binding cassette, sub-family G (WHITE), member 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
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    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043926">
        <property type="entry name" value="ABCG_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050352">
        <property type="entry name" value="ABCG_transporters"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005284">
        <property type="entry name" value="Pigment_permease/Abcg"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR00955">
        <property type="entry name" value="3a01204"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48041">
        <property type="entry name" value="ABC TRANSPORTER G FAMILY MEMBER 28"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48041:SF90">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01061">
        <property type="entry name" value="ABC2_membrane"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19055">
        <property type="entry name" value="ABC2_membrane_7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093384" description="ATP-binding cassette sub-family G member 1">
        <location>
            <begin position="1"/>
            <end position="678"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="1"/>
            <end position="426"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="427"/>
            <end position="445"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="446"/>
            <end position="456"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="457"/>
            <end position="477"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="478"/>
            <end position="506"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="507"/>
            <end position="525"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="526"/>
            <end position="533"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="534"/>
            <end position="555"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="556"/>
            <end position="567"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="568"/>
            <end position="586"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="587"/>
            <end position="649"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="650"/>
            <end position="669"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="670"/>
            <end position="678"/>
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    </feature>
    <feature type="domain" description="ABC transporter" evidence="2">
        <location>
            <begin position="77"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-2">
        <location>
            <begin position="415"/>
            <end position="673"/>
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    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="118"/>
            <end position="125"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="12">
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="12">
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="12">
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="12">
        <location>
            <position position="394"/>
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    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="12">
        <location>
            <position position="406"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010718" description="In isoform 8." evidence="16">
        <original>MACLMAAFSVGTAMNASSYSAEMTEPKSVCVSVDEVVSSNMEATETDLLNGHLKKVDNNLTEAQRFSSLPRRAAVNIEFRDLSYSVPEGPWWRKK</original>
        <variation>MVRRGWSVCTAILLARLWCLVPTHTFLSEYPEAAEYPHPGWVYWLQMAVAPGHLRAWVMRNNVTTNIPSAFSGTLTHEEKAVLTVFTGTATAVHVQVAALASAKLESSVFVTDCVSCKIENVCDSALQGKRVPMSGLQGSSIVIMPPSNRPLASAASCTWSVQVQGGPHHLGVVAISGKVLSAAHGAGRAYGWGFPGDPMEE</variation>
        <location>
            <begin position="1"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000050" description="In isoform 7." evidence="15">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000047" description="In isoform 2." evidence="15">
        <original>MACLMAAFSVGTAM</original>
        <variation>MRISLPRAPERDGGVSASSLLDTVT</variation>
        <location>
            <begin position="1"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000048" description="In isoform 3." evidence="15">
        <original>MACLMAAFSVGTAM</original>
        <variation>MLGTQGWTKQRKPCPQ</variation>
        <location>
            <begin position="1"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000049" description="In isoform 5." evidence="15">
        <original>MACLMAAFSVGTAM</original>
        <variation>MIMRLPQPHGT</variation>
        <location>
            <begin position="1"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000046" description="In isoform 6." evidence="15">
        <location>
            <begin position="1"/>
            <end position="4"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000051" description="In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6 and isoform 7." evidence="15 17 18">
        <location>
            <begin position="375"/>
            <end position="386"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012279" evidence="7">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="668"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect." evidence="12">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Affects ATP binding. Does not affect efflux of 7beta-hydroxycholesterol. Does not affect localization at plasma membrane. Does not affect homodimerization. Decreases cholesterol and phospholipids efflux. Does not affect heretodimerization with ABCG4." evidence="9 10 14">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect." evidence="12">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly decreases ABCG1-mediated cholesterol efflux." evidence="12">
        <original>C</original>
        <variation>A</variation>
        <variation>S</variation>
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect." evidence="12">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="394"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect." evidence="12">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="406"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces interaction with CAV1; when associated with A-493. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-493." evidence="13">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="491"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces interaction with CAV1; when associated with A-491. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-491." evidence="13">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="493"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces interaction with CAV1; when associated with A-499. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-499. Affects subcellular location at plasma membrane; when associated with A-499. Affects ABCG1 traffincking to the plasma membrane; when associated with A-499." evidence="13">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ABCG1-mediated cholesterol efflux; when associated with I-499." evidence="13">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Dramatically reduces the ability of ABCG1 to mediate cholesterol efflux; when associated with I-499." evidence="13">
        <original>Y</original>
        <variation>I</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ABCG1-mediated cholesterol efflux; when associated with I-499." evidence="13">
        <original>Y</original>
        <variation>W</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces interaction with CAV1; when associated with A-498. Significantly reduces ABCG1-mediated cholesterol efflux; when associated with A-498. Affects subcellular location at plasma membrane; when associated with A-498. Affects ABCG1 traffincking to the plasma membrane; when associated with A-498." evidence="13">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ABCG1-mediated cholesterol efflux; when associated with I-498." evidence="13">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Dramatically reduces the ability of ABCG1 to mediate cholesterol efflux; when associated with I-498." evidence="13">
        <original>Y</original>
        <variation>I</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ABCG1-mediated cholesterol efflux; when associated with I-498." evidence="13">
        <original>Y</original>
        <variation>W</variation>
        <location>
            <position position="499"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAK28839/AAK28841." evidence="19" ref="4">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="38"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA62631, 4; AAK28838/AAK28839/AAK28840/AAK28841/AAK28842 and 5; AAL06598." evidence="19" ref="1 4 5">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AAC51098." evidence="19" ref="8">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="533"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="77"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="101"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="110"/>
            <end position="112"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="114"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="124"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="131"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="140"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="152"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="155"/>
            <end position="157"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="158"/>
            <end position="162"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="170"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="174"/>
            <end position="185"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="190"/>
            <end position="203"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="210"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="214"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="219"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="236"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="243"/>
            <end position="247"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="249"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="268"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="278"/>
            <end position="281"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="285"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="294"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="301"/>
            <end position="303"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="304"/>
            <end position="309"/>
        </location>
    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="310"/>
            <end position="312"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="321"/>
            <end position="329"/>
        </location>
    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="330"/>
            <end position="333"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="337"/>
            <end position="345"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="401"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="421"/>
            <end position="424"/>
        </location>
    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="425"/>
            <end position="440"/>
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    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="441"/>
            <end position="443"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="451"/>
            <end position="489"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="495"/>
            <end position="521"/>
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    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="522"/>
            <end position="526"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="533"/>
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    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="558"/>
            <end position="561"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="562"/>
            <end position="578"/>
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    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="579"/>
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    </feature>
    <feature type="turn" evidence="22">
        <location>
            <begin position="586"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="591"/>
            <end position="598"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="601"/>
            <end position="613"/>
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    <feature type="turn" evidence="22">
        <location>
            <begin position="633"/>
            <end position="635"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="636"/>
            <end position="640"/>
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    </feature>
    <feature type="helix" evidence="22">
        <location>
            <begin position="648"/>
            <end position="677"/>
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    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10639163"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10799558"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11279031"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="11350058"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11500512"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12032171"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16702602"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="17408620"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="22042635"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="23388354"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="24576892"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="27228027"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="11162488"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="11500512"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="8659545"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="19"/>
    <evidence type="ECO:0000312" key="20">
        <source>
            <dbReference type="HGNC" id="HGNC:73"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="7FDV"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="7R8D"/>
        </source>
    </evidence>
    <sequence length="678" mass="75592" checksum="B901CABDA6C19E09" modified="2001-12-05" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-09-11" modified="2026-01-28" version="135" xmlns="https://uniprot.org/uniprot">
    <accession>Q0P651</accession>
    <accession>A1A4W8</accession>
    <accession>A1A4W9</accession>
    <accession>Q9H7A7</accession>
    <name>ABD18_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Protein ABHD18</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Alpha/beta hydrolase domain-containing protein 18</fullName>
            <shortName evidence="5">Abhydrolase domain-containing protein 18</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ABHD18</name>
        <name type="synonym">C4orf29</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Coronary artery</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <source>
            <tissue>Lymph</tissue>
        </source>
    </reference>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q0P651-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q0P651-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_027893"/>
        </isoform>
        <isoform>
            <id>Q0P651-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_027892 VSP_027894"/>
        </isoform>
        <isoform>
            <id>Q0P651-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_027891 VSP_027894"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the AB hydrolase superfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AK024759">
        <property type="protein sequence ID" value="BAB14990.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034253">
        <property type="protein sequence ID" value="AAH34253.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC128142">
        <property type="protein sequence ID" value="AAI28143.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC128143">
        <property type="protein sequence ID" value="AAI28144.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS93632.1">
        <molecule id="Q0P651-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001034806.1">
        <molecule id="Q0P651-1"/>
        <property type="nucleotide sequence ID" value="NM_001039717.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352973.1">
        <molecule id="Q0P651-3"/>
        <property type="nucleotide sequence ID" value="NM_001366044.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352974.1">
        <molecule id="Q0P651-3"/>
        <property type="nucleotide sequence ID" value="NM_001366045.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352976.1">
        <molecule id="Q0P651-3"/>
        <property type="nucleotide sequence ID" value="NM_001366047.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352977.1">
        <molecule id="Q0P651-2"/>
        <property type="nucleotide sequence ID" value="NM_001366048.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_079373.2">
        <molecule id="Q0P651-4"/>
        <property type="nucleotide sequence ID" value="NM_025097.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q0P651"/>
    <dbReference type="BioGRID" id="123153">
        <property type="interactions" value="41"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q0P651">
        <property type="interactions" value="581"/>
    </dbReference>
    <dbReference type="IntAct" id="Q0P651">
        <property type="interactions" value="31"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000496010"/>
    <dbReference type="ESTHER" id="human-ABHD18">
        <property type="family name" value="ABHD18"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q0P651">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q0P651">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q0P651"/>
    <dbReference type="PhosphoSitePlus" id="Q0P651"/>
    <dbReference type="BioMuta" id="ABHD18"/>
    <dbReference type="DMDM" id="121940364"/>
    <dbReference type="jPOST" id="Q0P651"/>
    <dbReference type="MassIVE" id="Q0P651"/>
    <dbReference type="PaxDb" id="9606-ENSP00000381937"/>
    <dbReference type="PeptideAtlas" id="Q0P651"/>
    <dbReference type="ProteomicsDB" id="58769">
        <molecule id="Q0P651-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58770">
        <molecule id="Q0P651-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58771">
        <molecule id="Q0P651-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58772">
        <molecule id="Q0P651-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q0P651"/>
    <dbReference type="Antibodypedia" id="64973">
        <property type="antibodies" value="82 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000444616.5">
        <molecule id="Q0P651-1"/>
        <property type="protein sequence ID" value="ENSP00000397229.1"/>
        <property type="gene ID" value="ENSG00000164074.18"/>
    </dbReference>
    <dbReference type="GeneID" id="80167"/>
    <dbReference type="KEGG" id="hsa:80167"/>
    <dbReference type="UCSC" id="uc021xrt.2">
        <molecule id="Q0P651-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:26111"/>
    <dbReference type="ClinPGx" id="PA147358673"/>
    <dbReference type="CTD" id="80167"/>
    <dbReference type="GeneCards" id="ABHD18"/>
    <dbReference type="HGNC" id="HGNC:26111">
        <property type="gene designation" value="ABHD18"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164074">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000164074"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000164074"/>
    <dbReference type="eggNOG" id="KOG1551">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000014635"/>
    <dbReference type="HOGENOM" id="CLU_035640_0_0_1"/>
    <dbReference type="InParanoid" id="Q0P651"/>
    <dbReference type="OMA" id="MACLACT"/>
    <dbReference type="OrthoDB" id="9987145at2759"/>
    <dbReference type="PAN-GO" id="Q0P651">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q0P651"/>
    <dbReference type="PathwayCommons" id="Q0P651"/>
    <dbReference type="SignaLink" id="Q0P651"/>
    <dbReference type="Agora" id="ENSG00000164074"/>
    <dbReference type="ChiTaRS" id="ABHD18">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="Q0P651">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q0P651"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="Q0P651">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000164074">
        <property type="expression patterns" value="Expressed in buccal mucosa cell and 189 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q0P651">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019149">
        <property type="entry name" value="ABHD18"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13617">
        <property type="entry name" value="PROTEIN ABHD18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13617:SF14">
        <property type="entry name" value="PROTEIN ABHD18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF09752">
        <property type="entry name" value="ABHD18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="1">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000301960" description="Protein ABHD18">
        <location>
            <begin position="25"/>
            <end position="414"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027891" description="In isoform 4." evidence="2">
        <location>
            <begin position="1"/>
            <end position="203"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027892" description="In isoform 3." evidence="3">
        <location>
            <begin position="1"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027893" description="In isoform 2." evidence="3">
        <original>MGVSKLDILYRRLLLTKLFIRGWGRPEDLKRLFEFRKMIGNRERCQNLVSSDYPVHIDKIEEQSDCKILDGHFVSPMAHYVPDIMPIESVIARF</original>
        <variation>MLDTNLILLPLF</variation>
        <location>
            <begin position="1"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_027894" description="In isoform 3 and isoform 4." evidence="2 3">
        <original>T</original>
        <variation>TGVLSKSINWRELEKQYYTQTVYEEEIIHMLEYCG</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB14990." evidence="4" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location sequence="Q0P651-4">
            <position position="36"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000303" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:26111"/>
        </source>
    </evidence>
    <sequence length="414" mass="46954" checksum="D62F491F23A02D4C" modified="2006-09-19" version="1" precursor="true">MGVSKLDILYRRLLLTKLFIRGWGRPEDLKRLFEFRKMIGNRERCQNLVSSDYPVHIDKIEEQSDCKILDGHFVSPMAHYVPDIMPIESVIARFQFIVPKEWNSKYRPVCIHLAGTGDHHYWRRRTLMARPMIKEARMASLLLENPYYGCRKPKDQVRSSLKNVSDLFVMGGALVLESAALLHWLEREGYGPLGMTGISMGGHMASLAVSNWPKPMPLIPCLSWSTASGVFTTTDSFKMGQEFVKHFTSSADKLTNLNLVSRTLNLDISNQVVSQKPADCHNSSKTSVSATSEGLLLQDTSKMKRFNQTLSTNKSGYTSRNPQSYHLLSKEQSRNSLRKESLIFMKGVMDECTHVANFSVPVDPSLIIVVQAKEDAYIPRTGVRSLQEIWPGCEIRYLEGGHISAYLFKQGLFR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-11-28" modified="2026-01-28" version="183" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N2K0</accession>
    <accession>A6NED4</accession>
    <accession>A6NJ90</accession>
    <accession>A8K450</accession>
    <accession>B4DE71</accession>
    <accession>Q5T710</accession>
    <accession>Q5T711</accession>
    <accession>Q96CR1</accession>
    <accession>Q9BX05</accession>
    <accession>Q9NPX7</accession>
    <accession>Q9UFV6</accession>
    <name>ABD12_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="22">Lysophosphatidylserine lipase ABHD12</fullName>
            <ecNumber evidence="13">3.1.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="22">2-arachidonoylglycerol hydrolase ABHD12</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22">Abhydrolase domain-containing protein 12</fullName>
            <shortName evidence="20 21">hABHD12</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22">Monoacylglycerol lipase ABHD12</fullName>
            <ecNumber evidence="5 13">3.1.1.23</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22">Oxidized phosphatidylserine lipase ABHD12</fullName>
            <ecNumber evidence="15">3.1.-.-</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="19 25" type="primary">ABHD12</name>
        <name evidence="25" type="synonym">C20orf22</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>INVOLVEMENT IN PHARC</scope>
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            <dbReference type="PubMed" id="24027063"/>
            <dbReference type="DOI" id="10.1002/humu.22437"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INVOLVEMENT IN PHARC</scope>
        <scope>VARIANT PHARC 377-LYS--HIS-398 DEL</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="PLoS ONE" volume="9" first="E98286" last="E98286">
            <title>Discovery of triterpenoids as reversible inhibitors of alpha/beta-hydrolase domain containing 12 (ABHD12).</title>
            <authorList>
                <person name="Parkkari T."/>
                <person name="Haavikko R."/>
                <person name="Laitinen T."/>
                <person name="Navia-Paldanius D."/>
                <person name="Rytilahti R."/>
                <person name="Vaara M."/>
                <person name="Lehtonen M."/>
                <person name="Alakurtti S."/>
                <person name="Yli-Kauhaluoma J."/>
                <person name="Nevalainen T."/>
                <person name="Savinainen J.R."/>
                <person name="Laitinen J.T."/>
            </authorList>
            <dbReference type="PubMed" id="24879289"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0098286"/>
        </citation>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2014" name="PLoS ONE" volume="9" first="E109869" last="E109869">
            <title>Biochemical and pharmacological characterization of the human lymphocyte antigen B-associated transcript 5 (BAT5/ABHD16A).</title>
            <authorList>
                <person name="Savinainen J.R."/>
                <person name="Patel J.Z."/>
                <person name="Parkkari T."/>
                <person name="Navia-Paldanius D."/>
                <person name="Marjamaa J.J."/>
                <person name="Laitinen T."/>
                <person name="Nevalainen T."/>
                <person name="Laitinen J.T."/>
            </authorList>
            <dbReference type="PubMed" id="25290914"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0109869"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2015" name="Ann. Otol. Rhinol. Laryngol." volume="124" first="77" last="83">
            <title>Novel ABHD12 mutations in PHARC patients: the differential diagnosis of deaf-blindness.</title>
            <authorList>
                <person name="Yoshimura H."/>
                <person name="Hashimoto T."/>
                <person name="Murata T."/>
                <person name="Fukushima K."/>
                <person name="Sugaya A."/>
                <person name="Nishio S.Y."/>
                <person name="Usami S."/>
            </authorList>
            <dbReference type="PubMed" id="25743180"/>
            <dbReference type="DOI" id="10.1177/0003489415574513"/>
        </citation>
        <scope>INVOLVEMENT IN PHARC</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2018" name="J. Biol. Chem." volume="293" first="16953" last="16963">
            <title>Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids.</title>
            <authorList>
                <person name="Joshi A."/>
                <person name="Shaikh M."/>
                <person name="Singh S."/>
                <person name="Rajendran A."/>
                <person name="Mhetre A."/>
                <person name="Kamat S.S."/>
            </authorList>
            <dbReference type="PubMed" id="30237167"/>
            <dbReference type="DOI" id="10.1074/jbc.ra118.005640"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>MUTAGENESIS OF SER-246</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2018" name="J. Neurol. Sci." volume="387" first="134" last="138">
            <title>Phenotypical features of two patients diagnosed with PHARC syndrome and carriers of a new homozygous mutation in the ABHD12 gene.</title>
            <authorList>
                <person name="Frasquet M."/>
                <person name="Lupo V."/>
                <person name="Chumillas M.J."/>
                <person name="Vazquez-Costa J.F."/>
                <person name="Espinos C."/>
                <person name="Sevilla T."/>
            </authorList>
            <dbReference type="PubMed" id="29571850"/>
            <dbReference type="DOI" id="10.1016/j.jns.2018.02.021"/>
        </citation>
        <scope>INVOLVEMENT IN PHARC</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2018" name="Nat. Chem. Biol." volume="14" first="1099" last="1108">
            <title>Selective blockade of the lyso-PS lipase ABHD12 stimulates immune responses in vivo.</title>
            <authorList>
                <person name="Ogasawara D."/>
                <person name="Ichu T.A."/>
                <person name="Vartabedian V.F."/>
                <person name="Benthuysen J."/>
                <person name="Jing H."/>
                <person name="Reed A."/>
                <person name="Ulanovskaya O.A."/>
                <person name="Hulce J.J."/>
                <person name="Roberts A."/>
                <person name="Brown S."/>
                <person name="Rosen H."/>
                <person name="Teijaro J.R."/>
                <person name="Cravatt B.F."/>
            </authorList>
            <dbReference type="PubMed" id="30420694"/>
            <dbReference type="DOI" id="10.1038/s41589-018-0155-8"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2019" name="J. Med. Chem." volume="62" first="1643" last="1656">
            <title>Discovery and optimization of selective and in vivo active inhibitors of the lysophosphatidylserine lipase alpha/beta-hydrolase domain-containing 12 (ABHD12).</title>
            <authorList>
                <person name="Ogasawara D."/>
                <person name="Ichu T.A."/>
                <person name="Jing H."/>
                <person name="Hulce J.J."/>
                <person name="Reed A."/>
                <person name="Ulanovskaya O.A."/>
                <person name="Cravatt B.F."/>
            </authorList>
            <dbReference type="PubMed" id="30720278"/>
            <dbReference type="DOI" id="10.1021/acs.jmedchem.8b01958"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2019" name="Nat. Chem. Biol." volume="15" first="169" last="178">
            <title>A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase.</title>
            <authorList>
                <person name="Kelkar D.S."/>
                <person name="Ravikumar G."/>
                <person name="Mehendale N."/>
                <person name="Singh S."/>
                <person name="Joshi A."/>
                <person name="Sharma A.K."/>
                <person name="Mhetre A."/>
                <person name="Rajendran A."/>
                <person name="Chakrapani H."/>
                <person name="Kamat S.S."/>
            </authorList>
            <dbReference type="PubMed" id="30643283"/>
            <dbReference type="DOI" id="10.1038/s41589-018-0195-0"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF SER-246</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2014" name="Ophthalmology" volume="121" first="1620" last="1627">
            <title>Exome sequencing extends the phenotypic spectrum for ABHD12 mutations: from syndromic to nonsyndromic retinal degeneration.</title>
            <authorList>
                <person name="Nishiguchi K.M."/>
                <person name="Avila-Fernandez A."/>
                <person name="van Huet R.A."/>
                <person name="Corton M."/>
                <person name="Perez-Carro R."/>
                <person name="Martin-Garrido E."/>
                <person name="Lopez-Molina M.I."/>
                <person name="Blanco-Kelly F."/>
                <person name="Hoefsloot L.H."/>
                <person name="van Zelst-Stams W.A."/>
                <person name="Garcia-Ruiz P.J."/>
                <person name="Del Val J."/>
                <person name="Di Gioia S.A."/>
                <person name="Klevering B.J."/>
                <person name="van de Warrenburg B.P."/>
                <person name="Vazquez C."/>
                <person name="Cremers F.P."/>
                <person name="Garcia-Sandoval B."/>
                <person name="Hoyng C.B."/>
                <person name="Collin R.W."/>
                <person name="Rivolta C."/>
                <person name="Ayuso C."/>
            </authorList>
            <dbReference type="PubMed" id="24697911"/>
            <dbReference type="DOI" id="10.1016/j.ophtha.2014.02.008"/>
        </citation>
        <scope>VARIANTS PHARC 159-TRP--HIS-398 DEL; PRO-186; ILE-202 AND GLN-372</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2017" name="Neurobiol. Dis." volume="98" first="36" last="51">
            <title>Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.</title>
            <authorList>
                <person name="Tingaud-Sequeira A."/>
                <person name="Raldua D."/>
                <person name="Lavie J."/>
                <person name="Mathieu G."/>
                <person name="Bordier M."/>
                <person name="Knoll-Gellida A."/>
                <person name="Rambeau P."/>
                <person name="Coupry I."/>
                <person name="Andre M."/>
                <person name="Malm E."/>
                <person name="Moeller C."/>
                <person name="Andreasson S."/>
                <person name="Rendtorff N.D."/>
                <person name="Tranebjaerg L."/>
                <person name="Koenig M."/>
                <person name="Lacombe D."/>
                <person name="Goizet C."/>
                <person name="Babin P.J."/>
            </authorList>
            <dbReference type="PubMed" id="27890673"/>
            <dbReference type="DOI" id="10.1016/j.nbd.2016.11.008"/>
        </citation>
        <scope>VARIANT PHARC ARG-253</scope>
        <scope>CHARACTERIZATION OF VARIANTS PHARC ILE-202; ARG-253 AND 352-ARG--HIS-398 DEL</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 6 9 13 14 15 16">Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed:30237167, PubMed:30420694, PubMed:30643283, PubMed:30720278). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:22969151, PubMed:24027063). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 13">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40499"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:64765"/>
            <dbReference type="ChEBI" id="CHEBI:74617"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9 13">
            <dbReference type="Rhea" id="RHEA:40500"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = sn-glycero-3-phospho-(1'-sn-glycerol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44584"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:64717"/>
            <dbReference type="ChEBI" id="CHEBI:72828"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = sn-glycero-3-phospho-1D-myo-inositol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44588"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:58444"/>
            <dbReference type="ChEBI" id="CHEBI:78762"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40895"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:74971"/>
            <dbReference type="ChEBI" id="CHEBI:143890"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41091"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28610"/>
            <dbReference type="ChEBI" id="CHEBI:75757"/>
            <dbReference type="ChEBI" id="CHEBI:295975"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 13">
            <text>2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38491"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:73990"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 13">
            <dbReference type="Rhea" id="RHEA:38492"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13">
            <text>1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44552"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:64765"/>
            <dbReference type="ChEBI" id="CHEBI:75020"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:44553"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 13">
            <text>2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:26132"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:52392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 13">
            <dbReference type="Rhea" id="RHEA:26133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 13">
            <text>Hydrolyzes glycerol monoesters of long-chain fatty acids.</text>
            <dbReference type="EC" id="3.1.1.23"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>1-decanoylglycerol + H2O = decanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44320"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:75547"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:44321"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44316"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:75539"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:44317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44312"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:75562"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:44313"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 13">
            <text>2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39963"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:75455"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 13">
            <dbReference type="Rhea" id="RHEA:39964"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 13">
            <text>1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:75342"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 13">
            <dbReference type="Rhea" id="RHEA:38488"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44732"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75457"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:44733"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 9 13">
            <text>1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44728"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:75612"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 9 13">
            <dbReference type="Rhea" id="RHEA:44729"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 9">
            <text>1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:48428"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75568"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5 9">
            <dbReference type="Rhea" id="RHEA:48429"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13">
            <text>1-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39959"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:69081"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:39960"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13">
            <text>1-octadecanoylglycerol + H2O = octadecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38363"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:75555"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:38364"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>1-octadecanoyl-2-(9,10-epoxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 9,10-epoxyoctadecanoate + 1-octadecanoyl-sn-glycero-3-phosphoserine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59364"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:84467"/>
            <dbReference type="ChEBI" id="CHEBI:85195"/>
            <dbReference type="ChEBI" id="CHEBI:143087"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:59365"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>1-octadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + 10-hydroxyoctadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59368"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:84467"/>
            <dbReference type="ChEBI" id="CHEBI:143088"/>
            <dbReference type="ChEBI" id="CHEBI:143089"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:59369"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15">
            <text>1-hexadecanoyl-2-(10-hydroxyoctadecanoyl)-sn-glycero-3-phospho-L-serine + H2O = 10-hydroxyoctadecanoate + 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59372"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:75020"/>
            <dbReference type="ChEBI" id="CHEBI:143089"/>
            <dbReference type="ChEBI" id="CHEBI:143094"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:59373"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="8 14 16">Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea) (PubMed:30420694, PubMed:30720278). Reversibly inhibited by triterpenoids, but with rather low potency (PubMed:24879289).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">117 uM for 2-arachidonoyglycerol</KM>
            <Vmax evidence="5">42.0 nmol/min/mg enzyme toward 2-arachidonoyglycerol</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="5">Optimum pH is 7.2-9 with 2-arachidonoyglycerol as substrate.</text>
        </phDependence>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13">Endoplasmic reticulum membrane</location>
            <topology evidence="2">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N2K0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N2K0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009097"/>
        </isoform>
        <isoform>
            <id>Q8N2K0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_037372"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="13">Glycosylated; glycosylation is required for optimal activity.</text>
    </comment>
    <comment type="disease" evidence="3 4 6 7 10 11 12">
        <disease id="DI-02920">
            <name>Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract</name>
            <acronym>PHARC</acronym>
            <description>A slowly progressive neurologic disorder with a variable phenotype resembling Refsum disease. Clinical features include sensorineural hearing loss, visual problems related to cataracts, retinitis pigmentosa, pes cavus, ataxic and/or spastic gait disturbances with a progressive sensorimotor peripheral neuropathy. Other features include hyporeflexia, hyperreflexia, extensor plantar responses.</description>
            <dbReference type="MIM" id="612674"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="22">Belongs to the serine esterase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">A family suffering from Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) was initially clinically diagnosed with Usher syndrome type 3 (PubMed:22938382). Reexamination of one affected member of this family revealed ataxia but not polyneuropathy, demonstrating the phenotypic heterogeneity in PHARC and the need for careful neurological assessments to distinguish this disease from other neuropathic disorders (PubMed:22938382).</text>
    </comment>
    <dbReference type="EC" id="3.1.-.-" evidence="13 15"/>
    <dbReference type="EC" id="3.1.1.23" evidence="5 13"/>
    <dbReference type="EMBL" id="AK075023">
        <property type="protein sequence ID" value="BAC11357.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290815">
        <property type="protein sequence ID" value="BAF83504.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293495">
        <property type="protein sequence ID" value="BAG56982.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121772">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL353812">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471133">
        <property type="protein sequence ID" value="EAX10089.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014049">
        <property type="protein sequence ID" value="AAH14049.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL117442">
        <property type="protein sequence ID" value="CAB55927.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13172.1">
        <molecule id="Q8N2K0-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42857.1">
        <molecule id="Q8N2K0-1"/>
    </dbReference>
    <dbReference type="PIR" id="T17237">
        <property type="entry name" value="T17237"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035937.1">
        <molecule id="Q8N2K0-1"/>
        <property type="nucleotide sequence ID" value="NM_001042472.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056415.1">
        <molecule id="Q8N2K0-2"/>
        <property type="nucleotide sequence ID" value="NM_015600.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8N2K0"/>
    <dbReference type="SMR" id="Q8N2K0"/>
    <dbReference type="BioGRID" id="117541">
        <property type="interactions" value="144"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8N2K0">
        <property type="interactions" value="1678"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N2K0">
        <property type="interactions" value="92"/>
    </dbReference>
    <dbReference type="MINT" id="Q8N2K0"/>
    <dbReference type="STRING" id="9606.ENSP00000365725"/>
    <dbReference type="BindingDB" id="Q8N2K0"/>
    <dbReference type="ChEMBL" id="CHEMBL5516"/>
    <dbReference type="DrugCentral" id="Q8N2K0"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="3070"/>
    <dbReference type="SwissLipids" id="SLP:000001043"/>
    <dbReference type="ESTHER" id="human-ABHD12">
        <property type="family name" value="ABHD12-PHARC"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.939"/>
    <dbReference type="GlyConnect" id="1517">
        <property type="glycosylation" value="3 N-Linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q8N2K0">
        <property type="glycosylation" value="2 sites, 4 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8N2K0">
        <property type="glycosylation" value="2 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8N2K0"/>
    <dbReference type="PhosphoSitePlus" id="Q8N2K0"/>
    <dbReference type="SwissPalm" id="Q8N2K0"/>
    <dbReference type="BioMuta" id="ABHD12"/>
    <dbReference type="DMDM" id="38604894"/>
    <dbReference type="jPOST" id="Q8N2K0"/>
    <dbReference type="MassIVE" id="Q8N2K0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000365725"/>
    <dbReference type="PeptideAtlas" id="Q8N2K0"/>
    <dbReference type="ProteomicsDB" id="71711">
        <molecule id="Q8N2K0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71712">
        <molecule id="Q8N2K0-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71713">
        <molecule id="Q8N2K0-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8N2K0"/>
    <dbReference type="Antibodypedia" id="10033">
        <property type="antibodies" value="180 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="26090"/>
    <dbReference type="Ensembl" id="ENST00000339157.10">
        <molecule id="Q8N2K0-1"/>
        <property type="protein sequence ID" value="ENSP00000341408.5"/>
        <property type="gene ID" value="ENSG00000100997.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000376542.8">
        <molecule id="Q8N2K0-2"/>
        <property type="protein sequence ID" value="ENSP00000365725.3"/>
        <property type="gene ID" value="ENSG00000100997.21"/>
    </dbReference>
    <dbReference type="GeneID" id="26090"/>
    <dbReference type="KEGG" id="hsa:26090"/>
    <dbReference type="MANE-Select" id="ENST00000339157.10">
        <property type="protein sequence ID" value="ENSP00000341408.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001042472.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001035937.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002wuq.4">
        <molecule id="Q8N2K0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15868"/>
    <dbReference type="ClinPGx" id="PA25738"/>
    <dbReference type="CTD" id="26090"/>
    <dbReference type="DisGeNET" id="26090"/>
    <dbReference type="GeneCards" id="ABHD12"/>
    <dbReference type="GeneReviews" id="ABHD12"/>
    <dbReference type="HGNC" id="HGNC:15868">
        <property type="gene designation" value="ABHD12"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100997">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABHD12"/>
    <dbReference type="MIM" id="612674">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="613599">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000100997"/>
    <dbReference type="Orphanet" id="171848">
        <property type="disease" value="Polyneuropathy-hearing loss-ataxia-retinitis pigmentosa-cataract syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000100997"/>
    <dbReference type="eggNOG" id="KOG1552">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160517"/>
    <dbReference type="HOGENOM" id="CLU_029375_1_0_1"/>
    <dbReference type="InParanoid" id="Q8N2K0"/>
    <dbReference type="OMA" id="YELHNCL"/>
    <dbReference type="OrthoDB" id="10249433at2759"/>
    <dbReference type="PAN-GO" id="Q8N2K0">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N2K0"/>
    <dbReference type="PathwayCommons" id="Q8N2K0"/>
    <dbReference type="Reactome" id="R-HSA-426048">
        <property type="pathway name" value="Arachidonate production from DAG"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8N2K0"/>
    <dbReference type="Agora" id="ENSG00000100997"/>
    <dbReference type="BioGRID-ORCS" id="26090">
        <property type="hits" value="18 hits in 1159 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD12">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="26090"/>
    <dbReference type="Pharos" id="Q8N2K0">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8N2K0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8N2K0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000100997">
        <property type="expression patterns" value="Expressed in C1 segment of cervical spinal cord and 184 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8N2K0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032281">
        <property type="term" value="C:AMPA glutamate receptor complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032839">
        <property type="term" value="C:dendrite cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004622">
        <property type="term" value="F:phosphatidylcholine lysophospholipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120560">
        <property type="term" value="F:phosphatidylserine lysophospholipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004620">
        <property type="term" value="F:phospholipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046464">
        <property type="term" value="P:acylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007628">
        <property type="term" value="P:adult walking behavior"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019369">
        <property type="term" value="P:arachidonate metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046475">
        <property type="term" value="P:glycerophospholipid catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052651">
        <property type="term" value="P:monoacylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006660">
        <property type="term" value="P:phosphatidylserine catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009395">
        <property type="term" value="P:phospholipid catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050727">
        <property type="term" value="P:regulation of inflammatory response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010996">
        <property type="term" value="P:response to auditory stimulus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000069">
        <property type="entry name" value="monoacylglycerol lipase ABHD12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF61">
        <property type="entry name" value="LYSOPHOSPHATIDYLSERINE LIPASE ABHD12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0898">Cataract</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0622">Neuropathy</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0682">Retinitis pigmentosa</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000079413" description="Lysophosphatidylserine lipase ABHD12">
        <location>
            <begin position="1"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="1"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="75"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="96"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="23 24">
        <location>
            <position position="246"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="23">
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="23">
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="123"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037372" description="In isoform 3." evidence="17">
        <location>
            <begin position="11"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009097" description="In isoform 2." evidence="18">
        <original>EFLGKSEPEHQH</original>
        <variation>PQQGPGSSPDPSMWSELV</variation>
        <location>
            <begin position="387"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081587" description="In PHARC." evidence="4">
        <location>
            <begin position="65"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081588" description="In PHARC; uncertain significance." evidence="7">
        <location>
            <begin position="159"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081589" description="In PHARC; uncertain significance; dbSNP:rs587777604." evidence="7">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081590" description="In PHARC; uncertain significance; abolished monoacyglycerol lipase activity." evidence="7 11">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081591" description="In PHARC; abolished monoacyglycerol lipase activity; dbSNP:rs772987424." evidence="11">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050630" description="In dbSNP:rs746748.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="349"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081592" description="In PHARC; abolished monoacyglycerol lipase activity." evidence="3 11">
        <location>
            <begin position="352"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081593" description="In PHARC; uncertain significance; dbSNP:rs587777602." evidence="7">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081594" description="In PHARC." evidence="6">
        <location>
            <begin position="377"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of lipase activity." evidence="5 13 15">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="246"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of 2-arachidonoyglycerol hydrolase activity." evidence="5">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of 2-arachidonoyglycerol hydrolase activity." evidence="5">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF83504." evidence="22" ref="1">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC11357." evidence="22" ref="1">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q99LR1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="20797687"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="22938382"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="22969151"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="24027063"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24697911"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="24879289"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="25290914"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="25743180"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="27890673"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="29571850"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="30237167"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="30420694"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="30643283"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="30720278"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="20797687"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="30237167"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="30643283"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="22"/>
    <evidence type="ECO:0000305" key="23">
        <source>
            <dbReference type="PubMed" id="22969151"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="24">
        <source>
            <dbReference type="PubMed" id="30237167"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="25">
        <source>
            <dbReference type="HGNC" id="HGNC:15868"/>
        </source>
    </evidence>
    <sequence length="398" mass="45097" checksum="E21425C1412B5607" modified="2003-11-28" version="2">MRKRTEPVALEHERCAAAGSSSSGSAAAALDADCRLKQNLRLTGPAAAEPRCAADAGMKRALGRRKGVWLRLRKILFCVLGLYIAIPFLIKLCPGIQAKLIFLNFVRVPYFIDLKKPQDQGLNHTCNYYLQPEEDVTIGVWHTVPAVWWKNAQGKDQMWYEDALASSHPIILYLHGNAGTRGGDHRVELYKVLSSLGYHVVTFDYRGWGDSVGTPSERGMTYDALHVFDWIKARSGDNPVYIWGHSLGTGVATNLVRRLCERETPPDALILESPFTNIREEAKSHPFSVIYRYFPGFDWFFLDPITSSGIKFANDENVKHISCPLLILHAEDDPVVPFQLGRKLYSIAAPARSFRDFKVQFVPFHSDLGYRHKYIYKSPELPRILREFLGKSEPEHQH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-12-05" modified="2026-01-28" version="185" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H172</accession>
    <accession>A8K1B5</accession>
    <accession>Q8WWH0</accession>
    <accession>Q8WWH1</accession>
    <accession>Q8WWH2</accession>
    <name>ABCG4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family G member 4</fullName>
            <ecNumber evidence="7 9">7.6.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="14" type="primary">ABCG4</name>
        <name type="synonym">WHITE2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>The human ABCG4 gene is regulated by oxysterols and retinoids in monocyte-derived macrophages.</title>
            <authorList>
                <person name="Engel T."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>MISCELLANEOUS</scope>
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    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Tanai H."/>
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                <person name="Ono Y."/>
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                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
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                <person name="Kumagai A."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="3">
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="Cytogenet. Cell Genet." volume="94" first="196" last="201">
            <title>Human and mouse orthologs of a new ATP-binding cassette gene, ABCG4.</title>
            <authorList>
                <person name="Annilo T."/>
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                <person name="Rzhetsky A."/>
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            </authorList>
            <dbReference type="PubMed" id="11856881"/>
            <dbReference type="DOI" id="10.1159/000048816"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-118 (ISOFORMS 2; 3 AND 4)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2002" name="Biochim. Biophys. Acta" volume="1591" first="175" last="179">
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            <authorList>
                <person name="Oldfield S."/>
                <person name="Lowry C."/>
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                <person name="Lightman S."/>
            </authorList>
            <dbReference type="PubMed" id="12183068"/>
            <dbReference type="DOI" id="10.1016/s0167-4889(02)00269-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 20-646 (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Spinal ganglion</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Biochem. Biophys. Res. Commun." volume="320" first="860" last="867">
            <title>Functional expression and characterization of the human ABCG1 and ABCG4 proteins: indications for heterodimerization.</title>
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                <person name="Cserepes J."/>
                <person name="Szentpetery Z."/>
                <person name="Seres L."/>
                <person name="Ozvegy-Laczka C."/>
                <person name="Langmann T."/>
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                <person name="Glavinas H."/>
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                <person name="Homolya L."/>
                <person name="Varadi A."/>
                <person name="Sarkadi B."/>
                <person name="Elkind N.B."/>
            </authorList>
            <dbReference type="PubMed" id="15240127"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2004.06.037"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF LYS-108</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2016" name="PLoS ONE" volume="11" first="e0156516" last="e0156516">
            <title>Functional Cooperativity between ABCG4 and ABCG1 Isoforms.</title>
            <authorList>
                <person name="Hegyi Z."/>
                <person name="Homolya L."/>
            </authorList>
            <dbReference type="PubMed" id="27228027"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0156516"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF LYS-108</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ABCG1</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2021" name="Biochim. Biophys. Acta" volume="1865" first="129769" last="129769">
            <title>Regulation of ABCG4 transporter expression by sterols and LXR ligands.</title>
            <authorList>
                <person name="Yang A."/>
                <person name="Alrosan A.Z."/>
                <person name="Sharpe L.J."/>
                <person name="Brown A.J."/>
                <person name="Callaghan R."/>
                <person name="Gelissen I.C."/>
            </authorList>
            <dbReference type="PubMed" id="33141061"/>
            <dbReference type="DOI" id="10.1016/j.bbagen.2020.129769"/>
        </citation>
        <scope>INDUCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 7 8 9">ATP-dependent transporter of the ATP-binding cassette (ABC) family that may be involved in the cellular efflux of sterols, in particular cholesterol and desmosterol (a cholesterol precursor), to high-density lipoprotein (HDL) (PubMed:15240127, PubMed:33141061). May play an important role in the removal of amyloid-beta peptides from brain, in a process that can be antagonized by desmosterol. However it is unclear whether ABCG4 can directly transport amyloid-beta peptides or whether peptide export may be facilitated due to changes in the membrane lipid environment (By similarity). Induces apoptosis in various cells (PubMed:27228027).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>desmosterol(in) + ATP + H2O = desmosterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67932"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17737"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:67933"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="8 12">Half-transporter that forms a functional transporter via homo- or heterodimerization. Homodimer (PubMed:27228027). Heterodimers with ABCG1 (Probable) (PubMed:27228027).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-8584087">
            <id>P45844-4</id>
            <label>ABCG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-13345167">
            <id>Q8TDT2</id>
            <label>GPR152</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-742388">
            <id>Q9H8W4</id>
            <label>PLEKHF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-744081">
            <id>Q96EQ0</id>
            <label>SGTB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-12903814">
            <id>O95807</id>
            <label>TMEM50A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8584118">
            <id>Q9H172</id>
        </interactant>
        <interactant intactId="EBI-720609">
            <id>O76024</id>
            <label>WFS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasmic vesicle membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endosome membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H172-1</id>
            <name>1</name>
            <name>B</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H172-2</id>
            <name>2</name>
            <name>T3</name>
            <name>T4</name>
            <sequence type="described" ref="VSP_054267"/>
        </isoform>
        <isoform>
            <id>Q9H172-3</id>
            <name>3</name>
            <name>M</name>
            <name>T1</name>
            <sequence type="described" ref="VSP_054268"/>
        </isoform>
        <isoform>
            <id>Q9H172-4</id>
            <name>4</name>
            <name>T2</name>
            <sequence type="described" ref="VSP_054266"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Expressed specifically in the brain and the eye.</text>
    </comment>
    <comment type="induction">
        <text evidence="9">Protein expression is stabilized by cellular cholesterol status and cholesterol synthesis intermediates desmosterol, lathosterol and lanosterol.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1 4 9">Whether ABCG4 is an LXR target gene, is still under debate. Studies performed in monocytes, and in one astrocyte cell line indicated that ABCG4 expression could be up-regulated by oxysterols and other LXR ligands (PubMed:11606068, PubMed:33141061). However, subsequent observations in a number of different cell types (primary mouse cells, oligodendrocytes and neuron-like cell lines) have not confirmed this observation (By similarity) (PubMed:33141061).</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="7 9"/>
    <dbReference type="EMBL" id="AJ308237">
        <property type="protein sequence ID" value="CAC87131.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK289830">
        <property type="protein sequence ID" value="BAF82519.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290035">
        <property type="protein sequence ID" value="BAF82724.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67464.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67465.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67466.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041091">
        <property type="protein sequence ID" value="AAH41091.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY055472">
        <property type="protein sequence ID" value="AAL16400.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY055472">
        <property type="protein sequence ID" value="AAL16401.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY055472">
        <property type="protein sequence ID" value="AAL16402.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ300465">
        <property type="protein sequence ID" value="CAC17140.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8415.1">
        <molecule id="Q9H172-1"/>
    </dbReference>
    <dbReference type="PIR" id="JC7777">
        <property type="entry name" value="JC7777"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001135977.1">
        <molecule id="Q9H172-1"/>
        <property type="nucleotide sequence ID" value="NM_001142505.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001335120.1">
        <molecule id="Q9H172-1"/>
        <property type="nucleotide sequence ID" value="NM_001348191.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001335121.1">
        <molecule id="Q9H172-2"/>
        <property type="nucleotide sequence ID" value="NM_001348192.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_071452.2">
        <molecule id="Q9H172-1"/>
        <property type="nucleotide sequence ID" value="NM_022169.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011541254.1">
        <molecule id="Q9H172-3"/>
        <property type="nucleotide sequence ID" value="XM_011542952.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054225605.1">
        <molecule id="Q9H172-3"/>
        <property type="nucleotide sequence ID" value="XM_054369630.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H172"/>
    <dbReference type="SMR" id="Q9H172"/>
    <dbReference type="BioGRID" id="122083">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9H172">
        <property type="interactions" value="749"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H172">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H172"/>
    <dbReference type="STRING" id="9606.ENSP00000481728"/>
    <dbReference type="TCDB" id="3.A.1.204.20">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9H172">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H172">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H172"/>
    <dbReference type="PhosphoSitePlus" id="Q9H172"/>
    <dbReference type="BioMuta" id="ABCG4"/>
    <dbReference type="DMDM" id="17432915"/>
    <dbReference type="MassIVE" id="Q9H172"/>
    <dbReference type="PaxDb" id="9606-ENSP00000481728"/>
    <dbReference type="PeptideAtlas" id="Q9H172"/>
    <dbReference type="ProteomicsDB" id="80375">
        <molecule id="Q9H172-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="32624">
        <property type="antibodies" value="195 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="64137"/>
    <dbReference type="Ensembl" id="ENST00000615496.4">
        <molecule id="Q9H172-1"/>
        <property type="protein sequence ID" value="ENSP00000479253.1"/>
        <property type="gene ID" value="ENSG00000172350.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000619701.5">
        <molecule id="Q9H172-1"/>
        <property type="protein sequence ID" value="ENSP00000481728.1"/>
        <property type="gene ID" value="ENSG00000172350.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000622721.1">
        <molecule id="Q9H172-1"/>
        <property type="protein sequence ID" value="ENSP00000484289.1"/>
        <property type="gene ID" value="ENSG00000172350.11"/>
    </dbReference>
    <dbReference type="GeneID" id="64137"/>
    <dbReference type="KEGG" id="hsa:64137"/>
    <dbReference type="MANE-Select" id="ENST00000619701.5">
        <property type="protein sequence ID" value="ENSP00000481728.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_022169.5"/>
        <property type="RefSeq protein sequence ID" value="NP_071452.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc031yhk.2">
        <molecule id="Q9H172-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:13884"/>
    <dbReference type="ClinPGx" id="PA24410"/>
    <dbReference type="CTD" id="64137"/>
    <dbReference type="DisGeNET" id="64137"/>
    <dbReference type="GeneCards" id="ABCG4"/>
    <dbReference type="HGNC" id="HGNC:13884">
        <property type="gene designation" value="ABCG4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000172350">
        <property type="expression patterns" value="Group enriched (brain, retina)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCG4"/>
    <dbReference type="MIM" id="607784">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000172350"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000172350"/>
    <dbReference type="eggNOG" id="KOG0061">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157853"/>
    <dbReference type="HOGENOM" id="CLU_000604_57_6_1"/>
    <dbReference type="InParanoid" id="Q9H172"/>
    <dbReference type="OMA" id="WIDVCIM"/>
    <dbReference type="OrthoDB" id="66620at2759"/>
    <dbReference type="PAN-GO" id="Q9H172">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H172"/>
    <dbReference type="PathwayCommons" id="Q9H172"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9H172"/>
    <dbReference type="Agora" id="ENSG00000172350"/>
    <dbReference type="BioGRID-ORCS" id="64137">
        <property type="hits" value="9 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCG4"/>
    <dbReference type="GenomeRNAi" id="64137"/>
    <dbReference type="Pharos" id="Q9H172">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H172"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H172">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000172350">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 140 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9H172">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031410">
        <property type="term" value="C:cytoplasmic vesicle"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010008">
        <property type="term" value="C:endosome membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034041">
        <property type="term" value="F:ABC-type sterol transporter activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046982">
        <property type="term" value="F:protein heterodimerization activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071403">
        <property type="term" value="P:cellular response to high density lipoprotein particle stimulus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990830">
        <property type="term" value="P:cellular response to leukemia inhibitory factor"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033344">
        <property type="term" value="P:cholesterol efflux"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042632">
        <property type="term" value="P:cholesterol homeostasis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045542">
        <property type="term" value="P:positive regulation of cholesterol biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010875">
        <property type="term" value="P:positive regulation of cholesterol efflux"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006355">
        <property type="term" value="P:regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055085">
        <property type="term" value="P:transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd03213">
        <property type="entry name" value="ABCG_EPDR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000267">
        <property type="entry name" value="ATP-binding cassette, sub-family G (WHITE), member 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013525">
        <property type="entry name" value="ABC2_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003439">
        <property type="entry name" value="ABC_transporter-like_ATP-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017871">
        <property type="entry name" value="ABC_transporter-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043926">
        <property type="entry name" value="ABCG_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050352">
        <property type="entry name" value="ABCG_transporters"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48041">
        <property type="entry name" value="ABC TRANSPORTER G FAMILY MEMBER 28"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48041:SF75">
        <property type="entry name" value="ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01061">
        <property type="entry name" value="ABC2_membrane"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19055">
        <property type="entry name" value="ABC2_membrane_7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00005">
        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00211">
        <property type="entry name" value="ABC_TRANSPORTER_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50893">
        <property type="entry name" value="ABC_TRANSPORTER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093392" description="ATP-binding cassette sub-family G member 4">
        <location>
            <begin position="1"/>
            <end position="646"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="1"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="2">
        <location>
            <begin position="394"/>
            <end position="414"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="415"/>
            <end position="425"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="2">
        <location>
            <begin position="426"/>
            <end position="446"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="447"/>
            <end position="472"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="2">
        <location>
            <begin position="473"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="494"/>
            <end position="503"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="2">
        <location>
            <begin position="504"/>
            <end position="524"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="525"/>
            <end position="532"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="2">
        <location>
            <begin position="533"/>
            <end position="553"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="554"/>
            <end position="617"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="2">
        <location>
            <begin position="618"/>
            <end position="638"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="639"/>
            <end position="646"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="3">
        <location>
            <begin position="61"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-2">
        <location>
            <begin position="386"/>
            <end position="641"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="102"/>
            <end position="109"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="422"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054266" description="In isoform 4." evidence="10">
        <location>
            <begin position="1"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054267" description="In isoform 2." evidence="10">
        <original>MAEKALEAVGCGLGPGAVAMAVTLEDGAEPPVLTTHLKKVENHITEAQRFSHLPKRSAVDIEFVELSYSVREGPCWRKR</original>
        <variation>MRDLELREVKQLARGHTA</variation>
        <location>
            <begin position="1"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054268" description="In isoform 3." evidence="10">
        <original>MAEKALEAVGCGLGPGAVAMAVTLEDGAEPPVLTTHLKKVENHITEAQRFSHLPKRSAVDIEFVELSYSVREGPCWRKR</original>
        <variation>MCGFSHAFQKRIVAS</variation>
        <location>
            <begin position="1"/>
            <end position="79"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048141" description="In dbSNP:rs35060365.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="352"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abrogates ATPase activity. Induces a dominant-negative effect on ABCG1 ATP-activity. Does not affect subcellular localization." evidence="7 8">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q91WA9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11606068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11856881"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12183068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15240127"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27228027"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="33141061"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="11856881"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="15240127"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13">
        <source>
            <dbReference type="PubMed" id="33141061"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="HGNC" id="HGNC:13884"/>
        </source>
    </evidence>
    <sequence length="646" mass="71896" checksum="9CCEC6E150772611" modified="2001-12-05" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-02-21" modified="2026-01-28" version="220" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NP58</accession>
    <accession>O75542</accession>
    <accession>Q49A66</accession>
    <accession>Q59GQ5</accession>
    <accession>Q6ZME6</accession>
    <accession>Q96ME8</accession>
    <accession>Q9HAQ6</accession>
    <accession>Q9HAQ7</accession>
    <name>ABCB6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="33">ATP-binding cassette sub-family B member 6</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="33">ABC-type heme transporter ABCB6</fullName>
            <ecNumber evidence="9 10">7.6.2.5</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="31">Mitochondrial ABC transporter 3</fullName>
            <shortName evidence="31">Mt-ABC transporter 3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>P-glycoprotein-related protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Ubiquitously-expressed mammalian ABC half transporter</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="37" type="primary">ABCB6</name>
        <name evidence="31" type="synonym">MTABC3</name>
        <name type="synonym">PRP</name>
        <name type="synonym">UMAT</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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                <person name="Mitsuhashi N."/>
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            <dbReference type="PubMed" id="10837493"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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                <person name="Emadi-Konjin H.-P."/>
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            <dbReference type="PubMed" id="11955620"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-229</scope>
        <source>
            <tissue>Colon</tissue>
            <tissue>Liver</tissue>
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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                <person name="Shigeta K."/>
                <person name="Senba T."/>
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                <person name="Mizuno T."/>
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                <person name="Sasaki M."/>
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                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 112-842 (ISOFORM 1)</scope>
        <source>
            <tissue>Hepatoma</tissue>
            <tissue>Neuroepithelium</tissue>
        </source>
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    <reference key="5">
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-842 (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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        <scope>FUNCTION</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <scope>INDUCTION BY CELLULAR PORPHYRINS</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH HEMIN</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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            <dbReference type="PubMed" id="17661442"/>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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                <person name="Tsuchida M."/>
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            <dbReference type="PubMed" id="18279659"/>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>GLYCOSYLATION</scope>
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        <scope>INDUCTION</scope>
        <scope>GLYCOSYLATION AT ASN-6</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ASN-6; CYS-8; CYS-26; CYS-50; CYS-120; ASN-447; ASN-498; ASN-677 AND ASN-775</scope>
        <scope>DISULFIDE BOND</scope>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
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    <comment type="function">
        <text evidence="1 6 9 10 14 20 24 27 28 29 30">ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:17661442, PubMed:23792964, PubMed:27507172, PubMed:33007128). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:10837493, PubMed:17006453, PubMed:23792964, PubMed:33007128). May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils (PubMed:29940187). In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (PubMed:21266531, PubMed:25202056, PubMed:31053883). In addition may play a role in the transition metal homeostasis (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 10 20">
            <text>heme b(in) + ATP + H2O = heme b(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19261"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:60344"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="7.6.2.5"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9 34">
            <dbReference type="Rhea" id="RHEA:19262"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="20 27 30">
            <text>coproporphyrin III(in) + ATP + H2O = coproporphyrin III(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66664"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:131725"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20 27">
            <dbReference type="Rhea" id="RHEA:66665"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 20">
            <text>pheophorbide a(in) + ATP + H2O = pheophorbide a(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61360"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58687"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="34">
            <dbReference type="Rhea" id="RHEA:61361"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>coproporphyrinogen III(in) + ATP + H2O = coproporphyrinogen III(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66680"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57309"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66681"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="20 30">
            <text>protoporphyrin IX(in) + ATP + H2O = protoporphyrin IX(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:61336"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57306"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20">
            <dbReference type="Rhea" id="RHEA:61337"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>coproporphyrin I(in) + ATP + H2O = coproporphyrin I(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66768"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167478"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66769"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>uroporphyrin I(in) + ATP + H2O = uroporphyrin I(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66772"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167480"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66773"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>uroporphyrin III(in) + ATP + H2O = uroporphyrin III(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66776"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167479"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66777"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="20 30">ATPase activity is inhibited by MgATP with an IC(50) of 1.03 mM and up-regulated by coporphyrin III&gt; hemin &gt; protoporphyrin IX (PubMed:23792964). ATPase activity for hemin is up-regulated by glutathione (PubMed:33007128). The ATPase activity is impaired by increasing copper concentrations (0-300 uM) (PubMed:33007128). The ATPase activity is stimulated in presence of glutathione for increasing copper concentrations (0-300 uM) (PubMed:33007128).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="20">0.99 mM for ATP (from purified mitochondrial ABCB6)</KM>
            <KM evidence="20">0.97 mM for ATP (from liposome-reconstituted purified mitochondrial ABCB6)</KM>
            <KM evidence="20">11.97 uM for coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6)</KM>
            <KM evidence="30">51 uM for glutathione (in the presence of 10 uM of hemin)</KM>
            <KM evidence="30">190 nM for hemin (in the presence of 1 mM of glutathione)</KM>
            <KM evidence="30">600 nM for hematin (in the presence of 1 mM of glutathione)</KM>
            <KM evidence="30">148 nM for Fe-coproporphyrin III (in the presence of 1 mM of glutathione)</KM>
            <Vmax evidence="20">492.3 nmol/min/mg enzyme toward ATP (from purified mitochondrial ABCB6)</Vmax>
            <Vmax evidence="20">614.0 nmol/min/mg enzyme toward ATP (from liposome-reconstituted purified mitochondrial ABCB6)</Vmax>
            <Vmax evidence="20">29.6 pmol/min/mg enzyme toward coproporphyrin III (from liposome-reconstituted purified mitochondrial ABCB6)</Vmax>
            <Vmax evidence="20">5.13 pmol/min/mg enzyme toward verteporfin</Vmax>
            <Vmax evidence="20">2.7 pmol/min/mg enzyme toward tomatine</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="7 9 20 26 30">Homodimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10 16 17 18 27">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 10">Mitochondrion outer membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11 13 15">Endoplasmic reticulum membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11 13 15">Golgi apparatus membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="26">Endosome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="17 26 28 29">Lysosome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Late endosome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Early endosome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="17">Secreted</location>
            <location evidence="17">Extracellular exosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 20">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="26">Endosome</location>
            <location evidence="26">Multivesicular body membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="28">Melanosome membrane</location>
        </subcellularLocation>
        <text evidence="1 11 13 17 26 28">Present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation (PubMed:22655043). Traffics from endoplasmic reticulum to Golgi during its glycans's maturation, therefrom is first targeted to the plasma membrane, and is rapidly internalized through endocytosis to be distributed to the limiting membrane of multivesicular bodies and lysosomes (PubMed:18279659, PubMed:21199866, PubMed:25627919). Localized on the limiting membrane of early melanosomes of pigment cells (PubMed:29940187). Targeted to the endolysosomal compartment (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NP58-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NP58-4</id>
            <name>2</name>
            <sequence type="described" ref="VSP_021973"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 15 17">Widely expressed. High expression is detected in the retinal epithelium (PubMed:10837493, PubMed:22226084). Expressed in mature erythrocytes (PubMed:22655043).</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="9">Highly expressed in fetal liver.</text>
    </comment>
    <comment type="induction">
        <text evidence="9 14 17 18">Up-regulated by cellular porphyrins (at protein level) (PubMed:17006453, PubMed:22655043, PubMed:23180570). Up-regulated during erythroid differentiation (at protein level) (PubMed:22655043). Induced by sodium arsenite in a dose-dependent manner (PubMed:21266531).</text>
    </comment>
    <comment type="domain">
        <text evidence="26">Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11 13 17 26">N-glycosylated.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="16">Genetic variations in ABCB6 define the Langereis blood group system (LAN) [MIM:111600]. Individuals with Lan(-) blood group lack the Lan antigen on their red blood cells. These individuals may have anti-Lan antibodies in their serum, which can cause transfusion reactions or hemolytic disease of the fetus or newborn. The Lan(-) blood group is only clinically significant in transfusion settings or during pregnancy; otherwise Lan(-) individuals have no clinical features.</text>
    </comment>
    <comment type="disease" evidence="15">
        <disease id="DI-03384">
            <name>Microphthalmia/Coloboma 7</name>
            <acronym>MCOPCB7</acronym>
            <description>A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).</description>
            <dbReference type="MIM" id="614497"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="19 21 22 25 28">
        <disease id="DI-03880">
            <name>Dyschromatosis universalis hereditaria 3</name>
            <acronym>DUH3</acronym>
            <description>An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body, that appear in infancy or early childhood. The trunk and extremities are the dominant sites of abnormal pigmentation. Facial lesions can be seen in 50% of affected individuals, but involvement of palms and soles is unusual. Abnormalities of hair and nails have also been reported. Dyschromatosis universalis hereditaria may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications.</description>
            <dbReference type="MIM" id="615402"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="18 23">
        <disease id="DI-04131">
            <name>Pseudohyperkalemia, familial, 2, due to red cell leak</name>
            <acronym>PSHK2</acronym>
            <description>A dominantly inherited condition characterized by increased serum potassium levels, measured in whole-blood specimens stored at or below room temperature. This condition is not accompanied by clinical symptoms or biological signs except for borderline abnormalities of red cell shape.</description>
            <dbReference type="MIM" id="609153"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text evidence="27">Defects in ABCB6 may be the cause of a severe porphyria. Affected individuals show higher urinary porphyrin concentrations.</text>
    </comment>
    <comment type="similarity">
        <text evidence="33">Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="6 9 10 17 26 28 29">To date, the intracellular localization of ABCB6 is a matter of debate, with conflicting reports suggesting mitochondrial (PubMed:10837493, PubMed:17006453, PubMed:17661442) or endolysosomal localization (PubMed:22655043, PubMed:25627919, PubMed:29940187, PubMed:31053883), therefore questioning the requirement of ABCB6 in the mitochondrial import of porphyrins.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAG33617" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAG33618" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAH43423" version="1"/>
        </conflict>
        <text>Intron retention.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAD18782" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="BAD92291" version="1"/>
        </conflict>
        <text>Chimeric cDNA.</text>
    </comment>
    <comment type="sequence caution" evidence="33">
        <molecule>Isoform 2</molecule>
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="BAB71347" version="1"/>
        </conflict>
        <text>splicing through aberrant splice sites.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.5" evidence="9 10"/>
    <dbReference type="EMBL" id="AB039371">
        <property type="protein sequence ID" value="BAA96733.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF076775">
        <property type="protein sequence ID" value="AAF75107.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF308472">
        <property type="protein sequence ID" value="AAG33617.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF308473">
        <property type="protein sequence ID" value="AAG33618.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ289233">
        <property type="protein sequence ID" value="CAB95766.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK057026">
        <property type="protein sequence ID" value="BAB71347.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK172812">
        <property type="protein sequence ID" value="BAD18782.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB209054">
        <property type="protein sequence ID" value="BAD92291.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000559">
        <property type="protein sequence ID" value="AAH00559.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC043423">
        <property type="protein sequence ID" value="AAH43423.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF070598">
        <property type="protein sequence ID" value="AAC28653.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2436.1">
        <molecule id="Q9NP58-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS86920.1">
        <molecule id="Q9NP58-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001336757.1">
        <molecule id="Q9NP58-4"/>
        <property type="nucleotide sequence ID" value="NM_001349828.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005680.1">
        <molecule id="Q9NP58-1"/>
        <property type="nucleotide sequence ID" value="NM_005689.4"/>
    </dbReference>
    <dbReference type="PDB" id="3NH6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=558-842"/>
    </dbReference>
    <dbReference type="PDB" id="3NH9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=558-842"/>
    </dbReference>
    <dbReference type="PDB" id="3NHA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=558-842"/>
    </dbReference>
    <dbReference type="PDB" id="3NHB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="A=558-842"/>
    </dbReference>
    <dbReference type="PDB" id="7D7N">
        <property type="method" value="EM"/>
        <property type="resolution" value="5.20 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="7D7R">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.00 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="7DNY">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="7DNZ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="7EKL">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="7EKM">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="8FWK">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDB" id="8K7B">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="A/B=238-827"/>
    </dbReference>
    <dbReference type="PDB" id="8K7C">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="A/B=240-826"/>
    </dbReference>
    <dbReference type="PDB" id="8YR3">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B=206-842"/>
    </dbReference>
    <dbReference type="PDB" id="8YR4">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B=206-842"/>
    </dbReference>
    <dbReference type="PDB" id="9DBQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B=1-842"/>
    </dbReference>
    <dbReference type="PDBsum" id="3NH6"/>
    <dbReference type="PDBsum" id="3NH9"/>
    <dbReference type="PDBsum" id="3NHA"/>
    <dbReference type="PDBsum" id="3NHB"/>
    <dbReference type="PDBsum" id="7D7N"/>
    <dbReference type="PDBsum" id="7D7R"/>
    <dbReference type="PDBsum" id="7DNY"/>
    <dbReference type="PDBsum" id="7DNZ"/>
    <dbReference type="PDBsum" id="7EKL"/>
    <dbReference type="PDBsum" id="7EKM"/>
    <dbReference type="PDBsum" id="8FWK"/>
    <dbReference type="PDBsum" id="8K7B"/>
    <dbReference type="PDBsum" id="8K7C"/>
    <dbReference type="PDBsum" id="8YR3"/>
    <dbReference type="PDBsum" id="8YR4"/>
    <dbReference type="PDBsum" id="9DBQ"/>
    <dbReference type="AlphaFoldDB" id="Q9NP58"/>
    <dbReference type="BMRB" id="Q9NP58"/>
    <dbReference type="EMDB" id="EMD-29511"/>
    <dbReference type="EMDB" id="EMD-30609"/>
    <dbReference type="EMDB" id="EMD-30610"/>
    <dbReference type="EMDB" id="EMD-30790"/>
    <dbReference type="EMDB" id="EMD-30791"/>
    <dbReference type="EMDB" id="EMD-31169"/>
    <dbReference type="EMDB" id="EMD-31170"/>
    <dbReference type="EMDB" id="EMD-36937"/>
    <dbReference type="EMDB" id="EMD-36938"/>
    <dbReference type="EMDB" id="EMD-39534"/>
    <dbReference type="EMDB" id="EMD-39535"/>
    <dbReference type="EMDB" id="EMD-46724"/>
    <dbReference type="SMR" id="Q9NP58"/>
    <dbReference type="BioGRID" id="115369">
        <property type="interactions" value="142"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NP58">
        <property type="interactions" value="1471"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NP58">
        <property type="interactions" value="71"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NP58"/>
    <dbReference type="STRING" id="9606.ENSP00000265316"/>
    <dbReference type="BindingDB" id="Q9NP58"/>
    <dbReference type="ChEMBL" id="CHEMBL2007630"/>
    <dbReference type="TCDB" id="3.A.1.210.6">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9NP58">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NP58">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NP58"/>
    <dbReference type="PhosphoSitePlus" id="Q9NP58"/>
    <dbReference type="SwissPalm" id="Q9NP58"/>
    <dbReference type="BioMuta" id="ABCB6"/>
    <dbReference type="DMDM" id="13123949"/>
    <dbReference type="jPOST" id="Q9NP58"/>
    <dbReference type="MassIVE" id="Q9NP58"/>
    <dbReference type="PaxDb" id="9606-ENSP00000265316"/>
    <dbReference type="PeptideAtlas" id="Q9NP58"/>
    <dbReference type="ProteomicsDB" id="81888">
        <molecule id="Q9NP58-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81889">
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    <feature type="transmembrane region" description="Helical" evidence="3 5">
        <location>
            <begin position="500"/>
            <end position="520"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="35 36">
        <location>
            <begin position="521"/>
            <end position="529"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3 5">
        <location>
            <begin position="530"/>
            <end position="550"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="33">
        <location>
            <begin position="551"/>
            <end position="842"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1" evidence="5">
        <location>
            <begin position="265"/>
            <end position="556"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="4">
        <location>
            <begin position="590"/>
            <end position="824"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for ATPase activity" evidence="30">
        <location>
            <begin position="1"/>
            <end position="236"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for the lysosomal targeting" evidence="26">
        <location>
            <begin position="1"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="binding site" evidence="12 38">
        <location>
            <position position="599"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="12 38">
        <location>
            <begin position="623"/>
            <end position="634"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="13">
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="13">
        <location>
            <begin position="8"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021973" description="In isoform 2." evidence="32">
        <location>
            <begin position="183"/>
            <end position="228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067394" description="In MCOPCB7; uncertain significance; hypomorphic mutation; dbSNP:rs387906911." evidence="15">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035732" description="In a breast cancer sample; somatic mutation." evidence="8">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070602" description="In DUH3; the protein is retained in the Golgi apparatus; dbSNP:rs397514757." evidence="19">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084494" description="Decrease expression; does not affect substrate binding; does not affect ATP-binding; loss of plasma membrane expression; dbSNP:rs150221689." evidence="27">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084495" description="May be a modifier of disease severity in porphyria patients; loss of expression; dbSNP:rs57467915." evidence="27">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_047552" description="In dbSNP:rs13018440.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="293"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073973" description="In DUH3; dbSNP:rs1574815954." evidence="25">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060986" description="In dbSNP:rs60322991.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070603" description="In DUH3; the protein is retained in the Golgi apparatus; dbSNP:rs397514756." evidence="19">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071133" description="In PSHK2; dbSNP:rs754667801." evidence="18">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071134" description="In PSHK2; dbSNP:rs764893806." evidence="18">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073974" description="In DUH3." evidence="25">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="424"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071135" description="In DUH3." evidence="22">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="453"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084496" description="May be a modifier of disease severity in porphyria patients; increases expression; does not affect substrate binding; impairs ATP-binding; Loss of ATP-dependent coproporphyrin III transport; Highly decrease plasma membrane expression; dbSNP:rs147445258." evidence="27">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="492"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084497" description="May be a modifier of disease severity in porphyria patients; loss of expression; dbSNP:rs149363094." evidence="27">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="521"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071136" description="In DUH3; dbSNP:rs796065353." evidence="21">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="555"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070604" description="In DUH3; the protein is retained in the Golgi apparatus. Does not affect subcellular location in early melanosome and lysosome. Does not rescue the normal amyloid fibril formation and normal maturation of pigmented melanosomes. Does not influence trafficking of melanosomal proteins.; dbSNP:rs397514758." evidence="19 28">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="579"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084498" description="May be a modifier of disease severity in porphyria patients; loss of expression; dbSNP:rs145526996." evidence="27">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="588"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029749" description="In dbSNP:rs13402964.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="648"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084499" description="May be a modifier of disease severity in porphyria patients; loss of expression; dbSNP:rs142421126." evidence="27">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="681"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076206" description="In PSHK2; dbSNP:rs148211042." evidence="23">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="723"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067395" description="In MCOPCB7; hypomorphic mutation; dbSNP:rs387906910." evidence="15">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="811"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of N-glycosylation. Loss of N-glycosylation; when associated with Q-447; Q-498; Q-677 and Q-775. Does not affect substrate binding." evidence="13">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of N-glycosylation." evidence="13">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect substrate binding. Does not affect N-glycosylation. Impairs endoplasmic reticulum exit. Impairs endoplasmic reticulum exit; when associated with C-8. Increases ABCB6 proteasomal degradation. Affects protein stability. Does not affect migration in the presence of DTT; when associated with A-50 and A-120." evidence="13">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases protein expression. Affects protein stability. Loss of ability to stimulate porphyrin synthesis." evidence="13">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases protein expression. Impairs endoplasmic reticulum exit; when associated with C-8. Affects protein stability." evidence="13">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases migration in the absence of DTT; when associated with A-120. Reduces migration in with the presence of DTT; when associated with A-120." evidence="13">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases migration in the absence of DTT; when associated with A-50. Reduces migration in with the presence of DTT; when associated with A-50." evidence="13">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of substrate-stimulate ATPase activity. Impairs protein expression." evidence="30">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="286"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect N-glycosylation. Does not affect N-glycosylation; when associated with Q-498; Q-677 and Q-775. Does not affect trafficking from endoplasmic reticulum; when associated with Q-498; Q-677 and Q-775." evidence="13">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="447"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect N-glycosylation. Does not affect N-glycosylation; when associated with Q-447; Q-677 and Q-775. Does not affect trafficking from endoplasmic reticulum; when associated with Q-447; Q-677 and Q-775." evidence="13">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of substrate-stimulate ATPase activity. Impairs protein expression." evidence="30">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="531"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of substrate-stimulate ATPase activity." evidence="30">
        <original>M</original>
        <variation>A</variation>
        <location>
            <position position="542"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of substrate-stimulate ATPase activity. Impairs protein expression." evidence="30">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect substrate-stimulate ATPase activity." evidence="30">
        <original>W</original>
        <variation>F</variation>
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of substrate-stimulate ATPase activity. Impairs protein expression." evidence="30">
        <original>W</original>
        <variation>V</variation>
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes ATP hydrolysis. Abolishes coproporphyrin III transport." evidence="20 26">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="629"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect subcellular location in early melanosome and lysosome. Does not rescue the normal amyloid fibril formation and normal maturation of pigmented melanosomes. Does not influence trafficking of melanosomal proteins. Fails to rescue vacuolar sequestration of cadmium in Schizosaccharomyces pombe and Caenorhabditis elegans strains defective for HMT-1. Fails to rescue the cadmium tolerance in Schizosaccharomyces pombe and Caenorhabditis elegans strains defective for HMT-1. Does not rescue vacuolar cadmium levels in hmt-1 mutant S.pombe." evidence="28 29">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="629"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect N-glycosylation. Does not affect N-glycosylation; when associated with Q-447; Q-498; and Q-775. Does not affect trafficking from endoplasmic reticulum; when associated with Q-447; Q-498; and Q-775." evidence="13">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="677"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect N-glycosylation. Does not affect N-glycosylation; when associated with Q-447; Q-498 and Q-677. Does not affect trafficking from endoplasmic reticulum; when associated with Q-447; Q-498 and Q-677." evidence="13">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="775"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAG33618." evidence="33" ref="2">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD18782." evidence="33" ref="4">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD18782." evidence="33" ref="4">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="413"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD18782." evidence="33" ref="4">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="616"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD18782." evidence="33" ref="4">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="238"/>
            <end position="253"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="259"/>
            <end position="294"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="299"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="319"/>
            <end position="322"/>
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    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="325"/>
            <end position="355"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="358"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="366"/>
            <end position="389"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="391"/>
            <end position="408"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="411"/>
            <end position="458"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="460"/>
            <end position="466"/>
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    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="469"/>
            <end position="521"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="527"/>
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    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="542"/>
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    <feature type="helix" evidence="44">
        <location>
            <begin position="547"/>
            <end position="549"/>
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    <feature type="helix" evidence="41">
        <location>
            <begin position="561"/>
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    <feature type="strand" evidence="41">
        <location>
            <begin position="590"/>
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    <feature type="strand" evidence="43">
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            <end position="613"/>
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    <feature type="strand" evidence="41">
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    <feature type="strand" evidence="41">
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22226084"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="22246506"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="22655043"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="23180570"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="23519333"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="23792964"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="24224009"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="24498303"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="24947683"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="24">
        <source>
            <dbReference type="PubMed" id="25202056"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="25">
        <source>
            <dbReference type="PubMed" id="25288164"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="26">
        <source>
            <dbReference type="PubMed" id="25627919"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="27">
        <source>
            <dbReference type="PubMed" id="27507172"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="28">
        <source>
            <dbReference type="PubMed" id="29940187"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="29">
        <source>
            <dbReference type="PubMed" id="31053883"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="30">
        <source>
            <dbReference type="PubMed" id="33007128"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="31">
        <source>
            <dbReference type="PubMed" id="10837493"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="32">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="33"/>
    <evidence type="ECO:0000305" key="34">
        <source>
            <dbReference type="PubMed" id="17661442"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="35">
        <source>
            <dbReference type="PubMed" id="18279659"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="36">
        <source>
            <dbReference type="PubMed" id="21199866"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="37">
        <source>
            <dbReference type="HGNC" id="HGNC:47"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="38">
        <source>
            <dbReference type="PDB" id="3NH9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="39">
        <source>
            <dbReference type="PDB" id="7D7N"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="40">
        <source>
            <dbReference type="PDB" id="7D7R"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="41">
        <source>
            <dbReference type="PDB" id="3NH6"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="42">
        <source>
            <dbReference type="PDB" id="3NH9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="43">
        <source>
            <dbReference type="PDB" id="7DNY"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="44">
        <source>
            <dbReference type="PDB" id="7EKL"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="45">
        <source>
            <dbReference type="PDB" id="9DBQ"/>
        </source>
    </evidence>
    <sequence length="842" mass="93886" checksum="E63A7D59DCE5B9ED" modified="2000-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="233" xmlns="https://uniprot.org/uniprot">
    <accession>P28288</accession>
    <accession>D3DT46</accession>
    <accession>Q15271</accession>
    <accession>Q6NUN5</accession>
    <accession>Q96DA3</accession>
    <accession>Q9H529</accession>
    <name>ABCD3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family D member 3</fullName>
            <ecNumber evidence="18 25">3.1.2.-</ecNumber>
            <ecNumber evidence="9 18 25">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20">70 kDa peroxisomal membrane protein</fullName>
            <shortName>PMP70</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="27" type="primary">ABCD3</name>
        <name type="synonym">PMP70</name>
        <name evidence="22" type="synonym">PXMP1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ASP-17</scope>
        <source>
            <tissue>Liver</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <tissue>Liver</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="16710414"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
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            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
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            <dbReference type="PubMed" id="9539740"/>
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        <scope>CAUTION</scope>
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            <dbReference type="PubMed" id="10551832"/>
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        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH ABCD1 AND ABCD2</scope>
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            <dbReference type="PubMed" id="17609205"/>
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        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH ABCD1</scope>
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        <scope>INTERACTION WITH PEX19</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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                <person name="Sacksteder K.A."/>
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            <dbReference type="PubMed" id="10704444"/>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH PEX19</scope>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF GLY-478 AND SER-572</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ATP-BINDING</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2005" name="Biochim. Biophys. Acta" volume="1746" first="116" last="128">
            <title>Role of Pex19p in the targeting of PMP70 to peroxisome.</title>
            <authorList>
                <person name="Kashiwayama Y."/>
                <person name="Asahina K."/>
                <person name="Shibata H."/>
                <person name="Morita M."/>
                <person name="Muntau A.C."/>
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            </authorList>
            <dbReference type="PubMed" id="16344115"/>
            <dbReference type="DOI" id="10.1016/j.bbamcr.2005.10.006"/>
        </citation>
        <scope>INTERACTION WITH PEX19</scope>
        <scope>REGION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="33831" last="33844">
            <title>Hydrophobic regions adjacent to transmembrane domains 1 and 5 are important for the targeting of the 70-kDa peroxisomal membrane protein.</title>
            <authorList>
                <person name="Kashiwayama Y."/>
                <person name="Asahina K."/>
                <person name="Morita M."/>
                <person name="Imanaka T."/>
            </authorList>
            <dbReference type="PubMed" id="17761678"/>
            <dbReference type="DOI" id="10.1074/jbc.m703369200"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH PEX19</scope>
        <scope>MUTAGENESIS OF 21-LEU--LEU-23; 70-ILE-LEU-71 AND 307-ILE-LEU-308</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-260 AND LYS-399</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
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                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2014" name="Biochim. Biophys. Acta" volume="1841" first="563" last="568">
            <title>A role for the human peroxisomal half-transporter ABCD3 in the oxidation of dicarboxylic acids.</title>
            <authorList>
                <person name="van Roermund C.W."/>
                <person name="Ijlst L."/>
                <person name="Wagemans T."/>
                <person name="Wanders R.J."/>
                <person name="Waterham H.R."/>
            </authorList>
            <dbReference type="PubMed" id="24333844"/>
            <dbReference type="DOI" id="10.1016/j.bbalip.2013.12.001"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2015" name="Hum. Mol. Genet." volume="24" first="361" last="370">
            <title>A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3.</title>
            <authorList>
                <person name="Ferdinandusse S."/>
                <person name="Jimenez-Sanchez G."/>
                <person name="Koster J."/>
                <person name="Denis S."/>
                <person name="Van Roermund C.W."/>
                <person name="Silva-Zolezzi I."/>
                <person name="Moser A.B."/>
                <person name="Visser W.F."/>
                <person name="Gulluoglu M."/>
                <person name="Durmaz O."/>
                <person name="Demirkol M."/>
                <person name="Waterham H.R."/>
                <person name="Goekcay G."/>
                <person name="Wanders R.J."/>
                <person name="Valle D."/>
            </authorList>
            <dbReference type="PubMed" id="25168382"/>
            <dbReference type="DOI" id="10.1093/hmg/ddu448"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INVOLVEMENT IN CBAS5</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2016" name="J. Cell Biol." volume="214" first="677" last="690">
            <title>PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation.</title>
            <authorList>
                <person name="Sargent G."/>
                <person name="van Zutphen T."/>
                <person name="Shatseva T."/>
                <person name="Zhang L."/>
                <person name="Di Giovanni V."/>
                <person name="Bandsma R."/>
                <person name="Kim P.K."/>
            </authorList>
            <dbReference type="PubMed" id="27597759"/>
            <dbReference type="DOI" id="10.1083/jcb.201511034"/>
        </citation>
        <scope>UBIQUITINATION</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2018" name="Biochem. Biophys. Res. Commun." volume="496" first="1122" last="1127">
            <title>Characterization of human ATP-binding cassette protein subfamily D reconstituted into proteoliposomes.</title>
            <authorList>
                <person name="Okamoto T."/>
                <person name="Kawaguchi K."/>
                <person name="Watanabe S."/>
                <person name="Agustina R."/>
                <person name="Ikejima T."/>
                <person name="Ikeda K."/>
                <person name="Nakano M."/>
                <person name="Morita M."/>
                <person name="Imanaka T."/>
            </authorList>
            <dbReference type="PubMed" id="29397936"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2018.01.153"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 9 14 15 16 18">Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-chain fatty acids-CoA and bile acids from the cytosol to the peroxisome lumen for beta-oxydation (PubMed:11248239, PubMed:24333844, PubMed:25168382, PubMed:29397936). Has fatty acyl-CoA thioesterase and ATPase activities (PubMed:29397936). Probably hydrolyzes fatty acyl-CoAs into free fatty acids prior to their ATP-dependent transport into peroxisomes (By similarity). Thus, play a role in regulation of LCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:24333844, PubMed:25944712).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="18">
            <text>a very long-chain fatty acyl-CoA + H2O = a very long-chain fatty acid + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67072"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58950"/>
            <dbReference type="ChEBI" id="CHEBI:138261"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:67073"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="18">
            <text>a very long-chain fatty acid(in) + ATP + H2O = a very long-chain fatty acid(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58950"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:67081"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>a long-chain fatty acyl-CoA + H2O = a long-chain fatty acid + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67680"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67681"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>a long-chain fatty acid(in) + ATP + H2O = a long-chain fatty acid(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67684"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67685"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>pristanoyl-CoA + H2O = 2,6,10,14-tetramethylpentadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40415"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77250"/>
            <dbReference type="ChEBI" id="CHEBI:77268"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:40416"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>2,6,10,14-tetramethylpentadecanoate(in) + ATP + H2O = 2,6,10,14-tetramethylpentadecanoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67688"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:77268"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67689"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>hexadecanedioyl-CoA + H2O = hexadecanedioate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67696"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76276"/>
            <dbReference type="ChEBI" id="CHEBI:77085"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67697"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>hexadecanedioate(in) + ATP + H2O = hexadecanedioate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67692"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:76276"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + H2O = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67712"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67713"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate(in) + ATP + H2O = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67708"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67709"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67700"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:67701"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="25 26">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate(in) + ATP + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67704"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="9">8.2 uM for ATP</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="6 7 8 11 12 13">Homodimers (PubMed:17609205). Can form heterodimers with ABCD1 and ABCD2 (PubMed:10551832, PubMed:10777694, PubMed:17609205). Dimerization is necessary to form an active transporter (PubMed:17609205). Interacts with PEX19; mediates the targeting of ABCD3 to peroxisomes (PubMed:10704444, PubMed:16344115, PubMed:17761678).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-80992">
            <id>P28288</id>
        </interactant>
        <interactant intactId="EBI-81045">
            <id>P33897</id>
            <label>ABCD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-80992">
            <id>P28288</id>
        </interactant>
        <interactant intactId="EBI-594747">
            <id>P40855</id>
            <label>PEX19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25889034">
            <id>P28288-2</id>
        </interactant>
        <interactant intactId="EBI-715087">
            <id>P09471</id>
            <label>GNAO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25889034">
            <id>P28288-2</id>
        </interactant>
        <interactant intactId="EBI-9091052">
            <id>Q6P4D5-2</id>
            <label>PABIR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25889034">
            <id>P28288-2</id>
        </interactant>
        <interactant intactId="EBI-998260">
            <id>P53999</id>
            <label>SUB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 11 13 14 18">Peroxisome membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P28288-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P28288-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_031189"/>
        </isoform>
        <isoform>
            <id>P28288-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_031187 VSP_031188"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="17">Ubiquitinated by PEX2 during pexophagy in response to starvation, leading to its degradation.</text>
    </comment>
    <comment type="disease" evidence="15">
        <disease id="DI-04360">
            <name>Congenital bile acid synthesis defect 5</name>
            <acronym>CBAS5</acronym>
            <description>An autosomal recessive disorder characterized by hepatosplenomegaly, hepatic fibrosis, progressive liver failure, and accumulation of peroxisomal C27-bile acid intermediates in plasma.</description>
            <dbReference type="MIM" id="616278"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="24">Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="10 19">Mutation in ABCD3 have been found in two individuals affected by Zellweger syndrome (PubMed:1301993). Later studies, however, showed unambiguously that a PEX1 defect was the underlying cause of the defect in peroxisome biogenesis in these patients (PubMed:9539740).</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
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<entry dataset="Swiss-Prot" created="2001-01-24" modified="2026-01-28" version="213" xmlns="https://uniprot.org/uniprot">
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            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
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    <reference key="1">
        <citation type="journal article" date="1998" name="Nat. Genet." volume="20" first="233" last="238">
            <title>A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.</title>
            <authorList>
                <person name="Strautnieks S.S."/>
                <person name="Bull L.N."/>
                <person name="Knisely A.S."/>
                <person name="Kocoshis S.A."/>
                <person name="Dahl N."/>
                <person name="Arnell H."/>
                <person name="Sokal E.M."/>
                <person name="Dahan K."/>
                <person name="Childs S."/>
                <person name="Ling V."/>
                <person name="Tanner M.S."/>
                <person name="Kagalwalla A.F."/>
                <person name="Nemeth A."/>
                <person name="Pawlowska J."/>
                <person name="Baker A."/>
                <person name="Mieli-Vergani G."/>
                <person name="Freimer N.B."/>
                <person name="Gardiner R.M."/>
                <person name="Thompson R.J."/>
            </authorList>
            <dbReference type="PubMed" id="9806540"/>
            <dbReference type="DOI" id="10.1038/3034"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <title>Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury.</title>
            <authorList>
                <person name="Lang C."/>
                <person name="Meier Y."/>
                <person name="Stieger B."/>
                <person name="Beuers U."/>
                <person name="Lang T."/>
                <person name="Kerb R."/>
                <person name="Kullak-Ublick G.A."/>
                <person name="Meier P.J."/>
                <person name="Pauli-Magnus C."/>
            </authorList>
            <dbReference type="PubMed" id="17264802"/>
            <dbReference type="DOI" id="10.1097/01.fpc.0000230418.28091.76"/>
        </citation>
        <scope>VARIANTS ALA-284; ALA-444; TYR-676; VAL-677; HIS-698 AND ARG-855</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CHARACTERIZATION OF VARIANTS ALA-444; TYR-676; VAL-677 AND ARG-855</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2009" name="Mol. Pharmacol." volume="75" first="143" last="150">
            <title>Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11).</title>
            <authorList>
                <person name="Hayashi H."/>
                <person name="Sugiyama Y."/>
            </authorList>
            <dbReference type="PubMed" id="18829893"/>
            <dbReference type="DOI" id="10.1124/mol.108.049288"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT PFIC2 GLY-297</scope>
        <scope>UBIQUITINATION</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2010" name="Pharmacogenet. Genomics" volume="20" first="45" last="57">
            <title>Polymorphic variants in the human bile salt export pump (BSEP; ABCB11): functional characterization and interindividual variability.</title>
            <authorList>
                <person name="Ho R.H."/>
                <person name="Leake B.F."/>
                <person name="Kilkenny D.M."/>
                <person name="Meyer Zu Schwabedissen H.E."/>
                <person name="Glaeser H."/>
                <person name="Kroetz D.L."/>
                <person name="Kim R.B."/>
            </authorList>
            <dbReference type="PubMed" id="20010382"/>
            <dbReference type="DOI" id="10.1097/fpc.0b013e3283349eb0"/>
        </citation>
        <scope>VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186</scope>
        <scope>CHARACTERIZATION OF VARIANTS LEU-56; VAL-206; ALA-444; HIS-558; SER-591; GLN-592; VAL-677 AND LYS-1186</scope>
        <scope>VARIANT PFIC2 GLY-297</scope>
        <scope>CHARACTERIZATION OF VARIANTS PFIC2 GLY-297; ARG-982 AND CYS-1153</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2014" name="Mol. Med. Report." volume="10" first="1264" last="1274">
            <title>Diagnosis of ABCB11 gene mutations in children with intrahepatic cholestasis using high resolution melting analysis and direct sequencing.</title>
            <authorList>
                <person name="Hu G."/>
                <person name="He P."/>
                <person name="Liu Z."/>
                <person name="Chen Q."/>
                <person name="Zheng B."/>
                <person name="Zhang Q."/>
            </authorList>
            <dbReference type="PubMed" id="24969679"/>
            <dbReference type="DOI" id="10.3892/mmr.2014.2349"/>
        </citation>
        <scope>VARIANTS PFIC2 HIS-337; CYS-472; TRP-696; PRO-931; VAL-1131 AND ARG-1198</scope>
        <scope>VARIANTS ALA-444 AND VAL-865</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2014" name="Mol. Pharmacol." volume="85" first="909" last="920">
            <title>Differential effects of membrane cholesterol content on the transport activity of multidrug resistance-associated protein 2 (ABCC2) and of the bile salt export pump (ABCB11).</title>
            <authorList>
                <person name="Guyot C."/>
                <person name="Hofstetter L."/>
                <person name="Stieger B."/>
            </authorList>
            <dbReference type="PubMed" id="24711118"/>
            <dbReference type="DOI" id="10.1124/mol.114.092262"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS BRIC2 GLY-297 AND THR-432</scope>
        <scope>CHARACTERIZATION VARIANT ALA-444</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2018" name="J. Hum. Genet." volume="63" first="569" last="577">
            <title>Clinical phenotype and molecular analysis of a homozygous ABCB11 mutation responsible for progressive infantile cholestasis.</title>
            <authorList>
                <person name="Imagawa K."/>
                <person name="Hayashi H."/>
                <person name="Sabu Y."/>
                <person name="Tanikawa K."/>
                <person name="Fujishiro J."/>
                <person name="Kajikawa D."/>
                <person name="Wada H."/>
                <person name="Kudo T."/>
                <person name="Kage M."/>
                <person name="Kusuhara H."/>
                <person name="Sumazaki R."/>
            </authorList>
            <dbReference type="PubMed" id="29507376"/>
            <dbReference type="DOI" id="10.1038/s10038-018-0431-1"/>
        </citation>
        <scope>VARIANT PFIC2 TYR-129</scope>
        <scope>CHARACTERIZATION OF VARIANT PFIC2 TYR-129</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2019" name="Mol. Med. Report." volume="19" first="195" last="204">
            <title>Functional analysis of the correlation between ABCB11 gene mutation and primary intrahepatic stone.</title>
            <authorList>
                <person name="Gan L."/>
                <person name="Pan S."/>
                <person name="Cui J."/>
                <person name="Bai J."/>
                <person name="Jiang P."/>
                <person name="He Y."/>
            </authorList>
            <dbReference type="PubMed" id="30431138"/>
            <dbReference type="DOI" id="10.3892/mmr.2018.9661"/>
        </citation>
        <scope>VARIANTS LYS-299; ALA-444 AND VAL-865</scope>
        <scope>CHARACTERIZATION OF VARIANT VAL-865</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="13 14 16 21 23 24 25 26 27 28 30 32">Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>cholate(in) + ATP + H2O = cholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50048"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29747"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50049"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13 14 16 23 24 25 26 27 28 30 32">
            <text>taurocholate(in) + ATP + H2O = taurocholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50052"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:36257"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13 14 16 23 24 25 26 27 28 30 38">
            <dbReference type="Rhea" id="RHEA:50053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13 16 32">
            <text>glycocholate(in) + ATP + H2O = glycocholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50056"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29746"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13 16 38">
            <dbReference type="Rhea" id="RHEA:50057"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>glycochenodeoxycholate(in) + ATP + H2O = glycochenodeoxycholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50060"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:36252"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50061"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>taurochenodeoxycholate(in) + ATP + H2O = taurochenodeoxycholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50064"/>
            <dbReference type="ChEBI" id="CHEBI:9407"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50065"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>glycoursodeoxycholate(in) + ATP + H2O = glycoursodeoxycholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50068"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:132030"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50069"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16 32">
            <text>tauroursodeoxycholate(in) + ATP + H2O = tauroursodeoxycholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50072"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:132028"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16 38">
            <dbReference type="Rhea" id="RHEA:50073"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>taurodeoxycholate(in) + ATP + H2O = taurodeoxycholate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:36261"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50081"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>taurolithocholate 3-sulfate(in) + ATP + H2O = taurolithocholate 3-sulfate(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50084"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58301"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:50085"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14">
            <text>pravastatin(in) + ATP + H2O = pravastatin(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:63908"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:63660"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:63909"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="14 16 23 24 26 28 32">The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM (PubMed:16332456). Pravastatin competitively inhibits the transport of taurocholic acid (PubMed:15901796, PubMed:18985798). Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (PubMed:18985798, PubMed:32203132). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (PubMed:19228692). The uptake of taurocholate is increased by short- and medium-chain fatty acids (PubMed:20398791). Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (PubMed:24711118).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="20">30.4 uM for taurocholate</KM>
            <KM evidence="16">6.2 uM for taurocholate</KM>
            <KM evidence="16">21.7 uM for glycocholate</KM>
            <KM evidence="16">6.6 uM for taurochenodeoxycholate</KM>
            <KM evidence="16">7.5 uM for glycochenodeoxycholate</KM>
            <KM evidence="16">9.5 uM for taurolithocholate sulfate</KM>
            <KM evidence="13">4.61 uM for taurocholate</KM>
            <KM evidence="14">4.64 uM for taurocholate</KM>
            <KM evidence="14">124 uM for pravastatin</KM>
            <KM evidence="23">19.9 uM for taurocholate</KM>
            <Vmax evidence="20">232.0 pmol/min/mg enzyme for taurocholate transport</Vmax>
            <Vmax evidence="16">2510.0 pmol/min/mg enzyme for taurocholate transport</Vmax>
            <Vmax evidence="13">2310.0 pmol/min/mg enzyme for taurocholate transport</Vmax>
            <Vmax evidence="14">4290.0 pmol/min/mg enzyme for taurocholate transport</Vmax>
            <Vmax evidence="14">1220.0 pmol/min/mg enzyme for pravastatin transport</Vmax>
            <Vmax evidence="23">98.5 pmol/min/mg enzyme for taurocholate transport</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="2 27">Interacts with HAX1 (By similarity). Interacts with the adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (PubMed:22262466).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3914067">
            <id>O95342</id>
        </interactant>
        <interactant intactId="EBI-742054">
            <id>Q96D03</id>
            <label>DDIT4L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13 27">Apical cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Recycling endosome membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="25 27 30 31">Cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="2 26 27">Internalized at the canalicular membrane through interaction with the adapter protein complex 2 (AP-2) (PubMed:22262466). At steady state, localizes in the canalicular membrane but is also present in recycling endosomes. ABCB11 constantly and rapidly exchanges between the two sites through tubulo-vesicles carriers that move along microtubules. Microtubule-dependent trafficking of ABCB11 is enhanced by taurocholate and cAMP and regulated by STK11 through a PKA-mediated pathway. Trafficking of newly synthesized ABCB11 through endosomal compartment to the bile canalicular membrane is accelerated by cAMP but not by taurocholate (By similarity). Cell membrane expression is up-regulated by short- and medium-chain fatty acids (PubMed:20398791).</text>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ.</text>
    </comment>
    <comment type="domain">
        <text>Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13 22">N-glycosylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="22">Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11.</text>
    </comment>
    <comment type="disease" evidence="8 9 13 22 25 29 30 33">
        <disease id="DI-00950">
            <name>Cholestasis, progressive familial intrahepatic, 2</name>
            <acronym>PFIC2</acronym>
            <description>A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC2 inheritance is autosomal recessive.</description>
            <dbReference type="MIM" id="601847"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="12 15 28">
        <disease id="DI-00186">
            <name>Cholestasis, benign recurrent intrahepatic, 2</name>
            <acronym>BRIC2</acronym>
            <description>A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.</description>
            <dbReference type="MIM" id="605479"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="36">Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="13 16 27"/>
    <dbReference type="EMBL" id="AF091582">
        <property type="protein sequence ID" value="AAC77455.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF136523">
        <property type="protein sequence ID" value="AAD28285.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008177">
        <property type="protein sequence ID" value="AAY24305.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093723">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC069137">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46444.1"/>
    <dbReference type="RefSeq" id="NP_003733.2">
        <property type="nucleotide sequence ID" value="NM_003742.2"/>
    </dbReference>
    <dbReference type="PDB" id="6LR0">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="U=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="7DV5">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="U=46-1315"/>
    </dbReference>
    <dbReference type="PDB" id="7E1A">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.66 A"/>
        <property type="chains" value="U=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="8PM6">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.22 A"/>
        <property type="chains" value="A=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="8PMD">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.95 A"/>
        <property type="chains" value="A=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="8PMJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.81 A"/>
        <property type="chains" value="A=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="9EGE">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A=1-1321"/>
    </dbReference>
    <dbReference type="PDB" id="9N1Y">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.23 A"/>
        <property type="chains" value="A=1-1321"/>
    </dbReference>
    <dbReference type="PDBsum" id="6LR0"/>
    <dbReference type="PDBsum" id="7DV5"/>
    <dbReference type="PDBsum" id="7E1A"/>
    <dbReference type="PDBsum" id="8PM6"/>
    <dbReference type="PDBsum" id="8PMD"/>
    <dbReference type="PDBsum" id="8PMJ"/>
    <dbReference type="PDBsum" id="9EGE"/>
    <dbReference type="PDBsum" id="9N1Y"/>
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    <dbReference type="PANTHER" id="PTHR43394:SF23">
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    <dbReference type="PANTHER" id="PTHR43394">
        <property type="entry name" value="ATP-DEPENDENT PERMEASE MDL1, MITOCHONDRIAL"/>
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        <property type="entry name" value="ABC_membrane"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ABC transporter transmembrane region"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ABC_TRANSPORTER_2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0988">Intrahepatic cholestasis</keyword>
    <keyword id="KW-0445">Lipid transport</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000093296" description="Bile salt export pump">
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            <begin position="1"/>
            <end position="1321"/>
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            <end position="215"/>
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            <end position="261"/>
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            <end position="319"/>
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    <feature type="transmembrane region" description="Helical" evidence="6">
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            <end position="340"/>
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            <end position="353"/>
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    <feature type="transmembrane region" description="Helical" evidence="6">
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            <end position="374"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="4">
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            <begin position="375"/>
            <end position="755"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="6">
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            <begin position="756"/>
            <end position="776"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="777"/>
            <end position="794"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="6">
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            <begin position="795"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="816"/>
            <end position="869"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="6">
        <location>
            <begin position="870"/>
            <end position="890"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="6">
        <location>
            <begin position="891"/>
            <end position="911"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
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            <begin position="912"/>
            <end position="979"/>
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    <feature type="transmembrane region" description="Helical" evidence="6">
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            <begin position="980"/>
            <end position="1000"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="1001"/>
            <end position="1011"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="6">
        <location>
            <begin position="1012"/>
            <end position="1032"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="1033"/>
            <end position="1321"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1 1" evidence="6">
        <location>
            <begin position="62"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="5">
        <location>
            <begin position="420"/>
            <end position="656"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1 2" evidence="6">
        <location>
            <begin position="755"/>
            <end position="1043"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="5">
        <location>
            <begin position="1078"/>
            <end position="1316"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="16"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with HAX1" evidence="1">
        <location>
            <begin position="651"/>
            <end position="672"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mediates internalization from the plasma membrane" evidence="27">
        <location>
            <begin position="1311"/>
            <end position="1314"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="7">
        <location>
            <begin position="21"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="455"/>
            <end position="462"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="1113"/>
            <end position="1120"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="41">
        <location>
            <position position="586"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="41">
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="690"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="701"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="41">
        <location>
            <position position="704"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="41">
        <location>
            <position position="1214"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="1321"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="19">
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="19">
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="19">
        <location>
            <position position="122"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="19">
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055472" description="Does not affect taurocholate transport activity; does not affect cell surface protein expression; dbSNP:rs11568361." evidence="25">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083783" description="In PFIC2; loss of cell membrane localization; significantly reduces taurocholate transport activity; dbSNP:rs1695246652." evidence="30">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030386" description="In BRIC2; dbSNP:rs72551307." evidence="12">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030387" description="Impairs taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; does not affect cell membrane localization; dbSNP:rs11568357." evidence="17 25">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030388" description="In PFIC2; dbSNP:rs72551306." evidence="8">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="238"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035349" description="In dbSNP:rs200739891." evidence="17 20">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013332" description="In PFIC2." evidence="9">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010271" description="In PFIC2 and BRIC2; reduces transport capacity for taurocholate; decreases protein expression; affects maturation of protein in the endoplasmic reticulum; does not affect apical membrane localization; does not affect cell surface expression of the mature form; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect protein expression; does not affect cell membrane localization; dbSNP:rs11568372." evidence="12 13 15 22 25 28 33">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="297"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030389" description="In dbSNP:rs2287617." evidence="17 31">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030390" description="In PFIC2; dbSNP:rs72551305." evidence="8">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073967" description="In PFIC2; uncertain significance." evidence="29">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043074" description="In dbSNP:rs371656014." evidence="11">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030391" description="In BRIC2; reduced transport capacity for taurocholate; reduces transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; dbSNP:rs121908935." evidence="15 28">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013333" description="Does not affect transport capacity for taurocholate; increases transport activity of taurocholate in a low cholesterol environment; increases transport activity of taurocholate in a high cholesterol environment; does not affect cell surface protein expression; does not affect protein expression; dbSNP:rs2287622." evidence="10 11 17 18 20 25 28 29 31 34">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="444"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059106" description="In dbSNP:rs2287622.">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="444"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059107" description="In dbSNP:rs2287622.">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="444"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013334" description="In PFIC2; dbSNP:rs1274558905." evidence="33">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="461"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073968" description="In PFIC2; dbSNP:rs369860506." evidence="29">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="472"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013335" description="In PFIC2; decreases protein expression; affects maturation of protein in the endoplasmic reticulum; decreases apical membrane localization; affects cell surface expression; does not affect transport of taurocholate and glycocholate; enhances ubiquitination susceptibility; dbSNP:rs72549402." evidence="13 22 33">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083784" description="Impairs taurocholate transport activity; does not affect protein expression; does not affect cell surface protein expression; does not affect cell membrane localization; dbSNP:rs11568369." evidence="25">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="558"/>
        </location>
    </feature>
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    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="16763017"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="16799996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="17082223"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="17264802"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="18245269"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="18829893"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="18985798"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="24">
        <source>
            <dbReference type="PubMed" id="19228692"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="25">
        <source>
            <dbReference type="PubMed" id="20010382"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="26">
        <source>
            <dbReference type="PubMed" id="20398791"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="27">
        <source>
            <dbReference type="PubMed" id="22262466"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="28">
        <source>
            <dbReference type="PubMed" id="24711118"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="29">
        <source>
            <dbReference type="PubMed" id="24969679"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="30">
        <source>
            <dbReference type="PubMed" id="29507376"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="31">
        <source>
            <dbReference type="PubMed" id="30431138"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="32">
        <source>
            <dbReference type="PubMed" id="32203132"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="33">
        <source>
            <dbReference type="PubMed" id="9806540"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="34">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000303" key="35">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="36"/>
    <evidence type="ECO:0000305" key="37">
        <source>
            <dbReference type="PubMed" id="15901796"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="38">
        <source>
            <dbReference type="PubMed" id="32203132"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="39">
        <source>
            <dbReference type="HGNC" id="HGNC:42"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="40">
        <source>
            <dbReference type="PDB" id="6LR0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="41">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="42">
        <source>
            <dbReference type="PDB" id="6LR0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="43">
        <source>
            <dbReference type="PDB" id="8PM6"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="44">
        <source>
            <dbReference type="PDB" id="8PMD"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="45">
        <source>
            <dbReference type="PDB" id="8PMJ"/>
        </source>
    </evidence>
    <sequence length="1321" mass="146407" checksum="61EE2173E2351D80" modified="2009-11-03" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="202" xmlns="https://uniprot.org/uniprot">
    <accession>Q99758</accession>
    <accession>B2RU09</accession>
    <accession>Q54A95</accession>
    <accession>Q6P5P9</accession>
    <accession>Q92473</accession>
    <name>ABCA3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="26">Phospholipid-transporting ATPase ABCA3</fullName>
            <ecNumber evidence="11 21 22">7.6.2.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ABC-C transporter</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="26">ATP-binding cassette sub-family A member 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ATP-binding cassette transporter 3</fullName>
            <shortName>ATP-binding cassette 3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="26">Xenobiotic-transporting ATPase ABCA3</fullName>
            <ecNumber evidence="27">7.6.2.2</ecNumber>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName evidence="28">150 Kda mature form</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="29" type="primary">ABCA3</name>
        <name type="synonym">ABC3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="FEBS Lett." volume="391" first="61" last="65">
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                <person name="Klugbauer N."/>
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            <dbReference type="PubMed" id="8706931"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <tissue>Thyroid carcinoma</tissue>
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    </reference>
    <reference key="2">
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                <person name="Connors T.D."/>
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            <dbReference type="PubMed" id="9027511"/>
            <dbReference type="DOI" id="10.1006/geno.1996.4500"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
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                <person name="Yamano G."/>
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            <dbReference type="PubMed" id="11718719"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(01)03056-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-05" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="SeattleSNPs variation discovery resource"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS HIS-140 AND SER-766</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nature" volume="432" first="988" last="994">
            <title>The sequence and analysis of duplication-rich human chromosome 16.</title>
            <authorList>
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                <person name="Tsai M."/>
                <person name="Ulanovsky L.E."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="White P.S."/>
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                <person name="Wills P.L."/>
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            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="6">
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                <person name="Walenz B."/>
                <person name="Shatkay H."/>
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                <person name="Fasulo D."/>
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                <person name="Reinert K."/>
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                <person name="Clark A.G."/>
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                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="8">
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            <authorList>
                <person name="Lundby A."/>
                <person name="Secher A."/>
                <person name="Lage K."/>
                <person name="Nordsborg N.B."/>
                <person name="Dmytriyev A."/>
                <person name="Lundby C."/>
                <person name="Olsen J.V."/>
            </authorList>
            <dbReference type="PubMed" id="22673903"/>
            <dbReference type="DOI" id="10.1038/ncomms1871"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 117-197</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
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            <title>Characterization and classification of ATP-binding cassette transporter ABCA3 mutants in fatal surfactant deficiency.</title>
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                <person name="Matsumura Y."/>
                <person name="Ban N."/>
                <person name="Ueda K."/>
                <person name="Inagaki N."/>
            </authorList>
            <dbReference type="PubMed" id="16959783"/>
            <dbReference type="DOI" id="10.1074/jbc.m600071200"/>
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        <scope>FUNCTION</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221; PRO-1553; PRO-1580 AND PRO-1591</scope>
        <scope>MUTAGENESIS OF GLY-1221 AND LEU-1580</scope>
    </reference>
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                <person name="Matsumura Y."/>
                <person name="Sakai H."/>
                <person name="Sasaki M."/>
                <person name="Ban N."/>
                <person name="Inagaki N."/>
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            <dbReference type="PubMed" id="17574245"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2007.05.078"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION OF VARIANT SMDP3 ASP-568</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <title>The surfactant lipid transporter ABCA3 is N-terminally cleaved inside LAMP3-positive vesicles.</title>
            <authorList>
                <person name="Engelbrecht S."/>
                <person name="Kaltenborn E."/>
                <person name="Griese M."/>
                <person name="Kern S."/>
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            <dbReference type="PubMed" id="20863830"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2010.09.026"/>
        </citation>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 LYS-215 AND VAL-292</scope>
    </reference>
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            <title>Disruption of N-linked glycosylation promotes proteasomal degradation of the human ATP-binding cassette transporter ABCA3.</title>
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                <person name="Beers M.F."/>
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                <person name="Zhang P."/>
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            <dbReference type="PubMed" id="24142515"/>
            <dbReference type="DOI" id="10.1152/ajplung.00184.2013"/>
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        <scope>GLYCOSYLATION AT ASN-124 AND ASN-140</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ASN-53; ASN-124; ASN-140 AND ASN-945</scope>
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            <title>ABCA3 protects alveolar epithelial cells against free cholesterol induced cell death.</title>
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                <person name="Zarbock R."/>
                <person name="Kaltenborn E."/>
                <person name="Frixel S."/>
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                <person name="Liebisch G."/>
                <person name="Schmitz G."/>
                <person name="Griese M."/>
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            <dbReference type="PubMed" id="25817392"/>
            <dbReference type="DOI" id="10.1016/j.bbalip.2015.03.004"/>
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        <scope>FUNCTION</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 LYS-215 AND VAL-292</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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                <person name="Frixel S."/>
                <person name="Lotz-Havla A.S."/>
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        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 LYS-215; CYS-280 AND LYS-288</scope>
        <scope>MUTAGENESIS OF SER-693</scope>
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                <person name="Dohmen L.C."/>
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            </authorList>
            <dbReference type="PubMed" id="26903515"/>
            <dbReference type="DOI" id="10.1074/jbc.m115.688168"/>
        </citation>
        <scope>INDUCTION</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2016" name="PLoS ONE" volume="11" first="e0152594" last="e0152594">
            <title>Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases.</title>
            <authorList>
                <person name="Hofmann N."/>
                <person name="Galetskiy D."/>
                <person name="Rauch D."/>
                <person name="Wittmann T."/>
                <person name="Marquardt A."/>
                <person name="Griese M."/>
                <person name="Zarbock R."/>
            </authorList>
            <dbReference type="PubMed" id="27031696"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0152594"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>SITE</scope>
        <scope>MUTAGENESIS OF 173-LEU-LYS-174</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2017" name="Biochim. Biophys. Acta" volume="1864" first="2330" last="2335">
            <title>Quantification of volume and lipid filling of intracellular vesicles carrying the ABCA3 transporter.</title>
            <authorList>
                <person name="Hoeppner S."/>
                <person name="Kinting S."/>
                <person name="Torrano A.A."/>
                <person name="Schindlbeck U."/>
                <person name="Braeuchle C."/>
                <person name="Zarbock R."/>
                <person name="Wittmann T."/>
                <person name="Griese M."/>
            </authorList>
            <dbReference type="PubMed" id="28887056"/>
            <dbReference type="DOI" id="10.1016/j.bbamcr.2017.08.013"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 VAL-292 AND ASN-1388</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2019" name="Biochim. Biophys. Acta" volume="1864" first="158516" last="158516">
            <title>Metabolic labelling of choline phospholipids probes ABCA3 transport in lamellar bodies.</title>
            <authorList>
                <person name="Li Y."/>
                <person name="Kinting S."/>
                <person name="Hoeppner S."/>
                <person name="Forstner M.E."/>
                <person name="Uhl O."/>
                <person name="Koletzko B."/>
                <person name="Griese M."/>
            </authorList>
            <dbReference type="PubMed" id="31473345"/>
            <dbReference type="DOI" id="10.1016/j.bbalip.2019.158516"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANTS SMDP3 ASP-568 AND PRO-1580</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2004" name="N. Engl. J. Med." volume="350" first="1296" last="1303">
            <title>ABCA3 gene mutations in newborns with fatal surfactant deficiency.</title>
            <authorList>
                <person name="Shulenin S."/>
                <person name="Nogee L.M."/>
                <person name="Annilo T."/>
                <person name="Wert S.E."/>
                <person name="Whitsett J.A."/>
                <person name="Dean M."/>
            </authorList>
            <dbReference type="PubMed" id="15044640"/>
            <dbReference type="DOI" id="10.1056/nejmoa032178"/>
        </citation>
        <scope>VARIANTS SMDP3 PRO-101; ASP-568; PRO-982; SER-1221; PRO-1553; PRO-1580 AND PRO-1591</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2005" name="Am. J. Respir. Crit. Care Med." volume="172" first="1026" last="1031">
            <title>ABCA3 mutations associated with pediatric interstitial lung disease.</title>
            <authorList>
                <person name="Bullard J.E."/>
                <person name="Wert S.E."/>
                <person name="Whitsett J.A."/>
                <person name="Dean M."/>
                <person name="Nogee L.M."/>
            </authorList>
            <dbReference type="PubMed" id="15976379"/>
            <dbReference type="DOI" id="10.1164/rccm.200503-504oc"/>
        </citation>
        <scope>VARIANTS SMDP3 VAL-292; LYS-690; LYS-1076; MET-1114; LEU-1301 AND GLU-1302</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2006" name="Am. J. Respir. Crit. Care Med." volume="174" first="571" last="580">
            <title>Alteration of the pulmonary surfactant system in full-term infants with hereditary ABCA3 deficiency.</title>
            <authorList>
                <person name="Brasch F."/>
                <person name="Schimanski S."/>
                <person name="Muehlfeld C."/>
                <person name="Barlage S."/>
                <person name="Langmann T."/>
                <person name="Aslanidis C."/>
                <person name="Boettcher A."/>
                <person name="Dada A."/>
                <person name="Schroten H."/>
                <person name="Mildenberger E."/>
                <person name="Prueter E."/>
                <person name="Ballmann M."/>
                <person name="Ochs M."/>
                <person name="Johnen G."/>
                <person name="Griese M."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="16728712"/>
            <dbReference type="DOI" id="10.1164/rccm.200509-1535oc"/>
        </citation>
        <scope>VARIANTS SMDP3 LEU-43; LYS-215; PRO-579; GLN-605 AND 1561-ARG--ARG-1704 DEL</scope>
        <scope>VARIANT LYS-288</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] MET-290; ASP-801 AND GLN-1069</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="J. Perinatol." volume="35" first="231" last="232">
            <title>Respiratory failure in a term infant with cis and trans mutations in ABCA3.</title>
            <authorList>
                <person name="Jackson T."/>
                <person name="Wegner D.J."/>
                <person name="White F.V."/>
                <person name="Hamvas A."/>
                <person name="Cole F.S."/>
                <person name="Wambach J.A."/>
            </authorList>
            <dbReference type="PubMed" id="25712598"/>
            <dbReference type="DOI" id="10.1038/jp.2014.236"/>
        </citation>
        <scope>VARIANTS SMDP3 CYS-280; MET-1399 AND 1589-GLN--ARG-1704 DEL</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2016" name="Pediatr. Pulmonol." volume="51" first="1284" last="1294">
            <title>Tools to explore ABCA3 mutations causing interstitial lung disease.</title>
            <authorList>
                <person name="Wittmann T."/>
                <person name="Schindlbeck U."/>
                <person name="Hoeppner S."/>
                <person name="Kinting S."/>
                <person name="Frixel S."/>
                <person name="Kroener C."/>
                <person name="Liebisch G."/>
                <person name="Hegermann J."/>
                <person name="Aslanidis C."/>
                <person name="Brasch F."/>
                <person name="Reu S."/>
                <person name="Lasch P."/>
                <person name="Zarbock R."/>
                <person name="Griese M."/>
            </authorList>
            <dbReference type="PubMed" id="27177387"/>
            <dbReference type="DOI" id="10.1002/ppul.23471"/>
        </citation>
        <scope>VARIANT SMDP3 ASN-1388</scope>
        <scope>CHARACTERIZATION OF VARIANT SMDP3 ASN-1388</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="9 11 16 17 19 21 22">Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:16959783, PubMed:17574245, PubMed:27177387, PubMed:28887056, PubMed:31473345). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:27177387). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (PubMed:25817392, PubMed:26903515, PubMed:27177387).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="27">
            <text>ATP + H2O + xenobioticSide 1 = ADP + phosphate + xenobioticSide 2.</text>
            <dbReference type="EC" id="7.6.2.2"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11 19 21 22">
            <text>a 1,2-diacyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66272"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57643"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11 19 21 22">
            <dbReference type="Rhea" id="RHEA:66273"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11 19 21 22">
            <text>ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.</text>
            <dbReference type="EC" id="7.6.2.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(in) + ATP + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66340"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:72999"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:66341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66344"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:64716"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66345"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="22">The ATP-dependent phosphatidylcholine transport is competitively inhibited by miltefosine.</text>
    </comment>
    <comment type="subunit">
        <text evidence="22">Homooligomer; disulfide-linked.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 12 19">Endosome</location>
            <location evidence="9 12 19">Multivesicular body membrane</location>
            <topology evidence="26">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 11 12 13 19 22">Cytoplasmic vesicle membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="19">Late endosome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9 11 12 14">Lysosome membrane</location>
        </subcellularLocation>
        <text evidence="5 9 12 13 14 19 20">Localized in the limiting membrane of lamellar bodies in lung alveolar type II cells (PubMed:11718719, PubMed:16959783, PubMed:22673903, PubMed:24142515, PubMed:27177387). Trafficks via the Golgi, sorting vesicles (SVs) and late endosome/multivesicular body network directly to the outer membrane of lamellar bodies in AT2 lung epithelial cells or to lysosomes and lysosomal-related organelles (LROs) in other cells where undergoes proteolytic cleavage and oligosaccharide processing from high mannose type to complex type (PubMed:16959783, PubMed:20863830, PubMed:24142515, PubMed:27177387). Oligomers formation takes place in a post-endoplasmic reticulum compartment (PubMed:27352740).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q99758-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q99758-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056262 VSP_056263"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 23">Expressed in brain, pancreas, skeletal muscle and heart (PubMed:8706931). Highly expressed in the lung in an AT2-cell-specific manner (PubMed:11718719, PubMed:8706931). Weakly expressed in placenta, kidney and liver (PubMed:8706931). Also expressed in medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma (PubMed:8706931).</text>
    </comment>
    <comment type="induction">
        <text evidence="17">Up-regulated in Leishmania Viannia (L.V.) panamensis-infected macrophages exposed to miltefosine (PubMed:26903515). Down-regulated by L.V.panamensis infection (PubMed:26903515).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9 14 19">N-glycosylated (PubMed:16959783, PubMed:24142515, PubMed:27177387). Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type (PubMed:16959783, PubMed:27177387). N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation (PubMed:24142515).</text>
    </comment>
    <comment type="PTM">
        <text evidence="9 12 18 19">Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 9 11 12 15 16 19 20 21 22">
        <disease id="DI-00962">
            <name>Pulmonary surfactant metabolism dysfunction 3</name>
            <acronym>SMDP3</acronym>
            <description>A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.</description>
            <dbReference type="MIM" id="610921"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="26">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.1" evidence="11 21 22"/>
    <dbReference type="EC" id="7.6.2.2" evidence="27"/>
    <dbReference type="EMBL" id="U78735">
        <property type="protein sequence ID" value="AAC50967.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X97187">
        <property type="protein sequence ID" value="CAA65825.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB070929">
        <property type="protein sequence ID" value="BAB86781.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ073080">
        <property type="protein sequence ID" value="AAY57325.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471112">
        <property type="protein sequence ID" value="EAW85515.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020724">
        <property type="protein sequence ID" value="AAH20724.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC062779">
        <property type="protein sequence ID" value="AAH62779.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009065">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC098805">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC106820">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC140895">
        <property type="protein sequence ID" value="AAI40896.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC146866">
        <property type="protein sequence ID" value="AAI46867.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10466.1">
        <molecule id="Q99758-1"/>
    </dbReference>
    <dbReference type="PIR" id="A59188">
        <property type="entry name" value="A59188"/>
    </dbReference>
    <dbReference type="PIR" id="S71363">
        <property type="entry name" value="S71363"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001080.2">
        <molecule id="Q99758-1"/>
        <property type="nucleotide sequence ID" value="NM_001089.3"/>
    </dbReference>
    <dbReference type="PDB" id="7W01">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=1-1704"/>
    </dbReference>
    <dbReference type="PDB" id="7W02">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=1-1704"/>
    </dbReference>
    <dbReference type="PDBsum" id="7W01"/>
    <dbReference type="PDBsum" id="7W02"/>
    <dbReference type="AlphaFoldDB" id="Q99758"/>
    <dbReference type="EMDB" id="EMD-32233"/>
    <dbReference type="EMDB" id="EMD-32234"/>
    <dbReference type="SMR" id="Q99758"/>
    <dbReference type="BioGRID" id="106539">
        <property type="interactions" value="75"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q99758">
        <property type="interactions" value="1278"/>
    </dbReference>
    <dbReference type="IntAct" id="Q99758">
        <property type="interactions" value="56"/>
    </dbReference>
    <dbReference type="MINT" id="Q99758"/>
    <dbReference type="STRING" id="9606.ENSP00000301732"/>
    <dbReference type="DrugBank" id="DB00619">
        <property type="generic name" value="Imatinib"/>
    </dbReference>
    <dbReference type="TCDB" id="3.A.1.211.5">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q99758">
        <property type="glycosylation" value="6 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q99758">
        <property type="glycosylation" value="6 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q99758"/>
    <dbReference type="PhosphoSitePlus" id="Q99758"/>
    <dbReference type="SwissPalm" id="Q99758"/>
    <dbReference type="BioMuta" id="ABCA3"/>
    <dbReference type="DMDM" id="85700402"/>
    <dbReference type="jPOST" id="Q99758"/>
    <dbReference type="MassIVE" id="Q99758"/>
    <dbReference type="PaxDb" id="9606-ENSP00000301732"/>
    <dbReference type="PeptideAtlas" id="Q99758"/>
    <dbReference type="ProteomicsDB" id="66998"/>
    <dbReference type="ProteomicsDB" id="78463">
        <molecule id="Q99758-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="1409">
        <property type="antibodies" value="72 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="21"/>
    <dbReference type="Ensembl" id="ENST00000301732.10">
        <molecule id="Q99758-1"/>
        <property type="protein sequence ID" value="ENSP00000301732.5"/>
        <property type="gene ID" value="ENSG00000167972.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000567910.1">
        <molecule id="Q99758-2"/>
        <property type="protein sequence ID" value="ENSP00000454397.1"/>
        <property type="gene ID" value="ENSG00000167972.15"/>
    </dbReference>
    <dbReference type="GeneID" id="21"/>
    <dbReference type="KEGG" id="hsa:21"/>
    <dbReference type="MANE-Select" id="ENST00000301732.10">
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            <end position="467"/>
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    <feature type="binding site" evidence="4">
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            <begin position="566"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
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        <location>
            <begin position="174"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="783"/>
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    </feature>
    <feature type="splice variant" id="VSP_056262" description="In isoform 2." evidence="25">
        <original>YIRE</original>
        <variation>EKLG</variation>
        <location>
            <begin position="206"/>
            <end position="209"/>
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    </feature>
    <feature type="splice variant" id="VSP_056263" description="In isoform 2." evidence="25">
        <location>
            <begin position="210"/>
            <end position="1704"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084240" description="In SMDP3; uncertain significance." evidence="8">
        <original>R</original>
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        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023497" description="In SMDP3; loss of intracellular vesicle membrane location; loss of proteolytic cleavage; does not affect N-glycosylation; loss of ATP hydrolysis activity; decreases ATP binding in vitro; dbSNP:rs121909182." evidence="6 9">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="101"/>
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    </feature>
    <feature type="sequence variant" id="VAR_025061" description="In dbSNP:rs45447801." evidence="24">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084241" description="In SMDP3; loss of lamellar bodies membrane location; loss of proteolytic cleavage; increases cellular free cholesterol and phosphatidylcholine transport; loss of vesicles formation; increases free cholesterol induced cell death; loss of protein oligomerization; dbSNP:rs879159551." evidence="8 12 16 20">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="215"/>
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    </feature>
    <feature type="sequence variant" id="VAR_084242" description="In SMDP3; uncertain significance; does not affect protein oligomerization; dbSNP:rs201299260." evidence="15 20">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="280"/>
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    </feature>
    <feature type="sequence variant" id="VAR_084243" description="In SMDP3; uncertain significance; does not affect protein oligomerization; dbSNP:rs117603931." evidence="8 20">
        <original>R</original>
        <variation>K</variation>
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            <position position="288"/>
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            <position position="290"/>
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            <position position="292"/>
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            <position position="982"/>
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            <position position="1076"/>
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            <position position="1114"/>
        </location>
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            <position position="1221"/>
        </location>
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            <position position="1301"/>
        </location>
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            <position position="1302"/>
        </location>
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            <position position="1388"/>
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            <position position="1399"/>
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            <position position="1553"/>
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            <begin position="1561"/>
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            <position position="1580"/>
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            <begin position="1589"/>
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            <position position="53"/>
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    <feature type="mutagenesis site" description="Loss of N-glycosylation. Reduces protein expression by 50%. Affects anterograde trafficking; when associated with Q-140. Reduces protein expression by 85%; when associated with Q-140. Does not affect lamellar body membrane location." evidence="14">
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            <position position="124"/>
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<entry dataset="Swiss-Prot" created="2002-09-19" modified="2026-01-28" version="168" xmlns="https://uniprot.org/uniprot">
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    <accession>B2R899</accession>
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            <taxon>Vertebrata</taxon>
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            <taxon>Mammalia</taxon>
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            <taxon>Hominidae</taxon>
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    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Skeletal muscle</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT THR-136</scope>
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            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>PNS</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="Cell" volume="145" first="423" last="434">
            <title>Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.</title>
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                <person name="Song H."/>
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            <dbReference type="PubMed" id="21496894"/>
            <dbReference type="DOI" id="10.1016/j.cell.2011.03.022"/>
        </citation>
        <scope>FUNCTION IN DNA DEMETHYLATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2007" name="Nature" volume="445" first="447" last="451">
            <title>The APOBEC-2 crystal structure and functional implications for the deaminase AID.</title>
            <authorList>
                <person name="Prochnow C."/>
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                <person name="Klein M.G."/>
                <person name="Goodman M.F."/>
                <person name="Chen X.S."/>
            </authorList>
            <dbReference type="PubMed" id="17187054"/>
            <dbReference type="DOI" id="10.1038/nature05492"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 41-224</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVE SITE</scope>
        <scope>ZINC-BINDING SITES</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Probable C to U editing enzyme whose physiological substrate is not yet known. Does not display detectable apoB mRNA editing. Has a low intrinsic cytidine deaminase activity. May play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>cytidine(6666) in apoB mRNA + H2O + H(+) = uridine(6666) in apoB mRNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:21772"/>
            <dbReference type="Rhea" id="RHEA-COMP:13888"/>
            <dbReference type="Rhea" id="RHEA-COMP:13889"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:65315"/>
            <dbReference type="ChEBI" id="CHEBI:82748"/>
            <dbReference type="EC" id="3.5.4.36"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="3">Binds 1 Zn(2+) ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Homotetramer.</text>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed exclusively in heart and skeletal muscle.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.36" evidence="3"/>
    <dbReference type="EMBL" id="AF161698">
        <property type="protein sequence ID" value="AAD45360.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223461">
        <property type="protein sequence ID" value="BAD97181.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313288">
        <property type="protein sequence ID" value="BAG36096.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL031778">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471081">
        <property type="protein sequence ID" value="EAX04009.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047767">
        <property type="protein sequence ID" value="AAH47767.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC069688">
        <property type="protein sequence ID" value="AAH69688.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC069764">
        <property type="protein sequence ID" value="AAH69764.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4848.1"/>
    <dbReference type="RefSeq" id="NP_006780.1">
        <property type="nucleotide sequence ID" value="NM_006789.4"/>
    </dbReference>
    <dbReference type="PDB" id="2NYT">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=41-224"/>
    </dbReference>
    <dbReference type="PDBsum" id="2NYT"/>
    <dbReference type="AlphaFoldDB" id="Q9Y235"/>
    <dbReference type="BMRB" id="Q9Y235"/>
    <dbReference type="SMR" id="Q9Y235"/>
    <dbReference type="BioGRID" id="116133">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-60263N"/>
    <dbReference type="FunCoup" id="Q9Y235">
        <property type="interactions" value="226"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000244669"/>
    <dbReference type="iPTMnet" id="Q9Y235"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y235"/>
    <dbReference type="BioMuta" id="APOBEC2"/>
    <dbReference type="DMDM" id="23396446"/>
    <dbReference type="MassIVE" id="Q9Y235"/>
    <dbReference type="PaxDb" id="9606-ENSP00000244669"/>
    <dbReference type="PeptideAtlas" id="Q9Y235"/>
    <dbReference type="ProteomicsDB" id="85628"/>
    <dbReference type="Antibodypedia" id="2816">
        <property type="antibodies" value="275 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10930"/>
    <dbReference type="Ensembl" id="ENST00000244669.3">
        <property type="protein sequence ID" value="ENSP00000244669.2"/>
        <property type="gene ID" value="ENSG00000124701.7"/>
    </dbReference>
    <dbReference type="GeneID" id="10930"/>
    <dbReference type="KEGG" id="hsa:10930"/>
    <dbReference type="MANE-Select" id="ENST00000244669.3">
        <property type="protein sequence ID" value="ENSP00000244669.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006789.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006780.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003opl.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:605"/>
    <dbReference type="ClinPGx" id="PA24890"/>
    <dbReference type="CTD" id="10930"/>
    <dbReference type="DisGeNET" id="10930"/>
    <dbReference type="GeneCards" id="APOBEC2"/>
    <dbReference type="HGNC" id="HGNC:605">
        <property type="gene designation" value="APOBEC2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000124701">
        <property type="expression patterns" value="Tissue enhanced (heart muscle, skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MIM" id="604797">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000124701"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000124701"/>
    <dbReference type="eggNOG" id="ENOG502RABR">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156616"/>
    <dbReference type="HOGENOM" id="CLU_080056_0_0_1"/>
    <dbReference type="InParanoid" id="Q9Y235"/>
    <dbReference type="OMA" id="WEEPDIQ"/>
    <dbReference type="OrthoDB" id="8841220at2759"/>
    <dbReference type="PAN-GO" id="Q9Y235">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y235"/>
    <dbReference type="PathwayCommons" id="Q9Y235"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000124701"/>
    <dbReference type="BioGRID-ORCS" id="10930">
        <property type="hits" value="11 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APOBEC2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9Y235"/>
    <dbReference type="GeneWiki" id="APOBEC2"/>
    <dbReference type="GenomeRNAi" id="10930"/>
    <dbReference type="Pharos" id="Q9Y235">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y235"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y235">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000124701">
        <property type="expression patterns" value="Expressed in skeletal muscle tissue of rectus abdominis and 137 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016556">
        <property type="term" value="P:mRNA modification"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006397">
        <property type="term" value="P:mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044029">
        <property type="term" value="P:positive regulation of gene expression via chromosomal CpG island demethylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000031">
        <property type="entry name" value="Probable C-&gt;U-editing enzyme APOBEC-2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF4">
        <property type="entry name" value="C-U-EDITING ENZYME APOBEC-2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18772">
        <property type="entry name" value="APOBEC2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0507">mRNA processing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171749" description="C-&gt;U-editing enzyme APOBEC-2">
        <location>
            <begin position="1"/>
            <end position="224"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="1">
        <location>
            <begin position="64"/>
            <end position="169"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="3">
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="60"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="98"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="128"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="131"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_024406" description="In dbSNP:rs2076472." evidence="5">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="48"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="turn" evidence="7">
        <location>
            <begin position="54"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="62"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="68"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="83"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="99"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="116"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="129"/>
            <end position="141"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="145"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="160"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="strand" evidence="7">
        <location>
            <begin position="175"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="181"/>
            <end position="191"/>
        </location>
    </feature>
    <feature type="helix" evidence="7">
        <location>
            <begin position="208"/>
            <end position="223"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="17187054"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="21496894"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0007829" key="7">
        <source>
            <dbReference type="PDB" id="2NYT"/>
        </source>
    </evidence>
    <sequence length="224" mass="25703" checksum="CA0905AFAA8C8FA1" modified="1999-11-01" version="1">MAQKEEAAVATEAASQNGEDLENLDDPEKLKELIELPPFEIVTGERLPANFFKFQFRNVEYSSGRNKTFLCYVVEAQGKGGQVQASRGYLEDEHAAAHAEEAFFNTILPAFDPALRYNVTWYVSSSPCAACADRIIKTLSKTKNLRLLILVGRLFMWEEPEIQAALKKLKEAGCKLRIMKPQDFEYVWQNFVEQEEGESKAFQPWEDIQENFLYYEEKLADILK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>O14678</accession>
    <accession>A8K5L7</accession>
    <accession>Q6IAQ0</accession>
    <accession>Q96E75</accession>
    <name>ABCD4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">Lysosomal cobalamin transporter ABCD4</fullName>
            <ecNumber evidence="12 19 20">7.6.2.8</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="22">ATP-binding cassette sub-family D member 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PMP70-related protein</fullName>
            <shortName>P70R</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal membrane protein 1-like</fullName>
            <shortName>PXMP1-L</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal membrane protein 69</fullName>
            <shortName>PMP69</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ABCD4</name>
        <name type="synonym">PXMP1L</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Biochem. Biophys. Res. Commun." volume="237" first="152" last="157">
            <title>Primary structure of human PMP69, a putative peroxisomal ABC-transporter.</title>
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                <person name="Holzinger A."/>
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            <dbReference type="PubMed" id="9266848"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
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                <person name="Holzinger A."/>
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            <dbReference type="PubMed" id="9599016"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="Hum. Mol. Genet." volume="6" first="1925" last="1931">
            <title>Identification of a fourth half ABC transporter in the human peroxisomal membrane.</title>
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                <person name="Shani N."/>
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                <person name="Valle D."/>
            </authorList>
            <dbReference type="PubMed" id="9302272"/>
            <dbReference type="DOI" id="10.1093/hmg/6.11.1925"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
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                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS THR-304 AND LYS-368</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Ota T."/>
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                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Noguchi S."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Tongue</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="Mol. Membr. Biol." volume="31" first="250" last="261">
            <title>Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4.</title>
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                <person name="Deme J.C."/>
                <person name="Hancock M.A."/>
                <person name="Xia X."/>
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                <person name="Plesa M."/>
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            <dbReference type="PubMed" id="25535791"/>
            <dbReference type="DOI" id="10.3109/09687688.2014.990998"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH LMBRD1 AND MMACHC</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2016" name="Sci. Rep." volume="6" first="30183" last="30183">
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                <person name="Kawaguchi K."/>
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            <dbReference type="PubMed" id="27456980"/>
            <dbReference type="DOI" id="10.1038/srep30183"/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH LMBRD1</scope>
    </reference>
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            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS THR-304 AND LYS-368</scope>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS THR-304 AND LYS-368</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="10">
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            <title>Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism.</title>
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                <person name="Coelho D."/>
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        <scope>FUNCTION</scope>
        <scope>VARIANT MAHCJ CYS-319</scope>
        <scope>INVOLVEMENT IN MAHCJ</scope>
        <scope>MUTAGENESIS OF LYS-427; ASP-548 AND GLU-549</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <dbReference type="PubMed" id="28572511"/>
            <dbReference type="DOI" id="10.1074/jbc.m117.784819"/>
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        <scope>INVOLVEMENT IN MAHCJ</scope>
        <scope>VARIANT MAHCJ GLN-432</scope>
        <scope>CHARACTERIZATION OF VARIANTS MAHCJ LYS-141 AND GLN-432</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH LMBRD1</scope>
        <scope>MUTAGENESIS OF GLY-426; LYS-427 AND ASP-548</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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                <person name="Kitai K."/>
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            <dbReference type="PubMed" id="33845046"/>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF ASN-141; TYR-319 AND LYS-427</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH LMBRD1</scope>
        <scope>CHARACTERIZATION OF VARIANTS MAHCJ CYS-319 AND ASN-141</scope>
        <scope>SUBUNIT</scope>
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            <dbReference type="PubMed" id="12111378"/>
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        <scope>VARIANTS THR-304 AND LYS-368</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2012" name="Mol. Genet. Metab." volume="107" first="664" last="668">
            <title>Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing.</title>
            <authorList>
                <person name="Kim J.C."/>
                <person name="Lee N.C."/>
                <person name="Hwu P.W."/>
                <person name="Chien Y.H."/>
                <person name="Fahiminiya S."/>
                <person name="Majewski J."/>
                <person name="Watkins D."/>
                <person name="Rosenblatt D.S."/>
            </authorList>
            <dbReference type="PubMed" id="23141461"/>
            <dbReference type="DOI" id="10.1016/j.ymgme.2012.10.005"/>
        </citation>
        <scope>VARIANT MAHCJ LYS-141</scope>
        <scope>INVOLVEMENT IN MAHCJ</scope>
    </reference>
    <reference evidence="23" key="15">
        <citation type="journal article" date="2019" name="Cell Res." volume="29" first="1039" last="1041">
            <title>Cryo-EM structure of human lysosomal cobalamin exporter ABCD4.</title>
            <authorList>
                <person name="Xu D."/>
                <person name="Feng Z."/>
                <person name="Hou W.T."/>
                <person name="Jiang Y.L."/>
                <person name="Wang L."/>
                <person name="Sun L."/>
                <person name="Zhou C.Z."/>
                <person name="Chen Y."/>
            </authorList>
            <dbReference type="PubMed" id="31467407"/>
            <dbReference type="DOI" id="10.1038/s41422-019-0222-z"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 2-606</scope>
        <scope>CHARACTERIZATION OF VARIANTS MAHCJ CYS-319 AND GLN-432</scope>
        <scope>MUTAGENESIS OF GLU-549</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <comment type="function">
        <text evidence="6 9 10 11 12 16">Lysosomal membrane protein that transports cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol in an ATP-dependent manner (PubMed:22922874, PubMed:28572511, PubMed:31467407, PubMed:33845046). Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane (PubMed:27456980). Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 19 20">
            <text>an R-cob(III)alamin(out) + ATP + H2O = an R-cob(III)alamin(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17873"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:140785"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="7.6.2.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:17874"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="12">426 uM for cobalamin</KM>
            <Vmax evidence="12">667.0 pmol/min/mg enzyme toward cobalamin</Vmax>
            <Vmax evidence="11">11.8 nmol/min/mg enzyme toward ATP</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="8 9 12">Homodimer or heterodimer (PubMed:27456980, PubMed:33845046). Interacts with LMBRD1; this interaction induces the translocation of ABCD4 from the ER to the lysosome membrane (PubMed:27456980, PubMed:28572511). Interacts with LMBRD1 and MMACHC; this interaction ensures the transport of cobalamin from the lysosome to the cytosol (PubMed:25535791).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714396">
            <id>O14678</id>
        </interactant>
        <interactant intactId="EBI-714396">
            <id>O14678</id>
            <label>ABCD4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714396">
            <id>O14678</id>
        </interactant>
        <interactant intactId="EBI-6911574">
            <id>A2RU67</id>
            <label>FAM234B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714396">
            <id>O14678</id>
        </interactant>
        <interactant intactId="EBI-2805231">
            <id>Q9NUN5</id>
            <label>LMBRD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Endoplasmic reticulum membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 8 9 10 12">Lysosome membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="9 10">Targeted by LMBRD1 lysosomal chaperone to the lysosomal membrane.</text>
    </comment>
    <comment type="tissue specificity">
        <text>Ubiquitous.</text>
    </comment>
    <comment type="disease" evidence="6 7 10 11 12">
        <disease id="DI-03558">
            <name>Methylmalonic aciduria and homocystinuria type cblJ</name>
            <acronym>MAHCJ</acronym>
            <description>A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay.</description>
            <dbReference type="MIM" id="614857"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="9 10 12 13">Originally proposed to be a peroxisomal protein (PubMed:9266848). Recent studies have suggested its localization to the endoplasmic reticulum and within the lysosome (PubMed:27456980).</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.8" evidence="12 19 20"/>
    <dbReference type="EMBL" id="Y14318">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14319">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14320">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14321">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14322">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14323">
        <property type="protein sequence ID" value="CAA74699.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF009746">
        <property type="protein sequence ID" value="AAB83967.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007412">
        <property type="protein sequence ID" value="AAP36080.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291332">
        <property type="protein sequence ID" value="BAF84021.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR457104">
        <property type="protein sequence ID" value="CAG33385.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012815">
        <property type="protein sequence ID" value="AAH12815.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9828.1"/>
    <dbReference type="PIR" id="JC5604">
        <property type="entry name" value="JC5604"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005041.1">
        <property type="nucleotide sequence ID" value="NM_005050.4"/>
    </dbReference>
    <dbReference type="PDB" id="6JBJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B=2-606"/>
    </dbReference>
    <dbReference type="PDBsum" id="6JBJ"/>
    <dbReference type="AlphaFoldDB" id="O14678"/>
    <dbReference type="EMDB" id="EMD-9791"/>
    <dbReference type="SMR" id="O14678"/>
    <dbReference type="BioGRID" id="111784">
        <property type="interactions" value="46"/>
    </dbReference>
    <dbReference type="CORUM" id="O14678"/>
    <dbReference type="FunCoup" id="O14678">
        <property type="interactions" value="1068"/>
    </dbReference>
    <dbReference type="IntAct" id="O14678">
        <property type="interactions" value="59"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000349396"/>
    <dbReference type="TCDB" id="3.A.1.203.9">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O14678"/>
    <dbReference type="PhosphoSitePlus" id="O14678"/>
    <dbReference type="BioMuta" id="ABCD4"/>
    <dbReference type="jPOST" id="O14678"/>
    <dbReference type="MassIVE" id="O14678"/>
    <dbReference type="PaxDb" id="9606-ENSP00000349396"/>
    <dbReference type="PeptideAtlas" id="O14678"/>
    <dbReference type="ProteomicsDB" id="48163"/>
    <dbReference type="Pumba" id="O14678"/>
    <dbReference type="Antibodypedia" id="184">
        <property type="antibodies" value="237 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="5826"/>
    <dbReference type="Ensembl" id="ENST00000356924.9">
        <property type="protein sequence ID" value="ENSP00000349396.4"/>
        <property type="gene ID" value="ENSG00000119688.22"/>
    </dbReference>
    <dbReference type="GeneID" id="5826"/>
    <dbReference type="KEGG" id="hsa:5826"/>
    <dbReference type="MANE-Select" id="ENST00000356924.9">
        <property type="protein sequence ID" value="ENSP00000349396.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005050.4"/>
        <property type="RefSeq protein sequence ID" value="NP_005041.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xpr.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:68"/>
    <dbReference type="ClinPGx" id="PA24403"/>
    <dbReference type="CTD" id="5826"/>
    <dbReference type="DisGeNET" id="5826"/>
    <dbReference type="GeneCards" id="ABCD4"/>
    <dbReference type="GeneReviews" id="ABCD4"/>
    <dbReference type="HGNC" id="HGNC:68">
        <property type="gene designation" value="ABCD4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000119688">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCD4"/>
    <dbReference type="MIM" id="603214">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="614857">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000119688"/>
    <dbReference type="Orphanet" id="369955">
        <property type="disease" value="Methylmalonic acidemia with homocystinuria, type cblJ"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000119688"/>
    <dbReference type="eggNOG" id="KOG0060">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182955"/>
    <dbReference type="HOGENOM" id="CLU_007587_7_0_1"/>
    <dbReference type="InParanoid" id="O14678"/>
    <dbReference type="OMA" id="KQFHDME"/>
    <dbReference type="OrthoDB" id="422637at2759"/>
    <dbReference type="PAN-GO" id="O14678">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O14678"/>
    <dbReference type="BRENDA" id="7.6.2.8">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O14678"/>
    <dbReference type="Reactome" id="R-HSA-5683329">
        <property type="pathway name" value="Defective ABCD4 causes MAHCJ"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9758881">
        <property type="pathway name" value="Uptake of dietary cobalamins into enterocytes"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9758890">
        <property type="pathway name" value="Transport of RCbl within the body"/>
    </dbReference>
    <dbReference type="SignaLink" id="O14678"/>
    <dbReference type="Agora" id="ENSG00000119688"/>
    <dbReference type="BioGRID-ORCS" id="5826">
        <property type="hits" value="31 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCD4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCD4"/>
    <dbReference type="GenomeRNAi" id="5826"/>
    <dbReference type="Pharos" id="O14678">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O14678"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="O14678">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000119688">
        <property type="expression patterns" value="Expressed in right uterine tube and 178 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O14678">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:ATP-binding cassette (ABC) transporter complex"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="C:endoplasmic reticulum membrane"/>
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        <property type="term" value="C:lysosomal membrane"/>
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        <property type="term" value="F:ABC-type vitamin B12 transporter activity"/>
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        <property type="project" value="MGI"/>
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        <property type="term" value="F:ATP binding"/>
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        <property type="term" value="F:identical protein binding"/>
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    </dbReference>
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        <property type="term" value="P:cellular response to leukemia inhibitory factor"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
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        <property type="term" value="P:cobalamin metabolic process"/>
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        <property type="project" value="MGI"/>
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        <property type="term" value="P:very long-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ATP-binding cassette sub-family D member 4"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="AAA+_ATPase"/>
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        <property type="entry name" value="ATP-BINDING CASSETTE, SUB-FAMILY D MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="LYSOSOMAL COBALAMIN TRANSPORTER ABCD4"/>
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    </dbReference>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-1278">Translocase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000093312" description="Lysosomal cobalamin transporter ABCD4">
        <location>
            <begin position="1"/>
            <end position="606"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="43"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="76"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="190"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="279"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="314"/>
            <end position="334"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transmembrane type-1" evidence="3">
        <location>
            <begin position="39"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter" evidence="2">
        <location>
            <begin position="389"/>
            <end position="603"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="421"/>
            <end position="428"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_084972" description="In MAHCJ; does not affect ATPase activity. Loss of cobalamin transport activity. Decreases interaction with LMBD1. Does not affect lysosomal subcellular location; dbSNP:rs776529140." evidence="7 10 12">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048134" description="In dbSNP:rs34992370.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020778" description="In dbSNP:rs4148077." evidence="4 5 14 15">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="304"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069097" description="In MAHCJ; strong decrease of ATPase activity. Strong decrease of cobalamin transport activity; dbSNP:rs201777056." evidence="6 11 12">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="319"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048135" description="In dbSNP:rs35073715.">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="350"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020222" description="In dbSNP:rs3742801." evidence="4 5 14 15">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084973" description="In MAHCJ; decreases interaction with LMBD1. Does not affect lysosomal subcellular location. Decreases ATPase activity; dbSNP:rs745414252." evidence="10 11">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase nor cobalamin transport activities." evidence="12">
        <original>N</original>
        <variation>A</variation>
        <variation>D</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases of ATPase activity. Decreases cobalamin transport activity." evidence="12">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="319"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect ATPase activity. Does not affect cobalamin transport activity." evidence="12">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="319"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity." evidence="10">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="426"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of ATPase activity. Loss of cobalamin transport activity." evidence="12">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases interaction with LMBD1. Decreases colocalization with LMBD1. Decreases cobalamin transport activity. Reduces synthesis of adenosylcobalamin and methylcobalamin." evidence="6 10">
        <original>K</original>
        <variation>L</variation>
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases interaction with LMBD1. Reduces synthesis of adenosylcobalamin and methylcobalamin." evidence="6 10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="548"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases ATPase activity. Reduces synthesis of adenosylcobalamin and methylcobalamin." evidence="6 11">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="549"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; BAF84021." evidence="17" ref="5">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="594"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; CAG33385." evidence="17" ref="8">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="606"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00441"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12111378"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="22922874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="23141461"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="25535791"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="27456980"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="28572511"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="31467407"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="33845046"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="9266848"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="25535791"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0000305" key="18">
        <source>
            <dbReference type="PubMed" id="27456980"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="28572511"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20">
        <source>
            <dbReference type="PubMed" id="31467407"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="33845046"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:68"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PDB" id="6JBJ"/>
        </source>
    </evidence>
    <sequence length="606" mass="68597" checksum="2D88DEFED0EA0777" modified="1998-01-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-12-05" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H222</accession>
    <accession>Q2T9G2</accession>
    <accession>Q96QZ2</accession>
    <accession>Q96QZ3</accession>
    <name>ABCG5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">ATP-binding cassette sub-family G member 5</fullName>
            <ecNumber evidence="1">7.6.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="15">Sterolin-1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ABCG5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT GLU-604</scope>
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        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
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                <person name="Lee M.-H."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS STSL2 HIS-389; HIS-419 AND PRO-419</scope>
        <scope>VARIANT GLU-604</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15815621"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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                <person name="Lu K."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-88 (ISOFORM 1)</scope>
        <scope>VARIANTS STSL2 GLN-146; HIS-389; PRO-419; HIS-419 AND SER-550</scope>
        <scope>VARIANT GLU-604</scope>
    </reference>
    <reference key="7">
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        <scope>REVIEW</scope>
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                <person name="Graf G.A."/>
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            <dbReference type="DOI" id="10.1074/jbc.m310223200"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="Biochemistry" volume="45" first="9929" last="9939">
            <title>Purification and ATP hydrolysis of the putative cholesterol transporters ABCG5 and ABCG8.</title>
            <authorList>
                <person name="Wang Z."/>
                <person name="Stalcup L.D."/>
                <person name="Harvey B.J."/>
                <person name="Weber J."/>
                <person name="Chloupkova M."/>
                <person name="Dumont M.E."/>
                <person name="Dean M."/>
                <person name="Urbatsch I.L."/>
            </authorList>
            <dbReference type="PubMed" id="16893193"/>
            <dbReference type="DOI" id="10.1021/bi0608055"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2010" name="Biochemistry" volume="49" first="3403" last="3411">
            <title>Bile acids stimulate ATP hydrolysis in the purified cholesterol transporter ABCG5/G8.</title>
            <authorList>
                <person name="Johnson B.J."/>
                <person name="Lee J.Y."/>
                <person name="Pickert A."/>
                <person name="Urbatsch I.L."/>
            </authorList>
            <dbReference type="PubMed" id="20210363"/>
            <dbReference type="DOI" id="10.1021/bi902064g"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF 92-LYS-THR-93</scope>
    </reference>
    <reference evidence="23" key="11">
        <citation type="journal article" date="2016" name="Nature" volume="533" first="561" last="564">
            <title>Crystal structure of the human sterol transporter ABCG5/ABCG8.</title>
            <authorList>
                <person name="Lee J.Y."/>
                <person name="Kinch L.N."/>
                <person name="Borek D.M."/>
                <person name="Wang J."/>
                <person name="Wang J."/>
                <person name="Urbatsch I.L."/>
                <person name="Xie X.S."/>
                <person name="Grishin N.V."/>
                <person name="Cohen J.C."/>
                <person name="Otwinowski Z."/>
                <person name="Hobbs H.H."/>
                <person name="Rosenbaum D.M."/>
            </authorList>
            <dbReference type="PubMed" id="27144356"/>
            <dbReference type="DOI" id="10.1038/nature17666"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.93 ANGSTROMS) IN COMPLEX WITH ABCG8</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF TYR-432 AND ALA-540</scope>
        <scope>SUBUNIT</scope>
        <scope>TOPOLOGY</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2001" name="Hum. Mutat." volume="18" first="359" last="360">
            <title>Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia.</title>
            <authorList>
                <person name="Hubacek J.A."/>
                <person name="Berge K.E."/>
                <person name="Cohen J.C."/>
                <person name="Hobbs H.H."/>
            </authorList>
            <dbReference type="PubMed" id="11668628"/>
            <dbReference type="DOI" id="10.1002/humu.1206"/>
        </citation>
        <scope>VARIANT STSL2 LYS-437</scope>
        <scope>VARIANTS VAL-523; TYR-600; GLU-604 AND VAL-622</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="24881" last="24888">
            <title>Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking.</title>
            <authorList>
                <person name="Graf G.A."/>
                <person name="Cohen J.C."/>
                <person name="Hobbs H.H."/>
            </authorList>
            <dbReference type="PubMed" id="15054092"/>
            <dbReference type="DOI" id="10.1074/jbc.m402634200"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS STSL2 GLN-146; HIS-389; PRO-419; HIS-419 AND LYS-437</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2022" name="Front. Cardiovasc. Med." volume="9" first="887618" last="887618">
            <title>Clinical and genetic analysis of a family with sitosterolemia caused by a novel ATP-binding cassette subfamily G member 5 compound heterozygous mutation.</title>
            <authorList>
                <person name="Shen M.F."/>
                <person name="Hu Y.N."/>
                <person name="Chen W.X."/>
                <person name="Liao L.S."/>
                <person name="Wu M."/>
                <person name="Wu Q.Y."/>
                <person name="Zhang J.H."/>
                <person name="Zhang Y.P."/>
                <person name="Luo J.W."/>
                <person name="Lin X.F."/>
            </authorList>
            <dbReference type="PubMed" id="35557526"/>
            <dbReference type="DOI" id="10.3389/fcvm.2022.887618"/>
        </citation>
        <scope>VARIANT STSL2 ARG-99</scope>
    </reference>
    <comment type="function">
        <text evidence="6 10 11 12 13 16 19">ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of dietary plant sterols and cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:11099417, PubMed:11138003, PubMed:15054092, PubMed:27144356). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11138003, PubMed:15054092). The heterodimer with ABCG8 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>cholesterol(in) + ATP + H2O = cholesterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39051"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16113"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:39052"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>sitosterol(in) + ATP + H2O = sitosterol(out) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39103"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27693"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:39104"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="12 13">The ATPase activity of the heterodimer is stimulated by cholate. Taurocholate, glycocholate, taurochenodeoxycholate, glycochenodeoxycholate and taurodeoxycholate also stimulate ATPase activity, but to a lower degree. Glycodeoxycholate has no significant effect on ATPase activity. ATPase activity is inhibited by vanadate and by berillium fluoride.</text>
    </comment>
    <comment type="subunit">
        <text evidence="11 12 13">Heterodimer with ABCG8.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1761423">
            <id>Q9H222</id>
        </interactant>
        <interactant intactId="EBI-3908684">
            <id>Q9H221</id>
            <label>ABCG8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1761423">
            <id>Q9H222</id>
        </interactant>
        <interactant intactId="EBI-389883">
            <id>P16333</id>
            <label>NCK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16205983">
            <id>Q9H222-1</id>
        </interactant>
        <interactant intactId="EBI-16205990">
            <id>Q9H221-1</id>
            <label>ABCG8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="20 21">Cell membrane</location>
            <topology evidence="13">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Apical cell membrane</location>
            <topology evidence="13">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H222-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H222-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055770"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Strongly expressed in the liver, lower levels in the small intestine and colon.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. Within this motif, the conserved Lys is essential for transport activity mediated by the heterodimer with ABCG8.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11 12">N-glycosylated.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 10 14">
        <disease id="DI-05695">
            <name>Sitosterolemia 2</name>
            <acronym>STSL2</acronym>
            <description>A form of sitosterolemia, an autosomal recessive metabolic disorder characterized by unregulated intestinal absorption of cholesterol, phytosterols and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.</description>
            <dbReference type="MIM" id="618666"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="18">Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="7.6.2.-" evidence="1"/>
    <dbReference type="EMBL" id="AF320293">
        <property type="protein sequence ID" value="AAG40003.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF312715">
        <property type="protein sequence ID" value="AAG53099.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011242">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC108476">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAX00286.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC111541">
        <property type="protein sequence ID" value="AAI11542.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF404106">
        <property type="protein sequence ID" value="AAK85387.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF404107">
        <property type="protein sequence ID" value="AAK85388.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1814.1">
        <molecule id="Q9H222-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_071881.1">
        <molecule id="Q9H222-1"/>
        <property type="nucleotide sequence ID" value="NM_022436.3"/>
    </dbReference>
    <dbReference type="PDB" id="5DO7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.93 A"/>
        <property type="chains" value="A/C=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7JR7">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7R87">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7R88">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7R89">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7R8A">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="7R8B">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A=1-651"/>
    </dbReference>
    <dbReference type="PDB" id="8CUB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="4.05 A"/>
        <property type="chains" value="A/C=3-651"/>
    </dbReference>
    <dbReference type="PDBsum" id="5DO7"/>
    <dbReference type="PDBsum" id="7JR7"/>
    <dbReference type="PDBsum" id="7R87"/>
    <dbReference type="PDBsum" id="7R88"/>
    <dbReference type="PDBsum" id="7R89"/>
    <dbReference type="PDBsum" id="7R8A"/>
    <dbReference type="PDBsum" id="7R8B"/>
    <dbReference type="PDBsum" id="8CUB"/>
    <dbReference type="AlphaFoldDB" id="Q9H222"/>
    <dbReference type="EMDB" id="EMD-22443"/>
    <dbReference type="EMDB" id="EMD-24310"/>
    <dbReference type="EMDB" id="EMD-24311"/>
    <dbReference type="EMDB" id="EMD-24312"/>
    <dbReference type="EMDB" id="EMD-24313"/>
    <dbReference type="EMDB" id="EMD-24314"/>
    <dbReference type="SMR" id="Q9H222"/>
    <dbReference type="BioGRID" id="122124">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9H222"/>
    <dbReference type="DIP" id="DIP-42630N"/>
    <dbReference type="FunCoup" id="Q9H222">
        <property type="interactions" value="89"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H222">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H222"/>
    <dbReference type="STRING" id="9606.ENSP00000384513"/>
    <dbReference type="DrugBank" id="DB08834">
        <property type="generic name" value="Tauroursodeoxycholic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11635">
        <property type="generic name" value="Tocofersolan"/>
    </dbReference>
    <dbReference type="TCDB" id="3.A.1.204.5">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9H222">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H222">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H222"/>
    <dbReference type="PhosphoSitePlus" id="Q9H222"/>
    <dbReference type="BioMuta" id="ABCG5"/>
    <dbReference type="DMDM" id="17432917"/>
    <dbReference type="MassIVE" id="Q9H222"/>
    <dbReference type="PaxDb" id="9606-ENSP00000260645"/>
    <dbReference type="PeptideAtlas" id="Q9H222"/>
    <dbReference type="Antibodypedia" id="14899">
        <property type="antibodies" value="228 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="64240"/>
    <dbReference type="Ensembl" id="ENST00000405322.8">
        <molecule id="Q9H222-1"/>
        <property type="protein sequence ID" value="ENSP00000384513.2"/>
        <property type="gene ID" value="ENSG00000138075.15"/>
    </dbReference>
    <dbReference type="GeneID" id="64240"/>
    <dbReference type="KEGG" id="hsa:64240"/>
    <dbReference type="MANE-Select" id="ENST00000405322.8">
        <property type="protein sequence ID" value="ENSP00000384513.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_022436.3"/>
        <property type="RefSeq protein sequence ID" value="NP_071881.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002rtn.3">
        <molecule id="Q9H222-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:13886"/>
    <dbReference type="ClinPGx" id="PA24411"/>
    <dbReference type="CTD" id="64240"/>
    <dbReference type="DisGeNET" id="64240"/>
    <dbReference type="GeneCards" id="ABCG5"/>
    <dbReference type="GeneReviews" id="ABCG5"/>
    <dbReference type="HGNC" id="HGNC:13886">
        <property type="gene designation" value="ABCG5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000138075">
        <property type="expression patterns" value="Group enriched (intestine, liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABCG5"/>
    <dbReference type="MIM" id="605459">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="618666">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000138075"/>
    <dbReference type="Orphanet" id="391665">
        <property type="disease" value="Homozygous familial hypercholesterolemia"/>
    </dbReference>
    <dbReference type="Orphanet" id="2882">
        <property type="disease" value="Sitosterolemia"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000138075"/>
    <dbReference type="eggNOG" id="KOG0061">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157985"/>
    <dbReference type="HOGENOM" id="CLU_000604_57_9_1"/>
    <dbReference type="InParanoid" id="Q9H222"/>
    <dbReference type="OMA" id="RVRPWWD"/>
    <dbReference type="OrthoDB" id="66620at2759"/>
    <dbReference type="PAN-GO" id="Q9H222">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H222"/>
    <dbReference type="PathwayCommons" id="Q9H222"/>
    <dbReference type="Reactome" id="R-HSA-1369062">
        <property type="pathway name" value="ABC transporters in lipid homeostasis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5679090">
        <property type="pathway name" value="Defective ABCG8 causes GBD4 and sitosterolemia"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5679096">
        <property type="pathway name" value="Defective ABCG5 causes sitosterolemia"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9029569">
        <property type="pathway name" value="NR1H3 &amp; NR1H2 regulate gene expression linked to cholesterol transport and efflux"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9H222"/>
    <dbReference type="SIGNOR" id="Q9H222"/>
    <dbReference type="Agora" id="ENSG00000138075"/>
    <dbReference type="BioGRID-ORCS" id="64240">
        <property type="hits" value="10 hits in 1149 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABCG5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABCG5"/>
    <dbReference type="GenomeRNAi" id="64240"/>
    <dbReference type="Pharos" id="Q9H222">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H222"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H222">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000138075">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 43 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016324">
        <property type="term" value="C:apical plasma membrane"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043190">
        <property type="term" value="C:ATP-binding cassette (ABC) transporter complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043235">
        <property type="term" value="C:receptor complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140359">
        <property type="term" value="F:ABC-type transporter activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042626">
        <property type="term" value="F:ATPase-coupled transmembrane transporter activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120020">
        <property type="term" value="F:cholesterol transfer activity"/>
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            <dbReference type="PubMed" id="11590207"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="18"/>
    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="11099417"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20">
        <source>
            <dbReference type="PubMed" id="16893193"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="27144356"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:13886"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PDB" id="5DO7"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="7R87"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="7R89"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="7R8A"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="7R8B"/>
        </source>
    </evidence>
    <sequence length="651" mass="72504" checksum="950BABFCBB6A1536" modified="2001-03-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-02-01" modified="2026-01-28" version="204" xmlns="https://uniprot.org/uniprot">
    <accession>P41238</accession>
    <accession>Q9UE64</accession>
    <accession>Q9UM71</accession>
    <name>ABEC1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">C-&gt;U-editing enzyme APOBEC-1</fullName>
            <ecNumber evidence="5 8">3.5.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="19">Apolipoprotein B mRNA-editing enzyme catalytic subunit 1</fullName>
            <shortName evidence="14">APO1</shortName>
            <shortName evidence="16">APOBEC-1</shortName>
            <shortName>Apolipoprotein B mRNA-editing enzyme 1</shortName>
            <ecNumber evidence="5">3.5.4.36</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="15">HEPR</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="18">mRNA(cytosine(6666)) deaminase 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="19" type="primary">APOBEC1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Nucleic Acids Res." volume="22" first="1874" last="1879">
            <title>Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein.</title>
            <authorList>
                <person name="Hadjiagapiou C."/>
                <person name="Giannoni F."/>
                <person name="Funahashi T."/>
                <person name="Skarosi S.F."/>
                <person name="Davidson N.O."/>
            </authorList>
            <dbReference type="PubMed" id="8208612"/>
            <dbReference type="DOI" id="10.1093/nar/22.10.1874"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT ILE-80</scope>
        <source>
            <tissue>Intestine</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="Proc. Natl. Acad. Sci. U.S.A." volume="91" first="8522" last="8526">
            <title>Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene.</title>
            <authorList>
                <person name="Lau P.P."/>
                <person name="Zhu H.-J."/>
                <person name="Baldini A."/>
                <person name="Charnsangavej C."/>
                <person name="Chan L."/>
            </authorList>
            <dbReference type="PubMed" id="8078915"/>
            <dbReference type="DOI" id="10.1073/pnas.91.18.8522"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>SUBUNIT</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT ILE-80</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="J. Lipid Res." volume="38" first="847" last="859">
            <title>Characterization of the human apobec-1 gene: expression in gastrointestinal tissues determined by alternative splicing with production of a novel truncated peptide.</title>
            <authorList>
                <person name="Hirano K."/>
                <person name="Min J."/>
                <person name="Funahashi T."/>
                <person name="Baunoch D.A."/>
                <person name="Davidson N.O."/>
            </authorList>
            <dbReference type="PubMed" id="9186903"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT ILE-80</scope>
        <source>
            <tissue>Osteosarcoma</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="Genomics" volume="47" first="266" last="275">
            <title>Human apolipoprotein B RNA editing deaminase gene (APOBEC1).</title>
            <authorList>
                <person name="Fujino T."/>
                <person name="Navaratnam N."/>
                <person name="Scott J."/>
            </authorList>
            <dbReference type="PubMed" id="9479499"/>
            <dbReference type="DOI" id="10.1006/geno.1997.5110"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ILE-80</scope>
        <source>
            <tissue>Peripheral blood leukocyte</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="1996-11" db="EMBL/GenBank/DDBJ databases">
            <title>A novel mutation in exon 3 of the human apoB editing protein gene.</title>
            <authorList>
                <person name="Hong S.H."/>
                <person name="Kim J.Q."/>
                <person name="Lee C.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 16-147</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1997" name="J. Biol. Chem." volume="272" first="1452" last="1455">
            <title>Cloning of an Apobec-1-binding protein that also interacts with apolipoprotein B mRNA and evidence for its involvement in RNA editing.</title>
            <authorList>
                <person name="Lau P.P."/>
                <person name="Zhu H.J."/>
                <person name="Nakamuta M."/>
                <person name="Chan L."/>
            </authorList>
            <dbReference type="PubMed" id="8999813"/>
            <dbReference type="DOI" id="10.1074/jbc.272.3.1452"/>
        </citation>
        <scope>INTERACTION WITH HNRPAB</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2001" name="Biochem. Biophys. Res. Commun." volume="282" first="977" last="983">
            <title>Two-hybrid cloning identifies an RNA-binding protein, GRY-RBP, as a component of apobec-1 editosome.</title>
            <authorList>
                <person name="Lau P.P."/>
                <person name="Chang B.-H."/>
                <person name="Chan L."/>
            </authorList>
            <dbReference type="PubMed" id="11352648"/>
            <dbReference type="DOI" id="10.1006/bbrc.2001.4679"/>
        </citation>
        <scope>INTERACTION WITH SYNCRIP</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="Am. J. Hum. Genet." volume="70" first="38" last="50">
            <title>C--&gt;U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme.</title>
            <authorList>
                <person name="Mukhopadhyay D."/>
                <person name="Anant S."/>
                <person name="Lee R.M."/>
                <person name="Kennedy S."/>
                <person name="Viskochil D."/>
                <person name="Davidson N.O."/>
            </authorList>
            <dbReference type="PubMed" id="11727199"/>
            <dbReference type="DOI" id="10.1086/337952"/>
        </citation>
        <scope>FUNCTION IN NF1 EDITING</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2012" name="Arterioscler. Thromb. Vasc. Biol." volume="32" first="1585" last="1595">
            <title>Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor.</title>
            <authorList>
                <person name="Sun H."/>
                <person name="Samarghandi A."/>
                <person name="Zhang N."/>
                <person name="Yao Z."/>
                <person name="Xiong M."/>
                <person name="Teng B.B."/>
            </authorList>
            <dbReference type="PubMed" id="22580899"/>
            <dbReference type="DOI" id="10.1161/atvbaha.112.250043"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2014" name="EMBO Rep." volume="15" first="903" last="910">
            <title>C to U RNA editing mediated by APOBEC1 requires RNA-binding protein RBM47.</title>
            <authorList>
                <person name="Fossat N."/>
                <person name="Tourle K."/>
                <person name="Radziewic T."/>
                <person name="Barratt K."/>
                <person name="Liebhold D."/>
                <person name="Studdert J.B."/>
                <person name="Power M."/>
                <person name="Jones V."/>
                <person name="Loebel D.A."/>
                <person name="Tam P.P."/>
            </authorList>
            <dbReference type="PubMed" id="24916387"/>
            <dbReference type="DOI" id="10.15252/embr.201438450"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RBM47</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2019" name="J. Mol. Biol." volume="431" first="1506" last="1517">
            <title>Comparison of RNA Editing Activity of APOBEC1-A1CF and APOBEC1-RBM47 Complexes Reconstituted in HEK293T Cells.</title>
            <authorList>
                <person name="Wolfe A.D."/>
                <person name="Arnold D.B."/>
                <person name="Chen X.S."/>
            </authorList>
            <dbReference type="PubMed" id="30844405"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2019.02.025"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INTERACTION WITH A1CF AND RBM47</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 7 8">Cytidine deaminase catalyzing the cytidine to uridine postranscriptional editing of a variety of mRNAs (PubMed:30844405). Form complexes with cofactors that confer differential editing activity and selectivity. Responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the apolipoprotein B mRNA (PubMed:24916387). Also involved in CGA (Arg) to UGA (Stop) editing in the NF1 mRNA (PubMed:11727199). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>a cytidine in mRNA + H2O + H(+) = a uridine in mRNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:74355"/>
            <dbReference type="Rhea" id="RHEA-COMP:14658"/>
            <dbReference type="Rhea" id="RHEA-COMP:15145"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:65315"/>
            <dbReference type="ChEBI" id="CHEBI:82748"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:74356"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>cytidine(6666) in apoB mRNA + H2O + H(+) = uridine(6666) in apoB mRNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:21772"/>
            <dbReference type="Rhea" id="RHEA-COMP:13888"/>
            <dbReference type="Rhea" id="RHEA-COMP:13889"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:65315"/>
            <dbReference type="ChEBI" id="CHEBI:82748"/>
            <dbReference type="EC" id="3.5.4.36"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:21773"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="2">Binds 1 Zn(2+) ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 8 9 11">Homodimer (PubMed:8078915). Interacts with A1CF; form an mRNA editing complex (PubMed:30844405). Interacts with RBM47; form an mRNA editing complex (PubMed:24916387, PubMed:30844405). Found in a complex with CELF2/CUGBP2 and A1CF. Interacts with HNRPAB (PubMed:8999813). Interacts with SYNCRIP (PubMed:11352648).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-295663">
            <id>Q00534</id>
            <label>CDK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-352986">
            <id>P52597</id>
            <label>HNRNPF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-7060731">
            <id>P61978-2</id>
            <label>HNRNPK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-1048945">
            <id>Q3LI72</id>
            <label>KRTAP19-5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-12111050">
            <id>Q3LI64</id>
            <label>KRTAP6-1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-11962084">
            <id>Q3LI66</id>
            <label>KRTAP6-2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-17490746">
            <id>A8MTQ0</id>
            <label>NOTO</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12819523">
            <id>P41238</id>
        </interactant>
        <interactant intactId="EBI-11153325">
            <id>Q9NUQ7</id>
            <label>UFSP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9">Expressed exclusively in the small intestine.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.-" evidence="5 8"/>
    <dbReference type="EC" id="3.5.4.36" evidence="5"/>
    <dbReference type="EMBL" id="L25877">
        <property type="protein sequence ID" value="AAA86766.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L26234">
        <property type="protein sequence ID" value="AAA64230.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U72891">
        <property type="protein sequence ID" value="AAD00185.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB009426">
        <property type="protein sequence ID" value="BAA23882.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U78720">
        <property type="protein sequence ID" value="AAD10701.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8579.1"/>
    <dbReference type="PIR" id="I59323">
        <property type="entry name" value="I59323"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001291495.1">
        <property type="nucleotide sequence ID" value="NM_001304566.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001635.2">
        <property type="nucleotide sequence ID" value="NM_001644.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005880.2">
        <property type="nucleotide sequence ID" value="NM_005889.3"/>
    </dbReference>
    <dbReference type="PDB" id="6X91">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.51 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=15-236"/>
    </dbReference>
    <dbReference type="PDBsum" id="6X91"/>
    <dbReference type="AlphaFoldDB" id="P41238"/>
    <dbReference type="SMR" id="P41238"/>
    <dbReference type="BioGRID" id="106836">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1097">
        <property type="entry name" value="C-to-U editosome complex"/>
    </dbReference>
    <dbReference type="FunCoup" id="P41238">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="IntAct" id="P41238">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000229304"/>
    <dbReference type="DrugBank" id="DB14533">
        <property type="generic name" value="Zinc chloride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14548">
        <property type="generic name" value="Zinc sulfate, unspecified form"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P41238"/>
    <dbReference type="PhosphoSitePlus" id="P41238"/>
    <dbReference type="BioMuta" id="APOBEC1"/>
    <dbReference type="DMDM" id="152013530"/>
    <dbReference type="PaxDb" id="9606-ENSP00000229304"/>
    <dbReference type="Antibodypedia" id="22955">
        <property type="antibodies" value="161 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="339"/>
    <dbReference type="Ensembl" id="ENST00000229304.5">
        <property type="protein sequence ID" value="ENSP00000229304.4"/>
        <property type="gene ID" value="ENSG00000111701.7"/>
    </dbReference>
    <dbReference type="GeneID" id="339"/>
    <dbReference type="KEGG" id="hsa:339"/>
    <dbReference type="MANE-Select" id="ENST00000229304.5">
        <property type="protein sequence ID" value="ENSP00000229304.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001644.5"/>
        <property type="RefSeq protein sequence ID" value="NP_001635.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001qtb.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:604"/>
    <dbReference type="ClinPGx" id="PA24889"/>
    <dbReference type="CTD" id="339"/>
    <dbReference type="DisGeNET" id="339"/>
    <dbReference type="GeneCards" id="APOBEC1"/>
    <dbReference type="HGNC" id="HGNC:604">
        <property type="gene designation" value="APOBEC1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000111701">
        <property type="expression patterns" value="Tissue enriched (intestine)"/>
    </dbReference>
    <dbReference type="MIM" id="600130">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000111701"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000111701"/>
    <dbReference type="eggNOG" id="ENOG502SNW2">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161190"/>
    <dbReference type="HOGENOM" id="CLU_080056_3_0_1"/>
    <dbReference type="InParanoid" id="P41238"/>
    <dbReference type="OMA" id="LTLQNCH"/>
    <dbReference type="OrthoDB" id="5956704at2759"/>
    <dbReference type="PAN-GO" id="P41238">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P41238"/>
    <dbReference type="BRENDA" id="3.5.4.36">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="3.5.4.37">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P41238"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="P41238"/>
    <dbReference type="Agora" id="ENSG00000111701"/>
    <dbReference type="BioGRID-ORCS" id="339">
        <property type="hits" value="11 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="APOBEC1"/>
    <dbReference type="GenomeRNAi" id="339"/>
    <dbReference type="Pharos" id="P41238">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P41238"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="P41238">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000111701">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 24 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P41238">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030895">
        <property type="term" value="C:apolipoprotein B mRNA editing enzyme complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045293">
        <property type="term" value="C:mRNA editing complex"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004126">
        <property type="term" value="F:cytidine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035925">
        <property type="term" value="F:mRNA 3'-UTR AU-rich region binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0141166">
        <property type="term" value="P:chromosomal 5-methylcytosine DNA demethylation pathway"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016554">
        <property type="term" value="P:cytidine to uridine editing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051649">
        <property type="term" value="P:establishment of localization in cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042158">
        <property type="term" value="P:lipoprotein biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042953">
        <property type="term" value="P:lipoprotein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016556">
        <property type="term" value="P:mRNA modification"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006397">
        <property type="term" value="P:mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048255">
        <property type="term" value="P:mRNA stabilization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000623">
        <property type="term" value="P:negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090209">
        <property type="term" value="P:negative regulation of triglyceride metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044029">
        <property type="term" value="P:positive regulation of gene expression via chromosomal CpG island demethylation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042127">
        <property type="term" value="P:regulation of cell population proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010332">
        <property type="term" value="P:response to gamma radiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006641">
        <property type="term" value="P:triglyceride metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd01283">
        <property type="entry name" value="cytidine_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.140.10:FF:000049">
        <property type="entry name" value="C-&gt;U-editing enzyme APOBEC-1 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016192">
        <property type="entry name" value="APOBEC/CMP_deaminase_Zn-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041547">
        <property type="entry name" value="APOBEC1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050610">
        <property type="entry name" value="APOBEC_Cyt_Deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857:SF26">
        <property type="entry name" value="C-U-EDITING ENZYME APOBEC-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13857">
        <property type="entry name" value="MRNA EDITING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18774">
        <property type="entry name" value="APOBEC4_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00903">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0507">mRNA processing</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000171742" description="C-&gt;U-editing enzyme APOBEC-1">
        <location>
            <begin position="1"/>
            <end position="236"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="3">
        <location>
            <begin position="10"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="2">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="61"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="93"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="96"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_013779" description="In dbSNP:rs2302515." evidence="9 10 12 13">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048720" description="In dbSNP:rs12820011.">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAD10701." evidence="17" ref="5">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAD10701." evidence="17" ref="5">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="83"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P51908"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9Y235"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11352648"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11727199"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="22580899"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24916387"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="30844405"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="8078915"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="8208612"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="8999813"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="9186903"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="9479499"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="30844405"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="8208612"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="9186903"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0000305" key="18">
        <source>
            <dbReference type="PubMed" id="11727199"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="19">
        <source>
            <dbReference type="HGNC" id="HGNC:604"/>
        </source>
    </evidence>
    <sequence length="236" mass="28192" checksum="28466B43F7FD82F7" modified="2007-03-06" version="3">MTSEKGPSTGDPTLRRRIEPWEFDVFYDPRELRKEACLLYEIKWGMSRKIWRSSGKNTTNHVEVNFIKKFTSERDFHPSMSCSITWFLSWSPCWECSQAIREFLSRHPGVTLVIYVARLFWHMDQQNRQGLRDLVNSGVTIQIMRASEYYHCWRNFVNYPPGDEAHWPQYPPLWMMLYALELHCIILSLPPCLKISRRWQNHLTFFRLHLQNCHYQTIPPHILLATGLIHPSVAWR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-13" modified="2026-01-28" version="149" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WW27</accession>
    <accession>Q8N7F6</accession>
    <name>ABEC4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Putative deaminase APOBEC-4</fullName>
            <ecNumber evidence="4">3.5.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">APOBEC4</name>
        <name evidence="5" type="synonym">C1orf169</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS SER-271 AND GLU-331</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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                <person name="Kaul R."/>
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                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Coville G.J."/>
                <person name="Davies J."/>
                <person name="Deadman R."/>
                <person name="Dunn M."/>
                <person name="Earthrowl M."/>
                <person name="Ellington A.G."/>
                <person name="Errington H."/>
                <person name="Frankish A."/>
                <person name="Frankland J."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gay L."/>
                <person name="Ghori M.R.J."/>
                <person name="Gibson R."/>
                <person name="Gilby L.M."/>
                <person name="Gillett W."/>
                <person name="Glithero R.J."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Hammond S."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E."/>
                <person name="Haugen E."/>
                <person name="Heath P.D."/>
                <person name="Holmes S."/>
                <person name="Holt K."/>
                <person name="Howden P.J."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Hunter G."/>
                <person name="Isherwood J."/>
                <person name="James R."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A."/>
                <person name="Kay M."/>
                <person name="Kershaw J.K."/>
                <person name="Kibukawa M."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A.J."/>
                <person name="Lad H."/>
                <person name="Laird G."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
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                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2005" name="Cell Cycle" volume="4" first="1281" last="1285">
            <title>APOBEC4, a new member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases predicted by computational analysis.</title>
            <authorList>
                <person name="Rogozin I.B."/>
                <person name="Basu M.K."/>
                <person name="Jordan I.K."/>
                <person name="Pavlov Y.I."/>
                <person name="Koonin E.V."/>
            </authorList>
            <dbReference type="PubMed" id="16082223"/>
            <dbReference type="DOI" id="10.4161/cc.4.9.1994"/>
        </citation>
        <scope>IDENTIFICATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Putative deaminase whose physiological substrate is not yet known.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25836284">
            <id>Q8WW27</id>
        </interactant>
        <interactant intactId="EBI-718729">
            <id>P55212</id>
            <label>CASP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25836284">
            <id>Q8WW27</id>
        </interactant>
        <interactant intactId="EBI-286642">
            <id>P62826</id>
            <label>RAN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Predominantly expressed in testis.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the cytidine and deoxycytidylate deaminase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.-" evidence="4"/>
    <dbReference type="EMBL" id="AK098557">
        <property type="protein sequence ID" value="BAC05332.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL137800">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC021711">
        <property type="protein sequence ID" value="AAH21711.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1358.1"/>
    <dbReference type="RefSeq" id="NP_982279.1">
        <property type="nucleotide sequence ID" value="NM_203454.3"/>
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    <dbReference type="AlphaFoldDB" id="Q8WW27"/>
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        <property type="interactions" value="3"/>
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    <dbReference type="FunCoup" id="Q8WW27">
        <property type="interactions" value="2"/>
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    <dbReference type="IntAct" id="Q8WW27">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000310622"/>
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    <dbReference type="Antibodypedia" id="2817">
        <property type="antibodies" value="261 antibodies from 28 providers"/>
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    <dbReference type="DNASU" id="403314"/>
    <dbReference type="Ensembl" id="ENST00000308641.6">
        <property type="protein sequence ID" value="ENSP00000310622.4"/>
        <property type="gene ID" value="ENSG00000173627.8"/>
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    <dbReference type="GeneID" id="403314"/>
    <dbReference type="KEGG" id="hsa:403314"/>
    <dbReference type="MANE-Select" id="ENST00000308641.6">
        <property type="protein sequence ID" value="ENSP00000310622.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_203454.3"/>
        <property type="RefSeq protein sequence ID" value="NP_982279.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001gqn.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32152"/>
    <dbReference type="ClinPGx" id="PA142672597"/>
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    <dbReference type="GeneCards" id="APOBEC4"/>
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        <property type="gene designation" value="APOBEC4"/>
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    <dbReference type="HPA" id="ENSG00000173627">
        <property type="expression patterns" value="Group enriched (fallopian tube, testis)"/>
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    <dbReference type="MIM" id="609908">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000173627"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000173627"/>
    <dbReference type="eggNOG" id="ENOG502QQXT">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000014243"/>
    <dbReference type="HOGENOM" id="CLU_832944_0_0_1"/>
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    <dbReference type="OMA" id="PASAWNR"/>
    <dbReference type="OrthoDB" id="9941981at2759"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WW27"/>
    <dbReference type="PathwayCommons" id="Q8WW27"/>
    <dbReference type="Reactome" id="R-HSA-72200">
        <property type="pathway name" value="mRNA Editing: C to U Conversion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75094">
        <property type="pathway name" value="Formation of the Editosome"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8WW27"/>
    <dbReference type="Agora" id="ENSG00000173627"/>
    <dbReference type="BioGRID-ORCS" id="403314">
        <property type="hits" value="29 hits in 1139 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APOBEC4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="APOBEC4"/>
    <dbReference type="GenomeRNAi" id="403314"/>
    <dbReference type="Pharos" id="Q8WW27">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WW27"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WW27">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000173627">
        <property type="expression patterns" value="Expressed in bronchial epithelial cell and 39 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016787">
        <property type="term" value="F:hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006397">
        <property type="term" value="P:mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038953">
        <property type="entry name" value="APOBEC4"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR35672">
        <property type="entry name" value="C-U-EDITING ENZYME APOBEC-4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR35672:SF1">
        <property type="entry name" value="C-U-EDITING ENZYME APOBEC-4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18778">
        <property type="entry name" value="NAD1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0507">mRNA processing</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000239355" description="Putative deaminase APOBEC-4">
        <location>
            <begin position="1"/>
            <end position="367"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="1">
        <location>
            <begin position="61"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="1">
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="93"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="127"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="134"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_026639" description="In dbSNP:rs16861394.">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026640" description="In dbSNP:rs1174658." evidence="2">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026641" description="In dbSNP:rs10911391.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="275"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048724" description="In dbSNP:rs16861381.">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026642" description="In dbSNP:rs1174657." evidence="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="331"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026643" description="In dbSNP:rs10911390.">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="16082223"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:32152"/>
        </source>
    </evidence>
    <sequence length="367" mass="41581" checksum="B5ACD9AB875482C6" modified="2002-03-01" version="1">MEPIYEEYLANHGTIVKPYYWLSFSLDCSNCPYHIRTGEEARVSLTEFCQIFGFPYGTTFPQTKHLTFYELKTSSGSLVQKGHASSCTGNYIHPESMLFEMNGYLDSAIYNNDSIRHIILYSNNSPCNEANHCCISKMYNFLITYPGITLSIYFSQLYHTEMDFPASAWNREALRSLASLWPRVVLSPISGGIWHSVLHSFISGVSGSHVFQPILTGRALADRHNAYEINAITGVKPYFTDVLLQTKRNPNTKAQEALESYPLNNAFPGQFFQMPSGQLQPNLPPDLRAPVVFVLVPLRDLPPMHMGQNPNKPRNIVRHLNMPQMSFQETKDLGRLPTGRSVEIVEITEQFASSKEADEKKKKKGKK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-07-22" modified="2026-01-28" version="133" xmlns="https://uniprot.org/uniprot">
    <accession>Q6UXT9</accession>
    <accession>Q96EC5</accession>
    <name>ABH15_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Protein ABHD15</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Alpha/beta hydrolase domain-containing protein 15</fullName>
            <shortName evidence="8">Abhydrolase domain-containing protein 15</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="8" type="primary">ABHD15</name>
        <name type="ORF">UNQ6510/PRO21435</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
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                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
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                <person name="Baldwin D.T."/>
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                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
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                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ALA-334</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
            <authorList>
                <person name="Zody M.C."/>
                <person name="Garber M."/>
                <person name="Adams D.J."/>
                <person name="Sharpe T."/>
                <person name="Harrow J."/>
                <person name="Lupski J.R."/>
                <person name="Nicholson C."/>
                <person name="Searle S.M."/>
                <person name="Wilming L."/>
                <person name="Young S.K."/>
                <person name="Abouelleil A."/>
                <person name="Allen N.R."/>
                <person name="Bi W."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Bugalter B.E."/>
                <person name="Butler J."/>
                <person name="Chang J.L."/>
                <person name="Chen C.-K."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="Cuomo C.A."/>
                <person name="de Jong P.J."/>
                <person name="DeCaprio D."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M."/>
                <person name="Gilbert J."/>
                <person name="Gibson R."/>
                <person name="Gnerre S."/>
                <person name="Goldstein S."/>
                <person name="Grafham D.V."/>
                <person name="Grocock R."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hart E."/>
                <person name="Norman C.H."/>
                <person name="Humphray S."/>
                <person name="Jaffe D.B."/>
                <person name="Jones M."/>
                <person name="Kamal M."/>
                <person name="Khodiyar V.K."/>
                <person name="LaButti K."/>
                <person name="Laird G."/>
                <person name="Lehoczky J."/>
                <person name="Liu X."/>
                <person name="Lokyitsang T."/>
                <person name="Loveland J."/>
                <person name="Lui A."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews L."/>
                <person name="Mauceli E."/>
                <person name="McCarroll S.A."/>
                <person name="Mihalev A.H."/>
                <person name="Mudge J."/>
                <person name="Nguyen C."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Osoegawa K."/>
                <person name="Schwartz D.C."/>
                <person name="Shaw-Smith C."/>
                <person name="Stankiewicz P."/>
                <person name="Steward C."/>
                <person name="Swarbreck D."/>
                <person name="Venkataraman V."/>
                <person name="Whittaker C.A."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Bradley A."/>
                <person name="Hubbard T."/>
                <person name="Birren B.W."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT ALA-334</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">May regulate adipocyte lipolysis and liver lipid accumulation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts with PDE3B; this interaction regulates PDE3B's stability and expression and, thereby, impacts the antilipolytic action of insulin.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2824666">
            <id>Q6UXT9</id>
        </interactant>
        <interactant intactId="EBI-1047093">
            <id>O76011</id>
            <label>KRT34</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2824666">
            <id>Q6UXT9</id>
        </interactant>
        <interactant intactId="EBI-11522433">
            <id>Q5JR59-3</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2824666">
            <id>Q6UXT9</id>
        </interactant>
        <interactant intactId="EBI-711613">
            <id>P21673</id>
            <label>SAT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2824666">
            <id>Q6UXT9</id>
        </interactant>
        <interactant intactId="EBI-11957238">
            <id>Q2TAL6</id>
            <label>VWC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2824666">
            <id>Q6UXT9</id>
        </interactant>
        <interactant intactId="EBI-751647">
            <id>Q15007</id>
            <label>WTAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.</text>
    </comment>
    <dbReference type="EMBL" id="AY358212">
        <property type="protein sequence ID" value="AAQ88579.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC104564">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012476">
        <property type="protein sequence ID" value="AAH12476.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32602.1"/>
    <dbReference type="RefSeq" id="NP_937790.2">
        <property type="nucleotide sequence ID" value="NM_198147.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6UXT9"/>
    <dbReference type="BioGRID" id="125492">
        <property type="interactions" value="45"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6UXT9">
        <property type="interactions" value="167"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6UXT9">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000302657"/>
    <dbReference type="ESTHER" id="human-ABHD15">
        <property type="family name" value="abh_upf0017"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6UXT9"/>
    <dbReference type="PhosphoSitePlus" id="Q6UXT9"/>
    <dbReference type="SwissPalm" id="Q6UXT9"/>
    <dbReference type="BioMuta" id="ABHD15"/>
    <dbReference type="DMDM" id="308153403"/>
    <dbReference type="jPOST" id="Q6UXT9"/>
    <dbReference type="MassIVE" id="Q6UXT9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000302657"/>
    <dbReference type="PeptideAtlas" id="Q6UXT9"/>
    <dbReference type="ProteomicsDB" id="67657"/>
    <dbReference type="Pumba" id="Q6UXT9"/>
    <dbReference type="Antibodypedia" id="2595">
        <property type="antibodies" value="50 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="116236"/>
    <dbReference type="Ensembl" id="ENST00000307201.5">
        <property type="protein sequence ID" value="ENSP00000302657.3"/>
        <property type="gene ID" value="ENSG00000168792.5"/>
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    <dbReference type="GeneID" id="116236"/>
    <dbReference type="KEGG" id="hsa:116236"/>
    <dbReference type="MANE-Select" id="ENST00000307201.5">
        <property type="protein sequence ID" value="ENSP00000302657.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_198147.3"/>
        <property type="RefSeq protein sequence ID" value="NP_937790.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002hed.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:26971"/>
    <dbReference type="ClinPGx" id="PA164714659"/>
    <dbReference type="CTD" id="116236"/>
    <dbReference type="DisGeNET" id="116236"/>
    <dbReference type="GeneCards" id="ABHD15"/>
    <dbReference type="HGNC" id="HGNC:26971">
        <property type="gene designation" value="ABHD15"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000168792">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="619894">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000168792"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000168792"/>
    <dbReference type="eggNOG" id="KOG1838">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182902"/>
    <dbReference type="HOGENOM" id="CLU_032487_3_0_1"/>
    <dbReference type="InParanoid" id="Q6UXT9"/>
    <dbReference type="OMA" id="AWSHEAT"/>
    <dbReference type="OrthoDB" id="247542at2759"/>
    <dbReference type="PAN-GO" id="Q6UXT9">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6UXT9"/>
    <dbReference type="PathwayCommons" id="Q6UXT9"/>
    <dbReference type="SignaLink" id="Q6UXT9"/>
    <dbReference type="Agora" id="ENSG00000168792"/>
    <dbReference type="BioGRID-ORCS" id="116236">
        <property type="hits" value="22 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD15">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="116236"/>
    <dbReference type="Pharos" id="Q6UXT9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6UXT9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6UXT9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000168792">
        <property type="expression patterns" value="Expressed in granulocyte and 122 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034338">
        <property type="term" value="F:short-chain carboxylesterase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060612">
        <property type="term" value="P:adipose tissue development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016042">
        <property type="term" value="P:lipid catabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000103">
        <property type="entry name" value="Abhydrolase domain-containing 15"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050960">
        <property type="entry name" value="AB_hydrolase_4_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794">
        <property type="entry name" value="ABHYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794:SF39">
        <property type="entry name" value="PROTEIN ABHD15"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000345395" description="Protein ABHD15">
        <location>
            <begin position="24"/>
            <end position="468"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="33"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="391"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="9">
        <location>
            <position position="434"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045821" description="In dbSNP:rs542939." evidence="5 6">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="334"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH12476." evidence="7" ref="3">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q5F2F2"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12975309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:26971"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="468" mass="51771" checksum="A910F5F4294B0CC3" modified="2010-10-05" version="2" precursor="true">MPPWGAALALILAVLALLGLLGPRLRGPWGRAVGERTLPGAQDRDDGEEADGGGPADQFSDGREPLPGGCSLVCKPSALAQCLLRALRRSEALEAGPRSWFSGPHLQTLCHFVLPVAPGPELAREYLQLADDGLVALDWVVGPCVRGRRITSAGGLPAVLLVIPNAWGRLTRNVLGLCLLALERGYYPVIFHRRGHHGCPLVSPRLQPFGDPSDLKEAVTYIRFRHPAAPLFAVSEGSGSALLLSYLGECGSSSYVTGAACISPVLRCREWFEAGLPWPYERGFLLHQKIALSRYATALEDTVDTSRLFRSRSLREFEEALFCHTKSFPISWDTYWDRNDPLRDVDEAAVPVLCICSADDPVCGPPDHTLTTELFHSNPYFFLLLSRHGGHCGFLRQEPLPAWSHEVILESFRALTEFFRTEERIKGLSRHRASFLGGRRRGGALQRREVSSSSNLEEIFNWKRSYTR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="195" xmlns="https://uniprot.org/uniprot">
    <accession>P61221</accession>
    <accession>O88793</accession>
    <accession>Q13181</accession>
    <accession>Q13864</accession>
    <accession>Q6NR76</accession>
    <accession>Q96AL0</accession>
    <accession>Q96B10</accession>
    <accession>Q99K66</accession>
    <name>ABCE1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ATP-binding cassette sub-family E member 1</fullName>
            <ecNumber evidence="7">3.6.5.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>2'-5'-oligoadenylate-binding protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>HuHP68</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>RNase L inhibitor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Ribonuclease 4 inhibitor</fullName>
            <shortName>RNS4I</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABCE1</name>
        <name type="synonym">RLI</name>
        <name type="synonym">RNASEL1</name>
        <name type="synonym">RNASELI</name>
        <name type="synonym">RNS4I</name>
        <name type="ORF">OK/SW-cl.40</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="J. Biol. Chem." volume="270" first="13308" last="13317">
            <title>Cloning and characterization of a RNase L inhibitor. A new component of the interferon-regulated 2-5A pathway.</title>
            <authorList>
                <person name="Bisbal C."/>
                <person name="Martinand C."/>
                <person name="Silhol M."/>
                <person name="Lebleu B."/>
                <person name="Salehzada T."/>
            </authorList>
            <dbReference type="PubMed" id="7539425"/>
            <dbReference type="DOI" id="10.1074/jbc.270.22.13308"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>CHARACTERIZATION</scope>
        <scope>INTERACTION WITH RNASEL</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="FEBS Lett." volume="381" first="135" last="139">
            <title>Chromosomal localization and expression pattern of the RNase L inhibitor gene.</title>
            <authorList>
                <person name="Aubry F."/>
                <person name="Mattei M.-G."/>
                <person name="Barque J.-P."/>
                <person name="Galibert F."/>
            </authorList>
            <dbReference type="PubMed" id="8641422"/>
            <dbReference type="DOI" id="10.1016/0014-5793(96)00099-3"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Duodenum</tissue>
            <tissue>Uterus</tissue>
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        <scope>FUNCTION</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
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        <scope>FUNCTION</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
        <scope>INDUCTION BY HIV-1</scope>
    </reference>
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            <dbReference type="PubMed" id="11585831"/>
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        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
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            <dbReference type="PubMed" id="11780123"/>
            <dbReference type="DOI" id="10.1038/415088a"/>
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        <scope>INTERACTION WITH HIV-1 VIF AND GAG PROTEINS (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="11">
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            <title>Conservation of a stepwise, energy-sensitive pathway involving HP68 for assembly of primate lentivirus capsids in cells.</title>
            <authorList>
                <person name="Dooher J.E."/>
                <person name="Lingappa J.R."/>
            </authorList>
            <dbReference type="PubMed" id="14747530"/>
            <dbReference type="DOI" id="10.1128/jvi.78.4.1645-1656.2004"/>
        </citation>
        <scope>INTERACTION WITH HIV-2 PROTEIN GAG (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="12">
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            <authorList>
                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="13">
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            <title>The role of ABCE1 in eukaryotic posttermination ribosomal recycling.</title>
            <authorList>
                <person name="Pisarev A.V."/>
                <person name="Skabkin M.A."/>
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            </authorList>
            <dbReference type="PubMed" id="20122402"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2009.12.034"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
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            <title>Dissociation by Pelota, Hbs1 and ABCE1 of mammalian vacant 80S ribosomes and stalled elongation complexes.</title>
            <authorList>
                <person name="Pisareva V.P."/>
                <person name="Skabkin M.A."/>
                <person name="Hellen C.U."/>
                <person name="Pestova T.V."/>
                <person name="Pisarev A.V."/>
            </authorList>
            <dbReference type="PubMed" id="21448132"/>
            <dbReference type="DOI" id="10.1038/emboj.2011.93"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="15">
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                <person name="Zhou H."/>
                <person name="Di Palma S."/>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-417 AND THR-550</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="16">
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            <authorList>
                <person name="Rajasekharan S."/>
                <person name="Kumar K."/>
                <person name="Rana J."/>
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            </authorList>
            <dbReference type="PubMed" id="25944354"/>
            <dbReference type="DOI" id="10.1016/j.actatropica.2015.04.027"/>
        </citation>
        <scope>INTERACTION WITH CHANDIPURA VIRUS MATRIX PROTEIN (MICROBIAL INFECTION)</scope>
    </reference>
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                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
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            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy.</title>
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            <dbReference type="PubMed" id="29861391"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2018.05.007"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PINK1; CNOT4 AND PELO</scope>
        <scope>UBIQUITINATION AT LYS-20</scope>
        <scope>MUTAGENESIS OF LYS-20</scope>
    </reference>
    <reference key="19">
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            <title>Detection and validation of non-synonymous coding SNPs from orthogonal analysis of shotgun proteomics data.</title>
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                <person name="Bunger M.K."/>
                <person name="Cargile B.J."/>
                <person name="Sevinsky J.R."/>
                <person name="Deyanova E."/>
                <person name="Yates N.A."/>
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            </authorList>
            <dbReference type="PubMed" id="17488105"/>
            <dbReference type="DOI" id="10.1021/pr0700908"/>
        </citation>
        <scope>VARIANT CYS-489</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <comment type="function">
        <text evidence="3 7 8 10 11 12">Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly (PubMed:20122402, PubMed:21448132). Able to hydrolyze ATP, GTP, UTP and CTP (PubMed:20122402). Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits (PubMed:20122402, PubMed:21448132). Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota) (PubMed:20122402, PubMed:21448132). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (PubMed:21448132). Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA (PubMed:29861391). As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy (PubMed:29861391). RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL (PubMed:9660177). Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway (PubMed:11585831, PubMed:9660177, PubMed:9847332).</text>
    </comment>
    <comment type="function">
        <text evidence="12">(Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly.</text>
    </comment>
    <comment type="function">
        <text evidence="11">(Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>GTP + H2O = GDP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19669"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58189"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>CTP + H2O = CDP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:29387"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:37563"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:58069"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>UTP + H2O = UDP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:64900"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:46398"/>
            <dbReference type="ChEBI" id="CHEBI:58223"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="9">(Microbial infection) Interacts with Chandipura virus matrix protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="10 14">Interacts with PINK1 (PubMed:29861391). Interacts with CNOT4 (PubMed:29861391). Interacts with PELO (PubMed:29861391). Probably heterodimerizes with RNASEL; this interaction inhibits RNASEL (Probable) (PubMed:9660177).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">(Microbial infection) Interacts with HIV-1 proteins Vif and Gag.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5">(Microbial infection) Interacts with HIV-2 protein Gag.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2510446">
            <id>P61221</id>
        </interactant>
        <interactant intactId="EBI-366647">
            <id>O75822</id>
            <label>EIF3J</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2510446">
            <id>P61221</id>
        </interactant>
        <interactant intactId="EBI-10687478">
            <id>P03347-1</id>
            <label>gag</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2510446">
            <id>P61221</id>
        </interactant>
        <interactant intactId="EBI-10823897">
            <id>Q9WH76</id>
            <label>M</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2510446">
            <id>P61221</id>
        </interactant>
        <interactant intactId="EBI-25568013">
            <id>P69479</id>
            <label>P</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="induction">
        <text evidence="11 12">Activated by encephalomyocarditis virus (EMCV) and HIV-1.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10">Ubiquitinated by CNOT4 (PubMed:29861391). Ubiquitination mediates the recruitment of autophagy receptors to the mitochondrial outer membrane and initiates mitophagy (PubMed:29861391).</text>
    </comment>
    <comment type="miscellaneous">
        <text>The ABC transporter domains seem not to be functional.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the ABC transporter superfamily. ABCE family.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
    </comment>
    <dbReference type="EC" id="3.6.5.-" evidence="7"/>
    <dbReference type="EMBL" id="X76388">
        <property type="protein sequence ID" value="CAA53972.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X74987">
        <property type="protein sequence ID" value="CAA52920.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB062293">
        <property type="protein sequence ID" value="BAB93476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT009779">
        <property type="protein sequence ID" value="AAP88781.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ148409">
        <property type="protein sequence ID" value="AAZ38723.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016283">
        <property type="protein sequence ID" value="AAH16283.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016988">
        <property type="protein sequence ID" value="AAH16988.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34071.1"/>
    <dbReference type="PIR" id="A57017">
        <property type="entry name" value="A57017"/>
    </dbReference>
    <dbReference type="PIR" id="S63672">
        <property type="entry name" value="S63672"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035809.1">
        <property type="nucleotide sequence ID" value="NM_001040876.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002931.2">
        <property type="nucleotide sequence ID" value="NM_002940.3"/>
    </dbReference>
    <dbReference type="PDB" id="6ZME">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="CI=1-599"/>
    </dbReference>
    <dbReference type="PDB" id="6ZVJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.80 A"/>
        <property type="chains" value="1=4-598"/>
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    <dbReference type="PDB" id="7A09">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="J=1-599"/>
    </dbReference>
    <dbReference type="PDBsum" id="6ZME"/>
    <dbReference type="PDBsum" id="6ZVJ"/>
    <dbReference type="PDBsum" id="7A09"/>
    <dbReference type="AlphaFoldDB" id="P61221"/>
    <dbReference type="EMDB" id="EMD-11289"/>
    <dbReference type="EMDB" id="EMD-11458"/>
    <dbReference type="EMDB" id="EMD-11602"/>
    <dbReference type="EMDB" id="EMD-3038"/>
    <dbReference type="EMDB" id="EMD-3039"/>
    <dbReference type="EMDB" id="EMD-3040"/>
    <dbReference type="SMR" id="P61221"/>
    <dbReference type="BioGRID" id="111986">
        <property type="interactions" value="418"/>
    </dbReference>
    <dbReference type="FunCoup" id="P61221">
        <property type="interactions" value="3957"/>
    </dbReference>
    <dbReference type="IntAct" id="P61221">
        <property type="interactions" value="103"/>
    </dbReference>
    <dbReference type="MINT" id="P61221"/>
    <dbReference type="STRING" id="9606.ENSP00000296577"/>
    <dbReference type="TCDB" id="3.A.1.31.4">
        <property type="family name" value="the atp-binding cassette (abc) superfamily"/>
    </dbReference>
    <dbReference type="CarbonylDB" id="P61221"/>
    <dbReference type="GlyGen" id="P61221">
        <property type="glycosylation" value="2 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P61221"/>
    <dbReference type="MetOSite" id="P61221"/>
    <dbReference type="PhosphoSitePlus" id="P61221"/>
    <dbReference type="SwissPalm" id="P61221"/>
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        <property type="gene designation" value="ABCE1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164163">
        <property type="expression patterns" value="Low tissue specificity"/>
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    <dbReference type="MalaCards" id="ABCE1"/>
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        <property type="type" value="gene"/>
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        <property type="match status" value="1"/>
    </dbReference>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ABC_tran"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="Fer4"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Fer4_RLI"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR01868">
        <property type="entry name" value="ABCEFAMILY"/>
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        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
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        <property type="match status" value="2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0004">4Fe-4S</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0143">Chaperone</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0408">Iron</keyword>
    <keyword id="KW-0411">Iron-sulfur</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0810">Translation regulation</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000093316" description="ATP-binding cassette sub-family E member 1">
        <location>
            <begin position="1"/>
            <end position="599"/>
        </location>
    </feature>
    <feature type="domain" description="4Fe-4S ferredoxin-type 1" evidence="2">
        <location>
            <begin position="7"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="domain" description="4Fe-4S ferredoxin-type 2" evidence="2">
        <location>
            <begin position="46"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 1" evidence="1">
        <location>
            <begin position="79"/>
            <end position="315"/>
        </location>
    </feature>
    <feature type="domain" description="ABC transporter 2" evidence="1">
        <location>
            <begin position="342"/>
            <end position="562"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="110"/>
            <end position="117"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="379"/>
            <end position="386"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="417"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="15">
        <location>
            <position position="550"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="10">
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068914" description="Confirmed at protein level; dbSNP:rs3816497." evidence="6">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="489"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes ubiquitination by CNOT4 and diminished the ability to recruit autophagy receptors to damaged mitochondria and to nuclear encoded respiratory chain component mRNA-ribonucleoproteins complexes." evidence="10">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA53972." evidence="13" ref="1">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA53972." evidence="13" ref="1">
        <original>DQIPKA</original>
        <variation>ARFLRL</variation>
        <location>
            <begin position="174"/>
            <end position="179"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA53972/CAA52920." evidence="13" ref="1">
        <original>ALA</original>
        <variation>RLR</variation>
        <location>
            <begin position="471"/>
            <end position="473"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00434"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00711"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11585831"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11780123"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14747530"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17488105"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="20122402"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="21448132"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="25944354"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="29861391"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="9660177"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="9847332"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="9660177"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="599" mass="67314" checksum="5D582B62E95BC7A6" modified="2004-05-10" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="153" xmlns="https://uniprot.org/uniprot">
    <accession>Q96SE0</accession>
    <accession>B3KSF6</accession>
    <accession>E9PDR9</accession>
    <accession>Q05BY3</accession>
    <accession>Q53SZ1</accession>
    <accession>Q8IXQ7</accession>
    <name>ABHD1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">Protein ABHD1</fullName>
            <ecNumber>3.1.1.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="6">Alpha/beta hydrolase domain-containing protein 1</fullName>
            <shortName evidence="7">Abhydrolase domain-containing protein 1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Lung alpha/beta hydrolase 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="7" type="primary">ABHD1</name>
        <name type="synonym">LABH1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="BMC Genomics" volume="4" first="18" last="18">
            <title>The gene structure and expression of human ABHD1: overlapping polyadenylation signal sequence with Sec12.</title>
            <authorList>
                <person name="Edgar A.J."/>
            </authorList>
            <dbReference type="PubMed" id="12735795"/>
            <dbReference type="DOI" id="10.1186/1471-2164-4-18"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
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                <person name="Tanai H."/>
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                <person name="Hiraoka S."/>
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                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
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                <person name="Hara H."/>
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                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
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                <person name="Momiyama H."/>
                <person name="Satoh N."/>
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                <person name="Suzuki O."/>
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                <person name="Senoh A."/>
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                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
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                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
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            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT ASP-137</scope>
    </reference>
    <reference key="4">
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            <authorList>
                <person name="Mural R.J."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="interaction">
        <interactant intactId="EBI-10293349">
            <id>Q96SE0</id>
        </interactant>
        <interactant intactId="EBI-749265">
            <id>Q8N6L0</id>
            <label>KASH5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Membrane</location>
            <topology evidence="6">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96SE0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96SE0-3</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054269 VSP_054270"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Ubiquitously expressed.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.-"/>
    <dbReference type="EMBL" id="AY033290">
        <property type="protein sequence ID" value="AAK44222.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093447">
        <property type="protein sequence ID" value="BAG52718.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC013403">
        <property type="protein sequence ID" value="AAX93169.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAX00633.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC039576">
        <property type="protein sequence ID" value="AAH39576.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1736.1">
        <molecule id="Q96SE0-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_115993.3">
        <molecule id="Q96SE0-1"/>
        <property type="nucleotide sequence ID" value="NM_032604.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011531438.1">
        <molecule id="Q96SE0-3"/>
        <property type="nucleotide sequence ID" value="XM_011533136.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054200199.1">
        <molecule id="Q96SE0-3"/>
        <property type="nucleotide sequence ID" value="XM_054344224.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96SE0"/>
    <dbReference type="BioGRID" id="124211">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96SE0">
        <property type="interactions" value="145"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96SE0">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000326491"/>
    <dbReference type="ESTHER" id="human-ABHD1">
        <property type="family name" value="abh_upf0017"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q96SE0">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q96SE0">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96SE0"/>
    <dbReference type="PhosphoSitePlus" id="Q96SE0"/>
    <dbReference type="BioMuta" id="ABHD1"/>
    <dbReference type="DMDM" id="308153404"/>
    <dbReference type="jPOST" id="Q96SE0"/>
    <dbReference type="MassIVE" id="Q96SE0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000326491"/>
    <dbReference type="PeptideAtlas" id="Q96SE0"/>
    <dbReference type="Antibodypedia" id="28175">
        <property type="antibodies" value="131 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84696"/>
    <dbReference type="Ensembl" id="ENST00000316470.9">
        <molecule id="Q96SE0-1"/>
        <property type="protein sequence ID" value="ENSP00000326491.4"/>
        <property type="gene ID" value="ENSG00000143994.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000448950.5">
        <molecule id="Q96SE0-3"/>
        <property type="protein sequence ID" value="ENSP00000410756.1"/>
        <property type="gene ID" value="ENSG00000143994.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000621324.4">
        <molecule id="Q96SE0-3"/>
        <property type="protein sequence ID" value="ENSP00000481238.1"/>
        <property type="gene ID" value="ENSG00000143994.15"/>
    </dbReference>
    <dbReference type="GeneID" id="84696"/>
    <dbReference type="KEGG" id="hsa:84696"/>
    <dbReference type="MANE-Select" id="ENST00000316470.9">
        <property type="protein sequence ID" value="ENSP00000326491.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032604.4"/>
        <property type="RefSeq protein sequence ID" value="NP_115993.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002rit.4">
        <molecule id="Q96SE0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17553"/>
    <dbReference type="ClinPGx" id="PA38459"/>
    <dbReference type="CTD" id="84696"/>
    <dbReference type="DisGeNET" id="84696"/>
    <dbReference type="GeneCards" id="ABHD1"/>
    <dbReference type="HGNC" id="HGNC:17553">
        <property type="gene designation" value="ABHD1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000143994">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="612195">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000143994"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000143994"/>
    <dbReference type="eggNOG" id="KOG1838">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182902"/>
    <dbReference type="HOGENOM" id="CLU_912033_0_0_1"/>
    <dbReference type="InParanoid" id="Q96SE0"/>
    <dbReference type="OMA" id="MMTTSWG"/>
    <dbReference type="OrthoDB" id="247542at2759"/>
    <dbReference type="PAN-GO" id="Q96SE0">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96SE0"/>
    <dbReference type="PathwayCommons" id="Q96SE0"/>
    <dbReference type="SignaLink" id="Q96SE0"/>
    <dbReference type="Agora" id="ENSG00000143994"/>
    <dbReference type="BioGRID-ORCS" id="84696">
        <property type="hits" value="14 hits in 1143 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84696"/>
    <dbReference type="Pharos" id="Q96SE0">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96SE0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96SE0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000143994">
        <property type="expression patterns" value="Expressed in left testis and 102 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96SE0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008126">
        <property type="term" value="F:acetylesterase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051792">
        <property type="term" value="P:medium-chain fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051793">
        <property type="term" value="P:medium-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000167">
        <property type="entry name" value="Abhydrolase domain containing 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000952">
        <property type="entry name" value="AB_hydrolase_4_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050960">
        <property type="entry name" value="AB_hydrolase_4_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012020">
        <property type="entry name" value="ABHD4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794">
        <property type="entry name" value="ABHYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794:SF60">
        <property type="entry name" value="PROTEIN ABHD1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF005211">
        <property type="entry name" value="Ab_hydro_YheT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01133">
        <property type="entry name" value="UPF0017"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000280204" description="Protein ABHD1">
        <location>
            <begin position="1"/>
            <end position="405"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="2">
        <location>
            <begin position="17"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="2">
        <location>
            <begin position="123"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="329"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054269" description="In isoform 2." evidence="5">
        <original>NRKVIEKVVDIDFVLQARTIRQFDERYTSVAFGYQDCVTYY</original>
        <variation>LSYGKTCRPVQSASLMSATHLWPLDIKTVLPTTKQQALEPR</variation>
        <location>
            <begin position="265"/>
            <end position="305"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054270" description="In isoform 2." evidence="5">
        <location>
            <begin position="306"/>
            <end position="405"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_052484" description="In dbSNP:rs34127901.">
        <original>P</original>
        <variation>Q</variation>
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031087" description="In dbSNP:rs6715286." evidence="4">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031088" description="In dbSNP:rs2304678.">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="371"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="12735795"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15815621"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:17553"/>
        </source>
    </evidence>
    <sequence length="405" mass="45221" checksum="1DC0BFB8FB2CD411" modified="2024-01-24" version="3">MLSSFLSPQNGTWADTFSLLLALAVALYLGYYWACVLQRPRLVAGPQFLAFLEPHCSITTETFYPTLWCFEGRLQSIFQVLLQSQPLVLYQSDILQTPDGGQLLLDWAKQPDSSQDPDPTTQPIVLLLPGITGSSQETYVLHLVNQALRDGYQAVVFNNRGCRGEELRTHRAFCASNTEDLETVVNHIKHRYPQAPLLAVGISFGGILVLNHLAQARQAAGLVAALTLSACWDSFETTRSLETPLNSLLFNQPLTAGLCQLVERNRKVIEKVVDIDFVLQARTIRQFDERYTSVAFGYQDCVTYYKAASPRTKIDAIRIPVLYLSAADDPFSPVCALPIQAAQHSPYVALLITARGGHIGFLEGLLPWQHWYMSRLLHQYAKAIFQDPEGLPDLRALLPSEDRNS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="170" xmlns="https://uniprot.org/uniprot">
    <accession>Q7L211</accession>
    <accession>B3KWE7</accession>
    <accession>Q8NBW1</accession>
    <accession>Q96JX9</accession>
    <name>ABHDD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="3">Protein ABHD13</fullName>
            <ecNumber>3.-.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="3">Alpha/beta hydrolase domain-containing protein 13</fullName>
            <shortName evidence="4">Abhydrolase domain-containing protein 13</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ABHD13</name>
        <name type="synonym">C13orf6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Itakura S."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Hippocampus</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2005" name="DNA Res." volume="12" first="117" last="126">
            <title>Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.</title>
            <authorList>
                <person name="Otsuki T."/>
                <person name="Ota T."/>
                <person name="Nishikawa T."/>
                <person name="Hayashi K."/>
                <person name="Suzuki Y."/>
                <person name="Yamamoto J."/>
                <person name="Wakamatsu A."/>
                <person name="Kimura K."/>
                <person name="Sakamoto K."/>
                <person name="Hatano N."/>
                <person name="Kawai Y."/>
                <person name="Ishii S."/>
                <person name="Saito K."/>
                <person name="Kojima S."/>
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                <person name="Okano K."/>
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            </authorList>
            <dbReference type="PubMed" id="16303743"/>
            <dbReference type="DOI" id="10.1093/dnares/12.2.117"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="15057823"/>
            <dbReference type="DOI" id="10.1038/nature02379"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="5">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <topology evidence="3">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the serine esterase family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH70226" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous termination">
            <sequence resource="EMBL" id="AK075195"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB55387" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.-.-.-"/>
    <dbReference type="EMBL" id="AK027812">
        <property type="protein sequence ID" value="BAB55387.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK124864">
        <property type="protein sequence ID" value="BAG54109.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK075195">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL157762">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471085">
        <property type="protein sequence ID" value="EAX09097.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022566">
        <property type="protein sequence ID" value="AAH22566.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC070226">
        <property type="protein sequence ID" value="AAH70226.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32007.1"/>
    <dbReference type="RefSeq" id="NP_116248.2">
        <property type="nucleotide sequence ID" value="NM_032859.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011519430.1">
        <property type="nucleotide sequence ID" value="XM_011521128.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054231049.1">
        <property type="nucleotide sequence ID" value="XM_054375074.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q7L211"/>
    <dbReference type="SMR" id="Q7L211"/>
    <dbReference type="BioGRID" id="124378">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q7L211">
        <property type="interactions" value="795"/>
    </dbReference>
    <dbReference type="IntAct" id="Q7L211">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000365063"/>
    <dbReference type="ESTHER" id="human-ABHD13">
        <property type="family name" value="ABHD13-BEM46"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.051"/>
    <dbReference type="GlyCosmos" id="Q7L211">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q7L211">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q7L211"/>
    <dbReference type="PhosphoSitePlus" id="Q7L211"/>
    <dbReference type="BioMuta" id="ABHD13"/>
    <dbReference type="DMDM" id="74749881"/>
    <dbReference type="jPOST" id="Q7L211"/>
    <dbReference type="MassIVE" id="Q7L211"/>
    <dbReference type="PaxDb" id="9606-ENSP00000365063"/>
    <dbReference type="PeptideAtlas" id="Q7L211"/>
    <dbReference type="ProteomicsDB" id="68754"/>
    <dbReference type="Pumba" id="Q7L211"/>
    <dbReference type="Antibodypedia" id="25425">
        <property type="antibodies" value="109 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84945"/>
    <dbReference type="Ensembl" id="ENST00000375898.4">
        <property type="protein sequence ID" value="ENSP00000365063.3"/>
        <property type="gene ID" value="ENSG00000139826.7"/>
    </dbReference>
    <dbReference type="GeneID" id="84945"/>
    <dbReference type="KEGG" id="hsa:84945"/>
    <dbReference type="MANE-Select" id="ENST00000375898.4">
        <property type="protein sequence ID" value="ENSP00000365063.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032859.3"/>
        <property type="RefSeq protein sequence ID" value="NP_116248.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001vqq.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:20293"/>
    <dbReference type="ClinPGx" id="PA134862303"/>
    <dbReference type="CTD" id="84945"/>
    <dbReference type="DisGeNET" id="84945"/>
    <dbReference type="GeneCards" id="ABHD13"/>
    <dbReference type="HGNC" id="HGNC:20293">
        <property type="gene designation" value="ABHD13"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000139826">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621039">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000139826"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000139826"/>
    <dbReference type="eggNOG" id="KOG4391">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158114"/>
    <dbReference type="HOGENOM" id="CLU_029375_2_0_1"/>
    <dbReference type="InParanoid" id="Q7L211"/>
    <dbReference type="OMA" id="QYWTSED"/>
    <dbReference type="OrthoDB" id="10249433at2759"/>
    <dbReference type="PAN-GO" id="Q7L211">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7L211"/>
    <dbReference type="PathwayCommons" id="Q7L211"/>
    <dbReference type="SignaLink" id="Q7L211"/>
    <dbReference type="Agora" id="ENSG00000139826"/>
    <dbReference type="BioGRID-ORCS" id="84945">
        <property type="hits" value="63 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84945"/>
    <dbReference type="Pharos" id="Q7L211">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7L211"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 13"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7L211">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000139826">
        <property type="expression patterns" value="Expressed in monocyte and 154 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q7L211">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032839">
        <property type="term" value="C:dendrite cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000058">
        <property type="entry name" value="Alpha/beta hydrolase domain-containing protein 13"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF81">
        <property type="entry name" value="PROTEIN ABHD13"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000281076" description="Protein ABHD13">
        <location>
            <begin position="1"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="2">
        <location>
            <begin position="37"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="268"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AK075195." evidence="3" ref="2">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AK075195." evidence="3" ref="2">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:20293"/>
        </source>
    </evidence>
    <sequence length="337" mass="38548" checksum="D8298BF81784827F" modified="2004-10-11" version="1">MEKSWMLWNFVERWLIALASWSWALCRISLLPLIVTFHLYGGIILLLLIFISIAGILYKFQDVLLYFPEQPSSSRLYVPMPTGIPHENIFIRTKDGIRLNLILIRYTGDNSPYSPTIIYFHGNAGNIGHRLPNALLMLVNLKVNLLLVDYRGYGKSEGEASEEGLYLDSEAVLDYVMTRPDLDKTKIFLFGRSLGGAVAIHLASENSHRISAIMVENTFLSIPHMASTLFSFFPMRYLPLWCYKNKFLSYRKISQCRMPSLFISGLSDQLIPPVMMKQLYELSPSRTKRLAIFPDGTHNDTWQCQGYFTALEQFIKEVVKSHSPEEMAKTSSNVTII</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="169" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BV23</accession>
    <accession>B2R7Y9</accession>
    <accession>Q6ZMF7</accession>
    <name>ABHD6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Monoacylglycerol lipase ABHD6</fullName>
            <ecNumber evidence="4">3.1.1.23</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="1">2-arachidonoylglycerol hydrolase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">Abhydrolase domain-containing protein 6</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ABHD6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Hepatoma</tissue>
            <tissue>Lung</tissue>
        </source>
    </reference>
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                <person name="Zhou J."/>
                <person name="Zhou Y."/>
                <person name="Nelson D."/>
                <person name="Lehrach H."/>
                <person name="Reinhardt R."/>
                <person name="Naylor S.L."/>
                <person name="Yang H."/>
                <person name="Olson M."/>
                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="J. Lipid Res." volume="53" first="2413" last="2424">
            <title>Biochemical and pharmacological characterization of human alpha/beta-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12).</title>
            <authorList>
                <person name="Navia-Paldanius D."/>
                <person name="Savinainen J.R."/>
                <person name="Laitinen J.T."/>
            </authorList>
            <dbReference type="PubMed" id="22969151"/>
            <dbReference type="DOI" id="10.1194/jlr.m030411"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF SER-148</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2021-06" db="PDB data bank">
            <title>Crystal structure of human monoacylglycerol lipase ABHD6 in complex with oleic acid and octyl glucoside.</title>
            <authorList>
                <person name="Nawrotek A."/>
                <person name="Talagas A."/>
                <person name="Vuillard L."/>
                <person name="Miallau L."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 43-337 IN COMPLEX WITH (9Z)-OCTADECENOATE</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2015" name="J. Biol. Chem." volume="290" first="29869" last="29881">
            <title>alpha/beta hydrolase domain-containing 6 (ABHD6) degrades the late endosomal/lysosomal lipid bis(monoacylglycero)phosphate.</title>
            <authorList>
                <person name="Pribasnig M.A."/>
                <person name="Mrak I."/>
                <person name="Grabner G.F."/>
                <person name="Taschler U."/>
                <person name="Knittelfelder O."/>
                <person name="Scherz B."/>
                <person name="Eichmann T.O."/>
                <person name="Heier C."/>
                <person name="Grumet L."/>
                <person name="Kowaliuk J."/>
                <person name="Romauch M."/>
                <person name="Holler S."/>
                <person name="Anderl F."/>
                <person name="Wolinski H."/>
                <person name="Lass A."/>
                <person name="Breinbauer R."/>
                <person name="Marsche G."/>
                <person name="Brown J.M."/>
                <person name="Zimmermann R."/>
            </authorList>
            <dbReference type="PubMed" id="26491015"/>
            <dbReference type="DOI" id="10.1074/jbc.m115.669168"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>VARIANTS HIS-113; CYS-148; LEU-204; PRO-206 AND VAL-231</scope>
        <scope>CHARACTERIZATION OF VARIANTS HIS-113; CYS-148; LEU-204; PRO-206 AND VAL-231</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5">Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol (PubMed:22969151). Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways (By similarity). Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids (By similarity). Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism (PubMed:26491015). BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting (PubMed:26491015).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>Hydrolyzes glycerol monoesters of long-chain fatty acids.</text>
            <dbReference type="EC" id="3.1.1.23"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-octanoylglycerol + H2O = octanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44328"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:85241"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44329"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-decanoylglycerol + H2O = decanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44320"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:75547"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44321"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44316"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:75539"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44312"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:75562"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44313"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39963"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:75455"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:39964"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38491"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:73990"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:38492"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:75342"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:38488"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44732"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75457"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44733"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:26132"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:52392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:26133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44728"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:75612"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44729"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:48428"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75568"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:48429"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>3-(9Z-octadecenoyl)-sn-glycero-1-phospho-(3'-(9Z-octadecenoyl)-1'-sn-glycerol) + H2O = 3-(9Z-octadecenoyl)-sn-glycero-1-phospho-(1'-sn-glycerol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55712"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:139150"/>
            <dbReference type="ChEBI" id="CHEBI:139152"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:55713"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(S,S)-2-(9Z-octadecenoyl)-sn-glycero-1-phospho-(2'-(9Z-octadecenoyl)-1'-sn-glycerol) + H2O = (S,S)-2-(9Z-octadecenoyl)-sn-glycero-1-phospho-(1'-sn-glycerol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55716"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:139156"/>
            <dbReference type="ChEBI" id="CHEBI:139157"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(R,R)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(2'-(9Z-octadecenoyl)-3'-sn-glycerol) + H2O = (R,R)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(3'-sn-glycerol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55804"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:139228"/>
            <dbReference type="ChEBI" id="CHEBI:139230"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">159 uM for 2-arachidonoyglycerol</KM>
            <Vmax evidence="4">45.0 nmol/min/mg enzyme toward 2-arachidonoyglycerol</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="4">Optimum pH is 7.2-9 with 2-arachidonoyglycerol as substrate.</text>
        </phDependence>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916106">
            <id>Q9BV23</id>
        </interactant>
        <interactant intactId="EBI-3385283">
            <id>Q9Y3D6</id>
            <label>FIS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916106">
            <id>Q9BV23</id>
        </interactant>
        <interactant intactId="EBI-10244780">
            <id>Q5QGT7</id>
            <label>RTP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916106">
            <id>Q9BV23</id>
        </interactant>
        <interactant intactId="EBI-4403649">
            <id>Q969E2</id>
            <label>SCAMP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916106">
            <id>Q9BV23</id>
        </interactant>
        <interactant intactId="EBI-11343401">
            <id>Q9NYZ1</id>
            <label>TVP23B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Late endosome membrane</location>
            <topology evidence="3">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Lysosome membrane</location>
            <topology evidence="3">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion membrane</location>
            <topology evidence="3">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.23" evidence="4"/>
    <dbReference type="EMBL" id="AK122983">
        <property type="protein sequence ID" value="BAG53832.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK172797">
        <property type="protein sequence ID" value="BAD18771.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313168">
        <property type="protein sequence ID" value="BAG35986.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC098479">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC137936">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471055">
        <property type="protein sequence ID" value="EAW65360.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001698">
        <property type="protein sequence ID" value="AAH01698.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2887.1"/>
    <dbReference type="RefSeq" id="NP_001307055.1">
        <property type="nucleotide sequence ID" value="NM_001320126.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_065727.4">
        <property type="nucleotide sequence ID" value="NM_020676.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047304586.1">
        <property type="nucleotide sequence ID" value="XM_047448630.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054203346.1">
        <property type="nucleotide sequence ID" value="XM_054347371.1"/>
    </dbReference>
    <dbReference type="PDB" id="7OTS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.79 A"/>
        <property type="chains" value="A/B=43-337"/>
    </dbReference>
    <dbReference type="PDBsum" id="7OTS"/>
    <dbReference type="AlphaFoldDB" id="Q9BV23"/>
    <dbReference type="SMR" id="Q9BV23"/>
    <dbReference type="BioGRID" id="121508">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BV23">
        <property type="interactions" value="323"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BV23">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000295962"/>
    <dbReference type="BindingDB" id="Q9BV23"/>
    <dbReference type="ChEMBL" id="CHEMBL2189127"/>
    <dbReference type="DrugCentral" id="Q9BV23"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="2919"/>
    <dbReference type="SwissLipids" id="SLP:000001042"/>
    <dbReference type="ESTHER" id="human-ABHD6">
        <property type="family name" value="ABHD6-Lip"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.997"/>
    <dbReference type="iPTMnet" id="Q9BV23"/>
    <dbReference type="MetOSite" id="Q9BV23"/>
    <dbReference type="PhosphoSitePlus" id="Q9BV23"/>
    <dbReference type="SwissPalm" id="Q9BV23"/>
    <dbReference type="BioMuta" id="ABHD6"/>
    <dbReference type="DMDM" id="74733280"/>
    <dbReference type="jPOST" id="Q9BV23"/>
    <dbReference type="MassIVE" id="Q9BV23"/>
    <dbReference type="PaxDb" id="9606-ENSP00000420315"/>
    <dbReference type="PeptideAtlas" id="Q9BV23"/>
    <dbReference type="ProteomicsDB" id="79154"/>
    <dbReference type="Pumba" id="Q9BV23"/>
    <dbReference type="Antibodypedia" id="2562">
        <property type="antibodies" value="122 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="57406"/>
    <dbReference type="Ensembl" id="ENST00000295962.8">
        <property type="protein sequence ID" value="ENSP00000295962.4"/>
        <property type="gene ID" value="ENSG00000163686.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000478253.6">
        <property type="protein sequence ID" value="ENSP00000420315.1"/>
        <property type="gene ID" value="ENSG00000163686.16"/>
    </dbReference>
    <dbReference type="GeneID" id="57406"/>
    <dbReference type="KEGG" id="hsa:57406"/>
    <dbReference type="MANE-Select" id="ENST00000478253.6">
        <property type="protein sequence ID" value="ENSP00000420315.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001320126.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001307055.1"/>
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        <property type="organism name" value="human"/>
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        <property type="gene designation" value="ABHD6"/>
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        <property type="expression patterns" value="Tissue enhanced (liver)"/>
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    <dbReference type="OpenTargets" id="ENSG00000163686"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000163686"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="OrthoDB" id="6431331at2759"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BV23"/>
    <dbReference type="PathwayCommons" id="Q9BV23"/>
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        <property type="pathway name" value="Arachidonate production from DAG"/>
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        <property type="development level" value="Tchem"/>
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        <property type="component" value="Chromosome 3"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:regulation of retrograde trans-synaptic signaling by endocanabinoid"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
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        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AB_hydrolase_1"/>
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        <property type="entry name" value="AB_hydrolase_fold"/>
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        <property type="entry name" value="AB_hydrolase_sf"/>
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    <dbReference type="InterPro" id="IPR000639">
        <property type="entry name" value="Epox_hydrolase-like"/>
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    <dbReference type="PANTHER" id="PTHR43798">
        <property type="entry name" value="MONOACYLGLYCEROL LIPASE"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR43798:SF5">
        <property type="entry name" value="MONOACYLGLYCEROL LIPASE ABHD6"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00111">
        <property type="entry name" value="ABHYDROLASE"/>
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    <dbReference type="PRINTS" id="PR00412">
        <property type="entry name" value="EPOXHYDRLASE"/>
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    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000281575" description="Monoacylglycerol lipase ABHD6">
        <location>
            <begin position="1"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="1"/>
            <end position="8"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
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            <begin position="9"/>
            <end position="29"/>
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    <feature type="domain" description="AB hydrolase-1" evidence="3">
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            <begin position="72"/>
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    <feature type="active site" description="Nucleophile" evidence="2 8">
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            <position position="148"/>
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    <feature type="active site" description="Charge relay system" evidence="2">
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            <position position="278"/>
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    <feature type="active site" description="Charge relay system" evidence="2">
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            <position position="306"/>
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    <feature type="binding site" evidence="6 10">
        <location>
            <position position="80"/>
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        <ligand>
            <name>(9Z)-octadecenoate</name>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
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            <position position="149"/>
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            <position position="306"/>
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        <ligand>
            <name>(9Z)-octadecenoate</name>
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        <variation>H</variation>
        <location>
            <position position="113"/>
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    <feature type="sequence variant" id="VAR_081596" description="Loss of bis(monoacylglycero)phosphate (BMP) hydrolase activity; dbSNP:rs11544004." evidence="5">
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        <variation>L</variation>
        <location>
            <position position="204"/>
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    <feature type="sequence variant" id="VAR_081598" description="Loss of lipase activity; dbSNP:rs199696239." evidence="5">
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            <position position="206"/>
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    </feature>
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        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of 2-arachidonoyglycerol hydrolase activity." evidence="4">
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        <variation>A</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAD18771." evidence="7" ref="1">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="11"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAD18771." evidence="7" ref="1">
        <original>L</original>
        <variation>P</variation>
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            <position position="135"/>
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            <begin position="49"/>
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    <feature type="strand" evidence="11">
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            <begin position="58"/>
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    <feature type="strand" evidence="11">
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            <begin position="74"/>
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            <begin position="84"/>
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            <begin position="88"/>
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            <begin position="100"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
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    <evidence type="ECO:0000250" key="2">
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            <dbReference type="UniProtKB" id="Q99685"/>
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    <evidence type="ECO:0000255" key="3"/>
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        <source>
            <dbReference type="PubMed" id="22969151"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="26491015"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source ref="6"/>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
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        <source>
            <dbReference type="PubMed" id="22969151"/>
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    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:21398"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PDB" id="7OTS"/>
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    </evidence>
    <evidence type="ECO:0007829" key="11">
        <source>
            <dbReference type="PDB" id="7OTS"/>
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    </evidence>
    <sequence length="337" mass="38331" checksum="D87CEE8316F94910" modified="2001-06-01" version="1">MDLDVVNMFVIAGGTLAIPILAFVASFLLWPSALIRIYYWYWRRTLGMQVRYVHHEDYQFCYSFRGRPGHKPSILMLHGFSAHKDMWLSVVKFLPKNLHLVCVDMPGHEGTTRSSLDDLSIDGQVKRIHQFVECLKLNKKPFHLVGTSMGGQVAGVYAAYYPSDVSSLCLVCPAGLQYSTDNQFVQRLKELQGSAAVEKIPLIPSTPEEMSEMLQLCSYVRFKVPQQILQGLVDVRIPHNNFYRKLFLEIVSEKSRYSLHQNMDKIKVPTQIIWGKQDQVLDVSGADMLAKSIANCQVELLENCGHSVVMERPRKTAKLIIDFLASVHNTDNNKKLD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-03" modified="2026-01-28" version="155" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BUJ0</accession>
    <accession>Q6UXU8</accession>
    <accession>Q9Y3T7</accession>
    <name>ABHEA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Protein ABHD14A</fullName>
            <ecNumber>3.-.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Alpha/beta hydrolase domain-containing protein 14A</fullName>
            <shortName evidence="5">Abhydrolase domain-containing protein 14A</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ABHD14A</name>
        <name type="ORF">UNQ1913/PRO4373</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="Genome Res." volume="13" first="2265" last="2270">
            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
            <authorList>
                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
                <person name="Abaya E."/>
                <person name="Baker K."/>
                <person name="Baldwin D.T."/>
                <person name="Brush J."/>
                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
                <person name="Currell B."/>
                <person name="Deuel B."/>
                <person name="Dowd P."/>
                <person name="Eaton D."/>
                <person name="Foster J.S."/>
                <person name="Grimaldi C."/>
                <person name="Gu Q."/>
                <person name="Hass P.E."/>
                <person name="Heldens S."/>
                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT GLN-32</scope>
        <source>
            <tissue>Lymph</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Possible role in granule neuron development.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Membrane</location>
            <topology evidence="4">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the AB hydrolase superfamily. ABHD14 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">It is uncertain whether Met-1 or Met-30 is the initiator.</text>
    </comment>
    <comment type="sequence caution" evidence="4">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAQ88568" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.-.-.-"/>
    <dbReference type="EMBL" id="AY358201">
        <property type="protein sequence ID" value="AAQ88568.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL050015">
        <property type="protein sequence ID" value="CAB43237.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002571">
        <property type="protein sequence ID" value="AAH02571.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2843.1"/>
    <dbReference type="PIR" id="T08702">
        <property type="entry name" value="T08702"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056222.2">
        <property type="nucleotide sequence ID" value="NM_015407.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BUJ0"/>
    <dbReference type="SMR" id="Q9BUJ0"/>
    <dbReference type="BioGRID" id="117383">
        <property type="interactions" value="74"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BUJ0">
        <property type="interactions" value="922"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BUJ0">
        <property type="interactions" value="56"/>
    </dbReference>
    <dbReference type="MINT" id="Q9BUJ0"/>
    <dbReference type="STRING" id="9606.ENSP00000273596"/>
    <dbReference type="ESTHER" id="human-ABHD14A">
        <property type="family name" value="CIB-CCG1-interacting-factor-B"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.981"/>
    <dbReference type="GlyCosmos" id="Q9BUJ0">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9BUJ0">
        <property type="glycosylation" value="5 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9BUJ0"/>
    <dbReference type="PhosphoSitePlus" id="Q9BUJ0"/>
    <dbReference type="SwissPalm" id="Q9BUJ0"/>
    <dbReference type="BioMuta" id="ABHD14A"/>
    <dbReference type="DMDM" id="143955271"/>
    <dbReference type="jPOST" id="Q9BUJ0"/>
    <dbReference type="MassIVE" id="Q9BUJ0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000273596"/>
    <dbReference type="PeptideAtlas" id="Q9BUJ0"/>
    <dbReference type="ProteomicsDB" id="79089"/>
    <dbReference type="Antibodypedia" id="51597">
        <property type="antibodies" value="127 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="25864"/>
    <dbReference type="Ensembl" id="ENST00000273596.8">
        <property type="protein sequence ID" value="ENSP00000273596.3"/>
        <property type="gene ID" value="ENSG00000248487.11"/>
    </dbReference>
    <dbReference type="GeneID" id="25864"/>
    <dbReference type="KEGG" id="hsa:25864"/>
    <dbReference type="MANE-Select" id="ENST00000273596.8">
        <property type="protein sequence ID" value="ENSP00000273596.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_015407.5"/>
        <property type="RefSeq protein sequence ID" value="NP_056222.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003dco.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24538"/>
    <dbReference type="ClinPGx" id="PA142672659"/>
    <dbReference type="CTD" id="25864"/>
    <dbReference type="DisGeNET" id="25864"/>
    <dbReference type="GeneCards" id="ABHD14A"/>
    <dbReference type="HGNC" id="HGNC:24538">
        <property type="gene designation" value="ABHD14A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000248487">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="618771">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000248487"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000248487"/>
    <dbReference type="eggNOG" id="ENOG502QR0B">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161296"/>
    <dbReference type="HOGENOM" id="CLU_020336_28_2_1"/>
    <dbReference type="InParanoid" id="Q9BUJ0"/>
    <dbReference type="OrthoDB" id="284184at2759"/>
    <dbReference type="PAN-GO" id="Q9BUJ0">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BUJ0"/>
    <dbReference type="PathwayCommons" id="Q9BUJ0"/>
    <dbReference type="SignaLink" id="Q9BUJ0"/>
    <dbReference type="Agora" id="ENSG00000248487"/>
    <dbReference type="BioGRID-ORCS" id="25864">
        <property type="hits" value="11 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="25864"/>
    <dbReference type="Pharos" id="Q9BUJ0">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BUJ0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BUJ0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000248487">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 199 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9BUJ0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016787">
        <property type="term" value="F:hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000093">
        <property type="entry name" value="protein ABHD14A isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46197:SF1">
        <property type="entry name" value="PROTEIN ABHD14A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46197">
        <property type="entry name" value="PROTEIN ABHD14B-LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12697">
        <property type="entry name" value="Abhydrolase_6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000282285" description="Protein ABHD14A">
        <location>
            <begin position="1"/>
            <end position="271"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="2">
        <location>
            <begin position="35"/>
            <end position="55"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="171"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="201"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031390" description="In dbSNP:rs17849626." evidence="3">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031391" description="In dbSNP:rs404527.">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="61"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAB43237." evidence="4" ref="2">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:24538"/>
        </source>
    </evidence>
    <sequence length="271" mass="29765" checksum="B9CAF975D3208F10" modified="2007-04-03" version="2">MVGALCGCWFRLGGARPLIPLGPTVVQTSMSRSQVALLGLSLLLMLLLYVGLPGPPEQTSCLWGDPNVTVLAGLTPGNSPIFYREVLPLNQAHRVEVVLLHGKAFNSHTWEQLGTLQLLSQRGYRAVALDLPGFGNSAPSKEASTEAGRAALLERALRDLEVQNAVLVSPSLSGHYALPFLMRGHHQLHGFVPIAPTSTQNYTQEQFWAVKTPTLILYGELDHILARESLRQLRHLPNHSVVKLRNAGHACYLHKPQDFHLVLLAFLDHLP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-10-10" modified="2026-01-28" version="162" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H3Z7</accession>
    <name>ABHGB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="5 6">ABHD16B</fullName>
            <ecNumber evidence="3">3.1.1.111</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="5 6">Alpha/beta hydrolase domain-containing protein 16B</fullName>
            <shortName evidence="8">Abhydrolase domain-containing protein 16B</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="8" type="primary">ABHD16B</name>
        <name type="synonym">C20orf135</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
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                <person name="Gilbert J.G.R."/>
                <person name="Jones M."/>
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                <person name="Babbage A.K."/>
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                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
                <person name="Beasley O.P."/>
                <person name="Bird C.P."/>
                <person name="Blakey S.E."/>
                <person name="Bridgeman A.M."/>
                <person name="Brown A.J."/>
                <person name="Buck D."/>
                <person name="Burrill W.D."/>
                <person name="Butler A.P."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clamp M."/>
                <person name="Clark G."/>
                <person name="Clark L.N."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Cobley V.E."/>
                <person name="Collier R.E."/>
                <person name="Connor R.E."/>
                <person name="Corby N.R."/>
                <person name="Coulson A."/>
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                <person name="Deadman R."/>
                <person name="Dhami P.D."/>
                <person name="Dunn M."/>
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                <person name="Fraser A."/>
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                <person name="Griffiths M.N.D."/>
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                <person name="Harley J.L."/>
                <person name="Heath P.D."/>
                <person name="Ho S."/>
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                <person name="Howden P.J."/>
                <person name="Huckle E."/>
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                <person name="Hunt S.E."/>
                <person name="Jekosch K."/>
                <person name="Johnson C.M."/>
                <person name="Johnson D."/>
                <person name="Kay M.P."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lehvaeslaiho M.H."/>
                <person name="Leversha M.A."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J.D."/>
                <person name="Marsh V.L."/>
                <person name="Martin S.L."/>
                <person name="McConnachie L.J."/>
                <person name="McLay K."/>
                <person name="McMurray A.A."/>
                <person name="Milne S.A."/>
                <person name="Mistry D."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Nickerson T."/>
                <person name="Oliver K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce T.A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Prathalingam S.R."/>
                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Scott C.E."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
                <person name="Sulston J.E."/>
                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2023" name="Biophys. Chem." volume="296" first="106976" last="106976">
            <title>Molecular insights on PS-PLA1 lipase activity of human ABHD16B.</title>
            <authorList>
                <person name="Narayanasamy R."/>
                <person name="Rajasekharan R."/>
                <person name="Usharani D."/>
            </authorList>
            <dbReference type="PubMed" id="36841071"/>
            <dbReference type="DOI" id="10.1016/j.bpc.2023.106976"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2024" name="Chem. Phys. Lipids" volume="258" first="105353" last="105353">
            <title>Elucidating the functional role of human ABHD16B lipase in regulating triacylglycerol mobilization and membrane lipid synthesis in Saccharomyces cerevisiae.</title>
            <authorList>
                <person name="Narayanasamy R."/>
                <person name="Usharani D."/>
                <person name="Rajasekharan R."/>
            </authorList>
            <dbReference type="PubMed" id="37944658"/>
            <dbReference type="DOI" id="10.1016/j.chemphyslip.2023.105353"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Hydrolyzes the sn-1 position of glycerophospholipids with high specificity towards phosphatidylserine (PS), PS-PLA1 enzyme (PubMed:36841071). Also hydrolyzes the acyl chain of glycerolipids with a preference for the monoacylglycerol (MAG) 1-acylglycerol, MAG lipase (PubMed:36841071). Plays a regulatory role in cellular lipid homeostasis by modulating genes involved in neutral lipid degradation and in phospholipid synthesis and composition (PubMed:37944658).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a 1,2-diacyl-sn-glycero-3-phospho-L-serine + H2O = a 2-acyl-sn-glycero-3-phospho-L-serine + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:42212"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:57262"/>
            <dbReference type="ChEBI" id="CHEBI:65214"/>
            <dbReference type="EC" id="3.1.1.111"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:42213"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a 1-acylglycerol + H2O = glycerol + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:34019"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:35759"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:34020"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:75342"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:38488"/>
        </physiologicalReaction>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily. ABHD16 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.111" evidence="3"/>
    <dbReference type="EMBL" id="AL118506">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13539.1"/>
    <dbReference type="RefSeq" id="NP_542189.1">
        <property type="nucleotide sequence ID" value="NM_080622.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H3Z7"/>
    <dbReference type="SMR" id="Q9H3Z7"/>
    <dbReference type="BioGRID" id="126662">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9H3Z7">
        <property type="interactions" value="205"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H3Z7">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000358932"/>
    <dbReference type="ESTHER" id="human-ABHD16B">
        <property type="family name" value="ABHD16"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.B13"/>
    <dbReference type="GlyGen" id="Q9H3Z7">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H3Z7"/>
    <dbReference type="PhosphoSitePlus" id="Q9H3Z7"/>
    <dbReference type="BioMuta" id="ABHD16B"/>
    <dbReference type="DMDM" id="23813959"/>
    <dbReference type="MassIVE" id="Q9H3Z7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000358932"/>
    <dbReference type="PeptideAtlas" id="Q9H3Z7"/>
    <dbReference type="ProteomicsDB" id="80774"/>
    <dbReference type="TopDownProteomics" id="Q9H3Z7"/>
    <dbReference type="Antibodypedia" id="70808">
        <property type="antibodies" value="9 antibodies from 7 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="140701"/>
    <dbReference type="Ensembl" id="ENST00000369916.5">
        <property type="protein sequence ID" value="ENSP00000358932.3"/>
        <property type="gene ID" value="ENSG00000183260.7"/>
    </dbReference>
    <dbReference type="GeneID" id="140701"/>
    <dbReference type="KEGG" id="hsa:140701"/>
    <dbReference type="MANE-Select" id="ENST00000369916.5">
        <property type="protein sequence ID" value="ENSP00000358932.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_080622.4"/>
        <property type="RefSeq protein sequence ID" value="NP_542189.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ygx.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16128"/>
    <dbReference type="ClinPGx" id="PA25677"/>
    <dbReference type="CTD" id="140701"/>
    <dbReference type="DisGeNET" id="140701"/>
    <dbReference type="GeneCards" id="ABHD16B"/>
    <dbReference type="HGNC" id="HGNC:16128">
        <property type="gene designation" value="ABHD16B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000183260">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="620190">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000183260"/>
    <dbReference type="eggNOG" id="KOG1553">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162803"/>
    <dbReference type="HOGENOM" id="CLU_040705_2_0_1"/>
    <dbReference type="InParanoid" id="Q9H3Z7"/>
    <dbReference type="OMA" id="GHRALTC"/>
    <dbReference type="OrthoDB" id="6412627at2759"/>
    <dbReference type="PAN-GO" id="Q9H3Z7">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H3Z7"/>
    <dbReference type="PathwayCommons" id="Q9H3Z7"/>
    <dbReference type="SignaLink" id="Q9H3Z7"/>
    <dbReference type="Agora" id="ENSG00000183260"/>
    <dbReference type="BioGRID-ORCS" id="140701">
        <property type="hits" value="14 hits in 1144 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD16B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="140701"/>
    <dbReference type="Pharos" id="Q9H3Z7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H3Z7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H3Z7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000183260">
        <property type="expression patterns" value="Expressed in right testis and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004620">
        <property type="term" value="F:phospholipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052651">
        <property type="term" value="P:monoacylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006660">
        <property type="term" value="P:phosphatidylserine catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000074">
        <property type="entry name" value="Abhydrolase domain containing 16A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12277:SF37">
        <property type="entry name" value="PROTEIN ABHD16B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-1208">Phospholipid metabolism</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000079463" description="ABHD16B">
        <location>
            <begin position="1"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="2">
        <location>
            <begin position="174"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050920" description="In dbSNP:rs2281534.">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="36841071"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="37944658"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="36841071"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="37944658"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:16128"/>
        </source>
    </evidence>
    <sequence length="469" mass="52555" checksum="85C72E84CCFFC9A1" modified="2001-03-01" version="1">MCVICFVKALVRVFKIYLTASYTYPFRGWPVAFRWDDVRAVGRSSSHRALTCAAAAAGVWLLRDETLGGDALGRPPRGARSQAQCLLQQLRELPGQLASYALAHSLGRWLVYPGSVSLMTRALLPLLQQGQERLVERYHGRRAKLVACDGNEIDTMFMDRRQHPGSHVHGPRLVICCEGNAGFYEMGCLSAPLEAGYSVLGWNHPGFGSSTGVPFPQHDANAMDVVVEYALHRLHFPPAHLVVYGWSVGGFTATWATMTYPELGALVLDATFDDLVPLALKVMPHSWKGLVVRTVREHFNLNVAEQLCCYPGPVLLLRRTQDDVVSTSGRLRPLSPGDVEGNRGNELLLRLLEHRYPVVMAREGRAVVTRWLRAGSLAQEAAFYARYRVDEDWCLALLRSYRARCEEELEGEEALGPHGPAFPWLVGQGLSSRRRRRLALFLARKHLKNVEATHFSPLEPEEFQLPWRL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-08-22" modified="2026-01-28" version="181" xmlns="https://uniprot.org/uniprot">
    <accession>Q96IU4</accession>
    <accession>Q86VK8</accession>
    <accession>Q8N8W5</accession>
    <name>ABHEB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Putative protein-lysine deacylase ABHD14B</fullName>
            <ecNumber evidence="9">2.3.1.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Alpha/beta hydrolase domain-containing protein 14B</fullName>
            <shortName evidence="10">Abhydrolase domain-containing protein 14B</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="4">CCG1-interacting factor B</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="6 10" type="primary">ABHD14B</name>
        <name evidence="4" type="synonym">CIB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Kidney</tissue>
            <tissue>Ovarian carcinoma</tissue>
            <tissue>Placenta</tissue>
        </source>
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            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            <tissue>Skin</tissue>
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                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2020" name="Biochemistry" volume="59" first="183" last="196">
            <title>Functional annotation of ABHD14B, an orphan serine hydrolase enzyme.</title>
            <authorList>
                <person name="Rajendran A."/>
                <person name="Vaidya K."/>
                <person name="Mendoza J."/>
                <person name="Bridwell-Rabb J."/>
                <person name="Kamat S.S."/>
            </authorList>
            <dbReference type="PubMed" id="31478652"/>
            <dbReference type="DOI" id="10.1021/acs.biochem.9b00703"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF SER-111</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2000" name="Acta Crystallogr. D" volume="56" first="1479" last="1481">
            <title>Purification, crystallization and preliminary X-ray crystallographic analysis of human CCG1-interacting factor B.</title>
            <authorList>
                <person name="Padmanabhan B."/>
                <person name="Kuzuhara T."/>
                <person name="Mizuno H."/>
                <person name="Horikoshi M."/>
            </authorList>
            <dbReference type="PubMed" id="11053859"/>
            <dbReference type="DOI" id="10.1107/s0907444900010957"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)</scope>
        <scope>INTERACTION WITH TAF1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="9615" last="9624">
            <title>The crystal structure of CCG1/TAF(II)250-interacting factor B (CIB).</title>
            <authorList>
                <person name="Padmanabhan B."/>
                <person name="Kuzuhara T."/>
                <person name="Adachi N."/>
                <person name="Horikoshi M."/>
            </authorList>
            <dbReference type="PubMed" id="14672934"/>
            <dbReference type="DOI" id="10.1074/jbc.m312165200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVE SITES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH TAF1</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 7">Acts as an atypical protein-lysine deacetylase in vitro (PubMed:31478652). Catalyzes the deacetylation of lysine residues using CoA as substrate, generating acetyl-CoA and the free amine of protein-lysine residues (PubMed:31478652). Additional experiments are however required to confirm the protein-lysine deacetylase activity in vivo (Probable). Has hydrolase activity towards various surrogate p-nitrophenyl (pNp) substrates, such as pNp-butyrate, pNp-acetate and pNp-octanoate in vitro, with a strong preference for pNp-acetate (PubMed:14672934, PubMed:31478652). May activate transcription (PubMed:14672934).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45948"/>
            <dbReference type="Rhea" id="RHEA-COMP:9752"/>
            <dbReference type="Rhea" id="RHEA-COMP:10731"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29969"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:61930"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="9">
            <dbReference type="Rhea" id="RHEA:45950"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">1.8 mM for p-nitrophenyl-acetate</KM>
            <KM evidence="3">3.1 mM for p-nitrophenyl-butyrate</KM>
            <KM evidence="3">3.9 mM for p-nitrophenyl-octanoate</KM>
            <text evidence="3">kcat is 2.2 min(-1) for p-nitrophenyl-acetate (PubMed:31478652). kcat is 0.6 min(-1) for p-nitrophenyl-butyrate (PubMed:31478652). kcat is 0.2 min(-1) for p-nitrophenyl-octanoate (PubMed:31478652).</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">May interact with TAF1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1 2 3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1 2 3">Nucleus</location>
        </subcellularLocation>
        <text evidence="2">Predominantly cytoplasmic.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96IU4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96IU4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_008058"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2">Ubiquitous (PubMed:14672934). Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte, heart, placenta, lung, liver, skeletal muscle, pancreas and kidney (PubMed:14672934).</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AB hydrolase superfamily. ABHD14 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="9">The protein-lysine deacetylase activity using CoA as substrate is unclear as this protein belongs to a family of serine hydrolases, and that the reaction shown in the publication is not hydrolyzing H(2)O. Additional experiments are therefore required to confirm this activity in vivo.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH50650" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="2.3.1.-" evidence="9"/>
    <dbReference type="EMBL" id="AK075034">
        <property type="protein sequence ID" value="BAC11366.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK075112">
        <property type="protein sequence ID" value="BAC11408.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK096073">
        <property type="protein sequence ID" value="BAC04696.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007234">
        <property type="protein sequence ID" value="AAH07234.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC050650">
        <property type="protein sequence ID" value="AAH50650.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC056411">
        <property type="protein sequence ID" value="AAH56411.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2842.1">
        <molecule id="Q96IU4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001139786.1">
        <molecule id="Q96IU4-1"/>
        <property type="nucleotide sequence ID" value="NM_001146314.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001241682.1">
        <molecule id="Q96IU4-2"/>
        <property type="nucleotide sequence ID" value="NM_001254753.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_116139.1">
        <molecule id="Q96IU4-1"/>
        <property type="nucleotide sequence ID" value="NM_032750.3"/>
    </dbReference>
    <dbReference type="PDB" id="1IMJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-210"/>
    </dbReference>
    <dbReference type="PDBsum" id="1IMJ"/>
    <dbReference type="AlphaFoldDB" id="Q96IU4"/>
    <dbReference type="SMR" id="Q96IU4"/>
    <dbReference type="BioGRID" id="124289">
        <property type="interactions" value="33"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96IU4">
        <property type="interactions" value="1412"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96IU4">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000420065"/>
    <dbReference type="ESTHER" id="human-CIB">
        <property type="family name" value="CIB-CCG1-interacting-factor-B"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.983"/>
    <dbReference type="GlyGen" id="Q96IU4">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96IU4"/>
    <dbReference type="MetOSite" id="Q96IU4"/>
    <dbReference type="PhosphoSitePlus" id="Q96IU4"/>
    <dbReference type="BioMuta" id="ABHD14B"/>
    <dbReference type="DMDM" id="34222621"/>
    <dbReference type="OGP" id="Q96IU4"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00063827"/>
    <dbReference type="jPOST" id="Q96IU4"/>
    <dbReference type="MassIVE" id="Q96IU4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000420065"/>
    <dbReference type="PeptideAtlas" id="Q96IU4"/>
    <dbReference type="ProteomicsDB" id="76854">
        <molecule id="Q96IU4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76855">
        <molecule id="Q96IU4-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q96IU4"/>
    <dbReference type="TopDownProteomics" id="Q96IU4-1">
        <molecule id="Q96IU4-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="46121">
        <property type="antibodies" value="246 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84836"/>
    <dbReference type="Ensembl" id="ENST00000361143.10">
        <molecule id="Q96IU4-1"/>
        <property type="protein sequence ID" value="ENSP00000354841.5"/>
        <property type="gene ID" value="ENSG00000114779.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000395008.6">
        <molecule id="Q96IU4-1"/>
        <property type="protein sequence ID" value="ENSP00000378455.2"/>
        <property type="gene ID" value="ENSG00000114779.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000483233.5">
        <molecule id="Q96IU4-1"/>
        <property type="protein sequence ID" value="ENSP00000420065.1"/>
        <property type="gene ID" value="ENSG00000114779.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000525795.1">
        <molecule id="Q96IU4-1"/>
        <property type="protein sequence ID" value="ENSP00000433388.1"/>
        <property type="gene ID" value="ENSG00000114779.21"/>
    </dbReference>
    <dbReference type="GeneID" id="84836"/>
    <dbReference type="KEGG" id="hsa:84836"/>
    <dbReference type="MANE-Select" id="ENST00000361143.10">
        <property type="protein sequence ID" value="ENSP00000354841.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001146314.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001139786.1"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28235"/>
    <dbReference type="ClinPGx" id="PA142672660"/>
    <dbReference type="CTD" id="84836"/>
    <dbReference type="DisGeNET" id="84836"/>
    <dbReference type="GeneCards" id="ABHD14B"/>
    <dbReference type="HGNC" id="HGNC:28235">
        <property type="gene designation" value="ABHD14B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000114779">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621040">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000114779"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000114779"/>
    <dbReference type="eggNOG" id="ENOG502QR0B">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159388"/>
    <dbReference type="HOGENOM" id="CLU_020336_28_0_1"/>
    <dbReference type="InParanoid" id="Q96IU4"/>
    <dbReference type="OMA" id="GEVVLWY"/>
    <dbReference type="OrthoDB" id="284184at2759"/>
    <dbReference type="PAN-GO" id="Q96IU4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96IU4"/>
    <dbReference type="BioCyc" id="MetaCyc:ENSG00000114779-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q96IU4"/>
    <dbReference type="Reactome" id="R-HSA-156584">
        <property type="pathway name" value="Cytosolic sulfonation of small molecules"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q96IU4"/>
    <dbReference type="Agora" id="ENSG00000114779"/>
    <dbReference type="BioGRID-ORCS" id="84836">
        <property type="hits" value="13 hits in 1167 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD14B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q96IU4"/>
    <dbReference type="GenomeRNAi" id="84836"/>
    <dbReference type="Pharos" id="Q96IU4">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96IU4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96IU4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000114779">
        <property type="expression patterns" value="Expressed in ileal mucosa and 169 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96IU4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016787">
        <property type="term" value="F:hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0061733">
        <property type="term" value="F:protein-lysine-acetyltransferase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050427">
        <property type="term" value="P:3'-phosphoadenosine 5'-phosphosulfate metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045944">
        <property type="term" value="P:positive regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000077">
        <property type="entry name" value="Abhydrolase domain containing 14B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46197">
        <property type="entry name" value="PROTEIN ABHD14B-LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46197:SF2">
        <property type="entry name" value="PROTEIN-LYSINE DEACYLASE ABHD14B-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12697">
        <property type="entry name" value="Abhydrolase_6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0012">Acyltransferase</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="initiator methionine" description="Removed" evidence="11">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000065038" description="Putative protein-lysine deacylase ABHD14B">
        <location>
            <begin position="2"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8 9">
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="188"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="11">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_008058" description="In isoform 2." evidence="5">
        <original>MAASVEQREGTIQVQGQALFFREALPGSGQARFSVLLLHGIRFSSETWQNLGTLHRLAQAGYRAVAIDL</original>
        <variation>MGPGLFPAFLLRPQVTASTRLLPVCASPRSS</variation>
        <location>
            <begin position="1"/>
            <end position="69"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished protein-lysine deacetylase activity in vitro." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="5"/>
            <end position="7"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="12"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="17"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="21"/>
            <end position="25"/>
        </location>
    </feature>
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    <evidence type="ECO:0000269" key="1">
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            <dbReference type="PubMed" id="31478652"/>
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        <source>
            <dbReference type="HGNC" id="HGNC:28235"/>
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            <dbReference type="PubMed" id="22814378"/>
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            <dbReference type="PubMed" id="24275569"/>
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    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="1IMJ"/>
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    <sequence length="210" mass="22346" checksum="3CACE8759A2ADFAD" modified="2001-12-01" version="1">MAASVEQREGTIQVQGQALFFREALPGSGQARFSVLLLHGIRFSSETWQNLGTLHRLAQAGYRAVAIDLPGLGHSKEAAAPAPIGELAPGSFLAAVVDALELGPPVVISPSLSGMYSLPFLTAPGSQLPGFVPVAPICTDKINAANYASVKTPALIVYGDQDPMGQTSFEHLKQLPNHRVLIMKGAGHPCYLDKPEEWHTGLLDFLQGLQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="160" xmlns="https://uniprot.org/uniprot">
    <accession>Q96I13</accession>
    <accession>Q9HAE9</accession>
    <name>ABHD8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="5">Protein ABHD8</fullName>
            <ecNumber>3.-.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="5">Alpha/beta hydrolase domain-containing protein 8</fullName>
            <shortName evidence="6">Abhydrolase domain-containing protein 8</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="6" type="primary">ABHD8</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Embryo</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Lymph</tissue>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2025" name="Autophagy" volume="21" first="338" last="351">
            <title>ABHD8 antagonizes inflammation by facilitating chaperone-mediated autophagy-mediated degradation of NLRP3.</title>
            <authorList>
                <person name="Yang S."/>
                <person name="Li M."/>
                <person name="Lian G."/>
                <person name="Wu Y."/>
                <person name="Cui J."/>
                <person name="Wang L."/>
            </authorList>
            <dbReference type="PubMed" id="39225180"/>
            <dbReference type="DOI" id="10.1080/15548627.2024.2395158"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH NLRP3 AND ZDHHC12</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH SARS-COV-2 N (MICROBIAL INFECTION)</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Negatively regulates NLRP3-driven inflammation (PubMed:39225180). Promotes NLRP3 degradation through the chaperone-mediated autophagy (CMA) pathway, hence attenuating inflammasome activation and IL1B secretion. Acts by recruiting palmitoyltransferase ZDHHC12 to NLRP3, facilitating NLRP3 palmitoylation and subsequent degradation (PubMed:39225180).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts with NLRP3 (via NACHT and LLR domains); this interaction is enhanced in the presence of NLRP3 inflammasome inducers, such as ATP, nigericin, silica, or alum (PubMed:39225180). Interacts with ZDHHC12 (PubMed:39225180).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">(Microbial infection) Interacts with SARS-CoV-2 nucleoprotein N; this interaction disrupts the NLRP3-ABHD8 association, enhancing NLRP3 stability, ultimately leading to increased inflammasome activation.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17180442">
            <id>Q96I13</id>
        </interactant>
        <interactant intactId="EBI-10242151">
            <id>Q53EP0-3</id>
            <label>FNDC3B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17180442">
            <id>Q96I13</id>
        </interactant>
        <interactant intactId="EBI-11741890">
            <id>Q86VK4-3</id>
            <label>ZNF410</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the AB hydrolase superfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="BAB13900.1"/>
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        <property type="development level" value="Tdark"/>
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        <property type="component" value="Chromosome 19"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 105 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="P:phosphatidic acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000017">
        <property type="entry name" value="Abhydrolase domain containing 8"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000639">
        <property type="entry name" value="Epox_hydrolase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886:SF83">
        <property type="entry name" value="PROTEIN ABHD8"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886">
        <property type="entry name" value="RE40534P-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00111">
        <property type="entry name" value="ABHYDROLASE"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00412">
        <property type="entry name" value="EPOXHYDRLASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0395">Inflammatory response</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000281382" description="Protein ABHD8">
        <location>
            <begin position="1"/>
            <end position="439"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="2">
        <location>
            <begin position="177"/>
            <end position="279"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="49"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="124"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="3">
        <location>
            <begin position="136"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="146"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="370"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB13900." evidence="5" ref="1">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="103"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="39225180"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0000312" key="6">
        <source>
            <dbReference type="HGNC" id="HGNC:23759"/>
        </source>
    </evidence>
    <sequence length="439" mass="47331" checksum="5D6DBB7BDD4A87C3" modified="2001-12-01" version="1">MLTGVTDGIFCCLLGTPPNAVGPLESVESSDGYTFVEVKPGRVLRVKHAGPAPAAAPPPPSSASSDAAQGDLSGLVRCQRRITVYRNGRLLVENLGRAPRADLLHGQNGSGEPPAALEVELADPAGSDGRLAPGSAGSGSGSGSGGRRRRARRPKRTIHIDCEKRITSCKGAQADVVLFFIHGVGGSLAIWKEQLDFFVRLGYEVVAPDLAGHGASSAPQVAAAYTFYALAEDMRAIFKRYAKKRNVLIGHSYGVSFCTFLAHEYPDLVHKVIMINGGGPTALEPSFCSIFNMPTCVLHCLSPCLAWSFLKAGFARQGAKEKQLLKEGNAFNVSSFVLRAMMSGQYWPEGDEVYHAELTVPVLLVHGMHDKFVPVEEDQRMAEILLLAFLKLIDEGSHMVMLECPETVNTLLHEFLLWEPEPSPKALPEPLPAPPEDKK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-11-01" modified="2026-01-28" version="193" xmlns="https://uniprot.org/uniprot">
    <accession>P08910</accession>
    <accession>Q53G48</accession>
    <accession>Q53GU0</accession>
    <accession>Q5FVD9</accession>
    <accession>Q8TC79</accession>
    <name>ABHD2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">Monoacylglycerol lipase ABHD2</fullName>
            <ecNumber evidence="6">3.1.1.23</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="9">2-arachidonoylglycerol hydrolase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">Abhydrolase domain-containing protein 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">Acetylesterase</fullName>
            <ecNumber evidence="7">3.1.1.6</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Lung alpha/beta hydrolase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">Progesterone-sensitive lipase</fullName>
            <ecNumber evidence="7">3.1.1.79</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="8">Protein PHPS1-2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">ABHD2</name>
        <name evidence="2" type="synonym">LABH2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="Nucleic Acids Res." volume="16" first="8721" last="8721">
            <title>Primary structure of a human protein which bears structural similarities to members of the rhodopsin/beta-adrenergic receptor family.</title>
            <authorList>
                <person name="Rapiejko P.J."/>
                <person name="George S.T."/>
                <person name="Malbon C.C."/>
            </authorList>
            <dbReference type="PubMed" id="2843827"/>
            <dbReference type="DOI" id="10.1093/nar/16.17.8721"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2002-09" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of an androgen-regulated a/b hydrolase.</title>
            <authorList>
                <person name="Utleg A."/>
                <person name="White J."/>
                <person name="Lin B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Suzuki Y."/>
                <person name="Sugano S."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Takeda T."/>
                <person name="Sakaki Y."/>
                <person name="Tanaka A."/>
                <person name="Yokoyama S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Gastric carcinoma</tissue>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT GLN-253</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2016" name="Biosci. Rep." volume="36" first="0" last="0">
            <title>Molecular characterization of human ABHD2 as TAG lipase and ester hydrolase.</title>
            <authorList>
                <person name="M N.K."/>
                <person name="V B S C T."/>
                <person name="G K V."/>
                <person name="B C.S."/>
                <person name="Guntupalli S."/>
                <person name="J S B."/>
            </authorList>
            <dbReference type="PubMed" id="27247428"/>
            <dbReference type="DOI" id="10.1042/bsr20160033"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2016" name="Science" volume="352" first="555" last="559">
            <title>Unconventional endocannabinoid signaling governs sperm activation via sex hormone progesterone.</title>
            <authorList>
                <person name="Miller M.R."/>
                <person name="Mannowetz N."/>
                <person name="Iavarone A.T."/>
                <person name="Safavi R."/>
                <person name="Gracheva E.O."/>
                <person name="Smith J.F."/>
                <person name="Hill R.Z."/>
                <person name="Bautista D.M."/>
                <person name="Kirichok Y."/>
                <person name="Lishko P.V."/>
            </authorList>
            <dbReference type="PubMed" id="26989199"/>
            <dbReference type="DOI" id="10.1126/science.aad6887"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <comment type="function">
        <text evidence="2 6 7">Progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell membrane (PubMed:26989199). Acts as a progesterone receptor: progesterone-binding activates the acylglycerol lipase activity, mediating degradation of 1-arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA) (PubMed:26989199). Also displays an ester hydrolase activity against acetyl ester, butanoate ester and hexadecanoate ester (PubMed:27247428). Plays a key role in sperm capacitation in response to progesterone by mediating degradation of 2AG, an inhibitor of the sperm calcium channel CatSper, leading to calcium influx via CatSper and sperm activation (PubMed:26989199). May also play a role in smooth muscle cells migration (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>an acetyl ester + H2O = an aliphatic alcohol + acetate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12957"/>
            <dbReference type="ChEBI" id="CHEBI:2571"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:47622"/>
            <dbReference type="EC" id="3.1.1.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:12958"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>Hydrolyzes glycerol monoesters of long-chain fatty acids.</text>
            <dbReference type="EC" id="3.1.1.23"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12044"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17855"/>
            <dbReference type="ChEBI" id="CHEBI:18035"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="EC" id="3.1.1.79"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:12045"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:26132"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:52392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:26133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a butanoate ester + H2O = an aliphatic alcohol + butanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:47348"/>
            <dbReference type="ChEBI" id="CHEBI:2571"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:50477"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:47349"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>hexadecanoate ester + H2O = an aliphatic alcohol + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:47392"/>
            <dbReference type="ChEBI" id="CHEBI:2571"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25835"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:47393"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="6">Acylglycerol lipase activity is activated upon binding to progesterone.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="7">12.4 mM for p-nitrophenyl acetate</KM>
            <KM evidence="7">11.76 mM for p-nitrophenyl butyrate</KM>
            <KM evidence="7">17.66 mM for p-nitrophenyl palmitate</KM>
            <Vmax evidence="7">2.69 umol/sec/mg enzyme toward p-nitrophenyl acetate</Vmax>
            <Vmax evidence="7">3.71 umol/sec/mg enzyme toward p-nitrophenyl butyrate</Vmax>
            <Vmax evidence="7">1.27 umol/sec/mg enzyme toward p-nitrophenyl palmitate</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="7">Optimum pH is 8.5 for p-nitrophenyl palmitate and 7.5 for p-nitrophenyl acetate and p-nitrophenyl butyrate.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="7">Optimum temperature is 45 degrees Celsius with p-nitrophenyl palmitate and 30 degrees Celsius with p-nitrophenyl acetate and p-nitrophenyl butyrate.</text>
        </temperatureDependence>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Cell projection</location>
            <location evidence="10">Cilium</location>
            <location evidence="10">Flagellum membrane</location>
            <topology evidence="9">Single-pass type II membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Cell membrane</location>
            <topology evidence="9">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Present in sperm (at protein level).</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="12">Was originally thought to be a G-coupled receptor.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.23" evidence="6"/>
    <dbReference type="EC" id="3.1.1.6" evidence="7"/>
    <dbReference type="EC" id="3.1.1.79" evidence="7"/>
    <dbReference type="EMBL" id="X12433">
        <property type="protein sequence ID" value="CAA30976.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF546700">
        <property type="protein sequence ID" value="AAQ12021.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK222841">
        <property type="protein sequence ID" value="BAD96561.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223083">
        <property type="protein sequence ID" value="BAD96803.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC019248">
        <property type="protein sequence ID" value="AAH19248.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC090052">
        <property type="protein sequence ID" value="AAH90052.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10348.1"/>
    <dbReference type="PIR" id="A31026">
        <property type="entry name" value="A31026"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403341.1">
        <property type="nucleotide sequence ID" value="NM_001416412.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403342.1">
        <property type="nucleotide sequence ID" value="NM_001416413.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403343.1">
        <property type="nucleotide sequence ID" value="NM_001416414.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403344.1">
        <property type="nucleotide sequence ID" value="NM_001416415.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403345.1">
        <property type="nucleotide sequence ID" value="NM_001416416.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403346.1">
        <property type="nucleotide sequence ID" value="NM_001416417.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403347.1">
        <property type="nucleotide sequence ID" value="NM_001416418.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403348.1">
        <property type="nucleotide sequence ID" value="NM_001416419.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403351.1">
        <property type="nucleotide sequence ID" value="NM_001416422.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403352.1">
        <property type="nucleotide sequence ID" value="NM_001416423.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001403353.1">
        <property type="nucleotide sequence ID" value="NM_001416424.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_008942.3">
        <property type="nucleotide sequence ID" value="NM_007011.7"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_690888.1">
        <property type="nucleotide sequence ID" value="NM_152924.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P08910"/>
    <dbReference type="BioGRID" id="116242">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="FunCoup" id="P08910">
        <property type="interactions" value="55"/>
    </dbReference>
    <dbReference type="IntAct" id="P08910">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000268129"/>
    <dbReference type="SwissLipids" id="SLP:000001546"/>
    <dbReference type="ESTHER" id="human-ABHD2">
        <property type="family name" value="abh_upf0017"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P08910">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P08910">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P08910"/>
    <dbReference type="PhosphoSitePlus" id="P08910"/>
    <dbReference type="SwissPalm" id="P08910"/>
    <dbReference type="BioMuta" id="ABHD2"/>
    <dbReference type="DMDM" id="123504"/>
    <dbReference type="jPOST" id="P08910"/>
    <dbReference type="MassIVE" id="P08910"/>
    <dbReference type="PaxDb" id="9606-ENSP00000268129"/>
    <dbReference type="PeptideAtlas" id="P08910"/>
    <dbReference type="ProteomicsDB" id="52174"/>
    <dbReference type="Pumba" id="P08910"/>
    <dbReference type="Antibodypedia" id="1104">
        <property type="antibodies" value="165 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="11057"/>
    <dbReference type="Ensembl" id="ENST00000352732.10">
        <property type="protein sequence ID" value="ENSP00000268129.5"/>
        <property type="gene ID" value="ENSG00000140526.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000565973.5">
        <property type="protein sequence ID" value="ENSP00000455639.1"/>
        <property type="gene ID" value="ENSG00000140526.19"/>
    </dbReference>
    <dbReference type="GeneID" id="11057"/>
    <dbReference type="KEGG" id="hsa:11057"/>
    <dbReference type="MANE-Select" id="ENST00000352732.10">
        <property type="protein sequence ID" value="ENSP00000268129.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_152924.5"/>
        <property type="RefSeq protein sequence ID" value="NP_690888.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002bnk.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18717"/>
    <dbReference type="ClinPGx" id="PA38658"/>
    <dbReference type="CTD" id="11057"/>
    <dbReference type="DisGeNET" id="11057"/>
    <dbReference type="GeneCards" id="ABHD2"/>
    <dbReference type="HGNC" id="HGNC:18717">
        <property type="gene designation" value="ABHD2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000140526">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="612196">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000140526"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000140526"/>
    <dbReference type="eggNOG" id="KOG1838">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182902"/>
    <dbReference type="HOGENOM" id="CLU_032487_5_0_1"/>
    <dbReference type="InParanoid" id="P08910"/>
    <dbReference type="OMA" id="HCTGEDV"/>
    <dbReference type="OrthoDB" id="5954035at2759"/>
    <dbReference type="PAN-GO" id="P08910">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P08910"/>
    <dbReference type="PathwayCommons" id="P08910"/>
    <dbReference type="SignaLink" id="P08910"/>
    <dbReference type="Agora" id="ENSG00000140526"/>
    <dbReference type="BioGRID-ORCS" id="11057">
        <property type="hits" value="9 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABHD2"/>
    <dbReference type="GenomeRNAi" id="11057"/>
    <dbReference type="Pharos" id="P08910">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P08910"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="P08910">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000140526">
        <property type="expression patterns" value="Expressed in corpus epididymis and 199 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P08910">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001669">
        <property type="term" value="C:acrosomal vesicle"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036126">
        <property type="term" value="C:sperm flagellum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097524">
        <property type="term" value="C:sperm plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008126">
        <property type="term" value="F:acetylesterase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120516">
        <property type="term" value="F:diacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0042562">
        <property type="term" value="F:hormone binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003707">
        <property type="term" value="F:nuclear steroid receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004806">
        <property type="term" value="F:triacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
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    <dbReference type="GO" id="GO:0007340">
        <property type="term" value="P:acrosome reaction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0046464">
        <property type="term" value="P:acylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051792">
        <property type="term" value="P:medium-chain fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051793">
        <property type="term" value="P:medium-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014912">
        <property type="term" value="P:negative regulation of smooth muscle cell migration"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032570">
        <property type="term" value="P:response to progesterone"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009611">
        <property type="term" value="P:response to wounding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014909">
        <property type="term" value="P:smooth muscle cell migration"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048240">
        <property type="term" value="P:sperm capacitation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043401">
        <property type="term" value="P:steroid hormone receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000053">
        <property type="entry name" value="Abhydrolase domain containing 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000952">
        <property type="entry name" value="AB_hydrolase_4_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050960">
        <property type="entry name" value="AB_hydrolase_4_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012020">
        <property type="entry name" value="ABHD4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794">
        <property type="entry name" value="ABHYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794:SF45">
        <property type="entry name" value="MONOACYLGLYCEROL LIPASE ABHD2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF005211">
        <property type="entry name" value="Ab_hydro_YheT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01133">
        <property type="entry name" value="UPF0017"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0969">Cilium</keyword>
    <keyword id="KW-0282">Flagellum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0442">Lipid degradation</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000212457" description="Monoacylglycerol lipase ABHD2">
        <location>
            <begin position="1"/>
            <end position="425"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="9">
        <location>
            <begin position="1"/>
            <end position="9"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
        <location>
            <begin position="10"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="9">
        <location>
            <begin position="31"/>
            <end position="425"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="3">
        <location>
            <begin position="128"/>
            <end position="382"/>
        </location>
    </feature>
    <feature type="active site" description="Nucleophile" evidence="1">
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031203" description="In dbSNP:rs17851730." evidence="5">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAD96803." evidence="9" ref="3">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAD96561." evidence="9" ref="3">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="388"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q86WA6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9QXM0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00498"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="26989199"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="27247428"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="2843827"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="26989199"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="27247428"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="2843827"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:18717"/>
        </source>
    </evidence>
    <sequence length="425" mass="48315" checksum="747C6AB2C99B3CC2" modified="1988-11-01" version="1">MNAMLETPELPAVFDGVKLAAVAAVLYVIVRCLNLKSPTAPPDLYFQDSGLSRFLLKSCPLLTKEYIPPLIWGKSGHIQTALYGKMGRVRSPHPYGHRKFITMSDGATSTFDLFEPLAEHCVGDDITMVICPGIANHSEKQYIRTFVDYAQKNGYRCAVLNHLGALPNIELTSPRMFTYGCTWEFGAMVNYIKKTYPLTQLVVVGFSLGGNIVCKYLGETQANQEKVLCCVSVCQGYSALRAQETFMQWDQCRRFYNFLMADNMKKIILSHRQALFGDHVKKPQSLEDTDLSRLYTATSLMQIDDNVMRKFHGYNSLKEYYEEESCMRYLHRIYVPLMLVNAADDPLVHESLLTIPKSLSEKRENVMFVLPLHGGHLGFFEGSVLFPEPLTWMDKLVVEYANAICQWERNKLQCSDTEQVEADLE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-19" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IZP0</accession>
    <accession>A9Z1Y6</accession>
    <accession>B3KX62</accession>
    <accession>B4DQ58</accession>
    <accession>H7BXI6</accession>
    <accession>O15147</accession>
    <accession>O76049</accession>
    <accession>O95060</accession>
    <accession>Q5T2R3</accession>
    <accession>Q5T2R4</accession>
    <accession>Q5T2R6</accession>
    <accession>Q5T2R7</accession>
    <accession>Q5T2R9</accession>
    <accession>Q5W070</accession>
    <accession>Q5W072</accession>
    <accession>Q8TB63</accession>
    <accession>Q96S81</accession>
    <accession>Q9NXZ9</accession>
    <accession>Q9NYB8</accession>
    <name>ABI1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Abl interactor 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Abelson interactor 1</fullName>
            <shortName>Abi-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Abl-binding protein 4</fullName>
            <shortName>AblBP4</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Eps8 SH3 domain-binding protein</fullName>
            <shortName>Eps8-binding protein</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Nap1-binding protein</fullName>
            <shortName>Nap1BP</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Spectrin SH3 domain-binding protein 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>e3B1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="27" type="primary">ABI1</name>
        <name type="synonym">SSH3BP1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Oncogene" volume="14" first="233" last="241">
            <title>Isolation and characterization of e3B1, an eps8 binding protein that regulates cell growth.</title>
            <authorList>
                <person name="Biesova Z."/>
                <person name="Piccoli C."/>
                <person name="Wong W.T."/>
            </authorList>
            <dbReference type="PubMed" id="9010225"/>
            <dbReference type="DOI" id="10.1038/sj.onc.1200822"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6)</scope>
        <scope>PHOSPHORYLATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH EPS8 AND ABL1</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="13681" last="13692">
            <title>Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton.</title>
            <authorList>
                <person name="Ziemnicka-Kotula D."/>
                <person name="Xu J."/>
                <person name="Gu H."/>
                <person name="Potempska A."/>
                <person name="Kim K.S."/>
                <person name="Jenkins E.C."/>
                <person name="Trenkner E."/>
                <person name="Kotula L."/>
            </authorList>
            <dbReference type="PubMed" id="9593709"/>
            <dbReference type="DOI" id="10.1074/jbc.273.22.13681"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORMS 3; 7; 8 AND 9)</scope>
        <scope>INTERACTION WITH SPTA1</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Gene" volume="271" first="159" last="169">
            <title>Isolation of hNap1BP which interacts with human Nap 1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.</title>
            <authorList>
                <person name="Yamamoto A."/>
                <person name="Suzuki T."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="11418237"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(01)00521-2"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INTERACTION WITH ABL1; NAP1 AND NCK1</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2003" name="FEBS Lett." volume="540" first="195" last="200">
            <title>Induction of colonic epithelial cell apoptosis by p47-dependent oxidants(1).</title>
            <authorList>
                <person name="Gu Y."/>
                <person name="Souza R.F."/>
                <person name="Wu R.F."/>
                <person name="Xu Y.C."/>
                <person name="Terada L.S."/>
            </authorList>
            <dbReference type="PubMed" id="12681507"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(03)00262-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5)</scope>
        <scope>INTERACTION WITH NCF1</scope>
        <source>
            <tissue>Umbilical vein endothelial cell</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="1997-04" db="EMBL/GenBank/DDBJ databases">
            <title>A new member of the Abl interactor protein family, AblBP4.</title>
            <authorList>
                <person name="Wilson L.A."/>
                <person name="Fields D."/>
                <person name="Cruz L."/>
                <person name="Friesen J."/>
                <person name="Siminovitch K.A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>T-cell</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2000-03" db="EMBL/GenBank/DDBJ databases">
            <title>In silico cloning of the human SSH3BP1/e3B1 gene.</title>
            <authorList>
                <person name="Chikri M.M."/>
                <person name="Boutin M.P."/>
                <person name="Vaxillaire M.M."/>
                <person name="Froguel M.P."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2000-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Quackenbush R.C."/>
                <person name="Pendergast A.M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225 AND THR-507</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="22814378"/>
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        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Zhou H."/>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; TYR-213; SER-225; SER-319 AND SER-323</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
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            <title>HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells.</title>
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                <person name="Stanton R.J."/>
                <person name="Prod'homme V."/>
                <person name="Purbhoo M.A."/>
                <person name="Moore M."/>
                <person name="Aicheler R.J."/>
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            </authorList>
            <dbReference type="PubMed" id="25121749"/>
            <dbReference type="DOI" id="10.1016/j.chom.2014.07.005"/>
        </citation>
        <scope>INTERACTION WITH HUMAN CYTOMEGALOVIRUS PROTEIN UL135 (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-174; THR-178; SER-183; SER-187; SER-222 AND SER-225</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="7 12">May act in negative regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2. May play a role in regulation of EGF-induced Erk pathway activation. Involved in cytoskeletal reorganization and EGFR signaling. Together with EPS8 participates in transduction of signals from Ras to Rac. In vitro, a trimeric complex of ABI1, EPS8 and SOS1 exhibits Rac specific guanine nucleotide exchange factor (GEF) activity and ABI1 seems to act as an adapter in the complex. Regulates ABL1/c-Abl-mediated phosphorylation of ENAH. Recruits WASF1 to lamellipodia and there seems to regulate WASF1 protein level. In brain, seems to regulate the dendritic outgrowth and branching as well as to determine the shape and number of synaptic contacts of developing neurons.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 7 8 10 11 13 15 16">Interacts with ABL1, ENAH, STX1A, SNAP25, VAMP2, EPS8, and through its N-terminus with WASF1. Part of a complex consisting of ABI1, STX1A and SNAP25. Part of a complex consisting of ABI1, EPS8 and SOS1 (By similarity). Interacts with SOS1, SOS2, GRB2, SPTA1 and the first SH3 domain of NCK1. Isoform 6 does not interact with NCK1. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2 (PubMed:16417406). Interacts (via SH3 domain) with SHANK2 and SHANK3, but not SHANK1; the interaction is direct. Interacts with the heterodimer MYC:MAX; the interaction may enhance MYC:MAX transcriptional activity. Interacts with FNBP1L (via the SH3 domain), WASF2, and CDC42, but only in the presence of FNBP1L (PubMed:19798448).</text>
    </comment>
    <comment type="subunit">
        <text evidence="14">(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL135.</text>
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            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
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    <comment type="interaction">
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            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
            <label>ABL2</label>
        </interactant>
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        <interactant intactId="EBI-766279">
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            <id>Q8IZP0</id>
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        <interactant intactId="EBI-744027">
            <id>Q13191</id>
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        <interactant intactId="EBI-1048143">
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>Q8IZP0</id>
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        <interactant intactId="EBI-2433893">
            <id>Q96F07</id>
            <label>CYFIP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-351896">
            <id>P11142</id>
            <label>HSPA8</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-395044">
            <id>P14598</id>
            <label>NCF1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-389883">
            <id>P16333</id>
            <label>NCK1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-389845">
            <id>Q9Y2A7</id>
            <label>NCKAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-79464">
            <id>P27986</id>
            <label>PIK3R1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-79893">
            <id>Q92569</id>
            <label>PIK3R3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-1026476">
            <id>P20936</id>
            <label>RASA1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
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        <interactant intactId="EBI-1539606">
            <id>O14512</id>
            <label>SOCS7</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-297487">
            <id>Q07889</id>
            <label>SOS1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-375617">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q8IZP0</id>
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        <interactant intactId="EBI-625518">
            <id>P15498</id>
            <label>VAV1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-297549">
            <id>P52735</id>
            <label>VAV2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-1548747">
            <id>Q92558</id>
            <label>WASF1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
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        <interactant intactId="EBI-4290615">
            <id>Q9Y6W5</id>
            <label>WASF2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
        </interactant>
        <interactant intactId="EBI-375596">
            <id>Q08509</id>
            <label>Eps8</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-375446">
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        <interactant intactId="EBI-641764">
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-7358775">
            <id>Q8IZP0-2</id>
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        <interactant intactId="EBI-518228">
            <id>P22681</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-703044">
            <id>P13612</id>
            <label>ITGA4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-8593095">
            <id>Q8IZP0-4</id>
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        <interactant intactId="EBI-8593082">
            <id>P00520-4</id>
            <label>Abl1</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
            <label>ABI2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q8IZP0-5</id>
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        <interactant intactId="EBI-12030460">
            <id>Q8WYQ4-2</id>
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        <interactant intactId="EBI-10961624">
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        <interactant intactId="EBI-10175300">
            <id>Q8TD31-3</id>
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        <interactant intactId="EBI-11984733">
            <id>O60941-5</id>
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        <interactant intactId="EBI-709735">
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            <label>HHEX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-7060731">
            <id>P61978-2</id>
            <label>HNRNPK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-746815">
            <id>Q86YM7</id>
            <label>HOMER1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-748420">
            <id>Q9NSC5</id>
            <label>HOMER3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-10188326">
            <id>Q5T5P2-6</id>
            <label>KIAA1217</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-8639312">
            <id>P25800</id>
            <label>LMO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-6659161">
            <id>Q9Y586</id>
            <label>MAB21L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-12035911">
            <id>O94856-3</id>
            <label>NFASC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-2859639">
            <id>Q5HYW2</id>
            <label>NHSL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-1383852">
            <id>P54646</id>
            <label>PRKAA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-12041043">
            <id>Q96T37-3</id>
            <label>RBM15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-1504830">
            <id>Q9P2K3-2</id>
            <label>RCOR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-358489">
            <id>Q96GM5</id>
            <label>SMARCD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-12037893">
            <id>O94875-10</id>
            <label>SORBS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-6550597">
            <id>Q15642-2</id>
            <label>TRIP10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-9090990">
            <id>Q5W5X9-3</id>
            <label>TTC23</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-2116622">
            <id>Q5ST30</id>
            <label>VARS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11743294">
            <id>Q8IZP0-5</id>
        </interactant>
        <interactant intactId="EBI-748201">
            <id>P50552</id>
            <label>VASP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Lamellipodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Filopodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Growth cone</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Postsynaptic density</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <text evidence="1">Localized to protruding lamellipodia and filopodia tips. Also localized to neuronal growth cones and synaptosomes. May shuttle from the postsynaptic densities to the nucleus (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IZP0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-2</id>
            <name>2</name>
            <name>long</name>
            <name>B48</name>
            <sequence type="described" ref="VSP_010749 VSP_010750 VSP_010751 VSP_010752"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_010750 VSP_010752"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_010750 VSP_010751 VSP_010752"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_010749 VSP_010750"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_010750 VSP_010751"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-7</id>
            <name>7</name>
            <name>4</name>
            <sequence type="described" ref="VSP_010750 VSP_010751 VSP_010754 VSP_010755"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-8</id>
            <name>8</name>
            <name>5</name>
            <sequence type="described" ref="VSP_010750 VSP_010751 VSP_010754 VSP_010752"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-9</id>
            <name>9</name>
            <name>2</name>
            <sequence type="described" ref="VSP_010750"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-10</id>
            <name>10</name>
            <name>B30</name>
            <sequence type="described" ref="VSP_010749 VSP_010750 VSP_010751 VSP_010754 VSP_010752 VSP_010753"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-11</id>
            <name>11</name>
            <sequence type="described" ref="VSP_043403 VSP_010750 VSP_010751 VSP_010754 VSP_010752 VSP_010753"/>
        </isoform>
        <isoform>
            <id>Q8IZP0-12</id>
            <name>12</name>
            <sequence type="described" ref="VSP_044604 VSP_010752"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Widely expressed, with highest expression in brain.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The t-SNARE coiled-coil homology domain is necessary and sufficient for interaction with STX1A.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12 15">Phosphorylated on tyrosine residues after serum stimulation or induction by v-Abl. Seems to be phosphorylated at Tyr-53 by ABL1, required for nuclear but not for synaptic localization.</text>
    </comment>
    <comment type="disease">
        <text evidence="17">A chromosomal aberration involving ABI1 is a cause of acute leukemias. Translocation t(10;11)(p11.2;q23) with KMT2A/MLL1. ABI1 isoform 2 was found to be present in acute leukemia KMT2A/MLL1-ABI1 fusion transcript.</text>
    </comment>
    <comment type="similarity">
        <text evidence="26">Belongs to the ABI family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/233/ABI1"/>
    </comment>
    <dbReference type="EMBL" id="AF006516">
        <property type="protein sequence ID" value="AAB62569.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U87166">
        <property type="protein sequence ID" value="AAC39757.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB040151">
        <property type="protein sequence ID" value="BAB55675.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF540955">
        <property type="protein sequence ID" value="AAN28379.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF001628">
        <property type="protein sequence ID" value="AAD00897.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277065">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277066">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277067">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277068">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277069">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277070">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277071">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277072">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277073">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ277074">
        <property type="protein sequence ID" value="CAB88006.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260262">
        <property type="protein sequence ID" value="AAF70309.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK126803">
        <property type="protein sequence ID" value="BAG54374.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298646">
        <property type="protein sequence ID" value="BAG60820.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291823">
        <property type="protein sequence ID" value="BAF84512.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73112.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAH73112.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73113.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAH73113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73114.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAH73114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73115.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAH73115.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73116.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAH73116.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73117.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAH73117.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73118.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAH73118.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAH73119.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAH73119.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17272.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAI17272.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17273.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAI17273.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17274.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAI17274.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17275.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAI17275.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17276.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAI17276.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17277.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAI17277.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17278.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139404">
        <property type="protein sequence ID" value="CAI17278.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390961">
        <property type="protein sequence ID" value="CAI17279.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW86079.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86080.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC024254">
        <property type="protein sequence ID" value="AAH24254.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31169.1">
        <molecule id="Q8IZP0-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31170.1">
        <molecule id="Q8IZP0-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31171.1">
        <molecule id="Q8IZP0-9"/>
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    <dbReference type="CCDS" id="CCDS53497.1">
        <molecule id="Q8IZP0-11"/>
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    <dbReference type="CCDS" id="CCDS53498.1">
        <molecule id="Q8IZP0-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53499.1">
        <molecule id="Q8IZP0-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53500.1">
        <molecule id="Q8IZP0-6"/>
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    <dbReference type="CCDS" id="CCDS53501.1">
        <molecule id="Q8IZP0-12"/>
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    <dbReference type="CCDS" id="CCDS7150.1">
        <molecule id="Q8IZP0-1"/>
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    <dbReference type="CCDS" id="CCDS73077.1">
        <molecule id="Q8IZP0-8"/>
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    <dbReference type="CCDS" id="CCDS73078.1">
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    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="222"/>
            <end position="235"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="248"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="278"/>
            <end position="290"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="307"/>
            <end position="322"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="337"/>
            <end position="347"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="393"/>
            <end position="403"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="410"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="site" description="Breakpoint for translocation to form KMT2A/MLL1-ABI1">
        <location>
            <begin position="95"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="18 34 35">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="3">
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="37">
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="37">
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="30 36 37">
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="37">
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by ABL1" evidence="12 36">
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="30">
        <location>
            <position position="216"/>
        </location>
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    <feature type="modified residue" description="Phosphoserine" evidence="33 37">
        <location>
            <position position="222"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="28 29 31 32 33 36 37">
        <location>
            <position position="225"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="36">
        <location>
            <position position="319"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="33 36">
        <location>
            <position position="323"/>
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    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="455"/>
        </location>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="466"/>
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    <feature type="modified residue" description="Phosphothreonine" evidence="32">
        <location>
            <position position="507"/>
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    <feature type="splice variant" id="VSP_044604" description="In isoform 12." evidence="21">
        <original>I</original>
        <variation>IQRHGFAVLLCLLSNSWP</variation>
        <location>
            <position position="38"/>
        </location>
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    <feature type="splice variant" id="VSP_043403" description="In isoform 11." evidence="21">
        <location>
            <begin position="96"/>
            <end position="159"/>
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    <feature type="splice variant" id="VSP_010749" description="In isoform 2, isoform 5 and isoform 10." evidence="20 21 22 25">
        <location>
            <begin position="154"/>
            <end position="158"/>
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    <feature type="splice variant" id="VSP_010750" description="In isoform 2, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7, isoform 8, isoform 9, isoform 10 and isoform 11." evidence="19 20 21 22 23 24 25">
        <location>
            <begin position="274"/>
            <end position="300"/>
        </location>
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    <feature type="splice variant" id="VSP_010751" description="In isoform 2, isoform 4, isoform 6, isoform 7, isoform 8, isoform 10 and isoform 11." evidence="20 21 22 23 24 25">
        <location>
            <position position="301"/>
        </location>
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    <feature type="splice variant" id="VSP_010754" description="In isoform 7, isoform 8, isoform 10 and isoform 11." evidence="20 21 22 24">
        <location>
            <begin position="302"/>
            <end position="359"/>
        </location>
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    <feature type="splice variant" id="VSP_010752" description="In isoform 2, isoform 3, isoform 4, isoform 8, isoform 10, isoform 11 and isoform 12." evidence="19 20 21 22 24 25">
        <location>
            <begin position="360"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010755" description="In isoform 7." evidence="24">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010753" description="In isoform 10 and isoform 11." evidence="21">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048159" description="In dbSNP:rs2306236.">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="331"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAC39757." evidence="26" ref="2">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAC39757 and 4; AAN28379." evidence="26" ref="2 4">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="410"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; BAG54374." evidence="26" ref="8">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="437"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8CBW3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9QZM5"/>
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    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00192"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00202"/>
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    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11003655"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="11418237"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12665801"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12681507"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="16417406"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="18328268"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="19798448"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="25121749"/>
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="9010225"/>
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    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="9593709"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="9694699"/>
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    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source ref="13"/>
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    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="11418237"/>
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    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="12681507"/>
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    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="9010225"/>
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    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source ref="5"/>
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    <evidence type="ECO:0000303" key="25">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000305" key="26"/>
    <evidence type="ECO:0000312" key="27">
        <source>
            <dbReference type="HGNC" id="HGNC:11320"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PubMed" id="17081983"/>
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    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="18088087"/>
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    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PubMed" id="18691976"/>
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    </evidence>
    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PubMed" id="20068231"/>
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    </evidence>
    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PubMed" id="22223895"/>
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    </evidence>
    <evidence type="ECO:0007744" key="35">
        <source>
            <dbReference type="PubMed" id="22814378"/>
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    </evidence>
    <evidence type="ECO:0007744" key="36">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007744" key="37">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="508" mass="55081" checksum="2D76F305934127CB" modified="2007-01-23" version="4">MAELQMLLEEEIPSGKRALIESYQNLTRVADYCENNYIQATDKRKALEETKAYTTQSLASVAYQINALANNVLQLLDIQASQLRRMESSINHISQTVDIHKEKVARREIGILTTNKNTSRTHKIIAPANMERPVRYIRKPIDYTVLDDVGHGVKWLKAKHGNNQPARTGTLSRTNPPTQKPPSPPMSGRGTLGRNTPYKTLEPVKPPTVPNDYMTSPARLGSQHSPGRTASLNQRPRTHSGSSGGSGSRENSGSSSIGIPIAVPTPSPPTIGPENISVPPPSGAPPAPPLAPLLPVSTVIAAPGSAPGSQYGTMTRQISRHNSTTSSTSSGGYRRTPSVTAQFSAQPHVNGGPLYSQNSISIAPPPPPMPQLTPQIPLTGFVARVQENIADSPTPPPPPPPDDIPMFDDSPPPPPPPPVDYEDEEAAVVQYNDPYADGDPAWAPKNYIEKVVAIYDYTKDKDDELSFMEGAIIYVIKKNDDGWYEGVCNRVTGLFPGNYVESIMHYTD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>O14639</accession>
    <accession>A6NI16</accession>
    <accession>A6NJ06</accession>
    <accession>A8MXA9</accession>
    <accession>B3KVH2</accession>
    <accession>Q15039</accession>
    <accession>Q5JVV1</accession>
    <accession>Q5JVV2</accession>
    <accession>Q5T6N2</accession>
    <accession>Q5T6N3</accession>
    <accession>Q5T6N5</accession>
    <accession>Q68CQ9</accession>
    <accession>Q9BUP1</accession>
    <name>ABLM1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-binding LIM protein 1</fullName>
            <shortName>abLIM-1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Actin-binding LIM protein family member 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Actin-binding double zinc finger protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>LIMAB1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Limatin</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABLIM1</name>
        <name type="synonym">ABLIM</name>
        <name type="synonym">KIAA0059</name>
        <name type="synonym">LIMAB1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="J. Cell Biol." volume="138" first="575" last="588">
            <title>Molecular characterization of abLIM, a novel actin-binding and double zinc finger protein.</title>
            <authorList>
                <person name="Roof D.J."/>
                <person name="Hayes A."/>
                <person name="Adamian M."/>
                <person name="Chishti A.H."/>
                <person name="Li T."/>
            </authorList>
            <dbReference type="PubMed" id="9245787"/>
            <dbReference type="DOI" id="10.1083/jcb.138.3.575"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Retina</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="223" last="229">
            <title>Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.</title>
            <authorList>
                <person name="Nomura N."/>
                <person name="Nagase T."/>
                <person name="Miyajima N."/>
                <person name="Sazuka T."/>
                <person name="Tanaka A."/>
                <person name="Sato S."/>
                <person name="Seki N."/>
                <person name="Kawarabayasi Y."/>
                <person name="Ishikawa K."/>
                <person name="Tabata S."/>
            </authorList>
            <dbReference type="PubMed" id="7584044"/>
            <dbReference type="DOI" id="10.1093/dnares/1.5.223"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2002" name="DNA Res." volume="9" first="99" last="106">
            <title>Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.</title>
            <authorList>
                <person name="Nakajima D."/>
                <person name="Okazaki N."/>
                <person name="Yamakawa H."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
            </authorList>
            <dbReference type="PubMed" id="12168954"/>
            <dbReference type="DOI" id="10.1093/dnares/9.3.99"/>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
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        <source>
            <tissue>Pericardium</tissue>
            <tissue>Uterus</tissue>
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        <scope>INTERACTION WITH ABRA</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-431; SER-435; SER-455; SER-458; SER-587; SER-640 AND SER-655</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367; TYR-373; SER-426; SER-431; THR-433 AND SER-435</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422; SER-431; SER-435; SER-452; SER-455; SER-458; SER-587 AND SER-655</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426; SER-435; SER-455 AND SER-706</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-620</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <comment type="function">
        <text evidence="1 8">May act as scaffold protein (By similarity). May play a role in the development of the retina. Has been suggested to play a role in axon guidance.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Binds F-actin. Interacts with ABRA.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-487024">
            <id>O14639</id>
        </interactant>
        <interactant intactId="EBI-751319">
            <id>Q9H257</id>
            <label>CARD9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>O14639</id>
        </interactant>
        <interactant intactId="EBI-740738">
            <id>O95751</id>
            <label>LDOC1</label>
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            <id>P31947</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
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        <experiments>7</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-487024">
            <id>O14639</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-11030084">
            <id>O14639-4</id>
        </interactant>
        <interactant intactId="EBI-10961624">
            <id>Q2TAC2-2</id>
            <label>CCDC57</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-11030084">
            <id>O14639-4</id>
        </interactant>
        <interactant intactId="EBI-701903">
            <id>Q14192</id>
            <label>FHL2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-11030084">
            <id>O14639-4</id>
        </interactant>
        <interactant intactId="EBI-7116203">
            <id>O75031</id>
            <label>HSF2BP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <text evidence="1">Associated with the cytoskeleton.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O14639-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O14639-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012100"/>
        </isoform>
        <isoform>
            <id>O14639-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_012099 VSP_012102"/>
        </isoform>
        <isoform>
            <id>O14639-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_012099 VSP_012101 VSP_012102"/>
        </isoform>
        <isoform>
            <id>O14639-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_012099 VSP_041185 VSP_012102"/>
        </isoform>
        <isoform>
            <id>O14639-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_012100 VSP_041185 VSP_057209"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Detected in liver, heart, skeletal muscle, brain and retina, where it is concentrated in the inner segment and in the outer plexiform layers.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA06681" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AF005654">
        <property type="protein sequence ID" value="AAC51676.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D31883">
        <property type="protein sequence ID" value="BAA06681.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK098277">
        <property type="protein sequence ID" value="BAG53605.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK122891">
        <property type="protein sequence ID" value="BAG53784.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR749819">
        <property type="protein sequence ID" value="CAH18679.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133384">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL354873">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL590109">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002448">
        <property type="protein sequence ID" value="AAH02448.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31288.1">
        <molecule id="O14639-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31289.1">
        <molecule id="O14639-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7590.1">
        <molecule id="O14639-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81508.1">
        <molecule id="O14639-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81509.1">
        <molecule id="O14639-6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001003407.1">
        <molecule id="O14639-2"/>
        <property type="nucleotide sequence ID" value="NM_001003407.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309811.1">
        <molecule id="O14639-6"/>
        <property type="nucleotide sequence ID" value="NM_001322882.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309821.1">
        <molecule id="O14639-3"/>
        <property type="nucleotide sequence ID" value="NM_001322892.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309822.1">
        <molecule id="O14639-3"/>
        <property type="nucleotide sequence ID" value="NM_001322893.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309825.1">
        <molecule id="O14639-4"/>
        <property type="nucleotide sequence ID" value="NM_001322896.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002304.3">
        <molecule id="O14639-1"/>
        <property type="nucleotide sequence ID" value="NM_002313.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006711.3">
        <molecule id="O14639-5"/>
        <property type="nucleotide sequence ID" value="NM_006720.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O14639"/>
    <dbReference type="SMR" id="O14639"/>
    <dbReference type="BioGRID" id="110171">
        <property type="interactions" value="206"/>
    </dbReference>
    <dbReference type="FunCoup" id="O14639">
        <property type="interactions" value="1038"/>
    </dbReference>
    <dbReference type="IntAct" id="O14639">
        <property type="interactions" value="120"/>
    </dbReference>
    <dbReference type="MINT" id="O14639"/>
    <dbReference type="STRING" id="9606.ENSP00000277895"/>
    <dbReference type="GlyConnect" id="2904">
        <property type="glycosylation" value="1 O-GlcNAc glycan (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O14639">
        <property type="glycosylation" value="15 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O14639">
        <property type="glycosylation" value="19 sites, 2 O-linked glycans (18 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O14639"/>
    <dbReference type="PhosphoSitePlus" id="O14639"/>
    <dbReference type="BioMuta" id="ABLIM1"/>
    <dbReference type="CPTAC" id="CPTAC-957"/>
    <dbReference type="jPOST" id="O14639"/>
    <dbReference type="MassIVE" id="O14639"/>
    <dbReference type="PaxDb" id="9606-ENSP00000277895"/>
    <dbReference type="PeptideAtlas" id="O14639"/>
    <dbReference type="ProteomicsDB" id="48133">
        <molecule id="O14639-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48134">
        <molecule id="O14639-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48135">
        <molecule id="O14639-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48136">
        <molecule id="O14639-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48137">
        <molecule id="O14639-5"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="64602"/>
    <dbReference type="Pumba" id="O14639"/>
    <dbReference type="Antibodypedia" id="31944">
        <property type="antibodies" value="188 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3983"/>
    <dbReference type="Ensembl" id="ENST00000369253.6">
        <molecule id="O14639-4"/>
        <property type="protein sequence ID" value="ENSP00000358257.2"/>
        <property type="gene ID" value="ENSG00000099204.23"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000369256.6">
        <molecule id="O14639-6"/>
        <property type="protein sequence ID" value="ENSP00000358260.3"/>
        <property type="gene ID" value="ENSG00000099204.23"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000392952.7">
        <molecule id="O14639-5"/>
        <property type="protein sequence ID" value="ENSP00000376679.3"/>
        <property type="gene ID" value="ENSG00000099204.23"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000392955.8">
        <molecule id="O14639-2"/>
        <property type="protein sequence ID" value="ENSP00000376682.4"/>
        <property type="gene ID" value="ENSG00000099204.23"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000533213.7">
        <molecule id="O14639-1"/>
        <property type="protein sequence ID" value="ENSP00000433629.3"/>
        <property type="gene ID" value="ENSG00000099204.23"/>
    </dbReference>
    <dbReference type="GeneID" id="3983"/>
    <dbReference type="KEGG" id="hsa:3983"/>
    <dbReference type="MANE-Select" id="ENST00000533213.7">
        <property type="protein sequence ID" value="ENSP00000433629.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_002313.7"/>
        <property type="RefSeq protein sequence ID" value="NP_002304.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc057wcr.1">
        <molecule id="O14639-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:78"/>
    <dbReference type="ClinPGx" id="PA35023"/>
    <dbReference type="CTD" id="3983"/>
    <dbReference type="DisGeNET" id="3983"/>
    <dbReference type="GeneCards" id="ABLIM1"/>
    <dbReference type="HGNC" id="HGNC:78">
        <property type="gene designation" value="ABLIM1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000099204">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="602330">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000099204"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000099204"/>
    <dbReference type="eggNOG" id="KOG1044">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182850"/>
    <dbReference type="HOGENOM" id="CLU_001357_12_2_1"/>
    <dbReference type="InParanoid" id="O14639"/>
    <dbReference type="OMA" id="NMLEPKA"/>
    <dbReference type="OrthoDB" id="1746725at2759"/>
    <dbReference type="PAN-GO" id="O14639">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O14639"/>
    <dbReference type="PathwayCommons" id="O14639"/>
    <dbReference type="Reactome" id="R-HSA-418885">
        <property type="pathway name" value="DCC mediated attractive signaling"/>
    </dbReference>
    <dbReference type="SignaLink" id="O14639"/>
    <dbReference type="Agora" id="ENSG00000099204"/>
    <dbReference type="BioGRID-ORCS" id="3983">
        <property type="hits" value="12 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="F345034F">
        <property type="entry name" value="Signaling cluster"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABLIM1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABLIM1"/>
    <dbReference type="GenomeRNAi" id="3983"/>
    <dbReference type="Pharos" id="O14639">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O14639"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="O14639">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000099204">
        <property type="expression patterns" value="Expressed in left ventricle myocardium and 215 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O14639">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030027">
        <property type="term" value="C:lamellipodium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014069">
        <property type="term" value="C:postsynaptic density"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001725">
        <property type="term" value="C:stress fiber"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003779">
        <property type="term" value="F:actin binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051015">
        <property type="term" value="F:actin filament binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009887">
        <property type="term" value="P:animal organ morphogenesis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007411">
        <property type="term" value="P:axon guidance"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060271">
        <property type="term" value="P:cilium assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007010">
        <property type="term" value="P:cytoskeleton organization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030032">
        <property type="term" value="P:lamellipodium assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045944">
        <property type="term" value="P:positive regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006366">
        <property type="term" value="P:transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007601">
        <property type="term" value="P:visual perception"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd09327">
        <property type="entry name" value="LIM1_abLIM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd09328">
        <property type="entry name" value="LIM2_abLIM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd09329">
        <property type="entry name" value="LIM3_abLIM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd09330">
        <property type="entry name" value="LIM4_abLIM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.110.10:FF:000003">
        <property type="entry name" value="actin-binding LIM protein 1 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.110.10:FF:000004">
        <property type="entry name" value="actin-binding LIM protein 1 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.110.10:FF:000007">
        <property type="entry name" value="actin-binding LIM protein 1 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.110.10:FF:000024">
        <property type="entry name" value="actin-binding LIM protein 1 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.950.10:FF:000001">
        <property type="entry name" value="actin-binding LIM protein 1 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.10.110.10">
        <property type="entry name" value="Cysteine Rich Protein"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.950.10">
        <property type="entry name" value="Villin headpiece domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032402">
        <property type="entry name" value="AbLIM_anchor"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051618">
        <property type="entry name" value="Actin-binding_LIM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003128">
        <property type="entry name" value="Villin_headpiece"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036886">
        <property type="entry name" value="Villin_headpiece_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001781">
        <property type="entry name" value="Znf_LIM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24213">
        <property type="entry name" value="ACTIN-BINDING LIM PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24213:SF18">
        <property type="entry name" value="ACTIN-BINDING LIM PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16182">
        <property type="entry name" value="AbLIM_anchor"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00412">
        <property type="entry name" value="LIM"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02209">
        <property type="entry name" value="VHP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00132">
        <property type="entry name" value="LIM"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="SMART" id="SM00153">
        <property type="entry name" value="VHP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57716">
        <property type="entry name" value="Glucocorticoid receptor-like (DNA-binding domain)"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47050">
        <property type="entry name" value="VHP, Villin headpiece domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51089">
        <property type="entry name" value="HP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00478">
        <property type="entry name" value="LIM_DOMAIN_1"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50023">
        <property type="entry name" value="LIM_DOMAIN_2"/>
        <property type="match status" value="4"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0009">Actin-binding</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0440">LIM domain</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000075697" description="Actin-binding LIM protein 1">
        <location>
            <begin position="1"/>
            <end position="778"/>
        </location>
    </feature>
    <feature type="domain" description="LIM zinc-binding 1" evidence="4">
        <location>
            <begin position="97"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="domain" description="LIM zinc-binding 2" evidence="4">
        <location>
            <begin position="156"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="domain" description="LIM zinc-binding 3" evidence="4">
        <location>
            <begin position="224"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="domain" description="LIM zinc-binding 4" evidence="4">
        <location>
            <begin position="283"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="domain" description="HP" evidence="5">
        <location>
            <begin position="710"/>
            <end position="778"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="339"/>
            <end position="370"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="414"/>
            <end position="510"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="552"/>
            <end position="597"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="3">
        <location>
            <begin position="590"/>
            <end position="614"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="360"/>
            <end position="369"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="423"/>
            <end position="434"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="449"/>
            <end position="474"/>
        </location>
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    <feature type="modified residue" description="Phosphoserine" evidence="2">
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            <position position="216"/>
        </location>
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    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="367"/>
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    <feature type="modified residue" description="Phosphotyrosine" evidence="17">
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="15">
        <location>
            <position position="396"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20">
        <location>
            <position position="422"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="17 21">
        <location>
            <position position="426"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="16 17 20">
        <location>
            <position position="431"/>
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    <feature type="modified residue" description="Phosphothreonine" evidence="17">
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            <position position="433"/>
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    <feature type="modified residue" description="Phosphotyrosine" evidence="14">
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            <position position="439"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="20">
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            <position position="452"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="16 20 21">
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    <feature type="modified residue" description="Phosphoserine" evidence="16 20">
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            <position position="458"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="2">
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    <feature type="modified residue" description="Phosphoserine" evidence="16 18">
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            <position position="640"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="16 20">
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            <position position="706"/>
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            <position position="620"/>
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            <begin position="1"/>
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        <original>MPAFLGLKCLGKLCSSEKSKVTSSERTSARGSNRKRLIVEDRRVSGTSFTAHRRATITHLLYLCPKDYCPRGRVCNSVDPF</original>
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        <original>H</original>
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            <position position="434"/>
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        <original>R</original>
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            <position position="637"/>
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            <position position="499"/>
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            <position position="563"/>
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            <position position="578"/>
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        <source>
            <dbReference type="PubMed" id="20068231"/>
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        <source>
            <dbReference type="PubMed" id="21406692"/>
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        <source>
            <dbReference type="PubMed" id="23186163"/>
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        <source>
            <dbReference type="PubMed" id="24275569"/>
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    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="28112733"/>
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</entry>
<entry dataset="Swiss-Prot" created="2002-10-10" modified="2026-01-28" version="200" xmlns="https://uniprot.org/uniprot">
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    <accession>Q5SRR2</accession>
    <accession>Q8WYH0</accession>
    <accession>Q9NW33</accession>
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            <fullName evidence="10">Alpha/beta hydrolase domain-containing protein 16A</fullName>
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        <alternativeName>
            <fullName evidence="10">Monoacylglycerol lipase ABHD16A</fullName>
            <ecNumber evidence="4">3.1.1.23</ecNumber>
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        <alternativeName>
            <fullName>Protein G5</fullName>
        </alternativeName>
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        <name type="synonym">NG26</name>
        <name type="ORF">PP199</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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                <person name="Joy A.A."/>
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                <person name="Lloyd D.M."/>
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                <person name="Mashreghi-Mohammadi M."/>
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            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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        </citation>
        <scope>PROTEIN SEQUENCE OF 2-12 (ISOFORM 1)</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="24275569"/>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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            <authorList>
                <person name="Savinainen J.R."/>
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            <dbReference type="PubMed" id="25290914"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="10">
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            <authorList>
                <consortium name="Care4Rare Canada Consortium"/>
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            <dbReference type="PubMed" id="34587489"/>
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        </citation>
        <scope>VARIANTS SPG86 HIS-118; ILE-121; GLN-252; ARG-409 AND 445-ARG--LEU-558 DEL</scope>
        <scope>INVOLVEMENT IN SPG86</scope>
    </reference>
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        <scope>VARIANTS SPG86 114-ARG--LEU-558 DEL AND GLN-457</scope>
        <scope>CHARACTERIZATION OF VARIANTS SPG86 114-ARG--LEU-558 DEL AND GLN-457</scope>
        <scope>INVOLVEMENT IN SPG86</scope>
    </reference>
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                <person name="Hirose M."/>
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            <dbReference type="PubMed" id="34866177"/>
            <dbReference type="DOI" id="10.1111/cge.14097"/>
        </citation>
        <scope>VARIANT SPG86 279-GLN--LEU-558 DEL</scope>
        <scope>INVOLVEMENT IN SPG86</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS) (By similarity). LPS constitutes a class of signaling lipids that regulates immunological and neurological processes (By similarity). Has no activity towards diacylglycerol, triacylglycerol or lysophosphatidylserine lipase (PubMed:25290914). Also has monoacylglycerol lipase activity, with preference for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) and 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G) (PubMed:25290914).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoserine + H2O = 1-heptadecanoyl-sn-glycero-3-phosphoserine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44500"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:84461"/>
            <dbReference type="ChEBI" id="CHEBI:84462"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41752"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:75020"/>
            <dbReference type="ChEBI" id="CHEBI:75029"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoserine + H2O = 1-octadecanoyl-sn-glycero-3-phosphoserine + (9Z,12Z)-octadecadienoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44516"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:84466"/>
            <dbReference type="ChEBI" id="CHEBI:84467"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-heptadecanoyl-sn-glycero-3-phosphocholine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44520"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:74340"/>
            <dbReference type="ChEBI" id="CHEBI:84470"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoglycerol + H2O = 1-hexadecanoyl-sn-glycero-3-phosphoglycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44524"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:84472"/>
            <dbReference type="ChEBI" id="CHEBI:84475"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44528"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:72833"/>
            <dbReference type="ChEBI" id="CHEBI:72837"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-heptadecanoyl-sn-glycero-3-phosphoethanolamine + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44540"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:84489"/>
            <dbReference type="ChEBI" id="CHEBI:84490"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O = 1-hexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40919"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:72841"/>
            <dbReference type="ChEBI" id="CHEBI:75158"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>Hydrolyzes glycerol monoesters of long-chain fatty acids.</text>
            <dbReference type="EC" id="3.1.1.23"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-tetradecanoylglycerol + H2O = tetradecanoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44312"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:75562"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44313"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-hexadecanoylglycerol + H2O = glycerol + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39963"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:75455"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:39964"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:75342"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:38488"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(9Z-octadecenoyl)-glycerol + H2O = glycerol + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38491"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:73990"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:38492"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44732"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75457"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44733"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44728"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:75612"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:44729"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = glycerol + (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:26132"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:52392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:26133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>prostaglandin D2-1-glycerol ester + H2O = prostaglandin D2 + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45412"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:57406"/>
            <dbReference type="ChEBI" id="CHEBI:85232"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:45413"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 + H2O = 15-deoxy-Delta(12,14)-prostaglandin J2 + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45416"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:85236"/>
            <dbReference type="ChEBI" id="CHEBI:85238"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:45417"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+)</text>
            <dbReference type="Rhea" id="RHEA:48428"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17754"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:75568"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:48429"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">Inhibited by beta-lactone-based lipid inhibitors, such as beta-lactone palmostatin-B.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">6.9 uM for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) (in absence of BSA)</KM>
            <KM evidence="4">137.8 uM for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) (in presence of BSA)</KM>
            <KM evidence="4">20.9 uM for 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G) (in presence of BSA)</KM>
            <Vmax evidence="4">7.3 nmol/min/mg enzyme with 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) as substrate (in absence of BSA)</Vmax>
            <Vmax evidence="4">13.2 nmol/min/mg enzyme with 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) as substrate (in presence of BSA)</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="4">Optimum pH is 7.2-8.0.</text>
        </phDependence>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2803601">
            <id>Q9NRZ7</id>
            <label>AGPAT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-13059134">
            <id>Q13520</id>
            <label>AQP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10489564">
            <id>Q6P5T0</id>
            <label>AQP7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2606700">
            <id>P18859</id>
            <label>ATP5PF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2874789">
            <id>O95415</id>
            <label>BRI3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-19051169">
            <id>Q8N350-4</id>
            <label>CBARP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-7062247">
            <id>Q9UHD4</id>
            <label>CIDEB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-17183330">
            <id>P05177</id>
            <label>CYP1A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-740376">
            <id>Q86UW9</id>
            <label>DTX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-3915253">
            <id>Q15125</id>
            <label>EBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-781551">
            <id>Q9Y282</id>
            <label>ERGIC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-948245">
            <id>P14324</id>
            <label>FDPS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-3918971">
            <id>Q9Y680</id>
            <label>FKBP7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-11110431">
            <id>Q8TB36</id>
            <label>GDAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-750433">
            <id>P36382</id>
            <label>GJA5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-17231387">
            <id>Q6ZVE7</id>
            <label>GOLT1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-3917143">
            <id>Q5T7V8</id>
            <label>GORAB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-13345167">
            <id>Q8TDT2</id>
            <label>GPR152</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-7797098">
            <id>P04921</id>
            <label>GYPC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-18053395">
            <id>Q7Z5P4</id>
            <label>HSD17B13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-7932862">
            <id>Q01628</id>
            <label>IFITM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2568251">
            <id>P11215</id>
            <label>ITGAM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-524105">
            <id>P01374</id>
            <label>LTA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-17183069">
            <id>Q96FX8</id>
            <label>PERP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-12257782">
            <id>Q99640-2</id>
            <label>PKMYT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-348526">
            <id>Q07864</id>
            <label>POLE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2506064">
            <id>O60831</id>
            <label>PRAF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10192441">
            <id>Q86VR2</id>
            <label>RETREG3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-17589229">
            <id>Q6NTF9-3</id>
            <label>RHBDD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-12104986">
            <id>O75783</id>
            <label>RHBDL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-348482">
            <id>Q99942</id>
            <label>RNF5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-1058865">
            <id>O75396</id>
            <label>SEC22B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-2115181">
            <id>O75920</id>
            <label>SERF1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-3923031">
            <id>Q14973</id>
            <label>SLC10A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-8644112">
            <id>Q9BRI3</id>
            <label>SLC30A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-13292283">
            <id>Q9UHI5</id>
            <label>SLC7A8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10819434">
            <id>Q9NPE6</id>
            <label>SPAG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-20117546">
            <id>Q9H169-2</id>
            <label>STMN4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-9071709">
            <id>P61266</id>
            <label>STX1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-6448756">
            <id>Q96DZ7</id>
            <label>TM4SF19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-7238458">
            <id>Q8IV31</id>
            <label>TMEM139</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-13342951">
            <id>Q96AN5</id>
            <label>TMEM143</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-348587">
            <id>Q9BVK8</id>
            <label>TMEM147</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-8638294">
            <id>Q9NUH8</id>
            <label>TMEM14B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10982110">
            <id>Q96Q45-2</id>
            <label>TMEM237</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-6656213">
            <id>Q6PI78</id>
            <label>TMEM65</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-3914288">
            <id>O60636</id>
            <label>TSPAN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-13356252">
            <id>Q86WB7-2</id>
            <label>UNC93A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10191195">
            <id>O95183</id>
            <label>VAMP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-1055364">
            <id>Q3ZAQ7</id>
            <label>VMA21</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-10316321">
            <id>Q9NX94</id>
            <label>WBP1L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-348517">
            <id>O95870</id>
        </interactant>
        <interactant intactId="EBI-25475897">
            <id>P0DTC6</id>
            <label>6</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O95870-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O95870-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043825"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="5 6 7">
        <disease id="DI-06330">
            <name>Spastic paraplegia 86, autosomal recessive</name>
            <acronym>SPG86</acronym>
            <description>A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG86 is an autosomal recessive form associated with impaired intellectual development, poor or absent speech, and behavioral abnormalities. Brain imaging shows thin corpus callosum and white matter abnormalities. Rare patients may have seizures.</description>
            <dbReference type="MIM" id="619735"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the AB hydrolase superfamily. ABHD16 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.-.-" evidence="2"/>
    <dbReference type="EC" id="3.1.1.23" evidence="4"/>
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        <property type="protein sequence ID" value="AAG22475.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK001207">
        <property type="protein sequence ID" value="BAA91553.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK023194">
        <property type="protein sequence ID" value="BAB14455.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK297712">
        <property type="protein sequence ID" value="BAH12652.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF129756">
        <property type="protein sequence ID" value="AAD18079.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BA000025">
        <property type="protein sequence ID" value="BAB63383.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_021160.3"/>
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    <dbReference type="FunCoup" id="O95870">
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    <dbReference type="MINT" id="O95870"/>
    <dbReference type="STRING" id="9606.ENSP00000379282"/>
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    <dbReference type="DrugCentral" id="O95870"/>
    <dbReference type="SwissLipids" id="SLP:000001120"/>
    <dbReference type="ESTHER" id="human-ABHD16A">
        <property type="family name" value="ABHD16"/>
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    <dbReference type="MEROPS" id="S09.065"/>
    <dbReference type="GlyGen" id="O95870">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O95870"/>
    <dbReference type="PhosphoSitePlus" id="O95870"/>
    <dbReference type="SwissPalm" id="O95870"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000379282"/>
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    <dbReference type="ProteomicsDB" id="51110">
        <molecule id="O95870-1"/>
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    <dbReference type="ProteomicsDB" id="51111">
        <molecule id="O95870-2"/>
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    <dbReference type="Pumba" id="O95870"/>
    <dbReference type="Antibodypedia" id="27504">
        <property type="antibodies" value="94 antibodies from 20 providers"/>
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    <dbReference type="DNASU" id="7920"/>
    <dbReference type="Ensembl" id="ENST00000395952.8">
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        <property type="protein sequence ID" value="ENSP00000379282.3"/>
        <property type="gene ID" value="ENSG00000204427.13"/>
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    <dbReference type="Ensembl" id="ENST00000440843.2">
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        <property type="protein sequence ID" value="ENSP00000410347.2"/>
        <property type="gene ID" value="ENSG00000204427.13"/>
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    <dbReference type="Ensembl" id="ENST00000446529.6">
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        <property type="protein sequence ID" value="ENSP00000395665.2"/>
        <property type="gene ID" value="ENSG00000206403.11"/>
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    <dbReference type="Ensembl" id="ENST00000548592.1">
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        <property type="protein sequence ID" value="ENSP00000448431.1"/>
        <property type="gene ID" value="ENSG00000206403.11"/>
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    <dbReference type="Ensembl" id="ENST00000549722.1">
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        <property type="protein sequence ID" value="ENSP00000447549.1"/>
        <property type="gene ID" value="ENSG00000230475.9"/>
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    <dbReference type="Ensembl" id="ENST00000549853.1">
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        <property type="protein sequence ID" value="ENSP00000447846.1"/>
        <property type="gene ID" value="ENSG00000236063.9"/>
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    <dbReference type="Ensembl" id="ENST00000550556.1">
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        <property type="protein sequence ID" value="ENSP00000447498.1"/>
        <property type="gene ID" value="ENSG00000235676.9"/>
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    <dbReference type="Ensembl" id="ENST00000551038.1">
        <molecule id="O95870-2"/>
        <property type="protein sequence ID" value="ENSP00000449579.1"/>
        <property type="gene ID" value="ENSG00000231488.9"/>
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    <dbReference type="Ensembl" id="ENST00000552042.1">
        <molecule id="O95870-2"/>
        <property type="protein sequence ID" value="ENSP00000448451.1"/>
        <property type="gene ID" value="ENSG00000224552.9"/>
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    <dbReference type="GeneID" id="7920"/>
    <dbReference type="KEGG" id="hsa:7920"/>
    <dbReference type="MANE-Select" id="ENST00000395952.8">
        <property type="protein sequence ID" value="ENSP00000379282.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_021160.3"/>
        <property type="RefSeq protein sequence ID" value="NP_066983.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003nvy.3">
        <molecule id="O95870-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:13921"/>
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    <dbReference type="GeneCards" id="ABHD16A"/>
    <dbReference type="HGNC" id="HGNC:13921">
        <property type="gene designation" value="ABHD16A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000204427">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABHD16A"/>
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        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="619735">
        <property type="type" value="phenotype"/>
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    <dbReference type="OpenTargets" id="ENSG00000204427"/>
    <dbReference type="Orphanet" id="631085">
        <property type="disease" value="Autosomal recessive spastic paraplegia type 86"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000204427"/>
    <dbReference type="eggNOG" id="KOG1553">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160908"/>
    <dbReference type="HOGENOM" id="CLU_040705_2_0_1"/>
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    <dbReference type="OrthoDB" id="6412627at2759"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="O95870"/>
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    <dbReference type="Agora" id="ENSG00000204427"/>
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        <property type="hits" value="23 hits in 1146 CRISPR screens"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD16A">
        <property type="organism name" value="human"/>
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    <dbReference type="GeneWiki" id="BAT5"/>
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        <property type="development level" value="Tchem"/>
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    <dbReference type="PRO" id="PR:O95870"/>
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        <property type="component" value="Chromosome 6"/>
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    <dbReference type="RNAct" id="O95870">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000204427">
        <property type="expression patterns" value="Expressed in pituitary gland and 98 other cell types or tissues"/>
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    <dbReference type="ExpressionAtlas" id="O95870">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0004620">
        <property type="term" value="F:phospholipase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0052651">
        <property type="term" value="P:monoacylglycerol catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006660">
        <property type="term" value="P:phosphatidylserine catabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:1905344">
        <property type="term" value="P:prostaglandin catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000074">
        <property type="entry name" value="Abhydrolase domain containing 16A"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AB_hydrolase_1"/>
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    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
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    <dbReference type="InterPro" id="IPR054518">
        <property type="entry name" value="ABHD16_N"/>
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    <dbReference type="PANTHER" id="PTHR12277">
        <property type="entry name" value="ALPHA/BETA HYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR12277:SF54">
        <property type="entry name" value="PHOSPHATIDYLSERINE LIPASE ABHD16A"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF22990">
        <property type="entry name" value="ABHD16_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0890">Hereditary spastic paraplegia</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0523">Neurodegeneration</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000064833" description="Phosphatidylserine lipase ABHD16A">
        <location>
            <begin position="1"/>
            <end position="558"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="60"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="93"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="114"/>
            <end position="558"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="3">
        <location>
            <begin position="281"/>
            <end position="407"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="430"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="507"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043825" description="In isoform 2." evidence="8">
        <original>MAKLLSCVLGPRLYKIYRERDSERAPASVPETPTAVTAPHSSSWDTYYQPRALEKHADSILALASVFWSISYYSSPFAFFYLYRK</original>
        <variation>MPPPALFLSSLYPRLEFQNDFYRSCIRRSSPQPPPNLAWRPESLYSGELAGG</variation>
        <location>
            <begin position="1"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086886" description="In SPG86; no protein detected in homozygous patient cells; increased levels of phosphatidylserine and decreased levels of lysophosphatidylserine in homozygous patient cells, indicating loss of function in phosphatidylserine catabolism." evidence="5">
        <location>
            <begin position="114"/>
            <end position="558"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086887" description="In SPG86." evidence="6">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086888" description="In SPG86; uncertain significance." evidence="6">
        <original>N</original>
        <variation>I</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086889" description="In SPG86; uncertain significance." evidence="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086890" description="In SPG86." evidence="7">
        <location>
            <begin position="279"/>
            <end position="558"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086891" description="In SPG86; uncertain significance." evidence="6">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="409"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086892" description="In SPG86." evidence="6">
        <location>
            <begin position="445"/>
            <end position="558"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086893" description="In SPG86; no protein detected in homozygous patient cells; increased levels of phosphatidylserine and decreased levels of lysophosphatidylserine in homozygous patient cells, indicating loss of function in phosphatidylserine catabolism." evidence="5">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="457"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG22475." evidence="10" ref="1">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8N2K0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9Z1Q2"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="25290914"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="34489854"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="34587489"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="34866177"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="25290914"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="HGNC" id="HGNC:13921"/>
        </source>
    </evidence>
    <sequence length="558" mass="63243" checksum="BC46EDA0725D44EA" modified="2007-01-23" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="180" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NUJ1</accession>
    <accession>B7Z6A8</accession>
    <accession>C9IZX5</accession>
    <accession>D3DN63</accession>
    <accession>Q8TCF9</accession>
    <name>ABHDA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Palmitoyl-protein thioesterase ABHD10, mitochondrial</fullName>
            <ecNumber evidence="4">3.1.2.22</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Acyl-protein thioesterase ABHD10</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Alpha/beta hydrolase domain-containing protein 10</fullName>
            <shortName evidence="6">Abhydrolase domain-containing protein 10</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Mycophenolic acid acyl-glucuronide esterase, mitochondrial</fullName>
            <ecNumber evidence="3">3.1.1.93</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">ABHD10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Placenta</tissue>
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            <dbReference type="PubMed" id="16641997"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Ovary</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-306 (ISOFORM 1)</scope>
        <source>
            <tissue>Melanoma</tissue>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="22294686"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="31740833"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF SER-152</scope>
        <scope>ACTIVE SITE</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Acts as an acyl-protein thioesterase that hydrolyzes fatty acids from acylated residues in proteins (PubMed:31740833). Regulates the mitochondrial S-depalmitoylation of the nucleophilic active site residue of peroxiredoxin-5/PRDX5, a key antioxidant protein, therefore modulating mitochondrial antioxidant ability (PubMed:31740833). Also catalyzes the deglucuronidation of mycophenolic acid acyl-glucuronide, an active metabolite of the immunosuppressant drug mycophenolate (PubMed:22294686).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19233"/>
            <dbReference type="Rhea" id="RHEA-COMP:10131"/>
            <dbReference type="Rhea" id="RHEA-COMP:11032"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29950"/>
            <dbReference type="ChEBI" id="CHEBI:74151"/>
            <dbReference type="EC" id="3.1.2.22"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:19234"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>mycophenolic acid O-acyl-beta-D-glucuronide + H2O = mycophenolate + D-glucuronate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:34179"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58720"/>
            <dbReference type="ChEBI" id="CHEBI:62932"/>
            <dbReference type="ChEBI" id="CHEBI:66982"/>
            <dbReference type="EC" id="3.1.1.93"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:34180"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">Inhibited by palmostatin-B.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">100.7 uM for mycophenolic acid O-acyl-beta-D-glucuronide</KM>
            <Vmax evidence="3">47.6 nmol/min/mg enzyme with mycophenolic acid O-acyl-beta-D-glucuronide as substrate</Vmax>
        </kinetics>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2564608">
            <id>Q9NUJ1</id>
        </interactant>
        <interactant intactId="EBI-720457">
            <id>Q96EW2</id>
            <label>HSPBAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NUJ1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NUJ1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056093"/>
        </isoform>
        <isoform>
            <id>Q9NUJ1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_056742 VSP_056743"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the AB hydrolase superfamily.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.22" evidence="4"/>
    <dbReference type="EC" id="3.1.1.93" evidence="3"/>
    <dbReference type="EMBL" id="AK002204">
        <property type="protein sequence ID" value="BAA92133.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300018">
        <property type="protein sequence ID" value="BAH13194.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC060225">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79688.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79689.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014516">
        <property type="protein sequence ID" value="AAH14516.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL713726">
        <property type="protein sequence ID" value="CAD28516.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2963.1">
        <molecule id="Q9NUJ1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS63718.1">
        <molecule id="Q9NUJ1-3"/>
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    <dbReference type="RefSeq" id="NP_001258998.1">
        <molecule id="Q9NUJ1-3"/>
        <property type="nucleotide sequence ID" value="NM_001272069.2"/>
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    <dbReference type="RefSeq" id="NP_060864.1">
        <molecule id="Q9NUJ1-1"/>
        <property type="nucleotide sequence ID" value="NM_018394.4"/>
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        <property type="interactions" value="105"/>
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    <dbReference type="DIP" id="DIP-56934N"/>
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        <property type="family name" value="ABHD10"/>
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    <dbReference type="MEROPS" id="S09.062"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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    <dbReference type="iPTMnet" id="Q9NUJ1"/>
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    <dbReference type="ProteomicsDB" id="7863"/>
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        <molecule id="Q9NUJ1-1"/>
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        <property type="antibodies" value="74 antibodies from 20 providers"/>
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        <molecule id="Q9NUJ1-1"/>
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        <property type="gene ID" value="ENSG00000144827.10"/>
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        <property type="protein sequence ID" value="ENSP00000273359.3"/>
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        <property type="RefSeq protein sequence ID" value="NP_060864.1"/>
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    <dbReference type="UCSC" id="uc003dyk.6">
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    <dbReference type="AGR" id="HGNC:25656"/>
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        <property type="gene designation" value="ABHD10"/>
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        <property type="pathway name" value="Glucuronidation"/>
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        <property type="hits" value="15 hits in 1157 CRISPR screens"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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    <dbReference type="GenomeRNAi" id="55347"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NUJ1"/>
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        <property type="component" value="Chromosome 3"/>
    </dbReference>
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        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000144827">
        <property type="expression patterns" value="Expressed in nephron tubule and 202 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:cytosol"/>
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        <property type="project" value="BHF-UCL"/>
    </dbReference>
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        <property type="term" value="C:mitochondrial matrix"/>
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        <property type="term" value="F:hydrolase activity, hydrolyzing O-glycosyl compounds"/>
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        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0102390">
        <property type="term" value="F:mycophenolic acid acyl-glucuronide esterase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008474">
        <property type="term" value="F:palmitoyl-(protein) hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019585">
        <property type="term" value="P:glucuronate metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002084">
        <property type="term" value="P:protein depalmitoylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006805">
        <property type="term" value="P:xenobiotic metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000164">
        <property type="entry name" value="Mycophenolic acid acyl-glucuronide esterase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052382">
        <property type="entry name" value="ABHD10_acyl-thioesterase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR16138">
        <property type="entry name" value="MYCOPHENOLIC ACID ACYL-GLUCURONIDE ESTERASE, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR16138:SF7">
        <property type="entry name" value="PALMITOYL-PROTEIN THIOESTERASE ABHD10, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000280733" description="Palmitoyl-protein thioesterase ABHD10, mitochondrial">
        <location>
            <begin position="53"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="2">
        <location>
            <begin position="78"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="10">
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056093" description="In isoform 2." evidence="5">
        <location>
            <begin position="1"/>
            <end position="157"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056742" description="In isoform 3." evidence="8">
        <original>LKKEVEMKGVWSM</original>
        <variation>DSGRKNYISLHSA</variation>
        <location>
            <begin position="193"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056743" description="In isoform 3." evidence="8">
        <location>
            <begin position="206"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031194" description="In dbSNP:rs17429033.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of palmitoyl-(protein) hydrolase activity." evidence="4">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8N2K0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="22294686"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="31740833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="22294686"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="31740833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="22294686"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="31740833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="HGNC" id="HGNC:25656"/>
        </source>
    </evidence>
    <sequence length="306" mass="33933" checksum="E41139D5C22A83FE" modified="2000-10-01" version="1" precursor="true">MAVARLAAVAAWVPCRSWGWAAVPFGPHRGLSVLLARIPQRAPRWLPACRQKTSLSFLNRPDLPNLAYKKLKGKSPGIIFIPGYLSYMNGTKALAIEEFCKSLGHACIRFDYSGVGSSDGNSEESTLGKWRKDVLSIIDDLADGPQILVGSSLGGWLMLHAAIARPEKVVALIGVATAADTLVTKFNQLPVELKKEVEMKGVWSMPSKYSEEGVYNVQYSFIKEAEHHCLLHSPIPVNCPIRLLHGMKDDIVPWHTSMQVADRVLSTDVDVILRKHSDHRMREKADIQLLVYTIDDLIDKLSTIVN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="227" xmlns="https://uniprot.org/uniprot">
    <accession>P78363</accession>
    <accession>O15112</accession>
    <accession>O60438</accession>
    <accession>O60915</accession>
    <accession>Q0QD48</accession>
    <accession>Q4LE31</accession>
    <name>ABCA4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="59">Retinal-specific phospholipid-transporting ATPase ABCA4</fullName>
            <ecNumber evidence="39">7.6.2.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP-binding cassette sub-family A member 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>RIM ABC transporter</fullName>
            <shortName>RIM proteinv</shortName>
            <shortName>RmP</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Retinal-specific ATP-binding cassette transporter</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Stargardt disease protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="63" type="primary">ABCA4</name>
        <name evidence="58" type="synonym">ABCR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Nat. Genet." volume="15" first="236" last="246">
            <title>A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.</title>
            <authorList>
                <person name="Allikmets R."/>
                <person name="Singh N."/>
                <person name="Sun H."/>
                <person name="Shroyer N.F."/>
                <person name="Hutchinson A."/>
                <person name="Chidambaram A."/>
                <person name="Gerrard B."/>
                <person name="Baird L."/>
                <person name="Stauffer D."/>
                <person name="Peiffer A."/>
                <person name="Rattner A."/>
                <person name="Smallwood P.M."/>
                <person name="Li Y."/>
                <person name="Anderson K.L."/>
                <person name="Lewis R.A."/>
                <person name="Nathans J."/>
                <person name="Leppert M."/>
                <person name="Dean M."/>
                <person name="Lupski J.R."/>
            </authorList>
            <dbReference type="PubMed" id="9054934"/>
            <dbReference type="DOI" id="10.1038/ng0397-236"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>INVOLVEMENT IN STGD1</scope>
        <scope>VARIANTS GLN-943 AND ASP-1817</scope>
        <scope>VARIANTS STGD1 GLU-818; HIS-846; ALA-863; MET-931; VAL-1028; ALA-1072; LYS-1087 AND TRP-2038</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="409" first="247" last="252">
            <title>The photoreceptor rim protein is an ABC transporter encoded by the gene for recessive Stargardt's disease (ABCR).</title>
            <authorList>
                <person name="Azarian S.M."/>
                <person name="Travis G.H."/>
            </authorList>
            <dbReference type="PubMed" id="9202155"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(97)00517-6"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1998" name="Genomics" volume="48" first="139" last="142">
            <title>Complete exon-intron structure of the retina-specific ATP binding transporter gene (ABCR) allows the identification of novel mutations underlying Stargardt disease.</title>
            <authorList>
                <person name="Gerber S."/>
                <person name="Rozet J.-M."/>
                <person name="van de Pol T.J.R."/>
                <person name="Hoyng C.B."/>
                <person name="Munnich A."/>
                <person name="Blankenagel A."/>
                <person name="Kaplan J."/>
                <person name="Cremers F.P.M."/>
            </authorList>
            <dbReference type="PubMed" id="9503029"/>
            <dbReference type="DOI" id="10.1006/geno.1997.5164"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS STGD1 TRP-18 AND CYS-212</scope>
        <scope>VARIANT ASP-1817</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="Hum. Genet." volume="102" first="21" last="26">
            <title>Mapping of the rod photoreceptor ABC transporter (ABCR) to 1p21-p22.1 and identification of novel mutations in Stargardt's disease.</title>
            <authorList>
                <person name="Nasonkin I."/>
                <person name="Illing M."/>
                <person name="Koehler M.R."/>
                <person name="Schmid M."/>
                <person name="Molday R.S."/>
                <person name="Weber B.H.F."/>
            </authorList>
            <dbReference type="PubMed" id="9490294"/>
            <dbReference type="DOI" id="10.1007/s004390050649"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANTS STGD1</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-03" db="EMBL/GenBank/DDBJ databases">
            <title>Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method.</title>
            <authorList>
                <person name="Nakajima D."/>
                <person name="Saito K."/>
                <person name="Yamakawa H."/>
                <person name="Kikuno R.F."/>
                <person name="Nakayama M."/>
                <person name="Ohara R."/>
                <person name="Okazaki N."/>
                <person name="Koga H."/>
                <person name="Nagase T."/>
                <person name="Ohara O."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT GLN-943</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Coville G.J."/>
                <person name="Davies J."/>
                <person name="Deadman R."/>
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        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF TYR-345 AND ARG-587</scope>
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        <scope>VARIANTS STGD1 HIS-846 AND ALA-863</scope>
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        <scope>VARIANTS FFM PRO-11; PRO-541; VAL-1038; GLU-1091; CYS-1508; PHE-1970 AND ARG-1971</scope>
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                <person name="Kaplan J."/>
                <person name="Assink J.J.M."/>
                <person name="ten Brink J.B."/>
                <person name="de Jong P.T.V.M."/>
                <person name="Bergen A.A.B."/>
                <person name="Maugeri A."/>
                <person name="van Driel M.A."/>
                <person name="Hoyng C.B."/>
                <person name="Cremers F.P.M."/>
                <person name="Paloma E."/>
                <person name="Coco R."/>
                <person name="Balcells S."/>
                <person name="Gonzalez-Duarte R."/>
                <person name="Kermani S."/>
                <person name="Stanga P."/>
                <person name="Bhattacharya S.S."/>
                <person name="Bird A.C."/>
            </authorList>
            <dbReference type="PubMed" id="10880298"/>
            <dbReference type="DOI" id="10.1086/303018"/>
        </citation>
        <scope>VARIANTS GLU-1961 AND ASN-2177</scope>
    </reference>
    <reference key="26">
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            <title>A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.</title>
            <authorList>
                <person name="Rivera A."/>
                <person name="White K."/>
                <person name="Stoehr H."/>
                <person name="Steiner K."/>
                <person name="Hemmrich N."/>
                <person name="Grimm T."/>
                <person name="Jurklies B."/>
                <person name="Lorenz B."/>
                <person name="Scholl H.P.N."/>
                <person name="Apfelstedt-Sylla E."/>
                <person name="Weber B.H.F."/>
            </authorList>
            <dbReference type="PubMed" id="10958763"/>
            <dbReference type="DOI" id="10.1086/303090"/>
        </citation>
        <scope>VARIANTS STGD1 GLU-60; THR-60; GLU-65; LEU-68; ARG-72; CYS-212; SER-230; SER-247; VAL-328; LYS-471; PRO-541; GLN-572; ARG-607; LYS-635; CYS-653; TYR-764; ARG-765; ALA-901; ILE-959; LYS-1036; VAL-1038; PRO-1063; ASP-1087; CYS-1097; CYS-1108; LEU-1380; LYS-1399; PRO-1430; VAL-1440; HIS-1443; LEU-1486; TYR-1488; MET-1537; PRO-1689; LEU-1705; THR-1733; ARG-1748; PRO-1763; LYS-1885; HIS-1898; GLU-1961; ARG-1975; SER-1977; GLY-2077; TRP-2077 AND VAL-2241</scope>
        <scope>VARIANTS GLN-152; HIS-212; ARG-423; ILE-552; ARG-914; GLN-943; THR-1562; ILE-1868; MET-1921; LEU-1948; PHE-1970; ALA-2059; ASN-2177 AND VAL-2216</scope>
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            <title>Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.</title>
            <authorList>
                <person name="Maugeri A."/>
                <person name="Klevering B.J."/>
                <person name="Rohrschneider K."/>
                <person name="Blankenagel A."/>
                <person name="Brunner H.G."/>
                <person name="Deutman A.F."/>
                <person name="Hoyng C.B."/>
                <person name="Cremers F.P.M."/>
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            <dbReference type="PubMed" id="10958761"/>
            <dbReference type="DOI" id="10.1086/303079"/>
        </citation>
        <scope>VARIANTS CORD3 GLU-65; CYS-212; PRO-541; ALA-863; VAL-1038; LYS-1122; TYR-1490 AND ASP-1598</scope>
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            <title>Complex inheritance of ABCR mutations in Stargardt disease: linkage disequilibrium, complex alleles, and pseudodominance.</title>
            <authorList>
                <person name="Shroyer N.F."/>
                <person name="Lewis R.A."/>
                <person name="Lupski J.R."/>
            </authorList>
            <dbReference type="PubMed" id="10746567"/>
            <dbReference type="DOI" id="10.1007/s004390051034"/>
        </citation>
        <scope>VARIANTS STGD1 ASP-340; GLN-572; ALA-863; SER-965; VAL-1038; ALA-1780 AND HIS-1898</scope>
        <scope>VARIANT GLN-943</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2000" name="Invest. Ophthalmol. Vis. Sci." volume="41" first="16" last="19">
            <title>An analysis of ABCR mutations in British patients with recessive retinal dystrophies.</title>
            <authorList>
                <person name="Papaioannou M."/>
                <person name="Ocaka L."/>
                <person name="Bessant D."/>
                <person name="Lois N."/>
                <person name="Bird A.C."/>
                <person name="Payne A."/>
                <person name="Bhattacharya S.S."/>
            </authorList>
            <dbReference type="PubMed" id="10634594"/>
        </citation>
        <scope>VARIANTS GLN-943 AND SER-1948</scope>
        <scope>VARIANTS STGD1 TYR-54; ASP-96; HIS-96; VAL-156; VAL-407; ALA-424; ARG-445; TRP-602; 779-CYS--ASP-2273 DEL; ALA-863; ALA-1429; TRP-1640; GLU-1703; 1779-TYR--ASP-2273 DEL AND ARG-2160</scope>
        <scope>VARIANTS CORD3 VAL-407; 2030-ARG--ASP-2273 DEL AND TYR-2150</scope>
        <scope>VARIANT RP19 ALA-424</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2000" name="Invest. Ophthalmol. Vis. Sci." volume="41" first="892" last="897">
            <title>New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease.</title>
            <authorList>
                <person name="Simonelli F."/>
                <person name="Testa F."/>
                <person name="de Crecchio G."/>
                <person name="Rinaldi E."/>
                <person name="Hutchinson A."/>
                <person name="Atkinson A."/>
                <person name="Dean M."/>
                <person name="D'Urso M."/>
                <person name="Allikmets R."/>
            </authorList>
            <dbReference type="PubMed" id="10711710"/>
        </citation>
        <scope>VARIANTS STGD1 CYS-212; ASP-767; ILE-897; VAL-1038; LYS-1087; LYS-1399; GLN-1640 AND GLU-1961</scope>
        <scope>VARIANT HIS-212</scope>
    </reference>
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            <title>Biochemical defects in ABCR protein variants associated with human retinopathies.</title>
            <authorList>
                <person name="Sun H."/>
                <person name="Smallwood P.M."/>
                <person name="Nathans J."/>
            </authorList>
            <dbReference type="PubMed" id="11017087"/>
            <dbReference type="DOI" id="10.1038/79994"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS</scope>
        <scope>MUTAGENESIS OF GLY-863; GLY-966; LYS-969; GLY-1975 AND LYS-1978</scope>
    </reference>
    <reference key="32">
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            <title>Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1).</title>
            <authorList>
                <person name="Eksandh L."/>
                <person name="Ekstroem U."/>
                <person name="Abrahamson M."/>
                <person name="Bauer B."/>
                <person name="Andreasson S."/>
            </authorList>
            <dbReference type="PubMed" id="11594993"/>
            <dbReference type="DOI" id="10.1034/j.1600-0420.2001.790520.x"/>
        </citation>
        <scope>VARIANT STGD1 ASN-972</scope>
        <scope>VARIANTS GLN-943; ILE-1868 AND LEU-1948</scope>
    </reference>
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            <title>Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?</title>
            <authorList>
                <person name="Shroyer N.F."/>
                <person name="Lewis R.A."/>
                <person name="Lupski J.R."/>
            </authorList>
            <dbReference type="PubMed" id="11384574"/>
            <dbReference type="DOI" id="10.1016/s0002-9394(01)00838-8"/>
        </citation>
        <scope>VARIANTS RETINAL TOXICITY CYS-1129; ARG-1201 AND HIS-2107</scope>
        <scope>VARIANTS HIS-212; ARG-423; ILE-1868 AND ILE-2255</scope>
    </reference>
    <reference key="34">
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            <title>Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration.</title>
            <authorList>
                <person name="Guymer R.H."/>
                <person name="Heon E."/>
                <person name="Lotery A.J."/>
                <person name="Munier F.L."/>
                <person name="Schorderet D.F."/>
                <person name="Baird P.N."/>
                <person name="McNeil R.J."/>
                <person name="Haines H.L."/>
                <person name="Sheffield V.C."/>
                <person name="Stone E.M."/>
            </authorList>
            <dbReference type="PubMed" id="11346402"/>
            <dbReference type="DOI" id="10.1001/archopht.119.5.745"/>
        </citation>
        <scope>VARIANTS GLU-1961 AND ASN-2177</scope>
    </reference>
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            <title>Late-onset Stargardt disease is associated with missense mutations that map outside known functional regions of ABCR (ABCA4).</title>
            <authorList>
                <person name="Yatsenko A.N."/>
                <person name="Shroyer N.F."/>
                <person name="Lewis R.A."/>
                <person name="Lupski J.R."/>
            </authorList>
            <dbReference type="PubMed" id="11379881"/>
            <dbReference type="DOI" id="10.1007/s004390100493"/>
        </citation>
        <scope>VARIANTS FFM GLY-339; ALA-863; TRP-943; ARG-991; VAL-1038; CYS-1108; ARG-1488; THR-1562; GLN-1640; PHE-2027; GLN-2030 AND CYS-2106</scope>
        <scope>VARIANTS HIS-212; ARG-423; GLN-943; THR-1148; ILE-1868 AND ILE-2255</scope>
    </reference>
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            <title>Spectrum of ABCA4 (ABCR) gene mutations in Spanish patients with autosomal recessive macular dystrophies.</title>
            <authorList>
                <person name="Paloma E."/>
                <person name="Martinez-Mir A."/>
                <person name="Vilageliu L."/>
                <person name="Gonzalez-Duarte R."/>
                <person name="Balcells S."/>
            </authorList>
            <dbReference type="PubMed" id="11385708"/>
            <dbReference type="DOI" id="10.1002/humu.1133"/>
        </citation>
        <scope>VARIANTS STGD1 SER-686; TRP-1055; CYS-1108; ASP-1799; ASP-1805 AND PRO-1940</scope>
        <scope>VARIANTS FFM MET-1253 AND PRO-1940</scope>
        <scope>VARIANTS CORD3 CYS-212 AND ARG-2060</scope>
        <scope>VARIANTS GLN-943; LEU-1948 AND ILE-2255</scope>
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            <title>An analysis of allelic variation in the ABCA4 gene.</title>
            <authorList>
                <person name="Webster A.R."/>
                <person name="Heon E."/>
                <person name="Lotery A.J."/>
                <person name="Vandenburgh K."/>
                <person name="Casavant T.L."/>
                <person name="Oh K.T."/>
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                <person name="Fishman G.A."/>
                <person name="Lam B.L."/>
                <person name="Levin A."/>
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                <person name="Jacobson S.G."/>
                <person name="Weleber R.G."/>
                <person name="Sheffield V.C."/>
                <person name="Stone E.M."/>
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            <dbReference type="PubMed" id="11328725"/>
        </citation>
        <scope>VARIANTS STGD1 PRO-100; THR-192; CYS-220; TRP-333; TRP-607; MET-716; TYR-764; ASN-765; THR-854; LEU-873; ASN-971; ALA-1019; GLU-1031; PRO-1250; LEU-1408; PHE-1488; ARG-1513; PRO-1525; ILE-1693; PRO-1736; GLU-1884; ASP-1896; PHE-2071; PRO-2229 AND LEU-2263</scope>
        <scope>VARIANT THR-1314</scope>
        <scope>REVIEW</scope>
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            <title>Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.</title>
            <authorList>
                <person name="Briggs C.E."/>
                <person name="Rucinski D."/>
                <person name="Rosenfeld P.J."/>
                <person name="Hirose T."/>
                <person name="Berson E.L."/>
                <person name="Dryja T.P."/>
            </authorList>
            <dbReference type="PubMed" id="11527935"/>
        </citation>
        <scope>VARIANTS STGD1 13-LYS--TRP-15 DEL; TYR-54; LYS-58; VAL-60; GLU-65; GLU-77; HIS-190; PRO-244; ARG-309; CYS-525; CYS-537; PRO-541; PRO-549; ARG-550; GLN-602; ARG-607; MET-643; ASP-767; PRO-797; ARG-821; THR-824; ALA-863; ALA-935; TRP-943; ALA-989; VAL-1038; CYS-1108; LEU-1108; LYS-1122; ARG-1201; GLN-1300; LEU-1380; PRO-1388; ARG-1408; LEU-1486; ARG-1488; TYR-1490; MET-1526; ASN-1532; THR-1562; TRP-1640; LEU-1776; THR-1846; GLU-1961; SER-1977; PHE-2027; GLN-2030; PRO-2035; LEU-2050; CYS-2107; HIS-2107; TRP-2139; ARG-2150 AND TYR-2150</scope>
        <scope>VARIANTS CORD3 GLN-1640 AND ASP-2146</scope>
        <scope>VARIANTS HIS-212; ARG-423; GLN-943; THR-1637; ILE-1868 AND LEU-1948</scope>
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            <authorList>
                <person name="Iida A."/>
                <person name="Saito S."/>
                <person name="Sekine A."/>
                <person name="Mishima C."/>
                <person name="Kitamura Y."/>
                <person name="Kondo K."/>
                <person name="Harigae S."/>
                <person name="Osawa S."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="12111378"/>
            <dbReference type="DOI" id="10.1007/s100380200041"/>
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        <scope>VARIANT ARG-423</scope>
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            <title>Functional analysis of genetic mutations in nucleotide binding domain 2 of the human retina specific ABC transporter.</title>
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                <person name="Biswas-Fiss E.E."/>
            </authorList>
            <dbReference type="PubMed" id="12962493"/>
            <dbReference type="DOI" id="10.1021/bi034481l"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS ARG-1971; PHE-2027; TRP-2038; ASP-2146 AND ASN-2177</scope>
        <scope>MUTAGENESIS OF LYS-2175</scope>
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                <person name="Fermo I."/>
                <person name="Battistella S."/>
                <person name="Galbiati S."/>
                <person name="Soriani N."/>
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                <person name="Manitto M.P."/>
                <person name="Martina E."/>
                <person name="Brancato R."/>
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            </authorList>
            <dbReference type="PubMed" id="15192030"/>
            <dbReference type="DOI" id="10.1373/clinchem.2004.033241"/>
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        <scope>VARIANTS STGD1 TRP-18; LYS-96; VAL-108; LEU-143; GLN-152; GLN-223; SER-230; 245-TYR--ASP-2273 DEL; THR-246; GLU-498; PRO-541; ARG-550; GLN-572; 639-TYR--ASP-2273 DEL; SER-641; CYS-653; VAL-690; 700-TRP--ASP-2273 DEL; ASP-767; ARG-821; ALA-863; 876-GLN--ASP-2273 DEL; ILE-897; ASP-954; SER-965; ASP-978; LYS-1022; VAL-1038; ASP-1050; LYS-1087; CYS-1098; PRO-1099; CYS-1108; HIS-1108; LEU-1129; ARG-1203; ASP-1203; ASN-1204; 1300-ARG--ASP-2273 DEL; GLN-1300; TYR-1490; ARG-1512; MET-1526; ASP-1598; 1652-TYR--ASP-2273 DEL; ASP-1762; ASN-1838; TYR-1838; GLU-1961; PHE-1970; PHE-2027; GLN-2030; LEU-2050; HIS-2107; TRP-2139; LEU-2149; TYR-2150; ASN-2177 AND VAL-2241</scope>
        <scope>VARIANTS HIS-212; ARG-423; GLN-943; LEU-1380; ILE-1868 AND LEU-1948</scope>
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                <person name="Sjoeblom T."/>
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                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
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                <person name="Ptak J."/>
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                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
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            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] MET-224</scope>
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                <person name="Riveiro-Alvarez R."/>
                <person name="Vallespin E."/>
                <person name="Wilke R."/>
                <person name="Garcia-Sandoval B."/>
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                <person name="Avila-Fernandez A."/>
                <person name="Gimenez A."/>
                <person name="Trujillo-Tiebas M.J."/>
                <person name="Ayuso C."/>
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        <scope>VARIANT STGD1 ASP-1805</scope>
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                <person name="Riveiro-Alvarez R."/>
                <person name="Maia-Lopes S."/>
                <person name="Cantalapiedra D."/>
                <person name="Vallespin E."/>
                <person name="Avila-Fernandez A."/>
                <person name="Villaverde-Montero C."/>
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                <person name="Ramos C."/>
                <person name="Ayuso C."/>
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            <dbReference type="PubMed" id="19028736"/>
            <dbReference type="DOI" id="10.1136/bjo.2008.145193"/>
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        <scope>VARIANTS STGD1 TRP-602; MET-931; MET-1019; HIS-1108; LEU-1129; LEU-1486; GLN-1640; GLU-1961; SER-1977; PHE-2027 AND HIS-2107</scope>
        <scope>VARIANTS CORD3 LEU-1129 AND ILE-1433</scope>
        <scope>VARIANTS RP19 VAL-156; LEU-1129 AND ILE-1433</scope>
        <scope>VARIANT ILE-552</scope>
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                <person name="Riveiro-Alvarez R."/>
                <person name="Aguirre-Lamban J."/>
                <person name="Lopez-Martinez M.A."/>
                <person name="Trujillo-Tiebas M.J."/>
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                <person name="Vallespin E."/>
                <person name="Avila-Fernandez A."/>
                <person name="Ramos C."/>
                <person name="Ayuso C."/>
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            <dbReference type="PubMed" id="18977788"/>
            <dbReference type="DOI" id="10.1136/bjo.2008.148155"/>
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        <scope>VARIANTS STGD1 VAL-156; CYS-212; LYS-380; ARG-550; PRO-572; TRP-602; ARG-607; CYS-653; ASP-767; ILE-897; ALA-901; MET-931; SER-965; MET-1019; HIS-1108; LEU-1129; LEU-1380; ILE-1433; LEU-1486; TYR-1490; GLN-1640; TRP-1640; ARG-1748; ASP-1799; PRO-1940; GLU-1961; SER-1977; PHE-2027; ARG-2060; HIS-2107; TYR-2150 AND VAL-2241</scope>
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            <title>Novel mutations in of the ABCR gene in Italian patients with Stargardt disease.</title>
            <authorList>
                <person name="Passerini I."/>
                <person name="Sodi A."/>
                <person name="Giambene B."/>
                <person name="Mariottini A."/>
                <person name="Menchini U."/>
                <person name="Torricelli F."/>
            </authorList>
            <dbReference type="PubMed" id="19265867"/>
            <dbReference type="DOI" id="10.1038/eye.2009.35"/>
        </citation>
        <scope>VARIANTS STGD1 21-GLN--ASP-2273 DEL; LEU-68; HIS-96; LYS-96; SER-172; CYS-212; LYS-415; PRO-541; 572-ARG--ASP-2273 DEL; LYS-616; CYS-653; VAL-690; 700-TRP--ASP-2273 DEL; ASP-767; ARG-821; ARG-840; MET-931; SER-965; PRO-970; PRO-977; ASP-978; MET-1019; VAL-1038; TRP-1055; GLU-1078; LYS-1087; CYS-1098; 1099-SER--ASP-2273 DEL; CYS-1108; 1177-CYS--ASP-2273 DEL; 1332-GLN--ASP-2273 DEL; LEU-1380; 1408-TRP--ASP-2273 DEL; ILE-1433; 1461-TRP--ASP-2273 DEL; 1479-TRP--ASP-2273 DEL; SER-1484; MET-1526; ASP-1598; ASN-1696; GLU-1961; PHE-1970; SER-1977; 2030-ARG--ASP-2273 DEL; LYS-2096; GLN-2140 AND PRO-2221</scope>
    </reference>
    <reference key="47">
        <citation type="journal article" date="2010" name="Invest. Ophthalmol. Vis. Sci." volume="51" first="4253" last="4265">
            <title>ABCA4 and ROM1: implications for modification of the PRPH2-associated macular dystrophy phenotype.</title>
            <authorList>
                <person name="Poloschek C.M."/>
                <person name="Bach M."/>
                <person name="Lagreze W.A."/>
                <person name="Glaus E."/>
                <person name="Lemke J.R."/>
                <person name="Berger W."/>
                <person name="Neidhardt J."/>
            </authorList>
            <dbReference type="PubMed" id="20335603"/>
            <dbReference type="DOI" id="10.1167/iovs.09-4655"/>
        </citation>
        <scope>VARIANT LEU-2050</scope>
    </reference>
    <reference key="48">
        <citation type="journal article" date="2012" name="Arch. Ophthalmol." volume="130" first="1486" last="1490">
            <title>Detection rate of pathogenic mutations in ABCA4 using direct sequencing: clinical and research implications.</title>
            <authorList>
                <person name="Downes S.M."/>
                <person name="Packham E."/>
                <person name="Cranston T."/>
                <person name="Clouston P."/>
                <person name="Seller A."/>
                <person name="Nemeth A.H."/>
            </authorList>
            <dbReference type="PubMed" id="23143460"/>
            <dbReference type="DOI" id="10.1001/archophthalmol.2012.1697"/>
        </citation>
        <scope>VARIANTS 219-ARG--ASP-2273 DEL; HIS-576; GLN-943; ARG-1488; MET-1526; CYS-1557; THR-1562; GLU-1773; ASP-1794; 2040-ARG--ASP-2273 DEL AND CYS-2107</scope>
        <scope>VARIANTS STGD1 TYR-54; GLN-152; ARG-184; PHE-184; CYS-212; SER-418; LYS-471; MET-643; CYS-653; 782-TRP--ASP-2273 DEL; ALA-863; ALA-989; ARG-991; MET-1019; LYS-1022; SER-1097; CYS-1108; LYS-1122; LEU-1129; ARG-1201; LEU-1380; LYS-1442; LEU-1486; TYR-1490; ASP-1598; ASP-1754; THR-1846; GLU-1961; PHE-2027; GLN-2030; CYS-2106; LYS-2131; TYR-2150 AND PRO-2237</scope>
    </reference>
    <reference key="49">
        <citation type="journal article" date="2013" name="Exp. Eye Res." volume="109" first="77" last="82">
            <title>ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation.</title>
            <authorList>
                <person name="Chacon-Camacho O.F."/>
                <person name="Granillo-Alvarez M."/>
                <person name="Ayala-Ramirez R."/>
                <person name="Zenteno J.C."/>
            </authorList>
            <dbReference type="PubMed" id="23419329"/>
            <dbReference type="DOI" id="10.1016/j.exer.2013.02.006"/>
        </citation>
        <scope>VARIANTS STGD1 TRP-18; HIS-24; 89-GLU--ASP-2273 DEL; CYS-212; ASP-241; TRP-290; TRP-602; GLU-818; SER-965; ARG-1014; LEU-1129; LEU-1380; PHE-1416 DEL; HIS-1443; TRP-1551 DEL; THR-1556; 1681-VAL--VAL-1685 DEL; GLN-1705; VAL-1773; ASN-1775; HIS-1779; GLN-1942; VAL-2074 AND ARG-2128</scope>
        <scope>VARIANTS GLN-943; ILE-1868 AND ILE-2255</scope>
    </reference>
    <reference key="50">
        <citation type="journal article" date="2013" name="Ophthalmology" volume="120" first="2332" last="2337">
            <title>Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.</title>
            <authorList>
                <person name="Riveiro-Alvarez R."/>
                <person name="Lopez-Martinez M.A."/>
                <person name="Zernant J."/>
                <person name="Aguirre-Lamban J."/>
                <person name="Cantalapiedra D."/>
                <person name="Avila-Fernandez A."/>
                <person name="Gimenez A."/>
                <person name="Lopez-Molina M.I."/>
                <person name="Garcia-Sandoval B."/>
                <person name="Blanco-Kelly F."/>
                <person name="Corton M."/>
                <person name="Tatu S."/>
                <person name="Fernandez-San Jose P."/>
                <person name="Trujillo-Tiebas M.J."/>
                <person name="Ramos C."/>
                <person name="Allikmets R."/>
                <person name="Ayuso C."/>
            </authorList>
            <dbReference type="PubMed" id="23755871"/>
            <dbReference type="DOI" id="10.1016/j.ophtha.2013.04.002"/>
        </citation>
        <scope>VARIANTS STGD1 TRP-18; LEU-153; CYS-212; ALA-291; CYS-537; PRO-541; TRP-602; PRO-611; CYS-653; SER-686; GLU-762; MET-931; ALA-989; MET-1019; ARG-1094; LEU-1096; CYS-1098; HIS-1108; LYS-1122; GLU-1127; LEU-1129; THR-1357; LEU-1380; LEU-1486; MET-1526; ASP-1598; GLN-1640; CYS-1724; ASP-1799; ASP-1805; ASP-1838; ASP-1844; PRO-1940; ARG-1961; GLU-1961; SER-1977; ASN-2047; ARG-2060; GLN-2077; TYR-2137; TYR-2150 AND SER-2188</scope>
        <scope>REVIEW</scope>
    </reference>
    <reference key="51">
        <citation type="journal article" date="2014" name="BMC Med. Genet." volume="15" first="11" last="11">
            <title>Whole exome sequencing detects homozygosity for ABCA4 p.Arg602Trp missense mutation in a pediatric patient with rapidly progressive retinal dystrophy.</title>
            <authorList>
                <person name="Ortube M.C."/>
                <person name="Strom S.P."/>
                <person name="Nelson S.F."/>
                <person name="Nusinowitz S."/>
                <person name="Martinez A."/>
                <person name="Gorin M.B."/>
            </authorList>
            <dbReference type="PubMed" id="24444108"/>
            <dbReference type="DOI" id="10.1186/1471-2350-15-11"/>
        </citation>
        <scope>VARIANT STGD1 TRP-602</scope>
    </reference>
    <reference key="52">
        <citation type="journal article" date="2014" name="Br. J. Ophthalmol." volume="98" first="513" last="518">
            <title>Predictors of visual acuity and genotype-phenotype correlates in a cohort of patients with Stargardt disease.</title>
            <authorList>
                <person name="Miraldi Utz V."/>
                <person name="Coussa R.G."/>
                <person name="Marino M.J."/>
                <person name="Chappelow A.V."/>
                <person name="Pauer G.J."/>
                <person name="Hagstrom S.A."/>
                <person name="Traboulsi E.I."/>
            </authorList>
            <dbReference type="PubMed" id="24457364"/>
            <dbReference type="DOI" id="10.1136/bjophthalmol-2013-304270"/>
        </citation>
        <scope>VARIANTS STGD1 CYS-212; PRO-541; LEU-640; ASP-767; VAL-1038; CYS-1108; ARG-1408; GLN-1640; TRP-1640; ASP-1838; GLU-1961 AND HIS-2107</scope>
    </reference>
    <reference key="53">
        <citation type="journal article" date="2015" name="Hum. Mutat." volume="36" first="39" last="42">
            <title>An augmented ABCA4 screen targeting noncoding regions reveals a deep intronic founder variant in Belgian Stargardt patients.</title>
            <authorList>
                <person name="Bauwens M."/>
                <person name="De Zaeytijd J."/>
                <person name="Weisschuh N."/>
                <person name="Kohl S."/>
                <person name="Meire F."/>
                <person name="Dahan K."/>
                <person name="Depasse F."/>
                <person name="De Jaegere S."/>
                <person name="De Ravel T."/>
                <person name="De Rademaeker M."/>
                <person name="Loeys B."/>
                <person name="Coppieters F."/>
                <person name="Leroy B.P."/>
                <person name="De Baere E."/>
            </authorList>
            <dbReference type="PubMed" id="25346251"/>
            <dbReference type="DOI" id="10.1002/humu.22716"/>
        </citation>
        <scope>VARIANTS CORD3 CYS-440; GLY-643; HIS-1145; GLU-1203; GLU-1961; LEU-2050 AND ASN-2177</scope>
        <scope>VARIANTS STGD1 HIS-24; GLU-65; SER-247; 431-TRP--ASP-2273 DEL; PRO-541; ARG-607; HIS-653; ALA-863; 1029-GLN--ASP-2273 DEL; VAL-1038; GLN-1300; MET-1537; TRP-1640; PRO-1763; HIS-1898; GLU-1961; PHE-1970; PHE-2027; GLN-2030 AND ARG-2033</scope>
        <scope>VARIANTS RP19 MET-455 AND ILE-552</scope>
        <scope>VARIANT 681-ARG--ASP-2273 DEL</scope>
    </reference>
    <reference key="54">
        <citation type="journal article" date="2016" name="Invest. Ophthalmol. Vis. Sci." volume="57" first="145" last="152">
            <title>Screening of ABCA4 Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations.</title>
            <authorList>
                <person name="Jiang F."/>
                <person name="Pan Z."/>
                <person name="Xu K."/>
                <person name="Tian L."/>
                <person name="Xie Y."/>
                <person name="Zhang X."/>
                <person name="Chen J."/>
                <person name="Dong B."/>
                <person name="Li Y."/>
            </authorList>
            <dbReference type="PubMed" id="26780318"/>
            <dbReference type="DOI" id="10.1167/iovs.15-18190"/>
        </citation>
        <scope>VARIANTS STGD1 LYS-14; PRO-18; HIS-24; VAL-72; CYS-97; 185-GLN--ASP-2273 DEL; ARG-240; LEU-291; 326-TYR--ASP-2273 DEL; VAL-328; SER-345; THR-410; CYS-508; CYS-511; ARG-519; 533-GLN--ASP-2273 DEL; CYS-537; ARG-548; ARG-550; LEU-593; TRP-602; CYS-603; ARG-607; ASN-645; HIS-653; SER-754; 808-TYR--ASP-2273 DEL; VAL-816; SER-965; TYR-965; SER-973; MET-1019; GLY-1022; LYS-1036; LEU-1074; THR-1094; HIS-1108; LYS-1122; THR-1130; TRP-1140; SER-1159; HIS-1161; 1300-ARG--ASP-2273 DEL; ASN-1371; 1453-TYR--ASP-2273 DEL; LEU-1503; HIS-1511; MET-1526; MET-1537; ARG-1591; 1724-TRP--ASP-2273 DEL; VAL-1773; LEU-1776; LYS-1885; GLY-1921; MET-1921; ARG-1961; SER-1977; TYR-2017; THR-2023; 2030-ARG--ASP-2273 DEL; ARG-2032; TRP-2038; 2040-ARG--ASP-2273 DEL; GLN-2040; GLY-2042; THR-2064; GLU-2078; SER-2097; ARG-2150 AND SER-2188</scope>
        <scope>VARIANTS ARG-423; TYR-1102; THR-1209; MET-1428; MET-1572; 1618-TRP--ASP-2273 DEL; VAL-1623; GLN-1640; 1652-TYR--ASP-2273 DEL; ILE-1868 AND ILE-2255</scope>
        <scope>VARIANTS CORD3 53-GLU--ASP-2273 DEL; ARG-55; PRO-63; 107-ARG--ASP-2273 DEL; 218-GLN--ASP-2273 DEL; CYS-320; 339-TRP--ASP-2273 DEL; 605-TRP--ASP-2273 DEL; LYS-636; ARG-661; CYS-1183; CYS-1368; 1479-TRP--ASP-2273 DEL; 1650-GLU--ASP-2273 DEL; ILE-1882; SER-2043; HIS-2107 AND ASP-2146</scope>
    </reference>
    <reference key="55">
        <citation type="journal article" date="2018" name="Invest. Ophthalmol. Vis. Sci." volume="59" first="2305" last="2315">
            <title>Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease.</title>
            <authorList>
                <person name="Garces F."/>
                <person name="Jiang K."/>
                <person name="Molday L.L."/>
                <person name="Stoehr H."/>
                <person name="Weber B.H."/>
                <person name="Lyons C.J."/>
                <person name="Maberley D."/>
                <person name="Molday R.S."/>
            </authorList>
            <dbReference type="PubMed" id="29847635"/>
            <dbReference type="DOI" id="10.1167/iovs.17-23364"/>
        </citation>
        <scope>VARIANTS STGD1 ARG-72; PRO-541; VAL-1038; GLU-1091; THR-1357; PRO-1794 AND TRP-2077</scope>
        <scope>CHARACTERIZATION OF VARIANTS STGD1 ARG-72; LYS-448; PRO-541; VAL-1038; GLU-1091; THR-1357; PRO-1794; GLU-1961; PHE-2027 AND TRP-2077</scope>
        <scope>CHARACTERIZATION OF VARIANT RP19 ILE-552</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="56">
        <citation type="journal article" date="2018" name="J. Med. Genet." volume="55" first="705" last="712">
            <title>Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa.</title>
            <authorList>
                <person name="de Bruijn S.E."/>
                <person name="Verbakel S.K."/>
                <person name="de Vrieze E."/>
                <person name="Kremer H."/>
                <person name="Cremers F.P.M."/>
                <person name="Hoyng C.B."/>
                <person name="van den Born L.I."/>
                <person name="Roosing S."/>
            </authorList>
            <dbReference type="PubMed" id="30120214"/>
            <dbReference type="DOI" id="10.1136/jmedgenet-2018-105364"/>
        </citation>
        <scope>VARIANT ILE-1868</scope>
    </reference>
    <reference key="57">
        <citation type="journal article" date="2020" name="Int. J. Mol. Sci." volume="22" first="0" last="0">
            <title>Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration.</title>
            <authorList>
                <person name="Garces F.A."/>
                <person name="Scortecci J.F."/>
                <person name="Molday R.S."/>
            </authorList>
            <dbReference type="PubMed" id="33375396"/>
            <dbReference type="DOI" id="10.3390/ijms22010185"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS STGD1 CYS-653; HIS-653; ARG-661; SER-686; VAL-690; MET-716; TYR-764; ARG-765; ASN-765; ASP-767; PRO-797; GLU-818; ARG-821; THR-824; ARG-840; ALA-849; ASP-851; THR-854; LEU-1380; LYS-1399; ASN-1696; GLU-1703; LYS-1703; LEU-1705; VAL-1773; ASP-1794; PRO-1794; ASP-1805; ASN-1838; ASP-1838; TYR-1838; TRP-1843 AND HIS-1898</scope>
        <scope>CHARACTERIZATION OF VARIANTS HIS-846; GLU-1773; ILE-1868 AND CYS-1898</scope>
        <scope>MUTAGENESIS OF GLN-1703 AND HIS-1838</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 33 34 36 39 44 47 48 50">Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes, where 11-cis-retinylidene-phosphatidylethanolamine is then isomerized to its all-trans isomer and reduced by RDH8 to produce all-trans-retinol. This transport activity ensures that all-trans-retinal generated from photoexcitation and 11-cis-retinal not needed for the regeneration of rhodopsin and cone opsins are effectively cleared from the photoreceptors, therefore preventing their accumulation and the formation of toxic bisretinoid (PubMed:10075733, PubMed:20404325, PubMed:22735453, PubMed:23144455, PubMed:24097981, PubMed:29847635, PubMed:33375396). Displays ATPase activity in vitro in absence of retinal substrate (PubMed:33605212, PubMed:39128720, PubMed:29847635, PubMed:33375396). May display GTPase activity that is strongly influenced by the lipid environment and the presence of retinoid compounds (PubMed:22735453). Binds the unprotonated form of N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP, and ATP binding and hydrolysis induce a protein conformational change that causes N-retinylidene-phosphatidylethanolamine release (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="34">
            <text>an N-all-trans-retinylidenephosphatidylethanolamine(out) + ATP + H2O = an N-all-trans-retinylidenephosphatidylethanolamine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67188"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167884"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="60">
            <dbReference type="Rhea" id="RHEA:67189"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="39">
            <text>ATP + H2O + phospholipidSide 1 = ADP + phosphate + phospholipidSide 2.</text>
            <dbReference type="EC" id="7.6.2.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="34 39">
            <text>a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66132"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:64612"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="61">
            <dbReference type="Rhea" id="RHEA:66133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-11-cis-retinylidenephosphatidylethanolamine(out) + ATP + H2O = N-11-cis-retinylidenephosphatidylethanolamine(in) + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:67192"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:167887"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:67193"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="44 47 48 50">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="39">ATPase activity is decreased by cholesterol and ceramide. Phospholipids translocase activity is highly reduced by berylium fluoride and aluminum floride. N-ethylmaleimide inhibits phospholipid translocase activity.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="48">80 uM for ATP (at 28 degrees Celsius)</KM>
            <KM evidence="50">240 uM for ATP (at 37 degrees Celsius)</KM>
            <KM evidence="49">50 uM for ATP (in the presence of phosphatidylethanolamine at 37 degrees Celsius)</KM>
            <KM evidence="49">69 uM for ATP (in the presence of all-trans retinal and phosphatidylethanolamine at 37 degrees Celsius)</KM>
            <Vmax evidence="48">112.5 nmol/min/mg enzyme (for basal ATP hydrolysis at 28 degrees Celsius)</Vmax>
            <Vmax evidence="50">136.0 nmol/min/mg enzyme (for basal ATP hydrolysis at 37 degrees Celsius)</Vmax>
            <Vmax evidence="49">75.0 nmol/min/mg enzyme (for ATP hydrolysis in the presence of phosphatidylethanolamine at 37 degrees Celsius)</Vmax>
            <Vmax evidence="49">140.0 nmol/min/mg enzyme (for N-Ret-PE-stimulated ATP hydrolysis in the presence of all-trans retinal and phosphatidylethanolamine at 37 degrees Celsius)</Vmax>
        </kinetics>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="39">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="44 47">Cytoplasmic vesicle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Cilium</location>
            <location evidence="1">Photoreceptor outer segment</location>
        </subcellularLocation>
        <text evidence="1">Localized to the rim and incisures of rod outer segments disks.</text>
    </comment>
    <comment type="tissue specificity">
        <text>Retinal-specific. Seems to be exclusively found in the rims of rod photoreceptor cells.</text>
    </comment>
    <comment type="domain">
        <text evidence="33 36">The second extracellular domain (ECD2, aa 1395-1680) undergoes conformational change in response to its specific interaction with its substrate all-trans-retinal (PubMed:20404325). Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal (PubMed:23144455).</text>
    </comment>
    <comment type="PTM">
        <text evidence="16">Proteolytic cleavage by trypsin leads to a 120-kDa N-terminal fragment and a 115-kDa C-terminal fragment that are linked through disulfide bonds.</text>
    </comment>
    <comment type="PTM">
        <text evidence="16">N-glycosylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylation is independent of light exposure and modulates ATPase activity.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 9 10 11 14 17 21 22 23 26 28 29 30 31 33 34 35 36 37 38 39 40 41 42 43 44 47 51 52 53 54 55 56">
        <disease id="DI-01084">
            <name>Stargardt disease 1</name>
            <acronym>STGD1</acronym>
            <description>An autosomal recessive form of Stargardt disease, a retinal degenerative disease characterized by macular dystrophy, progressive bilateral atrophy of the foveal retinal pigment epithelium, and accumulation of fluorescent flecks around the macula and/or in the central and near-peripheral areas of the retina. STGD1 patients typically lose central vision in their first or second decade of life.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 19 21 55">
        <disease id="DI-01640">
            <name>Fundus flavimaculatus</name>
            <acronym>FFM</acronym>
            <description>Autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course.</description>
            <dbReference type="MIM" id="248200"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="52">
        <disease id="DI-00056">
            <name>Macular degeneration, age-related, 2</name>
            <acronym>ARMD2</acronym>
            <description>A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.</description>
            <dbReference type="MIM" id="153800"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 13 21 22 30 42 43">
        <disease id="DI-00319">
            <name>Cone-rod dystrophy 3</name>
            <acronym>CORD3</acronym>
            <description>An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.</description>
            <dbReference type="MIM" id="604116"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 14 30 42 44">
        <disease id="DI-00985">
            <name>Retinitis pigmentosa 19</name>
            <acronym>RP19</acronym>
            <description>A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP19 is characterized by choroidal atrophy.</description>
            <dbReference type="MIM" id="601718"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="59">Belongs to the ABC transporter superfamily. ABCA family.</text>
    </comment>
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        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAE06122" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="ABCMdb">
        <link uri="http://abcm2.hegelab.org/search"/>
        <text>Database for mutations in ABC proteins</text>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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            <position position="1979"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>3</label>
            <note>in ATP-bound protein</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="48 62 65 68">
        <location>
            <position position="1980"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="48 65">
        <location>
            <position position="2073"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="site" description="Cleavage; by trypsin" evidence="1">
        <location>
            <position position="1309"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="901"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="1185"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="1313"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="1317"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="444"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 66 67">
        <location>
            <position position="504"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="1469"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="1529"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="1588"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 48 49 64 65 66 67">
        <location>
            <position position="1662"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="48 49 64 65 66 67">
        <location>
            <begin position="54"/>
            <end position="81"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="48 49 64 65 66 67">
        <location>
            <begin position="75"/>
            <end position="324"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="48 49 64 65 66 67">
        <location>
            <begin position="370"/>
            <end position="519"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain" evidence="48 49 64 65 66 67">
        <location>
            <begin position="641"/>
            <end position="1490"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="48 64 65">
        <location>
            <begin position="1444"/>
            <end position="1455"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="48 49 64 65 66 67">
        <location>
            <begin position="1488"/>
            <end position="1502"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012493" description="In FFM; dbSNP:rs62645946." evidence="55">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="11"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012494" description="In STGD1." evidence="22">
        <location>
            <begin position="13"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084833" description="In STGD1; uncertain significance." evidence="43">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="14"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084834" description="In STGD1; uncertain significance; dbSNP:rs868543294." evidence="43">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008398" description="In STGD1; dbSNP:rs121909205." evidence="26 37 38 54 55">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084835" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="21"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008399" description="In STGD1; uncertain significance; dbSNP:rs62645958." evidence="37 42 43">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084836" description="In CORD3; uncertain significance; dbSNP:rs764744217." evidence="43">
        <location>
            <begin position="53"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008400" description="In STGD1; dbSNP:rs150774447." evidence="8 9 22 35">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084837" description="In CORD3; uncertain significance." evidence="43">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012495" description="In STGD1; dbSNP:rs61748524." evidence="22">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012496" description="In STGD1." evidence="14">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012497" description="In STGD1; dbSNP:rs61751411." evidence="14">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008492" description="In STGD1; dbSNP:rs55732384." evidence="7 22">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084838" description="In CORD3; uncertain significance." evidence="43">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008401" description="In STGD1 and CORD3; dbSNP:rs62654395." evidence="13 14 22 42">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012498" description="In STGD1; dbSNP:rs62654397." evidence="14 31">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012499" description="In STGD1; dbSNP:rs62654397." evidence="56">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012500" description="In STGD1; pathogenic; does not affect intracellular vesicle localization; does not affect solubility; significantly reduces N-all-trans-retinylidenephosphatidylethanolamine binding; drastically reduces basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs61751412." evidence="14 44">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084839" description="In STGD1; uncertain significance; dbSNP:rs2101162548." evidence="43">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008402" description="In STGD1; dbSNP:rs61748526." evidence="56">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012501" description="In STGD1; dbSNP:rs61748527." evidence="22">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085009" description="In STGD1; uncertain significance." evidence="37">
        <location>
            <begin position="89"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008403" description="In STGD1; dbSNP:rs61748529." evidence="9">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008404" description="In STGD1; uncertain significance; dbSNP:rs61748529." evidence="9 31">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084840" description="In STGD1; uncertain significance; dbSNP:rs886039297." evidence="26 31">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084841" description="In STGD1; uncertain significance; dbSNP:rs755691060." evidence="43">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012502" description="In STGD1; likely pathogenic; decreased ATPase activity; decreased phospholipid translocase activity; dbSNP:rs61748530." evidence="17 39">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084842" description="In CORD3; uncertain significance; dbSNP:rs765429911." evidence="43">
        <location>
            <begin position="107"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084843" description="In STGD1; uncertain significance; dbSNP:rs1662508600." evidence="26">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084844" description="In STGD1; uncertain significance; dbSNP:rs62646860." evidence="26">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012503" description="In STGD1; dbSNP:rs62646862." evidence="14 26 35">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090218" description="In STGD1; uncertain significance." evidence="38">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012504" description="In STGD1 and RP19; dbSNP:rs62646863." evidence="9 29 30">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084845" description="In STGD1; uncertain significance; dbSNP:rs61748532." evidence="31">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084846" description="In STGD1; uncertain significance." evidence="35">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084847" description="In STGD1; uncertain significance." evidence="35">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084848" description="In STGD1; uncertain significance." evidence="43">
        <location>
            <begin position="185"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012505" description="In STGD1; dbSNP:rs281865397." evidence="22">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="190"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008405" description="In STGD1; dbSNP:rs61748535." evidence="17">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012506" description="In STGD1; uncertain significance; reduced basal and retinal-stimulated ATP-hydrolysis; dbSNP:rs61748536." evidence="7 15">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008406" description="In STGD1 and CORD3; likely pathogenic; common mutation in southern Europe; dbSNP:rs61750200." evidence="10 13 14 21 29 31 35 37 38 41 54 55">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012507" description="In dbSNP:rs6657239." evidence="10 14 19 20 22 26">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084849" description="In CORD3; uncertain significance." evidence="43">
        <location>
            <begin position="218"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084850" description="Found in a patient with chorioretinal atrophy; uncertain significance." evidence="35">
        <location>
            <begin position="219"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012508" description="In STGD1; dbSNP:rs61748538." evidence="17">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="220"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084851" description="In STGD1; uncertain significance; dbSNP:rs147619585." evidence="26">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="223"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035736" description="In a breast cancer sample; somatic mutation; dbSNP:rs373540612." evidence="27">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012509" description="In STGD1; dbSNP:rs1057518767." evidence="14 26">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="230"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084852" description="In STGD1; uncertain significance; dbSNP:rs1553195472." evidence="43">
        <original>I</original>
        <variation>R</variation>
        <location>
            <position position="240"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085010" description="In STGD1; uncertain significance." evidence="37">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012510" description="In STGD1; dbSNP:rs62646864." evidence="22">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084853" description="In STGD1; uncertain significance." evidence="26">
        <location>
            <begin position="245"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084854" description="In STGD1; uncertain significance; dbSNP:rs1662207986." evidence="26">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="246"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012511" description="In STGD1; dbSNP:rs62645950." evidence="14 42">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008407" description="In STGD1; dbSNP:rs62646865." evidence="56">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085011" description="In STGD1; uncertain significance; dbSNP:rs781716640." evidence="37">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090219" description="In STGD1; uncertain significance." evidence="38">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084855" description="In STGD1; uncertain significance; dbSNP:rs190540405." evidence="43">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008408" description="In STGD1; dbSNP:rs61748544." evidence="7">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012512" description="In STGD1; dbSNP:rs61748545." evidence="22">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084856" description="In CORD3; uncertain significance." evidence="43">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084857" description="In STGD1; uncertain significance; dbSNP:rs747540967." evidence="43">
        <location>
            <begin position="326"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012513" description="In STGD1; dbSNP:rs61751419." evidence="14 43">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012514" description="In STGD1; dbSNP:rs61748546." evidence="17">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008409" description="In STGD1; dbSNP:rs61748547." evidence="56">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084858" description="In CORD3; uncertain significance." evidence="43">
        <location>
            <begin position="339"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012515" description="In FFM; loss of N-Ret-PE-stimulated ATPase activity and no effect on basal activity; decreased N-retinylidene-phosphatidylethanolamine flippase activity; 2-fold decreased affinity for N-all-trans-retinylidenephosphatidylethanolamine compared to wild-type values; dbSNP:rs61751420." evidence="19 49">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="339"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008410" description="In STGD1; dbSNP:rs61748548." evidence="11">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="340"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084859" description="In STGD1; uncertain significance; dbSNP:rs1417184535." evidence="43">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012516" description="In STGD1; dbSNP:rs61748549." evidence="29">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008411" description="In STGD1 and CORD3; dbSNP:rs61751264." evidence="9">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084860" description="In STGD1; uncertain significance." evidence="43">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="410"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084861" description="In STGD1; uncertain significance; dbSNP:rs1661605073." evidence="31">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084862" description="In STGD1; uncertain significance; dbSNP:rs794726979." evidence="35">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012517" description="In dbSNP:rs3112831." evidence="14 19 20 22 24 26 43">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="423"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085012" description="In STGD1 and RP19; uncertain significance; dbSNP:rs1661603358." evidence="9">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="424"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084863" description="In STGD1; uncertain significance." evidence="42">
        <location>
            <begin position="431"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084864" description="In CORD3; uncertain significance; dbSNP:rs770439859." evidence="42">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="440"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008412" description="In STGD1; dbSNP:rs61748552." evidence="9">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090239" description="In STGD1; likely pathogenic; no effect on solubility; no effect on localization to cytoplasmic vesicle; decreased basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs777078540." evidence="44">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084865" description="In RP19; uncertain significance; dbSNP:rs764170051." evidence="42">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="455"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008413" description="In ARMD2 and STGD1; uncertain significance; ATP-binding capacity and retinal stimulation as in wild-type; dbSNP:rs1800548." evidence="14 15 35 52">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084866" description="In STGD1; uncertain significance; dbSNP:rs1661575300." evidence="26">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084867" description="In STGD1; uncertain significance; dbSNP:rs138157885." evidence="43">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="508"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084868" description="In STGD1; uncertain significance; dbSNP:rs752786160." evidence="43">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084869" description="In STGD1; uncertain significance; dbSNP:rs1224959251." evidence="43">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="519"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008414" description="In STGD1; dbSNP:rs62646868." evidence="56">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="523"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012518" description="In STGD1; dbSNP:rs1661181033." evidence="22">
        <original>F</original>
        <variation>C</variation>
        <location>
            <position position="525"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084870" description="In STGD1; uncertain significance." evidence="43">
        <location>
            <begin position="533"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012519" description="In STGD1; dbSNP:rs61748556." evidence="22 38 43">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="537"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008415" description="In STGD1, FFM and CORD3; pathogenic; does not affect solubility; does not affect intracellular vesicle localization; significantly reduces N-all-trans-retinylidenephosphatidylethanolamine binding; drastically reduces basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs61751392." evidence="7 13 14 15 22 26 31 38 41 42 44 55">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="541"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084871" description="In STGD1; uncertain significance." evidence="43">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="548"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012520" description="In STGD1; dbSNP:rs61748557." evidence="22">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="549"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012521" description="In STGD1; dbSNP:rs61748558." evidence="22 26 29 43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="550"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012522" description="In RP19; benign; no effect on N-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect intracellular vesicle localization; does not affect basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs145525174." evidence="14 30 42 44">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="552"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084872" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="572"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008416" description="In STGD1; dbSNP:rs61748559." evidence="29">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="572"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008417" description="In STGD1; dbSNP:rs61748559." evidence="11 14 26">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="572"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084873" description="Found in a patient with pattern dystrophy; uncertain significance; dbSNP:rs374224955." evidence="35">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="576"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084874" description="In STGD1; uncertain significance." evidence="43">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="593"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012523" description="In STGD1; dbSNP:rs61749410." evidence="22">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="602"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008418" description="In STGD1; dbSNP:rs61749409." evidence="9 29 30 37 38 40 43">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="602"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084875" description="In STGD1; uncertain significance." evidence="43">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="603"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084876" description="In CORD3; uncertain significance." evidence="43">
        <location>
            <begin position="605"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012524" description="In STGD1; dbSNP:rs61749412." evidence="14 22 29 42 43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="607"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012525" description="In STGD1; dbSNP:rs61749412." evidence="17">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="607"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008419" description="In STGD1; likely pathogenic; dbSNP:rs61752398." evidence="56">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="608"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090208" description="In STGD1; likely pathogenic; highly decreased ATPase activity; highly decreased phospholipid translocase activity; dbSNP:rs61752398." evidence="39">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="608"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090220" description="In STGD1; dbSNP:rs760735952." evidence="38">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="611"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084877" description="In STGD1; uncertain significance; dbSNP:rs1557787473." evidence="31">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="616"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012526" description="In STGD1; dbSNP:rs61749414." evidence="14">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="635"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012527" description="In STGD1; dbSNP:rs61752400." evidence="55">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="636"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084878" description="In CORD3; uncertain significance." evidence="43">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="636"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084879" description="In STGD1; uncertain significance." evidence="26">
        <location>
            <begin position="639"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085013" description="In STGD1; uncertain significance; dbSNP:rs760790294." evidence="41">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="640"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084880" description="In STGD1; uncertain significance; dbSNP:rs61749416." evidence="26">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="641"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008420" description="In CORD3; uncertain significance; dbSNP:rs61754024." evidence="42 52">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="643"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012528" description="In STGD1; dbSNP:rs61749417." evidence="22 35">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="643"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008421" description="In STGD1; dbSNP:rs61749418." evidence="43">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="645"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012529" description="In STGD1; likely pathogenic; severely decreased, if any, N-Ret-PE-stimulated ATPase activity although basal activity is unchanged; decreased N-retinylidene-phosphatidylethanolamine flippase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle; dbSNP:rs61749420." evidence="14 26 29 31 35 38 47 49">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="653"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084881" description="In STGD1; likely pathogenic; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs141823837." evidence="42 43 47">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="653"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084882" description="In CORD3; pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; severe decrease of basal and N-Ret-PE-stimulated ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding." evidence="43 47">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="661"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084883" description="Found in a patient with macular dystrophy; uncertain significance." evidence="42">
        <location>
            <begin position="681"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012530" description="In STGD1; pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; severe decrease of basal and N-Ret-PE-stimulated ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61752402." evidence="21 38 47">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="686"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084884" description="In STGD1; pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity below 50% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs942734318." evidence="26 31 47">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="690"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084885" description="In STGD1; uncertain significance." evidence="26 31">
        <location>
            <begin position="700"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012531" description="In STGD1; uncertain significance; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; modest decrease of N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749426." evidence="17 47">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="716"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014703" description="In dbSNP:rs1801369.">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="752"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084886" description="In STGD1; uncertain significance." evidence="43">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="754"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067427" description="In STGD1; dbSNP:rs1660993194." evidence="30 38">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="762"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012532" description="In STGD1; likely pathogenic; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; modest decrease of N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749428." evidence="14 17 47">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="764"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012534" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity below 50% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749429." evidence="17 47">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="765"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012533" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; severe decrease of basal and N-Ret-PE-stimulated ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61752404." evidence="14 47">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="765"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012535" description="In STGD1; pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity below 50% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61751395." evidence="10 22 26 29 31 41 47">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="767"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085014" description="In STGD1; uncertain significance." evidence="9">
        <location>
            <begin position="779"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084887" description="In STGD1; uncertain significance." evidence="35">
        <location>
            <begin position="782"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012536" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-induced ATPase activity to 20-30% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749432." evidence="22 47">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="797"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084888" description="In STGD1; uncertain significance." evidence="43">
        <location>
            <begin position="808"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084889" description="In STGD1; uncertain significance." evidence="43">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="816"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008422" description="In STGD1; pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61750202." evidence="37 47 51">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="818"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008423" description="In STGD1; pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity to 50-60% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749433." evidence="22 26 31 47 56">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="821"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012537" description="In STGD1; likely pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity to 60-70% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs1660942697." evidence="22 47">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="824"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084890" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity to 20-40% of wild-type values; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding." evidence="31 47">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="840"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008493" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61754027." evidence="47 51 52 56">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="846"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012538" description="In STGD1; uncertain significance; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; decreases N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749435." evidence="7 47">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="849"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008424" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal ATPase activity below 50%; severe decrease of N-Ret-PE-induced ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749436." evidence="15 47 56">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="851"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012539" description="In STGD1; uncertain significance; does not affect solubility; does not affect location in cytoplasmic vesicle; modest decrease of basal and N-Ret-PE-stimulated ATPase activity; modest decrease of N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61749437." evidence="17 47">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="854"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008425" description="In STGD1, FFM and CORD3; also found in a patient with bull's eye maculopathy; mild alteration probably leading to disease phenotype only in combination with a more severe allele; frequent mutation in northern Europe in linkage disequilibrium with the polymorphic variant Q-943; severely decreased basal and N-Ret-PE-stimulated ATPase activity; significantly reduces N-retinylidene-phosphatidylethanolamine transport; does not affect N-retinylidene-phosphatidylethanolamine binding; significantly attenuates 11-cis-retinal binding; significantly reduces phosphatidylethanolamine flippase activity; dbSNP:rs76157638." evidence="8 9 11 13 19 22 26 34 35 36 42 51 52">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="863"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012541" description="In STGD1; dbSNP:rs62642570." evidence="17">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="873"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084891" description="In STGD1; uncertain significance." evidence="26">
        <location>
            <begin position="876"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012542" description="In STGD1; dbSNP:rs61749440." evidence="10 26 29">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="897"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008426" description="In dbSNP:rs61754030." evidence="14 29">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="901"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012543" evidence="14">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="914"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008427" description="In STGD1; dbSNP:rs58331765." evidence="29 30 31 38 51">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="931"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012544" description="In STGD1; dbSNP:rs61749444." evidence="22">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="935"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008428" description="Risk factor for STGD1; risk factor for ARMD2; decreases 11-cis-Retinal binding affinity by 100-fold; dbSNP:rs1801581." evidence="9 11 14 19 21 22 23 26 35 36 37 51 52 57">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="943"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012545" description="In STGD1 and FFM; dbSNP:rs61749446." evidence="19 22">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="943"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084892" description="In STGD1; uncertain significance; dbSNP:rs61749447." evidence="26">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="954"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008429" description="In STGD1; dbSNP:rs61749448." evidence="6">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="957"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012546" description="In STGD1; likely pathogenic; highly decreased ATPase activity; highly decreased phospholipid translocase activity; dbSNP:rs61752409." evidence="14 39">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="959"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008430" description="In STGD1; pathogenic; severely decreased basal and N-Ret-PE-stimulated ATPase activity; reduces N-retinylidene-phosphatidylethanolamine transport; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; decreased phospholipid transport; decreased phosphatidylethanolamine flippase activity; dbSNP:rs201471607." evidence="11 15 26 29 31 34 37 39 43">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084893" description="In STGD1; likely pathogenic; results in minimal, if any, basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity; dbSNP:rs61749449." evidence="43 50">
        <original>N</original>
        <variation>Y</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084894" description="In STGD1; uncertain significance; dbSNP:rs1570377849." evidence="31">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="970"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012547" description="In STGD1; pathogenic; loss of basal and all-trans-retinal stimulated ATPase activity; dbSNP:rs61749450." evidence="15 17">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="971"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012548" description="In STGD1; uncertain significance; dbSNP:rs61749451." evidence="23">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="972"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084895" description="In STGD1; uncertain significance." evidence="43">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="973"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012549" description="In STGD1; dbSNP:rs281865400." evidence="7">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="974"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084896" description="In STGD1; uncertain significance; dbSNP:rs1660625648." evidence="31">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="977"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008431" description="In STGD1; dbSNP:rs61749452." evidence="6">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="978"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084897" description="In STGD1; uncertain significance; dbSNP:rs61749453." evidence="26 31">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="978"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012550" description="In STGD1; dbSNP:rs61749454." evidence="22 35 38">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="989"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012551" description="In FFM and STGD1; dbSNP:rs61749455." evidence="19 35">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="991"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012552" description="In STGD1; dbSNP:rs61749456." evidence="37">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="1014"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012553" description="In STGD1; dbSNP:rs61749457." evidence="17">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="1019"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012554" description="In STGD1; dbSNP:rs201855602." evidence="29 30 31 35 38 43 55">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1019"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084898" description="In STGD1; uncertain significance." evidence="43">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="1022"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012555" description="In STGD1; uncertain significance; dbSNP:rs61749459." evidence="26 35">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1022"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090221" description="In STGD1; uncertain significance; dbSNP:rs121909204." evidence="51">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="1028"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084899" description="In STGD1; uncertain significance." evidence="42">
        <location>
            <begin position="1029"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012556" description="In STGD1; dbSNP:rs61750060." evidence="17">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="1031"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008432" description="In STGD1; dbSNP:rs61750061." evidence="14 43">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1036"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008433" description="In STGD1, FFM and CORD3; pathogenic; common variant; decreased solubility; does not affect intracellular vesicle localization; significantly reduces N-all-trans-retinylidenephosphatidylethanolamine binding; severely reduces basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs61751374." evidence="7 10 11 13 14 15 19 22 26 31 41 42 44 55 56">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="1038"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084900" description="In STGD1; uncertain significance; dbSNP:rs61750062." evidence="26">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1050"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012557" description="In STGD1; dbSNP:rs61752412." evidence="21 31">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1055"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012558" description="In STGD1; dbSNP:rs61752413." evidence="14">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1063"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008434" description="In STGD1; likely pathogenic; dbSNP:rs61750065." evidence="15 56">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="1071"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008435" description="In STGD1; dbSNP:rs1660532719." evidence="51 56">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="1072"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084901" description="In STGD1; uncertain significance." evidence="43">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="1074"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084902" description="In STGD1; uncertain significance; dbSNP:rs1660532440." evidence="31">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1078"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012559" description="In STGD1; decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity; dbSNP:rs61752416." evidence="14 50">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="1087"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008436" description="In STGD1; dbSNP:rs61751398." evidence="10 26 31 51">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1087"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012560" description="In FFM and STGD1; likely pathogenic; decreased solubility; does not affect intracellular vesicle localization; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; decreased basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs61752417." evidence="44 55">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1091"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090222" description="In STGD1." evidence="38">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="1094"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084903" description="In STGD1; uncertain significance." evidence="43">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="1094"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090223" description="In STGD1; dbSNP:rs763267492." evidence="38">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="1096"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012561" description="In STGD1." evidence="14">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1097"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084904" description="In STGD1; uncertain significance; dbSNP:rs61750118." evidence="35">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="1097"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084905" description="In STGD1; uncertain significance; dbSNP:rs756840095." evidence="26 31 38">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1098"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084906" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="1099"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084907" description="In STGD1; uncertain significance; dbSNP:rs61750119." evidence="26">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1099"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084908" description="In dbSNP:rs138641544." evidence="43">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="1102"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012562" description="In STGD1 and FFM; dbSNP:rs61750120." evidence="7 14 19 21 22 26 31 35 41 55">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012563" description="In STGD1; dbSNP:rs61750121." evidence="26 29 30 38 43">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012564" description="In STGD1; dbSNP:rs61750121." evidence="22">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="1108"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008437" description="In STGD1; dbSNP:rs61750122." evidence="6">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="1112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008438" description="In STGD1 and CORD3; dbSNP:rs61751399." evidence="13 22 35 38 43">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1122"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090224" description="In STGD1; uncertain significance; dbSNP:rs1570370929." evidence="38">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1127"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012565" description="In STGD1; may predispose to develop retinal toxicity after treatment with chloroquine and hydroxychloroquine; dbSNP:rs779426136." evidence="20 56">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008439" description="In STGD1, CORD3 and RP19; pathogenic; also found in patients with fundus flavimaculatus; dbSNP:rs1801269." evidence="26 29 30 35 37 38 52 56">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="1129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084909" description="In STGD1; uncertain significance; dbSNP:rs1064793010." evidence="43">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1130"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084910" description="In STGD1; uncertain significance; dbSNP:rs2101048569." evidence="43">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="1140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084911" description="In CORD3; uncertain significance." evidence="42">
        <original>L</original>
        <variation>H</variation>
        <location>
            <position position="1145"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012566" evidence="19">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="1148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084912" description="In STGD1; uncertain significance; dbSNP:rs1340749727." evidence="43">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="1159"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084913" description="In STGD1; uncertain significance; dbSNP:rs768278935." evidence="43">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1161"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084914" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="1177"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084915" description="In CORD3; uncertain significance; dbSNP:rs75267647." evidence="43">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="1183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008440" description="In STGD1; may predispose to develop retinal toxicity after treatment with chloroquine and hydroxychloroquine; dbSNP:rs61750126." evidence="20 22 35">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="1201"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084916" description="In STGD1." evidence="26">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084917" description="In CORD3; uncertain significance; dbSNP:rs146786552." evidence="42">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084918" description="In STGD1; uncertain significance; dbSNP:rs1064793011." evidence="26">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008441" description="In STGD1; uncertain significance; dbSNP:rs61750127." evidence="26">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="1204"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084919" description="In dbSNP:rs76258939." evidence="43">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="1209"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012567" description="In STGD1; dbSNP:rs61750128." evidence="17">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1250"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012568" description="In FFM; uncertain significance; dbSNP:rs61752424." evidence="21">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1253"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084920" description="In STGD1; uncertain significance; dbSNP:rs61752427." evidence="26 43">
        <location>
            <begin position="1300"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012569" description="In STGD1; uncertain significance; dbSNP:rs61750129." evidence="22 26 42">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008442" description="In dbSNP:rs61754041." evidence="17">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="1314"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084921" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="1332"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090225" description="In STGD1; likely pathogenic; decreased solubility; loss of intracellular vesicle localization; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; decreased basal and N-Ret-PE-stimulated ATPase activity; dbSNP:rs754899711." evidence="38 44">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="1357"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084922" description="In CORD3; uncertain significance; dbSNP:rs1183074086." evidence="43">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1368"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084923" description="In STGD1; uncertain significance." evidence="43">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="1371"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008443" description="In STGD1; pathogenic; also found in a patient with chorioretinal atrophy; decreased solubility; loss of cytoplasmic vesicle localization; decreased basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61750130." evidence="14 22 26 29 31 35 37 38 47">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012570" description="In STGD1; dbSNP:rs61750131." evidence="22">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1388"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012571" description="In STGD1; likely pathogenic; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs62642573." evidence="10 14 47">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1399"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008444" description="In STGD1; dbSNP:rs61750133." evidence="56">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="1406"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084924" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="1408"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008445" description="In STGD1; likely pathogenic; does not affect secondary structure; decreased all-trans-retinal binding; dbSNP:rs61750134." evidence="7 17 33 56">
        <original>W</original>
        <variation>L</variation>
        <location>
            <position position="1408"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008446" description="In STGD1; likely pathogenic; reduced retinal-stimulated ATP hydrolysis; dbSNP:rs61750135." evidence="15 22 41">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="1408"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085015" description="In STGD1; uncertain significance." evidence="37">
        <location>
            <position position="1416"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008447" description="In dbSNP:rs1800549." evidence="43 52">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1428"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008448" description="In STGD1; dbSNP:rs61752432." evidence="9">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="1429"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012572" description="In STGD1; dbSNP:rs1660169151." evidence="14">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1430"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008449" description="In STGD1, CORD3 and RP19; dbSNP:rs56357060." evidence="29 30 31">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="1433"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008450" description="In STGD1; dbSNP:rs61750140." evidence="56">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1439"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008451" description="In STGD1; dbSNP:rs61750141." evidence="56">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="1440"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012573" description="In STGD1; dbSNP:rs61752433." evidence="14">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="1440"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084925" description="In STGD1; uncertain significance; dbSNP:rs762150575." evidence="35">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="1442"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012574" description="In STGD1; likely pathogenic; loss of the majority of alpha-helical secondary structure; loss of all-trans-retinal binding; dbSNP:rs61750142." evidence="14 33 37">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1443"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084926" description="In STGD1; uncertain significance." evidence="43">
        <location>
            <begin position="1453"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084927" description="In STGD1; uncertain significance." evidence="31">
        <location>
            <begin position="1461"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084928" description="In STGD1 and CORD3; uncertain significance; dbSNP:rs61752434." evidence="31 43">
        <location>
            <begin position="1479"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084929" description="In STGD1; uncertain significance; dbSNP:rs1660139125." evidence="31">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="1484"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008452" description="In STGD1; dbSNP:rs61750145." evidence="14 22 29 30 35 38">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1486"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012575" description="In STGD1; dbSNP:rs61750147." evidence="17">
        <original>C</original>
        <variation>F</variation>
        <location>
            <position position="1488"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008453" description="In STGD1 and FFM; pathogenic; also found in a patient with chorioretinal atrophy; reduced retinal-stimulated ATP hydrolysis; does not affect secondary structure; decreased all-trans-retinal binding; dbSNP:rs61750146." evidence="7 15 19 22 33 35 56">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="1488"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012576" description="In STGD1; dbSNP:rs61750147." evidence="14">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="1488"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008454" description="In STGD1 and CORD3; reduced retinal-stimulated ATP hydrolysis; dbSNP:rs61751402." evidence="13 15 22 26 29 35">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="1490"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084930" description="In STGD1; uncertain significance." evidence="43">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1503"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012577" description="In FFM; dbSNP:rs1444784969." evidence="55">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="1508"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084931" description="In STGD1; uncertain significance; dbSNP:rs886046564." evidence="43">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="1511"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084932" description="In STGD1; uncertain significance; dbSNP:rs61750150." evidence="26">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="1512"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012578" description="In STGD1; dbSNP:rs281865402." evidence="17">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="1513"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008455" description="In ARMD2; dbSNP:rs1800550." evidence="52">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="1517"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012579" description="In STGD1; dbSNP:rs61750151." evidence="17">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1525"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008456" description="In STGD1; likely pathogenic; also found in a patient with chorioretinal atrophy; reduced retinal-stimulated ATP hydrolysis; dbSNP:rs61750152." evidence="15 22 26 31 35 38 43">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1526"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008457" description="In STGD1; dbSNP:rs62642574." evidence="22">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="1532"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012580" description="In STGD1; likely pathogenic; moderately decreased ATPase activity; moderately decreased phospholipid translocase activity; dbSNP:rs62642575." evidence="14 39 42 43">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1537"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085016" description="In STGD1; uncertain significance." evidence="37">
        <location>
            <position position="1551"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085017" description="In STGD1; uncertain significance; dbSNP:rs1385119665." evidence="37">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="1556"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084933" description="Found in a patient with chorioretinal atrophy; uncertain significance; dbSNP:rs1401716074." evidence="35">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="1557"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008458" description="In STGD1, FFM and ARMD2; uncertain significance; dbSNP:rs1762111." evidence="14 19 22 35 52">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1562"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084934" description="In dbSNP:rs185093512." evidence="43">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1572"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008459" description="In ARMD2; dbSNP:rs1800551." evidence="52">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1578"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084935" description="In STGD1; uncertain significance; dbSNP:rs113106943." evidence="43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1591"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012581" description="In CORD3 and STGD1; pathogenic; dbSNP:rs61750155." evidence="13 26 31 35 38">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1598"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084936" evidence="43">
        <location>
            <begin position="1618"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084937" description="In dbSNP:rs1571257969." evidence="43">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1623"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008460" description="In STGD1; dbSNP:rs61750158." evidence="6">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1631"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012582" description="In dbSNP:rs61754056." evidence="22">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="1637"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012583" description="In STGD1, FFM and CORD3; dbSNP:rs61751403." evidence="10 19 22 29 30 38 41 43">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1640"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008461" description="In STGD1; dbSNP:rs61751404." evidence="9 22 29 41 42 55">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1640"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084938" description="In CORD3; uncertain significance." evidence="43">
        <location>
            <begin position="1650"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084939" description="In STGD1 and FFM; uncertain significance." evidence="26 43">
        <location>
            <begin position="1652"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008462" description="In STGD1; dbSNP:rs61750560." evidence="7">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="1652"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012584" description="In STGD1." evidence="37">
        <location>
            <begin position="1681"/>
            <end position="1685"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012585" description="In STGD1; dbSNP:rs61753020." evidence="14">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1689"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012586" description="In STGD1; dbSNP:rs61750563." evidence="17">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="1693"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008463" description="In STGD1; likely pathogenic; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61750564." evidence="31 47 56">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="1696"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085018" description="In STGD1; uncertain significance; does not affect solubility; does not affect location in cytoplasmic vesicle; decreased basal ATPase activity to less than 50% and N-Ret-PE-induced activity to less than 20% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61750565." evidence="9 47">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="1703"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012587" description="In STGD1; likely pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; results in a modest decrease of basal ATPase activity, while N-Ret-PE-stimulated activity is decreased to 50% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61753021." evidence="14 47">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="1705"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085019" description="In STGD1; uncertain significance; dbSNP:rs61753021." evidence="37">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1705"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084940" description="In STGD1; uncertain significance." evidence="43">
        <location>
            <begin position="1724"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067428" description="In STGD1; dbSNP:rs1557767754." evidence="30 38">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="1724"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008465" description="In STGD1; dbSNP:rs61750567." evidence="7">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1729"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012588" description="In STGD1; dbSNP:rs765563320." evidence="14">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="1733"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012589" description="In STGD1; dbSNP:rs61750568." evidence="17">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1736"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012590" description="In STGD1; dbSNP:rs61753025." evidence="14 29">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1748"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084941" description="In STGD1; uncertain significance." evidence="35">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="1754"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012591" description="In STGD1." evidence="56">
        <location>
            <begin position="1761"/>
            <end position="1763"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084942" description="In STGD1; uncertain significance; dbSNP:rs121909206." evidence="26">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1762"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012592" description="In STGD1; dbSNP:rs61753028." evidence="14 42">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1763"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084943" description="Found in a patient with chorioretinal atrophy; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreased basal ATPase activity to 30-50% and N-Ret-PE-induced activity to 20% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs760549861." evidence="35 47">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="1773"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084944" description="In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-induced ATPase activity to less than 30% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs760549861." evidence="37 43 47">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="1773"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085020" description="In STGD1; uncertain significance; dbSNP:rs771742619." evidence="37">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="1775"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012593" description="In STGD1; dbSNP:rs1553187939." evidence="22 43">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1776"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085021" description="In STGD1; uncertain significance." evidence="9">
        <location>
            <begin position="1779"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085022" description="In STGD1; uncertain significance." evidence="37">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="1779"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012594" description="In STGD1; dbSNP:rs121909207." evidence="11">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="1780"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008466" description="In STGD1; also found in a patient with bull's eye maculopathy; likely pathogenic; moderately decreases solubility; loss of cytoplasmic vesicle localization; decreased basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61751406." evidence="6 35 47">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1794"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085023" description="In STGD1; likely pathogenic; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity; decreases solubility; reduces N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs1571252997." evidence="44 47">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="1794"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012595" description="In STGD1; dbSNP:rs61750574." evidence="21 29 38">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="1799"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012596" description="In STGD1; likely pathogenic; decreases basal and N-Ret-PE-stimulated ATPase activity; reduces N-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle; dbSNP:rs61753029." evidence="21 28 38 47">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="1805"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012597" description="In dbSNP:rs1029950404." evidence="51 54">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="1817"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008467" description="In STGD1; dbSNP:rs62646875." evidence="56">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="1820"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085024" description="In STGD1; likely pathogenic; decreases solubility; loss of cytoplasmic vesicle localization; decreased basal and N-Ret-PE-stimulated ATPase activity below 50% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs62642562." evidence="38 41 47">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="1838"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084945" description="In STGD1; likely pathogenic; does not affect solubility; does not affect location in cytoplasmic vesicle; decreased basal and N-Ret-PE-stimulated ATPase activity to 50-60% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs62642562." evidence="26 47">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="1838"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008468" description="In STGD1; likely pathogenic; decreases solubility; loss of cytoplasmic vesicle localization; decreased basal and N-Ret-PE-stimulated ATPase activity below 50% of wild-type values; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs62642562." evidence="26 47 56">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="1838"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008469" description="In STGD1; likely pathogenic; does not affect solubility; does not affect location in cytoplasmic vesicle; decreased basal and N-Ret-PE-stimulated ATPase activity between 50% and 70% of wild-type values; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs62642576." evidence="47 56">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1843"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090226" description="In STGD1; dbSNP:rs1659540498." evidence="38">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1844"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008494" description="In STGD1; dbSNP:rs61750575." evidence="22 35">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1846"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008470" description="Found in patients with ABCA4-related ocular disorders; uncertain significance; slightly reduced retinal-stimulated ATP hydrolysis according to PubMed:11017087; no effect on both basal and N-Ret-PE-stimulated ATPase activity according to PubMed:33375396; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; does not affect solubility; does not affect location in cytoplasmic vesicle; dbSNP:rs1801466." evidence="14 15 19 20 22 23 26 37 43 45 47">
        <original>N</original>
        <variation>I</variation>
        <location>
            <position position="1868"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084946" description="In CORD3; uncertain significance; dbSNP:rs752160946." evidence="43">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="1882"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012598" description="In STGD1; dbSNP:rs62642578." evidence="17">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="1884"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012599" description="In STGD1; dbSNP:rs62642563." evidence="14 43">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="1885"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008471" description="In STGD1; likely pathogenic; dbSNP:rs62642579." evidence="56">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1886"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008472" description="In STGD1; dbSNP:rs61750635.">
        <location>
            <position position="1890"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012600" description="In STGD1; dbSNP:rs61750636." evidence="17">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="1896"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085025" description="Does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; modest decrease of N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs201357151." evidence="47">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="1898"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008473" description="In STGD1 and ARMD2; likely benign; does not affect solubility; does not affect location in cytoplasmic vesicle; does not affect both basal and N-Ret-PE-stimulated ATPase activity; does not affect N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs1800552." evidence="11 14 42 47 52">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1898"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084947" description="In STGD1; uncertain significance." evidence="43">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="1921"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012601" description="In STGD1; dbSNP:rs61753032." evidence="14 43">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="1921"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012602" description="In STGD1 and FFM; dbSNP:rs61753033." evidence="21 29 38">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1940"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085026" description="In STGD1; uncertain significance; dbSNP:rs760353830." evidence="37">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="1942"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008474" description="In dbSNP:rs56142141." evidence="14 21 22 23 26">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1948"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085027" evidence="9">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="1948"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008475" description="In STGD1, FFM and CORD3; pathogenic; risk factor for ARMD2; also found in patients with cone dystrophy and with macular dystrophy; does not affect solubility; does not affect location to cytoplasmic vesicle; severely decreased basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs1800553." evidence="7 10 12 14 15 18 22 26 29 30 31 35 38 41 42 44 52 56">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="1961"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084948" description="In STGD1; likely pathogenic; dbSNP:rs142253670." evidence="38 43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1961"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008476" description="In ARMD2, FFM and STGD1; also found in a patient with cone dystrophy; dbSNP:rs28938473." evidence="14 26 31 42 52 55">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="1970"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012603" description="In FFM; 4-fold decreased binding affinity for ATP; decreased basal ATPase activity; abolishes retinal-stimulated ATP hydrolysis; dbSNP:rs61753034." evidence="15 25 55">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="1971"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012604" description="In STGD1; dbSNP:rs61753036." evidence="14">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="1975"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008477" description="In STGD1; pathogenic; highly reduced ATP-binding capacity; loss of retinal-stimulated ATP hydrolysis; dbSNP:rs61750639." evidence="14 15 22 29 30 31 38 43 55">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="1977"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084949" description="In STGD1; uncertain significance." evidence="43">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="2017"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084950" description="In STGD1; uncertain significance; dbSNP:rs150633517." evidence="43">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="2023"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008478" description="In STGD1 and FFM; pathogenic; also found in a patient with chorioretinal atrophy; decreased basal and N-Ret-PE-stimulated ATPase activity; 34-fold decreased binding affinity for ATP; 4-fold decreased Vmax for basal ATP hydrolysis; decreased solubility; does not localize to cytoplasmic vesicle; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61751408." evidence="15 19 22 25 26 29 30 35 42 44">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="2027"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084951" description="In STGD1 and CORD3; uncertain significance; dbSNP:rs61751383." evidence="9 31 43">
        <location>
            <begin position="2030"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008480" description="In STGD1 and FFM; dbSNP:rs61750641." evidence="19 22 26 35 42">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="2030"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084952" description="In STGD1; uncertain significance; dbSNP:rs1242866408." evidence="43">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="2032"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084953" description="In STGD1; uncertain significance; dbSNP:rs1553186896." evidence="42">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="2033"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012605" description="In STGD1; dbSNP:rs61750642." evidence="22">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="2035"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008495" description="In STGD1; pathogenic; 2-fold decreased binding affinity for ATP; decreased basal ATPase activity; dbSNP:rs61750643." evidence="7 25 43 51">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="2038"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084954" description="In STGD1; uncertain significance; also found in a patient with chorioretinal atrophy; uncertain significance; dbSNP:rs61753038." evidence="35 43">
        <location>
            <begin position="2040"/>
            <end position="2273"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084955" description="In STGD1; uncertain significance; dbSNP:rs148460146." evidence="43">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="2040"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084956" description="In STGD1; uncertain significance." evidence="43">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="2042"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084957" description="In CORD3; uncertain significance; dbSNP:rs763230559." evidence="43">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="2043"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067429" description="In STGD1; dbSNP:rs1659351816." evidence="30 38">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="2047"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008481" description="In STGD1 and CORD3; may act as a modifier of macular dystrophy in patients who also have a Trp-172 mutation in PRPH2; dbSNP:rs41292677." evidence="22 26 32 42">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="2050"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012606" evidence="14">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="2059"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012607" description="In CORD3 and STGD1; dbSNP:rs61753039." evidence="21 29 38">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="2060"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084958" description="In STGD1; uncertain significance; dbSNP:rs61753040." evidence="43">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="2064"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012608" description="In STGD1; dbSNP:rs1659197100." evidence="17">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="2071"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085028" description="In STGD1; uncertain significance; dbSNP:rs367839100." evidence="37">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="2074"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012609" description="In STGD1; dbSNP:rs61750645." evidence="14">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="2077"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090227" description="In STGD1; dbSNP:rs886044759." evidence="38">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="2077"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008482" description="In STGD1; pathogenic; highly reduced ATP-binding capacity; decreased solubility; loss of intracellular vesicle localization; decreased basal and N-Ret-PE-stimulated ATPase activity; decreased N-all-trans-retinylidenephosphatidylethanolamine binding; dbSNP:rs61750645." evidence="7 14 15 44">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="2077"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084959" description="In STGD1; uncertain significance." evidence="43">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="2078"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008483" description="In STGD1; likely pathogenic; loss of retinal-stimulated ATPase activity; dbSNP:rs61750646." evidence="15 31">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="2096"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084960" description="In STGD1; uncertain significance; dbSNP:rs1166357291." evidence="43">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="2097"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008484" description="In STGD1 and FFM; likely pathogenic; dbSNP:rs61750648." evidence="19 35">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="2106"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012610" description="In STGD1; likely pathogenic; dbSNP:rs2297669." evidence="22 35">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="2107"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008485" description="In STGD1 and CORD3; likely pathogenic; may predispose to develop retinal toxicity after treatment with chloroquine and hydroxychloroquine; dbSNP:rs62642564." evidence="7 20 22 26 29 30 41 43 55">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="2107"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008486" description="In STGD1; dbSNP:rs61750651." evidence="7 37">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="2128"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008487" description="In STGD1; uncertain significance; dbSNP:rs61750652." evidence="35">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="2131"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067430" description="In STGD1; dbSNP:rs1659154730." evidence="30 38">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="2137"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008488" description="In STGD1; dbSNP:rs61750653." evidence="22 26">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="2139"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084961" description="In STGD1; uncertain significance; dbSNP:rs774475956." evidence="31">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="2140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012611" description="In CORD3; 2-fold decreased binding affinity for ATP; decreased basal ATPase activity; dbSNP:rs61753044." evidence="22 25 43">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="2146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012612" description="In STGD1; dbSNP:rs61750655." evidence="26">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="2149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012613" description="In STGD1; dbSNP:rs61750656." evidence="22 43">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="2150"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008489" description="In STGD1 and CORD3; dbSNP:rs61751384." evidence="7 9 22 26 29 35 38">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="2150"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008490" description="In STGD1; dbSNP:rs281865405." evidence="9">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="2160"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_008491" description="In CORD3 and STGD1; likely benign; also found in patients with age-related macular degeneration although association with disease in these patients is controversial; increased retinal-stimulated ATP hydrolysis; 4-fold decreased binding affinity for ATP; dbSNP:rs1800555." evidence="12 14 15 18 25 26 42 52">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="2177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084962" description="In STGD1; pathogenic; dbSNP:rs61750658." evidence="38 43">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="2188"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012614" description="In dbSNP:rs886044763." evidence="14">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="2216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084963" description="In STGD1; uncertain significance; dbSNP:rs1367504380." evidence="31">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="2221"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012615" description="In STGD1; dbSNP:rs61750659." evidence="17">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="2229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084964" description="In STGD1; uncertain significance; dbSNP:rs1659051890." evidence="35">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="2237"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012616" description="In STGD1; dbSNP:rs61748521." evidence="14 26 29">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="2241"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_009157" description="In dbSNP:rs6666652." evidence="19 20 21 37 43 52">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="2255"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012617" description="In STGD1; dbSNP:rs281865407." evidence="17">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="2263"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity." evidence="49">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity. Decreased N-retinylidene-phosphatidylethanolamine flippase activity. Decreased affinity for N-all-trans-retinylidenephosphatidylethanolamine." evidence="49">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of N-Ret-PE-stimulated ATPase activity. No effect on basal ATPase activity. Decreased N-retinylidene-phosphatidylethanolamine flippase activity. Decreased affinity for N-all-trans-retinylidenephosphatidylethanolamine." evidence="49">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced retinal-stimulated ATP hydrolysis." evidence="15">
        <location>
            <position position="863"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases 11-cis-Retinal binding affinity by 50%." evidence="36">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="940"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity." evidence="50">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased N-Ret-PE binding to 50%-63% of wild-type values." evidence="50">
        <original>N</original>
        <variation>D</variation>
        <variation>K</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Results in minimal, if any, basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity." evidence="50">
        <original>N</original>
        <variation>D</variation>
        <variation>K</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity." evidence="50">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="965"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes basal and retinal-stimulated ATP hydrolysis." evidence="15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="966"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes basal and retinal-stimulated ATP hydrolysis." evidence="15">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="969"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibits ATPase activity; when associated with M-1978. Decreases translocase activity; when associated with M-1978. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-1978. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect N-retinylidene-PE binding. Impairs ATP-dependent release of N-retinylidene-PE. Significantly reduces PE flippase activity." evidence="34 39">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="969"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Severely decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity. Does not affect protein folding; when associated with Q-2096. Loss of basal and N-Ret-PE-stimulated ATPase activity; when associated with Q-2096." evidence="48 50">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="1087"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Moderately decreased protein abundance. Moderately decreased ATPase activity. Moderately decreased phospholipid translocase activity." evidence="39">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="1502"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased solubility. Loss of cytoplasmic vesicle localization. Severely decreased basal and N-Ret-PE-induced ATPase activity. Decreased N-all-trans-retinylidenephosphatidylethanolamine binding." evidence="47">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="1703"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Severely decreases solubility. Loss of cytoplasmic vesicle localization. Decreases basal ATPase activity below 50%. Severe decrease of N-Ret-PE-induced stimulation in ATPase activity. Decreased N-all-trans-retinylidenephosphatidylethanolamine binding." evidence="47">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="1838"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased basal ATPase activity and loss of N-Ret-PE-stimulated ATPase activity." evidence="50">
        <original>N</original>
        <variation>D</variation>
        <variation>K</variation>
        <variation>Y</variation>
        <location>
            <position position="1974"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased N-Ret-PE binding to 25% of wild-type values." evidence="50">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="1974"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity." evidence="50">
        <original>N</original>
        <variation>S</variation>
        <variation>A</variation>
        <variation>Q</variation>
        <location>
            <position position="1974"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibition of retinal-stimulated ATP hydrolysis." evidence="15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="1975"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibits ATPase activity; when associated with M-969. Decreases translocase activity; when associated with M-969. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-969. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect ATP-independent N-retinylidene-PE binding. Does not affect ATP-dependent of N-retinylidene-PE release. Significantly reduces PE flippase activity. Inhibition of retinal-stimulated ATP hydrolysis." evidence="15 34 39">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="1978"/>
        </location>
    </feature>
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        <citation type="submission" date="1997-06" db="EMBL/GenBank/DDBJ databases">
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                <person name="Sarginson J."/>
                <person name="Gibbs R.A."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
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                <person name="Ono T."/>
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                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
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                <person name="Kobatake N."/>
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                <person name="Okitani R."/>
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                <person name="Senba T."/>
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                <person name="Mizuno T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2007-02" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NHLBI resequencing and genotyping service (RS&amp;G)"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <title>DNA sequence and analysis of human chromosome 18.</title>
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                <person name="Whittaker C.A."/>
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                <person name="Yang X."/>
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                <person name="Bugalter B."/>
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                <person name="Toyoda A."/>
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            </authorList>
            <dbReference type="PubMed" id="16177791"/>
            <dbReference type="DOI" id="10.1038/nature03983"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT CYS-3</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">Phospholipase that may play a role in phospholipids remodeling. May selectively cleave myristate (C14)-containing phosphatidylcholines through its predominant phospholipase 1 activity, cleaving preferentially acyl groups in sn1 position. In parallel, may have a minor phospholipase 2 activity acting on acyl groups in position sn2. In addition to (C14)-containing phosphatidylcholines, may also act on other medium-chain-containing and oxidatively truncated phospholipids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:15801"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:57643"/>
            <dbReference type="ChEBI" id="CHEBI:58168"/>
            <dbReference type="EC" id="3.1.1.4"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:15802"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:18689"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:57643"/>
            <dbReference type="ChEBI" id="CHEBI:57875"/>
            <dbReference type="EC" id="3.1.1.32"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:18690"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-tetradecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = 2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + tetradecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54388"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:76084"/>
            <dbReference type="ChEBI" id="CHEBI:86094"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54389"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-tetradecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + H2O = 1-tetradecanoyl-sn-glycero-3-phosphocholine + (9Z,12Z)-octadecadienoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54392"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:64489"/>
            <dbReference type="ChEBI" id="CHEBI:86094"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54393"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-tetradecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + tetradecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54396"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:76079"/>
            <dbReference type="ChEBI" id="CHEBI:86102"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54397"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-tetradecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + H2O = 2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine + tetradecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54400"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:76085"/>
            <dbReference type="ChEBI" id="CHEBI:86162"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54401"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1,2-ditetradecanoyl-sn-glycero-3-phosphocholine + H2O = 2-tetradecanoyl-sn-glycero-3-phosphocholine + tetradecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54404"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:45240"/>
            <dbReference type="ChEBI" id="CHEBI:131738"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54405"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-octadecanoyl-sn-glycero-3-phosphocholine + acetate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54408"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:73858"/>
            <dbReference type="ChEBI" id="CHEBI:75220"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54409"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1,2-ditetradecanoyl-sn-glycero-3-phosphocholine + H2O = 1-tetradecanoyl-sn-glycero-3-phosphocholine + tetradecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54456"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:45240"/>
            <dbReference type="ChEBI" id="CHEBI:64489"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54457"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine + H2O = pentanoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54460"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:31011"/>
            <dbReference type="ChEBI" id="CHEBI:73858"/>
            <dbReference type="ChEBI" id="CHEBI:138211"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54461"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-hexanoyl-sn-glycero-3-phosphocholine + H2O = hexanoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54464"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:73858"/>
            <dbReference type="ChEBI" id="CHEBI:138212"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54465"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-octanoyl-sn-glycero-3-phosphocholine + H2O = 1-octadecanoyl-sn-glycero-3-phosphocholine + octanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54468"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:73858"/>
            <dbReference type="ChEBI" id="CHEBI:138213"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54469"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-nonanoyl-sn-glycero-3-phosphocholine + H2O = nonanoate + 1-octadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54472"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32361"/>
            <dbReference type="ChEBI" id="CHEBI:73858"/>
            <dbReference type="ChEBI" id="CHEBI:138214"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54473"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-O-hexadecyl-2-nonadioyl-sn-glycero-3-phosphocholine + H2O = nonanedioate + 1-O-hexadecyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:54552"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:64496"/>
            <dbReference type="ChEBI" id="CHEBI:78208"/>
            <dbReference type="ChEBI" id="CHEBI:138269"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:54553"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-nonadioyl-sn-glycero-3-phosphocholine + H2O = nonanedioate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41388"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:72998"/>
            <dbReference type="ChEBI" id="CHEBI:78207"/>
            <dbReference type="ChEBI" id="CHEBI:78208"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:41389"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine + H2O = 9-oxononanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41179"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:61042"/>
            <dbReference type="ChEBI" id="CHEBI:72998"/>
            <dbReference type="ChEBI" id="CHEBI:77812"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:41180"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine + H2O = 5-oxopentanoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40483"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16120"/>
            <dbReference type="ChEBI" id="CHEBI:72998"/>
            <dbReference type="ChEBI" id="CHEBI:77890"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40484"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-hexadecanoyl-2-glutaroyl-sn-glycero-3-phosphocholine + H2O = glutarate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41159"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30921"/>
            <dbReference type="ChEBI" id="CHEBI:72998"/>
            <dbReference type="ChEBI" id="CHEBI:77756"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:41160"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40479"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:44811"/>
            <dbReference type="ChEBI" id="CHEBI:64496"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40480"/>
        </physiologicalReaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Membrane</location>
            <topology evidence="6">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WU67-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WU67-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056137 VSP_056138"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC19155" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.1.32" evidence="2"/>
    <dbReference type="EC" id="3.1.1.4" evidence="2"/>
    <dbReference type="EMBL" id="AF007152">
        <property type="protein sequence ID" value="AAC19155.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298728">
        <property type="protein sequence ID" value="BAH12858.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF444943">
        <property type="protein sequence ID" value="ACA05928.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC106037">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471088">
        <property type="protein sequence ID" value="EAX01131.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC021196">
        <property type="protein sequence ID" value="AAH21196.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32802.1">
        <molecule id="Q8WU67-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001295185.1">
        <property type="nucleotide sequence ID" value="NM_001308256.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001295186.1">
        <property type="nucleotide sequence ID" value="NM_001308257.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_612213.2">
        <molecule id="Q8WU67-1"/>
        <property type="nucleotide sequence ID" value="NM_138340.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8WU67"/>
    <dbReference type="BioGRID" id="128149">
        <property type="interactions" value="31"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8WU67">
        <property type="interactions" value="314"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WU67">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="MINT" id="Q8WU67"/>
    <dbReference type="STRING" id="9606.ENSP00000289119"/>
    <dbReference type="ESTHER" id="human-ABHD3">
        <property type="family name" value="abh_upf0017"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8WU67"/>
    <dbReference type="PhosphoSitePlus" id="Q8WU67"/>
    <dbReference type="BioMuta" id="ABHD3"/>
    <dbReference type="DMDM" id="134035377"/>
    <dbReference type="jPOST" id="Q8WU67"/>
    <dbReference type="MassIVE" id="Q8WU67"/>
    <dbReference type="PaxDb" id="9606-ENSP00000289119"/>
    <dbReference type="PeptideAtlas" id="Q8WU67"/>
    <dbReference type="ProteomicsDB" id="74636">
        <molecule id="Q8WU67-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8WU67"/>
    <dbReference type="Antibodypedia" id="2532">
        <property type="antibodies" value="120 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="171586"/>
    <dbReference type="Ensembl" id="ENST00000289119.7">
        <molecule id="Q8WU67-1"/>
        <property type="protein sequence ID" value="ENSP00000289119.2"/>
        <property type="gene ID" value="ENSG00000158201.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000577891.1">
        <molecule id="Q8WU67-2"/>
        <property type="protein sequence ID" value="ENSP00000463365.1"/>
        <property type="gene ID" value="ENSG00000158201.11"/>
    </dbReference>
    <dbReference type="GeneID" id="171586"/>
    <dbReference type="KEGG" id="hsa:171586"/>
    <dbReference type="MANE-Select" id="ENST00000289119.7">
        <property type="protein sequence ID" value="ENSP00000289119.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_138340.5"/>
        <property type="RefSeq protein sequence ID" value="NP_612213.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ktl.2">
        <molecule id="Q8WU67-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18718"/>
    <dbReference type="ClinPGx" id="PA38659"/>
    <dbReference type="CTD" id="171586"/>
    <dbReference type="DisGeNET" id="171586"/>
    <dbReference type="GeneCards" id="ABHD3"/>
    <dbReference type="HGNC" id="HGNC:18718">
        <property type="gene designation" value="ABHD3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000158201">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="612197">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000158201"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000158201"/>
    <dbReference type="eggNOG" id="KOG1838">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182902"/>
    <dbReference type="HOGENOM" id="CLU_032487_4_0_1"/>
    <dbReference type="InParanoid" id="Q8WU67"/>
    <dbReference type="OMA" id="LDWHGPH"/>
    <dbReference type="OrthoDB" id="247542at2759"/>
    <dbReference type="PAN-GO" id="Q8WU67">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WU67"/>
    <dbReference type="PathwayCommons" id="Q8WU67"/>
    <dbReference type="Reactome" id="R-HSA-1483191">
        <property type="pathway name" value="Synthesis of PC"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8WU67"/>
    <dbReference type="Agora" id="ENSG00000158201"/>
    <dbReference type="BioGRID-ORCS" id="171586">
        <property type="hits" value="24 hits in 1158 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="171586"/>
    <dbReference type="Pharos" id="Q8WU67">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WU67"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 18"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WU67">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000158201">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 191 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WU67">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008126">
        <property type="term" value="F:acetylesterase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047372">
        <property type="term" value="F:monoacylglycerol lipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008970">
        <property type="term" value="F:phospholipase A1 activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004623">
        <property type="term" value="F:phospholipase A2 activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051792">
        <property type="term" value="P:medium-chain fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051793">
        <property type="term" value="P:medium-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006656">
        <property type="term" value="P:phosphatidylcholine biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046470">
        <property type="term" value="P:phosphatidylcholine metabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000079">
        <property type="entry name" value="Abhydrolase domain-containing 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000952">
        <property type="entry name" value="AB_hydrolase_4_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050960">
        <property type="entry name" value="AB_hydrolase_4_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012020">
        <property type="entry name" value="ABHD4"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794">
        <property type="entry name" value="ABHYDROLASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10794:SF50">
        <property type="entry name" value="PHOSPHOLIPASE ABHD3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF005211">
        <property type="entry name" value="Ab_hydro_YheT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01133">
        <property type="entry name" value="UPF0017"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1208">Phospholipid metabolism</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000280208" description="Phospholipase ABHD3">
        <location>
            <begin position="1"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
        <location>
            <begin position="26"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="3">
        <location>
            <begin position="140"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="220"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="346"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056137" description="In isoform 2." evidence="5">
        <original>PQLVTGGESFSRFLQDHCPVVTETYYPTVWCWEGRGQTLLRPFITSKPPVQYRNELIKTADGGQISLDWFDNDNSTCYMDA</original>
        <variation>RTTRRSGAGRVEDRPCLDLSSLRSPRCSTGMNLLKLQMEDRFHWTGLIMITVRVIWMPAPDLLSYCCLASREQARSHISFI</variation>
        <location>
            <begin position="56"/>
            <end position="136"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056138" description="In isoform 2." evidence="5">
        <location>
            <begin position="137"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031089" description="In dbSNP:rs17851878." evidence="4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q91ZH7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:18718"/>
        </source>
    </evidence>
    <sequence length="409" mass="46009" checksum="9A3920EB7528273B" modified="2007-03-20" version="2">MQRLAMDLRMLSRELSLYLEHQVRVGFFGSGVGLSLILGFSVAYAFYYLSSIAKKPQLVTGGESFSRFLQDHCPVVTETYYPTVWCWEGRGQTLLRPFITSKPPVQYRNELIKTADGGQISLDWFDNDNSTCYMDASTRPTILLLPGLTGTSKESYILHMIHLSEELGYRCVVFNNRGVAGENLLTPRTYCCANTEDLETVIHHVHSLYPSAPFLAAGVSMGGMLLLNYLGKIGSKTPLMAAATFSVGWNTFACSESLEKPLNWLLFNYYLTTCLQSSVNKHRHMFVKQVDMDHVMKAKSIREFDKRFTSVMFGYQTIDDYYTDASPSPRLKSVGIPVLCLNSVDDVFSPSHAIPIETAKQNPNVALVLTSYGGHIGFLEGIWPRQSTYMDRVFKQFVQAMVEHGHELS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-19" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NYB9</accession>
    <accession>B4DSN1</accession>
    <accession>Q13147</accession>
    <accession>Q13249</accession>
    <accession>Q13801</accession>
    <accession>Q9BV70</accession>
    <name>ABI2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="18">Abl interactor 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="18">Abelson interactor 2</fullName>
            <shortName evidence="16">Abi-2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Abl-binding protein 3</fullName>
            <shortName>AblBP3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="17">Arg-binding protein 1</fullName>
            <shortName evidence="17">ArgBP1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15 22" type="primary">ABI2</name>
        <name type="synonym">ARGBPIA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="Genes Dev." volume="9" first="2569" last="2582">
            <title>Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.</title>
            <authorList>
                <person name="Dai Z."/>
                <person name="Pendergast A.M."/>
            </authorList>
            <dbReference type="PubMed" id="7590236"/>
            <dbReference type="DOI" id="10.1101/gad.9.21.2569"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION</scope>
        <scope>INTERACTION WITH ABL1</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DOMAIN</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="1995-07" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of a binding substrate of the Abl protein tyrosine kinase.</title>
            <authorList>
                <person name="Ren R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1996" name="Oncogene" volume="12" first="1921" last="1929">
            <title>Identification of ArgBP1, an Arg protein tyrosine kinase binding protein that is the human homologue of a CNS-specific Xenopus gene.</title>
            <authorList>
                <person name="Wang B."/>
                <person name="Mysliwiec T."/>
                <person name="Krainc D."/>
                <person name="Jensen R.A."/>
                <person name="Sonoda G."/>
                <person name="Testa J.R."/>
                <person name="Golemis E.A."/>
                <person name="Kruh G.D."/>
            </authorList>
            <dbReference type="PubMed" id="8649853"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH ABL2</scope>
        <scope>DOMAIN</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-08" db="EMBL/GenBank/DDBJ databases">
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    <comment type="function">
        <text evidence="1 5 7 8 11 12">Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia formation (PubMed:21107423). Acts as a regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2 involved in processes linked to cell growth and differentiation. Positively regulates ABL1-mediated phosphorylation of ENAH, which is required for proper polymerization of nucleated actin filaments at the leading edge (PubMed:10498863, PubMed:7590236, PubMed:8649853). Contributes to the regulation of actin assembly at the tips of neuron projections. In particular, controls dendritic spine morphogenesis and may promote dendritic spine specification toward large mushroom-type spines known as repositories of memory in the brain (By similarity). In hippocampal neurons, may mediate actin-dependent BDNF-NTRK2 early endocytic trafficking that triggers dendrite outgrowth (By similarity). Participates in ocular lens morphogenesis, likely by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface (By similarity). Also required for nascent adherens junction assembly in epithelial cells (PubMed:15572692).</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 11 12">Component of the WAVE complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1 (PubMed:21107423). Interacts (via SH3 domain) with ABL1 and ABL2 (PubMed:7590236, PubMed:8649853).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">(Microbial infection) Interacts with human cytomegalovirus UL135.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-8567699">
            <id>Q9H013</id>
            <label>ADAM19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-308663">
            <id>A7KAX9</id>
            <label>ARHGAP32</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-742909">
            <id>Q9H6L4</id>
            <label>ARMC7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-465781">
            <id>Q9UL45</id>
            <label>BLOC1S6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-10171570">
            <id>Q68D86</id>
            <label>CCDC102B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
        </interactant>
        <interactant intactId="EBI-949834">
            <id>Q8TD31</id>
            <label>CCHCR1</label>
        </interactant>
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            <id>O75886</id>
            <label>STAM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-8484990">
            <id>Q8N4C7</id>
            <label>STX19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-744942">
            <id>Q12846</id>
            <label>STX4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-11741437">
            <id>Q08117-2</id>
            <label>TLE5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-10977815">
            <id>P07951-2</id>
            <label>TPM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-742790">
            <id>Q13049</id>
            <label>TRIM32</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-2341648">
            <id>Q6ZMU5</id>
            <label>TRIM72</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-11059915">
            <id>Q8N7C3</id>
            <label>TRIML2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-947187">
            <id>Q9UHD9</id>
            <label>UBQLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-743272">
            <id>O75604</id>
            <label>USP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-2116622">
            <id>Q5ST30</id>
            <label>VARS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-2810325">
            <id>Q96NT0</id>
            <label>VMA22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-12146727">
            <id>Q9UK41-2</id>
            <label>VPS28</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-12026286">
            <id>Q9UPY6-2</id>
            <label>WASF3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-712969">
            <id>Q9Y3C0</id>
            <label>WASHC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-957615">
            <id>O00401</id>
            <label>WASL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-12052927">
            <id>O43516-4</id>
            <label>WIPF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-12040603">
            <id>Q9NZC7-5</id>
            <label>WWOX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-11419867">
            <id>Q8TF47</id>
            <label>ZFP90</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-12030590">
            <id>Q9H0C1</id>
            <label>ZMYND12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-17269964">
            <id>Q6S9Z5</id>
            <label>ZNF474</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-16429014">
            <id>A0A0S2Z5X4</id>
            <label>ZNF688</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-4395732">
            <id>P0C7X2</id>
            <label>ZNF688</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-10022">
            <id>Q12446</id>
            <label>LAS17</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-10736">
            <id>P16523</id>
            <label>MER1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-627">
            <id>Q03782</id>
            <label>SNU56</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
        </interactant>
        <interactant intactId="EBI-19616">
            <id>P25372</id>
            <label>TRX3</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 11 12">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="6 7">Cell projection</location>
            <location evidence="6 7">Lamellipodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cell projection</location>
            <location evidence="6">Filopodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
            <location evidence="7">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cell junction</location>
            <location evidence="7">Adherens junction</location>
        </subcellularLocation>
        <text evidence="6 7">Isoform 1 but not isoform 3 is localized to protruding lamellipodia and filopodia tips (PubMed:11516653, PubMed:15572692). Present at nascent adherens junctions, where it clusters adjacent to the tips of F-actin protrusions (PubMed:15572692).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NYB9-1</id>
            <name>1</name>
            <name>Abi-2b</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NYB9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_010761 VSP_010762 VSP_010763"/>
        </isoform>
        <isoform>
            <id>Q9NYB9-3</id>
            <name>3</name>
            <name>Abi-2a</name>
            <sequence type="described" ref="VSP_010759 VSP_010760 VSP_010761 VSP_010762"/>
        </isoform>
        <isoform>
            <id>Q9NYB9-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_010761"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="11">Widely expressed. Abundant in testes, ovary, thymus, and colon, with lower but detectable levels in prostate, peripheral blood leukocytes, and spleen.</text>
    </comment>
    <comment type="domain">
        <text evidence="11 12">The SH3 domain is critical for binding to ABL1 and ABL2.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Phosphorylated by ABL1.</text>
    </comment>
    <comment type="disease">
        <text evidence="10">There is evidence, including phenotypic data from ABI2-knockout mice, that loss-of-function variants in ABI2 may play a role in autosomal recessive intellectual disability.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the ABI family.</text>
    </comment>
    <dbReference type="EMBL" id="U23435">
        <property type="protein sequence ID" value="AAA92289.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U31089">
        <property type="protein sequence ID" value="AAA75446.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260261">
        <property type="protein sequence ID" value="AAF70308.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X95632">
        <property type="protein sequence ID" value="CAA64885.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT009920">
        <property type="protein sequence ID" value="AAP88922.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299824">
        <property type="protein sequence ID" value="BAG61693.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001439">
        <property type="protein sequence ID" value="AAH01439.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2358.1">
        <molecule id="Q9NYB9-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS63093.1">
        <molecule id="Q9NYB9-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS63094.1">
        <molecule id="Q9NYB9-4"/>
    </dbReference>
    <dbReference type="PIR" id="G01936">
        <property type="entry name" value="G01936"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269854.1">
        <property type="nucleotide sequence ID" value="NM_001282925.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269855.1">
        <property type="nucleotide sequence ID" value="NM_001282926.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269856.1">
        <molecule id="Q9NYB9-3"/>
        <property type="nucleotide sequence ID" value="NM_001282927.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001362683.1">
        <molecule id="Q9NYB9-3"/>
        <property type="nucleotide sequence ID" value="NM_001375754.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005750.4">
        <molecule id="Q9NYB9-2"/>
        <property type="nucleotide sequence ID" value="NM_005759.5"/>
    </dbReference>
    <dbReference type="PDB" id="2ED0">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=444-508"/>
    </dbReference>
    <dbReference type="PDB" id="3P8C">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.29 A"/>
        <property type="chains" value="F=1-154"/>
    </dbReference>
    <dbReference type="PDB" id="4N78">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.43 A"/>
        <property type="chains" value="F=1-513"/>
    </dbReference>
    <dbReference type="PDB" id="7USC">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="E=1-154"/>
    </dbReference>
    <dbReference type="PDB" id="7USD">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="E=1-154"/>
    </dbReference>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="E=1-154"/>
    </dbReference>
    <dbReference type="PDBsum" id="2ED0"/>
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    <dbReference type="PDBsum" id="7USC"/>
    <dbReference type="PDBsum" id="7USD"/>
    <dbReference type="PDBsum" id="7USE"/>
    <dbReference type="AlphaFoldDB" id="Q9NYB9"/>
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        <property type="interactions" value="303"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-37566N"/>
    <dbReference type="FunCoup" id="Q9NYB9">
        <property type="interactions" value="1508"/>
    </dbReference>
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        <property type="interactions" value="269"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NYB9"/>
    <dbReference type="STRING" id="9606.ENSP00000295851"/>
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        <property type="type" value="Predicted"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NYB9">
        <property type="glycosylation" value="5 sites, 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NYB9"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000295851"/>
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    <dbReference type="ProteomicsDB" id="83210">
        <molecule id="Q9NYB9-2"/>
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        <molecule id="Q9NYB9-3"/>
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    <dbReference type="ProteomicsDB" id="83212">
        <molecule id="Q9NYB9-4"/>
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    <dbReference type="Pumba" id="Q9NYB9"/>
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        <property type="antibodies" value="225 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10152"/>
    <dbReference type="Ensembl" id="ENST00000261017.9">
        <molecule id="Q9NYB9-2"/>
        <property type="protein sequence ID" value="ENSP00000261017.5"/>
        <property type="gene ID" value="ENSG00000138443.18"/>
    </dbReference>
    <dbReference type="GeneID" id="10152"/>
    <dbReference type="KEGG" id="hsa:10152"/>
    <dbReference type="UCSC" id="uc002uzz.5">
        <molecule id="Q9NYB9-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24011"/>
    <dbReference type="ClinPGx" id="PA134977642"/>
    <dbReference type="CTD" id="10152"/>
    <dbReference type="DisGeNET" id="10152"/>
    <dbReference type="GeneCards" id="ABI2"/>
    <dbReference type="HGNC" id="HGNC:24011">
        <property type="gene designation" value="ABI2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000138443">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="606442">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000138443"/>
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    <dbReference type="eggNOG" id="KOG2546">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
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        <property type="pathway name" value="Regulation of actin dynamics for phagocytic cup formation"/>
    </dbReference>
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        <property type="pathway name" value="VEGFA-VEGFR2 Pathway"/>
    </dbReference>
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        <property type="pathway name" value="RHO GTPases Activate WASPs and WAVEs"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9013149">
        <property type="pathway name" value="RAC1 GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013404">
        <property type="pathway name" value="RAC2 GTPase cycle"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9013423">
        <property type="pathway name" value="RAC3 GTPase cycle"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9664422">
        <property type="pathway name" value="FCGR3A-mediated phagocytosis"/>
    </dbReference>
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        <property type="hits" value="10 hits in 1158 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
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        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NYB9"/>
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    <dbReference type="Pharos" id="Q9NYB9">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NYB9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NYB9">
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4)</scope>
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            <tissue>Brain</tissue>
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            <dbReference type="PubMed" id="15815621"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <comment type="function">
        <text evidence="7">May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Interacts with F-actin and ABRA.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-16435510">
            <id>A0A0S2Z5Z3</id>
            <label>C6orf142</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-16435493">
            <id>A0A0S2Z6I7</id>
            <label>C6orf142</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-25837549">
            <id>P28329-3</id>
            <label>CHAT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-10976677">
            <id>G5E9A7</id>
            <label>DMWD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-348399">
            <id>P22607</id>
            <label>FGFR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-744302">
            <id>P14136</id>
            <label>GFAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-1055254">
            <id>Q8WXH2</id>
            <label>JPH3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-351935">
            <id>P02545</id>
            <label>LMNA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-1014472">
            <id>P35240</id>
            <label>NF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-25929070">
            <id>Q9BZ23-2</id>
            <label>PANK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16436655">
            <id>Q6H8Q1-8</id>
        </interactant>
        <interactant intactId="EBI-5235340">
            <id>Q7Z699</id>
            <label>SPRED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">In skeletal muscle, sarcomeric or cosarcomeric localization.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6H8Q1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012117"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_012113 VSP_012115 VSP_012117"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_012112 VSP_012113 VSP_012114 VSP_012116"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_012116 VSP_012117"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_012113 VSP_012115 VSP_012116 VSP_012118 VSP_012119"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_012115"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-8</id>
            <name>8</name>
            <sequence type="described" ref="VSP_012115 VSP_012116 VSP_012117"/>
        </isoform>
        <isoform>
            <id>Q6H8Q1-9</id>
            <name>9</name>
            <sequence type="described" ref="VSP_046646 VSP_012116"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7">Highly expressed in skeletal muscle.</text>
    </comment>
    <comment type="sequence caution" evidence="15">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH67214" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="DQ413177">
        <property type="protein sequence ID" value="ABD83330.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG38375.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG38376.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAC04414.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAC04427.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH67214.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI22568.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAB47437.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAD38885.2"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_001130083.2"/>
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        <property type="nucleotide sequence ID" value="NM_001130084.2"/>
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        <property type="nucleotide sequence ID" value="NM_001130085.2"/>
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        <property type="nucleotide sequence ID" value="NM_001130086.2"/>
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        <property type="nucleotide sequence ID" value="NM_001130087.2"/>
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        <property type="nucleotide sequence ID" value="NM_001130088.2"/>
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        <property type="nucleotide sequence ID" value="NM_032432.4"/>
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        <property type="chains" value="A=73-140"/>
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        <property type="chains" value="A=212-271"/>
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        <property type="chains" value="A=546-611"/>
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    <dbReference type="PDBsum" id="1V6G"/>
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    <dbReference type="AlphaFoldDB" id="Q6H8Q1"/>
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        <property type="interactions" value="18"/>
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    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000393511"/>
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        <property type="glycosylation" value="4 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q6H8Q1">
        <property type="glycosylation" value="6 sites, 1 O-linked glycan (6 sites)"/>
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        <molecule id="Q6H8Q1-1"/>
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        <property type="antibodies" value="48 antibodies from 16 providers"/>
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        <property type="protein sequence ID" value="ENSP00000342813.5"/>
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        <molecule id="Q6H8Q1-2"/>
        <property type="protein sequence ID" value="ENSP00000355003.5"/>
        <property type="gene ID" value="ENSG00000163995.22"/>
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    <dbReference type="Ensembl" id="ENST00000361737.9">
        <molecule id="Q6H8Q1-3"/>
        <property type="protein sequence ID" value="ENSP00000354887.5"/>
        <property type="gene ID" value="ENSG00000163995.22"/>
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        <property type="pathway name" value="DCC mediated attractive signaling"/>
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        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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        <property type="component" value="Chromosome 4"/>
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        <property type="project" value="GO_Central"/>
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        <property type="entry name" value="actin-binding LIM protein 1 isoform X1"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Actin-binding LIM protein family, member 2"/>
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        <property type="match status" value="4"/>
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        <property type="entry name" value="Villin headpiece domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AbLIM_anchor"/>
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        <property type="entry name" value="Actin-binding_LIM"/>
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        <property type="entry name" value="Villin_headpiece"/>
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        <property type="entry name" value="Villin_headpiece_dom_sf"/>
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        <property type="entry name" value="Znf_LIM"/>
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        <property type="entry name" value="ACTIN-BINDING LIM PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="ACTIN-BINDING LIM PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16182">
        <property type="entry name" value="AbLIM_anchor"/>
        <property type="match status" value="2"/>
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    <dbReference type="Pfam" id="PF00412">
        <property type="entry name" value="LIM"/>
        <property type="match status" value="4"/>
    </dbReference>
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        <property type="entry name" value="VHP"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="LIM"/>
        <property type="match status" value="4"/>
    </dbReference>
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        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="VHP, Villin headpiece domain"/>
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    </dbReference>
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        <property type="entry name" value="HP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00478">
        <property type="entry name" value="LIM_DOMAIN_1"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50023">
        <property type="entry name" value="LIM_DOMAIN_2"/>
        <property type="match status" value="4"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0440">LIM domain</keyword>
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    <keyword id="KW-0597">Phosphoprotein</keyword>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
            <name>Zn(2+)</name>
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</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
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            <fullName evidence="10">sn-1-specific diacylglycerol lipase ABHD11</fullName>
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            <fullName evidence="10">Alpha/beta hydrolase domain-containing protein 11</fullName>
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            <fullName>Williams-Beuren syndrome chromosomal region 21 protein</fullName>
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        <name evidence="12" type="primary">ABHD11</name>
        <name type="synonym">WBSCR21</name>
        <name type="ORF">PP1226</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Hum. Genet." volume="110" first="429" last="438">
            <title>Identification of additional transcripts in the Williams-Beuren syndrome critical region.</title>
            <authorList>
                <person name="Merla G."/>
                <person name="Ucla C."/>
                <person name="Guipponi M."/>
                <person name="Reymond A."/>
            </authorList>
            <dbReference type="PubMed" id="12073013"/>
            <dbReference type="DOI" id="10.1007/s00439-002-0710-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="15724" last="15729">
            <title>Large-scale cDNA transfection screening for genes related to cancer development and progression.</title>
            <authorList>
                <person name="Wan D."/>
                <person name="Gong Y."/>
                <person name="Qin W."/>
                <person name="Zhang P."/>
                <person name="Li J."/>
                <person name="Wei L."/>
                <person name="Zhou X."/>
                <person name="Li H."/>
                <person name="Qiu X."/>
                <person name="Zhong F."/>
                <person name="He L."/>
                <person name="Yu J."/>
                <person name="Yao G."/>
                <person name="Jiang H."/>
                <person name="Qian L."/>
                <person name="Yu Y."/>
                <person name="Shu H."/>
                <person name="Chen X."/>
                <person name="Xu H."/>
                <person name="Guo M."/>
                <person name="Pan Z."/>
                <person name="Chen Y."/>
                <person name="Ge C."/>
                <person name="Yang S."/>
                <person name="Gu J."/>
            </authorList>
            <dbReference type="PubMed" id="15498874"/>
            <dbReference type="DOI" id="10.1073/pnas.0404089101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Graves T.A."/>
                <person name="Pepin K.H."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Maas J."/>
                <person name="Jaeger S."/>
                <person name="Walker R."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="O'Laughlin M.D."/>
                <person name="Schaller M.E."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Cordes M."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Edwards J."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Andrews S."/>
                <person name="Isak A."/>
                <person name="Vanbrunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Lamar B."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Bielicki L."/>
                <person name="Scott K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Harris A."/>
                <person name="Strong C.M."/>
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                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Leonard S."/>
                <person name="Rohlfing T."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Abbott A."/>
                <person name="Minx P."/>
                <person name="Maupin R."/>
                <person name="Strowmatt C."/>
                <person name="Latreille P."/>
                <person name="Miller N."/>
                <person name="Johnson D."/>
                <person name="Murray J."/>
                <person name="Woessner J.P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Schultz B.R."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Nelson J.O."/>
                <person name="Berkowicz N."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Bedell J.A."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Chissoe S.L."/>
                <person name="Marra M.A."/>
                <person name="Raymond C."/>
                <person name="Haugen E."/>
                <person name="Gillett W."/>
                <person name="Zhou Y."/>
                <person name="James R."/>
                <person name="Phelps K."/>
                <person name="Iadanoto S."/>
                <person name="Bubb K."/>
                <person name="Simms E."/>
                <person name="Levy R."/>
                <person name="Clendenning J."/>
                <person name="Kaul R."/>
                <person name="Kent W.J."/>
                <person name="Furey T.S."/>
                <person name="Baertsch R.A."/>
                <person name="Brent M.R."/>
                <person name="Keibler E."/>
                <person name="Flicek P."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Bailey J.A."/>
                <person name="Portnoy M.E."/>
                <person name="Torrents D."/>
                <person name="Chinwalla A.T."/>
                <person name="Gish W.R."/>
                <person name="Eddy S.R."/>
                <person name="McPherson J.D."/>
                <person name="Olson M.V."/>
                <person name="Eichler E.E."/>
                <person name="Green E.D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Eye</tissue>
            <tissue>Lung</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2020" name="Nat. Commun." volume="11" first="4046" last="4046">
            <title>ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex.</title>
            <authorList>
                <person name="Bailey P.S.J."/>
                <person name="Ortmann B.M."/>
                <person name="Martinelli A.W."/>
                <person name="Houghton J.W."/>
                <person name="Costa A.S.H."/>
                <person name="Burr S.P."/>
                <person name="Antrobus R."/>
                <person name="Frezza C."/>
                <person name="Nathan J.A."/>
            </authorList>
            <dbReference type="PubMed" id="32792488"/>
            <dbReference type="DOI" id="10.1038/s41467-020-17862-6"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH OGDH AND DLST</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>MUTAGENESIS OF SER-132 AND HIS-287</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2020" name="PLoS ONE" volume="15" first="e0234780" last="e0234780">
            <title>ABHD11, a new diacylglycerol lipase involved in weight gain regulation.</title>
            <authorList>
                <person name="Escoubet J."/>
                <person name="Kenigsberg M."/>
                <person name="Derock M."/>
                <person name="Yaligara V."/>
                <person name="Bock M.D."/>
                <person name="Roche S."/>
                <person name="Massey F."/>
                <person name="de Foucauld H."/>
                <person name="Bettembourg C."/>
                <person name="Olivier A."/>
                <person name="Berthemy A."/>
                <person name="Capdevielle J."/>
                <person name="Legoux R."/>
                <person name="Perret E."/>
                <person name="Buzy A."/>
                <person name="Chardenot P."/>
                <person name="Destelle V."/>
                <person name="Leroy A."/>
                <person name="Cahours C."/>
                <person name="Teixeira S."/>
                <person name="Juvet P."/>
                <person name="Gauthier P."/>
                <person name="Leguet M."/>
                <person name="Rocheteau-Beaujouan L."/>
                <person name="Chatoux M.A."/>
                <person name="Deshayes W."/>
                <person name="Clement M."/>
                <person name="Kabiri M."/>
                <person name="Orsini C."/>
                <person name="Mikol V."/>
                <person name="Didier M."/>
                <person name="Guillemot J.C."/>
            </authorList>
            <dbReference type="PubMed" id="32579589"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0234780"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 6 7">Catalyzes the hydrolysis of diacylglycerol in vitro and may function as a key regulator in lipid metabolism, namely by regulating the intracellular levels of diacylglycerol (PubMed:32579589). 1,2-diacyl-sn-glycerols are the preferred substrate over 1,3-diacyl-sn-glycerols (By similarity). The enzyme hydrolyzes stearate in preference to palmitate from the sn-1 position of 1,2-diacyl-sn-glycerols (By similarity). Maintains the functional lipoylation of the 2-oxoglutarate dehydrogenase complex (OGDHc) through its interaction with the OGDHc by preventing the formation of lipoyl adducts (PubMed:32792488). In addition, is also required for the expansion and differentiation of embryonic stem cells (ESCs) (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38507"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:52392"/>
            <dbReference type="ChEBI" id="CHEBI:75728"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:33275"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17389"/>
            <dbReference type="ChEBI" id="CHEBI:17815"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="EC" id="3.1.1.116"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a 1,3-diacyl-sn-glycerol + H2O = a 1-acyl-sn-glycerol + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:38503"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:64683"/>
            <dbReference type="ChEBI" id="CHEBI:77272"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + H2O = 2-(9Z-octadecenoyl)-glycerol + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:77103"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:73990"/>
            <dbReference type="ChEBI" id="CHEBI:75468"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycerol + H2O = 2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:77107"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:77129"/>
            <dbReference type="ChEBI" id="CHEBI:186738"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1,2-didecanoylglycerol + H2O = decanoylglycerol + decanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:48596"/>
            <dbReference type="ChEBI" id="CHEBI:11152"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:90605"/>
        </reaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">18.6 uM for 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol</KM>
            <Vmax evidence="6">2600.0 nmol/min/mg enzyme toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="7">Interacts with OGDH and DLST; this interaction maintains the functional lipoylation of the 2-oxoglutarate dehydrogenase complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-17183751">
            <id>X5D778</id>
            <label>ANKRD11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-711360">
            <id>P33240</id>
            <label>CSTF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-2880244">
            <id>Q6PKX4</id>
            <label>DOK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-740376">
            <id>Q86UW9</id>
            <label>DTX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-10242151">
            <id>Q53EP0-3</id>
            <label>FNDC3B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-947242">
            <id>P28676</id>
            <label>GCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-2880706">
            <id>O43593</id>
            <label>HR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-724076">
            <id>Q99750</id>
            <label>MDFI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-9675802">
            <id>Q6PF18</id>
            <label>MORN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-11022007">
            <id>Q9HBE1-4</id>
            <label>PATZ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-748265">
            <id>P78337</id>
            <label>PITX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-1053424">
            <id>O43741</id>
            <label>PRKAB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-9027467">
            <id>O75360</id>
            <label>PROP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-11986293">
            <id>P0CG20</id>
            <label>PRR35</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-6257312">
            <id>Q9BVN2</id>
            <label>RUSC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-2107455">
            <id>Q08AM6</id>
            <label>VAC14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-10191303">
            <id>O95231</id>
            <label>VENTX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-2559305">
            <id>A5D8V6</id>
            <label>VPS37C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-12040603">
            <id>Q9NZC7-5</id>
            <label>WWOX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-1051237">
            <id>Q9BYJ9</id>
            <label>YTHDF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12318443">
            <id>Q8NFV4-4</id>
        </interactant>
        <interactant intactId="EBI-11963196">
            <id>Q15915</id>
            <label>ZIC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NFV4-1</id>
            <name>1</name>
            <name>A</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NFV4-2</id>
            <name>2</name>
            <name>B</name>
            <sequence type="described" ref="VSP_023925 VSP_023928"/>
        </isoform>
        <isoform>
            <id>Q8NFV4-3</id>
            <name>3</name>
            <name>C</name>
            <sequence type="described" ref="VSP_023926 VSP_023927"/>
        </isoform>
        <isoform>
            <id>Q8NFV4-4</id>
            <name>4</name>
            <name>D</name>
            <sequence type="described" ref="VSP_023924"/>
        </isoform>
        <isoform>
            <id>Q8NFV4-5</id>
            <name>5</name>
            <name>E</name>
            <sequence type="described" ref="VSP_023924 VSP_023929 VSP_023930"/>
        </isoform>
        <isoform>
            <id>Q8NFV4-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_046994"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6">Ubiquitously expressed (PubMed:12073013). Highly expressed in small intestine, prostate and thyroid, while aorta and colon tissues exhibit weak expression levels (PubMed:32579589).</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Phosphorylated.</text>
    </comment>
    <comment type="disease">
        <text>ABHD11 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="10">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="10">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the AB hydrolase superfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAG17214" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH08251" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH11712" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH67750" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAL14848" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAL14849" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAM62312" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAM62313" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAM62314" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAS07472" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.1.116" evidence="11"/>
    <dbReference type="EMBL" id="AF412030">
        <property type="protein sequence ID" value="AAM62312.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF412031">
        <property type="protein sequence ID" value="AAM62313.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF412032">
        <property type="protein sequence ID" value="AAM62314.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY053499">
        <property type="protein sequence ID" value="AAL14848.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY053500">
        <property type="protein sequence ID" value="AAL14849.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073846">
        <property type="protein sequence ID" value="AAS07472.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008251">
        <property type="protein sequence ID" value="AAH08251.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011712">
        <property type="protein sequence ID" value="AAH11712.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067750">
        <property type="protein sequence ID" value="AAH67750.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF217971">
        <property type="protein sequence ID" value="AAG17214.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47607.2">
        <molecule id="Q8NFV4-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47608.2">
        <molecule id="Q8NFV4-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5558.2">
        <molecule id="Q8NFV4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138836.2">
        <molecule id="Q8NFV4-6"/>
        <property type="nucleotide sequence ID" value="NM_001145364.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001287987.2">
        <property type="nucleotide sequence ID" value="NM_001301058.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_683710.2">
        <molecule id="Q8NFV4-1"/>
        <property type="nucleotide sequence ID" value="NM_148912.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_683711.2">
        <molecule id="Q8NFV4-4"/>
        <property type="nucleotide sequence ID" value="NM_148913.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8NFV4"/>
    <dbReference type="SMR" id="Q8NFV4"/>
    <dbReference type="BioGRID" id="123653">
        <property type="interactions" value="91"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8NFV4">
        <property type="interactions" value="875"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8NFV4">
        <property type="interactions" value="54"/>
    </dbReference>
    <dbReference type="MINT" id="Q8NFV4"/>
    <dbReference type="STRING" id="9606.ENSP00000222800"/>
    <dbReference type="BindingDB" id="Q8NFV4"/>
    <dbReference type="ChEMBL" id="CHEMBL2189134"/>
    <dbReference type="ESTHER" id="human-ABHD11">
        <property type="family name" value="ABHD11-Acetyl_transferase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.976"/>
    <dbReference type="GlyGen" id="Q8NFV4">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="PhosphoSitePlus" id="Q8NFV4"/>
    <dbReference type="SwissPalm" id="Q8NFV4"/>
    <dbReference type="BioMuta" id="ABHD11"/>
    <dbReference type="DMDM" id="74751292"/>
    <dbReference type="jPOST" id="Q8NFV4"/>
    <dbReference type="MassIVE" id="Q8NFV4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000222800"/>
    <dbReference type="PeptideAtlas" id="Q8NFV4"/>
    <dbReference type="ProteomicsDB" id="43672"/>
    <dbReference type="ProteomicsDB" id="73364">
        <molecule id="Q8NFV4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73365">
        <molecule id="Q8NFV4-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73366">
        <molecule id="Q8NFV4-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73367">
        <molecule id="Q8NFV4-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73368">
        <molecule id="Q8NFV4-5"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8NFV4"/>
    <dbReference type="TopDownProteomics" id="Q8NFV4-1">
        <molecule id="Q8NFV4-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="14446">
        <property type="antibodies" value="133 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="83451"/>
    <dbReference type="Ensembl" id="ENST00000222800.8">
        <molecule id="Q8NFV4-1"/>
        <property type="protein sequence ID" value="ENSP00000222800.4"/>
        <property type="gene ID" value="ENSG00000106077.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000357419.9">
        <molecule id="Q8NFV4-2"/>
        <property type="protein sequence ID" value="ENSP00000392945.3"/>
        <property type="gene ID" value="ENSG00000106077.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000395147.9">
        <molecule id="Q8NFV4-6"/>
        <property type="protein sequence ID" value="ENSP00000378579.5"/>
        <property type="gene ID" value="ENSG00000106077.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000437775.7">
        <molecule id="Q8NFV4-4"/>
        <property type="protein sequence ID" value="ENSP00000416970.3"/>
        <property type="gene ID" value="ENSG00000106077.20"/>
    </dbReference>
    <dbReference type="GeneID" id="83451"/>
    <dbReference type="KEGG" id="hsa:83451"/>
    <dbReference type="MANE-Select" id="ENST00000222800.8">
        <property type="protein sequence ID" value="ENSP00000222800.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_148912.4"/>
        <property type="RefSeq protein sequence ID" value="NP_683710.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003tzb.4">
        <molecule id="Q8NFV4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16407"/>
    <dbReference type="ClinPGx" id="PA38134"/>
    <dbReference type="CTD" id="83451"/>
    <dbReference type="DisGeNET" id="83451"/>
    <dbReference type="GeneCards" id="ABHD11"/>
    <dbReference type="HGNC" id="HGNC:16407">
        <property type="gene designation" value="ABHD11"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000106077">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621050">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000106077"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000106077"/>
    <dbReference type="eggNOG" id="KOG2382">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000015880"/>
    <dbReference type="HOGENOM" id="CLU_020336_53_0_1"/>
    <dbReference type="InParanoid" id="Q8NFV4"/>
    <dbReference type="OrthoDB" id="8119704at2759"/>
    <dbReference type="PAN-GO" id="Q8NFV4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NFV4"/>
    <dbReference type="PathwayCommons" id="Q8NFV4"/>
    <dbReference type="SignaLink" id="Q8NFV4"/>
    <dbReference type="Agora" id="ENSG00000106077"/>
    <dbReference type="BioGRID-ORCS" id="83451">
        <property type="hits" value="255 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD11">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABHD11"/>
    <dbReference type="GenomeRNAi" id="83451"/>
    <dbReference type="Pharos" id="Q8NFV4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NFV4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NFV4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000106077">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 200 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8NFV4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045252">
        <property type="term" value="C:oxoglutarate dehydrogenase complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016298">
        <property type="term" value="F:lipase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000039">
        <property type="entry name" value="Esterase ybfF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46118">
        <property type="entry name" value="PROTEIN ABHD11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46118:SF4">
        <property type="entry name" value="PROTEIN ABHD11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00111">
        <property type="entry name" value="ABHYDROLASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <keyword id="KW-0856">Williams-Beuren syndrome</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="10">
        <location>
            <begin position="1"/>
            <end status="unknown"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000281003" description="sn-1-specific diacylglycerol lipase ABHD11">
        <location>
            <begin status="unknown"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="19"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="4">
        <location>
            <begin position="23"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023924" description="In isoform 4 and isoform 5." evidence="8">
        <location>
            <begin position="42"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023925" description="In isoform 2." evidence="8 9">
        <original>RVLTVD</original>
        <variation>ADGGCS</variation>
        <location>
            <begin position="87"/>
            <end position="92"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023926" description="In isoform 3." evidence="8">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="88"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023927" description="In isoform 3." evidence="8">
        <location>
            <begin position="89"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023928" description="In isoform 2." evidence="8 9">
        <location>
            <begin position="93"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023929" description="In isoform 5." evidence="8">
        <original>DLLPQLGLVPCVVVGHSMGGKTAMLLAL</original>
        <variation>PAPHLGTEGLRQALCGHEVLQGWSDLRL</variation>
        <location>
            <begin position="116"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023930" description="In isoform 5." evidence="8">
        <location>
            <begin position="144"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046994" description="In isoform 6." evidence="10">
        <location>
            <begin position="146"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of p-nitrophenyl ester hydrolysis. Does not affect mitochondrion location. Loss of DLST lipoylation." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of DLST lipoylation." evidence="7">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3SZ73"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8K4F5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12073013"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="32579589"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="32792488"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="12073013"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15498874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="32579589"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:16407"/>
        </source>
    </evidence>
    <sequence length="306" mass="33747" checksum="AFA68D6E4A3234A0" modified="2024-01-24" version="2" precursor="true">MLRWTRAWRLPREGLGPHGPSFARVPVAPSSSSGGRGGAEPRPLPLSYRLLDGEAALPAVVFLHGLFGSKTNFNSIAKILAQQTGRRVLTVDARNHGDSPHSPDMSYEIMSQDLQDLLPQLGLVPCVVVGHSMGGKTAMLLALQRPELVERLIAVDISPVESTGVSHFATYVAAMRAINIADELPRSRARKLADEQLSSVIQDMAVRQHLLTNLVEVDGRFVWRVNLDALTQHLDKILAFPQRQESYLGPTLFLLGGNSQFVHPSHHPEIMRLFPRAQMQTVPNAGHWIHADRPQDFIAAIRGFLV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-11-07" modified="2026-01-28" version="152" xmlns="https://uniprot.org/uniprot">
    <accession>Q9P1F3</accession>
    <accession>Q5SZC8</accession>
    <accession>Q9P0A1</accession>
    <name>ABRAL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Costars family protein ABRACL</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ABRA C-terminal-like protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABRACL</name>
        <name type="synonym">C6orf115</name>
        <name type="ORF">HSPC280</name>
        <name type="ORF">PRO2013</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1998-12" db="EMBL/GenBank/DDBJ databases">
            <title>Functional prediction of the coding sequences of 121 new genes deduced by analysis of cDNA clones from human fetal liver.</title>
            <authorList>
                <person name="Zhang C."/>
                <person name="Yu Y."/>
                <person name="Zhang S."/>
                <person name="Wei H."/>
                <person name="Zhou G."/>
                <person name="Ouyang S."/>
                <person name="Luo L."/>
                <person name="Bi J."/>
                <person name="Liu M."/>
                <person name="He F."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Fetal liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Genome Res." volume="10" first="1546" last="1560">
            <title>Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.</title>
            <authorList>
                <person name="Zhang Q.-H."/>
                <person name="Ye M."/>
                <person name="Wu X.-Y."/>
                <person name="Ren S.-X."/>
                <person name="Zhao M."/>
                <person name="Zhao C.-J."/>
                <person name="Fu G."/>
                <person name="Shen Y."/>
                <person name="Fan H.-Y."/>
                <person name="Lu G."/>
                <person name="Zhong M."/>
                <person name="Xu X.-R."/>
                <person name="Han Z.-G."/>
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    <comment type="similarity">
        <text evidence="1">Belongs to the costars family.</text>
    </comment>
    <comment type="sequence caution" evidence="1">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAF28958" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
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    <dbReference type="RefSeq" id="XP_054212103.1">
        <property type="nucleotide sequence ID" value="XM_054356128.1"/>
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        <property type="nucleotide sequence ID" value="XM_054356129.1"/>
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        <property type="nucleotide sequence ID" value="XM_054356130.1"/>
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        </source>
    </evidence>
    <evidence type="ECO:0007744" key="3">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="4">
        <source>
            <dbReference type="PDB" id="2L2O"/>
        </source>
    </evidence>
    <sequence length="81" mass="9056" checksum="1F0DCE7A1D22B171" modified="2000-10-01" version="1">MNVDHEVNLLVEEIHRLGSKNADGKLSVKFGVLFRDDKCANLFEALVGTLKAAKRRKIVTYPGELLLQGVHDDVDIILLQD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-06-26" modified="2026-01-28" version="156" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NX38</accession>
    <accession>Q5JTR0</accession>
    <accession>Q5JTR1</accession>
    <name>ABITM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Protein Abitram</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Actin-binding transcription modulator</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Protein Simiate</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ABITRAM</name>
        <name type="synonym">C9orf6</name>
        <name evidence="4" type="synonym">FAM206A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
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                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="369" last="374">
            <title>DNA sequence and analysis of human chromosome 9.</title>
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            </authorList>
            <dbReference type="PubMed" id="15164053"/>
            <dbReference type="DOI" id="10.1038/nature02465"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2013" name="PLoS ONE" volume="8" first="E83007" last="E83007">
            <title>Identification and characterisation of Simiate, a novel protein linked to the fragile X syndrome.</title>
            <authorList>
                <person name="Derlig K."/>
                <person name="Giessl A."/>
                <person name="Brandstatter J.H."/>
                <person name="Enz R."/>
                <person name="Dahlhaus R."/>
            </authorList>
            <dbReference type="PubMed" id="24349419"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0083007"/>
        </citation>
        <scope>DEPLETION</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Actin-binding protein that regulates actin polymerization, filopodia dynamics and increases the branching of proximal dendrites of developing neurons.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with F-actin (By similarity). Interacts with G-actin (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9105722">
            <id>Q9NX38</id>
        </interactant>
        <interactant intactId="EBI-2549423">
            <id>Q6NT76</id>
            <label>HMBOX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9105722">
            <id>Q9NX38</id>
        </interactant>
        <interactant intactId="EBI-6165891">
            <id>Q14696</id>
            <label>MESD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9105722">
            <id>Q9NX38</id>
        </interactant>
        <interactant intactId="EBI-10216552">
            <id>Q8IY42</id>
            <label>PGCKA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9105722">
            <id>Q9NX38</id>
        </interactant>
        <interactant intactId="EBI-11983583">
            <id>Q3MIT2</id>
            <label>PUS10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Nucleus speckle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Lamellipodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Growth cone</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Dendrite</location>
        </subcellularLocation>
        <text evidence="1">Localizes to somata and dendrites in cortical neurons (By similarity). Colocalizes with G- and F-actin in lamellipodia (By similarity). Colocalizes in the nucleus with PTK2 (By similarity).</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="3">Depletion of ABITRAM by siRNA or neutralizing antibodies results in cell death within a few hours.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the ABITRAM family.</text>
    </comment>
    <dbReference type="EMBL" id="AF153417">
        <property type="protein sequence ID" value="AAG43367.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000464">
        <property type="protein sequence ID" value="BAA91183.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL354797">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015795">
        <property type="protein sequence ID" value="AAH15795.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6774.1"/>
    <dbReference type="RefSeq" id="NP_060302.1">
        <property type="nucleotide sequence ID" value="NM_017832.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NX38"/>
    <dbReference type="SMR" id="Q9NX38"/>
    <dbReference type="BioGRID" id="120282">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NX38">
        <property type="interactions" value="1053"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NX38">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000363753"/>
    <dbReference type="iPTMnet" id="Q9NX38"/>
    <dbReference type="PhosphoSitePlus" id="Q9NX38"/>
    <dbReference type="BioMuta" id="FAM206A"/>
    <dbReference type="DMDM" id="74753037"/>
    <dbReference type="jPOST" id="Q9NX38"/>
    <dbReference type="MassIVE" id="Q9NX38"/>
    <dbReference type="PaxDb" id="9606-ENSP00000363753"/>
    <dbReference type="PeptideAtlas" id="Q9NX38"/>
    <dbReference type="ProteomicsDB" id="83030"/>
    <dbReference type="Pumba" id="Q9NX38"/>
    <dbReference type="Antibodypedia" id="29387">
        <property type="antibodies" value="54 antibodies from 9 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="54942"/>
    <dbReference type="Ensembl" id="ENST00000322940.11">
        <property type="protein sequence ID" value="ENSP00000363753.3"/>
        <property type="gene ID" value="ENSG00000119328.13"/>
    </dbReference>
    <dbReference type="GeneID" id="54942"/>
    <dbReference type="KEGG" id="hsa:54942"/>
    <dbReference type="MANE-Select" id="ENST00000322940.11">
        <property type="protein sequence ID" value="ENSP00000363753.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_017832.4"/>
        <property type="RefSeq protein sequence ID" value="NP_060302.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004bdn.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1364"/>
    <dbReference type="ClinPGx" id="PA25981"/>
    <dbReference type="CTD" id="54942"/>
    <dbReference type="DisGeNET" id="54942"/>
    <dbReference type="GeneCards" id="ABITRAM"/>
    <dbReference type="HGNC" id="HGNC:1364">
        <property type="gene designation" value="ABITRAM"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000119328">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="620392">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000119328"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000119328"/>
    <dbReference type="eggNOG" id="KOG3266">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00450000040303"/>
    <dbReference type="HOGENOM" id="CLU_107323_1_0_1"/>
    <dbReference type="InParanoid" id="Q9NX38"/>
    <dbReference type="OMA" id="GKACEDH"/>
    <dbReference type="OrthoDB" id="48130at2759"/>
    <dbReference type="PAN-GO" id="Q9NX38">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NX38"/>
    <dbReference type="PathwayCommons" id="Q9NX38"/>
    <dbReference type="SignaLink" id="Q9NX38"/>
    <dbReference type="Agora" id="ENSG00000119328"/>
    <dbReference type="BioGRID-ORCS" id="54942">
        <property type="hits" value="10 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="FAM206A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="54942"/>
    <dbReference type="Pharos" id="Q9NX38">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NX38"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NX38">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000119328">
        <property type="expression patterns" value="Expressed in bronchial epithelial cell and 206 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NX38">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030425">
        <property type="term" value="C:dendrite"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032433">
        <property type="term" value="C:filopodium tip"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030426">
        <property type="term" value="C:growth cone"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030027">
        <property type="term" value="C:lamellipodium"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016607">
        <property type="term" value="C:nuclear speck"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051015">
        <property type="term" value="F:actin filament binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003785">
        <property type="term" value="F:actin monomer binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048813">
        <property type="term" value="P:dendrite morphogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030833">
        <property type="term" value="P:regulation of actin filament polymerization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051489">
        <property type="term" value="P:regulation of filopodium assembly"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.50.100:FF:000048">
        <property type="entry name" value="Protein Abitram"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.50.100">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039169">
        <property type="entry name" value="Abitram"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033753">
        <property type="entry name" value="GCV_H/Fam206"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011053">
        <property type="entry name" value="Single_hybrid_motif"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13651">
        <property type="entry name" value="PROTEIN ABITRAM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13651:SF0">
        <property type="entry name" value="PROTEIN ABITRAM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01597">
        <property type="entry name" value="GCV_H"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51230">
        <property type="entry name" value="Single hybrid motif"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0009">Actin-binding</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000291928" description="Protein Abitram">
        <location>
            <begin position="1"/>
            <end position="181"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q80ZQ9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="2"/>
    <evidence type="ECO:0000305" key="3">
        <source>
            <dbReference type="PubMed" id="24349419"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:1364"/>
        </source>
    </evidence>
    <sequence length="181" mass="20378" checksum="2336750B1E59EB32" modified="2000-10-01" version="1">MATEPEAAEPVVPSLVDRYFTRWYKPDVKGKFCEDHCILQHSNRICVITLAESHPVLQSGKTIKSISYQISTNCSRLQNKVSGKFKRGAQFLTELAPLCKIYCSDGEEYTVSSCVRGRLMEVNENILHKPSILQEKPSTEGYIAVVLPKFEESKSITEGLLTQKQYEEVMVKRINATTATS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-09-27" modified="2026-01-28" version="165" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TB40</accession>
    <accession>B4DDH7</accession>
    <accession>Q9H9E0</accession>
    <name>ABHD4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">(Lyso)-N-acylphosphatidylethanolamine lipase</fullName>
            <ecNumber>3.1.1.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="4">Alpha/beta hydrolase domain-containing protein 4</fullName>
            <shortName evidence="5">Abhydrolase domain-containing protein 4</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha/beta-hydrolase 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ABHD4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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                <person name="Nakagawa S."/>
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                <person name="Wakebe H."/>
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                <person name="Sugiyama A."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
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                <person name="Heilig R."/>
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                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
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                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
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                <person name="Segurens B."/>
                <person name="Aniere F."/>
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                <person name="Crespeau H."/>
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                <person name="Aiach N."/>
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                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
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                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
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                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
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                <person name="Bataille E."/>
                <person name="Bluet E."/>
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                <person name="Dubois M."/>
                <person name="Dumont C."/>
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                <person name="Pellouin V."/>
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                <person name="Gauguet G."/>
                <person name="Roy A."/>
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                <person name="Verdier-Discala C."/>
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                <person name="Fulton L."/>
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                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
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                <person name="Hood L."/>
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            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Cervix</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Lysophospholipase selective for N-acyl phosphatidylethanolamine (NAPE). Contributes to the biosynthesis of N-acyl ethanolamines, including the endocannabinoid anandamide by hydrolyzing the sn-1 and sn-2 acyl chains from N-acyl phosphatidylethanolamine (NAPE) generating glycerophospho-N-acyl ethanolamine (GP-NAE), an intermediate for N-acyl ethanolamine biosynthesis. Hydrolyzes substrates bearing saturated, monounsaturated, polyunsaturated N-acyl chains. Shows no significant activity towards other lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45424"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:78097"/>
            <dbReference type="ChEBI" id="CHEBI:85217"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45425"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>an N-acyl-1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = N,1-diacyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45460"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:62537"/>
            <dbReference type="ChEBI" id="CHEBI:85216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45461"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-hexadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-hexadecanoyl-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45384"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:85217"/>
            <dbReference type="ChEBI" id="CHEBI:85226"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45385"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-octadecanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-octadecanoyl-sn-glycero-3-phospho-ethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45388"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:85219"/>
            <dbReference type="ChEBI" id="CHEBI:85227"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45389"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-eicosanoyl-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-eicosanoyl-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45392"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:85221"/>
            <dbReference type="ChEBI" id="CHEBI:85228"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45393"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N,1-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45396"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:85222"/>
            <dbReference type="ChEBI" id="CHEBI:85229"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45397"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45400"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:85223"/>
            <dbReference type="ChEBI" id="CHEBI:85230"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45401"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(N-hexadecanoyl)-serine + H2O = 1-octadecanoyl-2-hydroxy-sn-glycero-3-phospho-(N-hexadecanoyl)-serine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55236"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:138661"/>
            <dbReference type="ChEBI" id="CHEBI:138662"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:55237"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>1-O-(1Z-octadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-hexadecanoyl-ethanolamine + H2O = 1-O-(1Z-octadecenyl)-sn-glycero-3-phospho-N-hexadecanoyl-ethanolamine + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55240"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:137009"/>
            <dbReference type="ChEBI" id="CHEBI:138663"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:55241"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N,1-diacyl-sn-glycero-3-phosphoethanolamine + H2O = N-acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:45420"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:85216"/>
            <dbReference type="ChEBI" id="CHEBI:85225"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:45421"/>
        </physiologicalReaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-448665">
            <id>Q9NWT8</id>
            <label>AURKAIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-752094">
            <id>Q12982</id>
            <label>BNIP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-11522780">
            <id>Q96DZ9-2</id>
            <label>CMTM5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-12211159">
            <id>P29400-2</id>
            <label>COL4A5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-398977">
            <id>Q9BUN8</id>
            <label>DERL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-12831978">
            <id>Q6ZPD8</id>
            <label>DGAT2L6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-12937691">
            <id>Q9BUP3-3</id>
            <label>HTATIP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-720480">
            <id>P24593</id>
            <label>IGFBP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-8503746">
            <id>Q9Y5U4</id>
            <label>INSIG2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-725795">
            <id>O60664</id>
            <label>PLIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-712367">
            <id>Q9UI14</id>
            <label>RABAC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7131019">
            <id>Q8TB40</id>
        </interactant>
        <interactant intactId="EBI-1549827">
            <id>Q00765</id>
            <label>REEP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8TB40-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8TB40-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056924 VSP_056925"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">Thr-291 is present instead of the conserved His which is expected to be an active site residue.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.-"/>
    <dbReference type="EMBL" id="AK022878">
        <property type="protein sequence ID" value="BAB14289.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293198">
        <property type="protein sequence ID" value="BAG56738.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL160314">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC024779">
        <property type="protein sequence ID" value="AAH24779.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9572.1">
        <molecule id="Q8TB40-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_071343.2">
        <molecule id="Q8TB40-1"/>
        <property type="nucleotide sequence ID" value="NM_022060.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TB40"/>
    <dbReference type="SMR" id="Q8TB40"/>
    <dbReference type="BioGRID" id="121967">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TB40">
        <property type="interactions" value="785"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TB40">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="MINT" id="Q8TB40"/>
    <dbReference type="STRING" id="9606.ENSP00000414558"/>
    <dbReference type="ESTHER" id="human-ABHD4">
        <property type="family name" value="CGI-58_ABHD5_ABHD4"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.013"/>
    <dbReference type="iPTMnet" id="Q8TB40"/>
    <dbReference type="PhosphoSitePlus" id="Q8TB40"/>
    <dbReference type="BioMuta" id="ABHD4"/>
    <dbReference type="DMDM" id="74762601"/>
    <dbReference type="jPOST" id="Q8TB40"/>
    <dbReference type="MassIVE" id="Q8TB40"/>
    <dbReference type="PaxDb" id="9606-ENSP00000414558"/>
    <dbReference type="PeptideAtlas" id="Q8TB40"/>
    <dbReference type="ProteomicsDB" id="3863"/>
    <dbReference type="ProteomicsDB" id="73960">
        <molecule id="Q8TB40-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8TB40"/>
    <dbReference type="Antibodypedia" id="4">
        <property type="antibodies" value="222 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="63874"/>
    <dbReference type="Ensembl" id="ENST00000418446.6">
        <molecule id="Q8TB40-2"/>
        <property type="protein sequence ID" value="ENSP00000388751.2"/>
        <property type="gene ID" value="ENSG00000100439.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000428304.7">
        <molecule id="Q8TB40-1"/>
        <property type="protein sequence ID" value="ENSP00000414558.2"/>
        <property type="gene ID" value="ENSG00000100439.12"/>
    </dbReference>
    <dbReference type="GeneID" id="63874"/>
    <dbReference type="KEGG" id="hsa:63874"/>
    <dbReference type="MANE-Select" id="ENST00000428304.7">
        <property type="protein sequence ID" value="ENSP00000414558.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_022060.3"/>
        <property type="RefSeq protein sequence ID" value="NP_071343.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001wgm.4">
        <molecule id="Q8TB40-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:20154"/>
    <dbReference type="ClinPGx" id="PA128394705"/>
    <dbReference type="CTD" id="63874"/>
    <dbReference type="DisGeNET" id="63874"/>
    <dbReference type="GeneCards" id="ABHD4"/>
    <dbReference type="HGNC" id="HGNC:20154">
        <property type="gene designation" value="ABHD4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100439">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="619728">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000100439"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000100439"/>
    <dbReference type="eggNOG" id="KOG4409">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000016277"/>
    <dbReference type="HOGENOM" id="CLU_017361_0_0_1"/>
    <dbReference type="InParanoid" id="Q8TB40"/>
    <dbReference type="OMA" id="ETAYHAM"/>
    <dbReference type="OrthoDB" id="7457040at2759"/>
    <dbReference type="PAN-GO" id="Q8TB40">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8TB40"/>
    <dbReference type="BioCyc" id="MetaCyc:ENSG00000100439-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q8TB40"/>
    <dbReference type="Reactome" id="R-HSA-1482839">
        <property type="pathway name" value="Acyl chain remodelling of PE"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8TB40"/>
    <dbReference type="Agora" id="ENSG00000100439"/>
    <dbReference type="BioGRID-ORCS" id="63874">
        <property type="hits" value="6 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="63874"/>
    <dbReference type="Pharos" id="Q8TB40">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8TB40"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TB40">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000100439">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 161 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8TB40">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005811">
        <property type="term" value="C:lipid droplet"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016787">
        <property type="term" value="F:hydrolase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042171">
        <property type="term" value="F:lysophosphatidic acid acyltransferase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004622">
        <property type="term" value="F:phosphatidylcholine lysophospholipase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016042">
        <property type="term" value="P:lipid catabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055088">
        <property type="term" value="P:lipid homeostasis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070292">
        <property type="term" value="P:N-acylphosphatidylethanolamine metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006654">
        <property type="term" value="P:phosphatidic acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036152">
        <property type="term" value="P:phosphatidylethanolamine acyl-chain remodeling"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000044">
        <property type="entry name" value="Abhydrolase domain containing 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886:SF21">
        <property type="entry name" value="(LYSO)-N-ACYLPHOSPHATIDYLETHANOLAMINE LIPASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886">
        <property type="entry name" value="RE40534P-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00111">
        <property type="entry name" value="ABHYDROLASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0442">Lipid degradation</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000080864" description="(Lyso)-N-acylphosphatidylethanolamine lipase">
        <location>
            <begin position="1"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="2">
        <location>
            <begin position="70"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056924" description="In isoform 2." evidence="3">
        <original>VKHLILVDPWGFPLRPTNP</original>
        <variation>AWSGAAIPAGLQTQVCRLL</variation>
        <location>
            <begin position="163"/>
            <end position="181"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056925" description="In isoform 2." evidence="3">
        <location>
            <begin position="182"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB14289." evidence="4" ref="1">
        <original>EIR</original>
        <variation>GIC</variation>
        <location>
            <begin position="183"/>
            <end position="185"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8VD66"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:20154"/>
        </source>
    </evidence>
    <sequence length="342" mass="38794" checksum="867EA9E0092559CB" modified="2002-06-01" version="1">MADDLEQQSQGWLSSWLPTWRPTSMSQLKNVEARILQCLQNKFLARYVSLPNQNKIWTVTVSPEQNDRTPLVMVHGFGGGVGLWILNMDSLSARRTLHTFDLLGFGRSSRPAFPRDPEGAEDEFVTSIETWRETMGIPSMILLGHSLGGFLATSYSIKYPDRVKHLILVDPWGFPLRPTNPSEIRAPPAWVKAVASVLGRSNPLAVLRVAGPWGPGLVQRFRPDFKRKFADFFEDDTISEYIYHCNAQNPSGETAFKAMMESFGWARRPMLERIHLIRKDVPITMIYGSDTWIDTSTGKKVKMQRPDSYVRDMEIKGASHHVYADQPHIFNAVVEEICDSVD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-19" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>Q9P2A4</accession>
    <accession>C9IZN8</accession>
    <accession>Q9H0P6</accession>
    <name>ABI3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ABI gene family member 3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>New molecule including SH3</fullName>
            <shortName>Nesh</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABI3</name>
        <name type="synonym">NESH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Biochim. Biophys. Acta" volume="1493" first="237" last="241">
            <title>Isolation and characterization of a novel human gene (NESH) which encodes a putative signaling molecule similar to e3B1 protein.</title>
            <authorList>
                <person name="Miyazaki K."/>
                <person name="Matsuda S."/>
                <person name="Ichigotani Y."/>
                <person name="Takenouchi Y."/>
                <person name="Hayashi K."/>
                <person name="Fukuda Y."/>
                <person name="Nimura Y."/>
                <person name="Hamaguchi M."/>
            </authorList>
            <dbReference type="PubMed" id="10978530"/>
            <dbReference type="DOI" id="10.1016/s0167-4781(00)00158-5"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT SER-209</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
                <person name="Wellenreuther R."/>
                <person name="Gassenhuber J."/>
                <person name="Glassl S."/>
                <person name="Ansorge W."/>
                <person name="Boecher M."/>
                <person name="Bloecker H."/>
                <person name="Bauersachs S."/>
                <person name="Blum H."/>
                <person name="Lauber J."/>
                <person name="Duesterhoeft A."/>
                <person name="Beyer A."/>
                <person name="Koehrer K."/>
                <person name="Strack N."/>
                <person name="Mewes H.-W."/>
                <person name="Ottenwaelder B."/>
                <person name="Obermaier B."/>
                <person name="Tampe J."/>
                <person name="Heubner D."/>
                <person name="Wambutt R."/>
                <person name="Korn B."/>
                <person name="Klein M."/>
                <person name="Poustka A."/>
            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS GLN-44 AND SER-209</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
            <authorList>
                <person name="Zody M.C."/>
                <person name="Garber M."/>
                <person name="Adams D.J."/>
                <person name="Sharpe T."/>
                <person name="Harrow J."/>
                <person name="Lupski J.R."/>
                <person name="Nicholson C."/>
                <person name="Searle S.M."/>
                <person name="Wilming L."/>
                <person name="Young S.K."/>
                <person name="Abouelleil A."/>
                <person name="Allen N.R."/>
                <person name="Bi W."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Bugalter B.E."/>
                <person name="Butler J."/>
                <person name="Chang J.L."/>
                <person name="Chen C.-K."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="Cuomo C.A."/>
                <person name="de Jong P.J."/>
                <person name="DeCaprio D."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M."/>
                <person name="Gilbert J."/>
                <person name="Gibson R."/>
                <person name="Gnerre S."/>
                <person name="Goldstein S."/>
                <person name="Grafham D.V."/>
                <person name="Grocock R."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hart E."/>
                <person name="Norman C.H."/>
                <person name="Humphray S."/>
                <person name="Jaffe D.B."/>
                <person name="Jones M."/>
                <person name="Kamal M."/>
                <person name="Khodiyar V.K."/>
                <person name="LaButti K."/>
                <person name="Laird G."/>
                <person name="Lehoczky J."/>
                <person name="Liu X."/>
                <person name="Lokyitsang T."/>
                <person name="Loveland J."/>
                <person name="Lui A."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews L."/>
                <person name="Mauceli E."/>
                <person name="McCarroll S.A."/>
                <person name="Mihalev A.H."/>
                <person name="Mudge J."/>
                <person name="Nguyen C."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Osoegawa K."/>
                <person name="Schwartz D.C."/>
                <person name="Shaw-Smith C."/>
                <person name="Stankiewicz P."/>
                <person name="Steward C."/>
                <person name="Swarbreck D."/>
                <person name="Venkataraman V."/>
                <person name="Whittaker C.A."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Bradley A."/>
                <person name="Hubbard T."/>
                <person name="Birren B.W."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-209</scope>
        <source>
            <tissue>B-cell</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2002" name="Cancer Res." volume="62" first="2215" last="2219">
            <title>Forced expression of NESH suppresses motility and metastatic dissemination of malignant cells.</title>
            <authorList>
                <person name="Ichigotani Y."/>
                <person name="Yokozaki S."/>
                <person name="Fukuda Y."/>
                <person name="Hamaguchi M."/>
                <person name="Matsuda S."/>
            </authorList>
            <dbReference type="PubMed" id="11956071"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2001" name="J. Hum. Genet." volume="46" first="483" last="486">
            <title>Cloning and sequencing of a novel human gene that encodes a putative target protein of Nesh-SH3.</title>
            <authorList>
                <person name="Matsuda S."/>
                <person name="Iriyama C."/>
                <person name="Yokozaki S."/>
                <person name="Ichigotani Y."/>
                <person name="Shirafuji N."/>
                <person name="Yamaki K."/>
                <person name="Hayakawa T."/>
                <person name="Hamaguchi M."/>
            </authorList>
            <dbReference type="PubMed" id="11501947"/>
            <dbReference type="DOI" id="10.1007/s100380170049"/>
        </citation>
        <scope>INTERACTION WITH TARSH</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-213; SER-216 AND SER-342</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] SER-209</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1 8">May inhibit tumor metastasis (By similarity). In vitro, reduces cell motility.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">May interact with PAK1 and PAK2. Probably interacts with TARSH.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
            <label>ABI3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-750254">
            <id>Q9BRR9</id>
            <label>ARHGAP9</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-742909">
            <id>Q9H6L4</id>
            <label>ARMC7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-10229433">
            <id>Q13515</id>
            <label>BFSP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-465861">
            <id>Q8TDH9</id>
            <label>BLOC1S5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2350265">
            <id>Q7L2Z9</id>
            <label>CENPQ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-744115">
            <id>Q9C0F1</id>
            <label>CEP44</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2433893">
            <id>Q96F07</id>
            <label>CYFIP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2806959">
            <id>Q6ICB0</id>
            <label>DESI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-740402">
            <id>O60941</id>
            <label>DTNB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-709735">
            <id>O15372</id>
            <label>EIF3H</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-353901">
            <id>Q7L2H7</id>
            <label>EIF3M</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-10184995">
            <id>Q6IB98</id>
            <label>EIF3S3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11748557">
            <id>Q9Y6C2-2</id>
            <label>EMILIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-346653">
            <id>Q9UI08</id>
            <label>EVL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-6448852">
            <id>Q9UI08-2</id>
            <label>EVL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11986315">
            <id>Q9H5Z6-2</id>
            <label>FAM124B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-725361">
            <id>Q9Y285</id>
            <label>FARSA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-10244131">
            <id>Q8TES7-6</id>
            <label>FBF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11427343">
            <id>Q9P2W3</id>
            <label>GNG13</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-712073">
            <id>Q8NBJ4</id>
            <label>GOLM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-746815">
            <id>Q86YM7</id>
            <label>HOMER1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-12017090">
            <id>Q9NSB8-2</id>
            <label>HOMER2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-748420">
            <id>Q9NSC5</id>
            <label>HOMER3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-9091197">
            <id>Q8IY31-3</id>
            <label>IFT20</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-8638439">
            <id>Q8IYA8</id>
            <label>IHO1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-2556193">
            <id>Q63ZY3</id>
            <label>KANK2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-739493">
            <id>Q6ZU52</id>
            <label>KIAA0408</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-14069005">
            <id>Q9BVG8-5</id>
            <label>KIFC3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-1643885">
            <id>Q6P597</id>
            <label>KLC3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>Q9P2A4</id>
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        <interactant intactId="EBI-949319">
            <id>Q9NSK0</id>
            <label>KLC4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-10171552">
            <id>A1A4E9</id>
            <label>KRT13</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-702178">
            <id>P02533</id>
            <label>KRT14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
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        <interactant intactId="EBI-2952736">
            <id>Q2M2I5</id>
            <label>KRT24</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11980489">
            <id>Q7Z3Y7</id>
            <label>KRT28</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-1058674">
            <id>Q92764</id>
            <label>KRT35</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11958506">
            <id>O76013-2</id>
            <label>KRT36</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-1047263">
            <id>O76015</id>
            <label>KRT38</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-749530">
            <id>P43365</id>
            <label>MAGEA12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-394656">
            <id>Q9NX70</id>
            <label>MED29</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-1104552">
            <id>Q9NYP9</id>
            <label>MIS18A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-995714">
            <id>Q9Y605</id>
            <label>MRFAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-748896">
            <id>Q96HT8</id>
            <label>MRFAP1L1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-713635">
            <id>O43639</id>
            <label>NCK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-928842">
            <id>Q9GZM8</id>
            <label>NDEL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2859639">
            <id>Q5HYW2</id>
            <label>NHSL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2811583">
            <id>Q9BVL2</id>
            <label>NUP58</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-536879">
            <id>O43482</id>
            <label>OIP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-359352">
            <id>P25786</id>
            <label>PSMA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-722392">
            <id>Q7L099</id>
            <label>RUFY3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11984663">
            <id>Q06455-2</id>
            <label>RUNX1T1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-10224192">
            <id>Q06455-4</id>
            <label>RUNX1T1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-346869">
            <id>Q9Y3L3</id>
            <label>SH3BP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-358489">
            <id>Q96GM5</id>
            <label>SMARCD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-712466">
            <id>Q16623</id>
            <label>STX1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-11956649">
            <id>P32856-2</id>
            <label>STX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-740595">
            <id>Q9UMX1</id>
            <label>SUFU</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-3650647">
            <id>Q9BUZ4</id>
            <label>TRAF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2932492">
            <id>Q99757</id>
            <label>TXN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2116622">
            <id>Q5ST30</id>
            <label>VARS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-748201">
            <id>P50552</id>
            <label>VASP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-346375">
            <id>P42768</id>
            <label>WAS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-1548747">
            <id>Q92558</id>
            <label>WASF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-4290615">
            <id>Q9Y6W5</id>
            <label>WASF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-10175581">
            <id>B2R8Y4</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-612">
            <id>P39682</id>
            <label>PRP39</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-21116">
            <id>P38340</id>
            <label>TAE1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742038">
            <id>Q9P2A4</id>
        </interactant>
        <interactant intactId="EBI-2343965">
            <id>O14468</id>
            <label>YOR304C-A</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Cytoplasm</location>
        </subcellularLocation>
        <text>Colocalizes with PAK2 at leading edge of cells.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9P2A4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9P2A4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041467"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expressed in heart, lung, liver, pancreas, kidney, placenta and at low levels in brain and skeletal muscle.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ABI family.</text>
    </comment>
    <dbReference type="EMBL" id="AB037886">
        <property type="protein sequence ID" value="BAA90667.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136709">
        <property type="protein sequence ID" value="CAB66644.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC004797">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC069454">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007780">
        <property type="protein sequence ID" value="AAH07780.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11546.1">
        <molecule id="Q9P2A4-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45725.1">
        <molecule id="Q9P2A4-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001128658.2">
        <molecule id="Q9P2A4-2"/>
        <property type="nucleotide sequence ID" value="NM_001135186.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057512.2">
        <molecule id="Q9P2A4-1"/>
        <property type="nucleotide sequence ID" value="NM_016428.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9P2A4"/>
    <dbReference type="SMR" id="Q9P2A4"/>
    <dbReference type="BioGRID" id="119389">
        <property type="interactions" value="91"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9P2A4"/>
    <dbReference type="FunCoup" id="Q9P2A4">
        <property type="interactions" value="63"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9P2A4">
        <property type="interactions" value="99"/>
    </dbReference>
    <dbReference type="MINT" id="Q9P2A4"/>
    <dbReference type="STRING" id="9606.ENSP00000225941"/>
    <dbReference type="GlyGen" id="Q9P2A4">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9P2A4"/>
    <dbReference type="PhosphoSitePlus" id="Q9P2A4"/>
    <dbReference type="BioMuta" id="ABI3"/>
    <dbReference type="DMDM" id="296434384"/>
    <dbReference type="jPOST" id="Q9P2A4"/>
    <dbReference type="MassIVE" id="Q9P2A4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000225941"/>
    <dbReference type="PeptideAtlas" id="Q9P2A4"/>
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        <molecule id="Q9P2A4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83764">
        <molecule id="Q9P2A4-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="53503">
        <property type="antibodies" value="92 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51225"/>
    <dbReference type="Ensembl" id="ENST00000225941.6">
        <molecule id="Q9P2A4-1"/>
        <property type="protein sequence ID" value="ENSP00000225941.1"/>
        <property type="gene ID" value="ENSG00000108798.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000419580.6">
        <molecule id="Q9P2A4-2"/>
        <property type="protein sequence ID" value="ENSP00000406651.2"/>
        <property type="gene ID" value="ENSG00000108798.10"/>
    </dbReference>
    <dbReference type="GeneID" id="51225"/>
    <dbReference type="KEGG" id="hsa:51225"/>
    <dbReference type="MANE-Select" id="ENST00000225941.6">
        <property type="protein sequence ID" value="ENSP00000225941.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016428.3"/>
        <property type="RefSeq protein sequence ID" value="NP_057512.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002iop.1">
        <molecule id="Q9P2A4-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:29859"/>
    <dbReference type="ClinPGx" id="PA134951642"/>
    <dbReference type="CTD" id="51225"/>
    <dbReference type="DisGeNET" id="51225"/>
    <dbReference type="GeneCards" id="ABI3"/>
    <dbReference type="HGNC" id="HGNC:29859">
        <property type="gene designation" value="ABI3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000108798">
        <property type="expression patterns" value="Tissue enhanced (lymphoid)"/>
    </dbReference>
    <dbReference type="MIM" id="606363">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="NIAGADS" id="ENSG00000108798"/>
    <dbReference type="OpenTargets" id="ENSG00000108798"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000108798"/>
    <dbReference type="eggNOG" id="KOG2546">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161380"/>
    <dbReference type="HOGENOM" id="CLU_035421_0_0_1"/>
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    <dbReference type="OMA" id="NVAYHIQ"/>
    <dbReference type="OrthoDB" id="5971719at2759"/>
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        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9P2A4"/>
    <dbReference type="PathwayCommons" id="Q9P2A4"/>
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    <dbReference type="Agora" id="ENSG00000108798">
        <property type="nominated target" value="Agora Nominated Target for Alzheimer's Disease"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="51225">
        <property type="hits" value="8 hits in 1135 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABI3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABI3"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9P2A4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9P2A4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000108798">
        <property type="expression patterns" value="Expressed in granulocyte and 137 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9P2A4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098858">
        <property type="term" value="C:actin-based cell projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="LIFEdb"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043198">
        <property type="term" value="C:dendritic shaft"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043197">
        <property type="term" value="C:dendritic spine"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030027">
        <property type="term" value="C:lamellipodium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014069">
        <property type="term" value="C:postsynaptic density"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031209">
        <property type="term" value="C:SCAR complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051015">
        <property type="term" value="F:actin filament binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
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    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
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        <property type="term" value="F:signaling adaptor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="P:actin cytoskeleton organization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
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        <property type="term" value="P:cell projection morphogenesis"/>
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        <property type="term" value="P:defense response to tumor cell"/>
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        <property type="term" value="P:modification of postsynaptic actin cytoskeleton"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:negative regulation of lamellipodium assembly"/>
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        <property type="project" value="ARUK-UCL"/>
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        <property type="term" value="P:negative regulation of protein localization to plasma membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
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        <property type="term" value="P:negative regulation of ruffle assembly"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ARUK-UCL"/>
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    <dbReference type="GO" id="GO:0001764">
        <property type="term" value="P:neuron migration"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:2000774">
        <property type="term" value="P:positive regulation of cellular senescence"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="ARUK-UCL"/>
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        <property type="term" value="P:regulation of cell migration"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0061001">
        <property type="term" value="P:regulation of dendritic spine morphogenesis"/>
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        <property type="project" value="ARUK-UCL"/>
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        <property type="term" value="P:regulation of postsynaptic density assembly"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd11826">
        <property type="entry name" value="SH3_Abi"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.30.30.40:FF:000170">
        <property type="entry name" value="ABI gene family member 3"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="SH3 Domains"/>
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        <property type="entry name" value="ABI"/>
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        <property type="entry name" value="ABI3_SH3"/>
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    <dbReference type="PANTHER" id="PTHR10460:SF7">
        <property type="entry name" value="ABI GENE FAMILY MEMBER 3"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR10460">
        <property type="entry name" value="ABL INTERACTOR FAMILY MEMBER"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF07815">
        <property type="entry name" value="Abi_HHR"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="SH3DOMAIN"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0728">SH3 domain</keyword>
    <feature type="chain" id="PRO_0000191792" description="ABI gene family member 3">
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            <begin position="1"/>
            <end position="366"/>
        </location>
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    <feature type="domain" description="SH3" evidence="3">
        <location>
            <begin position="308"/>
            <end position="366"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="161"/>
            <end position="195"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="215"/>
            <end position="302"/>
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    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="33"/>
            <end position="61"/>
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    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="4">
        <location>
            <begin position="232"/>
            <end position="248"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11">
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11">
        <location>
            <position position="216"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11">
        <location>
            <position position="342"/>
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    <feature type="splice variant" id="VSP_041467" description="In isoform 2." evidence="10">
        <location>
            <begin position="90"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022030" description="In dbSNP:rs2233369." evidence="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="44"/>
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    </feature>
    <feature type="sequence variant" id="VAR_060243" description="In dbSNP:rs616338.">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060993" description="In dbSNP:rs616338." evidence="5 6 9 11">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00192"/>
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    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10978530"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
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            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="366" mass="39035" checksum="23EC3838E41D8ECD" modified="2010-05-18" version="2">MAELQQLQEFEIPTGREALRGNHSALLRVADYCEDNYVQATDKRKALEETMAFTTQALASVAYQVGNLAGHTLRMLDLQGAALRQVEARVSTLGQMVNMHMEKVARREIGTLATVQRLPPGQKVIAPENLPPLTPYCRRPLNFGCLDDIGHGIKDLSTQLSRTGTLSRKSIKAPATPASATLGRPPRIPEPVHLPVVPDGRLSAASSAFSLASAGSAEGVGGAPTPKGQAAPPAPPLPSSLDPPPPPAAVEVFQRPPTLEELSPPPPDEELPLPLDLPPPPPLDGDELGLPPPPPGFGPDEPSWVPASYLEKVVTLYPYTSQKDNELSFSEGTVICVTRRYSDGWCEGVSSEGTGFFPGNYVEPSC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-07-25" modified="2026-01-28" version="154" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N0Z2</accession>
    <name>ABRA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-binding Rho-activating protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Striated muscle activator of Rho-dependent signaling</fullName>
            <shortName>STARS</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="6" type="primary">ABRA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="7" key="1">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="24453" last="24459">
            <title>STARS, a striated muscle activator of Rho signaling and serum response factor-dependent transcription.</title>
            <authorList>
                <person name="Arai A."/>
                <person name="Spencer J.A."/>
                <person name="Olson E.N."/>
            </authorList>
            <dbReference type="PubMed" id="11983702"/>
            <dbReference type="DOI" id="10.1074/jbc.m202216200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference evidence="8" key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue evidence="8">Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference evidence="5" key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Binds F-actin and ABLIM1, ABLIM2 and ABLIM3. Interaction with ABLIM2 and ABLIM3 enhances activity (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3893380">
            <id>Q8N0Z2</id>
        </interactant>
        <interactant intactId="EBI-2557469">
            <id>Q6NYC8</id>
            <label>PPP1R18</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Myofibril</location>
            <location evidence="1">Sarcomere</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <text evidence="1">Localized to the I-band of the sarcomere and to a lesser extent to the sarcomeric structure between Z-lines.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The actin-binding domain 1 (ABD1) is intrinsically disordered, and binds to F-actin with higher affinity than ABD2.</text>
    </comment>
    <dbReference type="EMBL" id="AF503617">
        <property type="protein sequence ID" value="AAM27268.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092694">
        <property type="protein sequence ID" value="BAC03948.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL833422">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC105103">
        <property type="protein sequence ID" value="AAI05104.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC105105">
        <property type="protein sequence ID" value="AAI05106.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6305.1"/>
    <dbReference type="RefSeq" id="NP_631905.1">
        <property type="nucleotide sequence ID" value="NM_139166.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054215727.1">
        <property type="nucleotide sequence ID" value="XM_054359752.1"/>
    </dbReference>
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            <dbReference type="EMBL" id="BAC03948.1"/>
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</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="292" xmlns="https://uniprot.org/uniprot">
    <accession>P00519</accession>
    <accession>A3KFJ3</accession>
    <accession>Q13869</accession>
    <accession>Q13870</accession>
    <accession>Q16133</accession>
    <accession>Q17R61</accession>
    <accession>Q45F09</accession>
    <name>ABL1_HUMAN</name>
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        <recommendedName>
            <fullName>Tyrosine-protein kinase ABL1</fullName>
            <ecNumber evidence="44 50">2.7.10.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Abelson murine leukemia viral oncogene homolog 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Abelson tyrosine-protein kinase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Proto-oncogene c-Abl</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>p150</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABL1</name>
        <name type="synonym">ABL</name>
        <name type="synonym">JTK7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1986" name="Cell" volume="47" first="277" last="284">
            <title>Alternative splicing of RNAs transcribed from the human abl gene and from the bcr-abl fused gene.</title>
            <authorList>
                <person name="Shtivelman E."/>
                <person name="Lifshitz B."/>
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                <person name="Roe B.A."/>
                <person name="Canaani E."/>
            </authorList>
            <dbReference type="PubMed" id="3021337"/>
            <dbReference type="DOI" id="10.1016/0092-8674(86)90450-2"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH BRC</scope>
        <scope>VARIANT PRO-140</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1989" name="Oncogene" volume="4" first="1477" last="1481">
            <title>Nucleotide sequence analysis of human abl and bcr-abl cDNAs.</title>
            <authorList>
                <person name="Fainstein E."/>
                <person name="Einat M."/>
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                <person name="Marcelle C."/>
                <person name="Croce C.M."/>
                <person name="Gale R.P."/>
                <person name="Canaani E."/>
            </authorList>
            <dbReference type="PubMed" id="2687768"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IA)</scope>
        <source>
            <tissue>Fibroblast</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Genomics" volume="27" first="67" last="82">
            <title>Sequence and analysis of the human ABL gene, the BCR gene, and regions involved in the Philadelphia chromosomal translocation.</title>
            <authorList>
                <person name="Chissoe S.L."/>
                <person name="Bodenteich A."/>
                <person name="Wang Y.-F."/>
                <person name="Wang Y.-P."/>
                <person name="Burian D."/>
                <person name="Clifton S.W."/>
                <person name="Crabtree J."/>
                <person name="Freeman A."/>
                <person name="Iyer K."/>
                <person name="Jian L."/>
                <person name="Ma Y."/>
                <person name="McLaury H.-J."/>
                <person name="Pan H.-Q."/>
                <person name="Sarhan O.H."/>
                <person name="Toth S."/>
                <person name="Wang Z."/>
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                <person name="Roe B.A."/>
            </authorList>
            <dbReference type="PubMed" id="7665185"/>
            <dbReference type="DOI" id="10.1006/geno.1995.1008"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS IA AND IB)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS VAL-706; PRO-852; SER-900 AND LEU-972</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="369" last="374">
            <title>DNA sequence and analysis of human chromosome 9.</title>
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                <person name="Humphray S.J."/>
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                <person name="Sycamore N."/>
                <person name="Tester J."/>
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                <person name="Tracey A."/>
                <person name="Tromans A."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-253; TYR-257; TYR-413; SER-559; SER-569; SER-620; SER-683; SER-718; THR-751; THR-781; THR-823; THR-844; THR-852; SER-855 AND SER-917</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-569</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="16424036"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 229-513 OF MUTANT PRO-396 IN COMPLEX WITH INHIBITOR VX-680</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-512</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>MYRISTOYLATION AT GLY-2 (ISOFORM IB)</scope>
        <scope>PHOSPHORYLATION AT SER-50</scope>
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        <scope>CONFORMATION CHANGES DURING ACTIVATION</scope>
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            <dbReference type="PubMed" id="20357770"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 121-232 IN COMPLEX WITH ANTIBODY MIMIC HA4</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>DISEASE</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH NUP214</scope>
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            <dbReference type="PubMed" id="17344846"/>
            <dbReference type="DOI" id="10.1038/nature05610"/>
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        <scope>VARIANTS GLY-47; LYS-166; VAL-706; LEU-810 AND LEU-972</scope>
    </reference>
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                <person name="Wang X."/>
                <person name="Charng W.L."/>
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        <scope>INVOLVEMENT IN CHDSKM</scope>
        <scope>VARIANTS CHDSKM CYS-226 AND THR-337</scope>
        <scope>CHARACTERIZATION OF VARIANTS CHDSKM CYS-226 AND THR-337</scope>
    </reference>
    <comment type="function">
        <text evidence="2 11 13 14 17 19 20 23 24 26 27 30 32 33 36 38 40 42 44 45 47 50 52 53 54">Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 44 50">
            <text>L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10596"/>
            <dbReference type="Rhea" id="RHEA-COMP:10136"/>
            <dbReference type="Rhea" id="RHEA-COMP:20101"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:46858"/>
            <dbReference type="ChEBI" id="CHEBI:61978"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.10.2"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 11 18 27 28 38 50">Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage. Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, also inhibits the tyrosine kinase activity (By similarity). Activated by 5-(1,3-diaryl-1H-pyrazol-4-yl)hydantoin, 5-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-2,4-imidazolidinedione (DPH) (PubMed:28428613). Inhibited by ABI1, whose activity is controlled by ABL1 itself through tyrosine phosphorylation. Also inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML), and by VX-680, an inhibitor that also acts on imatinib-resistant mutants (PubMed:28428613).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 10 11 12 13 14 15 21 24 25 27 30 31 35 36 37 39 41 43 44 46 47 48 53 54">Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16, ITGB1 and HCK (By similarity). Interacts with STX17; probably phosphorylates STX17. Interacts with INPPL1/SHIP2. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN and YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-735 and, sequesters ABL1 into the cytoplasm. Interacts with ABI1, ABI2, BCR, CRK, FGR, FYN, HCK, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases. Interacts with TBX21 (By similarity). Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1 (PubMed:22810897).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
            <label>ABI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
            <label>ADAM10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-608057">
            <id>P10275</id>
            <label>AR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-495465">
            <id>Q13315</id>
            <label>ATM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-7016840">
            <id>Q4KMG0</id>
            <label>CDON</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-886">
            <id>P46108</id>
            <label>CRK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-910">
            <id>P46109</id>
            <label>CRKL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-491549">
            <id>P35222</id>
            <label>CTNNB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-297353">
            <id>P00533</id>
            <label>EGFR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-641062">
            <id>P04626</id>
            <label>ERBB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-295284">
            <id>Q03468</id>
            <label>ERCC6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-489954">
            <id>Q14315</id>
            <label>FLNC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-3946257">
            <id>P36888</id>
            <label>FLT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-346340">
            <id>P08631</id>
            <label>HCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-300173">
            <id>P05107</id>
            <label>ITGB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1379503">
            <id>P10721</id>
            <label>KIT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1050422">
            <id>Q38SD2</id>
            <label>LRRK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-881">
            <id>Q92918</id>
            <label>MAP4K1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-995373">
            <id>Q7Z434</id>
            <label>MAVS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-6092730">
            <id>O43196</id>
            <label>MSH5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-2804728">
            <id>P15941</id>
            <label>MUC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-34603716">
            <id>P15941-12</id>
            <label>MUC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-389883">
            <id>P16333</id>
            <label>NCK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1751761">
            <id>O43900</id>
            <label>PRICKLE3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-976876">
            <id>Q13905</id>
            <label>RAPGEF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1043236">
            <id>Q86UR5</id>
            <label>RIMS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-366017">
            <id>Q13671</id>
            <label>RIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-476295">
            <id>P31947</id>
            <label>SFN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-4402156">
            <id>Q15464</id>
            <label>SHB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1752674">
            <id>O75751</id>
            <label>SLC22A3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-985879">
            <id>P37840</id>
            <label>SNCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-433642">
            <id>Q9BX66</id>
            <label>SORBS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1222956">
            <id>O60504-2</id>
            <label>SORBS3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-298181">
            <id>Q07890</id>
            <label>SOS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1186119">
            <id>P51692</id>
            <label>STAT5B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1220811">
            <id>Q9Y4G6</id>
            <label>TLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-876302">
            <id>P11387</id>
            <label>TOP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-366083">
            <id>P04637</id>
            <label>TP53</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-625518">
            <id>P15498</id>
            <label>VAV1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-1548747">
            <id>Q92558</id>
            <label>WASF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-4290615">
            <id>Q9Y6W5</id>
            <label>WASF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-375543">
            <id>P00519</id>
        </interactant>
        <interactant intactId="EBI-7016767">
            <id>O35158</id>
            <label>Cdon</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5278159">
            <id>P00519-1</id>
        </interactant>
        <interactant intactId="EBI-985879">
            <id>P37840</id>
            <label>SNCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9254597">
            <id>P00519-2</id>
        </interactant>
        <interactant intactId="EBI-17458373">
            <id>P48165</id>
            <label>GJA8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9254597">
            <id>P00519-2</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9254597">
            <id>P00519-2</id>
        </interactant>
        <interactant intactId="EBI-985879">
            <id>P37840</id>
            <label>SNCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion</location>
        </subcellularLocation>
        <text evidence="1">Shuttles between the nucleus and cytoplasm depending on environmental signals. Sequestered into the cytoplasm through interaction with 14-3-3 proteins. Localizes to mitochondria in response to oxidative stress (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform IB</molecule>
        <subcellularLocation>
            <location>Nucleus membrane</location>
            <topology>Lipid-anchor</topology>
        </subcellularLocation>
        <text>The myristoylated c-ABL protein is reported to be nuclear.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P00519-1</id>
            <name>IA</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P00519-2</id>
            <name>IB</name>
            <sequence type="described" ref="VSP_004957"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed.</text>
    </comment>
    <comment type="PTM">
        <text evidence="29">Acetylated at Lys-711 by EP300 which promotes the cytoplasmic translocation.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity. Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity. DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation (By similarity). Phosphorylation at Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division (By similarity). Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1. Phosphorylation on Thr-735 is required for binding 14-3-3 proteins for cytoplasmic translocation. Phosphorylated by PRKDC (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="16">Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation.</text>
    </comment>
    <comment type="disease">
        <disease id="DI-03735">
            <name>Leukemia, chronic myeloid</name>
            <acronym>CML</acronym>
            <description>A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts.</description>
            <dbReference type="MIM" id="608232"/>
        </disease>
        <text>The gene represented in this entry is involved in disease pathogenesis.</text>
    </comment>
    <comment type="disease">
        <text evidence="51">A chromosomal aberration involving ABL1 has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).</text>
    </comment>
    <comment type="disease">
        <text evidence="22">A chromosomal aberration involving ABL1 is found in a form of acute lymphoblastic leukemia (PubMed:15361874). Translocation t(9;9)(q34;q34) with NUP214 (PubMed:15361874).</text>
    </comment>
    <comment type="disease" evidence="49">
        <disease id="DI-05064">
            <name>Congenital heart defects and skeletal malformations syndrome</name>
            <acronym>CHDSKM</acronym>
            <description>An autosomal dominant disorder characterized by congenital heart disease with atrial and ventricular septal defects, variable skeletal abnormalities, and failure to thrive. Skeletal defects include pectus excavatum, scoliosis, and finger contractures. Some patient exhibit joint laxity.</description>
            <dbReference type="MIM" id="617602"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/1/ABL"/>
    </comment>
    <dbReference type="EC" id="2.7.10.2" evidence="44 50"/>
    <dbReference type="EMBL" id="M14752">
        <property type="protein sequence ID" value="AAA51561.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X16416">
        <property type="protein sequence ID" value="CAA34438.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U07563">
        <property type="protein sequence ID" value="AAB60394.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U07563">
        <property type="protein sequence ID" value="AAB60393.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U07561">
        <property type="protein sequence ID" value="AAB60393.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ145721">
        <property type="protein sequence ID" value="AAZ38718.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359092">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL161733">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471090">
        <property type="protein sequence ID" value="EAW87948.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117451">
        <property type="protein sequence ID" value="AAI17452.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S69223">
        <property type="protein sequence ID" value="AAD14034.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS35165.1">
        <molecule id="P00519-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS35166.1">
        <molecule id="P00519-1"/>
    </dbReference>
    <dbReference type="PIR" id="S08519">
        <property type="entry name" value="TVHUA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005148.2">
        <molecule id="P00519-1"/>
        <property type="nucleotide sequence ID" value="NM_005157.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_009297.2">
        <molecule id="P00519-2"/>
        <property type="nucleotide sequence ID" value="NM_007313.3"/>
    </dbReference>
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        <property type="method" value="NMR"/>
        <property type="chains" value="A=120-220"/>
    </dbReference>
    <dbReference type="PDB" id="1AWO">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=65-119"/>
    </dbReference>
    <dbReference type="PDB" id="1BBZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.65 A"/>
        <property type="chains" value="A/C/E/G=64-121"/>
    </dbReference>
    <dbReference type="PDB" id="1JU5">
        <property type="method" value="NMR"/>
        <property type="chains" value="C=62-122"/>
    </dbReference>
    <dbReference type="PDB" id="1OPL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.42 A"/>
        <property type="chains" value="A/B=27-512"/>
    </dbReference>
    <dbReference type="PDB" id="1ZZP">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=1007-1130"/>
    </dbReference>
    <dbReference type="PDB" id="2ABL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A=57-218"/>
    </dbReference>
    <dbReference type="PDB" id="2E2B">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=229-515"/>
    </dbReference>
    <dbReference type="PDB" id="2F4J">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.91 A"/>
        <property type="chains" value="A=229-513"/>
    </dbReference>
    <dbReference type="PDB" id="2FO0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.27 A"/>
        <property type="chains" value="A=38-512"/>
    </dbReference>
    <dbReference type="PDB" id="2G1T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=229-512"/>
    </dbReference>
    <dbReference type="PDB" id="2G2F">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B=229-512"/>
    </dbReference>
    <dbReference type="PDB" id="2G2H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=229-512"/>
    </dbReference>
    <dbReference type="PDB" id="2G2I">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.12 A"/>
        <property type="chains" value="A/B=229-512"/>
    </dbReference>
    <dbReference type="PDB" id="2GQG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B=229-500"/>
    </dbReference>
    <dbReference type="PDB" id="2HIW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=230-512"/>
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    <dbReference type="PDB" id="2HYY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C/D=228-500"/>
    </dbReference>
    <dbReference type="PDB" id="2HZ0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=228-497"/>
    </dbReference>
    <dbReference type="PDB" id="2HZ4">
        <property type="method" value="X-ray"/>
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        <property type="entry name" value="SH3_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008266">
        <property type="entry name" value="Tyr_kinase_AS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020635">
        <property type="entry name" value="Tyr_kinase_cat_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24418">
        <property type="entry name" value="TYROSINE-PROTEIN KINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08919">
        <property type="entry name" value="F_actin_bind"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07714">
        <property type="entry name" value="PK_Tyr_Ser-Thr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00017">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00018">
        <property type="entry name" value="SH3_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00401">
        <property type="entry name" value="SH2DOMAIN"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00109">
        <property type="entry name" value="TYRKINASE"/>
    </dbReference>
    <dbReference type="SMART" id="SM00808">
        <property type="entry name" value="FABD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00252">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00326">
        <property type="entry name" value="SH3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00219">
        <property type="entry name" value="TyrKc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55550">
        <property type="entry name" value="SH2 domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50044">
        <property type="entry name" value="SH3-domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00107">
        <property type="entry name" value="PROTEIN_KINASE_ATP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50011">
        <property type="entry name" value="PROTEIN_KINASE_DOM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00109">
        <property type="entry name" value="PROTEIN_KINASE_TYR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50001">
        <property type="entry name" value="SH2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50002">
        <property type="entry name" value="SH3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0072">Autophagy</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-0160">Chromosomal rearrangement</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0227">DNA damage</keyword>
    <keyword id="KW-0234">DNA repair</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0254">Endocytosis</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0519">Myristate</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0656">Proto-oncogene</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0727">SH2 domain</keyword>
    <keyword id="KW-0728">SH3 domain</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0829">Tyrosine-protein kinase</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000088050" description="Tyrosine-protein kinase ABL1">
        <location>
            <begin position="1"/>
            <end position="1130"/>
        </location>
    </feature>
    <feature type="domain" description="SH3" evidence="7">
        <location>
            <begin position="61"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="domain" description="SH2" evidence="6">
        <location>
            <begin position="127"/>
            <end position="217"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase" evidence="5">
        <location>
            <begin position="242"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="region of interest" description="CAP">
        <location>
            <begin position="1"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="9">
        <location>
            <begin position="518"/>
            <end position="996"/>
        </location>
    </feature>
    <feature type="region of interest" description="DNA-binding" evidence="1">
        <location>
            <begin position="869"/>
            <end position="968"/>
        </location>
    </feature>
    <feature type="region of interest" description="F-actin-binding">
        <location>
            <begin position="953"/>
            <end position="1130"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Kinase activation loop">
        <location>
            <begin position="381"/>
            <end position="405"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal 1" evidence="4">
        <location>
            <begin position="605"/>
            <end position="609"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal 2" evidence="4">
        <location>
            <begin position="709"/>
            <end position="715"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal 3" evidence="4">
        <location>
            <begin position="762"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="1">
        <location>
            <begin position="1090"/>
            <end position="1100"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="537"/>
            <end position="566"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="586"/>
            <end position="597"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="620"/>
            <end position="640"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="9">
        <location>
            <begin position="689"/>
            <end position="698"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="9">
        <location>
            <begin position="740"/>
            <end position="752"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="755"/>
            <end position="774"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="788"/>
            <end position="802"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="9">
        <location>
            <begin position="881"/>
            <end position="891"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="9">
        <location>
            <begin position="905"/>
            <end position="915"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="9">
        <location>
            <begin position="965"/>
            <end position="975"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="9">
        <location>
            <begin position="984"/>
            <end position="993"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="5 8">
        <location>
            <position position="363"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="248"/>
            <end position="256"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="271"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="316"/>
            <end position="322"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="site" description="Breakpoint for translocation to form BCR-ABL and NUP214-ABL1 fusion proteins" evidence="22 51">
        <location>
            <begin position="26"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="28 60 62">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by autocatalysis" evidence="31 39">
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="31">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by autocatalysis" evidence="31">
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="63">
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="63">
        <location>
            <position position="257"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by autocatalysis and SRC-type Tyr-kinases" evidence="31">
        <location>
            <position position="393"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="63">
        <location>
            <position position="413"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="446"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63">
        <location>
            <position position="559"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="58 59 60 61 62 63 64">
        <location>
            <position position="569"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by PAK2" evidence="37">
        <location>
            <position position="618"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by PAK2" evidence="37">
        <location>
            <position position="619"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63">
        <location>
            <position position="620"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="60">
        <location>
            <position position="659"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63">
        <location>
            <position position="683"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; by EP300" evidence="29">
        <location>
            <position position="711"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63">
        <location>
            <position position="718"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="25">
        <location>
            <position position="735"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="63">
        <location>
            <position position="751"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="63">
        <location>
            <position position="781"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="60">
        <location>
            <position position="814"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="63">
        <location>
            <position position="823"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="60 63">
        <location>
            <position position="844"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="59 63">
        <location>
            <position position="852"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="63">
        <location>
            <position position="855"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="59 63">
        <location>
            <position position="917"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="60">
        <location>
            <position position="977"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_004957" description="In isoform IB." evidence="56">
        <original>MLEICLKLVGCKSKKGLSSSSSCYLE</original>
        <variation>MGQQPGKVLGDQRRPSLPALHFIKGAGKKESSRHGGPHCNVFVEH</variation>
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032676" description="In a lung large cell carcinoma sample; somatic mutation." evidence="34">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051692" description="In dbSNP:rs1064152." evidence="51">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032677" description="In a melanoma sample; somatic mutation; dbSNP:rs2132958430." evidence="34">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079482" description="In CHDSKM; increases kinase activity; no effect on protein levels; dbSNP:rs1060499547." evidence="49">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051693" description="In dbSNP:rs34549764.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079483" description="In CHDSKM; increases kinase activity; no effect on protein levels; dbSNP:rs1060499548." evidence="49">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025043" description="In dbSNP:rs34634745." evidence="34 55">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="706"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032678" description="In dbSNP:rs2229071." evidence="34">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="810"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025044" description="In dbSNP:rs1588283506." evidence="55">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="852"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025045" description="In dbSNP:rs35266696." evidence="55">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="900"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051694" description="In dbSNP:rs1064165.">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="968"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025046" description="In dbSNP:rs2229067." evidence="34 55">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="972"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes phosphorylation. Loss of binding YWHAS and YWHAZ. Localizes to the nucleus. No effect on kinase activity." evidence="25">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="735"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9." evidence="57" ref="9">
        <original>AF</original>
        <variation>GK</variation>
        <location>
            <begin position="424"/>
            <end position="425"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="459"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="520"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="719"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA34438." evidence="57" ref="2">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="837"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="837"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="863"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="894"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>SPS</original>
        <variation>RPG</variation>
        <location>
            <begin position="917"/>
            <end position="919"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="952"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>QS</original>
        <variation>HP</variation>
        <location>
            <begin position="967"/>
            <end position="968"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>P</original>
        <variation>PL</variation>
        <location>
            <position position="982"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <location>
            <position position="1022"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="1045"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA51561." evidence="57" ref="1">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="1103"/>
        </location>
    </feature>
    <feature type="strand" evidence="80">
        <location>
            <begin position="26"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="strand" evidence="80">
        <location>
            <begin position="39"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="turn" evidence="80">
        <location>
            <begin position="45"/>
            <end position="47"/>
        </location>
    </feature>
    <feature type="helix" evidence="68">
        <location>
            <begin position="49"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="helix" evidence="68">
        <location>
            <begin position="58"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="strand" evidence="79">
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    <reference key="1">
        <citation type="journal article" date="2000" name="Mol. Cell. Biol." volume="20" first="1407" last="1418">
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            <authorList>
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            <dbReference type="PubMed" id="10648625"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Duodenum</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
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            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
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            <dbReference type="PubMed" id="19299493"/>
            <dbReference type="DOI" id="10.1093/hmg/ddp134"/>
        </citation>
        <scope>INTERACTION WITH IGHMBP2</scope>
    </reference>
    <reference key="6">
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            <title>Initial characterization of the human central proteome.</title>
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                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
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                <person name="Superti-Furga G."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Could be a novel TATA-binding protein (TBP) which can function as a basal transcription activator. Can act as a regulator of basal transcription for class II genes (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4">Interacts with ESF1/ABTAP (By similarity). Interacts with IGHMBP2.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-10171416">
            <id>Q96JN2-2</id>
            <label>CCDC136</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-5278764">
            <id>Q96GN5</id>
            <label>CDCA7L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-739624">
            <id>Q8NHQ1</id>
            <label>CEP70</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-739789">
            <id>Q92997</id>
            <label>DVL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-489887">
            <id>P50402</id>
            <label>EMD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-10175124">
            <id>Q8IZU0</id>
            <label>FAM9B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-2556193">
            <id>Q63ZY3</id>
            <label>KANK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-741037">
            <id>Q9BRK4</id>
            <label>LZTS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-10268010">
            <id>Q8N8X9</id>
            <label>MAB21L3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-79165">
            <id>Q9NRD5</id>
            <label>PICK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-12002474">
            <id>Q2KHN1</id>
            <label>RNF151</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-7131783">
            <id>Q8N205</id>
            <label>SYNE4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2602396">
            <id>Q9ULW3</id>
        </interactant>
        <interactant intactId="EBI-947459">
            <id>Q9H2G4</id>
            <label>TSPYL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
            <location evidence="1">Nucleolus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the ESF2/ABP1 family.</text>
    </comment>
    <dbReference type="EMBL" id="AB027258">
        <property type="protein sequence ID" value="BAA86886.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL513548">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC048812">
        <property type="protein sequence ID" value="AAH48812.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC066313">
        <property type="protein sequence ID" value="AAH66313.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4616.1"/>
    <dbReference type="RefSeq" id="NP_037507.1">
        <property type="nucleotide sequence ID" value="NM_013375.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9ULW3"/>
    <dbReference type="BioGRID" id="118909">
        <property type="interactions" value="429"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9ULW3">
        <property type="interactions" value="3393"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9ULW3">
        <property type="interactions" value="405"/>
    </dbReference>
    <dbReference type="MINT" id="Q9ULW3"/>
    <dbReference type="STRING" id="9606.ENSP00000274849"/>
    <dbReference type="iPTMnet" id="Q9ULW3"/>
    <dbReference type="PhosphoSitePlus" id="Q9ULW3"/>
    <dbReference type="BioMuta" id="ABT1"/>
    <dbReference type="DMDM" id="74753396"/>
    <dbReference type="jPOST" id="Q9ULW3"/>
    <dbReference type="MassIVE" id="Q9ULW3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000274849"/>
    <dbReference type="PeptideAtlas" id="Q9ULW3"/>
    <dbReference type="ProteomicsDB" id="85141"/>
    <dbReference type="Pumba" id="Q9ULW3"/>
    <dbReference type="Antibodypedia" id="11097">
        <property type="antibodies" value="191 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="29777"/>
    <dbReference type="Ensembl" id="ENST00000274849.3">
        <property type="protein sequence ID" value="ENSP00000274849.1"/>
        <property type="gene ID" value="ENSG00000146109.6"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000709933.1">
        <property type="protein sequence ID" value="ENSP00000517947.1"/>
        <property type="gene ID" value="ENSG00000292169.1"/>
    </dbReference>
    <dbReference type="GeneID" id="29777"/>
    <dbReference type="KEGG" id="hsa:29777"/>
    <dbReference type="MANE-Select" id="ENST00000274849.3">
        <property type="protein sequence ID" value="ENSP00000274849.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_013375.4"/>
        <property type="RefSeq protein sequence ID" value="NP_037507.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003nii.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17369"/>
    <dbReference type="ClinPGx" id="PA38451"/>
    <dbReference type="CTD" id="29777"/>
    <dbReference type="DisGeNET" id="29777"/>
    <dbReference type="GeneCards" id="ABT1"/>
    <dbReference type="HGNC" id="HGNC:17369">
        <property type="gene designation" value="ABT1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000146109">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="618750">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000146109"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000146109"/>
    <dbReference type="eggNOG" id="KOG3152">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000002062"/>
    <dbReference type="HOGENOM" id="CLU_054086_3_1_1"/>
    <dbReference type="InParanoid" id="Q9ULW3"/>
    <dbReference type="OMA" id="PNGSWAF"/>
    <dbReference type="OrthoDB" id="287393at2759"/>
    <dbReference type="PAN-GO" id="Q9ULW3">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9ULW3"/>
    <dbReference type="PathwayCommons" id="Q9ULW3"/>
    <dbReference type="SignaLink" id="Q9ULW3"/>
    <dbReference type="Agora" id="ENSG00000146109"/>
    <dbReference type="BioGRID-ORCS" id="29777">
        <property type="hits" value="538 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABT1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="29777"/>
    <dbReference type="Pharos" id="Q9ULW3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9ULW3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9ULW3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000146109">
        <property type="expression patterns" value="Expressed in granulocyte and 170 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9ULW3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005667">
        <property type="term" value="C:transcription regulator complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003713">
        <property type="term" value="F:transcription coactivator activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000480">
        <property type="term" value="P:endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000447">
        <property type="term" value="P:endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000472">
        <property type="term" value="P:endonucleolytic cleavage to generate mature 5'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA)"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006357">
        <property type="term" value="P:regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034462">
        <property type="term" value="P:small-subunit processome assembly"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0021522">
        <property type="term" value="P:spinal cord motor neuron differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006366">
        <property type="term" value="P:transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd12263">
        <property type="entry name" value="RRM_ABT1_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.330:FF:000447">
        <property type="entry name" value="Activator of basal transcription 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.330">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039119">
        <property type="entry name" value="ABT1/Esf2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034353">
        <property type="entry name" value="ABT1/ESF2_RRM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012677">
        <property type="entry name" value="Nucleotide-bd_a/b_plait_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035979">
        <property type="entry name" value="RBD_domain_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12311">
        <property type="entry name" value="ACTIVATOR OF BASAL TRANSCRIPTION 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12311:SF7">
        <property type="entry name" value="ACTIVATOR OF BASAL TRANSCRIPTION 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54928">
        <property type="entry name" value="RNA-binding domain, RBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000233168" description="Activator of basal transcription 1">
        <location>
            <begin position="1"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="domain" description="RRM">
        <location>
            <begin position="46"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="198"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="161"/>
            <end position="191"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="1"/>
            <end position="11"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="3">
        <location>
            <begin position="23"/>
            <end position="34"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="6">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="19299493"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <sequence length="272" mass="31079" checksum="FB9B44192C16BD8A" modified="2000-05-01" version="1">MEAEESEKAATEQEPLEGTEQTLDAEEEQEESEEAACGSKKRVVPGIVYLGHIPPRFRPLHVRNLLSAYGEVGRVFFQAEDRFVRRKKKAAAAAGGKKRSYTKDYTEGWVEFRDKRIAKRVAASLHNTPMGARRRSPFRYDLWNLKYLHRFTWSHLSEHLAFERQVRRQRLRAEVAQAKRETDFYLQSVERGQRFLAADGDPARPDGSWTFAQRPTEQELRARKAARPGGRERARLATAQDKARSNKGLLARIFGAPPPSESMEGPSLVRDS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-08-30" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WTS1</accession>
    <accession>B2R9K0</accession>
    <accession>Q9Y369</accession>
    <name>ABHD5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">1-acylglycerol-3-phosphate O-acyltransferase ABHD5</fullName>
            <ecNumber evidence="9">2.3.1.51</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Abhydrolase domain-containing protein 5</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Lipid droplet-binding protein CGI-58</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">ABHD5</name>
        <name type="synonym">NCIE2</name>
        <name type="ORF">CGI-58</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.</title>
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                <person name="Lefevre C."/>
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            <dbReference type="PubMed" id="11590543"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS CDS LYS-7; PRO-130 AND LYS-260</scope>
    </reference>
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            <dbReference type="PubMed" id="10810093"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Substantia nigra</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Cell Metab." volume="3" first="309" last="319">
            <title>Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.</title>
            <authorList>
                <person name="Lass A."/>
                <person name="Zimmermann R."/>
                <person name="Haemmerle G."/>
                <person name="Riederer M."/>
                <person name="Schoiswohl G."/>
                <person name="Schweiger M."/>
                <person name="Kienesberger P."/>
                <person name="Strauss J.G."/>
                <person name="Gorkiewicz G."/>
                <person name="Zechner R."/>
            </authorList>
            <dbReference type="PubMed" id="16679289"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2006.03.005"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CHARACTERIZATION OF VARIANTS CDS PRO-130 AND LYS-260</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="Am. J. Pathol." volume="173" first="1349" last="1360">
            <title>CGI-58 is an alpha/beta-hydrolase within lipid transporting lamellar granules of differentiated keratinocytes.</title>
            <authorList>
                <person name="Akiyama M."/>
                <person name="Sakai K."/>
                <person name="Takayama C."/>
                <person name="Yanagi T."/>
                <person name="Yamanaka Y."/>
                <person name="McMillan J.R."/>
                <person name="Shimizu H."/>
            </authorList>
            <dbReference type="PubMed" id="18832586"/>
            <dbReference type="DOI" id="10.2353/ajpath.2008.080005"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="24525" last="24533">
            <title>CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid.</title>
            <authorList>
                <person name="Ghosh A.K."/>
                <person name="Ramakrishnan G."/>
                <person name="Chandramohan C."/>
                <person name="Rajasekharan R."/>
            </authorList>
            <dbReference type="PubMed" id="18606822"/>
            <dbReference type="DOI" id="10.1074/jbc.m801783200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION OF VARIANTS CDS PRO-130 AND LYS-260</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2005" name="Arch. Dermatol." volume="141" first="798" last="800">
            <title>Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman syndrome: an uncommon lipid storage disease.</title>
            <authorList>
                <person name="Schleinitz N."/>
                <person name="Fischer J."/>
                <person name="Sanchez A."/>
                <person name="Veit V."/>
                <person name="Harle J.-R."/>
                <person name="Pelissier J.-F."/>
            </authorList>
            <dbReference type="PubMed" id="15967942"/>
            <dbReference type="DOI" id="10.1001/archderm.141.6.798"/>
        </citation>
        <scope>VARIANT ARG-82</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2007" name="J. Invest. Dermatol." volume="127" first="2273" last="2276">
            <title>A novel S115G mutation of CGI-58 in a Turkish patient with Dorfman-Chanarin syndrome.</title>
            <authorList>
                <person name="Ben Selma Z."/>
                <person name="Yilmaz S."/>
                <person name="Schischmanoff P.O."/>
                <person name="Blom A."/>
                <person name="Ozogul C."/>
                <person name="Laroche L."/>
                <person name="Caux F."/>
            </authorList>
            <dbReference type="PubMed" id="17495960"/>
            <dbReference type="DOI" id="10.1038/sj.jid.5700860"/>
        </citation>
        <scope>VARIANT CDS GLY-115</scope>
    </reference>
    <comment type="function">
        <text evidence="3 7 9 10">Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid (PubMed:18606822). Functions preferentially with 1-oleoyl-lysophosphatidic acid followed by 1-palmitoyl-lysophosphatidic acid, 1-stearoyl-lysophosphatidic acid and 1-arachidonoyl-lysophosphatidic acid as lipid acceptor. Functions preferentially with arachidonoyl-CoA followed by oleoyl-CoA as acyl group donors (By similarity). Functions in phosphatidic acid biosynthesis (PubMed:18606822). May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2 (PubMed:16679289). Involved in keratinocyte differentiation (PubMed:18832586). Regulates lipid droplet fusion (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:19709"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57970"/>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
            <dbReference type="ChEBI" id="CHEBI:58608"/>
            <dbReference type="EC" id="2.3.1.51"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:19710"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoyl-CoA = 1-(9Z)-octadecenoyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37143"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:74551"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:37144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + octadecanoyl-CoA = 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37147"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:74552"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:37148"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37131"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:74546"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:37132"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37443"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:74928"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:37444"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>eicosanoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-eicosanoyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37451"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:74937"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:37452"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-hexadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:33187"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:57518"/>
            <dbReference type="ChEBI" id="CHEBI:64839"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:33188"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-octadecanoyl-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37163"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:74560"/>
            <dbReference type="ChEBI" id="CHEBI:74565"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:37164"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + (9Z)-octadecenoyl-CoA = 1-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phosphate + CoA</text>
            <dbReference type="Rhea" id="RHEA:37455"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:74938"/>
            <dbReference type="ChEBI" id="CHEBI:74941"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:37456"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Acyltransferase activity is inhibited by detergents such as Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Acyltransferase activity is inhibited by the presence of magnesium and calcium.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with ADRP, PLIN and PNPLA2. Interacts with PLIN5; promotes interaction with PNPLA2 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-12261896">
            <id>Q5T4B2</id>
            <label>CERCAM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-22754239">
            <id>P51793</id>
            <label>CLCN4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-745535">
            <id>Q8NI60</id>
            <label>COQ8A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-12831978">
            <id>Q6ZPD8</id>
            <label>DGAT2L6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-9304251">
            <id>Q05329</id>
            <label>GAD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-18908258">
            <id>O00258</id>
            <label>GET1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-17517256">
            <id>P48058-2</id>
            <label>GRIA4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-740987">
            <id>Q9NQG6</id>
            <label>MIEF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-17616589">
            <id>A6NKB5-5</id>
            <label>PCNX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-2115275">
            <id>Q99541</id>
            <label>PLIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-725795">
            <id>O60664</id>
            <label>PLIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-21732470">
            <id>Q00G26</id>
            <label>PLIN5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-3232108">
            <id>Q8N0V3</id>
            <label>RBFA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-13044680">
            <id>Q9Y225-2</id>
            <label>RNF24</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-6257312">
            <id>Q9BVN2</id>
            <label>RUSC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-12056955">
            <id>Q8N4M1-3</id>
            <label>SLC44A3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-8638294">
            <id>Q9NUH8</id>
            <label>TMEM14B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-782604">
            <id>O43399</id>
            <label>TPD52L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2813554">
            <id>Q8WTS1</id>
        </interactant>
        <interactant intactId="EBI-748373">
            <id>Q6PEW1</id>
            <label>ZCCHC12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Lipid droplet</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
            <location evidence="3">Cytosol</location>
        </subcellularLocation>
        <text evidence="1">Colocalized with PLIN and ADRP on the surface of lipid droplets. The localization is dependent upon the metabolic status of the adipocytes and the activity of PKA (By similarity).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 10">Widely expressed in various tissues, including lymphocytes, liver, skeletal muscle and brain. Expressed by upper epidermal layers and dermal fibroblasts in skin, hepatocytes and neurons (at protein level).</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="10">Detected in fetal epidermis from 49 to 135 days estimated gestational age (at protein level).</text>
    </comment>
    <comment type="induction">
        <text evidence="10">Up-regulated upon keratinocyte differentiation (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.</text>
    </comment>
    <comment type="disease" evidence="5 7 8 9">
        <disease id="DI-00262">
            <name>Chanarin-Dorfman syndrome</name>
            <acronym>CDS</acronym>
            <description>An autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non-bullous congenital ichthyosiform erythroderma.</description>
            <dbReference type="MIM" id="275630"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.</text>
    </comment>
    <dbReference type="EC" id="2.3.1.51" evidence="9"/>
    <dbReference type="EMBL" id="AL606838">
        <property type="protein sequence ID" value="CAD12731.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF151816">
        <property type="protein sequence ID" value="AAD34053.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313811">
        <property type="protein sequence ID" value="BAG36547.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC105903">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471055">
        <property type="protein sequence ID" value="EAW64699.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC021958">
        <property type="protein sequence ID" value="AAH21958.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2711.1"/>
    <dbReference type="RefSeq" id="NP_001342115.1">
        <property type="nucleotide sequence ID" value="NM_001355186.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057090.2">
        <property type="nucleotide sequence ID" value="NM_016006.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047304199.1">
        <property type="nucleotide sequence ID" value="XM_047448243.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054202694.1">
        <property type="nucleotide sequence ID" value="XM_054346719.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8WTS1"/>
    <dbReference type="SMR" id="Q8WTS1"/>
    <dbReference type="BioGRID" id="119288">
        <property type="interactions" value="38"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8WTS1">
        <property type="interactions" value="2382"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WTS1">
        <property type="interactions" value="36"/>
    </dbReference>
    <dbReference type="MINT" id="Q8WTS1"/>
    <dbReference type="STRING" id="9606.ENSP00000495778"/>
    <dbReference type="SwissLipids" id="SLP:000000098"/>
    <dbReference type="ESTHER" id="human-ABHD5">
        <property type="family name" value="CGI-58_ABHD5_ABHD4"/>
    </dbReference>
    <dbReference type="MEROPS" id="S33.975"/>
    <dbReference type="GlyGen" id="Q8WTS1">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8WTS1"/>
    <dbReference type="PhosphoSitePlus" id="Q8WTS1"/>
    <dbReference type="SwissPalm" id="Q8WTS1"/>
    <dbReference type="BioMuta" id="ABHD5"/>
    <dbReference type="DMDM" id="73921640"/>
    <dbReference type="jPOST" id="Q8WTS1"/>
    <dbReference type="MassIVE" id="Q8WTS1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000390849"/>
    <dbReference type="PeptideAtlas" id="Q8WTS1"/>
    <dbReference type="ProteomicsDB" id="74594"/>
    <dbReference type="Pumba" id="Q8WTS1"/>
    <dbReference type="Antibodypedia" id="29395">
        <property type="antibodies" value="339 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51099"/>
    <dbReference type="Ensembl" id="ENST00000644371.2">
        <property type="protein sequence ID" value="ENSP00000495778.1"/>
        <property type="gene ID" value="ENSG00000011198.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000649763.1">
        <property type="protein sequence ID" value="ENSP00000497701.1"/>
        <property type="gene ID" value="ENSG00000011198.11"/>
    </dbReference>
    <dbReference type="GeneID" id="51099"/>
    <dbReference type="KEGG" id="hsa:51099"/>
    <dbReference type="MANE-Select" id="ENST00000644371.2">
        <property type="protein sequence ID" value="ENSP00000495778.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016006.6"/>
        <property type="RefSeq protein sequence ID" value="NP_057090.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003cmx.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21396"/>
    <dbReference type="ClinPGx" id="PA134891622"/>
    <dbReference type="CTD" id="51099"/>
    <dbReference type="DisGeNET" id="51099"/>
    <dbReference type="GeneCards" id="ABHD5"/>
    <dbReference type="HGNC" id="HGNC:21396">
        <property type="gene designation" value="ABHD5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000011198">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABHD5"/>
    <dbReference type="MIM" id="275630">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="604780">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000011198"/>
    <dbReference type="Orphanet" id="98907">
        <property type="disease" value="Neutral lipid storage disease with ichthyosis"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000011198"/>
    <dbReference type="eggNOG" id="KOG4409">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000016277"/>
    <dbReference type="HOGENOM" id="CLU_017361_0_0_1"/>
    <dbReference type="InParanoid" id="Q8WTS1"/>
    <dbReference type="OMA" id="DTTIRWC"/>
    <dbReference type="OrthoDB" id="7457040at2759"/>
    <dbReference type="PAN-GO" id="Q8WTS1">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WTS1"/>
    <dbReference type="PathwayCommons" id="Q8WTS1"/>
    <dbReference type="Reactome" id="R-HSA-163560">
        <property type="pathway name" value="Triglyceride catabolism"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8WTS1"/>
    <dbReference type="Agora" id="ENSG00000011198"/>
    <dbReference type="BioGRID-ORCS" id="51099">
        <property type="hits" value="9 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ABHD5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ABHD5"/>
    <dbReference type="GenomeRNAi" id="51099"/>
    <dbReference type="Pharos" id="Q8WTS1">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WTS1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WTS1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000011198">
        <property type="expression patterns" value="Expressed in amniotic fluid and 196 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WTS1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005811">
        <property type="term" value="C:lipid droplet"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003841">
        <property type="term" value="F:1-acylglycerol-3-phosphate O-acyltransferase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060229">
        <property type="term" value="F:lipase activator activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042171">
        <property type="term" value="F:lysophosphatidic acid acyltransferase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055088">
        <property type="term" value="P:lipid homeostasis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010891">
        <property type="term" value="P:negative regulation of triglyceride storage"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006654">
        <property type="term" value="P:phosphatidic acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010898">
        <property type="term" value="P:positive regulation of triglyceride catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000019">
        <property type="entry name" value="1-acylglycerol-3-phosphate O-acyltransferase ABHD5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000073">
        <property type="entry name" value="AB_hydrolase_1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886:SF34">
        <property type="entry name" value="1-ACYLGLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE ABHD5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42886">
        <property type="entry name" value="RE40534P-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00561">
        <property type="entry name" value="Abhydrolase_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00111">
        <property type="entry name" value="ABHYDROLASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0012">Acyltransferase</keyword>
    <keyword id="KW-0898">Cataract</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0977">Ichthyosis</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0551">Lipid droplet</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0594">Phospholipid biosynthesis</keyword>
    <keyword id="KW-1208">Phospholipid metabolism</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="initiator methionine" description="Removed" evidence="14">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000080866" description="1-acylglycerol-3-phosphate O-acyltransferase ABHD5">
        <location>
            <begin position="2"/>
            <end position="349"/>
        </location>
    </feature>
    <feature type="domain" description="AB hydrolase-1" evidence="4">
        <location>
            <begin position="77"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="HXXXXD motif">
        <location>
            <begin position="327"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="14">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="122"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023387" description="In CDS; dbSNP:rs104893676." evidence="5">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037574" description="In dbSNP:rs2302349.">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057953" description="Found in a patient with CDS but without evidence it may cause the disease; dbSNP:rs145548259." evidence="6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057954" description="In CDS." evidence="8">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023388" description="In CDS; loss of PNPLA2-dependent triacylclycerol hydrolysis but no effect on LPA acyltransferase activity; dbSNP:rs28939077." evidence="5 7 9">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023389" description="In CDS; loss of PNPLA2-dependent triacylclycerol hydrolysis but no effect on LPA acyltransferase activity; dbSNP:rs28939078." evidence="5 7 9">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAD34053." evidence="11" ref="2">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="263"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q6QA69"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9DBL9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11590543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15967942"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16679289"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17495960"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="18606822"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18832586"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="18606822"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:21396"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="349" mass="39096" checksum="85958A2DEC169C82" modified="2002-03-01" version="1">MAAEEEEVDSADTGERSGWLTGWLPTWCPTSISHLKEAEEKMLKCVPCTYKKEPVRISNGNKIWTLKFSHNISNKTPLVLLHGFGGGLGLWALNFGDLCTNRPVYAFDLLGFGRSSRPRFDSDAEEVENQFVESIEEWRCALGLDKMILLGHNLGGFLAAAYSLKYPSRVNHLILVEPWGFPERPDLADQDRPIPVWIRALGAALTPFNPLAGLRIAGPFGLSLVQRLRPDFKRKYSSMFEDDTVTEYIYHCNVQTPSGETAFKNMTIPYGWAKRPMLQRIGKMHPDIPVSVIFGARSCIDGNSGTSIQSLRPHSYVKTIAILGAGHYVYADQPEEFNQKVKEICDTVD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="199" xmlns="https://uniprot.org/uniprot">
    <accession>O94929</accession>
    <accession>A8K121</accession>
    <accession>Q19VH3</accession>
    <accession>Q658S1</accession>
    <accession>Q68CI5</accession>
    <accession>Q9BV32</accession>
    <name>ABLM3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-binding LIM protein 3</fullName>
            <shortName>abLIM-3</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Actin-binding LIM protein family member 3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABLIM3</name>
        <name type="synonym">KIAA0843</name>
        <name type="ORF">HMFN1661</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="8393" last="8403">
            <title>Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with STARS and directly bind F-actin.</title>
            <authorList>
                <person name="Barrientos T."/>
                <person name="Frank D."/>
                <person name="Kuwahara K."/>
                <person name="Bezprozvannaya S."/>
                <person name="Pipes G.C.T."/>
                <person name="Bassel-Duby R."/>
                <person name="Richardson J.A."/>
                <person name="Katus H.A."/>
                <person name="Olson E.N."/>
                <person name="Frey N."/>
            </authorList>
            <dbReference type="PubMed" id="17194709"/>
            <dbReference type="DOI" id="10.1074/jbc.m607549200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INTERACTION WITH F-ACTIN AND ABRA</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="355" last="364">
            <title>Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
                <person name="Suyama M."/>
                <person name="Kikuno R."/>
                <person name="Hirosawa M."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
                <person name="Nomura N."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="10048485"/>
            <dbReference type="DOI" id="10.1093/dnares/5.6.355"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Oncogene" volume="23" first="5901" last="5911">
            <title>Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.</title>
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                <person name="Yamada S."/>
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            </authorList>
            <dbReference type="PubMed" id="15221005"/>
            <dbReference type="DOI" id="10.1038/sj.onc.1207782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Hepatoblastoma</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 117-683 (ISOFORM 3)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Cell" volume="127" first="635" last="648">
            <title>Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
                <person name="Gnad F."/>
                <person name="Macek B."/>
                <person name="Kumar C."/>
                <person name="Mortensen P."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="17081983"/>
            <dbReference type="DOI" id="10.1016/j.cell.2006.09.026"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-503 AND SER-504</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="J. Proteome Res." volume="7" first="526" last="534">
            <title>Phosphoproteome of resting human platelets.</title>
            <authorList>
                <person name="Zahedi R.P."/>
                <person name="Lewandrowski U."/>
                <person name="Wiesner J."/>
                <person name="Wortelkamp S."/>
                <person name="Moebius J."/>
                <person name="Schuetz C."/>
                <person name="Walter U."/>
                <person name="Gambaryan S."/>
                <person name="Sickmann A."/>
            </authorList>
            <dbReference type="PubMed" id="18088087"/>
            <dbReference type="DOI" id="10.1021/pr0704130"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2008" name="Proteomics" volume="8" first="1346" last="1361">
            <title>Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.</title>
            <authorList>
                <person name="Han G."/>
                <person name="Ye M."/>
                <person name="Zhou H."/>
                <person name="Jiang X."/>
                <person name="Feng S."/>
                <person name="Jiang X."/>
                <person name="Tian R."/>
                <person name="Wan D."/>
                <person name="Zou H."/>
                <person name="Gu J."/>
            </authorList>
            <dbReference type="PubMed" id="18318008"/>
            <dbReference type="DOI" id="10.1002/pmic.200700884"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-503 AND SER-504</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282; SER-286; SER-372; SER-373; TYR-376; SER-388; SER-493; SER-503; SER-504; THR-543 AND SER-576</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="submission" date="2004-02" db="PDB data bank">
            <title>Solution structure of the villin headpiece domain of human actin-binding LIM protein homologue (KIAA0843 protein).</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 610-683</scope>
    </reference>
    <comment type="function">
        <text evidence="6">May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Directly interacts with F-actin and ABRA.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351267">
            <id>O94929</id>
        </interactant>
        <interactant intactId="EBI-747204">
            <id>Q9UKT9</id>
            <label>IKZF3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351267">
            <id>O94929</id>
        </interactant>
        <interactant intactId="EBI-2212028">
            <id>Q9Y2D8</id>
            <label>SSX2IP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-11524452">
            <id>Q8N9N5-2</id>
            <label>BANP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-744545">
            <id>Q8NEC5</id>
            <label>CATSPER1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-712912">
            <id>Q9HC52</id>
            <label>CBX8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-5453285">
            <id>Q2TBE0</id>
            <label>CWF19L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-6137602">
            <id>Q53FT3</id>
            <label>HIKESHI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-747204">
            <id>Q9UKT9</id>
            <label>IKZF3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-2811699">
            <id>Q9NP74</id>
            <label>PALMD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-632715">
            <id>Q13573</id>
            <label>SNW1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-1105213">
            <id>Q9UBB9</id>
            <label>TFIP11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11961672">
            <id>O94929-2</id>
        </interactant>
        <interactant intactId="EBI-4395669">
            <id>Q6ZNG0</id>
            <label>ZNF620</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O94929-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O94929-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012127 VSP_012128 VSP_012130"/>
        </isoform>
        <isoform>
            <id>O94929-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_012127 VSP_012129"/>
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        <isoform>
            <id>O94929-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_012126"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed predominantly in heart and brain.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA74866" version="2"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="DQ413174">
        <property type="protein sequence ID" value="ABD83327.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB020650">
        <property type="protein sequence ID" value="BAA74866.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK289736">
        <property type="protein sequence ID" value="BAF82425.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AB075881">
        <property type="protein sequence ID" value="BAD38663.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC001665">
        <property type="protein sequence ID" value="AAH01665.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL833021">
        <property type="protein sequence ID" value="CAH56270.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS4294.1">
        <molecule id="O94929-1"/>
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    <dbReference type="CCDS" id="CCDS78071.1">
        <molecule id="O94929-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS87335.1">
        <molecule id="O94929-3"/>
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    <dbReference type="RefSeq" id="NP_001287944.1">
        <molecule id="O94929-1"/>
        <property type="nucleotide sequence ID" value="NM_001301015.3"/>
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    <dbReference type="RefSeq" id="NP_001287947.1">
        <property type="nucleotide sequence ID" value="NM_001301018.2"/>
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    <dbReference type="RefSeq" id="NP_001287957.1">
        <molecule id="O94929-2"/>
        <property type="nucleotide sequence ID" value="NM_001301028.3"/>
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    <dbReference type="RefSeq" id="NP_001332787.1">
        <property type="nucleotide sequence ID" value="NM_001345858.1"/>
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    <dbReference type="RefSeq" id="NP_001332788.1">
        <molecule id="O94929-3"/>
        <property type="nucleotide sequence ID" value="NM_001345859.2"/>
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    <dbReference type="RefSeq" id="NP_001332789.1">
        <property type="nucleotide sequence ID" value="NM_001345860.1"/>
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    <dbReference type="RefSeq" id="NP_001332790.1">
        <molecule id="O94929-3"/>
        <property type="nucleotide sequence ID" value="NM_001345861.2"/>
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    <dbReference type="RefSeq" id="NP_055760.1">
        <molecule id="O94929-1"/>
        <property type="nucleotide sequence ID" value="NM_014945.5"/>
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        <property type="method" value="NMR"/>
        <property type="chains" value="A=609-683"/>
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    <dbReference type="PDB" id="2DJ7">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=141-207"/>
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    <dbReference type="PDBsum" id="1UJS"/>
    <dbReference type="PDBsum" id="2DJ7"/>
    <dbReference type="AlphaFoldDB" id="O94929"/>
    <dbReference type="BMRB" id="O94929"/>
    <dbReference type="SMR" id="O94929"/>
    <dbReference type="BioGRID" id="116552">
        <property type="interactions" value="40"/>
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    <dbReference type="FunCoup" id="O94929">
        <property type="interactions" value="272"/>
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    <dbReference type="IntAct" id="O94929">
        <property type="interactions" value="41"/>
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    <dbReference type="MINT" id="O94929"/>
    <dbReference type="STRING" id="9606.ENSP00000425394"/>
    <dbReference type="CarbonylDB" id="O94929"/>
    <dbReference type="GlyCosmos" id="O94929">
        <property type="glycosylation" value="4 sites, 1 glycan"/>
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    <dbReference type="GlyGen" id="O94929">
        <property type="glycosylation" value="4 sites, 1 O-linked glycan (4 sites)"/>
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    <dbReference type="iPTMnet" id="O94929"/>
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    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="18318008"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="1UJS"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="2DJ7"/>
        </source>
    </evidence>
    <sequence length="683" mass="77802" checksum="0392DBD9065EE08A" modified="2004-12-07" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-02-20" modified="2026-01-28" version="157" xmlns="https://uniprot.org/uniprot">
    <accession>Q6UWZ7</accession>
    <accession>A5JJ07</accession>
    <accession>Q9H8I1</accession>
    <accession>Q9H9N4</accession>
    <name>ABRX1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="21">BRCA1-A complex subunit Abraxas 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Coiled-coil domain-containing protein 98</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein FAM175A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="21" type="primary">ABRAXAS1</name>
        <name evidence="21" type="synonym">ABRA1</name>
        <name type="synonym">CCDC98</name>
        <name evidence="21" type="synonym">FAM175A</name>
        <name type="ORF">UNQ496/PRO1013</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH BRCA1 AND UIMC1</scope>
        <scope>PHOSPHORYLATION AT SER-406</scope>
        <scope>MUTAGENESIS OF SER-406</scope>
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            <dbReference type="PubMed" id="12975309"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ASN-373</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
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                <person name="Itakura S."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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                <person name="Hikiji T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
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                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
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                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT THR-348</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
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                <person name="Liu Z."/>
                <person name="Wu J."/>
                <person name="Yu X."/>
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            <dbReference type="PubMed" id="17643121"/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH BRCA1 AND UIMC1</scope>
        <scope>PHOSPHORYLATION AT SER-406</scope>
        <scope>MUTAGENESIS OF SER-406</scope>
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                <person name="Kim H."/>
                <person name="Huang J."/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH BRCA1 AND UIMC1</scope>
        <scope>PHOSPHORYLATION AT SER-406</scope>
        <scope>MUTAGENESIS OF SER-406</scope>
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        <scope>FUNCTION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386; SER-387; THR-390 AND SER-406</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks.</title>
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            <dbReference type="PubMed" id="19261746"/>
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        <scope>IDENTIFICATION IN THE BRCA1-A COMPLEX</scope>
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        <scope>IDENTIFICATION IN THE BRCA1-A COMPLEX</scope>
        <scope>DOMAIN MPN-LIKE</scope>
        <scope>INTERACTION WITH UIMC1; BRCC3; BABAM2; BABAM1 AND BRCA1</scope>
        <scope>UBIQUITIN-BINDING</scope>
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        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE BRCA1-A COMPLEX</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390 AND SER-406</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386; SER-387; THR-390 AND SER-406</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386; SER-387 AND THR-390</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2013" name="Cell Rep." volume="5" first="180" last="193">
            <title>A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses.</title>
            <authorList>
                <person name="Zheng H."/>
                <person name="Gupta V."/>
                <person name="Patterson-Fortin J."/>
                <person name="Bhattacharya S."/>
                <person name="Katlinski K."/>
                <person name="Wu J."/>
                <person name="Varghese B."/>
                <person name="Carbone C.J."/>
                <person name="Aressy B."/>
                <person name="Fuchs S.Y."/>
                <person name="Greenberg R.A."/>
            </authorList>
            <dbReference type="PubMed" id="24075985"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2013.08.025"/>
        </citation>
        <scope>IDENTIFICATION IN THE ARISC COMPLEX</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390 AND SER-406</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2013" name="Acta Crystallogr. F" volume="69" first="1401" last="1404">
            <title>Preliminary crystallographic studies of BRCA1 BRCT-ABRAXAS complex.</title>
            <authorList>
                <person name="Badgujar D.C."/>
                <person name="Sawant U."/>
                <person name="Vikrant X."/>
                <person name="Yadav L."/>
                <person name="Hosur M.V."/>
                <person name="Varma A.K."/>
            </authorList>
            <dbReference type="PubMed" id="24316840"/>
            <dbReference type="DOI" id="10.1107/s1744309113030649"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 399-409 IN COMPLEX WITH BRCA1</scope>
        <scope>INTERACTION WITH BRCA1</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2016" name="Mol. Cell" volume="61" first="434" last="448">
            <title>Structure of BRCA1-BRCT/Abraxas complex reveals phosphorylation-dependent BRCT dimerization at DNA damage sites.</title>
            <authorList>
                <person name="Wu Q."/>
                <person name="Paul A."/>
                <person name="Su D."/>
                <person name="Mehmood S."/>
                <person name="Foo T.K."/>
                <person name="Ochi T."/>
                <person name="Bunting E.L."/>
                <person name="Xia B."/>
                <person name="Robinson C.V."/>
                <person name="Wang B."/>
                <person name="Blundell T.L."/>
            </authorList>
            <dbReference type="PubMed" id="26778126"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2015.12.017"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 403-409 IN COMPLEX WITH BRCA1</scope>
        <scope>INTERACTION WITH BRCA1</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT SER-404 AND SER-406</scope>
        <scope>MUTAGENESIS OF PHE-400; GLU-402; TYR-403; SER-404 AND SER-406</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2009" name="Breast Cancer Res. Treat." volume="117" first="453" last="459">
            <title>Analysis of the genes coding for the BRCA1-interacting proteins, RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic breast cancer cases.</title>
            <authorList>
                <person name="Novak D.J."/>
                <person name="Sabbaghian N."/>
                <person name="Maillet P."/>
                <person name="Chappuis P.O."/>
                <person name="Foulkes W.D."/>
                <person name="Tischkowitz M."/>
            </authorList>
            <dbReference type="PubMed" id="18695986"/>
            <dbReference type="DOI" id="10.1007/s10549-008-0134-y"/>
        </citation>
        <scope>VARIANTS THR-348 AND ASN-373</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2012" name="Sci. Transl. Med." volume="4" first="122ra23" last="122ra23">
            <title>Breast cancer-associated Abraxas mutation disrupts nuclear localization and DNA damage response functions.</title>
            <authorList>
                <person name="Solyom S."/>
                <person name="Aressy B."/>
                <person name="Pylkas K."/>
                <person name="Patterson-Fortin J."/>
                <person name="Hartikainen J.M."/>
                <person name="Kallioniemi A."/>
                <person name="Kauppila S."/>
                <person name="Nikkila J."/>
                <person name="Kosma V.M."/>
                <person name="Mannermaa A."/>
                <person name="Greenberg R.A."/>
                <person name="Winqvist R."/>
            </authorList>
            <dbReference type="PubMed" id="22357538"/>
            <dbReference type="DOI" id="10.1126/scitranslmed.3003223"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>VARIANTS THR-348 AND ASN-373</scope>
        <scope>VARIANT BC GLN-361</scope>
        <scope>CHARACTERIZATION OF VARIANT BC GLN-361</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="J. Biomol. Struct. Dyn." volume="33" first="1291" last="1301">
            <title>Mislocalization of BRCA1-complex due to ABRAXAS Arg361Gln mutation.</title>
            <authorList>
                <person name="Kumar R.V."/>
                <person name="Siddiqui Q."/>
                <person name="Singh N."/>
                <person name="Waghmare S.K."/>
                <person name="Varma A.K."/>
            </authorList>
            <dbReference type="PubMed" id="25105795"/>
            <dbReference type="DOI" id="10.1080/07391102.2014.945484"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT BC GLN-361</scope>
    </reference>
    <comment type="function">
        <text evidence="7 8 9 10 13 15 19">Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7 8 9 12 13 14 16 17 19">Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985). Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the complex, interacts directly with UIMC1/RAP80, BRCC3/BRCC36 and BABAM2. Interacts directly (when phosphorylated at Ser-406) with BRCA1. Homodimer. The homodimer interacts directly (when phosphorylated at Ser-404 and Ser-406) with two BRCA1 chains, giving rise to a heterotetramer. Binds polyubiquitin.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-349905">
            <id>P38398</id>
            <label>BRCA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-750352">
            <id>P46736</id>
            <label>BRCC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
            <label>CFTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-396343">
            <id>O00629</id>
            <label>KPNA4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-725300">
            <id>Q96RL1</id>
            <label>UIMC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1263451">
            <id>Q6UWZ7</id>
        </interactant>
        <interactant intactId="EBI-9640371">
            <id>Q96RL1-1</id>
            <label>UIMC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 8 9">Nucleus</location>
        </subcellularLocation>
        <text evidence="20">Localizes at sites of DNA damage at double-strand breaks (DSBs).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6UWZ7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6UWZ7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_058196"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="7 8 9 19">Phosphorylation of Ser-406 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1 (PubMed:17525340, PubMed:17643121, PubMed:17643122). Ionizing radiation promotes rapid phosphorylation at Ser-404 and Ser-406 by ATM; this promotes recruitment of BRCA1 to sites of DNA damage (PubMed:26778126).</text>
    </comment>
    <comment type="disease" evidence="15 18">
        <disease id="DI-02602">
            <name>Breast cancer</name>
            <acronym>BC</acronym>
            <description>A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.</description>
            <dbReference type="MIM" id="114480"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the FAM175 family. Abraxas subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH39573" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AY358576">
        <property type="protein sequence ID" value="AAQ88939.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF531340">
        <property type="protein sequence ID" value="ABP87396.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471057">
        <property type="protein sequence ID" value="EAX05942.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC039573">
        <property type="protein sequence ID" value="AAH39573.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK022704">
        <property type="protein sequence ID" value="BAB14189.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK023676">
        <property type="protein sequence ID" value="BAB14635.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3605.2">
        <molecule id="Q6UWZ7-1"/>
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    <dbReference type="RefSeq" id="NP_001332891.1">
        <molecule id="Q6UWZ7-2"/>
        <property type="nucleotide sequence ID" value="NM_001345962.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_620775.2">
        <molecule id="Q6UWZ7-1"/>
        <property type="nucleotide sequence ID" value="NM_139076.3"/>
    </dbReference>
    <dbReference type="PDB" id="4JLU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="B=399-409"/>
    </dbReference>
    <dbReference type="PDB" id="4U4A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.51 A"/>
        <property type="chains" value="D/E/F=399-409"/>
    </dbReference>
    <dbReference type="PDB" id="4Y18">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="I/J/K/L/M/N/O/P=399-409"/>
    </dbReference>
    <dbReference type="PDB" id="4Y2G">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="B=403-409"/>
    </dbReference>
    <dbReference type="PDBsum" id="4JLU"/>
    <dbReference type="PDBsum" id="4U4A"/>
    <dbReference type="PDBsum" id="4Y18"/>
    <dbReference type="PDBsum" id="4Y2G"/>
    <dbReference type="AlphaFoldDB" id="Q6UWZ7"/>
    <dbReference type="SMR" id="Q6UWZ7"/>
    <dbReference type="BioGRID" id="123911">
        <property type="interactions" value="43"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4425">
        <property type="entry name" value="BRCA1-A complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q6UWZ7"/>
    <dbReference type="DIP" id="DIP-29615N"/>
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    <dbReference type="FunCoup" id="Q6UWZ7">
        <property type="interactions" value="2756"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6UWZ7">
        <property type="interactions" value="19"/>
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    <dbReference type="MINT" id="Q6UWZ7"/>
    <dbReference type="STRING" id="9606.ENSP00000369857"/>
    <dbReference type="GlyGen" id="Q6UWZ7">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6UWZ7"/>
    <dbReference type="PhosphoSitePlus" id="Q6UWZ7"/>
    <dbReference type="BioMuta" id="ABRAXAS1"/>
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    <dbReference type="Antibodypedia" id="25225">
        <property type="antibodies" value="195 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84142"/>
    <dbReference type="Ensembl" id="ENST00000321945.12">
        <molecule id="Q6UWZ7-1"/>
        <property type="protein sequence ID" value="ENSP00000369857.3"/>
        <property type="gene ID" value="ENSG00000163322.15"/>
    </dbReference>
    <dbReference type="GeneID" id="84142"/>
    <dbReference type="KEGG" id="hsa:84142"/>
    <dbReference type="MANE-Select" id="ENST00000321945.12">
        <property type="protein sequence ID" value="ENSP00000369857.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_139076.3"/>
        <property type="RefSeq protein sequence ID" value="NP_620775.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003hou.3">
        <molecule id="Q6UWZ7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25829"/>
    <dbReference type="ClinPGx" id="PA162387308"/>
    <dbReference type="CTD" id="84142"/>
    <dbReference type="DisGeNET" id="84142"/>
    <dbReference type="GeneCards" id="ABRAXAS1"/>
    <dbReference type="HGNC" id="HGNC:25829">
        <property type="gene designation" value="ABRAXAS1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000163322">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ABRAXAS1"/>
    <dbReference type="MIM" id="114480">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="611143">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000163322"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000163322"/>
    <dbReference type="eggNOG" id="ENOG502QVCD">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00530000063424"/>
    <dbReference type="HOGENOM" id="CLU_056671_0_1_1"/>
    <dbReference type="InParanoid" id="Q6UWZ7"/>
    <dbReference type="OrthoDB" id="6358435at2759"/>
    <dbReference type="PAN-GO" id="Q6UWZ7">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6UWZ7"/>
    <dbReference type="PathwayCommons" id="Q6UWZ7"/>
    <dbReference type="Reactome" id="R-HSA-5689901">
        <property type="pathway name" value="Metalloprotease DUBs"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5693565">
        <property type="pathway name" value="Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5693571">
        <property type="pathway name" value="Nonhomologous End-Joining (NHEJ)"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5693607">
        <property type="pathway name" value="Processing of DNA double-strand break ends"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-69473">
        <property type="pathway name" value="G2/M DNA damage checkpoint"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6UWZ7"/>
    <dbReference type="SIGNOR" id="Q6UWZ7"/>
    <dbReference type="Agora" id="ENSG00000163322"/>
    <dbReference type="BioGRID-ORCS" id="84142">
        <property type="hits" value="56 hits in 1167 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="FAM175A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q6UWZ7"/>
    <dbReference type="GenomeRNAi" id="84142"/>
    <dbReference type="Pharos" id="Q6UWZ7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6UWZ7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
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    <dbReference type="RNAct" id="Q6UWZ7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000163322">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 185 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6UWZ7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070531">
        <property type="term" value="C:BRCA1-A complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0016604">
        <property type="term" value="C:nuclear body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0008017">
        <property type="term" value="F:microtubule binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0031593">
        <property type="term" value="F:polyubiquitin modification-dependent protein binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008608">
        <property type="term" value="P:attachment of spindle microtubules to kinetochore"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006325">
        <property type="term" value="P:chromatin organization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006302">
        <property type="term" value="P:double-strand break repair"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007095">
        <property type="term" value="P:mitotic G2 DNA damage checkpoint signaling"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044818">
        <property type="term" value="P:mitotic G2/M transition checkpoint"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090307">
        <property type="term" value="P:mitotic spindle assembly"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0045739">
        <property type="term" value="P:positive regulation of DNA repair"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006282">
        <property type="term" value="P:regulation of DNA repair"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010212">
        <property type="term" value="P:response to ionizing radiation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd23523">
        <property type="entry name" value="Abraxas_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023239">
        <property type="entry name" value="BRISC_Abraxas1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023238">
        <property type="entry name" value="FAM175"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037518">
        <property type="entry name" value="MPN"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR31728">
        <property type="entry name" value="ABRAXAS FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR31728:SF2">
        <property type="entry name" value="BRCA1-A COMPLEX SUBUNIT ABRAXAS 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF21125">
        <property type="entry name" value="MPN_2A_DUB_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR02052">
        <property type="entry name" value="ABRAXAS"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR02051">
        <property type="entry name" value="PROTEINF175"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50249">
        <property type="entry name" value="MPN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0156">Chromatin regulator</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0227">DNA damage</keyword>
    <keyword id="KW-0234">DNA repair</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000278575" description="BRCA1-A complex subunit Abraxas 1">
        <location>
            <begin position="1"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="domain" description="MPN" evidence="3">
        <location>
            <begin position="7"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="362"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="206"/>
            <end position="260"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="pSXXF motif" evidence="20">
        <location>
            <begin position="406"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="362"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="4">
        <location>
            <begin position="373"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="22 24 25">
        <location>
            <position position="386"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="22 24 25">
        <location>
            <position position="387"/>
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    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="22 23 24 25 26">
        <location>
            <position position="390"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="404"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7 8 9 19 22 23 24 26">
        <location>
            <position position="406"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_058196" description="In isoform 2.">
        <location>
            <begin position="1"/>
            <end position="109"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030790" description="In dbSNP:rs752929794.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="239"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054054" description="In dbSNP:rs12642536." evidence="6 11 15">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="348"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071865" description="In BC; results in reduced DSB repair efficiency; primarily localizes to the cytoplasm and has reduced nuclear localization; does not affect interaction with BRCA1; results in highly reduced interaction with UIMC1/RAP80; dbSNP:rs201627097." evidence="15 18">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="361"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054055" description="In dbSNP:rs13125836." evidence="5 11 15">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on formation of a heterotetramer with BRCA1." evidence="19">
        <original>F</original>
        <variation>D</variation>
        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases formation of a heterotetramer with BRCA1." evidence="19">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="402"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on formation of a heterotetramer with BRCA1." evidence="19">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="403"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on homodimerization. Mildly decreased recruitment of BRCA1 to sites of DNA damage." evidence="19">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Permits formation of a heterotetramer with BRCA1." evidence="19">
        <original>S</original>
        <variation>D</variation>
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes formation of a heterotetramer with BRCA1. Does not affect interaction with a first BRCA1 chain." evidence="19">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes phosphorylation of the pSXXF motif and the interaction with BRCA1 but does not affect the interaction with UIMC1/RAP80. Strongly decreases recruitment of BRCA1 to sites of DNA damage. No effect on homodimerization." evidence="7 8 9 19">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="406"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8BPZ8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01182"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12975309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="17525340"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17643121"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17643122"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18077395"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18695986"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="19261746"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="19261748"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="19261749"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22357538"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="24075985"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="24316840"/>
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    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="25105795"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="26778126"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0000312" key="21">
        <source>
            <dbReference type="HGNC" id="HGNC:25829"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="409" mass="46663" checksum="A1ACA4F759BD1AEE" modified="2007-02-20" version="2">MEGESTSAVLSGFVLGALAFQHLNTDSDTEGFLLGEVKGEAKNSITDSQMDDVEVVYTIDIQKYIPCYQLFSFYNSSGEVNEQALKKILSNVKKNVVGWYKFRRHSDQIMTFRERLLHKNLQEHFSNQDLVFLLLTPSIITESCSTHRLEHSLYKPQKGLFHRVPLVVANLGMSEQLGYKTVSGSCMSTGFSRAVQTHSSKFFEEDGSLKEVHKINEMYASLQEELKSICKKVEDSEQAVDKLVKDVNRLKREIEKRRGAQIQAAREKNIQKDPQENIFLCQALRTFFPNSEFLHSCVMSLKNRHVSKSSCNYNHHLDVVDNLTLMVEHTDIPEASPASTPQIIKHKALDLDDRWQFKRSRLLDTQDKRSKADTGSSNQDKASKMSSPETDEEIEKMKGFGEYSRSPTF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-09-05" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q969K4</accession>
    <accession>D3DNB0</accession>
    <accession>Q6ZNU9</accession>
    <accession>Q71MF1</accession>
    <accession>Q96S62</accession>
    <accession>Q96S63</accession>
    <name>ABTB1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Ankyrin repeat and BTB/POZ domain-containing protein 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Elongation factor 1A-binding protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15" type="primary">ABTB1</name>
        <name evidence="6" type="synonym">BPOZ</name>
        <name type="ORF">PP2259</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="9 16" key="1">
        <citation type="journal article" date="2000" name="Biochem. Biophys. Res. Commun." volume="273" first="991" last="996">
            <title>Molecular cloning and characterization of a novel human gene containing ankyrin repeat and double BTB/POZ domain.</title>
            <authorList>
                <person name="Dai K.-S."/>
                <person name="Wei W."/>
                <person name="Liew C.-C."/>
            </authorList>
            <dbReference type="PubMed" id="10891360"/>
            <dbReference type="DOI" id="10.1006/bbrc.2000.3053"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue evidence="3">Leukocyte</tissue>
        </source>
    </reference>
    <reference evidence="9 13" key="2">
        <citation type="journal article" date="2001" name="Oncogene" volume="20" first="4457" last="4465">
            <title>Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.</title>
            <authorList>
                <person name="Unoki M."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="11494141"/>
            <dbReference type="DOI" id="10.1038/sj.onc.1204608"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="15724" last="15729">
            <title>Large-scale cDNA transfection screening for genes related to cancer development and progression.</title>
            <authorList>
                <person name="Wan D."/>
                <person name="Gong Y."/>
                <person name="Qin W."/>
                <person name="Zhang P."/>
                <person name="Li J."/>
                <person name="Wei L."/>
                <person name="Zhou X."/>
                <person name="Li H."/>
                <person name="Qiu X."/>
                <person name="Zhong F."/>
                <person name="He L."/>
                <person name="Yu J."/>
                <person name="Yao G."/>
                <person name="Jiang H."/>
                <person name="Qian L."/>
                <person name="Yu Y."/>
                <person name="Shu H."/>
                <person name="Chen X."/>
                <person name="Xu H."/>
                <person name="Guo M."/>
                <person name="Pan Z."/>
                <person name="Chen Y."/>
                <person name="Ge C."/>
                <person name="Yang S."/>
                <person name="Gu J."/>
            </authorList>
            <dbReference type="PubMed" id="15498874"/>
            <dbReference type="DOI" id="10.1073/pnas.0404089101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference evidence="9 14" key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue evidence="14">Spleen</tissue>
        </source>
    </reference>
    <reference evidence="9 12" key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="9 10" key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue evidence="10">B-cell</tissue>
        </source>
    </reference>
    <reference evidence="9 11" key="7">
        <citation type="thesis" date="2001" institute="University of Aarhus" country="Denmark">
            <title>Translation elongation factor 1A binding protein.</title>
            <authorList>
                <person name="Mansilla F."/>
                <person name="Clark B.F.C."/>
                <person name="Knudsen C.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue evidence="11">Skeletal muscle</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="3 4">May act as a mediator of the PTEN growth-suppressive signaling pathway. May play a role in developmental processes.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-456129">
            <id>Q13618</id>
            <label>CUL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-354943">
            <id>Q05639</id>
            <label>EEF1A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-358607">
            <id>P29692</id>
            <label>EEF1D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-5280572">
            <id>P29692-2</id>
            <label>EEF1D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-372899">
            <id>Q13148</id>
            <label>TARDBP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-1051048">
            <id>Q9ULJ3</id>
            <label>ZBTB21</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-7223971">
            <id>Q969K4</id>
        </interactant>
        <interactant intactId="EBI-23099">
            <id>P53212</id>
            <label>YGR021W</label>
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        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q969K4-1</id>
            <name evidence="3 4">2</name>
            <name evidence="4">BPOZ-2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q969K4-2</id>
            <name evidence="4">1</name>
            <name evidence="4">BPOZ-1</name>
            <sequence type="described" ref="VSP_052148"/>
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        <isoform>
            <id>Q969K4-3</id>
            <name evidence="4">3</name>
            <name evidence="4">BPOZ-3</name>
            <sequence type="described" ref="VSP_052149"/>
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        <isoform>
            <id>Q969K4-4</id>
            <name evidence="5">4</name>
            <sequence type="described" ref="VSP_052150 VSP_052151 VSP_052152 VSP_052153"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Ubiquitously expressed in all fetal tissues examined including heart, brain, liver, and kidney. Also expressed at lower levels in both adult heart and hypertrophic heart.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAQ04661" version="1"/>
        </conflict>
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        <property type="protein sequence ID" value="BAB55648.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAB55649.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAB55650.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF447886">
        <property type="protein sequence ID" value="AAQ04661.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK130594">
        <property type="protein sequence ID" value="BAC85392.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79333.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79334.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC011858">
        <property type="protein sequence ID" value="AAH11858.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAK57478.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="Q969K4-2"/>
        <property type="nucleotide sequence ID" value="NM_032548.4"/>
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        <property type="nucleotide sequence ID" value="NM_172027.3"/>
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    <dbReference type="Ensembl" id="ENST00000468137.5">
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        <property type="gene designation" value="ABTB1"/>
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    <dbReference type="HPA" id="ENSG00000114626">
        <property type="expression patterns" value="Low tissue specificity"/>
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    <dbReference type="MIM" id="608308">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000114626"/>
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    <dbReference type="eggNOG" id="KOG0511">
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    <dbReference type="GeneTree" id="ENSGT00390000017131"/>
    <dbReference type="HOGENOM" id="CLU_022885_0_0_1"/>
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    <dbReference type="OMA" id="EGARCIY"/>
    <dbReference type="OrthoDB" id="684045at2759"/>
    <dbReference type="PAN-GO" id="Q969K4">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="Q969K4"/>
    <dbReference type="PathwayCommons" id="Q969K4"/>
    <dbReference type="SignaLink" id="Q969K4"/>
    <dbReference type="SIGNOR" id="Q969K4"/>
    <dbReference type="Agora" id="ENSG00000114626"/>
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        <property type="hits" value="11 hits in 1193 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ABTB1">
        <property type="organism name" value="human"/>
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    <dbReference type="GeneWiki" id="ABTB1"/>
    <dbReference type="GenomeRNAi" id="80325"/>
    <dbReference type="Pharos" id="Q969K4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q969K4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
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    <dbReference type="RNAct" id="Q969K4">
        <property type="molecule type" value="protein"/>
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    <dbReference type="ExpressionAtlas" id="Q969K4">
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        <property type="project" value="GO_Central"/>
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        <property type="project" value="HPA"/>
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        <property type="term" value="F:translation elongation factor activity"/>
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        <property type="project" value="UniProtKB-KW"/>
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.710.10:FF:000063">
        <property type="entry name" value="Ankyrin repeat and BTB/POZ domain-containing protein 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.710.10:FF:000064">
        <property type="entry name" value="Ankyrin repeat and BTB/POZ domain-containing protein 1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.30.710.10">
        <property type="entry name" value="Potassium Channel Kv1.1, Chain A"/>
        <property type="match status" value="2"/>
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    <dbReference type="InterPro" id="IPR044515">
        <property type="entry name" value="ABTB1"/>
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    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
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    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
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    <dbReference type="InterPro" id="IPR000210">
        <property type="entry name" value="BTB/POZ_dom"/>
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    <dbReference type="InterPro" id="IPR011333">
        <property type="entry name" value="SKP1/BTB/POZ_sf"/>
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    <dbReference type="PANTHER" id="PTHR46231">
        <property type="entry name" value="ANKYRIN REPEAT AND BTB/POZ DOMAIN-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR46231:SF1">
        <property type="entry name" value="ANKYRIN REPEAT AND BTB_POZ DOMAIN-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="2"/>
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        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
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    <dbReference type="SMART" id="SM00225">
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        <property type="match status" value="2"/>
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        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF54695">
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        <property type="match status" value="2"/>
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50088">
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50097">
        <property type="entry name" value="BTB"/>
        <property type="match status" value="2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0251">Elongation factor</keyword>
    <keyword id="KW-0648">Protein biosynthesis</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000248267" description="Ankyrin repeat and BTB/POZ domain-containing protein 1">
        <location>
            <begin position="1"/>
            <end position="478"/>
        </location>
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    <feature type="repeat" description="ANK 1" evidence="1">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2" evidence="1">
        <location>
            <begin position="35"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="domain" description="BTB 1" evidence="2">
        <location>
            <begin position="115"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="domain" description="BTB 2" evidence="2">
        <location>
            <begin position="272"/>
            <end position="346"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="451"/>
            <end position="477"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052148" description="In isoform 1." evidence="6 8">
        <location>
            <begin position="1"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052149" description="In isoform 3." evidence="6">
        <original>MDTSDLFASCRKGDVGRVRYLLEQRDVEVNVRDKWDSTPL</original>
        <variation>MWAECGTCWSSETWR</variation>
        <location>
            <begin position="1"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052150" description="In isoform 4." evidence="7">
        <location>
            <begin position="24"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052151" description="In isoform 4." evidence="7">
        <original>DYKQVTASCRRRDYYDDFLQRLLEQGIHSDVVFVVHGKPFRVHRCVLGARSAYFANMLDTKWKGKSVVVLRHPLINPVAFGALLQYLYTGRLDIGVEHVSDCERLAKQCQ</original>
        <variation>LCGHEE</variation>
        <location>
            <begin position="87"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052152" description="In isoform 4." evidence="7">
        <location>
            <begin position="255"/>
            <end position="287"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_052153" description="In isoform 4." evidence="7">
        <original>EDLLVSIGLDC</original>
        <variation>LETSMCMRLCAALLPAPCTLRASWGVRGAQWGFSSLHEPGDPRGGSIWDEPPPPNAQASPQDPGGGHHSGKPGVGVGFGLSTFLLQIPPTHPSPKSSPLALA</variation>
        <location>
            <begin position="468"/>
            <end position="478"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00037"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10891360"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11494141"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="11494141"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15498874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="EMBL" id="AAH11858.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="EMBL" id="AAK57478.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="EMBL" id="AAQ04661.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="EMBL" id="BAB55649.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="EMBL" id="BAC85392.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:18275"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="PIR" id="JC7326"/>
        </source>
    </evidence>
    <sequence length="478" mass="53979" checksum="BF2B9959A5BF0BB5" modified="2001-12-01" version="1">MDTSDLFASCRKGDVGRVRYLLEQRDVEVNVRDKWDSTPLYYACLCGHEELVLYLLANGARCEANTFDGERCLYGALSDPIRRALRDYKQVTASCRRRDYYDDFLQRLLEQGIHSDVVFVVHGKPFRVHRCVLGARSAYFANMLDTKWKGKSVVVLRHPLINPVAFGALLQYLYTGRLDIGVEHVSDCERLAKQCQLWDLLSDLEAKCEKVSEFVASKPGTCVKVLTIEPPPADPRLREDMALLADCALPPELRGDLWELPFPCPDGFNSCPDICFRVAGCSFLCHKAFFCGRSDYFRALLDDHFRESEEPATSGGPPAVTLHGISPDVFTHVLYYMYSDHTELSPEAAYDVLSVADMYLLPGLKRLCGRSLAQMLDEDTVVGVWRVAKLFRLARLEDQCTEYMAKVIEKLVEREDFVEAVKEEAAAVAARQETDSIPLVDDIRFHVASTVQTYSAIEEAQQRLRALEDLLVSIGLDC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-02-01" modified="2026-01-28" version="178" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N961</accession>
    <accession>A8K6S9</accession>
    <accession>E9PRW7</accession>
    <accession>Q52LD6</accession>
    <accession>Q6MZW4</accession>
    <accession>Q8NB44</accession>
    <name>ABTB2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Ankyrin repeat and BTB/POZ domain-containing protein 2</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ABTB2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT GLN-250</scope>
        <source>
            <tissue>Fetal brain</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
                <person name="Bruford E."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Eichler E."/>
                <person name="FitzGerald M.G."/>
                <person name="Jaffe D.B."/>
                <person name="LaButti K."/>
                <person name="Nicol R."/>
                <person name="Park H.-S."/>
                <person name="Seaman C."/>
                <person name="Sougnez C."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Zody M.C."/>
                <person name="Birren B.W."/>
                <person name="Nusbaum C."/>
                <person name="Fujiyama A."/>
                <person name="Hattori M."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 626-1025 (ISOFORM 1/2)</scope>
        <source>
            <tissue>Rectum tumor</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">May be involved in the initiation of hepatocyte growth.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11603395">
            <id>Q8N961</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N961-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N961-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046439"/>
        </isoform>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH93968" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC03697" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAF84433" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAF84433" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AK091560">
        <property type="protein sequence ID" value="BAC03697.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK095632">
        <property type="protein sequence ID" value="BAC04595.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291744">
        <property type="protein sequence ID" value="BAF84433.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC090469">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL035079">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133294">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139174">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093968">
        <property type="protein sequence ID" value="AAH93968.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX640841">
        <property type="protein sequence ID" value="CAE45913.3"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7890.2">
        <molecule id="Q8N961-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_665803.2">
        <molecule id="Q8N961-1"/>
        <property type="nucleotide sequence ID" value="NM_145804.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8N961"/>
    <dbReference type="SMR" id="Q8N961"/>
    <dbReference type="BioGRID" id="117367">
        <property type="interactions" value="130"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8N961">
        <property type="interactions" value="135"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N961">
        <property type="interactions" value="88"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000410157"/>
    <dbReference type="GlyGen" id="Q8N961">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8N961"/>
    <dbReference type="PhosphoSitePlus" id="Q8N961"/>
    <dbReference type="BioMuta" id="ABTB2"/>
    <dbReference type="DMDM" id="485955977"/>
    <dbReference type="jPOST" id="Q8N961"/>
    <dbReference type="MassIVE" id="Q8N961"/>
    <dbReference type="PaxDb" id="9606-ENSP00000410157"/>
    <dbReference type="PeptideAtlas" id="Q8N961"/>
    <dbReference type="ProteomicsDB" id="23438"/>
    <dbReference type="ProteomicsDB" id="72494">
        <molecule id="Q8N961-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8N961"/>
    <dbReference type="Antibodypedia" id="12992">
        <property type="antibodies" value="67 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="25841"/>
    <dbReference type="Ensembl" id="ENST00000435224.3">
        <molecule id="Q8N961-1"/>
        <property type="protein sequence ID" value="ENSP00000410157.2"/>
        <property type="gene ID" value="ENSG00000166016.7"/>
    </dbReference>
    <dbReference type="GeneID" id="25841"/>
    <dbReference type="KEGG" id="hsa:25841"/>
    <dbReference type="MANE-Select" id="ENST00000435224.3">
        <property type="protein sequence ID" value="ENSP00000410157.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_145804.3"/>
        <property type="RefSeq protein sequence ID" value="NP_665803.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001mvl.3">
        <molecule id="Q8N961-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23842"/>
    <dbReference type="ClinPGx" id="PA134937734"/>
    <dbReference type="CTD" id="25841"/>
    <dbReference type="DisGeNET" id="25841"/>
    <dbReference type="GeneCards" id="ABTB2"/>
    <dbReference type="HGNC" id="HGNC:23842">
        <property type="gene designation" value="ABTB2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000166016">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="621014">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166016"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000166016"/>
    <dbReference type="eggNOG" id="ENOG502QSQY">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157661"/>
    <dbReference type="HOGENOM" id="CLU_001918_0_0_1"/>
    <dbReference type="InParanoid" id="Q8N961"/>
    <dbReference type="OMA" id="LQCNGST"/>
    <dbReference type="OrthoDB" id="2316821at2759"/>
    <dbReference type="PAN-GO" id="Q8N961">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N961"/>
    <dbReference type="PathwayCommons" id="Q8N961"/>
    <dbReference type="SignaLink" id="Q8N961"/>
    <dbReference type="Agora" id="ENSG00000166016"/>
    <dbReference type="BioGRID-ORCS" id="25841">
        <property type="hits" value="19 hits in 1192 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ABTB2">
        <property type="organism name" value="human"/>
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    <dbReference type="GenomeRNAi" id="25841"/>
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        <property type="development level" value="Tdark"/>
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    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
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    <dbReference type="RNAct" id="Q8N961">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000166016">
        <property type="expression patterns" value="Expressed in secondary oocyte and 165 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046982">
        <property type="term" value="F:protein heterodimerization activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0097237">
        <property type="term" value="P:cellular response to toxic substance"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="CDD" id="cd18526">
        <property type="entry name" value="BACK_ABTB2"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd18350">
        <property type="entry name" value="BTB_POZ_ABTB2_BPOZ2"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd22913">
        <property type="entry name" value="HFD_ABTB2-like"/>
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        <property type="entry name" value="Ankyrin repeat and BTB/POZ domain-containing protein 2"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.20.10:FF:000057">
        <property type="entry name" value="ankyrin repeat and BTB/POZ domain-containing protein 2"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.710.10:FF:000030">
        <property type="entry name" value="Ankyrin repeat and BTB/POZ domain-containing protein BTBD11"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Histone, subunit A"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.30.710.10">
        <property type="entry name" value="Potassium Channel Kv1.1, Chain A"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ABTB2/3_histone"/>
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    <dbReference type="InterPro" id="IPR048063">
        <property type="entry name" value="ABTB2_BTB_POZ"/>
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        <property type="entry name" value="Ankyrin-BTB/POZ_domain"/>
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        <property type="entry name" value="Ankyrin_rpt"/>
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    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
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    <dbReference type="InterPro" id="IPR000210">
        <property type="entry name" value="BTB/POZ_dom"/>
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    <dbReference type="InterPro" id="IPR009072">
        <property type="entry name" value="Histone-fold"/>
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    <dbReference type="InterPro" id="IPR011333">
        <property type="entry name" value="SKP1/BTB/POZ_sf"/>
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    <dbReference type="PANTHER" id="PTHR46071">
        <property type="entry name" value="ANKYRIN REPEAT AND BTB/POZ DOMAIN-CONTAINING"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR46071:SF3">
        <property type="entry name" value="ANKYRIN REPEAT AND BTB_POZ DOMAIN-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00651">
        <property type="entry name" value="BTB"/>
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    <dbReference type="Pfam" id="PF26281">
        <property type="entry name" value="Histone_ABTB"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="5"/>
    </dbReference>
    <dbReference type="SMART" id="SM00225">
        <property type="entry name" value="BTB"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF47113">
        <property type="entry name" value="Histone-fold"/>
        <property type="match status" value="2"/>
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    <dbReference type="SUPFAM" id="SSF54695">
        <property type="entry name" value="POZ domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50097">
        <property type="entry name" value="BTB"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000066887" description="Ankyrin repeat and BTB/POZ domain-containing protein 2">
        <location>
            <begin position="1"/>
            <end position="1025"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="521"/>
            <end position="550"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="567"/>
            <end position="596"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="606"/>
            <end position="635"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4">
        <location>
            <begin position="649"/>
            <end position="678"/>
        </location>
    </feature>
    <feature type="domain" description="BTB" evidence="2">
        <location>
            <begin position="845"/>
            <end position="914"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046439" description="In isoform 2." evidence="4">
        <location>
            <begin position="1"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022087" description="In dbSNP:rs1925368." evidence="3">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="250"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_024171" description="In dbSNP:rs2473928.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="918"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAF84433." evidence="5" ref="1">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="189"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00037"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="1025" mass="113656" checksum="E0DBA1B9BC0AFB82" modified="2013-05-01" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-12-20" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q15018</accession>
    <accession>B4DKR2</accession>
    <accession>Q96H11</accession>
    <name>ABRX2_HUMAN</name>
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        <recommendedName>
            <fullName evidence="21">BRISC complex subunit Abraxas 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="18">Abraxas brother protein 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein FAM175B</fullName>
        </alternativeName>
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    <gene>
        <name evidence="21" type="primary">ABRAXAS2</name>
        <name evidence="17" type="synonym">ABRO1</name>
        <name evidence="21" type="synonym">FAM175B</name>
        <name evidence="19" type="synonym">KIAA0157</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.</title>
            <authorList>
                <person name="Wang B."/>
                <person name="Hurov K."/>
                <person name="Hofmann K."/>
                <person name="Elledge S.J."/>
            </authorList>
            <dbReference type="PubMed" id="19261749"/>
            <dbReference type="DOI" id="10.1101/gad.1770309"/>
        </citation>
        <scope>DOMAIN MPN-LIKE</scope>
        <scope>UBIQUITIN-BINDING</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368; SER-372 AND SER-375</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2010" name="J. Biol. Chem." volume="285" first="10344" last="10352">
            <title>Specificity of the BRISC deubiquitinating enzyme is not due to selective binding to Lys63-linked polyubiquitin.</title>
            <authorList>
                <person name="Cooper E.M."/>
                <person name="Boeke J.D."/>
                <person name="Cohen R.E."/>
            </authorList>
            <dbReference type="PubMed" id="20032457"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.059667"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>IDENTIFICATION IN THE BRISC COMPLEX</scope>
        <scope>INTERACTION OF THE BRISC COMPLEX WITH UBIQUITIN</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="J. Biol. Chem." volume="285" first="30982" last="30988">
            <title>The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments.</title>
            <authorList>
                <person name="Feng L."/>
                <person name="Wang J."/>
                <person name="Chen J."/>
            </authorList>
            <dbReference type="PubMed" id="20656690"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.135392"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH BRCC3</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2011" name="J. Biol. Chem." volume="286" first="11734" last="11745">
            <title>NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes.</title>
            <authorList>
                <person name="Hu X."/>
                <person name="Kim J.A."/>
                <person name="Castillo A."/>
                <person name="Huang M."/>
                <person name="Liu J."/>
                <person name="Wang B."/>
            </authorList>
            <dbReference type="PubMed" id="21282113"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.200857"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH BABAM1</scope>
        <scope>IDENTIFICATION IN THE BRISC COMPLEX</scope>
        <scope>LACK OF INTERACTION WITH BRCA1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2011" name="J. Mol. Cell. Cardiol." volume="50" first="652" last="661">
            <title>Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination.</title>
            <authorList>
                <person name="Cilenti L."/>
                <person name="Balakrishnan M.P."/>
                <person name="Wang X.L."/>
                <person name="Ambivero C."/>
                <person name="Sterlicchi M."/>
                <person name="del Monte F."/>
                <person name="Ma X.L."/>
                <person name="Zervos A.S."/>
            </authorList>
            <dbReference type="PubMed" id="21195082"/>
            <dbReference type="DOI" id="10.1016/j.yjmcc.2010.12.015"/>
        </citation>
        <scope>INTERACTION WITH THAP5</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2012" name="Biochim. Biophys. Acta" volume="1823" first="2149" last="2156">
            <title>ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway.</title>
            <authorList>
                <person name="Ambivero C.T."/>
                <person name="Cilenti L."/>
                <person name="Zervos A.S."/>
            </authorList>
            <dbReference type="PubMed" id="22974638"/>
            <dbReference type="DOI" id="10.1016/j.bbamcr.2012.08.020"/>
        </citation>
        <scope>INTERACTION WITH ATF4</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2013" name="Cell Rep." volume="5" first="180" last="193">
            <title>A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses.</title>
            <authorList>
                <person name="Zheng H."/>
                <person name="Gupta V."/>
                <person name="Patterson-Fortin J."/>
                <person name="Bhattacharya S."/>
                <person name="Katlinski K."/>
                <person name="Wu J."/>
                <person name="Varghese B."/>
                <person name="Carbone C.J."/>
                <person name="Aressy B."/>
                <person name="Fuchs S.Y."/>
                <person name="Greenberg R.A."/>
            </authorList>
            <dbReference type="PubMed" id="24075985"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2013.08.025"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE BRISC COMPLEX</scope>
        <scope>INTERACTION WITH SHMT1 AND SHMT2</scope>
        <scope>IDENTIFICATION IN A COMPLEX WITH SHMT2 AND IFNAR1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF 215-ALA--ALA-222</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274 AND SER-280</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2014" name="Nat. Commun." volume="5" first="5059" last="5059">
            <title>ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53.</title>
            <authorList>
                <person name="Zhang J."/>
                <person name="Cao M."/>
                <person name="Dong J."/>
                <person name="Li C."/>
                <person name="Xu W."/>
                <person name="Zhan Y."/>
                <person name="Wang X."/>
                <person name="Yu M."/>
                <person name="Ge C."/>
                <person name="Ge Z."/>
                <person name="Yang X."/>
            </authorList>
            <dbReference type="PubMed" id="25283148"/>
            <dbReference type="DOI" id="10.1038/ncomms6059"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION BY DNA DAMAGE</scope>
        <scope>INTERACTION WITH USP7 AND TP53</scope>
        <scope>IDENTIFICATION IN THE BRISC COMPLEX</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2015" name="J. Cell Biol." volume="210" first="209" last="224">
            <title>The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.</title>
            <authorList>
                <person name="Yan K."/>
                <person name="Li L."/>
                <person name="Wang X."/>
                <person name="Hong R."/>
                <person name="Zhang Y."/>
                <person name="Yang H."/>
                <person name="Lin M."/>
                <person name="Zhang S."/>
                <person name="He Q."/>
                <person name="Zheng D."/>
                <person name="Tang J."/>
                <person name="Yin Y."/>
                <person name="Shao G."/>
            </authorList>
            <dbReference type="PubMed" id="26195665"/>
            <dbReference type="DOI" id="10.1083/jcb.201503039"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH NUMA1</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="Mol. Cell" volume="59" first="970" last="983">
            <title>Higher-order assembly of BRCC36-KIAA0157 is required for DUB activity and biological function.</title>
            <authorList>
                <person name="Zeqiraj E."/>
                <person name="Tian L."/>
                <person name="Piggott C.A."/>
                <person name="Pillon M.C."/>
                <person name="Duffy N.M."/>
                <person name="Ceccarelli D.F."/>
                <person name="Keszei A.F."/>
                <person name="Lorenzen K."/>
                <person name="Kurinov I."/>
                <person name="Orlicky S."/>
                <person name="Gish G.D."/>
                <person name="Heck A.J."/>
                <person name="Guarne A."/>
                <person name="Greenberg R.A."/>
                <person name="Sicheri F."/>
            </authorList>
            <dbReference type="PubMed" id="26344097"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2015.07.028"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE BRISC COMPLEX</scope>
        <scope>INTERACTION WITH BRCC3; BABAM2; BABAM1 AND SHMT2</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF 11-SER-ALA-12; VAL-220; GLU-231 AND VAL-241</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6 8 9 13 14">Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6 7 8 9 10 11 12 13 14 15 16">Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19214193, PubMed:20032457, PubMed:21282113, PubMed:24075985, PubMed:25283148, PubMed:26195665, PubMed:26344097). Interacts with BRCC3/BRCC36; the interaction is direct (PubMed:20032457, PubMed:20656690, PubMed:26344097). Interacts with BABAM1 (PubMed:21282113). Does not interact with BRCA1 (PubMed:17525340, PubMed:21282113). Interacts with SHMT1 and SHMT2; the interaction is direct. Identified in a complex with SHMT2 and the other subunits of the BRISC complex (PubMed:24075985). The BRISC complex binds monoubiquitin and both 'Lys-48'- and 'Lys-63'-linked polyubiquitin (PubMed:20032457). Identified in complexes with IFNAR1, IFNAR2 and SHMT2 (PubMed:24075985). Interacts with THAP5 (PubMed:21195082). Interacts with ATF4 (PubMed:22974638). Identified in a complex with p53/TP53 and USP7; interacts directly with both proteins (PubMed:25283148). Interacts with NUMA1 (PubMed:26195665). Interacts with microtubule minus ends (PubMed:26195665). Binds polyubiquitin (PubMed:19261749).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056583">
            <id>Q15018</id>
        </interactant>
        <interactant intactId="EBI-949389">
            <id>Q9NXR7</id>
            <label>BABAM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056583">
            <id>Q15018</id>
        </interactant>
        <interactant intactId="EBI-750352">
            <id>P46736</id>
            <label>BRCC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056583">
            <id>Q15018</id>
        </interactant>
        <interactant intactId="EBI-740086">
            <id>Q96GG9</id>
            <label>DCUN1D1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1056583">
            <id>Q15018</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 10 11 12 13 14">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11 12 13 14">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15">Cytoplasm</location>
            <location evidence="15">Cytoskeleton</location>
            <location evidence="15">Spindle pole</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15">Cytoplasm</location>
            <location evidence="15">Cytoskeleton</location>
        </subcellularLocation>
        <text evidence="11 12 14 15">A minor proportion is detected in the nucleus (PubMed:21282113, PubMed:22974638). Translocates into the nucleus in response to DNA damage (PubMed:25283148). Directly binds to microtubules and is detected at the minus end of K-fibers (PubMed:26195665). Co-localizes with NUMA1 at mitotic spindle poles (PubMed:26195665).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Detected in heart muscle (at protein level). Detected in heart and muscle, and at much lower levels in brain (PubMed:21195082).</text>
    </comment>
    <comment type="induction">
        <text evidence="10 14">Up-regulated in response to DNA damage (PubMed:25283148). Up-regulated in myocardial infarction area (at protein level) (PubMed:21195082).</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the FAM175 family. Abro1 subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="20">Although strongly related to the ABRAXAS1 protein, lacks the C-terminal pSXXF that constitutes a specific recognition motif for the BRCT domain of BRCA1.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA09927" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="D63877">
        <property type="protein sequence ID" value="BAA09927.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296677">
        <property type="protein sequence ID" value="BAG59274.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008999">
        <property type="protein sequence ID" value="AAH08999.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31308.2"/>
    <dbReference type="RefSeq" id="NP_115558.3">
        <property type="nucleotide sequence ID" value="NM_032182.3"/>
    </dbReference>
    <dbReference type="PDB" id="6H3C">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="A/F=1-415"/>
    </dbReference>
    <dbReference type="PDB" id="6R8F">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.80 A"/>
        <property type="chains" value="B/D=1-267"/>
    </dbReference>
    <dbReference type="PDB" id="8PVY">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.02 A"/>
        <property type="chains" value="B/D/H/J=1-267"/>
    </dbReference>
    <dbReference type="PDB" id="8PY2">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.32 A"/>
        <property type="chains" value="B/D/H/J=1-267"/>
    </dbReference>
    <dbReference type="PDBsum" id="6H3C"/>
    <dbReference type="PDBsum" id="6R8F"/>
    <dbReference type="PDBsum" id="8PVY"/>
    <dbReference type="PDBsum" id="8PY2"/>
    <dbReference type="AlphaFoldDB" id="Q15018"/>
    <dbReference type="EMDB" id="EMD-0132"/>
    <dbReference type="EMDB" id="EMD-17980"/>
    <dbReference type="EMDB" id="EMD-18009"/>
    <dbReference type="EMDB" id="EMD-4759"/>
    <dbReference type="EMDB" id="EMD-4760"/>
    <dbReference type="SMR" id="Q15018"/>
    <dbReference type="BioGRID" id="116784">
        <property type="interactions" value="100"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-9341">
        <property type="entry name" value="BRISC-SHMT2 complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-9421">
        <property type="entry name" value="BRISC complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q15018"/>
    <dbReference type="FunCoup" id="Q15018">
        <property type="interactions" value="2806"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15018">
        <property type="interactions" value="105"/>
    </dbReference>
    <dbReference type="MINT" id="Q15018"/>
    <dbReference type="STRING" id="9606.ENSP00000298492"/>
    <dbReference type="BindingDB" id="Q15018"/>
    <dbReference type="GlyGen" id="Q15018">
        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15018"/>
    <dbReference type="PhosphoSitePlus" id="Q15018"/>
    <dbReference type="SwissPalm" id="Q15018"/>
    <dbReference type="BioMuta" id="ABRAXAS2"/>
    <dbReference type="DMDM" id="84029317"/>
    <dbReference type="jPOST" id="Q15018"/>
    <dbReference type="MassIVE" id="Q15018"/>
    <dbReference type="PaxDb" id="9606-ENSP00000298492"/>
    <dbReference type="PeptideAtlas" id="Q15018"/>
    <dbReference type="ProteomicsDB" id="60367"/>
    <dbReference type="Pumba" id="Q15018"/>
    <dbReference type="Antibodypedia" id="32387">
        <property type="antibodies" value="88 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23172"/>
    <dbReference type="Ensembl" id="ENST00000298492.6">
        <property type="protein sequence ID" value="ENSP00000298492.5"/>
        <property type="gene ID" value="ENSG00000165660.9"/>
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    <dbReference type="GeneID" id="23172"/>
    <dbReference type="KEGG" id="hsa:23172"/>
    <dbReference type="MANE-Select" id="ENST00000298492.6">
        <property type="protein sequence ID" value="ENSP00000298492.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032182.4"/>
        <property type="RefSeq protein sequence ID" value="NP_115558.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001lib.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28975"/>
    <dbReference type="ClinPGx" id="PA162387331"/>
    <dbReference type="CTD" id="23172"/>
    <dbReference type="DisGeNET" id="23172"/>
    <dbReference type="GeneCards" id="ABRAXAS2"/>
    <dbReference type="HGNC" id="HGNC:28975">
        <property type="gene designation" value="ABRAXAS2"/>
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    <dbReference type="HPA" id="ENSG00000165660">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="611144">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000165660"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000165660"/>
    <dbReference type="eggNOG" id="ENOG502QTRN">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00530000063424"/>
    <dbReference type="HOGENOM" id="CLU_040659_0_0_1"/>
    <dbReference type="InParanoid" id="Q15018"/>
    <dbReference type="OMA" id="CPPRGMM"/>
    <dbReference type="OrthoDB" id="6358435at2759"/>
    <dbReference type="PAN-GO" id="Q15018">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15018"/>
    <dbReference type="PathwayCommons" id="Q15018"/>
    <dbReference type="Reactome" id="R-HSA-5689901">
        <property type="pathway name" value="Metalloprotease DUBs"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q15018"/>
    <dbReference type="Agora" id="ENSG00000165660"/>
    <dbReference type="BioGRID-ORCS" id="23172">
        <property type="hits" value="24 hits in 1165 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ABRAXAS2">
        <property type="organism name" value="human"/>
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    <dbReference type="GeneWiki" id="KIAA0157"/>
    <dbReference type="GenomeRNAi" id="23172"/>
    <dbReference type="Pharos" id="Q15018">
        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:Q15018"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
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    <dbReference type="RNAct" id="Q15018">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000165660">
        <property type="expression patterns" value="Expressed in secondary oocyte and 198 other cell types or tissues"/>
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    <dbReference type="GO" id="GO:0070552">
        <property type="term" value="C:BRISC complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0036064">
        <property type="term" value="C:ciliary basal body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
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        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
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        <property type="term" value="C:cytosol"/>
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        <property type="term" value="C:microtubule"/>
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        <property type="project" value="UniProtKB-KW"/>
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="C:spindle pole"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="term" value="P:attachment of spindle microtubules to kinetochore"/>
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        <property type="term" value="P:mitotic cell cycle"/>
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        <property type="term" value="P:mitotic spindle assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:protein K63-linked deubiquitination"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0002931">
        <property type="term" value="P:response to ischemia"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd23524">
        <property type="entry name" value="Abraxas_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="BRISC_Abraxas2"/>
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    <dbReference type="InterPro" id="IPR023238">
        <property type="entry name" value="FAM175"/>
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    <dbReference type="InterPro" id="IPR037518">
        <property type="entry name" value="MPN"/>
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    <dbReference type="PANTHER" id="PTHR31728">
        <property type="entry name" value="ABRAXAS FAMILY MEMBER"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="BRISC COMPLEX SUBUNIT ABRAXAS 2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF21125">
        <property type="entry name" value="MPN_2A_DUB_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR02053">
        <property type="entry name" value="BRISCABRO1"/>
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    <dbReference type="PRINTS" id="PR02051">
        <property type="entry name" value="PROTEINF175"/>
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    <dbReference type="PROSITE" id="PS50249">
        <property type="entry name" value="MPN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0131">Cell cycle</keyword>
    <keyword id="KW-0132">Cell division</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0493">Microtubule</keyword>
    <keyword id="KW-0498">Mitosis</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0833">Ubl conjugation pathway</keyword>
    <feature type="chain" id="PRO_0000050725" description="BRISC complex subunit Abraxas 2">
        <location>
            <begin position="1"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="domain" description="MPN" evidence="3">
        <location>
            <begin position="3"/>
            <end position="149"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for interaction with SHMT2" evidence="13">
        <location>
            <begin position="215"/>
            <end position="222"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for interaction with BBRC36 and other subunits of the BRISC complex" evidence="16">
        <location>
            <begin position="220"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="250"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="335"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="2">
        <location>
            <begin position="215"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="251"/>
            <end position="261"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="4">
        <location>
            <begin position="312"/>
            <end position="322"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="4">
        <location>
            <begin position="337"/>
            <end position="347"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="4">
        <location>
            <begin position="368"/>
            <end position="379"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="392"/>
            <end position="408"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="27">
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="23 25 27">
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="22 23 24 26">
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="22 23 24">
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="23 24">
        <location>
            <position position="375"/>
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    </feature>
    <feature type="mutagenesis site" description="Slightly reduces interaction with BBRC36. Abolishes interaction with SHMT2. Strongly reduces interactions with BABAM2 and BABAM1." evidence="16">
        <original>SA</original>
        <variation>RR</variation>
        <location>
            <begin position="11"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces interaction with SHMT2, but has no effect on interaction with BRCC3." evidence="13">
        <location>
            <begin position="215"/>
            <end position="222"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly reduces interaction with BBRC3; SHMT2; BABAM2 and BABAM1; when associated with Y-231. Abolishes interaction with BRCC3 and strongly reduces interaction with SHMT2; BABAM2 and BABAM1; when associated with Y-231 and Y-241." evidence="16">
        <original>V</original>
        <variation>R</variation>
        <location>
            <position position="220"/>
        </location>
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    <feature type="mutagenesis site" description="Strongly reduces interaction with BBRC3; SHMT2; BABAM2 and BABAM1; when associated with R-220. Abolishes interaction with BRCC3 and strongly reduces interaction with SHMT2; BABAM2 and BABAM1; when associated with R-220 and Y-241." evidence="16">
        <original>E</original>
        <variation>Y</variation>
        <location>
            <position position="231"/>
        </location>
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    <feature type="mutagenesis site" description="Abolishes interaction with BRCC3 and strongly reduces interaction with SHMT2; BABAM2 and BABAM1; when associated with R-220 and Y-231." evidence="16">
        <original>V</original>
        <variation>R</variation>
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA09927." evidence="20" ref="1">
        <original>EIH</original>
        <variation>QIY</variation>
        <location>
            <begin position="55"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG59274." evidence="20" ref="2">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="230"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="2"/>
            <end position="5"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="7"/>
            <end position="18"/>
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    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="24"/>
            <end position="34"/>
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    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="52"/>
            <end position="61"/>
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    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="63"/>
            <end position="66"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="77"/>
            <end position="83"/>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="84"/>
            <end position="86"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="87"/>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="91"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="107"/>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="126"/>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="141"/>
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    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="152"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="165"/>
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    <feature type="helix" evidence="28">
        <location>
            <begin position="183"/>
            <end position="192"/>
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    <feature type="turn" evidence="28">
        <location>
            <begin position="193"/>
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        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="199"/>
            <end position="203"/>
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    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="204"/>
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    <evidence type="ECO:0000250" key="1">
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            <dbReference type="UniProtKB" id="Q3TCJ1"/>
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    <evidence type="ECO:0000255" key="2"/>
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        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01182"/>
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        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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        <source>
            <dbReference type="PubMed" id="17525340"/>
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            <dbReference type="PubMed" id="19214193"/>
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        <source>
            <dbReference type="PubMed" id="19261749"/>
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        <source>
            <dbReference type="PubMed" id="20032457"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="20656690"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="21195082"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="21282113"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="22974638"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="24075985"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="25283148"/>
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    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="26195665"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="26344097"/>
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    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="21195082"/>
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    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="22974638"/>
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    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="8590280"/>
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    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0000312" key="21">
        <source>
            <dbReference type="HGNC" id="HGNC:28975"/>
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    <evidence type="ECO:0007744" key="22">
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            <dbReference type="PubMed" id="17081983"/>
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            <dbReference type="PubMed" id="18669648"/>
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        <source>
            <dbReference type="PubMed" id="19690332"/>
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            <dbReference type="PubMed" id="20068231"/>
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            <dbReference type="PubMed" id="21406692"/>
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        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="8PVY"/>
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    </evidence>
    <sequence length="415" mass="46901" checksum="EDA67ACB10C66C51" modified="2005-12-20" version="2">MAASISGYTFSAVCFHSANSNADHEGFLLGEVRQEETFSISDSQISNTEFLQVIEIHNHQPCSKLFSFYDYASKVNEESLDRILKDRRKKVIGWYRFRRNTQQQMSYREQVLHKQLTRILGVPDLVFLLFSFISTANNSTHALEYVLFRPNRRYNQRISLAIPNLGNTSQQEYKVSSVPNTSQSYAKVIKEHGTDFFDKDGVMKDIRAIYQVYNALQEKVQAVCADVEKSERVVESCQAEVNKLRRQITQRKNEKEQERRLQQAVLSRQMPSESLDPAFSPRMPSSGFAAEGRSTLGDAEASDPPPPYSDFHPNNQESTLSHSRMERSVFMPRPQAVGSSNYASTSAGLKYPGSGADLPPPQRAAGDSGEDSDDSDYENLIDPTEPSNSEYSHSKDSRPMAHPDEDPRNTQTSQI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="250" xmlns="https://uniprot.org/uniprot">
    <accession>P42684</accession>
    <accession>A0M8X0</accession>
    <accession>B7UEF2</accession>
    <accession>B7UEF3</accession>
    <accession>B7UEF4</accession>
    <accession>B7UEF5</accession>
    <accession>Q5T0X6</accession>
    <accession>Q5W0C5</accession>
    <accession>Q6NZY6</accession>
    <accession>Q7Z301</accession>
    <name>ABL2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Tyrosine-protein kinase ABL2</fullName>
            <ecNumber>2.7.10.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Abelson murine leukemia viral oncogene homolog 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Abelson tyrosine-protein kinase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Abelson-related gene protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Tyrosine-protein kinase ARG</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ABL2</name>
        <name type="synonym">ABLL</name>
        <name type="synonym">ARG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-647 (ISOFORM 4)</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-683 (ISOFORM 5)</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-662 (ISOFORM 7)</scope>
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        <scope>INTERACTION WITH CTTN</scope>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] HIS-78; GLN-99; ILE-519; SER-769; ARG-930 AND ARG-996</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] THR-12 (ISOFORM 4)</scope>
    </reference>
    <comment type="function">
        <text evidence="3 11 12 13 14 17">Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10596"/>
            <dbReference type="Rhea" id="RHEA-COMP:10136"/>
            <dbReference type="Rhea" id="RHEA-COMP:20101"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:46858"/>
            <dbReference type="ChEBI" id="CHEBI:61978"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.10.2"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="1">Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="12 13 18 19">Interacts with PSMA7. Interacts with CTTN. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-375446">
            <id>Q8IZP0</id>
            <label>ABI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-886">
            <id>P46108</id>
            <label>CRK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-297353">
            <id>P00533</id>
            <label>EGFR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-641062">
            <id>P04626</id>
            <label>ERBB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-720706">
            <id>P21860</id>
            <label>ERBB3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
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        <interactant intactId="EBI-80371">
            <id>Q15303</id>
            <label>ERBB4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
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        <interactant intactId="EBI-515315">
            <id>P06241</id>
            <label>FYN</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-1379503">
            <id>P10721</id>
            <label>KIT</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-389883">
            <id>P16333</id>
            <label>NCK1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-79464">
            <id>P27986</id>
            <label>PIK3R1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-79387">
            <id>P19174</id>
            <label>PLCG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-366017">
            <id>Q13671</id>
            <label>RIN1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>P42684</id>
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        <interactant intactId="EBI-744603">
            <id>Q15637</id>
            <label>SF1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1102694">
            <id>P42684</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10693977">
            <id>P42684-3</id>
        </interactant>
        <interactant intactId="EBI-11096309">
            <id>Q9NYB9-2</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10693977">
            <id>P42684-3</id>
        </interactant>
        <interactant intactId="EBI-6550597">
            <id>Q15642-2</id>
            <label>TRIP10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
            <location evidence="3">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P42684-1</id>
            <name>1</name>
            <name>IB</name>
            <name>1BLCTL</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P42684-2</id>
            <name>2</name>
            <name>IA</name>
            <name>1ASCTL</name>
            <sequence type="described" ref="VSP_004961"/>
        </isoform>
        <isoform>
            <id>P42684-3</id>
            <name>3</name>
            <name>IC</name>
            <name>1ALCTL</name>
            <sequence type="described" ref="VSP_017112"/>
        </isoform>
        <isoform>
            <id>P42684-4</id>
            <name>4</name>
            <name>1ASCTS</name>
            <sequence type="described" ref="VSP_004961 VSP_021308"/>
        </isoform>
        <isoform>
            <id>P42684-5</id>
            <name>5</name>
            <name>1BLCTS</name>
            <sequence type="described" ref="VSP_021308"/>
        </isoform>
        <isoform>
            <id>P42684-6</id>
            <name>6</name>
            <name>1BSCTL</name>
            <sequence type="described" ref="VSP_041772"/>
        </isoform>
        <isoform>
            <id>P42684-7</id>
            <name>7</name>
            <name>1BSCTS</name>
            <sequence type="described" ref="VSP_041772 VSP_021308"/>
        </isoform>
        <isoform>
            <id>P42684-10</id>
            <name>10</name>
            <name>1ALCTS</name>
            <sequence type="described" ref="VSP_017112 VSP_021308"/>
        </isoform>
        <isoform>
            <id>P42684-8</id>
            <name>8</name>
            <sequence type="described" ref="VSP_041772 VSP_041773 VSP_041774"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Contains two distinct classes of F-actin-binding domains. Although both can bind F-actin, the 2 are required to bundle actin filaments (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress. Phosphorylated by PDGFRB (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAD98092" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/226/ABL2"/>
    </comment>
    <dbReference type="EC" id="2.7.10.2"/>
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        <property type="protein sequence ID" value="AAA35553.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="FJ542283">
        <property type="protein sequence ID" value="ACK76601.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="ACK76602.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="FJ542285">
        <property type="protein sequence ID" value="ACK76603.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="FJ542286">
        <property type="protein sequence ID" value="ACK76604.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK311045">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX538317">
        <property type="protein sequence ID" value="CAD98092.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ009672">
        <property type="protein sequence ID" value="AAY16984.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139132">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359179">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW91040.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC065912">
        <property type="protein sequence ID" value="AAH65912.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="A35962"/>
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    <dbReference type="PIR" id="B35962">
        <property type="entry name" value="B35962"/>
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    <dbReference type="RefSeq" id="NP_001129472.1">
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        <property type="nucleotide sequence ID" value="NM_001136000.3"/>
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    <dbReference type="RefSeq" id="NP_001129473.1">
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        <property type="nucleotide sequence ID" value="NM_001136001.2"/>
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        <property type="nucleotide sequence ID" value="NM_001168236.2"/>
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        <property type="nucleotide sequence ID" value="NM_001168238.2"/>
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        <property type="nucleotide sequence ID" value="NM_001168239.2"/>
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        <property type="nucleotide sequence ID" value="NM_005158.4"/>
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        <property type="nucleotide sequence ID" value="NM_007314.4"/>
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    <dbReference type="RefSeq" id="XP_005245145.1">
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        <property type="nucleotide sequence ID" value="XM_005245088.3"/>
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        <property type="method" value="NMR"/>
        <property type="chains" value="A=163-268"/>
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        <property type="method" value="NMR"/>
        <property type="chains" value="A=1058-1182"/>
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    <dbReference type="PDB" id="2XYN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.81 A"/>
        <property type="chains" value="A/B/C=279-546"/>
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        <property type="resolution" value="2.05 A"/>
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        <property type="resolution" value="1.65 A"/>
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        <property type="resolution" value="1.20 A"/>
        <property type="chains" value="A=165-273"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="A/B=110-166"/>
    </dbReference>
    <dbReference type="PDBsum" id="2ECD"/>
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    <dbReference type="AlphaFoldDB" id="P42684"/>
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        <property type="interactions" value="113"/>
    </dbReference>
    <dbReference type="CORUM" id="P42684"/>
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        <property type="interactions" value="1292"/>
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    <dbReference type="IntAct" id="P42684">
        <property type="interactions" value="93"/>
    </dbReference>
    <dbReference type="MINT" id="P42684"/>
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        <property type="generic name" value="ATP"/>
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    <dbReference type="DrugBank" id="DB01254">
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    </dbReference>
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        <property type="generic name" value="K-00546"/>
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        <property type="type" value="Predicted"/>
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        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
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        <property type="protein sequence ID" value="ENSP00000339209.3"/>
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        <property type="gene ID" value="ENSG00000143322.22"/>
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        <property type="RefSeq protein sequence ID" value="NP_009298.1"/>
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        <property type="evidences" value="1 evidence item across 5 molecular profiles"/>
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        <property type="gene designation" value="ABL2"/>
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    <dbReference type="HPA" id="ENSG00000143322">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
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        <property type="type" value="gene"/>
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    <dbReference type="GeneTree" id="ENSGT00940000153838"/>
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        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
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        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P42684"/>
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        <property type="pathway name" value="Role of ABL in ROBO-SLIT signaling"/>
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<entry dataset="Swiss-Prot" created="2008-04-08" modified="2026-01-28" version="137" xmlns="https://uniprot.org/uniprot">
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            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 4 AND 5)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 338-1104 (ISOFORM 3)</scope>
        <source>
            <tissue>Hippocampus</tissue>
            <tissue>Tongue</tissue>
        </source>
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            <dbReference type="PubMed" id="16541075"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 550-1104 (ISOFORM 1)</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Cortical and hippocampal inhibitory interneuron-specific protein localized at glutamatergic (excitatory) synapses, where it supports cell type-specific synaptic function.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with core postsynaptic proteins, including DLG4; interaction with DLG4 stabilizes DLG4 at glutamatergic synapses.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Membrane</location>
            <topology evidence="2">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>A6QL63-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>A6QL63-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_032802"/>
        </isoform>
        <isoform>
            <id>A6QL63-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_032803"/>
        </isoform>
        <isoform>
            <id>A6QL63-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_032801"/>
        </isoform>
        <isoform>
            <id>A6QL63-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_045802 VSP_045803"/>
        </isoform>
    </comment>
    <comment type="induction">
        <text>By all-trans retinoic acid (ATRA).</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAI01562" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAI01564" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAI46825" version="1"/>
        </conflict>
        <text>Contaminating sequence. Potential poly-A sequence.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAR21078" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC85963" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="EAW97799" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK091276">
        <property type="protein sequence ID" value="BAC03626.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK124835">
        <property type="protein sequence ID" value="BAC85963.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK127295">
        <property type="protein sequence ID" value="BAG54475.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007540">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007649">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009774">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW97799.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW97800.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093627">
        <property type="protein sequence ID" value="AAH93627.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093629">
        <property type="protein sequence ID" value="AAH93629.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101561">
        <property type="protein sequence ID" value="AAI01562.1"/>
        <property type="status" value="ALT_INIT"/>
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    <dbReference type="GenomeRNAi" id="121551"/>
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        <property type="component" value="Chromosome 12"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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    </dbReference>
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        <property type="project" value="InterPro"/>
    </dbReference>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050821">
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035249">
        <property type="term" value="P:synaptic transmission, glutamatergic"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd18527">
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        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd18351">
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        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd22913">
        <property type="entry name" value="HFD_ABTB2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000045">
        <property type="entry name" value="Ankyrin repeat and BTB/POZ domain-containing protein 2"/>
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    <dbReference type="FunFam" id="3.30.710.10:FF:000030">
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.10.20.10">
        <property type="entry name" value="Histone, subunit A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.710.10">
        <property type="entry name" value="Potassium Channel Kv1.1, Chain A"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR059008">
        <property type="entry name" value="ABTB2/3_histone"/>
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    <dbReference type="InterPro" id="IPR052089">
        <property type="entry name" value="Ankyrin-BTB/POZ_domain"/>
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    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
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    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
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    <dbReference type="InterPro" id="IPR000210">
        <property type="entry name" value="BTB/POZ_dom"/>
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    <dbReference type="InterPro" id="IPR047824">
        <property type="entry name" value="BTBD11_BACK"/>
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    <dbReference type="InterPro" id="IPR009072">
        <property type="entry name" value="Histone-fold"/>
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        <property type="entry name" value="SKP1/BTB/POZ_sf"/>
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    <dbReference type="PANTHER" id="PTHR46071">
        <property type="entry name" value="ANKYRIN REPEAT AND BTB/POZ DOMAIN-CONTAINING"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ANKYRIN REPEAT AND BTB_POZ DOMAIN-CONTAINING PROTEIN 3"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00023">
        <property type="entry name" value="Ank"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="BTB"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF26281">
        <property type="entry name" value="Histone_ABTB"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="4"/>
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    <dbReference type="SMART" id="SM00225">
        <property type="entry name" value="BTB"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47113">
        <property type="entry name" value="Histone-fold"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54695">
        <property type="entry name" value="POZ domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50097">
        <property type="entry name" value="BTB"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000328827" description="Ankyrin repeat- and BTB/POZ domain-containing protein 3">
        <location>
            <begin position="1"/>
            <end position="1104"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="168"/>
            <end position="188"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1" evidence="2">
        <location>
            <begin position="603"/>
            <end position="632"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2" evidence="2">
        <location>
            <begin position="649"/>
            <end position="678"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3" evidence="2">
        <location>
            <begin position="687"/>
            <end position="716"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 4" evidence="2">
        <location>
            <begin position="730"/>
            <end position="759"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 5" evidence="2">
        <location>
            <begin position="825"/>
            <end position="854"/>
        </location>
    </feature>
    <feature type="domain" description="BTB" evidence="3">
        <location>
            <begin position="923"/>
            <end position="989"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="260"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="4">
        <location>
            <begin position="264"/>
            <end position="276"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_032801" description="In isoform 4." evidence="5">
        <location>
            <begin position="1"/>
            <end position="921"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045802" description="In isoform 5." evidence="5">
        <original>MARRGKKPVVRTLEDLTLDSGYGGAADSVRSSN</original>
        <variation>MRKLRPKDSREPAPGSPVRSGCLQRLSHYSGIQ</variation>
        <location>
            <begin position="1"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045803" description="In isoform 5." evidence="5">
        <location>
            <begin position="34"/>
            <end position="496"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_032802" description="In isoform 2." evidence="6">
        <location>
            <begin position="699"/>
            <end position="817"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_032803" description="In isoform 3." evidence="5">
        <original>LLSAAKFFQLEALQRHCEIICAKSINTDNCVDIYNHAKFLGVTELSAYCEGYFLKNMMVLIENEAFKQLLYDKNGEGTGQDVLQDLQRTLAIRIQSIHLSSSKGSVV</original>
        <variation>VRDPLWCWLS</variation>
        <location>
            <begin position="998"/>
            <end position="1104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055560" description="In dbSNP:rs1558781.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042534" description="In dbSNP:rs11610050.">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="1002"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042535" description="In dbSNP:rs12303478.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="1076"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAI46825." evidence="7" ref="4">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC85963." evidence="7" ref="1">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="361"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAG54475." evidence="7" ref="1">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="653"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC03626." evidence="7" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1043"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q6GQW0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00037"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:23844"/>
        </source>
    </evidence>
    <sequence length="1104" mass="120884" checksum="118D5C668CB78A3E" modified="2009-11-24" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1999-07-15" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>Q12979</accession>
    <accession>B3KW89</accession>
    <accession>B7Z6H7</accession>
    <accession>D3DTH3</accession>
    <accession>D3DTH4</accession>
    <accession>F5H3S2</accession>
    <accession>F5H8B3</accession>
    <accession>Q13693</accession>
    <accession>Q13694</accession>
    <name>ABR_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">Active breakpoint cluster region-related protein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="15" type="primary">ABR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="J. Biol. Chem." volume="268" first="27291" last="27298">
            <title>The human active breakpoint cluster region-related gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins.</title>
            <authorList>
                <person name="Tan E.-C."/>
                <person name="Leung T."/>
                <person name="Manser E."/>
                <person name="Lim L."/>
            </authorList>
            <dbReference type="PubMed" id="8262969"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)74248-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
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                <person name="Ono T."/>
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                <person name="Isogai T."/>
                <person name="Sugano S."/>
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4)</scope>
        <scope>VARIANT ARG-517</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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            <title>Human ABR encodes a protein with GAPrac activity and homology to the DBL nucleotide exchange factor domain.</title>
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                <person name="Heisterkamp N."/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <source>
            <tissue>Fibroblast</tissue>
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            <dbReference type="PubMed" id="16625196"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <title>ABR, an active BCR-related gene.</title>
            <authorList>
                <person name="Heisterkamp N."/>
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                <person name="Groffen J."/>
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            <dbReference type="DOI" id="10.1093/nar/17.21.8821"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 436-597</scope>
    </reference>
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            <authorList>
                <person name="Chuang T.H."/>
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            <dbReference type="PubMed" id="7479768"/>
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        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
    </reference>
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            <title>Abr and Bcr, two homologous Rac GTPase-activating proteins, control multiple cellular functions of murine macrophages.</title>
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                <person name="Cho Y.J."/>
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            <dbReference type="DOI" id="10.1128/mcb.00756-06"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ARG-683 AND ASN-795</scope>
    </reference>
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            <title>Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins.</title>
            <authorList>
                <person name="Oh D."/>
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            <dbReference type="PubMed" id="20962234"/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH DLG4</scope>
        <scope>MUTAGENESIS OF VAL-859</scope>
    </reference>
    <comment type="function">
        <text evidence="2 9 11">Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:17116687, PubMed:7479768). The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF-1 directed motility and phagocytosis through the modulation of RAC1 activity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="10">Interacts with DLG4.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Dendritic spine</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Axon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Synapse</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q12979-1</id>
            <name>Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q12979-2</id>
            <name>Short</name>
            <sequence type="described" ref="VSP_001815"/>
        </isoform>
        <isoform>
            <id>Q12979-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046029 VSP_046030"/>
        </isoform>
        <isoform>
            <id>Q12979-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046148"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Highly enriched in the brain. Much weaker expression in heart, lung and muscle.</text>
    </comment>
    <comment type="domain">
        <text evidence="14">The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.</text>
    </comment>
    <dbReference type="EMBL" id="U01147">
        <property type="protein sequence ID" value="AAC50063.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L19704">
        <property type="protein sequence ID" value="AAC37519.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L19705">
        <property type="protein sequence ID" value="AAC37518.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK124547">
        <property type="protein sequence ID" value="BAG54051.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300336">
        <property type="protein sequence ID" value="BAH13263.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC015884">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC016292">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC144836">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90631.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90633.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90634.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90635.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10999.1">
        <molecule id="Q12979-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11000.1">
        <molecule id="Q12979-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54060.1">
        <molecule id="Q12979-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58497.1">
        <molecule id="Q12979-3"/>
    </dbReference>
    <dbReference type="PIR" id="A47485">
        <property type="entry name" value="A47485"/>
    </dbReference>
    <dbReference type="PIR" id="A49307">
        <property type="entry name" value="A49307"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001083.2">
        <molecule id="Q12979-2"/>
        <property type="nucleotide sequence ID" value="NM_001092.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001153218.1">
        <molecule id="Q12979-4"/>
        <property type="nucleotide sequence ID" value="NM_001159746.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001243776.1">
        <molecule id="Q12979-3"/>
        <property type="nucleotide sequence ID" value="NM_001256847.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269078.1">
        <property type="nucleotide sequence ID" value="NM_001282149.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309769.1">
        <molecule id="Q12979-4"/>
        <property type="nucleotide sequence ID" value="NM_001322840.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068781.2">
        <molecule id="Q12979-1"/>
        <property type="nucleotide sequence ID" value="NM_021962.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q12979"/>
    <dbReference type="SMR" id="Q12979"/>
    <dbReference type="BioGRID" id="106547">
        <property type="interactions" value="45"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q12979">
        <property type="interactions" value="1333"/>
    </dbReference>
    <dbReference type="IntAct" id="Q12979">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="MINT" id="Q12979"/>
    <dbReference type="STRING" id="9606.ENSP00000303909"/>
    <dbReference type="GlyGen" id="Q12979">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q12979"/>
    <dbReference type="PhosphoSitePlus" id="Q12979"/>
    <dbReference type="BioMuta" id="ABR"/>
    <dbReference type="DMDM" id="357528764"/>
    <dbReference type="jPOST" id="Q12979"/>
    <dbReference type="MassIVE" id="Q12979"/>
    <dbReference type="PaxDb" id="9606-ENSP00000303909"/>
    <dbReference type="PeptideAtlas" id="Q12979"/>
    <dbReference type="ProteomicsDB" id="26359"/>
    <dbReference type="ProteomicsDB" id="27736"/>
    <dbReference type="ProteomicsDB" id="59072">
        <molecule id="Q12979-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="59073">
        <molecule id="Q12979-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q12979"/>
    <dbReference type="Antibodypedia" id="22668">
        <property type="antibodies" value="75 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="29"/>
    <dbReference type="Ensembl" id="ENST00000291107.6">
        <molecule id="Q12979-2"/>
        <property type="protein sequence ID" value="ENSP00000291107.2"/>
        <property type="gene ID" value="ENSG00000159842.17"/>
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        <property type="gene designation" value="ABR"/>
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    </dbReference>
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00940000153491"/>
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        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q12979"/>
    <dbReference type="PathwayCommons" id="Q12979"/>
    <dbReference type="Reactome" id="R-HSA-193648">
        <property type="pathway name" value="NRAGE signals death through JNK"/>
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    <dbReference type="Reactome" id="R-HSA-416482">
        <property type="pathway name" value="G alpha (12/13) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8980692">
        <property type="pathway name" value="RHOA GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013026">
        <property type="pathway name" value="RHOB GTPase cycle"/>
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        <property type="pathway name" value="RHOC GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013148">
        <property type="pathway name" value="CDC42 GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013149">
        <property type="pathway name" value="RAC1 GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013404">
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        <property type="pathway name" value="RAC3 GTPase cycle"/>
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    <dbReference type="SIGNOR" id="Q12979"/>
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        <property type="hits" value="17 hits in 1143 CRISPR screens"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 17"/>
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        <property type="molecule type" value="protein"/>
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    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="evidence" value="ECO:0000250"/>
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        <property type="evidence" value="ECO:0007005"/>
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        <property type="term" value="P:modulation of chemical synaptic transmission"/>
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        <property type="term" value="P:regulation of small GTPase mediated signal transduction"/>
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        <property type="term" value="P:small GTPase-mediated signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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    <dbReference type="CDD" id="cd08686">
        <property type="entry name" value="C2_ABR"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd13366">
        <property type="entry name" value="PH_ABR"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd04387">
        <property type="entry name" value="RhoGAP_Bcr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd00160">
        <property type="entry name" value="RhoGEF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.150:FF:000057">
        <property type="entry name" value="active breakpoint cluster region-related protein isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.900.10:FF:000014">
        <property type="entry name" value="active breakpoint cluster region-related protein isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000112">
        <property type="entry name" value="active breakpoint cluster region-related protein isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.555.10:FF:000004">
        <property type="entry name" value="active breakpoint cluster region-related protein-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.150">
        <property type="entry name" value="C2 domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.900.10">
        <property type="entry name" value="Dbl homology (DH) domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.555.10">
        <property type="entry name" value="Rho GTPase activation protein"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR037769">
        <property type="entry name" value="Abr/Bcr"/>
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    <dbReference type="InterPro" id="IPR037865">
        <property type="entry name" value="ABR_PH"/>
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    <dbReference type="InterPro" id="IPR000008">
        <property type="entry name" value="C2_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035892">
        <property type="entry name" value="C2_domain_sf"/>
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    <dbReference type="InterPro" id="IPR035899">
        <property type="entry name" value="DBL_dom_sf"/>
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    <dbReference type="InterPro" id="IPR000219">
        <property type="entry name" value="DH_dom"/>
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    <dbReference type="InterPro" id="IPR001331">
        <property type="entry name" value="GDS_CDC24_CS"/>
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    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
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    <dbReference type="InterPro" id="IPR008936">
        <property type="entry name" value="Rho_GTPase_activation_prot"/>
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    <dbReference type="InterPro" id="IPR000198">
        <property type="entry name" value="RhoGAP_dom"/>
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    <dbReference type="PANTHER" id="PTHR23182:SF5">
        <property type="entry name" value="ACTIVE BREAKPOINT CLUSTER REGION-RELATED PROTEIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR23182">
        <property type="entry name" value="BREAKPOINT CLUSTER REGION PROTEIN BCR"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00168">
        <property type="entry name" value="C2"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00620">
        <property type="entry name" value="RhoGAP"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00621">
        <property type="entry name" value="RhoGEF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00239">
        <property type="entry name" value="C2"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00324">
        <property type="entry name" value="RhoGAP"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00325">
        <property type="entry name" value="RhoGEF"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF49562">
        <property type="entry name" value="C2 domain (Calcium/lipid-binding domain, CaLB)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF48065">
        <property type="entry name" value="DBL homology domain (DH-domain)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF48350">
        <property type="entry name" value="GTPase activation domain, GAP"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50004">
        <property type="entry name" value="C2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00741">
        <property type="entry name" value="DH_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50010">
        <property type="entry name" value="DH_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50238">
        <property type="entry name" value="RHOGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0344">Guanine-nucleotide releasing factor</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <feature type="chain" id="PRO_0000080902" description="Active breakpoint cluster region-related protein">
        <location>
            <begin position="1"/>
            <end position="859"/>
        </location>
    </feature>
    <feature type="domain" description="DH" evidence="4">
        <location>
            <begin position="91"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="5">
        <location>
            <begin position="301"/>
            <end position="459"/>
        </location>
    </feature>
    <feature type="domain" description="C2" evidence="3">
        <location>
            <begin position="484"/>
            <end position="613"/>
        </location>
    </feature>
    <feature type="domain" description="Rho-GAP" evidence="6">
        <location>
            <begin position="647"/>
            <end position="845"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="26"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="7">
        <location>
            <begin position="54"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="site" description="Arginine finger; crucial for GTP hydrolysis by stabilizing the transition state" evidence="6">
        <location>
            <position position="683"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001815" description="In isoform Short." evidence="13">
        <original>MEPLSHRGLPRLSWIDTLYSNFSYGTDEYDGEGNEEQKGPPEGSETMPYIDESPTMSPQLSARSQGGGDGVSPTPPEGLAPG</original>
        <variation>MEEEEEAIGLLDKVLEDEDVFLLEECELGTPTSPGSGSPFLVAVK</variation>
        <location>
            <begin position="1"/>
            <end position="82"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046029" description="In isoform 3." evidence="12">
        <original>MEPLSHRGLPRLSWIDTLYSNFSYGTDEYDGEGNEEQKGPPEGSETMP</original>
        <variation>MTDVLPQPDCSPKAGREPLALEESGSKRPPNTGARLWGRVRNKLLRNK</variation>
        <location>
            <begin position="1"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046148" description="In isoform 4." evidence="12">
        <location>
            <begin position="1"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046030" description="In isoform 3." evidence="12">
        <location>
            <begin position="49"/>
            <end position="597"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057186" description="In dbSNP:rs34169260." evidence="8">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="517"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces GAP activity. Loss of GAP activity; when associated with A-795." evidence="9">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="683"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of GAP activity; when associated with A-683." evidence="9">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="795"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with DLG4. No effect on synaptic localization." evidence="10">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="859"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50063." evidence="13" ref="1">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG54051." evidence="13" ref="2">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="483"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAH13263." evidence="13" ref="2">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="625"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAC37519." evidence="13" ref="3">
        <original>RSKV</original>
        <variation>VQGA</variation>
        <location>
            <begin position="657"/>
            <end position="660"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAC37519." evidence="13" ref="3">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="761"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="A0A0G2JTR4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q5SSL4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00041"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00062"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00172"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17116687"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="20962234"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="7479768"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="7479768"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:81"/>
        </source>
    </evidence>
    <sequence length="859" mass="97598" checksum="3A5BE3AD2455A194" modified="2011-11-16" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-28" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKU7</accession>
    <accession>B7Z5W4</accession>
    <accession>Q6ZWP6</accession>
    <accession>Q9BUS8</accession>
    <name>ACAD8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Isobutyryl-CoA dehydrogenase, mitochondrial</fullName>
            <shortName evidence="11">IBDH</shortName>
            <ecNumber evidence="5 6 9">1.3.8.5</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Activator-recruited cofactor 42 kDa component</fullName>
            <shortName>ARC42</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="10">Acyl-CoA dehydrogenase family member 8</fullName>
            <shortName evidence="10">ACAD-8</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">ACAD8</name>
        <name type="synonym">ARC42</name>
        <name type="synonym">IBD</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>PROTEIN SEQUENCE OF 50-61; 70-80 AND 345-355</scope>
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        <scope>COFACTOR</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVE SITE</scope>
        <scope>REGION</scope>
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            <dbReference type="PubMed" id="12359132"/>
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        <scope>VARIANT IBDD GLN-302</scope>
        <scope>CHARACTERIZATION OF VARIANT IBDD GLN-302</scope>
        <scope>INVOLVEMENT IN IBDD</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>VARIANTS IBDD TYR-134; ARG-137; THR-152; GLN-302; THR-320; CYS-334 AND ARG-385</scope>
        <scope>CHARACTERIZATION OF VARIANTS IBDD ARG-137; GLN-302 AND THR-320</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
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    <comment type="function">
        <text evidence="5 6 9">Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway (PubMed:11013134, PubMed:12359132, PubMed:16857760). To a lesser extent, also able to catalyze the oxidation of (2S)-2-methylbutanoyl-CoA (PubMed:11013134, PubMed:12359132).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6 9">
            <text>2-methylpropanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = 2-methylpropenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:44180"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57338"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62500"/>
            <dbReference type="EC" id="1.3.8.5"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6 9">
            <dbReference type="Rhea" id="RHEA:44181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6">
            <text>(2S)-2-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48256"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57337"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:88166"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:48257"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>propanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = acryloyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:31287"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57367"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:31288"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="7">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">2.6 uM for 2-methylpropanoyl-CoA</KM>
            <KM evidence="6">18 uM for (2S)-2-methylbutanoyl-CoA</KM>
            <KM evidence="6">24 uM for n-propionyl-CoA</KM>
            <text evidence="6">kcat is 2.0 sec(-1) for the oxidation of 2-methylpropanoyl-CoA (PubMed:12359132). kcat is 4.1 sec(-1) for the oxidation of (2S)-methylbutanoyl-CoA (PubMed:12359132). kcat is 0.83 sec(-1) for the oxidation of n-propionyl-CoA (PubMed:12359132).</text>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="6 9">Amino-acid degradation; L-valine degradation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 5 7">Homotetramer, formed by a dimer of dimers (PubMed:11013134, PubMed:14752098). May be part of the large multiprotein complex ARC/DRIP (PubMed:10235267).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2339304">
            <id>Q9UKU7</id>
        </interactant>
        <interactant intactId="EBI-8994042">
            <id>Q8TAG5</id>
            <label>VSTM2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKU7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKU7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055780 VSP_055781"/>
        </isoform>
        <isoform>
            <id>Q9UKU7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_055779 VSP_055782"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Detected at comparable levels in heart, lung, brain, skeletal muscle, pancreas and placenta. Weakly expressed in liver and kidney.</text>
    </comment>
    <comment type="disease" evidence="6 8 9">
        <disease id="DI-01836">
            <name>Isobutyryl-CoA dehydrogenase deficiency</name>
            <acronym>IBDD</acronym>
            <description>An autosomal recessive metabolic disorder characterized by plasma carnitine deficiency and elevated C4-acylcarnitine. Patients manifest variable clinical features including failure to thrive, seizures, anemia, muscular hypotonia and developmental delay. Some patients may be asymptomatic.</description>
            <dbReference type="MIM" id="611283"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.5" evidence="5 6 9"/>
    <dbReference type="EMBL" id="AF126245">
        <property type="protein sequence ID" value="AAF12736.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260689">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260679">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260680">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260681">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260682">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260683">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260684">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260685">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260686">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260687">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260688">
        <property type="protein sequence ID" value="AAF97922.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000359">
        <property type="protein sequence ID" value="BAA91109.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074640">
        <property type="protein sequence ID" value="BAC11107.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299492">
        <property type="protein sequence ID" value="BAH13050.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP000859">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67833.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001964">
        <property type="protein sequence ID" value="AAH01964.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8498.1">
        <molecule id="Q9UKU7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055199.1">
        <molecule id="Q9UKU7-1"/>
        <property type="nucleotide sequence ID" value="NM_014384.3"/>
    </dbReference>
    <dbReference type="PDB" id="1RX0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.77 A"/>
        <property type="chains" value="A/B/C/D=24-415"/>
    </dbReference>
    <dbReference type="PDBsum" id="1RX0"/>
    <dbReference type="AlphaFoldDB" id="Q9UKU7"/>
    <dbReference type="SMR" id="Q9UKU7"/>
    <dbReference type="BioGRID" id="117965">
        <property type="interactions" value="39"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9UKU7"/>
    <dbReference type="FunCoup" id="Q9UKU7">
        <property type="interactions" value="723"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UKU7">
        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000281182"/>
    <dbReference type="DrugBank" id="DB03147">
        <property type="generic name" value="Flavin adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01675">
        <property type="generic name" value="Methacrylyl-Coenzyme A"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000001420"/>
    <dbReference type="GlyGen" id="Q9UKU7">
        <property type="glycosylation" value="1 site, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UKU7"/>
    <dbReference type="PhosphoSitePlus" id="Q9UKU7"/>
    <dbReference type="SwissPalm" id="Q9UKU7"/>
    <dbReference type="BioMuta" id="ACAD8"/>
    <dbReference type="DMDM" id="26006699"/>
    <dbReference type="jPOST" id="Q9UKU7"/>
    <dbReference type="MassIVE" id="Q9UKU7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000281182"/>
    <dbReference type="PeptideAtlas" id="Q9UKU7"/>
    <dbReference type="ProteomicsDB" id="6725"/>
    <dbReference type="ProteomicsDB" id="68496"/>
    <dbReference type="ProteomicsDB" id="84879">
        <molecule id="Q9UKU7-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9UKU7"/>
    <dbReference type="Antibodypedia" id="33180">
        <property type="antibodies" value="188 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="27034"/>
    <dbReference type="Ensembl" id="ENST00000281182.9">
        <molecule id="Q9UKU7-1"/>
        <property type="protein sequence ID" value="ENSP00000281182.5"/>
        <property type="gene ID" value="ENSG00000151498.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000374752.6">
        <molecule id="Q9UKU7-2"/>
        <property type="protein sequence ID" value="ENSP00000363884.4"/>
        <property type="gene ID" value="ENSG00000151498.13"/>
    </dbReference>
    <dbReference type="GeneID" id="27034"/>
    <dbReference type="KEGG" id="hsa:27034"/>
    <dbReference type="MANE-Select" id="ENST00000281182.9">
        <property type="protein sequence ID" value="ENSP00000281182.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014384.3"/>
        <property type="RefSeq protein sequence ID" value="NP_055199.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001qhk.4">
        <molecule id="Q9UKU7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:87"/>
    <dbReference type="ClinPGx" id="PA24423"/>
    <dbReference type="CTD" id="27034"/>
    <dbReference type="DisGeNET" id="27034"/>
    <dbReference type="GeneCards" id="ACAD8"/>
    <dbReference type="HGNC" id="HGNC:87">
        <property type="gene designation" value="ACAD8"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000151498">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACAD8"/>
    <dbReference type="MIM" id="604773">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="611283">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000151498"/>
    <dbReference type="Orphanet" id="79159">
        <property type="disease" value="Isobutyryl-CoA dehydrogenase deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000151498"/>
    <dbReference type="eggNOG" id="KOG0140">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157590"/>
    <dbReference type="HOGENOM" id="CLU_018204_0_2_1"/>
    <dbReference type="InParanoid" id="Q9UKU7"/>
    <dbReference type="OMA" id="NMATWML"/>
    <dbReference type="OrthoDB" id="10254877at2759"/>
    <dbReference type="PAN-GO" id="Q9UKU7">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UKU7"/>
    <dbReference type="PathwayCommons" id="Q9UKU7"/>
    <dbReference type="Reactome" id="R-HSA-70895">
        <property type="pathway name" value="Branched-chain amino acid catabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9837999">
        <property type="pathway name" value="Mitochondrial protein degradation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UKU7"/>
    <dbReference type="UniPathway" id="UPA00362"/>
    <dbReference type="Agora" id="ENSG00000151498"/>
    <dbReference type="BioGRID-ORCS" id="27034">
        <property type="hits" value="21 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACAD8">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9UKU7"/>
    <dbReference type="GeneWiki" id="ACAD8"/>
    <dbReference type="GenomeRNAi" id="27034"/>
    <dbReference type="Pharos" id="Q9UKU7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UKU7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9UKU7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000151498">
        <property type="expression patterns" value="Expressed in right lobe of thyroid gland and 189 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9UKU7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003995">
        <property type="term" value="F:acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003853">
        <property type="term" value="F:short-chain 2-methyl fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006574">
        <property type="term" value="P:L-valine catabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniPathway"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd01162">
        <property type="entry name" value="IBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000001">
        <property type="entry name" value="Acyl-CoA dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000020">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 8"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000001">
        <property type="entry name" value="Acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006089">
        <property type="entry name" value="Acyl-CoA_DH_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034178">
        <property type="entry name" value="IBD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052547">
        <property type="entry name" value="Mito_Isobutyryl-CoADH"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43831">
        <property type="entry name" value="ISOBUTYRYL-COA DEHYDROGENASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43831:SF1">
        <property type="entry name" value="ISOBUTYRYL-COA DEHYDROGENASE, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016578">
        <property type="entry name" value="HsaA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00072">
        <property type="entry name" value="ACYL_COA_DH_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0101">Branched-chain amino acid catabolism</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000522" description="Isobutyryl-CoA dehydrogenase, mitochondrial">
        <location>
            <begin position="23"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="15">
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="binding site" description="in other chain" evidence="7">
        <location>
            <begin position="158"/>
            <end position="167"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="167"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="7">
        <location>
            <begin position="191"/>
            <end position="193"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <begin position="274"/>
            <end position="277"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="302"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <begin position="312"/>
            <end position="313"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <begin position="371"/>
            <end position="375"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="7">
        <location>
            <begin position="400"/>
            <end position="402"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="410"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="1">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="1">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="1">
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055779" description="In isoform 3." evidence="12">
        <location>
            <begin position="1"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055780" description="In isoform 2." evidence="12">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055781" description="In isoform 2." evidence="12">
        <location>
            <begin position="38"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055782" description="In isoform 3." evidence="12">
        <original>GSNEVMRILISRSLLQE</original>
        <variation>ELFWQGPGVQSRSFVPFGGPQIALLLPFSSGDLREG</variation>
        <location>
            <begin position="399"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035071" description="In IBDD; dbSNP:rs374317179." evidence="8">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035072" description="In IBDD; dbSNP:rs367857040." evidence="9">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035073" description="In IBDD; loss of protein solubility; complete loss of isobutyryl-CoA dehydrogenase activity; dbSNP:rs371449613." evidence="9">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035074" description="In IBDD; dbSNP:rs121908418." evidence="9">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035075" description="In IBDD; dbSNP:rs759877257." evidence="8">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035076" description="In IBDD; no effect on localization to the mitochondrion; complete loss of isobutyryl-CoA dehydrogenase activity; loss of protein expression in patient cells; dbSNP:rs121908422." evidence="6 9">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="302"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035077" description="In IBDD; decreased isobutyryl-CoA dehydrogenase activity; less than 20% of wild-type; dbSNP:rs200620279." evidence="9">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035078" description="In IBDD; dbSNP:rs778823613." evidence="9">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="334"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035079" description="In IBDD; dbSNP:rs367996531." evidence="9">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="385"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH01964." evidence="13" ref="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="210"/>
        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="37"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="43"/>
            <end position="59"/>
        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="60"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="64"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="75"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="93"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="102"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="117"/>
            <end position="136"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="139"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="156"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="165"/>
            <end position="168"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="169"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="175"/>
            <end position="179"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="182"/>
            <end position="193"/>
        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="194"/>
            <end position="197"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="199"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="212"/>
            <end position="214"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="215"/>
            <end position="221"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="227"/>
            <end position="229"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="235"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="243"/>
            <end position="254"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="255"/>
            <end position="257"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="258"/>
            <end position="261"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="265"/>
            <end position="301"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="309"/>
            <end position="311"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="313"/>
            <end position="341"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="347"/>
            <end position="372"/>
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    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="373"/>
            <end position="378"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="384"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="394"/>
            <end position="396"/>
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    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="397"/>
            <end position="399"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="401"/>
            <end position="414"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9D7B6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10235267"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10524212"/>
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    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11013134"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12359132"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="14752098"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15505379"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16857760"/>
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        <source>
            <dbReference type="PubMed" id="10524212"/>
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    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="12359132"/>
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    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="12359132"/>
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    </evidence>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="14752098"/>
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    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:87"/>
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    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="1RX0"/>
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    </evidence>
    <sequence length="415" mass="45070" checksum="CAFFE91B74E2362D" modified="2000-05-01" version="1" precursor="true">MLWSGCRRFGARLGCLPGGLRVLVQTGHRSLTSCIDPSMGLNEEQKEFQKVAFDFAAREMAPNMAEWDQKELFPVDVMRKAAQLGFGGVYIQTDVGGSGLSRLDTSVIFEALATGCTSTTAYISIHNMCAWMIDSFGNEEQRHKFCPPLCTMEKFASYCLTEPGSGSDAASLLTSAKKQGDHYILNGSKAFISGAGESDIYVVMCRTGGPGPKGISCIVVEKGTPGLSFGKKEKKVGWNSQPTRAVIFEDCAVPVANRIGSEGQGFLIAVRGLNGGRINIASCSLGAAHASVILTRDHLNVRKQFGEPLASNQYLQFTLADMATRLVAARLMVRNAAVALQEERKDAVALCSMAKLFATDECFAICNQALQMHGGYGYLKDYAVQQYVRDSRVHQILEGSNEVMRILISRSLLQE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-07-15" modified="2026-01-28" version="221" xmlns="https://uniprot.org/uniprot">
    <accession>Q15057</accession>
    <accession>A8K2V4</accession>
    <accession>Q8N5Z8</accession>
    <accession>Q9UQR3</accession>
    <name>ACAP2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-beta-2</fullName>
            <shortName>Cnt-b2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACAP2</name>
        <name type="synonym">CENTB2</name>
        <name type="synonym">KIAA0041</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="J. Cell Biol." volume="151" first="627" last="638">
            <title>ACAPs are arf6 GTPase-activating proteins that function in the cell periphery.</title>
            <authorList>
                <person name="Jackson T.R."/>
                <person name="Brown F.D."/>
                <person name="Nie Z."/>
                <person name="Miura K."/>
                <person name="Foroni L."/>
                <person name="Sun J."/>
                <person name="Hsu V.W."/>
                <person name="Donaldson J.G."/>
                <person name="Randazzo P.A."/>
            </authorList>
            <dbReference type="PubMed" id="11062263"/>
            <dbReference type="DOI" id="10.1083/jcb.151.3.627"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF ARG-442</scope>
        <source>
            <tissue>Leukocyte</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="223" last="229">
            <title>Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.</title>
            <authorList>
                <person name="Nomura N."/>
                <person name="Nagase T."/>
                <person name="Miyajima N."/>
                <person name="Sazuka T."/>
                <person name="Tanaka A."/>
                <person name="Sato S."/>
                <person name="Seki N."/>
                <person name="Kawarabayasi Y."/>
                <person name="Ishikawa K."/>
                <person name="Tabata S."/>
            </authorList>
            <dbReference type="PubMed" id="7584044"/>
            <dbReference type="DOI" id="10.1093/dnares/1.5.223"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Nomura N."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Tongue</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Placenta</tissue>
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    </reference>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-742</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-384</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <dbReference type="PubMed" id="19413330"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Leukemic T-cell</tissue>
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            <dbReference type="PubMed" id="20068231"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="13">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
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            <dbReference type="PubMed" id="21406692"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="15">
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            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-581 AND SER-775</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="16">
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
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                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2019" name="Structure" volume="27" first="729" last="740.e3">
            <title>Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase.</title>
            <authorList>
                <person name="Lin L."/>
                <person name="Shi Y."/>
                <person name="Wang M."/>
                <person name="Wang C."/>
                <person name="Zhu J."/>
                <person name="Zhang R."/>
            </authorList>
            <dbReference type="PubMed" id="30905672"/>
            <dbReference type="DOI" id="10.1016/j.str.2019.02.008"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RAB35</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF ASP-721; ARG-727; MET-731 AND ASP-756</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7">GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6). Doesn't show GAP activity for RAB35 (PubMed:30905672).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="6">GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 7">Interacts (via KANK domains) with RAB35 (GTP-bound form); the interaction is direct and probably recruits ACAP2 to membranes including plasma membrane (PubMed:30905672). Interacts with MICALL1; the interaction is indirect through RAB35 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-4401196">
            <id>Q15057</id>
        </interactant>
        <interactant intactId="EBI-715726">
            <id>Q96P50</id>
            <label>ACAP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endosome membrane</location>
            <topology evidence="1">Peripheral membrane protein</topology>
        </subcellularLocation>
        <text evidence="7">Colocalizes with RAB35 at the membrane protrusions of HEK293T cells.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Widely expressed. Highest level in lung.</text>
    </comment>
    <comment type="domain">
        <text evidence="7">The ANK domains are required for interaction with RAB35.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA05064" version="2"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="CAB41450" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AJ238248">
        <property type="protein sequence ID" value="CAB41450.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D26069">
        <property type="protein sequence ID" value="BAA05064.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290369">
        <property type="protein sequence ID" value="BAF83058.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW78027.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031005">
        <property type="protein sequence ID" value="AAH31005.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC060767">
        <property type="protein sequence ID" value="AAH60767.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33924.1"/>
    <dbReference type="RefSeq" id="NP_036419.3">
        <property type="nucleotide sequence ID" value="NM_012287.5"/>
    </dbReference>
    <dbReference type="PDB" id="6IF3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A=601-770"/>
    </dbReference>
    <dbReference type="PDBsum" id="6IF3"/>
    <dbReference type="AlphaFoldDB" id="Q15057"/>
    <dbReference type="SMR" id="Q15057"/>
    <dbReference type="BioGRID" id="117073">
        <property type="interactions" value="57"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q15057">
        <property type="interactions" value="2664"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15057">
        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="MINT" id="Q15057"/>
    <dbReference type="STRING" id="9606.ENSP00000324287"/>
    <dbReference type="GlyCosmos" id="Q15057">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15057">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15057"/>
    <dbReference type="MetOSite" id="Q15057"/>
    <dbReference type="PhosphoSitePlus" id="Q15057"/>
    <dbReference type="BioMuta" id="ACAP2"/>
    <dbReference type="DMDM" id="39932727"/>
    <dbReference type="jPOST" id="Q15057"/>
    <dbReference type="MassIVE" id="Q15057"/>
    <dbReference type="PaxDb" id="9606-ENSP00000324287"/>
    <dbReference type="PeptideAtlas" id="Q15057"/>
    <dbReference type="ProteomicsDB" id="60412"/>
    <dbReference type="Pumba" id="Q15057"/>
    <dbReference type="Antibodypedia" id="19460">
        <property type="antibodies" value="215 antibodies from 36 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23527"/>
    <dbReference type="Ensembl" id="ENST00000326793.11">
        <property type="protein sequence ID" value="ENSP00000324287.6"/>
        <property type="gene ID" value="ENSG00000114331.17"/>
    </dbReference>
    <dbReference type="GeneID" id="23527"/>
    <dbReference type="KEGG" id="hsa:23527"/>
    <dbReference type="MANE-Select" id="ENST00000326793.11">
        <property type="protein sequence ID" value="ENSP00000324287.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_012287.6"/>
        <property type="RefSeq protein sequence ID" value="NP_036419.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003fun.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16469"/>
    <dbReference type="ClinPGx" id="PA26407"/>
    <dbReference type="CTD" id="23527"/>
    <dbReference type="DisGeNET" id="23527"/>
    <dbReference type="GeneCards" id="ACAP2"/>
    <dbReference type="HGNC" id="HGNC:16469">
        <property type="gene designation" value="ACAP2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000114331">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="607766">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000114331"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000114331"/>
    <dbReference type="eggNOG" id="KOG0521">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156389"/>
    <dbReference type="HOGENOM" id="CLU_012513_0_1_1"/>
    <dbReference type="InParanoid" id="Q15057"/>
    <dbReference type="OMA" id="FGFREAM"/>
    <dbReference type="OrthoDB" id="10070851at2759"/>
    <dbReference type="PAN-GO" id="Q15057">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15057"/>
    <dbReference type="PathwayCommons" id="Q15057"/>
    <dbReference type="SignaLink" id="Q15057"/>
    <dbReference type="Agora" id="ENSG00000114331"/>
    <dbReference type="BioGRID-ORCS" id="23527">
        <property type="hits" value="47 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACAP2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CENTB2"/>
    <dbReference type="GenomeRNAi" id="23527"/>
    <dbReference type="Pharos" id="Q15057">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q15057"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q15057">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000114331">
        <property type="expression patterns" value="Expressed in epithelium of nasopharynx and 203 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q15057">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010008">
        <property type="term" value="C:endosome membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001726">
        <property type="term" value="C:ruffle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030029">
        <property type="term" value="P:actin filament-based process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990090">
        <property type="term" value="P:cellular response to nerve growth factor stimulus"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032456">
        <property type="term" value="P:endocytic recycling"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd08851">
        <property type="entry name" value="ArfGap_ACAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd07638">
        <property type="entry name" value="BAR_ACAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13250">
        <property type="entry name" value="PH_ACAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000007">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000020">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000026">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1270.60:FF:000025">
        <property type="entry name" value="arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.1270.60">
        <property type="entry name" value="Arfaptin homology (AH) domain/BAR domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR045258">
        <property type="entry name" value="ACAP1/2/3-like"/>
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    <dbReference type="InterPro" id="IPR027267">
        <property type="entry name" value="AH/BAR_dom_sf"/>
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    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
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    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
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    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
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    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
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    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
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    <dbReference type="InterPro" id="IPR004148">
        <property type="entry name" value="BAR_dom"/>
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    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
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    <dbReference type="PANTHER" id="PTHR23180:SF241">
        <property type="entry name" value="ARF-GAP WITH COILED-COIL, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR23180">
        <property type="entry name" value="CENTAURIN/ARF"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF16746">
        <property type="entry name" value="BAR_3"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
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    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="3"/>
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    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF103657">
        <property type="entry name" value="BAR/IMD domain-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="2"/>
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    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000074210" description="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2">
        <location>
            <begin position="1"/>
            <end position="778"/>
        </location>
    </feature>
    <feature type="domain" description="BAR">
        <location>
            <begin position="1"/>
            <end position="226"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="3">
        <location>
            <begin position="266"/>
            <end position="361"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="4">
        <location>
            <begin position="399"/>
            <end position="520"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="640"/>
            <end position="669"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="673"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="706"/>
            <end position="735"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="4">
        <location>
            <begin position="414"/>
            <end position="437"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="371"/>
            <end position="391"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="540"/>
            <end position="599"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="379"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="552"/>
            <end position="569"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="384"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="387"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12">
        <location>
            <position position="521"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="581"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="584"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="9">
        <location>
            <position position="742"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="775"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of GAP activity." evidence="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="442"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strong decrease in interaction with RAB35." evidence="7">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="721"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased interaction with RAB35." evidence="7">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="727"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with RAB35." evidence="7">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="727"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strong decrease in interaction with RAB35." evidence="7">
        <original>M</original>
        <variation>A</variation>
        <location>
            <position position="731"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased interaction with RAB35." evidence="7">
        <original>D</original>
        <variation>K</variation>
        <location>
            <position position="756"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAB41450." evidence="8" ref="1">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH60767." evidence="8" ref="6">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="564"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="606"/>
            <end position="615"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="619"/>
            <end position="627"/>
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    </feature>
    <feature type="turn" evidence="13">
        <location>
            <begin position="637"/>
            <end position="641"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="644"/>
            <end position="651"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="654"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="677"/>
            <end position="684"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="687"/>
            <end position="695"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="710"/>
            <end position="716"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="720"/>
            <end position="737"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="753"/>
            <end position="757"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q6ZQK5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="11062263"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="30905672"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="15592455"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="6IF3"/>
        </source>
    </evidence>
    <sequence length="778" mass="88029" checksum="64B620957FEE6195" modified="2003-12-15" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="150" xmlns="https://uniprot.org/uniprot">
    <accession>Q5FVE4</accession>
    <accession>B3KSF2</accession>
    <accession>Q6UWJ3</accession>
    <accession>Q7Z5A0</accession>
    <accession>Q8WW03</accession>
    <accession>Q96M36</accession>
    <accession>Q9BYZ3</accession>
    <accession>Q9H0C4</accession>
    <name>ACBG2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="12">Long-chain-fatty-acid--CoA ligase ACSBG2</fullName>
            <ecNumber evidence="6 7">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase bubblegum family member 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">Arachidonate--CoA ligase ACSBG2</fullName>
            <ecNumber evidence="7">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="11">Bubblegum-related protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PRTD-NY3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">ACSBG2</name>
        <name evidence="11" type="synonym">BGR</name>
        <name type="ORF">UNQ2443/PRO5005</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <citation type="journal article" date="2005" name="Asian J. Androl." volume="7" first="21" last="32">
            <title>Identification and characterization of the BGR-like gene with a potential role in human testicular development/spermatogenesis.</title>
            <authorList>
                <person name="Zheng Y."/>
                <person name="Zhou Z.-M."/>
                <person name="Min X."/>
                <person name="Li J.-M."/>
                <person name="Sha J.-H."/>
            </authorList>
            <dbReference type="PubMed" id="15685348"/>
            <dbReference type="DOI" id="10.1111/j.1745-7262.2005.00014.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <scope>VARIANT ALA-143</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Arch. Biochem. Biophys." volume="451" first="23" last="33">
            <title>A novel mammalian bubblegum-related acyl-CoA synthetase restricted to testes and possibly involved in spermatogenesis.</title>
            <authorList>
                <person name="Fraisl P."/>
                <person name="Tanaka H."/>
                <person name="Forss-Petter S."/>
                <person name="Lassmann H."/>
                <person name="Nishimune Y."/>
                <person name="Berger J."/>
            </authorList>
            <dbReference type="PubMed" id="16762313"/>
            <dbReference type="DOI" id="10.1016/j.abb.2006.04.013"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT ALA-143</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
                <person name="Wellenreuther R."/>
                <person name="Gassenhuber J."/>
                <person name="Glassl S."/>
                <person name="Ansorge W."/>
                <person name="Boecher M."/>
                <person name="Bloecker H."/>
                <person name="Bauersachs S."/>
                <person name="Blum H."/>
                <person name="Lauber J."/>
                <person name="Duesterhoeft A."/>
                <person name="Beyer A."/>
                <person name="Koehrer K."/>
                <person name="Strack N."/>
                <person name="Mewes H.-W."/>
                <person name="Ottenwaelder B."/>
                <person name="Obermaier B."/>
                <person name="Tampe J."/>
                <person name="Heubner D."/>
                <person name="Wambutt R."/>
                <person name="Korn B."/>
                <person name="Klein M."/>
                <person name="Poustka A."/>
            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-143</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
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                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT ALA-143</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS ALA-143; ASP-584; ASP-586; LYS-624 AND GLN-626</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2006" name="J. Biol. Chem." volume="281" first="6632" last="6641">
            <title>The second member of the human and murine 'bubblegum' family is a testis- and brainstem-specific acyl-CoA synthetase.</title>
            <authorList>
                <person name="Pei Z."/>
                <person name="Jia Z."/>
                <person name="Watkins P.A."/>
            </authorList>
            <dbReference type="PubMed" id="16371355"/>
            <dbReference type="DOI" id="10.1074/jbc.m511558200"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF HIS-511</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7">Catalyzes the conversion of fatty acids such as long chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation. Can activate diverse saturated, monosaturated and polyunsaturated fatty acids (PubMed:16371355, PubMed:16762313). Has increased ability to activate oleic and linoleic acid (PubMed:16371355). May play a role in spermatogenesis (PubMed:15685348).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33607"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:33608"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>(9Z,12Z)-octadecadienoate + ATP + CoA = (9Z,12Z)-octadecadienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33651"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:33652"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>tetracosanoate + ATP + CoA = tetracosanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33639"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:31014"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:33640"/>
        </physiologicalReaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Peripheral membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5FVE4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5FVE4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_030719"/>
        </isoform>
        <isoform>
            <id>Q5FVE4-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_030718"/>
        </isoform>
        <isoform>
            <id>Q5FVE4-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_030717"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6 7">Testis-specific.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="5">Weakly or not expressed in fetal testis. Highly expressed in adult testis and moderately in elderly testis.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAE12157" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="6 7"/>
    <dbReference type="EC" id="6.2.1.15" evidence="7"/>
    <dbReference type="EMBL" id="AY009107">
        <property type="protein sequence ID" value="AAG49398.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ577571">
        <property type="protein sequence ID" value="CAE12156.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ577571">
        <property type="protein sequence ID" value="CAE12157.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136854">
        <property type="protein sequence ID" value="CAB66788.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358766">
        <property type="protein sequence ID" value="AAQ89126.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK057412">
        <property type="protein sequence ID" value="BAB71476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093433">
        <property type="protein sequence ID" value="BAG52714.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471139">
        <property type="protein sequence ID" value="EAW69111.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022027">
        <property type="protein sequence ID" value="AAH22027.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC090046">
        <property type="protein sequence ID" value="AAH90046.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12159.1">
        <molecule id="Q5FVE4-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS82282.1">
        <molecule id="Q5FVE4-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001276106.1">
        <molecule id="Q5FVE4-1"/>
        <property type="nucleotide sequence ID" value="NM_001289177.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001276107.1">
        <molecule id="Q5FVE4-1"/>
        <property type="nucleotide sequence ID" value="NM_001289178.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001276108.1">
        <property type="nucleotide sequence ID" value="NM_001289179.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001276109.1">
        <molecule id="Q5FVE4-3"/>
        <property type="nucleotide sequence ID" value="NM_001289180.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308313.1">
        <molecule id="Q5FVE4-2"/>
        <property type="nucleotide sequence ID" value="NM_001321384.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_112186.3">
        <molecule id="Q5FVE4-1"/>
        <property type="nucleotide sequence ID" value="NM_030924.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016882821.1">
        <molecule id="Q5FVE4-1"/>
        <property type="nucleotide sequence ID" value="XM_017027332.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047295434.1">
        <molecule id="Q5FVE4-3"/>
        <property type="nucleotide sequence ID" value="XM_047439478.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054178228.1">
        <molecule id="Q5FVE4-3"/>
        <property type="nucleotide sequence ID" value="XM_054322253.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5FVE4"/>
    <dbReference type="SMR" id="Q5FVE4"/>
    <dbReference type="BioGRID" id="123551">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5FVE4">
        <property type="interactions" value="425"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5FVE4">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000465589"/>
    <dbReference type="SwissLipids" id="SLP:000001212"/>
    <dbReference type="GlyGen" id="Q5FVE4">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5FVE4"/>
    <dbReference type="PhosphoSitePlus" id="Q5FVE4"/>
    <dbReference type="BioMuta" id="ACSBG2"/>
    <dbReference type="DMDM" id="296434386"/>
    <dbReference type="MassIVE" id="Q5FVE4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000465589"/>
    <dbReference type="PeptideAtlas" id="Q5FVE4"/>
    <dbReference type="ProteomicsDB" id="62803">
        <molecule id="Q5FVE4-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62804">
        <molecule id="Q5FVE4-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62805">
        <molecule id="Q5FVE4-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62806">
        <molecule id="Q5FVE4-4"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="24085">
        <property type="antibodies" value="133 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="81616"/>
    <dbReference type="Ensembl" id="ENST00000586696.5">
        <molecule id="Q5FVE4-1"/>
        <property type="protein sequence ID" value="ENSP00000465589.1"/>
        <property type="gene ID" value="ENSG00000130377.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000588304.5">
        <molecule id="Q5FVE4-2"/>
        <property type="protein sequence ID" value="ENSP00000464938.1"/>
        <property type="gene ID" value="ENSG00000130377.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000588485.6">
        <molecule id="Q5FVE4-1"/>
        <property type="protein sequence ID" value="ENSP00000466336.2"/>
        <property type="gene ID" value="ENSG00000130377.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000591403.5">
        <molecule id="Q5FVE4-1"/>
        <property type="protein sequence ID" value="ENSP00000467755.1"/>
        <property type="gene ID" value="ENSG00000130377.14"/>
    </dbReference>
    <dbReference type="GeneID" id="81616"/>
    <dbReference type="KEGG" id="hsa:81616"/>
    <dbReference type="MANE-Select" id="ENST00000588485.6">
        <property type="protein sequence ID" value="ENSP00000466336.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_030924.5"/>
        <property type="RefSeq protein sequence ID" value="NP_112186.3"/>
    </dbReference>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
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    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <feature type="chain" id="PRO_0000315812" description="Long-chain-fatty-acid--CoA ligase ACSBG2">
        <location>
            <begin position="1"/>
            <end position="666"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="230"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="1">
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        <ligand>
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        <ligand>
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        <ligand>
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    <feature type="splice variant" id="VSP_030717" description="In isoform 4." evidence="9">
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            <begin position="1"/>
            <end position="200"/>
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            <begin position="1"/>
            <end position="50"/>
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    <feature type="sequence variant" id="VAR_038317" description="In dbSNP:rs4807840." evidence="2 3 4 5 7">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="143"/>
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            <position position="152"/>
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    <feature type="sequence variant" id="VAR_038319" description="In dbSNP:rs17851959." evidence="4">
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        <variation>D</variation>
        <location>
            <position position="584"/>
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    </feature>
    <feature type="sequence variant" id="VAR_038320" description="In dbSNP:rs17851960." evidence="4">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="586"/>
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    </feature>
    <feature type="sequence variant" id="VAR_038321" description="In dbSNP:rs35609668.">
        <original>P</original>
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        <location>
            <position position="601"/>
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    </feature>
    <feature type="sequence variant" id="VAR_038322" description="In dbSNP:rs17856650." evidence="4">
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        <location>
            <position position="624"/>
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    </feature>
    <feature type="sequence variant" id="VAR_038323" description="In dbSNP:rs17856651." evidence="4">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="626"/>
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    </feature>
    <feature type="sequence variant" id="VAR_038324" description="In dbSNP:rs35605352.">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="650"/>
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    </feature>
    <feature type="mutagenesis site" description="Results in a shift of the pH optimum to a more acidic pH without affecting substrate specificity." evidence="6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="511"/>
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    <feature type="sequence conflict" description="In Ref. 4; AAQ89126." evidence="12" ref="4">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="71"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAG49398." evidence="12" ref="1">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="332"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAE12156/CAE12157 and 3; CAB66788." evidence="12" ref="2 3">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="595"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="PubMed" id="11230166"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="12975309"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15685348"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16371355"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16762313"/>
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    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="12975309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="15685348"/>
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    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="16762313"/>
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    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:24174"/>
        </source>
    </evidence>
    <sequence length="666" mass="74354" checksum="4EE300654EF17150" modified="2010-05-18" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-07-03" modified="2026-01-28" version="199" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H845</accession>
    <accession>D3DNB8</accession>
    <accession>Q8WXX3</accession>
    <name>ACAD9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">Complex I assembly factor ACAD9, mitochondrial</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="18">Acyl-CoA dehydrogenase family member 9</fullName>
            <shortName evidence="18">ACAD-9</shortName>
            <ecNumber evidence="3">1.3.8.7</ecNumber>
            <ecNumber evidence="2 3 8 12">1.3.8.8</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="23" type="primary">ACAD9</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Biochem. Biophys. Res. Commun." volume="297" first="1033" last="1042">
            <title>Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family.</title>
            <authorList>
                <person name="Zhang J."/>
                <person name="Zhang W."/>
                <person name="Zou D."/>
                <person name="Chen G."/>
                <person name="Wan T."/>
                <person name="Zhang M."/>
                <person name="Cao X."/>
            </authorList>
            <dbReference type="PubMed" id="12359260"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(02)02336-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Dendritic cell</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lung</tissue>
            <tissue>Uterus</tissue>
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        <scope>FUNCTION</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CLEAVAGE OF TRANSIT PEPTIDE AFTER ARG-37</scope>
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            <dbReference type="PubMed" id="17564966"/>
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        <scope>INVOLVEMENT IN MC1DN20</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-41</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH NDUFAF1 AND ECSIT</scope>
        <scope>INVOLVEMENT IN MC1DN20</scope>
        <scope>VARIANTS MC1DN20 LYS-413 AND HIS-518</scope>
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            <authorList>
                <person name="Haack T.B."/>
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            <dbReference type="PubMed" id="21057504"/>
            <dbReference type="DOI" id="10.1038/ng.706"/>
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        <scope>INVOLVEMENT IN MC1DN20</scope>
        <scope>VARIANTS MC1DN20 ILE-44; TRP-193; PHE-234; GLN-266; SER-303; THR-326; CYS-417 AND TRP-532</scope>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="He M."/>
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            </authorList>
            <dbReference type="PubMed" id="21237683"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
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                <person name="Nouws J."/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF GLU-426</scope>
    </reference>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
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            <title>N-terminome analysis of the human mitochondrial proteome.</title>
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            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I.</title>
            <authorList>
                <person name="Formosa L.E."/>
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            </authorList>
            <dbReference type="PubMed" id="32320651"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2020.107541"/>
        </citation>
        <scope>IDENTIFICATION IN THE MCIA COMPLEX</scope>
        <scope>FUNCTION</scope>
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            </authorList>
            <dbReference type="PubMed" id="33753518"/>
            <dbReference type="DOI" id="10.1073/pnas.2100558118"/>
        </citation>
        <scope>INTERACTION WITH TMEM70 AND TMEM242</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2023" name="Nat. Commun." volume="14" first="8248" last="8248">
            <title>The assembly of the Mitochondrial Complex I Assembly complex uncovers a redox pathway coordination.</title>
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            <dbReference type="PubMed" id="38086790"/>
            <dbReference type="DOI" id="10.1038/s41467-023-43865-0"/>
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        <scope>FUNCTION</scope>
    </reference>
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            <authorList>
                <person name="Fabbian S."/>
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            </authorList>
            <dbReference type="PubMed" id="40255280"/>
            <dbReference type="DOI" id="10.1021/acsbiomedchemau.4c00140"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
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            <title>Riboflavin-responsive oxidative phosphorylation complex I deficiency caused by defective ACAD9: new function for an old gene.</title>
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            </authorList>
            <dbReference type="PubMed" id="20929961"/>
            <dbReference type="DOI" id="10.1093/brain/awq273"/>
        </citation>
        <scope>VARIANTS MC1DN20 LYS-127; TRP-469 AND TRP-532</scope>
    </reference>
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            <dbReference type="PubMed" id="22499348"/>
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        <scope>VARIANT MC1DN20 TRP-532</scope>
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            <dbReference type="PubMed" id="23836383"/>
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        <scope>VARIANT MC1DN20 CYS-414</scope>
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            <dbReference type="PubMed" id="23996478"/>
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        <scope>VARIANT MC1DN20 VAL-220</scope>
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        <scope>VARIANTS MC1DN20 GLY-271; MET-384 AND HIS-606</scope>
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    <comment type="function">
        <text evidence="2 3 4 5 8 12 14 16">Together with NDUFAF1 and ECSIT, forms part of the mitochondrial complex I (MCIA),which is required for the biogenesis of respiratory Complex I (CI) and is therefore crucial for the activation of the oxidative phosphorylation system (PubMed:20816094, PubMed:24158852, PubMed:32320651, PubMed:38086790). ECSIT binding triggers a large conformational change, switching ACAD9 from a fatty acid oxidation (FAO) enzyme to a CI assembly factor (PubMed:38086790). The function in CI assembly is independent of the FAO activity of the protein (PubMed:24158852). As FAO enzyme, it catalyzes the first step in FAO, which consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). Its preferred substrates are both saturated and unsaturated long-chain acyl-CoA substrates, with optimum activity toward the latter (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACADV and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the central nervous system (PubMed:16020546, PubMed:17564966, PubMed:24158852).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3 4 8 12 17">
            <text>a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:17721"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83721"/>
            <dbReference type="ChEBI" id="CHEBI:83727"/>
            <dbReference type="EC" id="1.3.8.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:17722"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a medium-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a medium-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:14477"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83723"/>
            <dbReference type="ChEBI" id="CHEBI:83726"/>
            <dbReference type="EC" id="1.3.8.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:14478"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>nonanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-nonenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48208"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:76291"/>
            <dbReference type="ChEBI" id="CHEBI:76292"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48209"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>decanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48176"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61406"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>undecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = trans-2-undecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48200"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77547"/>
            <dbReference type="ChEBI" id="CHEBI:77548"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48201"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47316"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>pentadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-pentadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48204"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74309"/>
            <dbReference type="ChEBI" id="CHEBI:77545"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48205"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3 8 12 17">
            <text>oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:43449"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>heptadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = trans-2-heptadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48196"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74307"/>
            <dbReference type="ChEBI" id="CHEBI:77551"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48197"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3 4 8">
            <text>octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47240"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:71412"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47241"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 8">
            <text>eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47236"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47237"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4">
            <text>(9Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47304"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
            <dbReference type="ChEBI" id="CHEBI:77549"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47305"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>(9E)-octadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9E)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48192"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77537"/>
            <dbReference type="ChEBI" id="CHEBI:77552"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48193"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4">
            <text>oxidized [electron-transfer flavoprotein] + (9Z)-octadecenoyl-CoA + H(+) = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47300"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77553"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47301"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>(9Z,12Z)-octadecadienoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z,12Z)-octadecatrienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48188"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77558"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48189"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,4Z,7Z,10Z,13Z,16Z,19Z)-docosaheptaenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48184"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77559"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:48185"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="21">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">2.8 uM for hexadecanoyl-CoA</KM>
            <KM evidence="3">0.7 uM for (9Z)-hexadecenoyl-CoA</KM>
            <KM evidence="3">2.1 uM for (9Z,12Z)-octadecadienoyl-CoA</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="3 5 14 15">Homodimer (PubMed:16020546). Interacts with NDUFAF1 and ECSIT (PubMed:20816094). Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (PubMed:32320651). Interacts with TMEM70 and TMEM242 (PubMed:33753518).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3 5">Mitochondrion inner membrane</location>
            <topology evidence="3">Peripheral membrane protein</topology>
            <orientation evidence="3">Matrix side</orientation>
        </subcellularLocation>
        <text evidence="3">Essentially associated with membranes.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 4 8">Ubiquitously expressed in most normal human tissues and cancer cell lines with higher levels in heart, skeletal muscles, and the central nervous system (where it is the highest expressed ACAD) (PubMed:12359260, PubMed:17564966). Highly expressed (at protein level) in the cerebellum (Purkinje neurons, dentate nucleus, and in the granular layer), where ACADV is not found (PubMed:17564966, PubMed:21237683).</text>
    </comment>
    <comment type="disease" evidence="4 5 6 7 9 10 11 13">
        <disease id="DI-01173">
            <name>Mitochondrial complex I deficiency, nuclear type 20</name>
            <acronym>MC1DN20</acronym>
            <description>An autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction.</description>
            <dbReference type="MIM" id="611126"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.7" evidence="3"/>
    <dbReference type="EC" id="1.3.8.8" evidence="2 3 8 12"/>
    <dbReference type="EMBL" id="AF327351">
        <property type="protein sequence ID" value="AAL56011.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK024012">
        <property type="protein sequence ID" value="BAB14775.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79295.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79296.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC013354">
        <property type="protein sequence ID" value="AAH13354.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007970">
        <property type="protein sequence ID" value="AAH07970.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3053.1"/>
    <dbReference type="PIR" id="JC7892">
        <property type="entry name" value="JC7892"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_054768.2">
        <property type="nucleotide sequence ID" value="NM_014049.4"/>
    </dbReference>
    <dbReference type="PDB" id="8PHE">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B=38-621"/>
    </dbReference>
    <dbReference type="PDB" id="8PHF">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B=38-621"/>
    </dbReference>
    <dbReference type="PDBsum" id="8PHE"/>
    <dbReference type="PDBsum" id="8PHF"/>
    <dbReference type="AlphaFoldDB" id="Q9H845"/>
    <dbReference type="EMDB" id="EMD-17659"/>
    <dbReference type="EMDB" id="EMD-17660"/>
    <dbReference type="EMDB" id="EMD-17661"/>
    <dbReference type="SASBDB" id="Q9H845"/>
    <dbReference type="SMR" id="Q9H845"/>
    <dbReference type="BioGRID" id="118799">
        <property type="interactions" value="464"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-6322">
        <property type="entry name" value="Mitochondrial complex I intermediate assembly (MCIA) complex"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-53699N"/>
    <dbReference type="FunCoup" id="Q9H845">
        <property type="interactions" value="1888"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H845">
        <property type="interactions" value="145"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H845"/>
    <dbReference type="STRING" id="9606.ENSP00000312618"/>
    <dbReference type="SwissLipids" id="SLP:000000619"/>
    <dbReference type="GlyGen" id="Q9H845">
        <property type="glycosylation" value="4 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H845"/>
    <dbReference type="MetOSite" id="Q9H845"/>
    <dbReference type="PhosphoSitePlus" id="Q9H845"/>
    <dbReference type="SwissPalm" id="Q9H845"/>
    <dbReference type="BioMuta" id="ACAD9"/>
    <dbReference type="DMDM" id="32469596"/>
    <dbReference type="jPOST" id="Q9H845"/>
    <dbReference type="MassIVE" id="Q9H845"/>
    <dbReference type="PaxDb" id="9606-ENSP00000312618"/>
    <dbReference type="PeptideAtlas" id="Q9H845"/>
    <dbReference type="ProteomicsDB" id="81177"/>
    <dbReference type="Pumba" id="Q9H845"/>
    <dbReference type="Antibodypedia" id="33213">
        <property type="antibodies" value="171 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="28976"/>
    <dbReference type="Ensembl" id="ENST00000308982.12">
        <property type="protein sequence ID" value="ENSP00000312618.7"/>
        <property type="gene ID" value="ENSG00000177646.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000681583.1">
        <property type="protein sequence ID" value="ENSP00000506340.1"/>
        <property type="gene ID" value="ENSG00000177646.21"/>
    </dbReference>
    <dbReference type="GeneID" id="28976"/>
    <dbReference type="KEGG" id="hsa:28976"/>
    <dbReference type="MANE-Select" id="ENST00000308982.12">
        <property type="protein sequence ID" value="ENSP00000312618.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014049.5"/>
        <property type="RefSeq protein sequence ID" value="NP_054768.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ela.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21497"/>
    <dbReference type="ClinPGx" id="PA134900655"/>
    <dbReference type="CTD" id="28976"/>
    <dbReference type="DisGeNET" id="28976"/>
    <dbReference type="GeneCards" id="ACAD9"/>
    <dbReference type="HGNC" id="HGNC:21497">
        <property type="gene designation" value="ACAD9"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000177646">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACAD9"/>
    <dbReference type="MIM" id="611103">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="611126">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000177646"/>
    <dbReference type="Orphanet" id="99901">
        <property type="disease" value="Acyl-CoA dehydrogenase 9 deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000177646"/>
    <dbReference type="eggNOG" id="KOG0137">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157312"/>
    <dbReference type="HOGENOM" id="CLU_018204_11_2_1"/>
    <dbReference type="InParanoid" id="Q9H845"/>
    <dbReference type="OMA" id="CDLANDW"/>
    <dbReference type="OrthoDB" id="2588832at2759"/>
    <dbReference type="PAN-GO" id="Q9H845">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H845"/>
    <dbReference type="PathwayCommons" id="Q9H845"/>
    <dbReference type="Reactome" id="R-HSA-6799198">
        <property type="pathway name" value="Complex I biogenesis"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9H845"/>
    <dbReference type="SignaLink" id="Q9H845"/>
    <dbReference type="Agora" id="ENSG00000177646"/>
    <dbReference type="BioGRID-ORCS" id="28976">
        <property type="hits" value="103 hits in 1173 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACAD9"/>
    <dbReference type="GenomeRNAi" id="28976"/>
    <dbReference type="Pharos" id="Q9H845">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H845"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
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    <feature type="sequence variant" id="VAR_071894" description="In MC1DN20; uncertain significance; dbSNP:rs377547811." evidence="7">
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        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="33753518"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="38086790"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="40255280"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="12359260"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="24158852"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="16020546"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="22">
        <source>
            <dbReference type="PubMed" id="24158852"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="23">
        <source>
            <dbReference type="HGNC" id="HGNC:21497"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="8PHE"/>
        </source>
    </evidence>
    <sequence length="621" mass="68760" checksum="064BCE0378877F54" modified="2001-03-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-04-18" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BR61</accession>
    <name>ACBD6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA-binding domain-containing protein 6</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACBD6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="16710414"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Lung</tissue>
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    </reference>
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            <dbReference type="PubMed" id="18268358"/>
            <dbReference type="DOI" id="10.1194/jlr.m800007-jlr200"/>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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                <person name="Olsen J.V."/>
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            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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                <person name="Burkard T.R."/>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Zhou H."/>
                <person name="Di Palma S."/>
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            <dbReference type="PubMed" id="23186163"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
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    </reference>
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            <title>Neurodevelopmental Disorder, Obesity, Pancytopenia, Diabetes Mellitus, Cirrhosis, and Renal Failure in ACBD6-Associated Syndrome: A Case Report.</title>
            <authorList>
                <person name="Yeetong P."/>
                <person name="Tanpowpong N."/>
                <person name="Rakwongkhachon S."/>
                <person name="Suphapeetiporn K."/>
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            </authorList>
            <dbReference type="PubMed" id="36457943"/>
            <dbReference type="DOI" id="10.1212/nxg.0000000000200046"/>
        </citation>
        <scope>INVOLVEMENT IN NEDPM</scope>
    </reference>
    <reference key="9">
        <citation type="submission" date="2005-11" db="PDB data bank">
            <title>Solution structure of RSGI RUH-040, an ACBP domain from human cDNA.</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 42-137</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2024" name="Brain" volume="147" first="1436" last="1456">
            <title>Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders.</title>
            <authorList>
                <person name="Kaiyrzhanov R."/>
                <person name="Rad A."/>
                <person name="Lin S.J."/>
                <person name="Bertoli-Avella A."/>
                <person name="Kallemeijn W.W."/>
                <person name="Godwin A."/>
                <person name="Zaki M.S."/>
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                <person name="Lau T."/>
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                <person name="Hempel M."/>
                <person name="Normand E.A."/>
                <person name="Rudnik-Schoeneborn S."/>
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                <person name="Ilyas M."/>
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                <person name="Ganieva M."/>
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                <person name="Yeetong P."/>
                <person name="Azam M."/>
                <person name="Babaei M."/>
                <person name="Monajemi G.B."/>
                <person name="Mohammadi P."/>
                <person name="Samie S."/>
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                <person name="Kortuem F."/>
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                <person name="Bauer P."/>
                <person name="Beetz C."/>
                <person name="Garshasbi M."/>
                <person name="Issa A.H."/>
                <person name="Eyaid W."/>
                <person name="Ahmed H."/>
                <person name="Hashemi N."/>
                <person name="Hassanpour K."/>
                <person name="Herman I."/>
                <person name="Ibrohimov S."/>
                <person name="Abdul-Majeed B.A."/>
                <person name="Imdad M."/>
                <person name="Isrofilov M."/>
                <person name="Kaiyal Q."/>
                <person name="Khan S."/>
                <person name="Kirmse B."/>
                <person name="Koster J."/>
                <person name="Lourenco C.M."/>
                <person name="Mitani T."/>
                <person name="Moldovan O."/>
                <person name="Murphy D."/>
                <person name="Najafi M."/>
                <person name="Pehlivan D."/>
                <person name="Rocha M.E."/>
                <person name="Salpietro V."/>
                <person name="Schmidts M."/>
                <person name="Shalata A."/>
                <person name="Mahroum M."/>
                <person name="Talbeya J.K."/>
                <person name="Taylor R.W."/>
                <person name="Vazquez D."/>
                <person name="Vetro A."/>
                <person name="Waterham H.R."/>
                <person name="Zaman M."/>
                <person name="Schrader T.A."/>
                <person name="Chung W.K."/>
                <person name="Guerrini R."/>
                <person name="Lupski J.R."/>
                <person name="Gleeson J."/>
                <person name="Suri M."/>
                <person name="Jamshidi Y."/>
                <person name="Bhatia K.P."/>
                <person name="Vona B."/>
                <person name="Schrader M."/>
                <person name="Severino M."/>
                <person name="Guille M."/>
                <person name="Tate E.W."/>
                <person name="Varshney G.K."/>
                <person name="Houlden H."/>
                <person name="Maroofian R."/>
            </authorList>
            <dbReference type="PubMed" id="37951597"/>
            <dbReference type="DOI" id="10.1093/brain/awad380"/>
        </citation>
        <scope>VARIANTS NEDPM 54-GLN--ALA-282 DEL; 63-GLU--ALA-282 DEL; 72-TYR--ALA-282 DEL; 73-LYS--ALA-282 DEL; 94-GLN--ALA-282 DEL; 180-SER--ALA-282 DEL; 198-TRP--ALA-282 DEL; GLY-201; ASN-219 INS AND 254-ARG--ALA-282 DEL</scope>
        <scope>INVOLVEMENT IN NEDPM</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6">Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA, lower affinity for unsaturated C20:4-CoA, and very weak affinity for saturated C16:0-CoA. Does not bind fatty acids. Plays a role in protein N-myristoylation (PubMed:37951597).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2848793">
            <id>Q9BR61</id>
        </interactant>
        <interactant intactId="EBI-5280164">
            <id>P30419</id>
            <label>NMT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2848793">
            <id>Q9BR61</id>
        </interactant>
        <interactant intactId="EBI-3920273">
            <id>O60551</id>
            <label>NMT2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>18</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 6">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Detected in placenta and spleen (at protein level). Detected in placenta, umbilical cord blood, CD34-positive hematopoietic progenitor cells and bone marrow.</text>
    </comment>
    <comment type="disease" evidence="5 6">
        <disease id="DI-06884">
            <name>Neurodevelopmental disorder with progressive movement abnormalities</name>
            <acronym>NEDPM</acronym>
            <description>An autosomal recessive, progressive disorder characterized by global developmental delay, intellectual disability, significant expressive language impairment, behavioral abnormalities, and movement disorders including dystonia, spasticity and cerebellar ataxia associated with gait impairment. Additional features include facial dysmorphism, oculomotor anomalies, microcephaly, seizures and brain imaging abnormalities. Parkinsonism may develop in older patients.</description>
            <dbReference type="MIM" id="620785"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <dbReference type="EMBL" id="AL445469">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139141">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL358354">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006505">
        <property type="protein sequence ID" value="AAH06505.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1339.1"/>
    <dbReference type="RefSeq" id="NP_115736.1">
        <property type="nucleotide sequence ID" value="NM_032360.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288036.1">
        <property type="nucleotide sequence ID" value="XM_047432080.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288037.1">
        <property type="nucleotide sequence ID" value="XM_047432081.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288038.1">
        <property type="nucleotide sequence ID" value="XM_047432082.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288039.1">
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-1023">Dystonia</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0446">Lipid-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0908">Parkinsonism</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
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            <begin position="1"/>
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            <begin position="42"/>
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    <feature type="repeat" description="ANK 1">
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            <begin position="224"/>
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    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
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        <location>
            <begin position="69"/>
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        <ligand>
            <name>an acyl-CoA</name>
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            <name>an acyl-CoA</name>
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            <position position="106"/>
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            <begin position="54"/>
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            <begin position="72"/>
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            <position position="201"/>
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            <begin position="57"/>
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            <dbReference type="SAM" id="MobiDB-lite"/>
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    <sequence length="282" mass="31151" checksum="0EA01CFDB5C5ECB2" modified="2001-06-01" version="1">MASSFLPAGAITGDSGGELSSGDDSGEVEFPHSPEIEETSCLAELFEKAAAHLQGLIQVASREQLLYLYARYKQVKVGNCNTPKPSFFDFEGKQKWEAWKALGDSSPSQAMQEYIAVVKKLDPGWNPQIPEKKGKEANTGFGGPVISSLYHEETIREEDKNIFDYCRENNIDHITKAIKSKNVDVNVKDEEGRALLHWACDRGHKELVTVLLQHRADINCQDNEGQTALHYASACEFLDIVELLLQSGADPTLRDQDGCLPEEVTGCKTVSLVLQRHTTGKA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-04-01" modified="2026-01-28" version="237" xmlns="https://uniprot.org/uniprot">
    <accession>P16219</accession>
    <accession>P78331</accession>
    <name>ACADS_HUMAN</name>
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        <recommendedName>
            <fullName>Short-chain specific acyl-CoA dehydrogenase, mitochondrial</fullName>
            <shortName>SCAD</shortName>
            <ecNumber evidence="7">1.3.8.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Butyryl-CoA dehydrogenase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACADS</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="J. Clin. Invest." volume="83" first="1605" last="1613">
            <title>Molecular cloning and nucleotide sequence of complementary DNAs encoding human short chain acyl-coenzyme A dehydrogenase and the study of the molecular basis of human short chain acyl-coenzyme A dehydrogenase deficiency.</title>
            <authorList>
                <person name="Naito E."/>
                <person name="Ozasa H."/>
                <person name="Ikeda Y."/>
                <person name="Tanaka K."/>
            </authorList>
            <dbReference type="PubMed" id="2565344"/>
            <dbReference type="DOI" id="10.1172/jci114058"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="Mamm. Genome" volume="8" first="922" last="926">
            <title>Structural organization of the human short-chain acyl-CoA dehydrogenase gene.</title>
            <authorList>
                <person name="Corydon M.J."/>
                <person name="Andresen B.S."/>
                <person name="Bross P."/>
                <person name="Kjeldsen M."/>
                <person name="Andreasen P.H."/>
                <person name="Eiberg H."/>
                <person name="Koelvraa S."/>
                <person name="Gregersen N."/>
            </authorList>
            <dbReference type="PubMed" id="9383286"/>
            <dbReference type="DOI" id="10.1007/s003359900612"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1997-01" db="EMBL/GenBank/DDBJ databases">
            <title>Transcription map of the 5cM region surrounding the hepatocyte nuclear factor-1a/MODY3 gene on chromosome 12.</title>
            <authorList>
                <person name="Yamagata K."/>
                <person name="Oda N."/>
                <person name="Furuta H."/>
                <person name="Vaxillaire M."/>
                <person name="Southam L."/>
                <person name="Boriraj V."/>
                <person name="Chen X."/>
                <person name="Oda Y."/>
                <person name="Takeda J."/>
                <person name="Yamada S."/>
                <person name="Nishigori H."/>
                <person name="Lebeau M.M."/>
                <person name="Lathrop M."/>
                <person name="Cox R.D."/>
                <person name="Bell G.I."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Retinal pigment epithelium</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1992" name="Electrophoresis" volume="13" first="992" last="1001">
            <title>Human liver protein map: a reference database established by microsequencing and gel comparison.</title>
            <authorList>
                <person name="Hochstrasser D.F."/>
                <person name="Frutiger S."/>
                <person name="Paquet N."/>
                <person name="Bairoch A."/>
                <person name="Ravier F."/>
                <person name="Pasquali C."/>
                <person name="Sanchez J.-C."/>
                <person name="Tissot J.-D."/>
                <person name="Bjellqvist B."/>
                <person name="Vargas R."/>
                <person name="Appel R.D."/>
                <person name="Hughes G.J."/>
            </authorList>
            <dbReference type="PubMed" id="1286669"/>
            <dbReference type="DOI" id="10.1002/elps.11501301201"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 25-34</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="Mol. Genet. Metab." volume="102" first="418" last="429">
            <title>Identification and characterization of new long chain acyl-CoA dehydrogenases.</title>
            <authorList>
                <person name="He M."/>
                <person name="Pei Z."/>
                <person name="Mohsen A.W."/>
                <person name="Watkins P."/>
                <person name="Murdoch G."/>
                <person name="Van Veldhoven P.P."/>
                <person name="Ensenauer R."/>
                <person name="Vockley J."/>
            </authorList>
            <dbReference type="PubMed" id="21237683"/>
            <dbReference type="DOI" id="10.1016/j.ymgme.2010.12.005"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="submission" date="2009-02" db="PDB data bank">
            <title>Crystal structure of human RAB14.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 30-412 IN COMPLEX WITH FAD AND SUBSTRATE ANALOG</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1990" name="J. Clin. Invest." volume="85" first="1575" last="1582">
            <title>Identification of two variant short chain acyl-coenzyme A dehydrogenase alleles, each containing a different point mutation in a patient with short chain acyl-coenzyme A dehydrogenase deficiency.</title>
            <authorList>
                <person name="Naito E."/>
                <person name="Indo Y."/>
                <person name="Tanaka K."/>
            </authorList>
            <dbReference type="PubMed" id="1692038"/>
            <dbReference type="DOI" id="10.1172/jci114607"/>
        </citation>
        <scope>VARIANTS ACADSD TRP-46 AND CYS-107</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1998" name="Hum. Mol. Genet." volume="7" first="619" last="627">
            <title>Identification of four new mutations in the short-chain acyl-CoA dehydrogenase (SCAD) gene in two patients: one of the variant alleles, 511C--&gt;T, is present at an unexpectedly high frequency in the general population, as was the case for 625G--&gt;A, together conferring susceptibility to ethylmalonic aciduria.</title>
            <authorList>
                <person name="Gregersen N."/>
                <person name="Winter V.S."/>
                <person name="Corydon M.J."/>
                <person name="Corydon T.J."/>
                <person name="Rinaldo P."/>
                <person name="Ribes A."/>
                <person name="Martinez G."/>
                <person name="Bennett M.J."/>
                <person name="Vianey-Saban C."/>
                <person name="Bhala A."/>
                <person name="Hale D.E."/>
                <person name="Lehnert W."/>
                <person name="Kmoch S."/>
                <person name="Roig M."/>
                <person name="Riudor E."/>
                <person name="Eiberg H."/>
                <person name="Andresen B.S."/>
                <person name="Bross P."/>
                <person name="Bolund L.A."/>
                <person name="Koelvraa S."/>
            </authorList>
            <dbReference type="PubMed" id="9499414"/>
            <dbReference type="DOI" id="10.1093/hmg/7.4.619"/>
        </citation>
        <scope>VARIANTS ACADSD CYS-92; ARG-177 AND CYS-383</scope>
        <scope>VARIANTS TRP-171 AND SER-209</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2001" name="Pediatr. Res." volume="49" first="18" last="23">
            <title>Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency.</title>
            <authorList>
                <person name="Corydon M.J."/>
                <person name="Vockley J."/>
                <person name="Rinaldo P."/>
                <person name="Rhead W.J."/>
                <person name="Kjeldsen M."/>
                <person name="Winter V.S."/>
                <person name="Riggs C."/>
                <person name="Babovic-Vuksanovic D."/>
                <person name="Smeitink J."/>
                <person name="De Jong J."/>
                <person name="Levy H."/>
                <person name="Sewell A.C."/>
                <person name="Roe C."/>
                <person name="Matern D."/>
                <person name="Dasouki M."/>
                <person name="Gregersen N."/>
            </authorList>
            <dbReference type="PubMed" id="11134486"/>
            <dbReference type="DOI" id="10.1203/00006450-200101000-00008"/>
        </citation>
        <scope>VARIANTS ACADSD SER-90; GLU-104 DEL; VAL-192; TRP-325; LEU-353 AND TRP-380</scope>
        <scope>VARIANTS TRP-171 AND SER-209</scope>
        <scope>CHARACTERIZATION OF VARIANTS ACADSD SER-90; GLU-104 DEL; VAL-192; TRP-325; LEU-353 AND TRP-380</scope>
        <scope>CHARACTERIZATION OF VARIANTS TRP-171 AND SER-209</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 7">Short-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (By similarity). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity). Among the different mitochondrial acyl-CoA dehydrogenases, short-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 4 to 6 carbons long primary chains (PubMed:11134486, PubMed:21237683).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a short-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a short-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47196"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:87487"/>
            <dbReference type="ChEBI" id="CHEBI:87488"/>
            <dbReference type="EC" id="1.3.8.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:47197"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>butanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-butenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:24004"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57332"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="EC" id="1.3.8.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:24005"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>pentanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-pentenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43456"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57389"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:86160"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:43457"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>hexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43464"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62077"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:43465"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
        <text evidence="9">Binds 1 FAD per subunit.</text>
    </comment>
    <comment type="pathway">
        <text evidence="11">Lipid metabolism; mitochondrial fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">Homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3904404">
            <id>P16219</id>
        </interactant>
        <interactant intactId="EBI-749514">
            <id>P16444</id>
            <label>DPEP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="4 6 8">
        <disease id="DI-02301">
            <name>Acyl-CoA dehydrogenase short-chain deficiency</name>
            <acronym>ACADSD</acronym>
            <description>An inborn error of mitochondrial fatty acid beta-oxidation resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.</description>
            <dbReference type="MIM" id="201470"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Butyryl_CoA_dehydrogenase"/>
        <text>Butyryl-CoA dehydrogenase entry</text>
    </comment>
    <dbReference type="EC" id="1.3.8.1" evidence="7"/>
    <dbReference type="EMBL" id="M26393">
        <property type="protein sequence ID" value="AAA60307.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z80345">
        <property type="protein sequence ID" value="CAB02492.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z80347">
        <property type="protein sequence ID" value="CAB02492.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U83992">
        <property type="protein sequence ID" value="AAD00552.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="U83991">
        <property type="protein sequence ID" value="AAD00552.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC025963">
        <property type="protein sequence ID" value="AAH25963.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS9207.1"/>
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        <property type="entry name" value="A30605"/>
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    <dbReference type="RefSeq" id="NP_000008.1">
        <property type="nucleotide sequence ID" value="NM_000017.4"/>
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    <dbReference type="RefSeq" id="NP_001289483.1">
        <property type="nucleotide sequence ID" value="NM_001302554.1"/>
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    <dbReference type="PDB" id="2VIG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=30-412"/>
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    <dbReference type="PDB" id="7Y0A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.32 A"/>
        <property type="chains" value="A/B/C/D=25-412"/>
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    <dbReference type="PDB" id="7Y0B">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.08 A"/>
        <property type="chains" value="A/B/C/D=25-412"/>
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    <dbReference type="PDB" id="8SGS">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.15 A"/>
        <property type="chains" value="A/B/C/D=1-412"/>
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    <dbReference type="PDBsum" id="2VIG"/>
    <dbReference type="PDBsum" id="7Y0A"/>
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    <dbReference type="PDBsum" id="8SGS"/>
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    <dbReference type="EMDB" id="EMD-40466"/>
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        <property type="interactions" value="29"/>
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        <property type="interactions" value="842"/>
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        <property type="interactions" value="23"/>
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    <dbReference type="STRING" id="9606.ENSP00000242592"/>
    <dbReference type="DrugBank" id="DB03059">
        <property type="generic name" value="Acetoacetyl-CoA"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03147">
        <property type="generic name" value="Flavin adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
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    <dbReference type="SwissLipids" id="SLP:000001403"/>
    <dbReference type="GlyGen" id="P16219">
        <property type="glycosylation" value="1 site"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000242592"/>
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    <dbReference type="Pumba" id="P16219"/>
    <dbReference type="Antibodypedia" id="1579">
        <property type="antibodies" value="275 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="35"/>
    <dbReference type="Ensembl" id="ENST00000242592.9">
        <property type="protein sequence ID" value="ENSP00000242592.4"/>
        <property type="gene ID" value="ENSG00000122971.10"/>
    </dbReference>
    <dbReference type="GeneID" id="35"/>
    <dbReference type="KEGG" id="hsa:35"/>
    <dbReference type="MANE-Select" id="ENST00000242592.9">
        <property type="protein sequence ID" value="ENSP00000242592.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000017.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000008.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001tza.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:90"/>
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    <dbReference type="GeneCards" id="ACADS"/>
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    <dbReference type="HGNC" id="HGNC:90">
        <property type="gene designation" value="ACADS"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000122971">
        <property type="expression patterns" value="Tissue enhanced (liver, skeletal muscle)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACADS"/>
    <dbReference type="MIM" id="201470">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="606885">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000122971"/>
    <dbReference type="Orphanet" id="26792">
        <property type="disease" value="Short chain acyl-CoA dehydrogenase deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000122971"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P16219"/>
    <dbReference type="BioCyc" id="MetaCyc:HS04619-MONOMER"/>
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    <dbReference type="Reactome" id="R-HSA-77350">
        <property type="pathway name" value="Beta oxidation of hexanoyl-CoA to butanoyl-CoA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-77352">
        <property type="pathway name" value="Beta oxidation of butanoyl-CoA to acetyl-CoA"/>
    </dbReference>
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    <dbReference type="Agora" id="ENSG00000122971"/>
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        <property type="hits" value="11 hits in 1158 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ACADS">
        <property type="organism name" value="human"/>
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        <property type="component" value="Chromosome 12"/>
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    <dbReference type="Bgee" id="ENSG00000122971">
        <property type="expression patterns" value="Expressed in right lobe of liver and 158 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0003995">
        <property type="term" value="F:acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
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        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016937">
        <property type="term" value="F:short-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046359">
        <property type="term" value="P:butyrate catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006635">
        <property type="term" value="P:fatty acid beta-oxidation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033539">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA dehydrogenase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd01158">
        <property type="entry name" value="SCAD_SBCAD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000002">
        <property type="entry name" value="Acyl-CoA dehydrogenase FadE19"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000004">
        <property type="entry name" value="Acyl-CoA dehydrogenase FadE25"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000001">
        <property type="entry name" value="Acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006089">
        <property type="entry name" value="Acyl-CoA_DH_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43884">
        <property type="entry name" value="ACYL-COA DEHYDROGENASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43884:SF12">
        <property type="entry name" value="ISOVALERYL-COA DEHYDROGENASE, MITOCHONDRIAL-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016578">
        <property type="entry name" value="HsaA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00072">
        <property type="entry name" value="ACYL_COA_DH_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00073">
        <property type="entry name" value="ACYL_COA_DH_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="5">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000498" description="Short-chain specific acyl-CoA dehydrogenase, mitochondrial">
        <location>
            <begin position="25"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="392"/>
        </location>
    </feature>
    <feature type="binding site" description="in other chain" evidence="9">
        <location>
            <begin position="152"/>
            <end position="161"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="161"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="9">
        <location>
            <begin position="185"/>
            <end position="187"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="269"/>
            <end position="272"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <position position="297"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="9">
        <location>
            <position position="308"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="9">
        <location>
            <begin position="365"/>
            <end position="369"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="393"/>
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        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="9">
        <location>
            <begin position="394"/>
            <end position="396"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="208"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="306"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="306"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000310" description="In ACADSD; dbSNP:rs121908003." evidence="6">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013565" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs121908005." evidence="4">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000311" description="In ACADSD; dbSNP:rs121908004." evidence="8">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013566" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs387906308." evidence="4">
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000312" description="In ACADSD; dbSNP:rs61732144." evidence="6">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013567" description="69% of wild-type acyl-CoA dehydrogenase activity; confers susceptibility to ethylmalonicaciduria; dbSNP:rs1800556." evidence="4 8">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="171"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000314" description="In ACADSD; dbSNP:rs57443665." evidence="8">
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        <variation>R</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013568" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs28940874." evidence="4">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000315" description="86% of wild-type acyl-CoA dehydrogenase activity; confers susceptibility to ethylmalonicaciduria; dbSNP:rs1799958." evidence="4 8">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013569" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs121908006." evidence="4">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="325"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013570" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs28941773." evidence="4">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013571" description="In ACADSD; loss of acyl-CoA dehydrogenase activity; dbSNP:rs28940875." evidence="4">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000316" description="In ACADSD; dbSNP:rs28940872." evidence="8">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033458" description="In dbSNP:rs35233375.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="36"/>
            <end position="52"/>
        </location>
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    <feature type="turn" evidence="12">
        <location>
            <begin position="53"/>
            <end position="56"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="57"/>
            <end position="63"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="68"/>
            <end position="77"/>
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    <feature type="turn" evidence="12">
        <location>
            <begin position="78"/>
            <end position="80"/>
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    <feature type="strand" evidence="14">
        <location>
            <begin position="82"/>
            <end position="84"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="86"/>
            <end position="88"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="95"/>
            <end position="108"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="110"/>
            <end position="121"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="124"/>
            <end position="130"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="133"/>
            <end position="139"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="141"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="144"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="150"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="159"/>
            <end position="162"/>
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        <location>
            <begin position="163"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="169"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="176"/>
            <end position="187"/>
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    <feature type="turn" evidence="12">
        <location>
            <begin position="188"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="193"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="203"/>
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        <location>
            <begin position="206"/>
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    <feature type="strand" evidence="12">
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            <begin position="210"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="222"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="230"/>
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    <feature type="strand" evidence="12">
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            <begin position="238"/>
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            <begin position="253"/>
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            <begin position="260"/>
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    <feature type="helix" evidence="12">
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            <begin position="304"/>
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        <location>
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            <begin position="368"/>
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        <location>
            <begin position="378"/>
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        <location>
            <begin position="389"/>
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        <location>
            <begin position="395"/>
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        <source>
            <dbReference type="UniProtKB" id="P15651"/>
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        <source>
            <dbReference type="UniProtKB" id="Q07417"/>
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        <source>
            <dbReference type="UniProtKB" id="Q3ZBF6"/>
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        <source>
            <dbReference type="PubMed" id="11134486"/>
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    <evidence type="ECO:0000269" key="5">
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            <dbReference type="PDB" id="7Y0A"/>
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        <source>
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    <sequence length="412" mass="44297" checksum="3E946ADFC3DA3C0E" modified="1990-04-01" version="1" precursor="true">MAAALLARASGPARRALCPRAWRQLHTIYQSVELPETHQMLLQTCRDFAEKELFPIAAQVDKEHLFPAAQVKKMGGLGLLAMDVPEELGGAGLDYLAYAIAMEEISRGCASTGVIMSVNNSLYLGPILKFGSKEQKQAWVTPFTSGDKIGCFALSEPGNGSDAGAASTTARAEGDSWVLNGTKAWITNAWEASAAVVFASTDRALQNKGISAFLVPMPTPGLTLGKKEDKLGIRGSSTANLIFEDCRIPKDSILGEPGMGFKIAMQTLDMGRIGIASQALGIAQTALDCAVNYAENRMAFGAPLTKLQVIQFKLADMALALESARLLTWRAAMLKDNKKPFIKEAAMAKLAASEAATAISHQAIQILGGMGYVTEMPAERHYRDARITEIYEGTSEIQRLVIAGHLLRSYRS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="234" xmlns="https://uniprot.org/uniprot">
    <accession>Q13085</accession>
    <accession>B2RP68</accession>
    <accession>B2ZZ90</accession>
    <accession>Q6KEV6</accession>
    <accession>Q6XDA8</accession>
    <accession>Q7Z2G8</accession>
    <accession>Q7Z561</accession>
    <accession>Q7Z563</accession>
    <accession>Q7Z564</accession>
    <accession>Q86WB2</accession>
    <accession>Q86WB3</accession>
    <name>ACACA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="21">Acetyl-CoA carboxylase 1</fullName>
            <shortName>ACC1</shortName>
            <ecNumber evidence="16 17 18">6.4.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acetyl-Coenzyme A carboxylase alpha</fullName>
            <shortName>ACC-alpha</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="28" type="primary">ACACA</name>
        <name type="synonym">ACAC</name>
        <name type="synonym">ACC1</name>
        <name type="synonym">ACCA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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        <scope>PROTEIN SEQUENCE OF 1-18; 39-45; 77-86; 99-111; 121-132; 153-170; 218-224; 267-276; 278-288; 323-335; 568-579; 589-615; 646-657; 748-755; 818-838; 985-992; 997-1008; 1083-1096; 1147-1169; 1192-1199; 1233-1247; 1283-1294; 1317-1325; 1327-1334; 1372-1385; 1401-1420; 1508-1514; 1553-1564; 1668-1687; 1714-1731; 1750-1759; 1782-1798; 1824-1833; 1838-1856; 1905-1916; 1922-1929; 1978-2009; 2063-2072; 2104-2111; 2115-2127; 2139-2161; 2200-2209; 2213-2218; 2221-2229 AND 2261-2293</scope>
        <scope>ACETYLATION AT MET-1</scope>
        <scope>PHOSPHORYLATION AT SER-80</scope>
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        <scope>PHOSPHORYLATION AT SER-1263</scope>
        <scope>MUTAGENESIS OF SER-78; SER-344; SER-432; SER-1201; SER-1263; SER-1585; SER-1952 AND SER-2211</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5 AND SER-29</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1334</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-23; SER-29; SER-48 AND SER-80</scope>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-25; SER-29; SER-80; THR-610; SER-835 AND THR-2153</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 78-617</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (4.60 ANGSTROMS) OF OLIGOMER IN COMPLEX WITH BRCA1 BRCT DOMAIN</scope>
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        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH BRCA1</scope>
        <scope>DOMAIN</scope>
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        <scope>PHOSPHORYLATION AT SER-80 AND SER-1263</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] GLN-1687</scope>
    </reference>
    <comment type="function">
        <text evidence="16 17 18">Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16 17 18">
            <text>hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11308"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17544"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:57384"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="6.4.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="25">
            <dbReference type="Rhea" id="RHEA:11309"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4 5">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="4 5">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="4 5">Binds 2 magnesium or manganese ions per subunit.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6 18">
            <name>biotin</name>
            <dbReference type="ChEBI" id="CHEBI:57586"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="12 18">Inhibited by phosphorylation (PubMed:16326698, PubMed:29899443). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (PubMed:29899443). Inhibited by palmitoyl-CoA (PubMed:29899443).</text>
    </comment>
    <comment type="pathway">
        <text evidence="25 26">Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="10 12 15 16 17 18">Monomer, homodimer, and homotetramer (PubMed:20952656, PubMed:29899443). Can form filamentous polymers (PubMed:20457939, PubMed:20952656, PubMed:29899443). Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis (PubMed:12360400, PubMed:16326698, PubMed:18452305, PubMed:29899443). Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity (PubMed:20457939).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
            <label>ACACA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-1572139">
            <id>O60218</id>
            <label>AKR1B10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-349905">
            <id>P38398</id>
            <label>BRCA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-747644">
            <id>Q13418</id>
            <label>ILK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-447544">
            <id>P01106</id>
            <label>MYC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-714158">
            <id>Q13526</id>
            <label>PIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-1802965">
            <id>Q96EB6</id>
            <label>SIRT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717681">
            <id>Q13085</id>
        </interactant>
        <interactant intactId="EBI-473024">
            <id>Q9CQ20</id>
            <label>Mid1ip1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12562760">
            <id>Q13085-4</id>
        </interactant>
        <interactant intactId="EBI-1220105">
            <id>P02654</id>
            <label>APOC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12562760">
            <id>Q13085-4</id>
        </interactant>
        <interactant intactId="EBI-12836320">
            <id>Q92915-2</id>
            <label>FGF14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12562760">
            <id>Q13085-4</id>
        </interactant>
        <interactant intactId="EBI-17589229">
            <id>Q6NTF9-3</id>
            <label>RHBDD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
            <location evidence="3">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative promoter"/>
        <isoform>
            <id>Q13085-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13085-2</id>
            <name>2</name>
            <name>E5A</name>
            <sequence type="described" ref="VSP_026099"/>
        </isoform>
        <isoform>
            <id>Q13085-3</id>
            <name>3</name>
            <name>E5B</name>
            <sequence type="described" ref="VSP_026098"/>
        </isoform>
        <isoform>
            <id>Q13085-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_026100"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in brain, placenta, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver.</text>
    </comment>
    <comment type="domain">
        <text evidence="27">Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (Probable). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (Probable).</text>
    </comment>
    <comment type="PTM">
        <text evidence="13 20">Phosphorylation on Ser-1263 is required for interaction with BRCA1.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Phosphorylation at Ser-80 by AMPK inactivates enzyme activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18">The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.</text>
    </comment>
    <comment type="disease" evidence="19">
        <disease id="DI-01164">
            <name>Acetyl-CoA carboxylase-alpha deficiency</name>
            <acronym>ACACAD</acronym>
            <description>An autosomal recessive inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.</description>
            <dbReference type="MIM" id="613933"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Acetyl-CoA_carboxylase"/>
        <text>Acetyl-CoA carboxylase entry</text>
    </comment>
    <dbReference type="EC" id="6.4.1.2" evidence="16 17 18"/>
    <dbReference type="EMBL" id="U19822">
        <property type="protein sequence ID" value="AAC50139.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY315619">
        <property type="protein sequence ID" value="AAP94114.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY315620">
        <property type="protein sequence ID" value="AAP94115.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY315621">
        <property type="protein sequence ID" value="AAP94116.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY315623">
        <property type="protein sequence ID" value="AAP94118.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY315627">
        <property type="protein sequence ID" value="AAP94122.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY237919">
        <property type="protein sequence ID" value="AAP69841.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB371587">
        <property type="protein sequence ID" value="BAG48316.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471199">
        <property type="protein sequence ID" value="EAW57582.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471199">
        <property type="protein sequence ID" value="EAW57577.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471199">
        <property type="protein sequence ID" value="EAW57578.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471199">
        <property type="protein sequence ID" value="EAW57581.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137287">
        <property type="protein sequence ID" value="AAI37288.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ534888">
        <property type="protein sequence ID" value="CAD59556.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ534889">
        <property type="protein sequence ID" value="CAD59557.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ564444">
        <property type="protein sequence ID" value="CAD92089.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11317.1">
        <molecule id="Q13085-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11318.1">
        <molecule id="Q13085-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42302.1">
        <molecule id="Q13085-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42303.1">
        <molecule id="Q13085-3"/>
    </dbReference>
    <dbReference type="PIR" id="I38928">
        <property type="entry name" value="I38928"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942131.1">
        <molecule id="Q13085-4"/>
        <property type="nucleotide sequence ID" value="NM_198834.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942133.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="NM_198836.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942134.1">
        <molecule id="Q13085-2"/>
        <property type="nucleotide sequence ID" value="NM_198837.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942135.1">
        <molecule id="Q13085-3"/>
        <property type="nucleotide sequence ID" value="NM_198838.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942136.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="NM_198839.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005257324.1">
        <molecule id="Q13085-3"/>
        <property type="nucleotide sequence ID" value="XM_005257267.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011523005.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="XM_011524703.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011523006.1">
        <molecule id="Q13085-3"/>
        <property type="nucleotide sequence ID" value="XM_011524704.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047291834.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="XM_047435878.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047291835.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="XM_047435879.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047291836.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="XM_047435880.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047291837.1">
        <molecule id="Q13085-1"/>
        <property type="nucleotide sequence ID" value="XM_047435881.1"/>
    </dbReference>
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        <property type="entry name" value="Rudment_hybrid_motif"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011053">
        <property type="entry name" value="Single_hybrid_motif"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45728:SF5">
        <property type="entry name" value="ACETYL-COA CARBOXYLASE 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45728">
        <property type="entry name" value="ACETYL-COA CARBOXYLASE, ISOFORM A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08326">
        <property type="entry name" value="ACC_central"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF21385">
        <property type="entry name" value="ACCA_BT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02785">
        <property type="entry name" value="Biotin_carb_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00289">
        <property type="entry name" value="Biotin_carb_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00364">
        <property type="entry name" value="Biotin_lipoyl"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01039">
        <property type="entry name" value="Carboxyl_trans"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02786">
        <property type="entry name" value="CPSase_L_D2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00878">
        <property type="entry name" value="Biotin_carb_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52096">
        <property type="entry name" value="ClpP/crotonase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56059">
        <property type="entry name" value="Glutathione synthetase ATP-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52440">
        <property type="entry name" value="PreATP-grasp domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51246">
        <property type="entry name" value="Rudiment single hybrid motif"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51230">
        <property type="entry name" value="Single hybrid motif"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50975">
        <property type="entry name" value="ATP_GRASP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50979">
        <property type="entry name" value="BC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00188">
        <property type="entry name" value="BIOTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50968">
        <property type="entry name" value="BIOTINYL_LIPOYL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50989">
        <property type="entry name" value="COA_CT_CTER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50980">
        <property type="entry name" value="COA_CT_NTER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00866">
        <property type="entry name" value="CPSASE_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00867">
        <property type="entry name" value="CPSASE_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0021">Allosteric enzyme</keyword>
    <keyword id="KW-0877">Alternative promoter usage</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0092">Biotin</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0275">Fatty acid biosynthesis</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0511">Multifunctional enzyme</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000146764" description="Acetyl-CoA carboxylase 1">
        <location>
            <begin position="1"/>
            <end position="2346"/>
        </location>
    </feature>
    <feature type="domain" description="Biotin carboxylation" evidence="5">
        <location>
            <begin position="117"/>
            <end position="618"/>
        </location>
    </feature>
    <feature type="domain" description="ATP-grasp" evidence="4">
        <location>
            <begin position="275"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="domain" description="Biotinyl-binding" evidence="6">
        <location>
            <begin position="745"/>
            <end position="819"/>
        </location>
    </feature>
    <feature type="domain" description="CoA carboxyltransferase N-terminal" evidence="7">
        <location>
            <begin position="1576"/>
            <end position="1914"/>
        </location>
    </feature>
    <feature type="domain" description="CoA carboxyltransferase C-terminal" evidence="8">
        <location>
            <begin position="1918"/>
            <end position="2234"/>
        </location>
    </feature>
    <feature type="region of interest" description="Carboxyltransferase" evidence="9">
        <location>
            <begin position="1576"/>
            <end position="2234"/>
        </location>
    </feature>
    <feature type="active site" evidence="1">
        <location>
            <position position="441"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="315"/>
            <end position="320"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="424"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="424"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="437"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="437"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="437"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="437"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="439"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 5">
        <location>
            <position position="439"/>
        </location>
        <ligand>
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="1823"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="2127"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="2129"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="20 33 36">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="33 36 38">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="31 35 36">
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="31 35 38 39">
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29 31 32 33 35 36 37 38 39">
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="36">
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="29">
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="3">
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="18 20 31 36 37 38">
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="30">
        <location>
            <position position="488"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="38">
        <location>
            <position position="610"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-biotinyllysine" evidence="2 6">
        <location>
            <position position="786"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="38">
        <location>
            <position position="835"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="1201"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="1216"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="1218"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="3">
        <location>
            <position position="1227"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="1259"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13 18">
        <location>
            <position position="1263"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="39">
        <location>
            <position position="1273"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="34">
        <location>
            <position position="1334"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="38">
        <location>
            <position position="2153"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026098" description="In isoform 3." evidence="21 22">
        <location>
            <begin position="1"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026099" description="In isoform 2." evidence="21 22">
        <original>MDEPSPLAQPLELNQHSRFIIGSVSEDNSEDEISNLVKLDLLEEKEGSLSPASVGSDTLSDLGISSLQDGLALHI</original>
        <variation>MEGSPEENKEMRYYMLQ</variation>
        <location>
            <begin position="1"/>
            <end position="75"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026100" description="In isoform 4." evidence="21 23">
        <original>M</original>
        <variation>MWWSTLMSILRARSFWKWISTQTVRIIRAVRAHFGGIM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042941" description="In dbSNP:rs2287351.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="838"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036514" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs1357271377." evidence="14">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1687"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028929" description="Frequency &lt;0.004; may play a role in breast cancer susceptibility; dbSNP:rs146351326." evidence="11">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="2271"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1201"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1263"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1585"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1952"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with BRCA1." evidence="13">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="2211"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>M</original>
        <variation>W</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAP94122." evidence="24" ref="2">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="446"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="494"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="622"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="640"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAP94122." evidence="24" ref="2">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="814"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="1061"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>EL</original>
        <variation>DV</variation>
        <location>
            <begin position="1094"/>
            <end position="1095"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1225"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="1257"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="1297"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="1320"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="1444"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="1474"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>TF</original>
        <variation>SL</variation>
        <location>
            <begin position="1665"/>
            <end position="1666"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="1677"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="1741"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="1762"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="1822"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="1875"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC50139." evidence="24" ref="1">
        <original>D</original>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
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                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
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                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
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                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
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                <person name="Nomura N."/>
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                <person name="Nakai K."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Ovary</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166 AND SER-171</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2009-04" db="PDB data bank">
            <title>Crystal structure of human acyl-CoA binding domain 4.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 7-110 IN COMPLEX WITH THE ACYL-COA STEAROYL-COENZYME A</scope>
    </reference>
    <comment type="function">
        <text>Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-11954292">
            <id>Q86V38</id>
            <label>ATN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-6875961">
            <id>P02489</id>
            <label>CRYAA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-10976677">
            <id>G5E9A7</id>
            <label>DMWD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-348399">
            <id>P22607</id>
            <label>FGFR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-25913156">
            <id>O14908-2</id>
            <label>GIPC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-351506">
            <id>P06396</id>
            <label>GSN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-2432309">
            <id>Q92876</id>
            <label>KLK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-5235340">
            <id>Q7Z699</id>
            <label>SPRED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12811089">
            <id>Q8NC06-3</id>
        </interactant>
        <interactant intactId="EBI-750487">
            <id>Q8WW24</id>
            <label>TEKT4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NC06-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NC06-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_014089"/>
        </isoform>
        <isoform>
            <id>Q8NC06-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_014088 VSP_014090"/>
        </isoform>
    </comment>
    <dbReference type="EMBL" id="AB073387">
        <property type="protein sequence ID" value="BAD38638.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK023384">
        <property type="protein sequence ID" value="BAB14553.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK075104">
        <property type="protein sequence ID" value="BAC11403.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471178">
        <property type="protein sequence ID" value="EAW51550.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471178">
        <property type="protein sequence ID" value="EAW51551.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471178">
        <property type="protein sequence ID" value="EAW51552.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC029164">
        <property type="protein sequence ID" value="AAH29164.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041143">
        <property type="protein sequence ID" value="AAH41143.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42348.1">
        <molecule id="Q8NC06-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45710.1">
        <molecule id="Q8NC06-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45711.1">
        <molecule id="Q8NC06-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001129177.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="NM_001135705.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001129178.1">
        <molecule id="Q8NC06-3"/>
        <property type="nucleotide sequence ID" value="NM_001135706.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001129179.1">
        <molecule id="Q8NC06-1"/>
        <property type="nucleotide sequence ID" value="NM_001135707.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308281.1">
        <molecule id="Q8NC06-3"/>
        <property type="nucleotide sequence ID" value="NM_001321352.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001308282.1">
        <molecule id="Q8NC06-3"/>
        <property type="nucleotide sequence ID" value="NM_001321353.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_078998.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="NM_024722.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016880577.1">
        <molecule id="Q8NC06-3"/>
        <property type="nucleotide sequence ID" value="XM_017025088.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016880581.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_017025092.3"/>
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    <dbReference type="RefSeq" id="XP_047292719.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_047436763.1"/>
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    <dbReference type="RefSeq" id="XP_047292720.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_047436764.1"/>
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    <dbReference type="RefSeq" id="XP_047292721.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_047436765.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173210.1">
        <molecule id="Q8NC06-3"/>
        <property type="nucleotide sequence ID" value="XM_054317235.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173217.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317242.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173218.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317243.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173219.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317244.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173220.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317245.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173221.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317246.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054173222.1">
        <molecule id="Q8NC06-2"/>
        <property type="nucleotide sequence ID" value="XM_054317247.1"/>
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    <dbReference type="PDB" id="2WH5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C/D/E/F=7-110"/>
    </dbReference>
    <dbReference type="PDBsum" id="2WH5"/>
    <dbReference type="AlphaFoldDB" id="Q8NC06"/>
    <dbReference type="SMR" id="Q8NC06"/>
    <dbReference type="BioGRID" id="122878">
        <property type="interactions" value="14"/>
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    <dbReference type="FunCoup" id="Q8NC06">
        <property type="interactions" value="481"/>
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    <dbReference type="IntAct" id="Q8NC06">
        <property type="interactions" value="12"/>
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    <dbReference type="STRING" id="9606.ENSP00000405969"/>
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        <molecule id="Q8NC06-1"/>
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    <dbReference type="ProteomicsDB" id="72842">
        <molecule id="Q8NC06-2"/>
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    <dbReference type="ProteomicsDB" id="72843">
        <molecule id="Q8NC06-3"/>
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    <dbReference type="Antibodypedia" id="29971">
        <property type="antibodies" value="144 antibodies from 28 providers"/>
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    <dbReference type="DNASU" id="79777"/>
    <dbReference type="Ensembl" id="ENST00000321854.13">
        <molecule id="Q8NC06-2"/>
        <property type="protein sequence ID" value="ENSP00000314440.8"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000376955.8">
        <molecule id="Q8NC06-1"/>
        <property type="protein sequence ID" value="ENSP00000366154.3"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000398322.7">
        <molecule id="Q8NC06-2"/>
        <property type="protein sequence ID" value="ENSP00000381367.2"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000431281.5">
        <molecule id="Q8NC06-3"/>
        <property type="protein sequence ID" value="ENSP00000405969.1"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000586346.5">
        <molecule id="Q8NC06-3"/>
        <property type="protein sequence ID" value="ENSP00000465484.1"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000591859.5">
        <molecule id="Q8NC06-3"/>
        <property type="protein sequence ID" value="ENSP00000465610.1"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="Ensembl" id="ENST00000619916.4">
        <molecule id="Q8NC06-1"/>
        <property type="protein sequence ID" value="ENSP00000482750.1"/>
        <property type="gene ID" value="ENSG00000181513.16"/>
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    <dbReference type="GeneID" id="79777"/>
    <dbReference type="KEGG" id="hsa:79777"/>
    <dbReference type="MANE-Select" id="ENST00000321854.13">
        <molecule id="Q8NC06-2"/>
        <property type="protein sequence ID" value="ENSP00000314440.8"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001135705.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001129177.1"/>
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    <dbReference type="UCSC" id="uc002iic.4">
        <molecule id="Q8NC06-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:23337"/>
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        <property type="gene designation" value="ACBD4"/>
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    <dbReference type="HPA" id="ENSG00000181513">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000181513"/>
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    <dbReference type="OMA" id="NIPPEHG"/>
    <dbReference type="OrthoDB" id="71307at2759"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NC06"/>
    <dbReference type="PathwayCommons" id="Q8NC06"/>
    <dbReference type="Reactome" id="R-HSA-390918">
        <property type="pathway name" value="Peroxisomal lipid metabolism"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8NC06"/>
    <dbReference type="Agora" id="ENSG00000181513"/>
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        <property type="hits" value="26 hits in 1160 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ACBD4">
        <property type="organism name" value="human"/>
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    <dbReference type="EvolutionaryTrace" id="Q8NC06"/>
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        <property type="development level" value="Tdark"/>
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    <dbReference type="PRO" id="PR:Q8NC06"/>
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        <property type="component" value="Chromosome 17"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000181513">
        <property type="expression patterns" value="Expressed in right lobe of liver and 128 other cell types or tissues"/>
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    <dbReference type="ExpressionAtlas" id="Q8NC06">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000062">
        <property type="term" value="F:fatty-acyl-CoA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
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        <property type="entry name" value="ACBP"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Acyl-CoA-binding domain-containing protein 5"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR022408">
        <property type="entry name" value="Acyl-CoA-binding_prot_CS"/>
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    <dbReference type="InterPro" id="IPR000582">
        <property type="entry name" value="Acyl-CoA-binding_protein"/>
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    <dbReference type="InterPro" id="IPR035984">
        <property type="entry name" value="Acyl-CoA-binding_sf"/>
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    <dbReference type="InterPro" id="IPR014352">
        <property type="entry name" value="FERM/acyl-CoA-bd_prot_sf"/>
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    <dbReference type="PANTHER" id="PTHR23310:SF53">
        <property type="entry name" value="ACYL-COA-BINDING DOMAIN-CONTAINING PROTEIN 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23310">
        <property type="entry name" value="ACYL-COA-BINDING PROTEIN, ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00887">
        <property type="entry name" value="ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00689">
        <property type="entry name" value="ACOABINDINGP"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47027">
        <property type="entry name" value="Acyl-CoA binding protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00880">
        <property type="entry name" value="ACB_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51228">
        <property type="entry name" value="ACB_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0446">Lipid-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000214032" description="Acyl-CoA-binding domain-containing protein 4">
        <location>
            <begin position="1"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="domain" description="ACB" evidence="1">
        <location>
            <begin position="12"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="151"/>
            <end position="175"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="2">
        <location>
            <begin position="156"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="23"/>
            <end position="32"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="43"/>
            <end position="47"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="69"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="88"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="171"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_014088" description="In isoform 3." evidence="4 5">
        <original>ESHSPRDLDSEVFCDSLEQLEPEL</original>
        <variation>ASLWAVTLPTPPQSPIHPGTWTPRFSVIPWSSWSLSWFGQ</variation>
        <location>
            <begin position="168"/>
            <end position="191"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_014089" description="In isoform 2." evidence="3 5">
        <original>SSGQHLEESVIPGTAPCPPQRKRGCGAARRGPRSWTCGCWGQFEHYRRACRRCRRGCRAWRACPGPLSSLTLSVRLE</original>
        <variation>VWTEQRAASGGKRDPRNSPVPPTKKEGLRGSPPGPQELDVWLLGTVRALQESMQEVQARVQSLESMPRPPEQRPQPRPSARPWPLGLPGPALLFFLLWPFVVQWLFRMFRTQKR</variation>
        <location>
            <begin position="192"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_014090" description="In isoform 3." evidence="4 5">
        <original>SLTLSVRLE</original>
        <variation>RGRSPGPVLGHGPLGSRGPRCSSSSCGPSSSSGSSECFGPKRGDCQWRGLCSQLRLSCCALSLPRV</variation>
        <location>
            <begin position="260"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055478" description="In dbSNP:rs901754.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059109" description="In dbSNP:rs16939879.">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC11403." evidence="6" ref="2">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="helix" evidence="8">
        <location>
            <begin position="14"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="helix" evidence="8">
        <location>
            <begin position="36"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="helix" evidence="8">
        <location>
            <begin position="64"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="turn" evidence="8">
        <location>
            <begin position="75"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="helix" evidence="8">
        <location>
            <begin position="81"/>
            <end position="100"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00573"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15221005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="8">
        <source>
            <dbReference type="PDB" id="2WH5"/>
        </source>
    </evidence>
    <sequence length="268" mass="30308" checksum="0F337D89924CDE2E" modified="2005-06-07" version="2">MGTEKESPEPDCQKQFQAAVSVIQNLPKNGSYRPSYEEMLRFYSYYKQATMGPCLVPRPGFWDPIGRYKWDAWNSLGKMSREEAMSAYITEMKLVAQKVIDTVPLGEVAEDMFGYFEPLYQVIPDMPRPPETFLRRVTGWKEQVVNGDVGAVSEPPCLPKEPAPPSPESHSPRDLDSEVFCDSLEQLEPELSSGQHLEESVIPGTAPCPPQRKRGCGAARRGPRSWTCGCWGQFEHYRRACRRCRRGCRAWRACPGPLSSLTLSVRLE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-27" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>Q96P50</accession>
    <accession>B1AMF5</accession>
    <accession>Q5TA42</accession>
    <accession>Q5TA43</accession>
    <accession>Q86UT3</accession>
    <accession>Q9BSR9</accession>
    <accession>Q9C0E7</accession>
    <name>ACAP3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-beta-5</fullName>
            <shortName>Cnt-b5</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACAP3</name>
        <name type="synonym">CENTB5</name>
        <name type="synonym">KIAA1716</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2001-08" db="EMBL/GenBank/DDBJ databases">
            <title>Centaurin beta5, a new member of centaurin family.</title>
            <authorList>
                <person name="Hong W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="DNA Res." volume="7" first="347" last="355">
            <title>Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Hattori A."/>
                <person name="Kondo Y."/>
                <person name="Okumura K."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="11214970"/>
            <dbReference type="DOI" id="10.1093/dnares/7.6.347"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Coville G.J."/>
                <person name="Davies J."/>
                <person name="Deadman R."/>
                <person name="Dunn M."/>
                <person name="Earthrowl M."/>
                <person name="Ellington A.G."/>
                <person name="Errington H."/>
                <person name="Frankish A."/>
                <person name="Frankland J."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gay L."/>
                <person name="Ghori M.R.J."/>
                <person name="Gibson R."/>
                <person name="Gilby L.M."/>
                <person name="Gillett W."/>
                <person name="Glithero R.J."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Hammond S."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E."/>
                <person name="Haugen E."/>
                <person name="Heath P.D."/>
                <person name="Holmes S."/>
                <person name="Holt K."/>
                <person name="Howden P.J."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Hunter G."/>
                <person name="Isherwood J."/>
                <person name="James R."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A."/>
                <person name="Kay M."/>
                <person name="Kershaw J.K."/>
                <person name="Kibukawa M."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A.J."/>
                <person name="Lad H."/>
                <person name="Laird G."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Hippocampus</tissue>
            <tissue>Lymph</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Nat. Biotechnol." volume="24" first="1285" last="1292">
            <title>A probability-based approach for high-throughput protein phosphorylation analysis and site localization.</title>
            <authorList>
                <person name="Beausoleil S.A."/>
                <person name="Villen J."/>
                <person name="Gerber S.A."/>
                <person name="Rush J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="16964243"/>
            <dbReference type="DOI" id="10.1038/nbt1240"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="6">GTPase-activating protein for the ADP ribosylation factor family.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-715726">
            <id>Q96P50</id>
        </interactant>
        <interactant intactId="EBI-4401196">
            <id>Q15057</id>
            <label>ACAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96P50-3</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96P50-1</id>
            <name>2</name>
            <sequence type="described" ref="VSP_035993 VSP_035994"/>
        </isoform>
        <isoform>
            <id>Q96P50-4</id>
            <name>3</name>
            <sequence type="described" ref="VSP_035992"/>
        </isoform>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB21807" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF411981">
        <property type="protein sequence ID" value="AAL04165.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB051503">
        <property type="protein sequence ID" value="BAB21807.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL139287">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL162741">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471183">
        <property type="protein sequence ID" value="EAW56248.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471183">
        <property type="protein sequence ID" value="EAW56249.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004874">
        <property type="protein sequence ID" value="AAH04874.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051194">
        <property type="protein sequence ID" value="AAH51194.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS19.2">
        <molecule id="Q96P50-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_085152.2">
        <molecule id="Q96P50-3"/>
        <property type="nucleotide sequence ID" value="NM_030649.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96P50"/>
    <dbReference type="SMR" id="Q96P50"/>
    <dbReference type="BioGRID" id="125546">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96P50">
        <property type="interactions" value="1528"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96P50">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="MINT" id="Q96P50"/>
    <dbReference type="STRING" id="9606.ENSP00000346733"/>
    <dbReference type="iPTMnet" id="Q96P50"/>
    <dbReference type="PhosphoSitePlus" id="Q96P50"/>
    <dbReference type="BioMuta" id="ACAP3"/>
    <dbReference type="DMDM" id="218511905"/>
    <dbReference type="jPOST" id="Q96P50"/>
    <dbReference type="MassIVE" id="Q96P50"/>
    <dbReference type="PaxDb" id="9606-ENSP00000346733"/>
    <dbReference type="PeptideAtlas" id="Q96P50"/>
    <dbReference type="ProteomicsDB" id="77629">
        <molecule id="Q96P50-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77630">
        <molecule id="Q96P50-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77631">
        <molecule id="Q96P50-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q96P50"/>
    <dbReference type="Antibodypedia" id="46438">
        <property type="antibodies" value="119 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="116983"/>
    <dbReference type="Ensembl" id="ENST00000353662.4">
        <molecule id="Q96P50-1"/>
        <property type="protein sequence ID" value="ENSP00000321139.4"/>
        <property type="gene ID" value="ENSG00000131584.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000354700.10">
        <molecule id="Q96P50-3"/>
        <property type="protein sequence ID" value="ENSP00000346733.5"/>
        <property type="gene ID" value="ENSG00000131584.20"/>
    </dbReference>
    <dbReference type="GeneID" id="116983"/>
    <dbReference type="KEGG" id="hsa:116983"/>
    <dbReference type="MANE-Select" id="ENST00000354700.10">
        <property type="protein sequence ID" value="ENSP00000346733.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_030649.3"/>
        <property type="RefSeq protein sequence ID" value="NP_085152.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001aeb.3">
        <molecule id="Q96P50-3"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16754"/>
    <dbReference type="ClinPGx" id="PA26408"/>
    <dbReference type="CTD" id="116983"/>
    <dbReference type="DisGeNET" id="116983"/>
    <dbReference type="GeneCards" id="ACAP3"/>
    <dbReference type="HGNC" id="HGNC:16754">
        <property type="gene designation" value="ACAP3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000131584">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
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        <property type="component" value="Chromosome 1"/>
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        <property type="entry name" value="PH-like_dom_sf"/>
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        <property type="entry name" value="CENTAURIN/ARF"/>
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        <property type="entry name" value="BAR_3"/>
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        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="REVINTRACTNG"/>
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    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
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    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF103657">
        <property type="entry name" value="BAR/IMD domain-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000356159" description="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3">
        <location>
            <begin position="1"/>
            <end position="834"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="268"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="403"/>
            <end position="525"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="702"/>
            <end position="731"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="735"/>
            <end position="764"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="768"/>
            <end position="797"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="418"/>
            <end position="441"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="375"/>
            <end position="400"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="633"/>
            <end position="653"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="382"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="3">
        <location>
            <begin position="634"/>
            <end position="653"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035992" description="In isoform 3." evidence="6">
        <location>
            <begin position="1"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035993" description="In isoform 2." evidence="4 5">
        <location>
            <begin position="1"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035994" description="In isoform 2." evidence="4 5">
        <original>SLSSDSGLGGSSDGSSDVLAFGSGSVVDSVTEEE</original>
        <variation>K</variation>
        <location>
            <begin position="605"/>
            <end position="638"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH51194." evidence="6" ref="5">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="11214970"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="834" mass="92495" checksum="D4C00A06EDB72F68" modified="2008-12-16" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-07-25" modified="2026-01-28" version="149" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N6N7</accession>
    <accession>A6NCI2</accession>
    <accession>B3KTG8</accession>
    <name>ACBD7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA-binding domain-containing protein 7</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACBD7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        </source>
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                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
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                <person name="Hammond S."/>
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                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
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                <person name="Skuce C.D."/>
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                <person name="Tester J."/>
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                <person name="Torcasso W."/>
                <person name="Tracey A."/>
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                <person name="Hubbard T."/>
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                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2009-01" db="PDB data bank">
            <title>Crystal structure of human acyl-COA binding domain 7 complexed with palmitoyl-COA.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)</scope>
    </reference>
    <comment type="function">
        <text>Binds medium- and long-chain acyl-CoA esters.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18657673">
            <id>Q8N6N7</id>
        </interactant>
        <interactant intactId="EBI-6165891">
            <id>Q14696</id>
            <label>MESD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18657673">
            <id>Q8N6N7</id>
        </interactant>
        <interactant intactId="EBI-11139477">
            <id>Q96N21</id>
            <label>TEPSIN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the ACBD7 family.</text>
    </comment>
    <dbReference type="EMBL" id="AK095538">
        <property type="protein sequence ID" value="BAG53080.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL590365">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86243.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC029526">
        <property type="protein sequence ID" value="AAH29526.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31153.1"/>
    <dbReference type="RefSeq" id="NP_001034933.1">
        <property type="nucleotide sequence ID" value="NM_001039844.3"/>
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    <dbReference type="PDB" id="3EPY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=1-88"/>
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    <dbReference type="PDBsum" id="3EPY"/>
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        <property type="interactions" value="248"/>
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        <property type="interactions" value="13"/>
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    <dbReference type="STRING" id="9606.ENSP00000367453"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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        <property type="antibodies" value="148 antibodies from 19 providers"/>
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        <property type="protein sequence ID" value="ENSP00000367453.4"/>
        <property type="gene ID" value="ENSG00000176244.7"/>
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    <dbReference type="GeneID" id="414149"/>
    <dbReference type="KEGG" id="hsa:414149"/>
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        <property type="protein sequence ID" value="ENSP00000367453.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001039844.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001034933.1"/>
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    <dbReference type="UCSC" id="uc001inv.4">
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:17715"/>
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        <property type="gene designation" value="ACBD7"/>
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        <property type="expression patterns" value="Tissue enriched (brain)"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
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    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
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        <property type="hits" value="18 hits in 1141 CRISPR screens"/>
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        <property type="development level" value="Tdark"/>
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        <property type="component" value="Chromosome 10"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000176244">
        <property type="expression patterns" value="Expressed in caudate nucleus and 100 other cell types or tissues"/>
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    <dbReference type="GO" id="GO:0000062">
        <property type="term" value="F:fatty-acyl-CoA binding"/>
        <property type="evidence" value="ECO:0000318"/>
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        <property type="term" value="P:fatty acid metabolic process"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Acyl-CoA-binding_protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035984">
        <property type="entry name" value="Acyl-CoA-binding_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014352">
        <property type="entry name" value="FERM/acyl-CoA-bd_prot_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23310:SF51">
        <property type="entry name" value="ACYL-COA-BINDING DOMAIN-CONTAINING PROTEIN 7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23310">
        <property type="entry name" value="ACYL-COA-BINDING PROTEIN, ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00887">
        <property type="entry name" value="ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00689">
        <property type="entry name" value="ACOABINDINGP"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47027">
        <property type="entry name" value="Acyl-CoA binding protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51228">
        <property type="entry name" value="ACB_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0446">Lipid-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000247588" description="Acyl-CoA-binding domain-containing protein 7">
        <location>
            <begin position="1"/>
            <end position="88"/>
        </location>
    </feature>
    <feature type="domain" description="ACB" evidence="1">
        <location>
            <begin position="3"/>
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        </location>
    </feature>
    <feature type="binding site">
        <location>
            <position position="15"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="30"/>
            <end position="34"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="56"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="75"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="2"/>
            <end position="13"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="14"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="23"/>
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        </location>
    </feature>
    <feature type="turn" evidence="3">
        <location>
            <begin position="46"/>
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        </location>
    </feature>
    <feature type="helix" evidence="3">
        <location>
            <begin position="51"/>
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    </feature>
    <feature type="turn" evidence="3">
        <location>
            <begin position="62"/>
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    </feature>
    <feature type="helix" evidence="3">
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            <begin position="68"/>
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    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00573"/>
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    </evidence>
    <evidence type="ECO:0000305" key="2"/>
    <evidence type="ECO:0007829" key="3">
        <source>
            <dbReference type="PDB" id="3EPY"/>
        </source>
    </evidence>
    <sequence length="88" mass="9790" checksum="F79EFF3BD7B2138B" modified="2002-10-01" version="1">MALQADFDRAAEDVRKLKARPDDGELKELYGLYKQAIVGDINIACPGMLDLKGKAKWEAWNLKKGLSTEDATSAYISKAKELIEKYGI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="215" xmlns="https://uniprot.org/uniprot">
    <accession>P28330</accession>
    <accession>B2R8T3</accession>
    <accession>Q8IUN8</accession>
    <name>ACADL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Long-chain specific acyl-CoA dehydrogenase, mitochondrial</fullName>
            <shortName>LCAD</shortName>
            <ecNumber evidence="5 6 8 9 10">1.3.8.8</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Medium-chain acyl-CoA dehydrogenase, mitochondrial</fullName>
            <ecNumber evidence="6 9 10">1.3.8.7</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="18" type="primary">ACADL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Genomics" volume="11" first="609" last="620">
            <title>Molecular cloning and nucleotide sequence of cDNAs encoding human long-chain acyl-CoA dehydrogenase and assignment of the location of its gene (ACADL) to chromosome 2.</title>
            <authorList>
                <person name="Indo Y."/>
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            </authorList>
            <dbReference type="PubMed" id="1774065"/>
            <dbReference type="DOI" id="10.1016/0888-7543(91)90068-p"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1992" name="Genomics" volume="12" first="626" last="626">
            <authorList>
                <person name="Indo Y."/>
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                <person name="Glassberg R."/>
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            </authorList>
            <dbReference type="PubMed" id="1559716"/>
            <dbReference type="DOI" id="10.1016/0888-7543(92)90462-2"/>
        </citation>
        <scope>ERRATUM OF PUBMED:1774065</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>FUNCTION</scope>
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        <scope>TISSUE SPECIFICITY</scope>
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    <comment type="function">
        <text evidence="5 6 7 8 10 12">Long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:17564966, PubMed:24591516, PubMed:32389575). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:17564966, PubMed:21237683). Among the different mitochondrial acyl-CoA dehydrogenases, long-chain specific acyl-CoA dehydrogenase activity overlaps with that of ACADV and ACAD9, acting on saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to 18 carbons long primary chains (PubMed:17564966, PubMed:21237683, PubMed:8823175). Plays a primary role in FAO in tissues where it is the main long-chain ACAD expressed, such as the lung, specifically in type 2 alveolar cells (responsible for surfactant production) (PubMed:17564966, PubMed:24591516). Probably responsible for beta-oxidation of bulky substrates including branched chain fatty acyl-CoAs and sterol derivatives thanks to its enlarged substrate-binding cavity (PubMed:38839792).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6 8 9 10">
            <text>a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:17721"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83721"/>
            <dbReference type="ChEBI" id="CHEBI:83727"/>
            <dbReference type="EC" id="1.3.8.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:17722"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 9 10">
            <text>a medium-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a medium-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:14477"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83723"/>
            <dbReference type="ChEBI" id="CHEBI:83726"/>
            <dbReference type="EC" id="1.3.8.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="17">
            <dbReference type="Rhea" id="RHEA:14478"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 10">
            <text>hexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43464"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62077"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="17">
            <dbReference type="Rhea" id="RHEA:43465"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 9 10">
            <text>octanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48180"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62242"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="17">
            <dbReference type="Rhea" id="RHEA:48181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 9 10">
            <text>decanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48176"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61406"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="17">
            <dbReference type="Rhea" id="RHEA:48177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8 10">
            <text>dodecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47296"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57330"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:47297"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8 10">
            <text>tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47316"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:47317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8 9 10">
            <text>oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:43449"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6 8 10">
            <text>octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47240"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:71412"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:47241"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47236"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:47237"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>docosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-docosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47228"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65059"/>
            <dbReference type="ChEBI" id="CHEBI:74692"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:47229"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>tetracosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetracosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47232"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:74693"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:47233"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(5E)-tetradecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,5E)-tetradecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:49828"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:131943"/>
            <dbReference type="ChEBI" id="CHEBI:131944"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:49829"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(5Z)-tetradecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,5Z)-tetradecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:84650"/>
            <dbReference type="ChEBI" id="CHEBI:87701"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:47449"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(9Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47304"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
            <dbReference type="ChEBI" id="CHEBI:77549"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:47305"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>oxidized [electron-transfer flavoprotein] + (9Z)-octadecenoyl-CoA + H(+) = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47300"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77553"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:47301"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,4Z,7Z,10Z,13Z,16Z,19Z)-docosaheptaenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48184"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77559"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:48185"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="10">29 uM for hexanoyl-CoA</KM>
            <KM evidence="10">8 uM for octanoyl-CoA</KM>
            <KM evidence="10">10 uM for decanoyl-CoA</KM>
            <KM evidence="10">7 uM for dodecanoyl-CoA</KM>
            <KM evidence="10">10 uM for tetradecanoyl-CoA</KM>
            <KM evidence="10">14 uM for hexadecanoyl-CoA</KM>
            <KM evidence="10">8 uM for octadecanoyl-CoA</KM>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="1">Lipid metabolism; mitochondrial fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12059321">
            <id>P28330</id>
        </interactant>
        <interactant intactId="EBI-8032987">
            <id>Q8N9I0</id>
            <label>SYT2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12059321">
            <id>P28330</id>
        </interactant>
        <interactant intactId="EBI-2562368">
            <id>P22735</id>
            <label>TGM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 7">Expressed at mRNA and protein levels in lungs, where it localizes specifically in alveolar epithelial cells (alveolar type II pneumocytes) (PubMed:17564966, PubMed:24591516). Also expressed at mRNA levels in prostate, thyroid gland, kidney, heart and muscle (PubMed:17564966).</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-binding sites strongly reduces catalytic activity. These sites are deacetylated by SIRT3.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="7 8">Originally thought to be responsible for the oxidation of long-chain fatty acyl-CoAs in human, however, in contrast to other mammals, LCAD is not widely expressed in human tissues, instead ACADV is the enzyme responsible for this catalytic activity in the high energy producing tissues muscle and heart.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.8" evidence="5 6 8 9 10"/>
    <dbReference type="EC" id="1.3.8.7" evidence="6 9 10"/>
    <dbReference type="EMBL" id="M74096">
        <property type="protein sequence ID" value="AAA51565.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313498">
        <property type="protein sequence ID" value="BAG36280.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006994">
        <property type="protein sequence ID" value="AAY14881.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471063">
        <property type="protein sequence ID" value="EAW70481.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC039063">
        <property type="protein sequence ID" value="AAH39063.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064549">
        <property type="protein sequence ID" value="AAH64549.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2389.1"/>
    <dbReference type="PIR" id="A40559">
        <property type="entry name" value="A40559"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001599.1">
        <property type="nucleotide sequence ID" value="NM_001608.4"/>
    </dbReference>
    <dbReference type="PDB" id="8W0T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=31-430"/>
    </dbReference>
    <dbReference type="PDB" id="8W0U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=31-430"/>
    </dbReference>
    <dbReference type="PDB" id="8W0Z">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=31-430"/>
    </dbReference>
    <dbReference type="PDBsum" id="8W0T"/>
    <dbReference type="PDBsum" id="8W0U"/>
    <dbReference type="PDBsum" id="8W0Z"/>
    <dbReference type="AlphaFoldDB" id="P28330"/>
    <dbReference type="SMR" id="P28330"/>
    <dbReference type="BioGRID" id="106551">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="FunCoup" id="P28330">
        <property type="interactions" value="361"/>
    </dbReference>
    <dbReference type="IntAct" id="P28330">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000233710"/>
    <dbReference type="SwissLipids" id="SLP:000001327"/>
    <dbReference type="iPTMnet" id="P28330"/>
    <dbReference type="PhosphoSitePlus" id="P28330"/>
    <dbReference type="SwissPalm" id="P28330"/>
    <dbReference type="BioMuta" id="ACADL"/>
    <dbReference type="DMDM" id="223590148"/>
    <dbReference type="jPOST" id="P28330"/>
    <dbReference type="MassIVE" id="P28330"/>
    <dbReference type="PaxDb" id="9606-ENSP00000233710"/>
    <dbReference type="PeptideAtlas" id="P28330"/>
    <dbReference type="ProteomicsDB" id="54469"/>
    <dbReference type="Pumba" id="P28330"/>
    <dbReference type="Antibodypedia" id="1641">
        <property type="antibodies" value="314 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="33"/>
    <dbReference type="Ensembl" id="ENST00000233710.4">
        <property type="protein sequence ID" value="ENSP00000233710.3"/>
        <property type="gene ID" value="ENSG00000115361.9"/>
    </dbReference>
    <dbReference type="GeneID" id="33"/>
    <dbReference type="KEGG" id="hsa:33"/>
    <dbReference type="MANE-Select" id="ENST00000233710.4">
        <property type="protein sequence ID" value="ENSP00000233710.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001608.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001599.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002vdz.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:88"/>
    <dbReference type="ClinPGx" id="PA24424"/>
    <dbReference type="CTD" id="33"/>
    <dbReference type="DisGeNET" id="33"/>
    <dbReference type="GeneCards" id="ACADL"/>
    <dbReference type="HGNC" id="HGNC:88">
        <property type="gene designation" value="ACADL"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000115361">
        <property type="expression patterns" value="Tissue enhanced (liver, pancreas)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACADL"/>
    <dbReference type="MIM" id="609576">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000115361"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000115361"/>
    <dbReference type="eggNOG" id="KOG0141">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157652"/>
    <dbReference type="HOGENOM" id="CLU_018204_0_3_1"/>
    <dbReference type="InParanoid" id="P28330"/>
    <dbReference type="OMA" id="MWEYPVA"/>
    <dbReference type="OrthoDB" id="9988775at2759"/>
    <dbReference type="PAN-GO" id="P28330">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P28330"/>
    <dbReference type="BioCyc" id="MetaCyc:HS03876-MONOMER"/>
    <dbReference type="PathwayCommons" id="P28330"/>
    <dbReference type="Reactome" id="R-HSA-77285">
        <property type="pathway name" value="Beta oxidation of myristoyl-CoA to lauroyl-CoA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-77288">
        <property type="pathway name" value="mitochondrial fatty acid beta-oxidation of unsaturated fatty acids"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-77310">
        <property type="pathway name" value="Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P28330"/>
    <dbReference type="SignaLink" id="P28330"/>
    <dbReference type="UniPathway" id="UPA00660"/>
    <dbReference type="Agora" id="ENSG00000115361"/>
    <dbReference type="BioGRID-ORCS" id="33">
        <property type="hits" value="12 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACADL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="33"/>
    <dbReference type="Pharos" id="P28330">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P28330"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="P28330">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000115361">
        <property type="expression patterns" value="Expressed in body of pancreas and 137 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004466">
        <property type="term" value="F:long-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042413">
        <property type="term" value="P:carnitine catabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019254">
        <property type="term" value="P:carnitine metabolic process, CoA-linked"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033539">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA dehydrogenase"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016042">
        <property type="term" value="P:lipid catabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042758">
        <property type="term" value="P:long-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045717">
        <property type="term" value="P:negative regulation of fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046322">
        <property type="term" value="P:negative regulation of fatty acid oxidation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120162">
        <property type="term" value="P:positive regulation of cold-induced thermogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="YuBioLab"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090181">
        <property type="term" value="P:regulation of cholesterol metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001659">
        <property type="term" value="P:temperature homeostasis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd01160">
        <property type="entry name" value="LCAD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000002">
        <property type="entry name" value="Acyl-CoA dehydrogenase fadE12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000020">
        <property type="entry name" value="Long-chain specific acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000017">
        <property type="entry name" value="long-chain specific acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050741">
        <property type="entry name" value="Acyl-CoA_dehydrogenase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006089">
        <property type="entry name" value="Acyl-CoA_DH_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034179">
        <property type="entry name" value="LCAD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083:SF20">
        <property type="entry name" value="LONG-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083">
        <property type="entry name" value="MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00072">
        <property type="entry name" value="ACYL_COA_DH_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00073">
        <property type="entry name" value="ACYL_COA_DH_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000509" description="Long-chain specific acyl-CoA dehydrogenase, mitochondrial">
        <location>
            <begin position="31"/>
            <end position="430"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="9">
        <location>
            <position position="291"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="170"/>
            <end position="179"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="179"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="203"/>
            <end position="205"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="227"/>
            <end position="228"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="282"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="289"/>
            <end position="292"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="317"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="328"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="385"/>
            <end position="389"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="412"/>
            <end position="413"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="414"/>
            <end position="416"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="165"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="240"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="318"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000328" description="In dbSNP:rs1801204." evidence="11">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000329" description="In dbSNP:rs2286963." evidence="4 11">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of long-chain-acyl-CoA dehydrogenase activity. No effect on protein abundance. No effect on solubility. No effect on substrate binding." evidence="9">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="291"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P15650"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P26440"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P51174"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17564966"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21237683"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24591516"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="32389575"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="8155643"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="8823175"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source ref="15"/>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="38839792"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="17564966"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="21237683"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="32389575"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17">
        <source>
            <dbReference type="PubMed" id="8823175"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="18">
        <source>
            <dbReference type="HGNC" id="HGNC:88"/>
        </source>
    </evidence>
    <sequence length="430" mass="47656" checksum="72F9803685406DF9" modified="2009-02-10" version="2" precursor="true">MAARLLRGSLRVLGGHRAPRQLPAARCSHSGGEERLETPSAKKLTDIGIRRIFSPEHDIFRKSVRKFFQEEVIPHHSEWEKAGEVSREVWEKAGKQGLLGVNIAEHLGGIGGDLYSAAIVWEEQAYSNCSGPGFSIHSGIVMSYITNHGSEEQIKHFIPQMTAGKCIGAIAMTEPGAGSDLQGIKTNAKKDGSDWILNGSKVFISNGSLSDVVIVVAVTNHEAPSPAHGISLFLVENGMKGFIKGRKLHKMGLKAQDTAELFFEDIRLPASALLGEENKGFYYIMKELPQERLLIADVAISASEFMFEETRNYVKQRKAFGKTVAHLQTVQHKLAELKTHICVTRAFVDNCLQLHEAKRLDSATACMAKYWASELQNSVAYDCVQLHGGWGYMWEYPIAKAYVDARVQPIYGGTNEIMKELIAREIVFDK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q96GR2</accession>
    <accession>B2RB61</accession>
    <accession>O75126</accession>
    <accession>Q76N27</accession>
    <accession>Q9HC26</accession>
    <name>ACBG1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="12">Long-chain-fatty-acid--CoA ligase ACSBG1</fullName>
            <ecNumber evidence="5 9">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase bubblegum family member 1</fullName>
            <shortName>hBG1</shortName>
            <shortName>hsBG</shortName>
            <shortName>hsBGM</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Lipidosin</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">ACSBG1</name>
        <name type="synonym">BGM</name>
        <name type="synonym">KIAA0631</name>
        <name type="synonym">LPD</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="35162" last="35169">
            <title>Very long-chain acyl-CoA synthetases. Human 'bubblegum' represents a new family of proteins capable of activating very long-chain fatty acids.</title>
            <authorList>
                <person name="Steinberg S.J."/>
                <person name="Morgenthaler J."/>
                <person name="Heinzer A.K."/>
                <person name="Smith K.D."/>
                <person name="Watkins P.A."/>
            </authorList>
            <dbReference type="PubMed" id="10954726"/>
            <dbReference type="DOI" id="10.1074/jbc.m006403200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>ENZYME ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="169" last="176">
            <title>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</title>
            <authorList>
                <person name="Ishikawa K."/>
                <person name="Nagase T."/>
                <person name="Suyama M."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
                <person name="Nomura N."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="9734811"/>
            <dbReference type="DOI" id="10.1093/dnares/5.3.169"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT VAL-633</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2002" name="DNA Res." volume="9" first="99" last="106">
            <title>Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.</title>
            <authorList>
                <person name="Nakajima D."/>
                <person name="Okazaki N."/>
                <person name="Yamakawa H."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
            </authorList>
            <dbReference type="PubMed" id="12168954"/>
            <dbReference type="DOI" id="10.1093/dnares/9.3.99"/>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
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                <person name="Tanai H."/>
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                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
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                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
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                <person name="Hara R."/>
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                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
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                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Nakagawa K."/>
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                <person name="Nagase T."/>
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                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS VAL-633 AND VAL-673</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Analysis of the DNA sequence and duplication history of human chromosome 15.</title>
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            </authorList>
            <dbReference type="PubMed" id="16572171"/>
            <dbReference type="DOI" id="10.1038/nature04601"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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            <authorList>
                <person name="Mural R.J."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT VAL-633</scope>
    </reference>
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        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT VAL-633</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="47070" last="47078">
            <title>The acyl-CoA synthetase 'bubblegum' (lipidosin): further characterization and role in neuronal fatty acid beta-oxidation.</title>
            <authorList>
                <person name="Pei Z."/>
                <person name="Oey N.A."/>
                <person name="Zuidervaart M.M."/>
                <person name="Jia Z."/>
                <person name="Li Y."/>
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                <person name="Smith K.D."/>
                <person name="Watkins P.A."/>
            </authorList>
            <dbReference type="PubMed" id="12975357"/>
            <dbReference type="DOI" id="10.1074/jbc.m310075200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2013" name="Biochem. Biophys. Res. Commun." volume="442" first="195" last="201">
            <title>Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway.</title>
            <authorList>
                <person name="Ohkuni A."/>
                <person name="Ohno Y."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="24269233"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2013.11.036"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 9">Catalyzes the conversion of fatty acids such as long-chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:10954726, PubMed:12975357, PubMed:24269233). Can activate diverse saturated, monosaturated and polyunsaturated fatty acids (PubMed:10954726).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 9">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasmic vesicle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Microsome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Cell membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 6 9">Expressed primarily in brain. Expressed at lower level in testis and adrenal gland. Present in all regions of brain except pituitary.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA31606" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="5 9"/>
    <dbReference type="EMBL" id="AF179481">
        <property type="protein sequence ID" value="AAG09404.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB014531">
        <property type="protein sequence ID" value="BAA31606.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314508">
        <property type="protein sequence ID" value="BAG37108.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC090260">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC090607">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471136">
        <property type="protein sequence ID" value="EAW99180.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009289">
        <property type="protein sequence ID" value="AAH09289.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10298.1"/>
    <dbReference type="RefSeq" id="NP_001186306.1">
        <property type="nucleotide sequence ID" value="NM_001199377.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055977.3">
        <property type="nucleotide sequence ID" value="NM_015162.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96GR2"/>
    <dbReference type="SMR" id="Q96GR2"/>
    <dbReference type="BioGRID" id="116813">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96GR2">
        <property type="interactions" value="277"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96GR2">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="MINT" id="Q96GR2"/>
    <dbReference type="STRING" id="9606.ENSP00000258873"/>
    <dbReference type="BindingDB" id="Q96GR2"/>
    <dbReference type="DrugBank" id="DB08326">
        <property type="generic name" value="2-(6-HYDROXY-1,3-BENZOTHIAZOL-2-YL)-1,3-THIAZOL-4(5H)-ONE"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000450"/>
    <dbReference type="iPTMnet" id="Q96GR2"/>
    <dbReference type="PhosphoSitePlus" id="Q96GR2"/>
    <dbReference type="BioMuta" id="ACSBG1"/>
    <dbReference type="DMDM" id="296434385"/>
    <dbReference type="MassIVE" id="Q96GR2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000258873"/>
    <dbReference type="PeptideAtlas" id="Q96GR2"/>
    <dbReference type="ProteomicsDB" id="76656"/>
    <dbReference type="Antibodypedia" id="27568">
        <property type="antibodies" value="170 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23205"/>
    <dbReference type="Ensembl" id="ENST00000258873.9">
        <property type="protein sequence ID" value="ENSP00000258873.4"/>
        <property type="gene ID" value="ENSG00000103740.11"/>
    </dbReference>
    <dbReference type="GeneID" id="23205"/>
    <dbReference type="KEGG" id="hsa:23205"/>
    <dbReference type="MANE-Select" id="ENST00000258873.9">
        <property type="protein sequence ID" value="ENSP00000258873.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_015162.5"/>
        <property type="RefSeq protein sequence ID" value="NP_055977.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002bdh.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:29567"/>
    <dbReference type="ClinPGx" id="PA142672648"/>
    <dbReference type="CTD" id="23205"/>
    <dbReference type="DisGeNET" id="23205"/>
    <dbReference type="GeneCards" id="ACSBG1"/>
    <dbReference type="HGNC" id="HGNC:29567">
        <property type="gene designation" value="ACSBG1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000103740">
        <property type="expression patterns" value="Group enriched (brain, skin)"/>
    </dbReference>
    <dbReference type="MIM" id="614362">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000103740"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000103740"/>
    <dbReference type="eggNOG" id="KOG1256">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160380"/>
    <dbReference type="InParanoid" id="Q96GR2"/>
    <dbReference type="OMA" id="IGDHRKY"/>
    <dbReference type="OrthoDB" id="3633556at2759"/>
    <dbReference type="PAN-GO" id="Q96GR2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96GR2"/>
    <dbReference type="BioCyc" id="MetaCyc:HS02532-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q96GR2"/>
    <dbReference type="Reactome" id="R-HSA-75876">
        <property type="pathway name" value="Synthesis of very long-chain fatty acyl-CoAs"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q96GR2"/>
    <dbReference type="Agora" id="ENSG00000103740"/>
    <dbReference type="BioGRID-ORCS" id="23205">
        <property type="hits" value="12 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSBG1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACSBG1"/>
    <dbReference type="GenomeRNAi" id="23205"/>
    <dbReference type="Pharos" id="Q96GR2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96GR2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96GR2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000103740">
        <property type="expression patterns" value="Expressed in upper leg skin and 130 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96GR2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031410">
        <property type="term" value="C:cytoplasmic vesicle"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004467">
        <property type="term" value="F:long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031957">
        <property type="term" value="F:very long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042759">
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        <property type="project" value="HGNC-UCL"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:very long-chain fatty acid metabolic process"/>
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        <property type="project" value="HGNC-UCL"/>
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        <property type="entry name" value="ACSBG_like"/>
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        <property type="entry name" value="Long-chain-fatty-acid--CoA ligase ACSBG1 isoform 1"/>
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        <property type="entry name" value="N-terminal domain of ligase-like"/>
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        <property type="entry name" value="ACYL-COA SYNTHETASE BUBBLEGUM FAMILY MEMBER 1"/>
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            <begin position="1"/>
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            <begin position="1"/>
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            <begin position="20"/>
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        <ligand>
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    <feature type="binding site" evidence="1">
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        <ligand>
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        <ligand>
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    <feature type="binding site" evidence="1">
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        <ligand>
            <name>ATP</name>
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            <position position="53"/>
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        <location>
            <position position="56"/>
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            <position position="658"/>
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            <position position="194"/>
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            <position position="633"/>
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            <dbReference type="UniProtKB" id="Q924N5"/>
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            <dbReference type="UniProtKB" id="Q99PU5"/>
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            <dbReference type="SAM" id="MobiDB-lite"/>
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        <source>
            <dbReference type="PubMed" id="10954726"/>
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        <source>
            <dbReference type="PubMed" id="12975357"/>
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    <evidence type="ECO:0000269" key="7">
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        <source>
            <dbReference type="PubMed" id="15489334"/>
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        <source>
            <dbReference type="PubMed" id="24269233"/>
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    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="9734811"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source ref="6"/>
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    <evidence type="ECO:0000305" key="12"/>
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        <source>
            <dbReference type="HGNC" id="HGNC:29567"/>
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    <sequence length="724" mass="81290" checksum="2C27BA65CE95CE17" modified="2010-05-18" version="2"> </sequence>
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    <accession>Q8N6E3</accession>
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        <recommendedName>
            <fullName>Acyl-CoA-binding domain-containing protein 5</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
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            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 252-534</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="23105016"/>
            <dbReference type="DOI" id="10.1101/gr.144105.112"/>
        </citation>
        <scope>INVOLVEMENT IN RDLKD</scope>
    </reference>
    <reference key="15">
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-279 AND SER-313</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="16">
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            <title>ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism.</title>
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                <person name="Ferdinandusse S."/>
                <person name="Falkenberg K.D."/>
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                <person name="Mooyer P.A."/>
                <person name="Jones R."/>
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                <person name="Pizzino A."/>
                <person name="Schrader M."/>
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                <person name="Vanderver A."/>
                <person name="Waterham H.R."/>
            </authorList>
            <dbReference type="PubMed" id="27799409"/>
            <dbReference type="DOI" id="10.1136/jmedgenet-2016-104132"/>
        </citation>
        <scope>INVOLVEMENT IN RDLKD</scope>
    </reference>
    <reference key="17">
        <citation type="submission" date="2011-07" db="PDB data bank">
            <title>The crystal structure of human acyl-coenzyme A binding domain containing 5.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 41-136 IN COMPLEX WITH THE ACYL-COA ANALOGS COENZYME A AND STEARIC ACID</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10961679">
            <id>Q5T8D3-2</id>
        </interactant>
        <interactant intactId="EBI-10232876">
            <id>Q14416</id>
            <label>GRM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10961679">
            <id>Q5T8D3-2</id>
        </interactant>
        <interactant intactId="EBI-10314552">
            <id>Q9NVC3</id>
            <label>SLC38A7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10961679">
            <id>Q5T8D3-2</id>
        </interactant>
        <interactant intactId="EBI-9071709">
            <id>P61266</id>
            <label>STX1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10961679">
            <id>Q5T8D3-2</id>
        </interactant>
        <interactant intactId="EBI-12195227">
            <id>Q8NBD8</id>
            <label>TMEM229B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Peroxisome membrane</location>
            <topology evidence="1">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5T8D3-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5T8D3-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_025447 VSP_025449"/>
        </isoform>
        <isoform>
            <id>Q5T8D3-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_025446 VSP_025449"/>
        </isoform>
        <isoform>
            <id>Q5T8D3-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_025448 VSP_025449"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="6 8">
        <disease id="DI-05818">
            <name>Retinal dystrophy with leukodystrophy</name>
            <acronym>RDLKD</acronym>
            <description>An autosomal recessive disorder characterized by progressive leukodystrophy associated with developmental delay, spastic paraparesis, ataxia, and retinal dystrophy. Patients may show facial dysmorphism. Laboratory investigations reveal an abnormal profile of very-long chain fatty acid in plasma.</description>
            <dbReference type="MIM" id="618863"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the ATG37 family.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH30555" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AF505653">
        <property type="protein sequence ID" value="AAP30852.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK057469">
        <property type="protein sequence ID" value="BAG51918.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL160291">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86062.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86061.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471072">
        <property type="protein sequence ID" value="EAW86063.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC030555">
        <property type="protein sequence ID" value="AAH30555.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133064">
        <property type="protein sequence ID" value="CAB61388.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44368.1">
        <molecule id="Q5T8D3-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7154.1">
        <molecule id="Q5T8D3-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS76290.1">
        <molecule id="Q5T8D3-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS86078.1">
        <molecule id="Q5T8D3-1"/>
    </dbReference>
    <dbReference type="PIR" id="T42665">
        <property type="entry name" value="T42665"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001035938.1">
        <molecule id="Q5T8D3-2"/>
        <property type="nucleotide sequence ID" value="NM_001042473.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001288180.1">
        <molecule id="Q5T8D3-4"/>
        <property type="nucleotide sequence ID" value="NM_001301251.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001288181.1">
        <molecule id="Q5T8D3-4"/>
        <property type="nucleotide sequence ID" value="NM_001301252.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001288182.1">
        <molecule id="Q5T8D3-4"/>
        <property type="nucleotide sequence ID" value="NM_001301253.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339500.1">
        <molecule id="Q5T8D3-1"/>
        <property type="nucleotide sequence ID" value="NM_001352571.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339506.1">
        <molecule id="Q5T8D3-2"/>
        <property type="nucleotide sequence ID" value="NM_001352577.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339507.1">
        <molecule id="Q5T8D3-2"/>
        <property type="nucleotide sequence ID" value="NM_001352578.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339508.1">
        <molecule id="Q5T8D3-2"/>
        <property type="nucleotide sequence ID" value="NM_001352579.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339512.1">
        <molecule id="Q5T8D3-4"/>
        <property type="nucleotide sequence ID" value="NM_001352583.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001339513.1">
        <molecule id="Q5T8D3-4"/>
        <property type="nucleotide sequence ID" value="NM_001352584.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_663736.2">
        <molecule id="Q5T8D3-3"/>
        <property type="nucleotide sequence ID" value="NM_145698.5"/>
    </dbReference>
    <dbReference type="PDB" id="3FLV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A/B=41-136"/>
    </dbReference>
    <dbReference type="PDBsum" id="3FLV"/>
    <dbReference type="AlphaFoldDB" id="Q5T8D3"/>
    <dbReference type="SMR" id="Q5T8D3"/>
    <dbReference type="BioGRID" id="124836">
        <property type="interactions" value="237"/>
    </dbReference>
    <dbReference type="CORUM" id="Q5T8D3"/>
    <dbReference type="FunCoup" id="Q5T8D3">
        <property type="interactions" value="2305"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5T8D3">
        <property type="interactions" value="45"/>
    </dbReference>
    <dbReference type="MINT" id="Q5T8D3"/>
    <dbReference type="STRING" id="9606.ENSP00000365049"/>
    <dbReference type="TCDB" id="1.R.1.1.1">
        <property type="family name" value="the membrane contact site (mcs) family"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5T8D3">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5T8D3"/>
    <dbReference type="PhosphoSitePlus" id="Q5T8D3"/>
    <dbReference type="SwissPalm" id="Q5T8D3"/>
    <dbReference type="BioMuta" id="ACBD5"/>
    <dbReference type="DMDM" id="74745508"/>
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        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0072">Autophagy</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-1026">Leukodystrophy</keyword>
    <keyword id="KW-0446">Lipid-binding</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000287377" description="Acyl-CoA-binding domain-containing protein 5">
        <location>
            <begin position="1"/>
            <end position="534"/>
        </location>
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            <begin position="506"/>
            <end position="526"/>
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            <end position="130"/>
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    </feature>
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            <end position="225"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
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            <end position="442"/>
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    </feature>
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        <location>
            <begin position="190"/>
            <end position="219"/>
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    </feature>
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        <location>
            <begin position="447"/>
            <end position="476"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="207"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
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            <begin position="376"/>
            <end position="385"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="431"/>
            <end position="441"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="52"/>
            <end position="61"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="72"/>
            <end position="76"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="98"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="117"/>
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        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="194"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13 14 15 16 18">
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="279"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="16">
        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="16">
        <location>
            <position position="428"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="469"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_025448" description="In isoform 4." evidence="11">
        <location>
            <begin position="1"/>
            <end position="107"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_025447" description="In isoform 2." evidence="9">
        <location>
            <begin position="1"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_025446" description="In isoform 3." evidence="10">
        <original>MFQ</original>
        <variation>MLFLS</variation>
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_025449" description="In isoform 2, isoform 3 and isoform 4." evidence="9 10 11">
        <location>
            <begin position="162"/>
            <end position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032301" description="In dbSNP:rs7918793.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="472"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP30852." evidence="12" ref="1">
        <original>P</original>
        <variation>Q</variation>
        <location>
            <position position="332"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP30852." evidence="12" ref="1">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="419"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP30852." evidence="12" ref="1">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="478"/>
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    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="41"/>
            <end position="58"/>
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    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="65"/>
            <end position="79"/>
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    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="93"/>
            <end position="104"/>
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    </feature>
    <feature type="turn" evidence="20">
        <location>
            <begin position="105"/>
            <end position="107"/>
        </location>
    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="110"/>
            <end position="127"/>
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    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="15 17">
        <location sequence="Q5T8D3-2">
            <position position="137"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="15 17">
        <location sequence="Q5T8D3-3">
            <position position="172"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="15 17">
        <location sequence="Q5T8D3-4">
            <position position="63"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q5XG73"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00573"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="23105016"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24535825"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27799409"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source ref="1"/>
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    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="18318008"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="3FLV"/>
        </source>
    </evidence>
    <sequence length="534" mass="60092" checksum="8BE9A09967717653" modified="2004-12-21" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="224" xmlns="https://uniprot.org/uniprot">
    <accession>O00763</accession>
    <accession>A6NK36</accession>
    <accession>Q16852</accession>
    <accession>Q1HEC1</accession>
    <accession>Q6KE87</accession>
    <accession>Q6KE89</accession>
    <accession>Q6TY48</accession>
    <name>ACACB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="27">Acetyl-CoA carboxylase 2</fullName>
            <ecNumber evidence="14 18 19 20 21 22">6.4.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ACC-beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="31" type="primary">ACACB</name>
        <name type="synonym">ACC2</name>
        <name type="synonym">ACCB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
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                <person name="Cho Y.S."/>
                <person name="Lee J.I."/>
                <person name="Shin D."/>
                <person name="Kim H.T."/>
                <person name="Jung H.Y."/>
                <person name="Lee T.G."/>
                <person name="Kang L.W."/>
                <person name="Ahn Y.J."/>
                <person name="Cho H.S."/>
                <person name="Heo Y.S."/>
            </authorList>
            <dbReference type="PubMed" id="19900410"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2009.11.029"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 217-775 IN COMPLEX WITH SORAPHEN A</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>PATHWAY</scope>
        <scope>SUBUNIT</scope>
        <scope>PHOSPHORYLATION AT SER-222</scope>
        <scope>MUTAGENESIS OF ARG-277 AND GLU-671</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2016" name="Proc. Natl. Acad. Sci. U.S.A." volume="113" first="E1796" last="E1805">
            <title>Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats.</title>
            <authorList>
                <person name="Harriman G."/>
                <person name="Greenwood J."/>
                <person name="Bhat S."/>
                <person name="Huang X."/>
                <person name="Wang R."/>
                <person name="Paul D."/>
                <person name="Tong L."/>
                <person name="Saha A.K."/>
                <person name="Westlin W.F."/>
                <person name="Kapeller R."/>
                <person name="Harwood H.J. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="26976583"/>
            <dbReference type="DOI" id="10.1073/pnas.1520686113"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 238-760 IN COMPLEX WITH INHIBITOR</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
                <person name="Kern S.E."/>
                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] LEU-193</scope>
    </reference>
    <comment type="function">
        <text evidence="2 14 18 19 20 21 22">Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (PubMed:16854592, PubMed:19236960, PubMed:19900410, PubMed:20457939, PubMed:20952656, PubMed:26976583). Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:19236960, PubMed:20457939, PubMed:20952656, PubMed:26976583). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14 18 19 20 21 22">
            <text>hydrogencarbonate + acetyl-CoA + ATP = malonyl-CoA + ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11308"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17544"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:57384"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="6.4.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19 22">
            <dbReference type="Rhea" id="RHEA:11309"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="14 15">
            <name>biotin</name>
            <dbReference type="ChEBI" id="CHEBI:57586"/>
        </cofactor>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="5 6">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="5 6">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="5 6">Binds 2 magnesium or manganese ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="13 14 19 20 29">Activity is increased by oligomerization of the protein into filaments (PubMed:19900410). The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-222 (PubMed:12488245). Inhibited by its product, malonyl-CoA (PubMed:16854592). Activated by citrate (PubMed:16854592). Activation by MID1IP1 is citrate-dependent (PubMed:20457939). Soraphen A, inhibits the enzyme by preventing the formation of active filamentous oligomers (Probable).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="14">120 uM for ATP</KM>
            <KM evidence="17">110 uM for ATP (isoform 2)</KM>
            <KM evidence="14">58 uM for acetyl-CoA</KM>
            <KM evidence="17">94 uM for acetyl-CoA (isoform 3)</KM>
            <KM evidence="17">6.5 mM for NaHCO3 (isoform 3)</KM>
            <KM evidence="14">3 mM for NaHCO(3)</KM>
        </kinetics>
        <phDependence>
            <text evidence="29">Optimum pH is 7.5.</text>
        </phDependence>
    </comment>
    <comment type="pathway">
        <text evidence="19 22">Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="16 19 20 21">Monomer, homodimer, and homotetramer (PubMed:18772397, PubMed:20952656). Forms filamentous polymers (PubMed:19900410, PubMed:20457939, PubMed:20952656). Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity in a citrate-dependent manner (PubMed:20457939, PubMed:20952656).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2211739">
            <id>O00763</id>
        </interactant>
        <interactant intactId="EBI-2211739">
            <id>O00763</id>
            <label>ACACB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2211739">
            <id>O00763</id>
        </interactant>
        <interactant intactId="EBI-3915568">
            <id>P50747</id>
            <label>HLCS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2211739">
            <id>O00763</id>
        </interactant>
        <interactant intactId="EBI-473024">
            <id>Q9CQ20</id>
            <label>Mid1ip1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O00763-1</id>
            <name>1</name>
            <name>Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O00763-2</id>
            <name>2</name>
            <name>Short</name>
            <sequence type="described" ref="VSP_000547"/>
        </isoform>
        <isoform>
            <id>O00763-3</id>
            <name evidence="27">3</name>
            <name evidence="25">ACC2.v2</name>
            <sequence type="described" ref="VSP_057081 VSP_057082"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="17 23">Widely expressed with highest levels in heart, skeletal muscle, liver, adipose tissue, mammary gland, adrenal gland and colon (PubMed:9099716). Isoform 3 is expressed in skeletal muscle, adipose tissue and liver (at protein level) (PubMed:19190759). Isoform 3 is detected at high levels in adipose tissue with lower levels in heart, liver, skeletal muscle and testis (PubMed:19190759).</text>
    </comment>
    <comment type="domain">
        <text evidence="28 30">Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (Probable). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (Probable).</text>
    </comment>
    <comment type="PTM">
        <text evidence="28">The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2 13">Phosphorylation at Ser-222 by AMPK inactivates the enzyme (PubMed:12488245). Required for the maintenance of skeletal muscle lipid and glucose homeostasis (By similarity).</text>
    </comment>
    <comment type="biotechnology">
        <text evidence="27">Inhibition of ACACB may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme a potential pharmaceutical target for treatment of obesity and type 2 diabetes.</text>
    </comment>
    <comment type="sequence caution" evidence="27">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAB58382" version="1"/>
        </conflict>
        <text>Many Frameshifts and conflicts.</text>
    </comment>
    <comment type="sequence caution" evidence="27">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="CAE01470" version="2"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <dbReference type="EC" id="6.4.1.2" evidence="14 18 19 20 21 22"/>
    <dbReference type="EMBL" id="U89344">
        <property type="protein sequence ID" value="AAB58382.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ493870">
        <property type="protein sequence ID" value="ABF48723.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ575431">
        <property type="protein sequence ID" value="CAE01470.2"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ575592">
        <property type="protein sequence ID" value="CAE01471.3"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY382667">
        <property type="protein sequence ID" value="AAR37018.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007637">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U34591">
        <property type="protein sequence ID" value="AAC50571.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31898.1">
        <molecule id="O00763-1"/>
    </dbReference>
    <dbReference type="PIR" id="S71091">
        <property type="entry name" value="S71091"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001084.3">
        <molecule id="O00763-1"/>
        <property type="nucleotide sequence ID" value="NM_001093.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399663.1">
        <molecule id="O00763-1"/>
        <property type="nucleotide sequence ID" value="NM_001412734.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399664.1">
        <molecule id="O00763-1"/>
        <property type="nucleotide sequence ID" value="NM_001412735.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399665.1">
        <molecule id="O00763-3"/>
        <property type="nucleotide sequence ID" value="NM_001412736.1"/>
    </dbReference>
    <dbReference type="PDB" id="2DN8">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=885-971"/>
    </dbReference>
    <dbReference type="PDB" id="2HJW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A=217-775"/>
    </dbReference>
    <dbReference type="PDB" id="2KCC">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=891-965"/>
    </dbReference>
    <dbReference type="PDB" id="3FF6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.19 A"/>
        <property type="chains" value="A/B/C/D=1693-2450"/>
    </dbReference>
    <dbReference type="PDB" id="3GID">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=238-760"/>
    </dbReference>
    <dbReference type="PDB" id="3GLK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=238-760"/>
    </dbReference>
    <dbReference type="PDB" id="3JRW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=217-775"/>
    </dbReference>
    <dbReference type="PDB" id="3JRX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A=217-775"/>
    </dbReference>
    <dbReference type="PDB" id="3TDC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.41 A"/>
        <property type="chains" value="A=1690-2445"/>
    </dbReference>
    <dbReference type="PDB" id="4HQ6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=217-776"/>
    </dbReference>
    <dbReference type="PDB" id="5KKN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="B/C=238-760"/>
    </dbReference>
    <dbReference type="PDBsum" id="2DN8"/>
    <dbReference type="PDBsum" id="2HJW"/>
    <dbReference type="PDBsum" id="2KCC"/>
    <dbReference type="PDBsum" id="3FF6"/>
    <dbReference type="PDBsum" id="3GID"/>
    <dbReference type="PDBsum" id="3GLK"/>
    <dbReference type="PDBsum" id="3JRW"/>
    <dbReference type="PDBsum" id="3JRX"/>
    <dbReference type="PDBsum" id="3TDC"/>
    <dbReference type="PDBsum" id="4HQ6"/>
    <dbReference type="PDBsum" id="5KKN"/>
    <dbReference type="AlphaFoldDB" id="O00763"/>
    <dbReference type="SMR" id="O00763"/>
    <dbReference type="BioGRID" id="106550">
        <property type="interactions" value="180"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-51617N"/>
    <dbReference type="FunCoup" id="O00763">
        <property type="interactions" value="2599"/>
    </dbReference>
    <dbReference type="IntAct" id="O00763">
        <property type="interactions" value="69"/>
    </dbReference>
    <dbReference type="MINT" id="O00763"/>
    <dbReference type="STRING" id="9606.ENSP00000341044"/>
    <dbReference type="BindingDB" id="O00763"/>
    <dbReference type="ChEMBL" id="CHEMBL4829"/>
    <dbReference type="DrugBank" id="DB03781">
        <property type="generic name" value="2-[4-(2,4-Dichlorophenoxy)Phenoxy]Propanoic Acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00173">
        <property type="generic name" value="Adenine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00121">
        <property type="generic name" value="Biotin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB07870">
        <property type="generic name" value="Haloxyfop-P"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00331">
        <property type="generic name" value="Metformin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12096">
        <property type="generic name" value="PF-05175157"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02859">
        <property type="generic name" value="Soraphen A"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1264"/>
    <dbReference type="SwissLipids" id="SLP:000000730"/>
    <dbReference type="GlyGen" id="O00763">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O00763"/>
    <dbReference type="PhosphoSitePlus" id="O00763"/>
    <dbReference type="BioMuta" id="ACACB"/>
    <dbReference type="jPOST" id="O00763"/>
    <dbReference type="MassIVE" id="O00763"/>
    <dbReference type="PaxDb" id="9606-ENSP00000341044"/>
    <dbReference type="PeptideAtlas" id="O00763"/>
    <dbReference type="ProteomicsDB" id="48022">
        <molecule id="O00763-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48023">
        <molecule id="O00763-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="1321">
        <property type="antibodies" value="163 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="32"/>
    <dbReference type="Ensembl" id="ENST00000338432.12">
        <molecule id="O00763-1"/>
        <property type="protein sequence ID" value="ENSP00000341044.7"/>
        <property type="gene ID" value="ENSG00000076555.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377848.7">
        <molecule id="O00763-1"/>
        <property type="protein sequence ID" value="ENSP00000367079.3"/>
        <property type="gene ID" value="ENSG00000076555.16"/>
    </dbReference>
    <dbReference type="GeneID" id="32"/>
    <dbReference type="KEGG" id="hsa:32"/>
    <dbReference type="MANE-Select" id="ENST00000338432.12">
        <property type="protein sequence ID" value="ENSP00000341044.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001093.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001084.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001tob.4">
        <molecule id="O00763-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:85"/>
    <dbReference type="ClinPGx" id="PA24422"/>
    <dbReference type="CTD" id="32"/>
    <dbReference type="DisGeNET" id="32"/>
    <dbReference type="GeneCards" id="ACACB"/>
    <dbReference type="HGNC" id="HGNC:85">
        <property type="gene designation" value="ACACB"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000076555">
        <property type="expression patterns" value="Tissue enhanced (adipose tissue, skeletal muscle)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACACB"/>
    <dbReference type="MIM" id="601557">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000076555"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000076555"/>
    <dbReference type="eggNOG" id="KOG0368">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155049"/>
    <dbReference type="HOGENOM" id="CLU_000395_5_0_1"/>
    <dbReference type="InParanoid" id="O00763"/>
    <dbReference type="OMA" id="TEHCKVA"/>
    <dbReference type="OrthoDB" id="14612at2759"/>
    <dbReference type="PAN-GO" id="O00763">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O00763"/>
    <dbReference type="BioCyc" id="MetaCyc:HS01211-MONOMER"/>
    <dbReference type="BRENDA" id="6.3.4.14">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="6.4.1.2">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O00763"/>
    <dbReference type="Reactome" id="R-HSA-163765">
        <property type="pathway name" value="ChREBP activates metabolic gene expression"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-196780">
        <property type="pathway name" value="Biotin transport and metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-200425">
        <property type="pathway name" value="Carnitine shuttle"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2426168">
        <property type="pathway name" value="Activation of gene expression by SREBF (SREBP)"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="O00763"/>
    <dbReference type="SignaLink" id="O00763"/>
    <dbReference type="SIGNOR" id="O00763"/>
    <dbReference type="UniPathway" id="UPA00655">
        <property type="reaction ID" value="UER00711"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000076555"/>
    <dbReference type="BioGRID-ORCS" id="32">
        <property type="hits" value="8 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACACB">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="O00763"/>
    <dbReference type="GeneWiki" id="ACACB"/>
    <dbReference type="GenomeRNAi" id="32"/>
    <dbReference type="Pharos" id="O00763">
        <property type="development level" value="Tchem"/>
    </dbReference>
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        <source>
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        <source>
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    <sequence length="2458" mass="276541" checksum="ED12674A1A8A0706" modified="2010-10-05" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-04-01" modified="2026-01-28" version="226" xmlns="https://uniprot.org/uniprot">
    <accession>P07108</accession>
    <accession>B8ZWD2</accession>
    <accession>B8ZWD6</accession>
    <accession>B8ZWD7</accession>
    <accession>P08869</accession>
    <accession>Q4VWZ6</accession>
    <accession>Q53SQ7</accession>
    <accession>Q6IB48</accession>
    <accession>Q9UCI8</accession>
    <name>ACBP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA-binding protein</fullName>
            <shortName>ACBP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Diazepam-binding inhibitor</fullName>
            <shortName>DBI</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Endozepine</fullName>
            <shortName>EP</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">DBI</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 4 AND 5)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <scope>ALTERNATIVE PROMOTER USAGE</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
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        <scope>ACETYLATION AT SER-2</scope>
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            <dbReference type="PubMed" id="19413330"/>
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        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>HYDROXYBUTYRYLATION AT LYS-55</scope>
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    <reference key="24">
        <citation type="journal article" date="2007" name="Proteins" volume="66" first="229" last="238">
            <title>High resolution crystal structures of unliganded and liganded human liver ACBP reveal a new mode of binding for the acyl-CoA ligand.</title>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ACYL-COENZYME A</scope>
    </reference>
    <comment type="function">
        <text>Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12847580">
            <id>P07108-2</id>
        </interactant>
        <interactant intactId="EBI-742054">
            <id>Q96D03</id>
            <label>DDIT4L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12847580">
            <id>P07108-2</id>
        </interactant>
        <interactant intactId="EBI-359873">
            <id>Q9UHV9</id>
            <label>PFDN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 6">Golgi apparatus</location>
        </subcellularLocation>
        <text evidence="5">Golgi localization is dependent on ligand binding (PubMed:17953517).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative promoter"/>
        <event type="alternative splicing"/>
        <isoform>
            <id>P07108-1</id>
            <name>1</name>
            <name>ACBP-1a</name>
            <name>Short</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P07108-2</id>
            <name>2</name>
            <name>ACBP-1b</name>
            <name>Long</name>
            <sequence type="described" ref="VSP_000068"/>
        </isoform>
        <isoform>
            <id>P07108-3</id>
            <name>3</name>
            <name>ACBP-1c</name>
            <sequence type="described" ref="VSP_038680"/>
        </isoform>
        <isoform>
            <id>P07108-4</id>
            <name>4</name>
            <name>ACBP-1a1-g</name>
            <sequence type="described" ref="VSP_043437"/>
        </isoform>
        <isoform>
            <id>P07108-5</id>
            <name>5</name>
            <name>ACBP-1g</name>
            <sequence type="described" ref="VSP_043438"/>
        </isoform>
        <isoform>
            <id>P07108-6</id>
            <name>6</name>
            <name>ACBP-1e</name>
            <sequence type="described" ref="VSP_044114"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 6">Isoform 1 is ubiquitous, with a moderate expression level. Isoform 2 is ubiquitous with high level in liver and adipose tissue. Isoform 3 is ubiquitous with strong expression in adipose tissue and heart.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 6</molecule>
        <text evidence="15">Predominantly expressed in adipose tissue and hippocampus.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ACBP family.</text>
    </comment>
    <dbReference type="EMBL" id="M14200">
        <property type="protein sequence ID" value="AAA52171.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="M15887">
        <property type="protein sequence ID" value="AAA35788.1"/>
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        <property type="protein sequence ID" value="CAR82405.1"/>
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        <property type="protein sequence ID" value="CAR82406.1"/>
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        <property type="RefSeq protein sequence ID" value="NP_001073331.1"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000155368"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000155368"/>
    <dbReference type="eggNOG" id="KOG0817">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000154846"/>
    <dbReference type="HOGENOM" id="CLU_118853_4_1_1"/>
    <dbReference type="InParanoid" id="P07108"/>
    <dbReference type="OMA" id="RYKFEAW"/>
    <dbReference type="OrthoDB" id="346910at2759"/>
    <dbReference type="PAN-GO" id="P07108">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P07108"/>
    <dbReference type="PathwayCommons" id="P07108"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P07108"/>
    <dbReference type="SIGNOR" id="P07108"/>
    <dbReference type="Agora" id="ENSG00000155368">
        <property type="nominated target" value="Agora Nominated Target for Alzheimer's Disease"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="1622">
        <property type="hits" value="16 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="DBI">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P07108"/>
    <dbReference type="GeneWiki" id="Diazepam_binding_inhibitor"/>
    <dbReference type="GenomeRNAi" id="1622"/>
    <dbReference type="Pharos" id="P07108">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P07108"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="P07108">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000155368">
        <property type="expression patterns" value="Expressed in mammalian vulva and 212 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P07108">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005788">
        <property type="term" value="C:endoplasmic reticulum lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0097038">
        <property type="term" value="C:perinuclear endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032994">
        <property type="term" value="C:protein-lipid complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030156">
        <property type="term" value="F:benzodiazepine receptor binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000062">
        <property type="term" value="F:fatty-acyl-CoA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036042">
        <property type="term" value="F:long-chain fatty acyl-CoA binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036151">
        <property type="term" value="P:phosphatidylcholine acyl-chain remodeling"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:2001140">
        <property type="term" value="P:positive regulation of phospholipid transport"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd00435">
        <property type="entry name" value="ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.80.10:FF:000010">
        <property type="entry name" value="Acyl-CoA-binding domain-containing protein 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.80.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR022408">
        <property type="entry name" value="Acyl-CoA-binding_prot_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000582">
        <property type="entry name" value="Acyl-CoA-binding_protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035984">
        <property type="entry name" value="Acyl-CoA-binding_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014352">
        <property type="entry name" value="FERM/acyl-CoA-bd_prot_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23310:SF54">
        <property type="entry name" value="ACYL-COA-BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23310">
        <property type="entry name" value="ACYL-COA-BINDING PROTEIN, ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00887">
        <property type="entry name" value="ACBP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00689">
        <property type="entry name" value="ACOABINDINGP"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47027">
        <property type="entry name" value="Acyl-CoA binding protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00880">
        <property type="entry name" value="ACB_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51228">
        <property type="entry name" value="ACB_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0877">Alternative promoter usage</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0379">Hydroxylation</keyword>
    <keyword id="KW-0446">Lipid-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="initiator methionine" description="Removed" evidence="9 17 20">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000214004" description="Acyl-CoA-binding protein">
        <location>
            <begin position="2"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="domain" description="ACB" evidence="2">
        <location>
            <begin position="2"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4 16">
        <location>
            <position position="14"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 16">
        <location>
            <begin position="29"/>
            <end position="33"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 16">
        <location>
            <position position="55"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 16">
        <location>
            <position position="74"/>
        </location>
        <ligand>
            <name>an acyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:58342"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylserine" evidence="9 17 20">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="18">
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="1">
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="1">
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="18">
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="19">
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-(2-hydroxyisobutyryl)lysine; alternate" evidence="8">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="18">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-malonyllysine; alternate" evidence="7">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="1">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="18">
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="1">
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000068" description="In isoform 2." evidence="10 12 14">
        <original>MSQ</original>
        <variation>MWGDLWLLPPASANPGTGTE</variation>
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_038680" description="In isoform 3." evidence="11">
        <original>MSQ</original>
        <variation>MPAF</variation>
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043437" description="In isoform 4." evidence="12">
        <original>MSQ</original>
        <variation>MSQHRAGRRGGVGKRGVRGRELGGQGKYGAGCSECGTRRIAARGE</variation>
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043438" description="In isoform 5." evidence="12">
        <original>MSQ</original>
        <variation>MERWGKGLHGLEERGDSVPIPKHRAGRRGGVGKRGVRGRELGGQGKYGAGCSECGTRRIAARGE</variation>
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044114" description="In isoform 6." evidence="13">
        <original>ERPGMLDFTGKAKWDAWNELKGTSKEDAMKAYINKVEELKKKYGI</original>
        <variation>GMQSGGWKGICSSKQAQQLRLEVPGNFTLKLPEALLFRWGMVMVPEVEKTMFRILSVSSSNRIQILVLEGLYWPSPAATLY</variation>
        <location>
            <begin position="43"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048160" description="In dbSNP:rs8192504.">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048161" description="In dbSNP:rs8192506.">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048162" description="In dbSNP:rs8192507.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="3"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="13"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="22"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="50"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="turn" evidence="21">
        <location>
            <begin position="61"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="67"/>
            <end position="85"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P31786"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00573"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="16055366"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="17044054"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17953517"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21698759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21908771"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="29192674"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="3525533"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="16055366"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="20345851"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="21698759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="3020548"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PDB" id="2CB8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="2CB8"/>
        </source>
    </evidence>
    <sequence length="87" mass="10044" checksum="B343A309F1B1AE28" modified="2007-01-23" version="2">MSQAEFEKAAEEVRHLKTKPSDEEMLFIYGHYKQATVGDINTERPGMLDFTGKAKWDAWNELKGTSKEDAMKAYINKVEELKKKYGI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-12-20" modified="2026-01-28" version="180" xmlns="https://uniprot.org/uniprot">
    <accession>O00400</accession>
    <accession>B2R5Q2</accession>
    <accession>D3DNK4</accession>
    <name>ACATN_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="12">Acetyl-coenzyme A transporter 1</fullName>
            <shortName evidence="11">AT-1</shortName>
            <shortName>Acetyl-CoA transporter 1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Solute carrier family 33 member 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">SLC33A1</name>
        <name type="synonym">ACATN</name>
        <name type="synonym">AT1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Proc. Natl. Acad. Sci. U.S.A." volume="94" first="2897" last="2902">
            <title>Expression cloning and characterization of a cDNA encoding a novel membrane protein required for the formation of O-acetylated gangliosides: a putative acetyl CoA transporter.</title>
            <authorList>
                <person name="Kanamori A."/>
                <person name="Nakayama J."/>
                <person name="Fukuda M.N."/>
                <person name="Stallcup W.B."/>
                <person name="Sasaki K."/>
                <person name="Fukuda M."/>
                <person name="Hirabayashi Y."/>
            </authorList>
            <dbReference type="PubMed" id="9096318"/>
            <dbReference type="DOI" id="10.1073/pnas.94.7.2897"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Melanoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Kidney</tissue>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] ALA-400</scope>
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        <scope>VARIANT SPG42 ARG-113</scope>
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        <scope>VARIANT HPBDS PRO-110</scope>
        <scope>CHARACTERIZATION OF VARIANT HPBDS PRO-110</scope>
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        <scope>ERRATUM OF PUBMED:22243965</scope>
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            <dbReference type="PubMed" id="24828632"/>
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        <scope>CHARACTERIZATION OF VARIANT SPG42 ARG-113</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="6 8 9 10">Acetyl-CoA transporter that mediates active acetyl-CoA import through the endoplasmic reticulum (ER) membrane into the ER lumen where specific ER-based acetyl-CoA:lysine acetyltransferases are responsible for the acetylation of ER-based protein substrates, such as BACE1 (PubMed:20826464, PubMed:24828632). Necessary for O-acetylation of gangliosides (PubMed:9096318).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8">
            <text>acetyl-CoA(in) = acetyl-CoA(out)</text>
            <dbReference type="Rhea" id="RHEA:75039"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6 8">
            <dbReference type="Rhea" id="RHEA:75040"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="8">Homodimerizes.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11135403">
            <id>O00400</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
            <label>CFTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 8">Endoplasmic reticulum membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Ubiquitous. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. With strongest signals in pancreas.</text>
    </comment>
    <comment type="induction">
        <text evidence="6">Expression is induced in presence of ceramide.</text>
    </comment>
    <comment type="disease" evidence="5 8 9">
        <disease id="DI-01042">
            <name>Spastic paraplegia 42, autosomal dominant</name>
            <acronym>SPG42</acronym>
            <description>A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.</description>
            <dbReference type="MIM" id="612539"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="7">
        <disease id="DI-03388">
            <name>Huppke-Brendel syndrome</name>
            <acronym>HPBDS</acronym>
            <description>An autosomal recessive disorder characterized by congenital cataracts, severe psychomotor retardation, and hearing loss associated with decreased serum ceruloplasmin and copper. Brain MRI shows cerebral and cerebellar atrophy and hypomyelination.</description>
            <dbReference type="MIM" id="614482"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the SLC33A transporter family.</text>
    </comment>
    <comment type="online information" name="Mendelian genes solute carrier family 33 (acetyl-CoA transporter), member 1 (SLC33A1)">
        <link uri="https://databases.lovd.nl/shared/genes/SLC33A1"/>
        <text>Leiden Open Variation Database (LOVD)</text>
    </comment>
    <dbReference type="EMBL" id="D88152">
        <property type="protein sequence ID" value="BAA20072.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312268">
        <property type="protein sequence ID" value="BAG35199.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW78743.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW78744.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014416">
        <property type="protein sequence ID" value="AAH14416.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3173.1"/>
    <dbReference type="RefSeq" id="NP_001177921.1">
        <property type="nucleotide sequence ID" value="NM_001190992.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004724.1">
        <property type="nucleotide sequence ID" value="NM_004733.4"/>
    </dbReference>
    <dbReference type="PDB" id="9M0S">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A=1-549"/>
    </dbReference>
    <dbReference type="PDBsum" id="9M0S"/>
    <dbReference type="AlphaFoldDB" id="O00400"/>
    <dbReference type="EMDB" id="EMD-63562"/>
    <dbReference type="SMR" id="O00400"/>
    <dbReference type="BioGRID" id="114632">
        <property type="interactions" value="261"/>
    </dbReference>
    <dbReference type="FunCoup" id="O00400">
        <property type="interactions" value="1206"/>
    </dbReference>
    <dbReference type="IntAct" id="O00400">
        <property type="interactions" value="147"/>
    </dbReference>
    <dbReference type="MINT" id="O00400"/>
    <dbReference type="STRING" id="9606.ENSP00000496241"/>
    <dbReference type="BindingDB" id="O00400"/>
    <dbReference type="ChEMBL" id="CHEMBL3638338"/>
    <dbReference type="TCDB" id="2.A.1.25.1">
        <property type="family name" value="the major facilitator superfamily (mfs)"/>
    </dbReference>
    <dbReference type="GlyConnect" id="2835">
        <property type="glycosylation" value="1 N-Linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O00400">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O00400">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O00400"/>
    <dbReference type="PhosphoSitePlus" id="O00400"/>
    <dbReference type="SwissPalm" id="O00400"/>
    <dbReference type="BioMuta" id="SLC33A1"/>
    <dbReference type="jPOST" id="O00400"/>
    <dbReference type="MassIVE" id="O00400"/>
    <dbReference type="PaxDb" id="9606-ENSP00000376587"/>
    <dbReference type="PeptideAtlas" id="O00400"/>
    <dbReference type="ProteomicsDB" id="47866"/>
    <dbReference type="Pumba" id="O00400"/>
    <dbReference type="Antibodypedia" id="33630">
        <property type="antibodies" value="165 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="9197"/>
    <dbReference type="Ensembl" id="ENST00000359479.7">
        <property type="protein sequence ID" value="ENSP00000352456.3"/>
        <property type="gene ID" value="ENSG00000169359.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000643144.2">
        <property type="protein sequence ID" value="ENSP00000496241.1"/>
        <property type="gene ID" value="ENSG00000169359.17"/>
    </dbReference>
    <dbReference type="GeneID" id="9197"/>
    <dbReference type="KEGG" id="hsa:9197"/>
    <dbReference type="MANE-Select" id="ENST00000643144.2">
        <property type="protein sequence ID" value="ENSP00000496241.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004733.4"/>
        <property type="RefSeq protein sequence ID" value="NP_004724.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003fan.6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:95"/>
    <dbReference type="ClinPGx" id="PA24432"/>
    <dbReference type="CTD" id="9197"/>
    <dbReference type="DisGeNET" id="9197"/>
    <dbReference type="GeneCards" id="SLC33A1"/>
    <dbReference type="GeneReviews" id="SLC33A1"/>
    <dbReference type="HGNC" id="HGNC:95">
        <property type="gene designation" value="SLC33A1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000169359">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="SLC33A1"/>
    <dbReference type="MIM" id="603690">
        <property type="type" value="gene"/>
    </dbReference>
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<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="233" xmlns="https://uniprot.org/uniprot">
    <accession>P49748</accession>
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            <fullName evidence="19">Very long-chain acyl-CoA dehydrogenase, mitochondrial</fullName>
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            <fullName>Long-chain acyl-CoA dehydrogenase, mitochondrial</fullName>
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        <name evidence="25" type="primary">ACADVL</name>
        <name evidence="19" type="synonym">VLCAD</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
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            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1995" name="Am. J. Hum. Genet." volume="57" first="273" last="283">
            <title>Cloning of human very-long-chain acyl-coenzyme A dehydrogenase and molecular characterization of its deficiency in two patients.</title>
            <authorList>
                <person name="Aoyama T."/>
                <person name="Souri M."/>
                <person name="Ueno I."/>
                <person name="Kamijo T."/>
                <person name="Yamaguchi S."/>
                <person name="Rhead W.J."/>
                <person name="Tanaka K."/>
                <person name="Hashimoto T."/>
            </authorList>
            <dbReference type="PubMed" id="7668252"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>INVOLVEMENT IN ACADVLD</scope>
        <scope>TRANSIT PEPTIDE</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="Hum. Mol. Genet." volume="5" first="461" last="472">
            <title>Cloning and characterization of human very-long-chain acyl-CoA dehydrogenase cDNA, chromosomal assignment of the gene and identification in four patients of nine different mutations within the VLCAD gene.</title>
            <authorList>
                <person name="Andresen B.S."/>
                <person name="Bross P."/>
                <person name="Vianey-Saban C."/>
                <person name="Divry P."/>
                <person name="Zabot M.-T."/>
                <person name="Roe C.R."/>
                <person name="Nada M.A."/>
                <person name="Byskov A."/>
                <person name="Kruse T.A."/>
                <person name="Neve S."/>
                <person name="Kristiansen K."/>
                <person name="Knudsen I."/>
                <person name="Corydon M.J."/>
                <person name="Gregersen N."/>
            </authorList>
            <dbReference type="PubMed" id="8845838"/>
            <dbReference type="DOI" id="10.1093/hmg/5.4.461"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANTS ACADVLD MET-260; ASP-281; ALA-283; ALA-317; CYS-366; GLU-381 DEL; ASP-441 AND ILE-602</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Biochem. Biophys. Res. Commun." volume="217" first="987" last="992">
            <title>Genomic DNA organization of human mitochondrial very-long-chain acyl-CoA dehydrogenase and mutation analysis.</title>
            <authorList>
                <person name="Orii K.O."/>
                <person name="Aoyama T."/>
                <person name="Souri M."/>
                <person name="Orii K.E."/>
                <person name="Kondo N."/>
                <person name="Orii T."/>
                <person name="Hashimoto T."/>
            </authorList>
            <dbReference type="PubMed" id="8554625"/>
            <dbReference type="DOI" id="10.1006/bbrc.1995.2867"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Peripheral blood</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
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            <dbReference type="DOI" id="10.1161/01.cir.99.10.1337"/>
        </citation>
        <scope>VARIANTS ACADVLD GLU-130 DEL; PRO-213; GLU-247; MET-260; LYS-278 DEL; ALA-283; ASP-441; LEU-458; PRO-490; LYS-534; TRP-613 AND GLN-615</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 8 11 13 14">Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:17564966, PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9599005, PubMed:9839948). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:18227065, PubMed:7668252, PubMed:9461620, PubMed:9839948). Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on fatty acyl-CoAs with saturated 12 to 24 carbons long primary chains (PubMed:17564966, PubMed:21237683, PubMed:9839948).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 7 8 11 13 14">
            <text>a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:17721"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83721"/>
            <dbReference type="ChEBI" id="CHEBI:83727"/>
            <dbReference type="EC" id="1.3.8.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:17722"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a very-long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a very-long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:19181"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83724"/>
            <dbReference type="ChEBI" id="CHEBI:83728"/>
            <dbReference type="EC" id="1.3.8.9"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:19182"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 14">
            <text>dodecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47296"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57330"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:47297"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 14">
            <text>tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47316"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:47317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 11 13 14">
            <text>oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:43449"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 7 14">
            <text>octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47240"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:71412"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:47241"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47236"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:47237"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>docosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-docosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47228"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65059"/>
            <dbReference type="ChEBI" id="CHEBI:74692"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:47229"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>tetracosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetracosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47232"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:74693"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:47233"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(9Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47304"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
            <dbReference type="ChEBI" id="CHEBI:77549"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47305"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>oxidized [electron-transfer flavoprotein] + (9Z)-octadecenoyl-CoA + H(+) = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47300"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77553"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="22">
            <dbReference type="Rhea" id="RHEA:47301"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:17721"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83721"/>
            <dbReference type="ChEBI" id="CHEBI:83727"/>
            <dbReference type="EC" id="1.3.8.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:17722"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47316"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:47317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:43449"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>(9Z)-hexadecenoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E,9Z)-hexadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47304"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
            <dbReference type="ChEBI" id="CHEBI:77549"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:47305"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>octadecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47240"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:71412"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:47241"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>oxidized [electron-transfer flavoprotein] + (9Z)-octadecenoyl-CoA + H(+) = (2E,9Z)-octadecadienoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47300"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:77553"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:47301"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="4">
            <text>eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47236"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:47237"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6 11">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="11">4.4 uM for hexadecanoyl-CoA</KM>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="8 13 14">Lipid metabolism; mitochondrial fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 6 11 13">Homodimer (PubMed:17374501, PubMed:18227065, PubMed:9461620, PubMed:9599005). Homodimerizes after import into the mitochondrion (PubMed:9599005).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-727618">
            <id>P49748</id>
        </interactant>
        <interactant intactId="EBI-1560239">
            <id>Q53T94</id>
            <label>TAF1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11 13">Mitochondrion inner membrane</location>
            <topology evidence="13">Peripheral membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="4">Mitochondrion inner membrane</location>
            <topology evidence="4">Peripheral membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P49748-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P49748-2</id>
            <name>2</name>
            <name evidence="18">DeltaEx3 VLCAD</name>
            <sequence type="described" ref="VSP_007734"/>
        </isoform>
        <isoform>
            <id>P49748-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046031"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 10">Predominantly expressed in heart and skeletal muscle (at both mRNA and protein levels) (PubMed:17564966, PubMed:8845838). Also detected in kidney and liver (at protein level) (PubMed:8845838).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">S-nitrosylation at Cys-237 in liver improves catalytic efficiency.</text>
    </comment>
    <comment type="disease" evidence="3 4 8 9 10 11 12 13 14 15">
        <disease id="DI-02411">
            <name>Acyl-CoA dehydrogenase very long-chain deficiency</name>
            <acronym>ACADVLD</acronym>
            <description>An inborn error of mitochondrial fatty acid beta-oxidation which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form characterized by early onset, high mortality and high incidence of cardiomyopathy; a milder childhood form with later onset, characterized by hypoketotic hypoglycemia, low mortality and rare cardiomyopathy; an adult form, with isolated skeletal muscle involvement, rhabdomyolysis and myoglobinuria, usually triggered by exercise or fasting.</description>
            <dbReference type="MIM" id="201475"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.9" evidence="7"/>
    <dbReference type="EC" id="1.3.8.8" evidence="4 7 8 11 13 14"/>
    <dbReference type="EMBL" id="D43682">
        <property type="protein sequence ID" value="BAA07781.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L46590">
        <property type="protein sequence ID" value="AAA79002.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X86556">
        <property type="protein sequence ID" value="CAA60253.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D78298">
        <property type="protein sequence ID" value="BAA29057.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293549">
        <property type="protein sequence ID" value="BAG57027.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC120057">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000399">
        <property type="protein sequence ID" value="AAH00399.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012912">
        <property type="protein sequence ID" value="AAH12912.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020218">
        <property type="protein sequence ID" value="AAH20218.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11090.1">
        <molecule id="P49748-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42249.1">
        <molecule id="P49748-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58509.1">
        <molecule id="P49748-3"/>
    </dbReference>
    <dbReference type="PIR" id="S54183">
        <property type="entry name" value="S54183"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000009.1">
        <molecule id="P49748-1"/>
        <property type="nucleotide sequence ID" value="NM_000018.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001029031.1">
        <molecule id="P49748-2"/>
        <property type="nucleotide sequence ID" value="NM_001033859.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001257376.1">
        <molecule id="P49748-3"/>
        <property type="nucleotide sequence ID" value="NM_001270447.2"/>
    </dbReference>
    <dbReference type="PDB" id="2UXW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.45 A"/>
        <property type="chains" value="A=72-655"/>
    </dbReference>
    <dbReference type="PDB" id="3B96">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.91 A"/>
        <property type="chains" value="A=69-655"/>
    </dbReference>
    <dbReference type="PDB" id="7S7G">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.34 A"/>
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        <location>
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    <feature type="binding site" evidence="6 26 27">
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            <begin position="461"/>
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        <ligand>
            <name>substrate</name>
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            <position position="562"/>
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        <ligand>
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        <location>
            <position position="51"/>
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        <location>
            <position position="639"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046031" description="In isoform 3." evidence="16">
        <original>MQAARMAASLGRQLLRLGGG</original>
        <variation>MLGGLAAAAGTRIMGKEIEAEAQRPLRQTWRPGQPPAMTAKTM</variation>
        <location>
            <begin position="1"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_007734" description="In isoform 2." evidence="17">
        <location>
            <begin position="47"/>
            <end position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029286" description="In dbSNP:rs2230179.">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000330" description="In ACADVLD; benign; dbSNP:rs2230178." evidence="15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048176" description="In dbSNP:rs28934585.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000331" description="In ACADVLD; dbSNP:rs387906251." evidence="3 9">
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000332" description="In ACADVLD." evidence="15">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="158"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000333" description="In ACADVLD; uncertain significance; dbSNP:rs746688190." evidence="15">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000334" description="In ACADVLD; dbSNP:rs369560930." evidence="15">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000335" description="In ACADVLD; likely pathogenic; dbSNP:rs545215807." evidence="15">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010101" description="In ACADVLD; likely pathogenic; dbSNP:rs140629318." evidence="3">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000336" description="In ACADVLD; likely pathogenic; dbSNP:rs1432183079." evidence="15">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="218"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000337" description="In ACADVLD." evidence="15">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010102" description="In ACADVLD; dbSNP:rs387906253." evidence="3">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000338" description="In ACADVLD." evidence="15">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000339" description="In ACADVLD; likely pathogenic; dbSNP:rs113994168." evidence="3 10 15">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000340" description="In ACADVLD." evidence="3 15">
        <location>
            <position position="278"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000341" description="In ACADVLD." evidence="10 15">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000342" description="In ACADVLD; pathogenic; dbSNP:rs113994167." evidence="3 10 15">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="283"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000343" description="In ACADVLD; dbSNP:rs866464446." evidence="15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000344" description="In ACADVLD; uncertain significance; dbSNP:rs200573371." evidence="15">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000345" description="In ACADVLD; dbSNP:rs774716484." evidence="15">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000346" description="In ACADVLD." evidence="9">
        <location>
            <position position="299"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000347" description="In ACADVLD; dbSNP:rs398123095." evidence="10 15">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="317"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000348" description="In ACADVLD; dbSNP:rs2071296420." evidence="15">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="352"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011990" description="In dbSNP:rs1051701.">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000349" description="In ACADVLD; dbSNP:rs771874163." evidence="10 15">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="366"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000350" description="In ACADVLD; likely pathogenic; dbSNP:rs112406105." evidence="15">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="366"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000351" description="In ACADVLD; dbSNP:rs1057517281." evidence="10 15">
        <location>
            <position position="381"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000352" description="In ACADVLD; likely pathogenic; dbSNP:rs118204015." evidence="9">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="382"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000353" description="In ACADVLD." evidence="15">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="405"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000354" description="In ACADVLD; likely pathogenic; dbSNP:rs2309689." evidence="3 10 15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="441"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000355" description="In ACADVLD; likely pathogenic; dbSNP:rs118204016." evidence="12 15">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="450"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000356" description="In ACADVLD; likely pathogenic; dbSNP:rs138058572." evidence="15">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="453"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000357" description="In ACADVLD; dbSNP:rs1419606204." evidence="15">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="454"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000358" description="In ACADVLD; likely pathogenic; dbSNP:rs794727112." evidence="15">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="456"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010103" description="In ACADVLD; likely pathogenic; loss of acyl-CoA dehydrogenase activity; Loss of FAD cofactor-binding; dbSNP:rs118204017." evidence="3 11">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="458"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000359" description="In ACADVLD; dbSNP:rs766742117." evidence="15">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="459"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000360" description="In ACADVLD; dbSNP:rs200366828." evidence="15">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="463"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000361" description="In ACADVLD; likely pathogenic; dbSNP:rs398123083." evidence="15">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="469"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000362" description="In ACADVLD; likely pathogenic; dbSNP:rs113994170." evidence="15">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="469"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010104" description="In ACADVLD; likely pathogenic; decreased association with mitochondrial inner membrane; may affect substrate specificity, possibly reducing the affinity for long-chain acyl-CoA substrates; dbSNP:rs759775666." evidence="3 4 14">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="490"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000363" description="In ACADVLD; decreased association with mitochondrial inner membrane; decreased specific activity towards several substrates in vitro." evidence="4 15">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="502"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010105" description="In ACADVLD; uncertain significance; dbSNP:rs2230180." evidence="3">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="534"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083892" description="In ACADVLD; Loss of homodimerization; loss of localization to mitochondrial inner membrane; dbSNP:rs1085307648." evidence="13">
        <original>S</original>
        <variation>W</variation>
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000364" description="In ACADVLD." evidence="10 15">
        <original>L</original>
        <variation>I</variation>
        <location>
            <position position="602"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000365" description="In ACADVLD; likely pathogenic; dbSNP:rs118204014." evidence="3 9 15">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="613"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010106" description="In ACADVLD; likely benign; dbSNP:rs148584617." evidence="3">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="615"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011991" description="In dbSNP:rs13383.">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="623"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased acyl-CoA dehydrogenase activity. Decreased affinity for acyl-CoA. No effect on FAD cofactor-binding." evidence="11">
        <original>F</original>
        <variation>T</variation>
        <location>
            <position position="458"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of acyl-CoA dehydrogenase activity. Loss of FAD cofactor-binding." evidence="11">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="458"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased acyl-CoA dehydrogenase activity. No effect on affinity for acyl-CoA. Decreased FAD cofactor-binding." evidence="11">
        <original>F</original>
        <variation>Y</variation>
        <location>
            <position position="458"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased acyl-CoA dehydrogenase activity. No effect on affinity for acyl-CoA. No effect on FAD cofactor-binding." evidence="11">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="462"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of acyl-CoA dehydrogenase activity. No effect on FAD cofactor-binding." evidence="11">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="462"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Changed substrate specificity with decreased affinity for tetradecanoyl-CoA and hexadecanoyl-CoA." evidence="14">
        <original>A</original>
        <variation>G</variation>
        <variation>V</variation>
        <variation>S</variation>
        <variation>D</variation>
        <variation>H</variation>
        <location>
            <position position="490"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAA29057." evidence="20" ref="3">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAG57027." evidence="20" ref="4">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAG57027." evidence="20" ref="4">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="541"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="73"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="turn" evidence="31">
        <location>
            <begin position="85"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="96"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="119"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="130"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="turn" evidence="31">
        <location>
            <begin position="139"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="148"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="157"/>
            <end position="170"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="172"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="turn" evidence="31">
        <location>
            <begin position="183"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="187"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="195"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="strand" evidence="31">
        <location>
            <begin position="212"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="strand" evidence="31">
        <location>
            <begin position="221"/>
            <end position="223"/>
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    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="225"/>
            <end position="227"/>
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    </feature>
    <feature type="strand" evidence="31">
        <location>
            <begin position="231"/>
            <end position="234"/>
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    <feature type="strand" evidence="31">
        <location>
            <begin position="238"/>
            <end position="251"/>
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            <end position="255"/>
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    <feature type="strand" evidence="31">
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    <feature type="strand" evidence="31">
        <location>
            <begin position="275"/>
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        <location>
            <begin position="286"/>
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        <location>
            <begin position="289"/>
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        <location>
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        <location>
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        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="17374501"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="22">
        <source>
            <dbReference type="PubMed" id="17564966"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="23">
        <source>
            <dbReference type="PubMed" id="18227065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="24">
        <source>
            <dbReference type="PubMed" id="21237683"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="25">
        <source>
            <dbReference type="HGNC" id="HGNC:92"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="2UXW"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PDB" id="3B96"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="31">
        <source>
            <dbReference type="PDB" id="7S7G"/>
        </source>
    </evidence>
    <sequence length="655" mass="70390" checksum="A5594D1EA7911D19" modified="1996-10-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-07-01" modified="2026-01-28" version="248" xmlns="https://uniprot.org/uniprot">
    <accession>P11310</accession>
    <accession>Q5T4U4</accession>
    <accession>Q9NYF1</accession>
    <name>ACADM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="36">Medium-chain specific acyl-CoA dehydrogenase, mitochondrial</fullName>
            <shortName evidence="31">MCAD</shortName>
            <ecNumber evidence="16 17 26">1.3.8.7</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="32">Medium chain acyl-CoA dehydrogenase</fullName>
            <shortName evidence="32">MCADH</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="39" type="primary">ACADM</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Hoffmann G.F."/>
                <person name="Penzien J."/>
                <person name="Ruiter J.P.N."/>
                <person name="Wanders R.J.A."/>
                <person name="Mayatepek E."/>
            </authorList>
            <dbReference type="PubMed" id="11409868"/>
            <dbReference type="DOI" id="10.1007/s004390100501"/>
        </citation>
        <scope>VARIANT ACADMD LEU-245</scope>
    </reference>
    <reference key="39">
        <citation type="journal article" date="2001" name="J. Inherit. Metab. Dis." volume="24" first="417" last="418">
            <title>Compound heterozygosity in four asymptomatic siblings with medium-chain acyl-CoA dehydrogenase deficiency.</title>
            <authorList>
                <person name="Albers S."/>
                <person name="Levy H.L."/>
                <person name="Irons M."/>
                <person name="Strauss A.W."/>
                <person name="Marsden D."/>
            </authorList>
            <dbReference type="PubMed" id="11486912"/>
            <dbReference type="DOI" id="10.1023/a:1010533408635"/>
        </citation>
        <scope>VARIANTS ACADMD THR-281 AND GLU-329</scope>
    </reference>
    <reference key="40">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] ARG-132</scope>
    </reference>
    <comment type="function">
        <text evidence="8 16 17 18 22 26">Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175). The first step of FAO consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:2251268). ETF is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (PubMed:15159392, PubMed:25416781). Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase has preference for fatty acyl-CoAs with saturated 6 to 12 carbons long primary chains, making it but can also catalyze longer chains such as C14 and C16 (PubMed:1970566, PubMed:21237683, PubMed:2251268, PubMed:8823175).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16 17 26">
            <text>a medium-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a medium-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:14477"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83723"/>
            <dbReference type="ChEBI" id="CHEBI:83726"/>
            <dbReference type="EC" id="1.3.8.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="35">
            <dbReference type="Rhea" id="RHEA:14478"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>pentanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-pentenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43456"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57389"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:86160"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:43457"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="17 26">
            <text>hexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43464"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62077"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:43465"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="16 17 26">
            <text>octanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-octenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48180"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62242"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="35">
            <dbReference type="Rhea" id="RHEA:48181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="17 26">
            <text>decanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-decenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48176"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61406"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:48177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="17 26">
            <text>dodecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-dodecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47296"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57330"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:47297"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="17 26">
            <text>tetradecanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetradecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47316"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:47317"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="17 26">
            <text>oxidized [electron-transfer flavoprotein] + hexadecanoyl-CoA + H(+) = (2E)-hexadecenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43448"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="37">
            <dbReference type="Rhea" id="RHEA:43449"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8 9 27 30">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="26">175 uM for butyryl-CoA</KM>
            <KM evidence="26">15 uM for hexanoyl-CoA</KM>
            <KM evidence="26">3.4 uM for octanoyl-CoA</KM>
            <KM evidence="26">2.5 uM for decanoyl-CoA</KM>
            <KM evidence="26">2.5 uM for dodecanoyl-CoA</KM>
            <KM evidence="26">2.3 uM for tetradecanoyl-CoA</KM>
            <KM evidence="26">1.6 uM for hexadecanoyl-CoA</KM>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="18">Lipid metabolism; mitochondrial fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 9 27 30">Homotetramer (PubMed:8823176, Ref.24). Interacts with the heterodimeric electron transfer flavoprotein ETF.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-44440161">
            <id>PRO_0000000502</id>
        </interactant>
        <interactant intactId="EBI-44440161">
            <id>PRO_0000000502</id>
            <label>ACADM</label>
            <dbReference type="UniProtKB" id="P11310"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P11310-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P11310-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_038420"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14">Expressed ubiquitously with highest levels in heart and muscle.</text>
    </comment>
    <comment type="PTM">
        <text evidence="21">Acetylated. Could occur at proximity of the cofactor-binding sites and reduce the catalytic activity. Could be deacetylated by SIRT3.</text>
    </comment>
    <comment type="disease" evidence="3 4 5 6 7 11 12 15 18 19 20 23 24 25 28 29">
        <disease id="DI-01956">
            <name>Acyl-CoA dehydrogenase medium-chain deficiency</name>
            <acronym>ACADMD</acronym>
            <description>An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy.</description>
            <dbReference type="MIM" id="201450"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="34">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.7" evidence="16 17 26"/>
    <dbReference type="EMBL" id="M16827">
        <property type="protein sequence ID" value="AAA51566.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91432">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91421">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91422">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91423">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91425">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91426">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91427">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91428">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91429">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91430">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M91431">
        <property type="protein sequence ID" value="AAA59567.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF251043">
        <property type="protein sequence ID" value="AAF63626.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312629">
        <property type="protein sequence ID" value="BAG35514.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL357314">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471059">
        <property type="protein sequence ID" value="EAX06401.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC005377">
        <property type="protein sequence ID" value="AAH05377.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M60505">
        <property type="protein sequence ID" value="AAB59625.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44165.1">
        <molecule id="P11310-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS668.1">
        <molecule id="P11310-1"/>
    </dbReference>
    <dbReference type="PIR" id="A29031">
        <property type="entry name" value="DEHUCM"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000007.1">
        <molecule id="P11310-1"/>
        <property type="nucleotide sequence ID" value="NM_000016.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001120800.1">
        <molecule id="P11310-2"/>
        <property type="nucleotide sequence ID" value="NM_001127328.3"/>
    </dbReference>
    <dbReference type="PDB" id="1EGC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C/D=26-421"/>
    </dbReference>
    <dbReference type="PDB" id="1EGD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C/D=26-421"/>
    </dbReference>
    <dbReference type="PDB" id="1EGE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.75 A"/>
        <property type="chains" value="A/B/C/D=26-421"/>
    </dbReference>
    <dbReference type="PDB" id="1T9G">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B/C/D=26-421"/>
    </dbReference>
    <dbReference type="PDB" id="2A1T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-421"/>
    </dbReference>
    <dbReference type="PDB" id="4P13">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.73 A"/>
        <property type="chains" value="A/B/C/D=35-421"/>
    </dbReference>
    <dbReference type="PDB" id="8SGP">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.69 A"/>
        <property type="chains" value="A/B/C/D=1-421"/>
    </dbReference>
    <dbReference type="PDBsum" id="1EGC"/>
    <dbReference type="PDBsum" id="1EGD"/>
    <dbReference type="PDBsum" id="1EGE"/>
    <dbReference type="PDBsum" id="1T9G"/>
    <dbReference type="PDBsum" id="2A1T"/>
    <dbReference type="PDBsum" id="4P13"/>
    <dbReference type="PDBsum" id="8SGP"/>
    <dbReference type="AlphaFoldDB" id="P11310"/>
    <dbReference type="EMDB" id="EMD-40463"/>
    <dbReference type="SMR" id="P11310"/>
    <dbReference type="BioGRID" id="106552">
        <property type="interactions" value="148"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-34281N"/>
    <dbReference type="FunCoup" id="P11310">
        <property type="interactions" value="1145"/>
    </dbReference>
    <dbReference type="IntAct" id="P11310">
        <property type="interactions" value="53"/>
    </dbReference>
    <dbReference type="MINT" id="P11310"/>
    <dbReference type="STRING" id="9606.ENSP00000359871"/>
    <dbReference type="ChEMBL" id="CHEMBL4295713"/>
    <dbReference type="DrugBank" id="DB03415">
        <property type="generic name" value="3-thiaoctanoyl-CoA"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03147">
        <property type="generic name" value="Flavin adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02910">
        <property type="generic name" value="Octanoyl-Coenzyme A"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000001334"/>
    <dbReference type="GlyGen" id="P11310">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P11310"/>
    <dbReference type="PhosphoSitePlus" id="P11310"/>
    <dbReference type="SwissPalm" id="P11310"/>
    <dbReference type="BioMuta" id="ACADM"/>
    <dbReference type="DMDM" id="113017"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00005040"/>
    <dbReference type="jPOST" id="P11310"/>
    <dbReference type="MassIVE" id="P11310"/>
    <dbReference type="PaxDb" id="9606-ENSP00000359871"/>
    <dbReference type="PeptideAtlas" id="P11310"/>
    <dbReference type="ProteomicsDB" id="52743">
        <molecule id="P11310-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="52744">
        <molecule id="P11310-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P11310"/>
    <dbReference type="Antibodypedia" id="1642">
        <property type="antibodies" value="470 antibodies from 39 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="34"/>
    <dbReference type="Ensembl" id="ENST00000370841.9">
        <molecule id="P11310-1"/>
        <property type="protein sequence ID" value="ENSP00000359878.5"/>
        <property type="gene ID" value="ENSG00000117054.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000420607.6">
        <molecule id="P11310-2"/>
        <property type="protein sequence ID" value="ENSP00000409612.2"/>
        <property type="gene ID" value="ENSG00000117054.16"/>
    </dbReference>
    <dbReference type="GeneID" id="34"/>
    <dbReference type="KEGG" id="hsa:34"/>
    <dbReference type="MANE-Select" id="ENST00000370841.9">
        <property type="protein sequence ID" value="ENSP00000359878.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000016.6"/>
        <property type="RefSeq protein sequence ID" value="NP_000007.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001dgw.6">
        <molecule id="P11310-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:89"/>
    <dbReference type="ClinPGx" id="PA24425"/>
    <dbReference type="CTD" id="34"/>
    <dbReference type="DisGeNET" id="34"/>
    <dbReference type="GeneCards" id="ACADM"/>
    <dbReference type="GeneReviews" id="ACADM"/>
    <dbReference type="HGNC" id="HGNC:89">
        <property type="gene designation" value="ACADM"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000117054">
        <property type="expression patterns" value="Tissue enhanced (liver, skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACADM"/>
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        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000117054"/>
    <dbReference type="Orphanet" id="42">
        <property type="disease" value="Medium chain acyl-CoA dehydrogenase deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000117054"/>
    <dbReference type="eggNOG" id="KOG0140">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158429"/>
    <dbReference type="InParanoid" id="P11310"/>
    <dbReference type="OMA" id="NYDKMGV"/>
    <dbReference type="OrthoDB" id="434771at2759"/>
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        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
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    <dbReference type="BioCyc" id="MetaCyc:HS04089-MONOMER"/>
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        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P11310"/>
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        <property type="pathway name" value="PPARA activates gene expression"/>
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        <property type="pathway name" value="mitochondrial fatty acid beta-oxidation of unsaturated fatty acids"/>
    </dbReference>
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        <property type="pathway name" value="Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA"/>
    </dbReference>
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        <property type="pathway name" value="Beta oxidation of octanoyl-CoA to hexanoyl-CoA"/>
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        <property type="hits" value="15 hits in 1160 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACADM">
        <property type="organism name" value="human"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 1"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in jejunal mucosa and 206 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="GO_Central"/>
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        <property type="term" value="F:flavin adenine dinucleotide binding"/>
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        <property type="project" value="InterPro"/>
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        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="P:cardiac muscle cell differentiation"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:carnitine biosynthetic process"/>
        <property type="evidence" value="ECO:0000315"/>
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    <dbReference type="GO" id="GO:0019254">
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        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0006635">
        <property type="term" value="P:fatty acid beta-oxidation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0033539">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA dehydrogenase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005978">
        <property type="term" value="P:glycogen biosynthetic process"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0001889">
        <property type="term" value="P:liver development"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0051793">
        <property type="term" value="P:medium-chain fatty acid catabolic process"/>
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    <dbReference type="GO" id="GO:0051791">
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        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0009791">
        <property type="term" value="P:post-embryonic development"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0006111">
        <property type="term" value="P:regulation of gluconeogenesis"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:response to cold"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0042594">
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        <property type="project" value="Ensembl"/>
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    <dbReference type="CDD" id="cd01157">
        <property type="entry name" value="MCAD"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.540.10:FF:000010">
        <property type="entry name" value="Medium-chain specific acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000011">
        <property type="entry name" value="Medium-chain specific acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.40.110.10:FF:000007">
        <property type="entry name" value="Medium-chain specific acyl-CoA dehydrogenase, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050741">
        <property type="entry name" value="Acyl-CoA_dehydrogenase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006089">
        <property type="entry name" value="Acyl-CoA_DH_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034180">
        <property type="entry name" value="MCAD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083:SF2">
        <property type="entry name" value="MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083">
        <property type="entry name" value="MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016578">
        <property type="entry name" value="HsaA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00072">
        <property type="entry name" value="ACYL_COA_DH_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00073">
        <property type="entry name" value="ACYL_COA_DH_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="38">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000502" description="Medium-chain specific acyl-CoA dehydrogenase, mitochondrial">
        <location>
            <begin position="26"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="16 27">
        <location>
            <position position="401"/>
        </location>
    </feature>
    <feature type="binding site" description="in other chain" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="158"/>
            <end position="167"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27 40">
        <location>
            <position position="167"/>
        </location>
        <ligand>
            <name>octanoyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="191"/>
            <end position="193"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27 40">
        <location>
            <position position="278"/>
        </location>
        <ligand>
            <name>octanoyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27 40">
        <location>
            <position position="281"/>
        </location>
        <ligand>
            <name>octanoyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="306"/>
            <end position="308"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="316"/>
            <end position="317"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="374"/>
            <end position="378"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="8 9 27 30 40 41 42 43 44 45">
        <location>
            <begin position="401"/>
            <end position="405"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27 40">
        <location>
            <position position="401"/>
        </location>
        <ligand>
            <name>octanoyl-CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="46">
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="46">
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="2">
        <location>
            <position position="351"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_038420" description="In isoform 2." evidence="33">
        <original>R</original>
        <variation>RCSLQ</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000317" description="In ACADMD; dbSNP:rs398123072." evidence="7">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013698" description="In ACADMD; mild; dbSNP:rs121434280." evidence="4">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015954" description="In ACADMD; dbSNP:rs398123074." evidence="4">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000318" description="In ACADMD." evidence="23">
        <location>
            <begin position="115"/>
            <end position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015955" description="In ACADMD; dbSNP:rs875989859." evidence="28">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015956" description="In ACADMD; dbSNP:rs121434283." evidence="4">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035716" description="In a breast cancer sample; somatic mutation; dbSNP:rs875989854." evidence="13">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000319" description="In ACADMD; dbSNP:rs121434277." evidence="12">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000320" description="In ACADMD; the thermostability is markedly decreased; dbSNP:rs121434279." evidence="28 29">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000321" description="In ACADMD; dbSNP:rs121434278." evidence="24">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="195"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015957" description="In ACADMD; dbSNP:rs200724875." evidence="3">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000322" description="In ACADMD; dbSNP:rs121434276." evidence="12">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="244"/>
        </location>
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<entry dataset="Swiss-Prot" created="1998-07-15" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>Q15027</accession>
    <accession>Q53XN9</accession>
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            <fullName>Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1</fullName>
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        <name type="synonym">CENTB1</name>
        <name type="synonym">KIAA0050</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="223" last="229">
            <title>Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.</title>
            <authorList>
                <person name="Nomura N."/>
                <person name="Nagase T."/>
                <person name="Miyajima N."/>
                <person name="Sazuka T."/>
                <person name="Tanaka A."/>
                <person name="Sato S."/>
                <person name="Seki N."/>
                <person name="Kawarabayasi Y."/>
                <person name="Ishikawa K."/>
                <person name="Tabata S."/>
            </authorList>
            <dbReference type="PubMed" id="7584044"/>
            <dbReference type="DOI" id="10.1093/dnares/1.5.223"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-08" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
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            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lymph</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2000" name="J. Cell Biol." volume="151" first="627" last="638">
            <title>ACAPs are arf6 GTPase-activating proteins that function in the cell periphery.</title>
            <authorList>
                <person name="Jackson T.R."/>
                <person name="Brown F.D."/>
                <person name="Nie Z."/>
                <person name="Miura K."/>
                <person name="Foroni L."/>
                <person name="Sun J."/>
                <person name="Hsu V.W."/>
                <person name="Donaldson J.G."/>
                <person name="Randazzo P.A."/>
            </authorList>
            <dbReference type="PubMed" id="11062263"/>
            <dbReference type="DOI" id="10.1083/jcb.151.3.627"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF ARG-448</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2005" name="Dev. Cell" volume="9" first="663" last="673">
            <title>Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration.</title>
            <authorList>
                <person name="Li J."/>
                <person name="Ballif B.A."/>
                <person name="Powelka A.M."/>
                <person name="Dai J."/>
                <person name="Gygi S.P."/>
                <person name="Hsu V.W."/>
            </authorList>
            <dbReference type="PubMed" id="16256741"/>
            <dbReference type="DOI" id="10.1016/j.devcel.2005.09.012"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT SER-554</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH ITGB1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF SER-14; SER-29; SER-277; THR-289; SER-358; THR-389; THR-461; SER-554; SER-568; THR-711; TYR-712 AND SER-724</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Anal. Biochem." volume="354" first="279" last="289">
            <title>Nitroproteins from a human pituitary adenoma tissue discovered with a nitrotyrosine affinity column and tandem mass spectrometry.</title>
            <authorList>
                <person name="Zhan X."/>
                <person name="Desiderio D.M."/>
            </authorList>
            <dbReference type="PubMed" id="16777052"/>
            <dbReference type="DOI" id="10.1016/j.ab.2006.05.024"/>
        </citation>
        <scope>NITRATION [LARGE SCALE ANALYSIS] AT TYR-485</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Pituitary adenoma</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Traffic" volume="7" first="1539" last="1550">
            <title>Cooperation of phosphoinositides and BAR domain proteins in endosomal tubulation.</title>
            <authorList>
                <person name="Shinozaki-Narikawa N."/>
                <person name="Kodama T."/>
                <person name="Shibasaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="17010122"/>
            <dbReference type="DOI" id="10.1111/j.1600-0854.2006.00480.x"/>
        </citation>
        <scope>INTERACTION WITH PHOSPHOLIPIDS</scope>
        <scope>MUTAGENESIS OF LYS-274</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2007" name="Curr. Biol." volume="17" first="722" last="727">
            <title>Regulation of Arf6 and ACAP1 signaling by the PTB-domain-containing adaptor protein GULP.</title>
            <authorList>
                <person name="Ma Z."/>
                <person name="Nie Z."/>
                <person name="Luo R."/>
                <person name="Casanova J.E."/>
                <person name="Ravichandran K.S."/>
            </authorList>
            <dbReference type="PubMed" id="17398097"/>
            <dbReference type="DOI" id="10.1016/j.cub.2007.03.014"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH GULP AND ARF6</scope>
        <scope>MUTAGENESIS OF ARG-448</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2007" name="J. Cell Biol." volume="178" first="453" last="464">
            <title>An ACAP1-containing clathrin coat complex for endocytic recycling.</title>
            <authorList>
                <person name="Li J."/>
                <person name="Peters P.J."/>
                <person name="Bai M."/>
                <person name="Dai J."/>
                <person name="Bos E."/>
                <person name="Kirchhausen T."/>
                <person name="Kandror K.V."/>
                <person name="Hsu V.W."/>
            </authorList>
            <dbReference type="PubMed" id="17664335"/>
            <dbReference type="DOI" id="10.1083/jcb.200608033"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH CLTC</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2012" name="J. Biol. Chem." volume="287" first="28675" last="28685">
            <title>Mechanistic insights into regulated cargo binding by ACAP1 protein.</title>
            <authorList>
                <person name="Bai M."/>
                <person name="Pang X."/>
                <person name="Lou J."/>
                <person name="Zhou Q."/>
                <person name="Zhang K."/>
                <person name="Ma J."/>
                <person name="Li J."/>
                <person name="Sun F."/>
                <person name="Hsu V.W."/>
            </authorList>
            <dbReference type="PubMed" id="22645133"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.378810"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 378-740 WILD TYPE AND MUTANT ASP-554 IN COMPLEX WITH ITGB1 PEPTIDE AND ZINC IONS</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ITGB1</scope>
        <scope>MUTAGENESIS OF SER-554</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="Dev. Cell" volume="31" first="73" last="86">
            <title>A PH domain in ACAP1 possesses key features of the BAR domain in promoting membrane curvature.</title>
            <authorList>
                <person name="Pang X."/>
                <person name="Fan J."/>
                <person name="Zhang Y."/>
                <person name="Zhang K."/>
                <person name="Gao B."/>
                <person name="Ma J."/>
                <person name="Li J."/>
                <person name="Deng Y."/>
                <person name="Zhou Q."/>
                <person name="Egelman E.H."/>
                <person name="Hsu V.W."/>
                <person name="Sun F."/>
            </authorList>
            <dbReference type="PubMed" id="25284369"/>
            <dbReference type="DOI" id="10.1016/j.devcel.2014.08.020"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-377</scope>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (12.0 ANGSTROMS) OF 1-377</scope>
        <scope>SUBUNIT</scope>
        <scope>BAR DOMAIN</scope>
        <scope>PH DOMAIN</scope>
        <scope>MUTAGENESIS OF PHE-280</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] ARG-114 AND GLN-129</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 8 9 10">GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 7 8 9 10 11">Banana-shaped homodimer laterally assembling into tetramers, the tetramers further pack helically onto the membrane. Interacts with GTP-bound ARF6. Interacts with third cytoplasmic loop of SLC2A4/GLUT4. Interacts with CLTC. Interacts with GULP1. Forms a complex with GDP-bound ARF6 and GULP1. Interacts with ITGB1; required for ITGB1 recycling.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-11958845">
            <id>O94868-3</id>
            <label>FCHSD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-399080">
            <id>Q92993</id>
            <label>KAT5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-11742507">
            <id>Q8TAP4-4</id>
            <label>LMO3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-2880203">
            <id>O76041</id>
            <label>NEBL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-1383528">
            <id>P17252</id>
            <label>PRKCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-9090795">
            <id>Q15047-2</id>
            <label>SETDB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-743128">
            <id>P14927</id>
            <label>UQCRB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-1051424">
            <id>P22695</id>
            <label>UQCRC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-751746">
            <id>Q15027</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Recycling endosome membrane</location>
            <topology evidence="5">Peripheral membrane protein</topology>
            <orientation evidence="5">Cytoplasmic side</orientation>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Highest level in lung and spleen. Low level in heart, kidney, liver and pancreas.</text>
    </comment>
    <comment type="domain">
        <text evidence="11">PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate ACAP1-binding to PIP2 or PIP3 containing membranes. Only one PH domain of one ACAP1 dimer inserts into the membrane, while the other PH domain acts primaryly to interact with adjacent ACAP1 dimers.</text>
    </comment>
    <comment type="domain">
        <text evidence="11">The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5">Phosphorylation at Ser-554 by PKB is required for interaction with ITGB1, export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Cells overexpressing ACAP1 show an accumulation of ITGB1 in recycling endosomes and inhibition of stimulation-dependent cell migration. Cells with reduced levels of ACAP1 or AKT1 and AKT2 show inhibition of stimulation-dependent cell migration. Cells overexpressing ACAP1 and PIP5K1C show formation of tubular structures derived from endosomal membranes.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA06418" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="D30758">
        <property type="protein sequence ID" value="BAA06418.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT009788">
        <property type="protein sequence ID" value="AAP88790.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC018543">
        <property type="protein sequence ID" value="AAH18543.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11101.1"/>
    <dbReference type="RefSeq" id="NP_055531.1">
        <property type="nucleotide sequence ID" value="NM_014716.4"/>
    </dbReference>
    <dbReference type="PDB" id="3JUE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=378-740"/>
    </dbReference>
    <dbReference type="PDB" id="3T9K">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=378-740"/>
    </dbReference>
    <dbReference type="PDB" id="4CKG">
        <property type="method" value="EM"/>
        <property type="resolution" value="12.00 A"/>
        <property type="chains" value="A/B/C/D=1-377"/>
    </dbReference>
    <dbReference type="PDB" id="4CKH">
        <property type="method" value="EM"/>
        <property type="resolution" value="14.00 A"/>
        <property type="chains" value="A/B/C/D=1-377"/>
    </dbReference>
    <dbReference type="PDB" id="4F1P">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=378-740"/>
    </dbReference>
    <dbReference type="PDB" id="4NSW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=1-377"/>
    </dbReference>
    <dbReference type="PDB" id="5H3D">
        <property type="method" value="EM"/>
        <property type="resolution" value="14.00 A"/>
        <property type="chains" value="A/B/C/D=1-377"/>
    </dbReference>
    <dbReference type="PDBsum" id="3JUE"/>
    <dbReference type="PDBsum" id="3T9K"/>
    <dbReference type="PDBsum" id="4CKG"/>
    <dbReference type="PDBsum" id="4CKH"/>
    <dbReference type="PDBsum" id="4F1P"/>
    <dbReference type="PDBsum" id="4NSW"/>
    <dbReference type="PDBsum" id="5H3D"/>
    <dbReference type="AlphaFoldDB" id="Q15027"/>
    <dbReference type="EMDB" id="EMD-2546"/>
    <dbReference type="EMDB" id="EMD-2547"/>
    <dbReference type="SMR" id="Q15027"/>
    <dbReference type="BioGRID" id="115092">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="CORUM" id="Q15027"/>
    <dbReference type="FunCoup" id="Q15027">
        <property type="interactions" value="564"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15027">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="MINT" id="Q15027"/>
    <dbReference type="STRING" id="9606.ENSP00000158762"/>
    <dbReference type="GlyCosmos" id="Q15027">
        <property type="glycosylation" value="2 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15027">
        <property type="glycosylation" value="4 sites, 2 O-linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15027"/>
    <dbReference type="PhosphoSitePlus" id="Q15027"/>
    <dbReference type="BioMuta" id="ACAP1"/>
    <dbReference type="DMDM" id="3183210"/>
    <dbReference type="jPOST" id="Q15027"/>
    <dbReference type="MassIVE" id="Q15027"/>
    <dbReference type="PaxDb" id="9606-ENSP00000158762"/>
    <dbReference type="PeptideAtlas" id="Q15027"/>
    <dbReference type="ProteomicsDB" id="60378"/>
    <dbReference type="Pumba" id="Q15027"/>
    <dbReference type="Antibodypedia" id="24069">
        <property type="antibodies" value="234 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="9744"/>
    <dbReference type="Ensembl" id="ENST00000158762.8">
        <property type="protein sequence ID" value="ENSP00000158762.3"/>
        <property type="gene ID" value="ENSG00000072818.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000672212.1">
        <property type="protein sequence ID" value="ENSP00000499859.1"/>
        <property type="gene ID" value="ENSG00000288169.1"/>
    </dbReference>
    <dbReference type="GeneID" id="9744"/>
    <dbReference type="KEGG" id="hsa:9744"/>
    <dbReference type="MANE-Select" id="ENST00000158762.8">
        <property type="protein sequence ID" value="ENSP00000158762.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014716.4"/>
        <property type="RefSeq protein sequence ID" value="NP_055531.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ggd.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16467"/>
    <dbReference type="ClinPGx" id="PA26406"/>
    <dbReference type="CTD" id="9744"/>
    <dbReference type="DisGeNET" id="9744"/>
    <dbReference type="GeneCards" id="ACAP1"/>
    <dbReference type="HGNC" id="HGNC:16467">
        <property type="gene designation" value="ACAP1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000072818">
        <property type="expression patterns" value="Tissue enhanced (bone marrow, intestine, lymphoid tissue)"/>
    </dbReference>
    <dbReference type="MIM" id="607763">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000072818"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000072818"/>
    <dbReference type="eggNOG" id="KOG0521">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160289"/>
    <dbReference type="HOGENOM" id="CLU_012513_0_0_1"/>
    <dbReference type="InParanoid" id="Q15027"/>
    <dbReference type="OMA" id="QYCAHSK"/>
    <dbReference type="OrthoDB" id="10070851at2759"/>
    <dbReference type="PAN-GO" id="Q15027">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15027"/>
    <dbReference type="PathwayCommons" id="Q15027"/>
    <dbReference type="SignaLink" id="Q15027"/>
    <dbReference type="SIGNOR" id="Q15027"/>
    <dbReference type="Agora" id="ENSG00000072818"/>
    <dbReference type="BioGRID-ORCS" id="9744">
        <property type="hits" value="9 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="DEE660B4">
        <property type="entry name" value="Stress granule"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACAP1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q15027"/>
    <dbReference type="GeneWiki" id="CENTB1"/>
    <dbReference type="GenomeRNAi" id="9744"/>
    <dbReference type="Pharos" id="Q15027">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q15027"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q15027">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000072818">
        <property type="expression patterns" value="Expressed in granulocyte and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q15027">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055038">
        <property type="term" value="C:recycling endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015031">
        <property type="term" value="P:protein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08852">
        <property type="entry name" value="ArfGap_ACAP1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13250">
        <property type="entry name" value="PH_ACAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.1270.60:FF:000062">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000007">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000020">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000026">
        <property type="entry name" value="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1270.60">
        <property type="entry name" value="Arfaptin homology (AH) domain/BAR domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045258">
        <property type="entry name" value="ACAP1/2/3-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027267">
        <property type="entry name" value="AH/BAR_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004148">
        <property type="entry name" value="BAR_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23180:SF197">
        <property type="entry name" value="ARF-GAP WITH COILED-COIL, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23180">
        <property type="entry name" value="CENTAURIN/ARF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16746">
        <property type="entry name" value="BAR_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF103657">
        <property type="entry name" value="BAR/IMD domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0944">Nitration</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000074209" description="Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1">
        <location>
            <begin position="1"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="domain" description="BAR">
        <location>
            <begin position="1"/>
            <end position="226"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="265"/>
            <end position="360"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="405"/>
            <end position="527"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="606"/>
            <end position="635"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="639"/>
            <end position="668"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 3">
        <location>
            <begin position="672"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="420"/>
            <end position="443"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for formation of endosomal tubules when overexpressed with PIP5K1C">
        <location>
            <begin position="1"/>
            <end position="382"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with GULP1">
        <location>
            <begin position="405"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="525"/>
            <end position="581"/>
        </location>
    </feature>
    <feature type="region of interest" description="Prevents interaction with ITGB1 when S-554 is not phosphorylated">
        <location>
            <begin position="525"/>
            <end position="566"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="3">
        <location>
            <begin position="538"/>
            <end position="549"/>
        </location>
    </feature>
    <feature type="modified residue" description="3'-nitrotyrosine" evidence="13">
        <location>
            <position position="485"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by PKB" evidence="5">
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048328" description="In dbSNP:rs35933585.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036178" description="In a breast cancer sample; somatic mutation; dbSNP:rs759855054." evidence="6">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036179" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs754740225." evidence="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048329" description="In dbSNP:rs35019942.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="533"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="14"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of binding to PIP2 and PIP3. Loss of association with endosomal tubules when coexpressed with PIP5K1C." evidence="7">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced membrane binding and ability to induce liposome tubulation." evidence="11">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes membrane binding." evidence="11">
        <original>F</original>
        <variation>E</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Preserves membrane binding and ability to tubulate liposomes." evidence="11">
        <original>F</original>
        <variation>W</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of GAP activity. No effect on GULP1 binding or association with endosomal tubules when coexpressed with PIP5K1C." evidence="4 8">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="461"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of phosphorylation by PKB, interaction with ITGB1 and ITGB1-dependent cell migration." evidence="5 10">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Enhances interaction with ITGB1." evidence="5 10">
        <original>S</original>
        <variation>D</variation>
        <location>
            <position position="554"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="568"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="711"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with ITGB1." evidence="5">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="712"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of phosphorylation at S-554, interaction with ITGB1 and ITGB1-dependent cell migration." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="724"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Enhances interaction with ITGB1." evidence="5">
        <original>S</original>
        <variation>D</variation>
        <location>
            <position position="724"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="1"/>
            <end position="4"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="7"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="15"/>
            <end position="68"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="69"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="74"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="115"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="118"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="149"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="214"/>
            <end position="248"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="258"/>
            <end position="260"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="263"/>
            <end position="265"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="267"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="turn" evidence="16">
        <location>
            <begin position="277"/>
            <end position="279"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="283"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="294"/>
            <end position="303"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="306"/>
            <end position="310"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="312"/>
            <end position="314"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="315"/>
            <end position="319"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="323"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="328"/>
            <end position="335"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="337"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="345"/>
            <end position="361"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="407"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="415"/>
            <end position="418"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="421"/>
            <end position="423"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="430"/>
            <end position="432"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="433"/>
            <end position="436"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="437"/>
            <end position="439"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="441"/>
            <end position="450"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="452"/>
            <end position="454"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="457"/>
            <end position="459"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="460"/>
            <end position="462"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="467"/>
            <end position="475"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="478"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="486"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="503"/>
            <end position="514"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="571"/>
            <end position="578"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="580"/>
            <end position="582"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="585"/>
            <end position="593"/>
        </location>
    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="603"/>
            <end position="606"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="610"/>
            <end position="616"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="620"/>
            <end position="628"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="643"/>
            <end position="650"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="653"/>
            <end position="661"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="676"/>
            <end position="682"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="686"/>
            <end position="696"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="713"/>
            <end position="720"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11062263"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16256741"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="17010122"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17398097"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17664335"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="22645133"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="25284369"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="16777052"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="3JUE"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="3T9K"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="4NSW"/>
        </source>
    </evidence>
    <sequence length="740" mass="81536" checksum="64891DA3CE00189C" modified="1996-11-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="171" xmlns="https://uniprot.org/uniprot">
    <accession>Q6JQN1</accession>
    <accession>G3XAJ0</accession>
    <accession>Q8N828</accession>
    <accession>Q8NAP2</accession>
    <accession>Q96BX5</accession>
    <name>ACD10_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA dehydrogenase family member 10</fullName>
            <shortName>ACAD-10</shortName>
            <ecNumber>1.3.99.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACAD10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <text>a 2,3-saturated acyl-CoA + A = a 2,3-dehydroacyl-CoA + AH2</text>
            <dbReference type="Rhea" id="RHEA:48608"/>
            <dbReference type="ChEBI" id="CHEBI:13193"/>
            <dbReference type="ChEBI" id="CHEBI:17499"/>
            <dbReference type="ChEBI" id="CHEBI:60015"/>
            <dbReference type="ChEBI" id="CHEBI:65111"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6JQN1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6JQN1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_024634 VSP_024635"/>
        </isoform>
        <isoform>
            <id>Q6JQN1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_024630 VSP_024633 VSP_024634 VSP_024635"/>
        </isoform>
        <isoform>
            <id>Q6JQN1-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_024631 VSP_024632"/>
        </isoform>
        <isoform>
            <id>Q6JQN1-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_044980"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 4">Widely expressed with highest expression in fetal brain, followed by heart, muscle, kidney and adult brain. Expression levels varying from isoform to isoform.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH15056" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="1.3.99.-"/>
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        <property type="protein sequence ID" value="AAQ88260.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092356">
        <property type="protein sequence ID" value="BAC03869.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK097425">
        <property type="protein sequence ID" value="BAC05046.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832043">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC002996">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW97962.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015056">
        <property type="protein sequence ID" value="AAH15056.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC126358">
        <property type="protein sequence ID" value="AAI26359.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31903.1">
        <molecule id="Q6JQN1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44973.1">
        <molecule id="Q6JQN1-5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001130010.1">
        <molecule id="Q6JQN1-5"/>
        <property type="nucleotide sequence ID" value="NM_001136538.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_079523.3">
        <molecule id="Q6JQN1-1"/>
        <property type="nucleotide sequence ID" value="NM_025247.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6JQN1"/>
    <dbReference type="SMR" id="Q6JQN1"/>
    <dbReference type="BioGRID" id="123274">
        <property type="interactions" value="143"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6JQN1">
        <property type="interactions" value="1644"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6JQN1">
        <property type="interactions" value="88"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000389813"/>
    <dbReference type="ChEMBL" id="CHEMBL4105816"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6JQN1"/>
    <dbReference type="PhosphoSitePlus" id="Q6JQN1"/>
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    <dbReference type="DMDM" id="74748862"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000389813"/>
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    <dbReference type="ProteomicsDB" id="33762"/>
    <dbReference type="ProteomicsDB" id="66515">
        <molecule id="Q6JQN1-1"/>
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    <dbReference type="ProteomicsDB" id="66516">
        <molecule id="Q6JQN1-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="66517">
        <molecule id="Q6JQN1-3"/>
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    <dbReference type="ProteomicsDB" id="66518">
        <molecule id="Q6JQN1-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q6JQN1"/>
    <dbReference type="Antibodypedia" id="31114">
        <property type="antibodies" value="167 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="80724"/>
    <dbReference type="Ensembl" id="ENST00000313698.9">
        <molecule id="Q6JQN1-1"/>
        <property type="protein sequence ID" value="ENSP00000325137.5"/>
        <property type="gene ID" value="ENSG00000111271.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000455480.6">
        <molecule id="Q6JQN1-5"/>
        <property type="protein sequence ID" value="ENSP00000389813.2"/>
        <property type="gene ID" value="ENSG00000111271.16"/>
    </dbReference>
    <dbReference type="GeneID" id="80724"/>
    <dbReference type="KEGG" id="hsa:80724"/>
    <dbReference type="MANE-Select" id="ENST00000313698.9">
        <property type="protein sequence ID" value="ENSP00000325137.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_025247.6"/>
        <property type="RefSeq protein sequence ID" value="NP_079523.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001tsq.4">
        <molecule id="Q6JQN1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21597"/>
    <dbReference type="ClinPGx" id="PA134976754"/>
    <dbReference type="CTD" id="80724"/>
    <dbReference type="DisGeNET" id="80724"/>
    <dbReference type="GeneCards" id="ACAD10"/>
    <dbReference type="HGNC" id="HGNC:21597">
        <property type="gene designation" value="ACAD10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000111271">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="611181">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000111271"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000111271"/>
    <dbReference type="eggNOG" id="KOG1469">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="eggNOG" id="KOG3085">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161620"/>
    <dbReference type="HOGENOM" id="CLU_007526_2_1_1"/>
    <dbReference type="InParanoid" id="Q6JQN1"/>
    <dbReference type="OMA" id="AIAMIKI"/>
    <dbReference type="OrthoDB" id="434771at2759"/>
    <dbReference type="PAN-GO" id="Q6JQN1">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6JQN1"/>
    <dbReference type="PathwayCommons" id="Q6JQN1"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6JQN1"/>
    <dbReference type="Agora" id="ENSG00000111271"/>
    <dbReference type="BioGRID-ORCS" id="80724">
        <property type="hits" value="16 hits in 1166 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACAD10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="80724"/>
    <dbReference type="Pharos" id="Q6JQN1">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6JQN1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6JQN1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000111271">
        <property type="expression patterns" value="Expressed in apex of heart and 194 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6JQN1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003995">
        <property type="term" value="F:acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006635">
        <property type="term" value="P:fatty acid beta-oxidation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033539">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA dehydrogenase"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd05154">
        <property type="entry name" value="ACAD10_11_N-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd02603">
        <property type="entry name" value="HAD_sEH-N_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000002">
        <property type="entry name" value="Acyl-CoA dehydrogenase fadE12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.150.240:FF:000015">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000018">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.200.20:FF:000343">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.1200.10:FF:000009">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000016">
        <property type="entry name" value="acyl-CoA dehydrogenase family member 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.1200.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1000">
        <property type="entry name" value="HAD superfamily/HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.200.20">
        <property type="entry name" value="Phosphorylase Kinase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.150.240">
        <property type="entry name" value="Putative phosphatase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052898">
        <property type="entry name" value="ACAD10-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041726">
        <property type="entry name" value="ACAD10_11_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002575">
        <property type="entry name" value="Aminoglycoside_PTrfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036412">
        <property type="entry name" value="HAD-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006439">
        <property type="entry name" value="HAD-SF_hydro_IA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011945">
        <property type="entry name" value="HAD-SF_ppase_IA/epoxid_hydro_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023214">
        <property type="entry name" value="HAD_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023198">
        <property type="entry name" value="PGP-like_dom2"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR02247">
        <property type="entry name" value="HAD-1A3-hyp"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01509">
        <property type="entry name" value="HAD-SF-IA-v3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR47829:SF3">
        <property type="entry name" value="AMINOGLYCOSIDE PHOSPHOTRANSFERASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR47829">
        <property type="entry name" value="HYDROLASE, PUTATIVE (AFU_ORTHOLOGUE AFUA_1G12880)-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01636">
        <property type="entry name" value="APH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00702">
        <property type="entry name" value="Hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00413">
        <property type="entry name" value="HADHALOGNASE"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDG01129">
        <property type="entry name" value="C1.5:_HAD__Beta-PGM__Phosphata"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SFLD" id="SFLDS00003">
        <property type="entry name" value="Haloacid_Dehalogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56784">
        <property type="entry name" value="HAD-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000284770" description="Acyl-CoA dehydrogenase family member 10">
        <location>
            <begin position="1"/>
            <end position="1059"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="792"/>
            <end position="802"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="828"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="943"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="1013"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="1044"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="413"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="1052"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="1052"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024630" description="In isoform 3." evidence="5">
        <location>
            <begin position="1"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044980" description="In isoform 5." evidence="7">
        <original>K</original>
        <variation>KRQGFAVLPKLVSNSWAQAIYPPYPPKVVRLQ</variation>
        <location>
            <position position="230"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024631" description="In isoform 4." evidence="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024632" description="In isoform 4." evidence="6">
        <location>
            <begin position="286"/>
            <end position="1059"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024633" description="In isoform 3." evidence="5">
        <original>HSVDLQAVGLEDYGK</original>
        <variation>MLEYLSLTFLISVKI</variation>
        <location>
            <begin position="399"/>
            <end position="413"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024634" description="In isoform 2 and isoform 3." evidence="5">
        <original>GHGEVRFE</original>
        <variation>CFLPSFSL</variation>
        <location>
            <begin position="883"/>
            <end position="890"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_024635" description="In isoform 2 and isoform 3." evidence="5">
        <location>
            <begin position="891"/>
            <end position="1059"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031811" description="In dbSNP:rs35276160.">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031812" description="In dbSNP:rs35753710.">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031813" description="In dbSNP:rs36046440.">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="463"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031814" description="In dbSNP:rs34245489.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="880"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC03869." evidence="8" ref="2">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC05046." evidence="8" ref="2">
        <original>C</original>
        <variation>M</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AL832043." evidence="8" ref="3">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="511"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AL832043." evidence="8" ref="3">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="641"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC03869." evidence="8" ref="2">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="663"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC03869." evidence="8" ref="2">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="688"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8K370"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15560374"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="21237683"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <sequence length="1059" mass="118834" checksum="B8D4376FCF73D746" modified="2004-07-05" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-31" modified="2026-01-28" version="176" xmlns="https://uniprot.org/uniprot">
    <accession>Q709F0</accession>
    <accession>Q08AF0</accession>
    <accession>Q658N9</accession>
    <accession>Q658Y2</accession>
    <accession>Q6ZND2</accession>
    <accession>Q8WUT6</accession>
    <accession>Q9H9R3</accession>
    <name>ACD11_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA dehydrogenase family member 11</fullName>
            <shortName>ACAD-11</shortName>
            <ecNumber evidence="3">1.3.8.8</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACAD11</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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                <person name="Ono T."/>
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                <person name="Ozaki K."/>
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                <person name="Senba T."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-563 (ISOFORM 3)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 343-780 (ISOFORM 1)</scope>
        <source>
            <tissue>Tongue</tissue>
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            <dbReference type="PubMed" id="16641997"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="21237683"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <dbReference type="PubMed" id="24275569"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 355-780 IN COMPLEX WITH FAD</scope>
        <scope>COFACTOR</scope>
        <scope>SUBUNIT</scope>
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    <comment type="function">
        <text evidence="3">Participates in fatty acid beta-oxidation (FAO) and energy production in the central nervous system (CNS), and to a lesser extent in the liver (PubMed:21237683). Catalyzes the first step in FAO, which consists in the proR-proR stereospecific alpha,beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, with maximal activity towards saturated docosanoyl-CoA (CoA 22:0) in both the cerebellum and the liver (PubMed:21237683). Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACADV and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the CNS, where together with ACAD9, they accommodate the full spectrum of long chain fatty acid substrates (PubMed:21237683).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a long-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a long-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:17721"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:83721"/>
            <dbReference type="ChEBI" id="CHEBI:83727"/>
            <dbReference type="EC" id="1.3.8.8"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:17722"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>eicosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-eicosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47236"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47237"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>docosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-docosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47228"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65059"/>
            <dbReference type="ChEBI" id="CHEBI:74692"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47229"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>tetracosanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-tetracosenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47232"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:74693"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:47233"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="pathway">
        <text evidence="8">Lipid metabolism; fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880718">
            <id>Q709F0</id>
        </interactant>
        <interactant intactId="EBI-768015">
            <id>O95400</id>
            <label>CD2BP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Peroxisome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Mitochondrion membrane</location>
        </subcellularLocation>
        <text evidence="3">Has been detected associated with mitochondrial membrane, but no matrix, in kidney and cerebellum, as well as in a neuroblastoma cell line, but not in skin fibroblasts, where it is observed in cytoplasmic vesicles (PubMed:21237683). No mitochondrial targeting signals could be predicted for any known isoform, including a putative isoform starting at Met-316.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q709F0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q709F0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_021188"/>
        </isoform>
        <isoform>
            <id>Q709F0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_021187"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Widely expressed with highest levels in brain (white matter of cerebellum) followed by liver, heart and kidney.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB14158" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.8" evidence="3"/>
    <dbReference type="EMBL" id="AJ608287">
        <property type="protein sequence ID" value="CAE55233.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL833721">
        <property type="protein sequence ID" value="CAH56228.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL832873">
        <property type="protein sequence ID" value="CAH56354.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK022654">
        <property type="protein sequence ID" value="BAB14158.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK131265">
        <property type="protein sequence ID" value="BAD18443.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC020632">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF457683">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF457684">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC019607">
        <property type="protein sequence ID" value="AAH19607.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125204">
        <property type="protein sequence ID" value="AAI25205.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3074.1">
        <molecule id="Q709F0-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_115545.3">
        <molecule id="Q709F0-1"/>
        <property type="nucleotide sequence ID" value="NM_032169.4"/>
    </dbReference>
    <dbReference type="PDB" id="2WBI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=355-780"/>
    </dbReference>
    <dbReference type="PDBsum" id="2WBI"/>
    <dbReference type="AlphaFoldDB" id="Q709F0"/>
    <dbReference type="SMR" id="Q709F0"/>
    <dbReference type="BioGRID" id="123902">
        <property type="interactions" value="192"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q709F0">
        <property type="interactions" value="1440"/>
    </dbReference>
    <dbReference type="IntAct" id="Q709F0">
        <property type="interactions" value="103"/>
    </dbReference>
    <dbReference type="MINT" id="Q709F0"/>
    <dbReference type="STRING" id="9606.ENSP00000264990"/>
    <dbReference type="ChEMBL" id="CHEMBL4105707"/>
    <dbReference type="DrugCentral" id="Q709F0"/>
    <dbReference type="SwissLipids" id="SLP:000001326"/>
    <dbReference type="GlyGen" id="Q709F0">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q709F0"/>
    <dbReference type="PhosphoSitePlus" id="Q709F0"/>
    <dbReference type="BioMuta" id="ACAD11"/>
    <dbReference type="DMDM" id="117949774"/>
    <dbReference type="jPOST" id="Q709F0"/>
    <dbReference type="MassIVE" id="Q709F0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000264990"/>
    <dbReference type="PeptideAtlas" id="Q709F0"/>
    <dbReference type="ProteomicsDB" id="68516">
        <molecule id="Q709F0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="68517">
        <molecule id="Q709F0-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="68518">
        <molecule id="Q709F0-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q709F0"/>
    <dbReference type="Antibodypedia" id="34898">
        <property type="antibodies" value="104 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84129"/>
    <dbReference type="Ensembl" id="ENST00000264990.11">
        <molecule id="Q709F0-1"/>
        <property type="protein sequence ID" value="ENSP00000264990.6"/>
        <property type="gene ID" value="ENSG00000240303.9"/>
    </dbReference>
    <dbReference type="GeneID" id="84129"/>
    <dbReference type="KEGG" id="hsa:84129"/>
    <dbReference type="MANE-Select" id="ENST00000264990.11">
        <property type="protein sequence ID" value="ENSP00000264990.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032169.5"/>
        <property type="RefSeq protein sequence ID" value="NP_115545.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003eov.5">
        <molecule id="Q709F0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30211"/>
    <dbReference type="ClinPGx" id="PA142672658"/>
    <dbReference type="CTD" id="84129"/>
    <dbReference type="DisGeNET" id="84129"/>
    <dbReference type="GeneCards" id="ACAD11"/>
    <dbReference type="HGNC" id="HGNC:30211">
        <property type="gene designation" value="ACAD11"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000240303">
        <property type="expression patterns" value="Group enriched (choroid plexus, kidney, liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614288">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000240303"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000240303"/>
    <dbReference type="eggNOG" id="KOG1469">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160993"/>
    <dbReference type="HOGENOM" id="CLU_007526_3_1_1"/>
    <dbReference type="InParanoid" id="Q709F0"/>
    <dbReference type="OMA" id="LHGGHFE"/>
    <dbReference type="OrthoDB" id="434771at2759"/>
    <dbReference type="PAN-GO" id="Q709F0">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q709F0"/>
    <dbReference type="PathwayCommons" id="Q709F0"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q709F0"/>
    <dbReference type="UniPathway" id="UPA00659"/>
    <dbReference type="Agora" id="ENSG00000240303"/>
    <dbReference type="BioGRID-ORCS" id="84129">
        <property type="hits" value="12 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q709F0"/>
    <dbReference type="GenomeRNAi" id="84129"/>
    <dbReference type="Pharos" id="Q709F0">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q709F0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q709F0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000240303">
        <property type="expression patterns" value="Expressed in right lobe of liver and 96 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q709F0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003995">
        <property type="term" value="F:acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004466">
        <property type="term" value="F:long-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070991">
        <property type="term" value="F:medium-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017099">
        <property type="term" value="F:very-long-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006635">
        <property type="term" value="P:fatty acid beta-oxidation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033539">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA dehydrogenase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd05154">
        <property type="entry name" value="ACAD10_11_N-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01155">
        <property type="entry name" value="ACAD_FadE2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000002">
        <property type="entry name" value="Acyl-CoA dehydrogenase fadE12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000018">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.200.20:FF:000343">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.1200.10:FF:000009">
        <property type="entry name" value="Acyl-CoA dehydrogenase family member 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000016">
        <property type="entry name" value="acyl-CoA dehydrogenase family member 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.1200.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.200.20">
        <property type="entry name" value="Phosphorylase Kinase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041726">
        <property type="entry name" value="ACAD10_11_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050741">
        <property type="entry name" value="Acyl-CoA_dehydrogenase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013786">
        <property type="entry name" value="AcylCoA_DH/ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002575">
        <property type="entry name" value="Aminoglycoside_PTrfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083:SF13">
        <property type="entry name" value="ACYL-COA DEHYDROGENASE FAMILY MEMBER 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48083">
        <property type="entry name" value="MEDIUM-CHAIN SPECIFIC ACYL-COA DEHYDROGENASE, MITOCHONDRIAL-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00441">
        <property type="entry name" value="Acyl-CoA_dh_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02771">
        <property type="entry name" value="Acyl-CoA_dh_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01636">
        <property type="entry name" value="APH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000254145" description="Acyl-CoA dehydrogenase family member 11">
        <location>
            <begin position="1"/>
            <end position="780"/>
        </location>
    </feature>
    <feature type="binding site" description="in other chain" evidence="4">
        <location>
            <begin position="504"/>
            <end position="514"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="514"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" description="in other chain" evidence="4">
        <location>
            <begin position="538"/>
            <end position="540"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="629"/>
            <end position="632"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="657"/>
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        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="727"/>
            <end position="731"/>
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        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
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    <feature type="binding site" description="in other chain" evidence="4">
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            <position position="727"/>
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        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="755"/>
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        <ligand>
            <name>substrate</name>
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    <feature type="binding site" description="in other chain" evidence="4">
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            <begin position="756"/>
            <end position="758"/>
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        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
        </ligand>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="177"/>
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    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="391"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021187" description="In isoform 3." evidence="5">
        <location>
            <begin position="1"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_021188" description="In isoform 2." evidence="6">
        <location>
            <begin position="564"/>
            <end position="667"/>
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    </feature>
    <feature type="sequence variant" id="VAR_028826" description="In dbSNP:rs6776576.">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAH56354." evidence="7" ref="2">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="414"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAE55233 and 3; BAB14158." evidence="7" ref="1 3">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="549"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAH56228." evidence="7" ref="2">
        <original>S</original>
        <variation>SRLT</variation>
        <location>
            <position position="562"/>
        </location>
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    <feature type="helix" evidence="9">
        <location>
            <begin position="377"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="394"/>
            <end position="402"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="404"/>
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        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="419"/>
            <end position="430"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="439"/>
            <end position="442"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="446"/>
            <end position="456"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="462"/>
            <end position="465"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="472"/>
            <end position="482"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="485"/>
            <end position="490"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="492"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="499"/>
            <end position="505"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="516"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="522"/>
            <end position="526"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="529"/>
            <end position="540"/>
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    <feature type="turn" evidence="9">
        <location>
            <begin position="541"/>
            <end position="543"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="547"/>
            <end position="555"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="563"/>
            <end position="565"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="567"/>
            <end position="573"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="579"/>
            <end position="584"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="593"/>
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    </feature>
    <feature type="strand" evidence="9">
        <location>
            <begin position="598"/>
            <end position="609"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="610"/>
            <end position="612"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="620"/>
            <end position="656"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="664"/>
            <end position="666"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="668"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="704"/>
            <end position="728"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="730"/>
            <end position="734"/>
        </location>
    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="740"/>
            <end position="750"/>
        </location>
    </feature>
    <feature type="turn" evidence="9">
        <location>
            <begin position="751"/>
            <end position="754"/>
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    </feature>
    <feature type="helix" evidence="9">
        <location>
            <begin position="757"/>
            <end position="776"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q80XL6"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="21237683"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source ref="9"/>
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    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="21237683"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="9">
        <source>
            <dbReference type="PDB" id="2WBI"/>
        </source>
    </evidence>
    <sequence length="780" mass="87264" checksum="E4DC30F6ABE70463" modified="2018-09-12" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-05-30" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>Q96AP0</accession>
    <accession>A0A0C4DGT6</accession>
    <accession>Q562H5</accession>
    <accession>Q9H8F9</accession>
    <name>ACD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="16">Adrenocortical dysplasia protein homolog</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>POT1 and TIN2-interacting protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="17" type="primary">ACD</name>
        <name evidence="15" type="synonym">PIP1</name>
        <name evidence="14" type="synonym">PTOP</name>
        <name type="synonym">TINT1</name>
        <name type="synonym">TPP1</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Liu D."/>
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            <dbReference type="PubMed" id="15181449"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>MOTIF</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH POT1 AND TINF2</scope>
        <scope>FUNCTION</scope>
        <scope>VARIANT ALA-432</scope>
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    <reference key="2">
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                <person name="Keegan C.E."/>
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            </authorList>
            <dbReference type="PubMed" id="15537664"/>
            <dbReference type="DOI" id="10.1093/hmg/ddi011"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="3">
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
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                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
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                <person name="Okumura K."/>
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                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <authorList>
                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>VARIANT ALA-432</scope>
        <source>
            <tissue>Duodenum</tissue>
        </source>
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            <dbReference type="PubMed" id="15231715"/>
            <dbReference type="DOI" id="10.1101/gad.1215404"/>
        </citation>
        <scope>INTERACTION WITH POT1 AND TINF2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="7">
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        <scope>IDENTIFICATION IN THE SHELTERIN COMPLEX</scope>
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        <scope>IDENTIFICATION IN THE SHELTERIN COMPLEX</scope>
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                <person name="de Lange T."/>
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            <dbReference type="PubMed" id="16166375"/>
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        <scope>FUNCTION OF THE SHELTERIN COMPLEX</scope>
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            <title>A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly.</title>
            <authorList>
                <person name="O'Connor M.S."/>
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            </authorList>
            <dbReference type="PubMed" id="16880378"/>
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        <scope>FUNCTION IN SHELTERIN COMPLEX ASSEMBLY</scope>
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            <title>Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.</title>
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            </authorList>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            </authorList>
            <dbReference type="PubMed" id="19648609"/>
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        <scope>INTERACTION WITH STN1</scope>
    </reference>
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            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
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                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
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            <authorList>
                <person name="Zaug A.J."/>
                <person name="Podell E.R."/>
                <person name="Nandakumar J."/>
                <person name="Cech T.R."/>
            </authorList>
            <dbReference type="PubMed" id="20231318"/>
            <dbReference type="DOI" id="10.1101/gad.1881810"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
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            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
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                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
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                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
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                <person name="Di Palma S."/>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
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    </reference>
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            <title>Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1.</title>
            <authorList>
                <person name="Guo Y."/>
                <person name="Kartawinata M."/>
                <person name="Li J."/>
                <person name="Pickett H.A."/>
                <person name="Teo J."/>
                <person name="Kilo T."/>
                <person name="Barbaro P.M."/>
                <person name="Keating B."/>
                <person name="Chen Y."/>
                <person name="Tian L."/>
                <person name="Al-Odaib A."/>
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                <person name="Xu X."/>
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            </authorList>
            <dbReference type="PubMed" id="25205116"/>
            <dbReference type="DOI" id="10.1182/blood-2014-08-596445"/>
        </citation>
        <scope>INVOLVEMENT IN DKCA6</scope>
        <scope>VARIANT DKCA6 LYS-84 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT DKCA6 LYS-84 DEL</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <title>Hoyeraal-Hreidarsson syndrome caused by a germline mutation in the TEL patch of the telomere protein TPP1.</title>
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                <consortium name="NCI DCEG Cancer Genomics Research Laboratory"/>
                <consortium name="NCI DCEG Cancer Sequencing Working Group"/>
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                <person name="Giri N."/>
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            </authorList>
            <dbReference type="PubMed" id="25233904"/>
            <dbReference type="DOI" id="10.1101/gad.248567.114"/>
        </citation>
        <scope>INVOLVEMENT IN DKCB7</scope>
        <scope>VARIANTS DKCB7 LYS-84 DEL AND THR-405</scope>
        <scope>CHARACTERIZATION OF VARIANTS DKCB7 LYS-84 DEL AND THR-405</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH TINF2</scope>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
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                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="22">
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            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-381</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <title>The POT1-TPP1 telomere complex is a telomerase processivity factor.</title>
            <authorList>
                <person name="Wang F."/>
                <person name="Podell E.R."/>
                <person name="Zaug A.J."/>
                <person name="Yang Y."/>
                <person name="Baciu P."/>
                <person name="Cech T.R."/>
                <person name="Lei M."/>
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            <dbReference type="PubMed" id="17237768"/>
            <dbReference type="DOI" id="10.1038/nature05454"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 4-164</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>IDENTIFICATION IN A COMPLEX WITH POT1 AND SINGLE-STRANDED TELOMERIC DNA</scope>
    </reference>
    <comment type="function">
        <text evidence="2 7 8 9 11 12 13">Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity. May play a role in organogenesis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3 4 5 9 10 13">Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Forms heterodimers with POT1. Identified in a complex with POT1 and single-stranded telomeric DNA. Interacts with STN1 and TINF2.</text>
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        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-717399">
            <id>Q9BSI4</id>
            <label>TINF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>18</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-717418">
            <id>Q9BSI4-3</id>
            <label>TINF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-711595">
            <id>Q13885</id>
            <label>TUBB2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-373471">
            <id>Q92900</id>
            <label>UPF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-356498">
            <id>P62258</id>
            <label>YWHAE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-7051001">
            <id>Q91WC1</id>
            <label>Pot1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-717666">
            <id>Q96AP0</id>
        </interactant>
        <interactant intactId="EBI-15954293">
            <id>Q8VC56</id>
            <label>Rnf8</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 12 13">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2 12 13">Chromosome</location>
            <location evidence="2 12 13">Telomere</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96AP0-3</id>
            <name>3</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96AP0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_060243"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-04521">
            <name>Dyskeratosis congenita, autosomal dominant, 6</name>
            <acronym>DKCA6</acronym>
            <description>A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.</description>
            <dbReference type="MIM" id="616553"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-04522">
            <name>Dyskeratosis congenita, autosomal recessive, 7</name>
            <acronym>DKCB7</acronym>
            <description>A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.</description>
            <dbReference type="MIM" id="616553"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH16904" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAS80318" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB14658" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AY502940">
        <property type="protein sequence ID" value="AAS80318.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY971883">
        <property type="protein sequence ID" value="AAX82621.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AK023726">
        <property type="protein sequence ID" value="BAB14658.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC010530">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC016904">
        <property type="protein sequence ID" value="AAH16904.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS10842.2">
        <molecule id="Q96AP0-2"/>
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    <dbReference type="CCDS" id="CCDS42181.2">
        <molecule id="Q96AP0-3"/>
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    <dbReference type="RefSeq" id="NP_001075955.2">
        <molecule id="Q96AP0-3"/>
        <property type="nucleotide sequence ID" value="NM_001082486.2"/>
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    <dbReference type="RefSeq" id="NP_075065.3">
        <molecule id="Q96AP0-2"/>
        <property type="nucleotide sequence ID" value="NM_022914.3"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B=4-164"/>
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    <dbReference type="PDB" id="5H65">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="B=180-230"/>
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    <dbReference type="PDB" id="5I2X">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=4-164"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="B=169-251"/>
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    <dbReference type="PDB" id="5XYF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="B=424-458"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="O=1-458"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.91 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="B/E/H/K=159-251"/>
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    <dbReference type="PDB" id="7TRE">
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        <property type="resolution" value="3.50 A"/>
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        <property type="method" value="EM"/>
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        <property type="resolution" value="4.10 A"/>
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        <property type="method" value="EM"/>
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        <property type="resolution" value="3.80 A"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="O=1-458"/>
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    <dbReference type="PDBsum" id="2I46"/>
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    <dbReference type="AlphaFoldDB" id="Q96AP0"/>
    <dbReference type="EMDB" id="EMD-14198"/>
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    <dbReference type="BioGRID" id="122379">
        <property type="interactions" value="85"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-152">
        <property type="entry name" value="Shelterin complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q96AP0"/>
    <dbReference type="DIP" id="DIP-29611N"/>
    <dbReference type="FunCoup" id="Q96AP0">
        <property type="interactions" value="1089"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96AP0">
        <property type="interactions" value="91"/>
    </dbReference>
    <dbReference type="MINT" id="Q96AP0"/>
    <dbReference type="STRING" id="9606.ENSP00000483117"/>
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        <property type="type" value="Predicted"/>
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    <dbReference type="GlyGen" id="Q96AP0">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96AP0"/>
    <dbReference type="PhosphoSitePlus" id="Q96AP0"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000483117"/>
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        <molecule id="Q96AP0-2"/>
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    <dbReference type="Pumba" id="Q96AP0"/>
    <dbReference type="Antibodypedia" id="29595">
        <property type="antibodies" value="352 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="65057"/>
    <dbReference type="Ensembl" id="ENST00000219251.13">
        <molecule id="Q96AP0-2"/>
        <property type="protein sequence ID" value="ENSP00000219251.8"/>
        <property type="gene ID" value="ENSG00000102977.19"/>
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    <dbReference type="Ensembl" id="ENST00000620761.6">
        <molecule id="Q96AP0-3"/>
        <property type="protein sequence ID" value="ENSP00000478084.1"/>
        <property type="gene ID" value="ENSG00000102977.19"/>
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    <dbReference type="GeneID" id="65057"/>
    <dbReference type="KEGG" id="hsa:65057"/>
    <dbReference type="MANE-Select" id="ENST00000620761.6">
        <property type="protein sequence ID" value="ENSP00000478084.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001082486.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001075955.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002etp.5">
        <molecule id="Q96AP0-3"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:25070"/>
    <dbReference type="ClinPGx" id="PA134882431"/>
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    <dbReference type="GeneReviews" id="ACD"/>
    <dbReference type="HGNC" id="HGNC:25070">
        <property type="gene designation" value="ACD"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000102977">
        <property type="expression patterns" value="Low tissue specificity"/>
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    <dbReference type="MalaCards" id="ACD"/>
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        <property type="type" value="gene"/>
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    <dbReference type="MIM" id="616553">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000102977"/>
    <dbReference type="Orphanet" id="618">
        <property type="disease" value="Familial melanoma"/>
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    <dbReference type="Orphanet" id="397692">
        <property type="disease" value="Hereditary isolated aplastic anemia"/>
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    <dbReference type="Orphanet" id="3322">
        <property type="disease" value="Hoyeraal-Hreidarsson syndrome"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="Q96AP0"/>
    <dbReference type="PathwayCommons" id="Q96AP0"/>
    <dbReference type="Reactome" id="R-HSA-110328">
        <property type="pathway name" value="Recognition and association of DNA glycosylase with site containing an affected pyrimidine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-110329">
        <property type="pathway name" value="Cleavage of the damaged pyrimidine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-110330">
        <property type="pathway name" value="Recognition and association of DNA glycosylase with site containing an affected purine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-110331">
        <property type="pathway name" value="Cleavage of the damaged purine"/>
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    <dbReference type="Reactome" id="R-HSA-1221632">
        <property type="pathway name" value="Meiotic synapsis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-171306">
        <property type="pathway name" value="Packaging Of Telomere Ends"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-171319">
        <property type="pathway name" value="Telomere Extension By Telomerase"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-174411">
        <property type="pathway name" value="Polymerase switching on the C-strand of the telomere"/>
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    <dbReference type="Reactome" id="R-HSA-174414">
        <property type="pathway name" value="Processive synthesis on the C-strand of the telomere"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-174417">
        <property type="pathway name" value="Telomere C-strand (Lagging Strand) Synthesis"/>
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    <dbReference type="Reactome" id="R-HSA-174430">
        <property type="pathway name" value="Telomere C-strand synthesis initiation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-174437">
        <property type="pathway name" value="Removal of the Flap Intermediate from the C-strand"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2559586">
        <property type="pathway name" value="DNA Damage/Telomere Stress Induced Senescence"/>
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    <dbReference type="Reactome" id="R-HSA-9670095">
        <property type="pathway name" value="Inhibition of DNA recombination at telomere"/>
    </dbReference>
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        <property type="hits" value="135 hits in 1158 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACD">
        <property type="organism name" value="human"/>
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    <dbReference type="EvolutionaryTrace" id="Q96AP0"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96AP0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
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        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000102977">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 193 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96AP0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:chromosome, telomeric region"/>
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        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016604">
        <property type="term" value="C:nuclear body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0000783">
        <property type="term" value="C:nuclear telomere cap complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005697">
        <property type="term" value="C:telomerase holoenzyme complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070182">
        <property type="term" value="F:DNA polymerase binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044877">
        <property type="term" value="F:protein-containing complex binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010521">
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042162">
        <property type="term" value="F:telomeric DNA binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030326">
        <property type="term" value="P:embryonic limb morphogenesis"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070200">
        <property type="term" value="P:establishment of protein localization to telomere"/>
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        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006886">
        <property type="term" value="P:intracellular protein transport"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032211">
        <property type="term" value="P:negative regulation of telomere maintenance via telomerase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032206">
        <property type="term" value="P:positive regulation of telomere maintenance"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
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        <property type="term" value="P:protection from non-homologous end joining at telomere"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0070198">
        <property type="term" value="P:protein localization to chromosome, telomeric region"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0070203">
        <property type="term" value="P:regulation of establishment of protein localization to telomere"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0035282">
        <property type="term" value="P:segmentation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0001501">
        <property type="term" value="P:skeletal system development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0032202">
        <property type="term" value="P:telomere assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0016233">
        <property type="term" value="P:telomere capping"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0000723">
        <property type="term" value="P:telomere maintenance"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0007004">
        <property type="term" value="P:telomere maintenance via telomerase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="P:urogenital system development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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        <property type="entry name" value="ACD, shelterin complex subunit and telomerase recruitment factor"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ACD"/>
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    <dbReference type="InterPro" id="IPR019437">
        <property type="entry name" value="TPP1/Est3"/>
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        <property type="entry name" value="ADRENOCORTICAL DYSPLASIA PROTEIN ACD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADRENOCORTICAL DYSPLASIA PROTEIN HOMOLOG"/>
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        <property type="entry name" value="TPP1"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0158">Chromosome</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-1011">Dyskeratosis congenita</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0779">Telomere</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000239019" description="Adrenocortical dysplasia protein homolog">
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            <begin position="1"/>
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    <feature type="region of interest" description="Interaction with POT1">
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            <begin position="158"/>
            <end position="251"/>
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    <feature type="region of interest" description="Disordered" evidence="1">
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            <begin position="265"/>
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    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="387"/>
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    <feature type="short sequence motif" description="PWI">
        <location>
            <begin position="11"/>
            <end position="13"/>
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    <feature type="compositionally biased region" description="Low complexity" evidence="1">
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            <begin position="265"/>
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    <feature type="compositionally biased region" description="Low complexity" evidence="1">
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            <begin position="293"/>
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    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="333"/>
            <end position="350"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="18 20">
        <location>
            <position position="25"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="349"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="21">
        <location>
            <position position="381"/>
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    <feature type="splice variant" id="VSP_060243" description="In isoform 2.">
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            <begin position="34"/>
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    <feature type="sequence variant" id="VAR_075693" description="In DKCA6 and DKCB7; localizes properly on telomeres; unable to recruit telomerase to the telomeres; dbSNP:rs797045144." evidence="12 13">
        <location>
            <position position="84"/>
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    <feature type="sequence variant" id="VAR_060224" description="In dbSNP:rs72547495.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="215"/>
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    <feature type="sequence variant" id="VAR_075694" description="In DKCB7; localizes properly on telomeres; decreased interaction with TINF2; dbSNP:rs201441120." evidence="13">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="405"/>
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        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="432"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAB14658." evidence="16" ref="3">
        <original>C</original>
        <variation>R</variation>
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            <position position="138"/>
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            <begin position="7"/>
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            <begin position="13"/>
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        <location>
            <begin position="19"/>
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    <feature type="strand" evidence="22">
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            <begin position="27"/>
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    <feature type="strand" evidence="22">
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            <begin position="56"/>
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    <feature type="strand" evidence="22">
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            <begin position="66"/>
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            <begin position="115"/>
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            <begin position="142"/>
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            <dbReference type="PubMed" id="16880378"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17237768"/>
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        <source>
            <dbReference type="PubMed" id="19648609"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="20231318"/>
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    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="25205116"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="25233904"/>
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    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="15181449"/>
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    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="15231715"/>
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    </evidence>
    <evidence type="ECO:0000305" key="16"/>
    <evidence type="ECO:0000312" key="17">
        <source>
            <dbReference type="HGNC" id="HGNC:25070"/>
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    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="19690332"/>
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    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="24275569"/>
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    <evidence type="ECO:0007744" key="21">
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            <dbReference type="PubMed" id="28112733"/>
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            <dbReference type="PDB" id="2I46"/>
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            <dbReference type="PDB" id="5H65"/>
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            <dbReference type="PDB" id="5I2X"/>
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            <dbReference type="PDB" id="5UN7"/>
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            <dbReference type="PDB" id="5XYF"/>
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            <dbReference type="PDB" id="7QXA"/>
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    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="7S1T"/>
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    <sequence length="458" mass="48967" checksum="6EA98FFC753E9A10" modified="2019-09-18" version="4">MAGSGRLVLRPWIRELILGSETPSSPRAGQLLEVLQDAEAAVAGPSHAPDTSDVGATLLVSDGTHSVRCLVTREALDTSDWEEKEFGFRGTEGRLLLLQDCGVHVQVAEGGAPAEFYLQVDRFSLLPTEQPRLRVPGCNQDLDVQKKLYDCLEEHLSESTSSNAGLSLSQLLDEMREDQEHQGALVCLAESCLTLEGPCTAPPVTHWAASRCKATGEAVYTVPSSMLCISENDQLILSSLGPCQRTQGPELPPPDPALQDLSLTLIASPPSSPSSSGTPALPGHMSSEESGTSISLLPALSLAAPDPGQRSSSQPSPAICSAPATLTPRSPHASRTPSSPLQSCTPSLSPRSHVPSPHQALVTRPQKPSLEFKEFVGLPCKNRPPFPRTGATRGAQEPCSVWEPPKRHRDGSAFQYEYEPPCTSLCARVQAVRLPPQLMAWALHFLMDAQPGSEPTPM</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>P45954</accession>
    <accession>B4DQ51</accession>
    <accession>Q5SQN6</accession>
    <accession>Q96CX7</accession>
    <name>ACDSB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial</fullName>
            <shortName evidence="16">SBCAD</shortName>
            <ecNumber evidence="5 12">1.3.8.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>2-methyl branched chain acyl-CoA dehydrogenase</fullName>
            <shortName>2-MEBCAD</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>2-methylbutyryl-coenzyme A dehydrogenase</fullName>
            <shortName>2-methylbutyryl-CoA dehydrogenase</shortName>
            <ecNumber evidence="3 11">1.3.8.5</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">ACADSB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Genomics" volume="24" first="280" last="287">
            <title>Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family.</title>
            <authorList>
                <person name="Rozen R."/>
                <person name="Vockley J."/>
                <person name="Zhou L."/>
                <person name="Milos R."/>
                <person name="Willard J."/>
                <person name="Fu K."/>
                <person name="Vicanek C."/>
                <person name="Low-Nang L."/>
                <person name="Torban E."/>
                <person name="Fournier B."/>
            </authorList>
            <dbReference type="PubMed" id="7698750"/>
            <dbReference type="DOI" id="10.1006/geno.1994.1617"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>TRANSIT PEPTIDE</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Am. J. Hum. Genet." volume="67" first="1095" last="1103">
            <title>Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism.</title>
            <authorList>
                <person name="Andresen B.S."/>
                <person name="Christensen E."/>
                <person name="Corydon T.J."/>
                <person name="Bross P."/>
                <person name="Pilgaard B."/>
                <person name="Wanders R.J.A."/>
                <person name="Ruiter J.P.N."/>
                <person name="Simonsen H."/>
                <person name="Winter V."/>
                <person name="Knudsen I."/>
                <person name="Schroeder L.D."/>
                <person name="Gregersen N."/>
                <person name="Skovby F."/>
            </authorList>
            <dbReference type="PubMed" id="11013134"/>
            <dbReference type="DOI" id="10.1086/303105"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>INVOLVEMENT IN SBCADD</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
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    <comment type="function">
        <text evidence="3 4 11 12 13">Short and branched chain specific acyl-CoA dehydrogenase that catalyzes the proR-proR stereospecific alpha,beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:10832746, PubMed:11013134, PubMed:21430231, PubMed:7698750). Among the different mitochondrial acyl-CoA dehydrogenases, acts specifically on short and branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such as butyryl-CoA (butanoyl-CoA) (PubMed:10832746, PubMed:11013134, PubMed:21430231, PubMed:7698750). Plays an important role in the metabolism of L-isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-isoleucine catabolic pathway (PubMed:10832746, PubMed:11013134). Can also act on valproyl-CoA, a metabolite of valproic acid, an antiepileptic drug (PubMed:8660691).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 10 12">
            <text>a short-chain 2,3-saturated fatty acyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = a short-chain (2E)-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:47196"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:87487"/>
            <dbReference type="ChEBI" id="CHEBI:87488"/>
            <dbReference type="EC" id="1.3.8.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:47197"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 11">
            <text>2-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43780"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57336"/>
            <dbReference type="ChEBI" id="CHEBI:57337"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="EC" id="1.3.8.5"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:43781"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5 12">
            <text>(2S)-2-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-2-methylbut-2-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48256"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57337"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:88166"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:48257"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(2R)-2-methylbutanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = ethylacryloyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:65296"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:156439"/>
            <dbReference type="ChEBI" id="CHEBI:156440"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:65297"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>2-methylpropanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = 2-methylpropenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:44180"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57338"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62500"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:44181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12">
            <text>2-methylhexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = 2-methylhexenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:48272"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:90156"/>
            <dbReference type="ChEBI" id="CHEBI:90157"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:48273"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13">
            <text>valproyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-2-propylpent-2-enoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:65344"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:156457"/>
            <dbReference type="ChEBI" id="CHEBI:156458"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20">
            <dbReference type="Rhea" id="RHEA:65345"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 12">
            <text>butanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-butenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:24004"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57332"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:24005"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 10 12">
            <text>hexanoyl-CoA + oxidized [electron-transfer flavoprotein] + H(+) = (2E)-hexenoyl-CoA + reduced [electron-transfer flavoprotein]</text>
            <dbReference type="Rhea" id="RHEA:43464"/>
            <dbReference type="Rhea" id="RHEA-COMP:10685"/>
            <dbReference type="Rhea" id="RHEA-COMP:10686"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <dbReference type="ChEBI" id="CHEBI:58307"/>
            <dbReference type="ChEBI" id="CHEBI:62077"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:43465"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="14">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="11">Competitively inhibited by valproyl-CoA.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="11">12 uM for 2-methylbutanoyl-CoA (at pH 8.0 and 37 degrees Celsius)</KM>
            <KM evidence="5">2.7 uM for (2S)-2-methylbutanoyl-CoA (at 32 degrees Celsius)</KM>
            <KM evidence="5">36 uM for hexanoyl-CoA (at 32 degrees Celsius)</KM>
            <KM evidence="5">130 uM for 2-methylpropanoyl-CoA (at 32 degrees Celsius)</KM>
            <Vmax evidence="11">12.0 umol/min/mg enzyme with 2-methylbutanoyl-CoA as substrate (at pH 8.0 and 37 degrees Celsius)</Vmax>
            <text evidence="5">kcat is 9700 sec(-1) for the dehydrogenation of (2S)-2-methylbutanoyl-CoA (PubMed:12855692). kcat is 7600 sec(-1) for the dehydrogenation of hexanoyl-CoA (PubMed:12855692). kcat is 2900 sec(-1) for the dehydrogenation of hexanoyl-CoA (PubMed:12855692).</text>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="4">Lipid metabolism; mitochondrial fatty acid beta-oxidation.</text>
    </comment>
    <comment type="pathway">
        <text evidence="4">Amino-acid degradation; L-isoleucine degradation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 14">Homotetramer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="18">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P45954-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P45954-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055778"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8 13">Ubiquitously expressed, with highest levels in heart, muscle and liver.</text>
    </comment>
    <comment type="disease" evidence="3 4 7">
        <disease id="DI-02302">
            <name>Short/branched-chain acyl-CoA dehydrogenase deficiency</name>
            <acronym>SBCADD</acronym>
            <description>Autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features.</description>
            <dbReference type="MIM" id="610006"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the acyl-CoA dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.8.1" evidence="5 12"/>
    <dbReference type="EC" id="1.3.8.5" evidence="3 11"/>
    <dbReference type="EMBL" id="U12778">
        <property type="protein sequence ID" value="AAA74424.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260678">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260668">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260669">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260670">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260671">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260672">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260673">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260674">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260675">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260676">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF260677">
        <property type="protein sequence ID" value="AAF97921.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298638">
        <property type="protein sequence ID" value="BAG60813.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314241">
        <property type="protein sequence ID" value="BAG36909.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012391">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073585">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL731666">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49291.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC013756">
        <property type="protein sequence ID" value="AAH13756.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL831821">
        <property type="protein sequence ID" value="CAD38535.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7634.1">
        <molecule id="P45954-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81518.1">
        <molecule id="P45954-2"/>
    </dbReference>
    <dbReference type="PIR" id="A55680">
        <property type="entry name" value="A55680"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001317103.1">
        <molecule id="P45954-2"/>
        <property type="nucleotide sequence ID" value="NM_001330174.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001600.1">
        <molecule id="P45954-1"/>
        <property type="nucleotide sequence ID" value="NM_001609.4"/>
    </dbReference>
    <dbReference type="PDB" id="2JIF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B/C/D=52-432"/>
    </dbReference>
    <dbReference type="PDBsum" id="2JIF"/>
    <dbReference type="AlphaFoldDB" id="P45954"/>
    <dbReference type="SMR" id="P45954"/>
    <dbReference type="BioGRID" id="106554">
        <property type="interactions" value="82"/>
    </dbReference>
    <dbReference type="FunCoup" id="P45954">
        <property type="interactions" value="1257"/>
    </dbReference>
    <dbReference type="IntAct" id="P45954">
        <property type="interactions" value="40"/>
    </dbReference>
    <dbReference type="MINT" id="P45954"/>
    <dbReference type="STRING" id="9606.ENSP00000357873"/>
    <dbReference type="DrugBank" id="DB00167">
        <property type="generic name" value="Isoleucine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00313">
        <property type="generic name" value="Valproic acid"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000001415"/>
    <dbReference type="iPTMnet" id="P45954"/>
    <dbReference type="PhosphoSitePlus" id="P45954"/>
    <dbReference type="SwissPalm" id="P45954"/>
    <dbReference type="BioMuta" id="ACADSB"/>
    <dbReference type="DMDM" id="1168283"/>
    <dbReference type="jPOST" id="P45954"/>
    <dbReference type="MassIVE" id="P45954"/>
    <dbReference type="PaxDb" id="9606-ENSP00000357873"/>
    <dbReference type="PeptideAtlas" id="P45954"/>
    <dbReference type="ProteomicsDB" id="4844"/>
    <dbReference type="ProteomicsDB" id="55690">
        <molecule id="P45954-1"/>
    </dbReference>
    <dbReference type="Pumba" id="P45954"/>
    <dbReference type="Antibodypedia" id="19074">
        <property type="antibodies" value="155 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="36"/>
    <dbReference type="Ensembl" id="ENST00000358776.7">
        <molecule id="P45954-1"/>
        <property type="protein sequence ID" value="ENSP00000357873.3"/>
        <property type="gene ID" value="ENSG00000196177.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000368869.8">
        <molecule id="P45954-2"/>
        <property type="protein sequence ID" value="ENSP00000357862.4"/>
        <property type="gene ID" value="ENSG00000196177.14"/>
    </dbReference>
    <dbReference type="GeneID" id="36"/>
    <dbReference type="KEGG" id="hsa:36"/>
    <dbReference type="MANE-Select" id="ENST00000358776.7">
        <property type="protein sequence ID" value="ENSP00000357873.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001609.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001600.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001lhb.4">
        <molecule id="P45954-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:91"/>
    <dbReference type="ClinPGx" id="PA24427"/>
    <dbReference type="CTD" id="36"/>
    <dbReference type="DisGeNET" id="36"/>
    <dbReference type="GeneCards" id="ACADSB"/>
    <dbReference type="HGNC" id="HGNC:91">
        <property type="gene designation" value="ACADSB"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000196177">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACADSB"/>
    <dbReference type="MIM" id="600301">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="610006">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000196177"/>
    <dbReference type="Orphanet" id="79157">
        <property type="disease" value="2-methylbutyryl-CoA dehydrogenase deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000196177"/>
    <dbReference type="eggNOG" id="KOG0139">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156525"/>
    <dbReference type="HOGENOM" id="CLU_018204_0_0_1"/>
    <dbReference type="InParanoid" id="P45954"/>
    <dbReference type="OMA" id="DAMFSYC"/>
    <dbReference type="OrthoDB" id="10262177at2759"/>
    <dbReference type="PAN-GO" id="P45954">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P45954"/>
    <dbReference type="BioCyc" id="MetaCyc:HS10828-MONOMER"/>
    <dbReference type="PathwayCommons" id="P45954"/>
    <dbReference type="Reactome" id="R-HSA-70895">
        <property type="pathway name" value="Branched-chain amino acid catabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9837999">
        <property type="pathway name" value="Mitochondrial protein degradation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P45954"/>
    <dbReference type="UniPathway" id="UPA00364"/>
    <dbReference type="UniPathway" id="UPA00660"/>
    <dbReference type="Agora" id="ENSG00000196177"/>
    <dbReference type="BioGRID-ORCS" id="36">
        <property type="hits" value="11 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACADSB">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P45954"/>
    <dbReference type="GenomeRNAi" id="36"/>
    <dbReference type="Pharos" id="P45954">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P45954"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="P45954">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000196177">
        <property type="expression patterns" value="Expressed in right lobe of liver and 195 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P45954">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003995">
        <property type="term" value="F:acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003853">
        <property type="term" value="F:short-chain 2-methyl fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016937">
        <property type="term" value="F:short-chain fatty acyl-CoA dehydrogenase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:L-isoleucine catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
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        <property type="entry name" value="SCAD_SBCAD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
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    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
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    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
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    <dbReference type="InterPro" id="IPR009075">
        <property type="entry name" value="AcylCo_DH/oxidase_C"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Acyl-CoA_dh_M"/>
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    <keyword id="KW-0809">Transit peptide</keyword>
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    <feature type="chain" id="PRO_0000000519" description="Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial">
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            <begin position="34"/>
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    <feature type="active site" description="Proton acceptor" evidence="21">
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    <feature type="binding site" description="in other chain" evidence="14">
        <location>
            <begin position="174"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
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    <feature type="binding site" evidence="14">
        <location>
            <position position="183"/>
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        <ligand>
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    <feature type="binding site" description="in other chain" evidence="14">
        <location>
            <begin position="207"/>
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        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
            <note>ligand shared between dimeric partners</note>
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    <feature type="binding site" evidence="14">
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            <position position="229"/>
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        <ligand>
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    <feature type="binding site" evidence="14">
        <location>
            <position position="283"/>
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        <ligand>
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    <feature type="binding site" evidence="14">
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            <begin position="291"/>
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        <ligand>
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    <feature type="binding site" evidence="14">
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        <ligand>
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            <note>ligand shared between dimeric partners</note>
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    <feature type="binding site" evidence="14">
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            <position position="330"/>
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        <ligand>
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            <note>ligand shared between dimeric partners</note>
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    <feature type="binding site" evidence="14">
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            <begin position="387"/>
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        <ligand>
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            <note>ligand shared between dimeric partners</note>
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        <ligand>
            <name>FAD</name>
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            <note>ligand shared between dimeric partners</note>
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    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="70"/>
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    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="70"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="24">
        <location>
            <position position="183"/>
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    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="23">
        <location>
            <position position="284"/>
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    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
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            <position position="284"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="426"/>
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    <feature type="splice variant" id="VSP_055778" description="In isoform 2." evidence="15">
        <location>
            <begin position="1"/>
            <end position="102"/>
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        <original>R</original>
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        <location>
            <position position="13"/>
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            <position position="209"/>
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        <location>
            <position position="255"/>
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            <position position="316"/>
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        <original>E</original>
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        <location>
            <position position="376"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreased acyl-CoA dehydrogenase activity." evidence="5">
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        <location>
            <position position="137"/>
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    <feature type="mutagenesis site" description="Increased acyl-CoA dehydrogenase activity. No effect on substrate specificity." evidence="5">
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            <position position="138"/>
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    <feature type="mutagenesis site" description="Increased acyl-CoA dehydrogenase activity. No effect on substrate specificity." evidence="5">
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            <position position="416"/>
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    <feature type="helix" evidence="25">
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    <feature type="helix" evidence="25">
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    <feature type="turn" evidence="25">
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            <begin position="100"/>
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    <feature type="strand" evidence="25">
        <location>
            <begin position="104"/>
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        <location>
            <begin position="109"/>
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    <feature type="helix" evidence="25">
        <location>
            <begin position="118"/>
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    <feature type="helix" evidence="25">
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    <feature type="helix" evidence="25">
        <location>
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        <location>
            <begin position="156"/>
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            <begin position="172"/>
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            <begin position="181"/>
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    <sequence length="432" mass="47485" checksum="1EB5F894B1944E99" modified="1995-11-01" version="1" precursor="true">MEGLAVRLLRGSRLLRRNFLTCLSSWKIPPHVSKSSQSEALLNITNNGIHFAPLQTFTDEEMMIKSSVKKFAQEQIAPLVSTMDENSKMEKSVIQGLFQQGLMGIEVDPEYGGTGASFLSTVLVIEELAKVDASVAVFCEIQNTLINTLIRKHGTEEQKATYLPQLTTEKVGSFCLSEAGAGSDSFALKTRADKEGDYYVLNGSKMWISSAEHAGLFLVMANVDPTIGYKGITSFLVDRDTPGLHIGKPENKLGLRASSTCPLTFENVKVPEANILGQIGHGYKYAIGSLNEGRIGIAAQMLGLAQGCFDYTIPYIKERIQFGKRLFDFQGLQHQVAHVATQLEAARLLTYNAARLLEAGKPFIKEASMAKYYASEIAGQTTSKCIEWMGGVGYTKDYPVEKYFRDAKIGTIYEGASNIQLNTIAKHIDAEY</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-07-25" modified="2026-01-28" version="152" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TDN7</accession>
    <name>ACER1_HUMAN</name>
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        <recommendedName>
            <fullName evidence="9">Alkaline ceramidase 1</fullName>
            <shortName>AlkCDase 1</shortName>
            <shortName>Alkaline CDase 1</shortName>
            <ecNumber evidence="6 7">3.5.1.-</ecNumber>
            <ecNumber evidence="5">3.5.1.23</ecNumber>
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        <alternativeName>
            <fullName>Acylsphingosine deacylase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>N-acylsphingosine amidohydrolase 3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="10" type="primary">ACER1</name>
        <name type="synonym">ASAH3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="31184" last="31191">
            <title>Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides.</title>
            <authorList>
                <person name="Mao C."/>
                <person name="Xu R."/>
                <person name="Szulc Z.M."/>
                <person name="Bielawski J."/>
                <person name="Becker K.P."/>
                <person name="Bielawska A."/>
                <person name="Galadari S.H."/>
                <person name="Hu W."/>
                <person name="Obeid L.M."/>
            </authorList>
            <dbReference type="PubMed" id="12783875"/>
            <dbReference type="DOI" id="10.1074/jbc.m303875200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="J. Lipid Res." volume="47" first="1063" last="1070">
            <title>Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis.</title>
            <authorList>
                <person name="Houben E."/>
                <person name="Holleran W.M."/>
                <person name="Yaginuma T."/>
                <person name="Mao C."/>
                <person name="Obeid L.M."/>
                <person name="Rogiers V."/>
                <person name="Takagi Y."/>
                <person name="Elias P.M."/>
                <person name="Uchida Y."/>
            </authorList>
            <dbReference type="PubMed" id="16477081"/>
            <dbReference type="DOI" id="10.1194/jlr.m600001-jlr200"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2008" name="J. Invest. Dermatol." volume="128" first="389" last="397">
            <title>Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes.</title>
            <authorList>
                <person name="Sun W."/>
                <person name="Xu R."/>
                <person name="Hu W."/>
                <person name="Jin J."/>
                <person name="Crellin H.A."/>
                <person name="Bielawski J."/>
                <person name="Szulc Z.M."/>
                <person name="Thiers B.H."/>
                <person name="Obeid L.M."/>
                <person name="Mao C."/>
            </authorList>
            <dbReference type="PubMed" id="17713573"/>
            <dbReference type="DOI" id="10.1038/sj.jid.5701025"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>PATHWAY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION BY CALCIUM</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2010" name="FASEB J." volume="24" first="2507" last="2515">
            <title>Role of alkaline ceramidases in the generation of sphingosine and its phosphate in erythrocytes.</title>
            <authorList>
                <person name="Xu R."/>
                <person name="Sun W."/>
                <person name="Jin J."/>
                <person name="Obeid L.M."/>
                <person name="Mao C."/>
            </authorList>
            <dbReference type="PubMed" id="20207939"/>
            <dbReference type="DOI" id="10.1096/fj.09-153635"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2010" name="J. Biol. Chem." volume="285" first="29078" last="29090">
            <title>Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells.</title>
            <authorList>
                <person name="Mao Z."/>
                <person name="Sun W."/>
                <person name="Xu R."/>
                <person name="Novgorodov S."/>
                <person name="Szulc Z.M."/>
                <person name="Bielawski J."/>
                <person name="Obeid L.M."/>
                <person name="Mao C."/>
            </authorList>
            <dbReference type="PubMed" id="20628055"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.105296"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 8">Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline pH (PubMed:17713573, PubMed:20207939, PubMed:20628055). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:12783875). Exhibits a strong substrate specificity towards the natural stereoisomer of ceramides with D-erythro-sphingosine as a backbone and has a higher activity towards very long-chain unsaturated fatty acids like the C24:1-ceramide (PubMed:17713573, PubMed:20207939). May also hydrolyze dihydroceramides to produce dihydrosphingosine (PubMed:20207939, PubMed:20628055). ACER1 is a skin-specific ceramidase that regulates the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes and more generally plays an important role in skin homeostasis (PubMed:17713573).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:20856"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:52639"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="EC" id="3.5.1.23"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:20857"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>N-tetracosanoyl-sphing-4-enine + H2O = tetracosanoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41283"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:31014"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72965"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:41284"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7">
            <text>an N-acylsphinganine + H2O = sphinganine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:33551"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:31488"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:33552"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>N-(9Z-octadecenoyl)-sphing-4-enine + H2O = sphing-4-enine + (9Z)-octadecenoate</text>
            <dbReference type="Rhea" id="RHEA:41299"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:77996"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:41300"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>N-(15Z-tetracosenoyl)-sphing-4-enine + H2O = (15Z)-tetracosenoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41267"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32392"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:74450"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:41268"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 5">Inhibited by sphingosine (By similarity). Activity is Ca(2+)-dependent (PubMed:17713573).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <phDependence>
            <text evidence="5">Optimum pH is 8.0.</text>
        </phDependence>
    </comment>
    <comment type="pathway">
        <text evidence="5 6">Lipid metabolism; sphingolipid metabolism.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13074986">
            <id>Q8TDN7</id>
        </interactant>
        <interactant intactId="EBI-711788">
            <id>Q00013</id>
            <label>MPP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Endoplasmic reticulum membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5">Mainly expressed in epidermis.</text>
    </comment>
    <comment type="induction">
        <text evidence="5">Up-regulated by Ca(2+) (PubMed:17713573). Down-regulated by epidermal growth factor/EGF (PubMed:17713573).</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the alkaline ceramidase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.-" evidence="6 7"/>
    <dbReference type="EC" id="3.5.1.23" evidence="5"/>
    <dbReference type="EMBL" id="AF347024">
        <property type="protein sequence ID" value="AAL83822.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC112122">
        <property type="protein sequence ID" value="AAI12123.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC112124">
        <property type="protein sequence ID" value="AAI12125.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12161.1"/>
    <dbReference type="RefSeq" id="NP_597999.1">
        <property type="nucleotide sequence ID" value="NM_133492.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TDN7"/>
    <dbReference type="SMR" id="Q8TDN7"/>
    <dbReference type="BioGRID" id="125942">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TDN7">
        <property type="interactions" value="316"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TDN7">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000301452"/>
    <dbReference type="ChEMBL" id="CHEMBL3351194"/>
    <dbReference type="SwissLipids" id="SLP:000000165"/>
    <dbReference type="BioMuta" id="ACER1"/>
    <dbReference type="DMDM" id="74715919"/>
    <dbReference type="MassIVE" id="Q8TDN7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000301452"/>
    <dbReference type="PeptideAtlas" id="Q8TDN7"/>
    <dbReference type="Antibodypedia" id="49939">
        <property type="antibodies" value="144 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="125981"/>
    <dbReference type="Ensembl" id="ENST00000301452.5">
        <property type="protein sequence ID" value="ENSP00000301452.3"/>
        <property type="gene ID" value="ENSG00000167769.5"/>
    </dbReference>
    <dbReference type="GeneID" id="125981"/>
    <dbReference type="KEGG" id="hsa:125981"/>
    <dbReference type="MANE-Select" id="ENST00000301452.5">
        <property type="protein sequence ID" value="ENSP00000301452.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_133492.3"/>
        <property type="RefSeq protein sequence ID" value="NP_597999.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002mel.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18356"/>
    <dbReference type="ClinPGx" id="PA164714838"/>
    <dbReference type="CTD" id="125981"/>
    <dbReference type="DisGeNET" id="125981"/>
    <dbReference type="GeneCards" id="ACER1"/>
    <dbReference type="HGNC" id="HGNC:18356">
        <property type="gene designation" value="ACER1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000167769">
        <property type="expression patterns" value="Tissue enriched (skin)"/>
    </dbReference>
    <dbReference type="MIM" id="613491">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000167769"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000167769"/>
    <dbReference type="eggNOG" id="KOG2329">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00730000110920"/>
    <dbReference type="HOGENOM" id="CLU_088280_1_0_1"/>
    <dbReference type="InParanoid" id="Q8TDN7"/>
    <dbReference type="OMA" id="NYKHSEH"/>
    <dbReference type="OrthoDB" id="187171at2759"/>
    <dbReference type="PAN-GO" id="Q8TDN7">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8TDN7"/>
    <dbReference type="BRENDA" id="3.5.1.23">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q8TDN7"/>
    <dbReference type="Reactome" id="R-HSA-9845614">
        <property type="pathway name" value="Sphingolipid catabolism"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8TDN7"/>
    <dbReference type="UniPathway" id="UPA00222"/>
    <dbReference type="Agora" id="ENSG00000167769"/>
    <dbReference type="BioGRID-ORCS" id="125981">
        <property type="hits" value="23 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACER1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACER1"/>
    <dbReference type="GenomeRNAi" id="125981"/>
    <dbReference type="Pharos" id="Q8TDN7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8TDN7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TDN7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000167769">
        <property type="expression patterns" value="Expressed in skin of leg and 75 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017040">
        <property type="term" value="F:N-acylsphingosine amidohydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071277">
        <property type="term" value="P:cellular response to calcium ion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046514">
        <property type="term" value="P:ceramide catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008544">
        <property type="term" value="P:epidermis development"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030216">
        <property type="term" value="P:keratinocyte differentiation"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019216">
        <property type="term" value="P:regulation of lipid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010446">
        <property type="term" value="P:response to alkaline pH"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048733">
        <property type="term" value="P:sebaceous gland development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030148">
        <property type="term" value="P:sphingolipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030149">
        <property type="term" value="P:sphingolipid catabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006665">
        <property type="term" value="P:sphingolipid metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046512">
        <property type="term" value="P:sphingosine biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008901">
        <property type="entry name" value="ACER"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46139">
        <property type="entry name" value="ALKALINE CERAMIDASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46139:SF2">
        <property type="entry name" value="ALKALINE CERAMIDASE 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05875">
        <property type="entry name" value="Ceramidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0746">Sphingolipid metabolism</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000247745" description="Alkaline ceramidase 1">
        <location>
            <begin position="1"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="1"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="28"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="49"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="58"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="79"/>
            <end position="81"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="82"/>
            <end position="102"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="103"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="120"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="139"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="160"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="177"/>
            <end position="197"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="198"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="207"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="228"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="13"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="14"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
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        <location>
            <position position="16"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="18"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="27"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="77"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
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            <position position="206"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
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    <feature type="binding site" evidence="2">
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            <position position="210"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8R4X1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9NUN7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16477081"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17713573"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="20207939"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="20628055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="12783875"/>
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    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="HGNC" id="HGNC:18356"/>
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    <sequence length="264" mass="31095" checksum="E16E5DB81D064F60" modified="2002-06-01" version="1">MPSIFAYQSSEVDWCESNFQYSELVAEFYNTFSNIPFFIFGPLMMLLMHPYAQKRSRYIYVVWVLFMIIGLFSMYFHMTLSFLGQLLDEIAILWLLGSGYSIWMPRCYFPSFLGGNRSQFIRLVFITTVVSTLLSFLRPTVNAYALNSIALHILYIVCQEYRKTSNKELRHLIEVSVVLWAVALTSWISDRLLCSFWQRIHFFYLHSIWHVLISITFPYGMVTMALVDANYEMPGETLKVRYWPRDSWPVGLPYVEIRGDDKDC</sequence>
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<entry dataset="Swiss-Prot" created="2005-08-02" modified="2026-01-28" version="207" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BYF1</accession>
    <accession>A0A7D6JAD5</accession>
    <accession>C7ECU1</accession>
    <accession>Q6UWP0</accession>
    <accession>Q86WT0</accession>
    <accession>Q9NRA7</accession>
    <accession>Q9UFZ6</accession>
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        <recommendedName>
            <fullName>Angiotensin-converting enzyme 2</fullName>
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        <alternativeName>
            <fullName evidence="66">Angiotensin-converting enzyme homolog</fullName>
            <shortName evidence="66">ACEH</shortName>
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        <alternativeName>
            <fullName evidence="67">Angiotensin-converting enzyme-related carboxypeptidase</fullName>
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        <alternativeName>
            <fullName evidence="71">Metalloprotease MPROT15</fullName>
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        <component>
            <recommendedName>
                <fullName evidence="68">Processed angiotensin-converting enzyme 2</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="83" type="primary">ACE2</name>
        <name type="ORF">UNQ868/PRO1885</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>SUBSTRATE SPECIFICITY</scope>
        <source>
            <tissue>Heart</tissue>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>FUNCTION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>ACTIVITY REGULATION</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION (ISOFORM 2)</scope>
        <scope>INDUCTION BY IFN (ISOFORM 2)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ARG-26</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Brain</tissue>
            <tissue>Testis</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH ITGB1</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) OF 19-615</scope>
        <scope>GLYCOSYLATION AT ASN-90 AND ASN-546 IN COMPLEX WITH HUMAN CORONAVIRUS NL63 SPIKE PROTEIN</scope>
        <scope>INTERACTION WITH HUMAN CORONAVIRUS NL63 SPIKE PROTEIN (MICROBIAL INFECTION)</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
    </reference>
    <reference evidence="88 89 90" key="66">
        <citation type="journal article" date="2018" name="PLoS Pathog." volume="14" first="e1007236" last="e1007236">
            <title>Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2.</title>
            <authorList>
                <person name="Song W."/>
                <person name="Gui M."/>
                <person name="Wang X."/>
                <person name="Xiang Y."/>
            </authorList>
            <dbReference type="PubMed" id="30102747"/>
            <dbReference type="DOI" id="10.1371/journal.ppat.1007236"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 19-615</scope>
    </reference>
    <reference evidence="91" key="67">
        <citation type="journal article" date="2018" name="Sci. Rep." volume="8" first="15701" last="15701">
            <title>Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis.</title>
            <authorList>
                <person name="Kirchdoerfer R.N."/>
                <person name="Wang N."/>
                <person name="Pallesen J."/>
                <person name="Wrapp D."/>
                <person name="Turner H.L."/>
                <person name="Cottrell C.A."/>
                <person name="Corbett K.S."/>
                <person name="Graham B.S."/>
                <person name="McLellan J.S."/>
                <person name="Ward A.B."/>
            </authorList>
            <dbReference type="PubMed" id="30356097"/>
            <dbReference type="DOI" id="10.1038/s41598-018-34171-7"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 19-615</scope>
    </reference>
    <reference evidence="92" key="68">
        <citation type="journal article" date="2020" name="Nature" volume="581" first="215" last="220">
            <title>Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.</title>
            <authorList>
                <person name="Lan J."/>
                <person name="Ge J."/>
                <person name="Yu J."/>
                <person name="Shan S."/>
                <person name="Zhou H."/>
                <person name="Fan S."/>
                <person name="Zhang Q."/>
                <person name="Shi X."/>
                <person name="Wang Q."/>
                <person name="Zhang L."/>
                <person name="Wang X."/>
            </authorList>
            <dbReference type="PubMed" id="32225176"/>
            <dbReference type="DOI" id="10.1038/s41586-020-2180-5"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 19-615 IN COMPLEX WITH SARS-COV-2 SPIKE GLYCOPROTEIN</scope>
    </reference>
    <reference evidence="96" key="69">
        <citation type="journal article" date="2020" name="Nature" volume="581" first="221" last="224">
            <title>Structural basis of receptor recognition by SARS-CoV-2.</title>
            <authorList>
                <person name="Shang J."/>
                <person name="Ye G."/>
                <person name="Shi K."/>
                <person name="Wan Y."/>
                <person name="Luo C."/>
                <person name="Aihara H."/>
                <person name="Geng Q."/>
                <person name="Auerbach A."/>
                <person name="Li F."/>
            </authorList>
            <dbReference type="PubMed" id="32225175"/>
            <dbReference type="DOI" id="10.1038/s41586-020-2179-y"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 19-615 AND IN COMPLEX WITH SARS-COV-2 SPIKE GLYCOPROTEIN</scope>
        <scope>INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN (MICROBIAL INFECTION)</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
    </reference>
    <reference evidence="93 94 95" key="70">
        <citation type="journal article" date="2020" name="Science" volume="367" first="1444" last="1448">
            <title>Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2.</title>
            <authorList>
                <person name="Yan R."/>
                <person name="Zhang Y."/>
                <person name="Li Y."/>
                <person name="Xia L."/>
                <person name="Guo Y."/>
                <person name="Zhou Q."/>
            </authorList>
            <dbReference type="PubMed" id="32132184"/>
            <dbReference type="DOI" id="10.1126/science.abb2762"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 18-805</scope>
        <scope>INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH SLC6A19</scope>
        <scope>SUBUNIT</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
    </reference>
    <reference key="71">
        <citation type="journal article" date="2020" name="Front. Genet." volume="11" first="551220" last="551220">
            <title>Analysis of the Spectrum of ACE2 Variation Suggests a Possible Influence of Rare and Common Variants on Susceptibility to COVID-19 and Severity of Outcome.</title>
            <authorList>
                <person name="Shikov A.E."/>
                <person name="Barbitoff Y.A."/>
                <person name="Glotov A.S."/>
                <person name="Danilova M.M."/>
                <person name="Tonyan Z.N."/>
                <person name="Nasykhova Y.A."/>
                <person name="Mikhailova A.A."/>
                <person name="Bespalova O.N."/>
                <person name="Kalinin R.S."/>
                <person name="Mirzorustamova A.M."/>
                <person name="Kogan I.Y."/>
                <person name="Baranov V.S."/>
                <person name="Chernov A.N."/>
                <person name="Pavlovich D.M."/>
                <person name="Azarenko S.V."/>
                <person name="Fedyakov M.A."/>
                <person name="Tsay V.V."/>
                <person name="Eismont Y.A."/>
                <person name="Romanova O.V."/>
                <person name="Hobotnikov D.N."/>
                <person name="Vologzhanin D.A."/>
                <person name="Mosenko S.V."/>
                <person name="Ponomareva T.A."/>
                <person name="Talts Y.A."/>
                <person name="Anisenkova A.U."/>
                <person name="Lisovets D.G."/>
                <person name="Sarana A.M."/>
                <person name="Urazov S.P."/>
                <person name="Scherbak S.G."/>
                <person name="Glotov O.S."/>
            </authorList>
            <dbReference type="PubMed" id="33133145"/>
            <dbReference type="DOI" id="10.3389/fgene.2020.551220"/>
        </citation>
        <scope>VARIANT ASP-720</scope>
    </reference>
    <reference key="72">
        <citation type="journal article" date="2020" name="Mol. Genet. Genomic Med." volume="0" first="0" last="0">
            <title>Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations.</title>
            <authorList>
                <person name="Li Q."/>
                <person name="Cao Z."/>
                <person name="Rahman P."/>
            </authorList>
            <dbReference type="PubMed" id="32558308"/>
            <dbReference type="DOI" id="10.1002/mgg3.1344"/>
        </citation>
        <scope>VARIANTS ARG-26; VAL-468; SER-638 AND ASP-720</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7 8 11 26 27 29 34">Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis (PubMed:27217402). Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II (PubMed:10924499, PubMed:10969042, PubMed:11815627, PubMed:14504186, PubMed:19021774). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity (PubMed:18424768, PubMed:19185582).</text>
    </comment>
    <comment type="function">
        <text evidence="12 19 21 22 30 33 38 40 41 51 53 56">(Microbial infection) Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="52">Non-functional as a carboxypeptidase.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="52 57">(Microbial infection) Non-functional as a receptor for human coronavirus SARS-CoV-2.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8 27 76">
            <text>angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:26554"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:58506"/>
            <dbReference type="ChEBI" id="CHEBI:58922"/>
            <dbReference type="EC" id="3.4.17.23"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:26555"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7 8 27">
            <text>angiotensin I + H2O = angiotensin-(1-9) + L-leucine</text>
            <dbReference type="Rhea" id="RHEA:63532"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57427"/>
            <dbReference type="ChEBI" id="CHEBI:147350"/>
            <dbReference type="ChEBI" id="CHEBI:147351"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="73 74 75 78">
            <dbReference type="Rhea" id="RHEA:63533"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>bradykinin(1-8) + H2O = bradykinin(1-7) + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:63536"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:133069"/>
            <dbReference type="ChEBI" id="CHEBI:147352"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="74 75">
            <dbReference type="Rhea" id="RHEA:63537"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>neurotensin + H2O = neurotensin-(1-12) + L-leucine</text>
            <dbReference type="Rhea" id="RHEA:63540"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57427"/>
            <dbReference type="ChEBI" id="CHEBI:147362"/>
            <dbReference type="ChEBI" id="CHEBI:147363"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="74">
            <dbReference type="Rhea" id="RHEA:63541"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>neurotensin-(1-8) + H2O = neurotensin-(1-7) + L-arginine</text>
            <dbReference type="Rhea" id="RHEA:63572"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32682"/>
            <dbReference type="ChEBI" id="CHEBI:147393"/>
            <dbReference type="ChEBI" id="CHEBI:147394"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="75">
            <dbReference type="Rhea" id="RHEA:63573"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>kinetensin + H2O = kinetensin-(1-8) + L-leucine</text>
            <dbReference type="Rhea" id="RHEA:63544"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57427"/>
            <dbReference type="ChEBI" id="CHEBI:147364"/>
            <dbReference type="ChEBI" id="CHEBI:147365"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="74">
            <dbReference type="Rhea" id="RHEA:63545"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine</text>
            <dbReference type="Rhea" id="RHEA:63556"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32551"/>
            <dbReference type="ChEBI" id="CHEBI:147381"/>
            <dbReference type="ChEBI" id="CHEBI:147383"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="75">
            <dbReference type="Rhea" id="RHEA:63557"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>apelin-13 + H2O = apelin-12 + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:63564"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:147395"/>
            <dbReference type="ChEBI" id="CHEBI:147396"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="75">
            <dbReference type="Rhea" id="RHEA:63565"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="34 35">
            <text>[Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:63604"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:147415"/>
            <dbReference type="ChEBI" id="CHEBI:147416"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="34">
            <dbReference type="Rhea" id="RHEA:63605"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="34">
            <text>apelin-17 + H2O = apelin-16 + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:63608"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:147421"/>
            <dbReference type="ChEBI" id="CHEBI:147422"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="34">
            <dbReference type="Rhea" id="RHEA:63609"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>beta-casomorphin-7 + H2O = beta-casomorphin-6 + L-isoleucine</text>
            <dbReference type="Rhea" id="RHEA:63568"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58045"/>
            <dbReference type="ChEBI" id="CHEBI:147390"/>
            <dbReference type="ChEBI" id="CHEBI:147391"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="75">
            <dbReference type="Rhea" id="RHEA:63569"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>neocasomorphin + H2O = neocasomorphin-(1-5) + L-isoleucine</text>
            <dbReference type="Rhea" id="RHEA:63600"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58045"/>
            <dbReference type="ChEBI" id="CHEBI:147417"/>
            <dbReference type="ChEBI" id="CHEBI:147418"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="75">
            <dbReference type="Rhea" id="RHEA:63601"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="8">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8">
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </cofactor>
        <text evidence="8">Binds 1 Cl(-) ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="6 7 8 9 17 27">Regulated by chloride and fluoride, but not bromide (PubMed:11815627). Chloride increases angiotensin I and decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by the ACE inhibitors lisinopril, captopril and enalaprilat (PubMed:10924499, PubMed:10969042). Highly potent and selective in vitro ACE2 inhibitors were identified (PubMed:12358520).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="8">6.9 uM for angiotensin I</KM>
            <KM evidence="8">2 uM for angiotensin II</KM>
            <KM evidence="8">6.8 uM for apelin-13</KM>
            <KM evidence="8">290 uM for [des-Arg(9)]-bradykinin</KM>
            <KM evidence="8">130 uM for Lys-[des-Arg(9)]-bradykinin</KM>
            <KM evidence="8">31 uM for beta-casomorphin</KM>
            <KM evidence="8">5.5 uM for dynorphin A-(1-13)</KM>
            <KM evidence="8">300 uM for neurotensin-(1-8)</KM>
            <KM evidence="27">58.6 uM for angiotensin II</KM>
            <KM evidence="34">12 uM for [Pyr1]apelin-13</KM>
            <KM evidence="34">19 uM for apelin-17</KM>
            <Vmax evidence="27">28.7 nmol/min/mg enzyme with angiotensin II as substrate</Vmax>
            <text evidence="8 34">kcat is 0.034 sec(-1) with angiotensin I as substrate. kcat is 3.5 sec(-1) with angiotensin II as substrate. kcat is 13 sec(-1) with apelin-13 as substrate. kcat is 62 sec(-1) with [des-Arg(9)]-bradykinin as substrate. kcat is 26 sec(-1) with Lys-[des-Arg(9)]-bradykinin as substrate. kcat is 6.8 sec(-1) with beta-casomorphin as substrate. kcat is 16 sec(-1) with dynorphin A-(1-13) as substrate. kcat is 57 sec(-1) with neurotensin-(1-8) as substrate (PubMed:11815627). kcat is 19.1 sec(-1) with [Pyr1]apelin-13 as substrate. kcat is 7.7 sec(-1) with apelin-17 as substrate (PubMed:27217402).</text>
        </kinetics>
        <phDependence>
            <text evidence="8">Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="1 18 31 37 54 58 60">Homodimer (PubMed:32132184). Interacts with the catalytically active form of TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (By similarity). Interacts with ITGA5:ITGB1 (PubMed:15276642, PubMed:33102950). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (PubMed:33436498). Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (PubMed:34189428).</text>
    </comment>
    <comment type="subunit">
        <text evidence="12 19 21 41">(Microbial infection) Interacts with SARS coronavirus/SARS-CoV spike protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="36 37 41 50 54 56 61 62 63">(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein (via RBD domain).</text>
    </comment>
    <comment type="subunit">
        <text evidence="30">(Microbial infection) Interacts with human coronavirus NL63 spike protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="22">(Microbial infection) Interacts with human coronavirus NL63/HCoV-NL63 spike glycoprotein.</text>
    </comment>
    <comment type="subunit">
        <molecule>Processed angiotensin-converting enzyme 2</molecule>
        <text evidence="59">(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein; the interaction is increased by AVP/Arg-vasopressin with which they may form a complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
            <label>ACE2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25493366">
            <id>PRO_0000032457</id>
            <label>AGT</label>
            <dbReference type="UniProtKB" id="P01019"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-6622938">
            <id>PRO_0000032458</id>
            <label>AGT</label>
            <dbReference type="UniProtKB" id="P01019"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-297683">
            <id>Q96CW1</id>
            <label>AP2M1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-821758">
            <id>PRO_0000000092</id>
            <label>APP</label>
            <dbReference type="UniProtKB" id="P05067"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-1391211">
            <id>Q9H2X3</id>
            <label>CLEC4M</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25634589">
            <id>PRO_0000417390</id>
            <label>DEFA5</label>
            <dbReference type="UniProtKB" id="Q01523"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-10232876">
            <id>Q14416</id>
            <label>GRM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-354921">
            <id>P11021</id>
            <label>HSPA5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-703066">
            <id>P05556</id>
            <label>ITGB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-710124">
            <id>O60341</id>
            <label>KDM1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>19</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-6623273">
            <id>PRO_0000006688</id>
            <label>KNG1</label>
            <dbReference type="UniProtKB" id="P01042"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-3385920">
            <id>Q9Y2H9</id>
            <label>MAST1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-493777">
            <id>Q6P0Q8</id>
            <label>MAST2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-349787">
            <id>O14745</id>
            <label>NHERF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-1149760">
            <id>Q15599</id>
            <label>NHERF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-6655817">
            <id>PRO_0000019524</id>
            <label>NTS</label>
            <dbReference type="UniProtKB" id="P30990"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-349819">
            <id>Q5T2W1</id>
            <label>PDZK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-1047946">
            <id>P26045</id>
            <label>PTPN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-11316157">
            <id>P35247</id>
            <label>SFTPD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-3442234">
            <id>Q9Y566</id>
            <label>SHANK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25475705">
            <id>Q695T7</id>
            <label>SLC6A19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-2514865">
            <id>Q96L92</id>
            <label>SNX27</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-2806496">
            <id>Q7Z6J2</id>
            <label>TAMALIN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-12549863">
            <id>O15393</id>
            <label>TMPRSS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-353844">
            <id>P08670</id>
            <label>VIM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-3043908">
            <id>P52293</id>
            <label>Kpna2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-26997256">
            <id>A0A6G6A1M4</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-26997195">
            <id>A0A6M3G9R1</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25474821">
            <id>P0DTC2</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>242</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25490323">
            <id>PRO_0000449647</id>
            <label>S</label>
            <dbReference type="UniProtKB" id="P0DTC2"/>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-15582614">
            <id>P59594</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>56</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25475261">
            <id>PRO_0000037209</id>
            <label>S</label>
            <dbReference type="UniProtKB" id="P59594"/>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-25566398">
            <id>Q5GDB5</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7730807">
            <id>Q9BYF1</id>
        </interactant>
        <interactant intactId="EBI-15814420">
            <id>Q6Q1S2</id>
            <label>S</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Processed angiotensin-converting enzyme 2</molecule>
        <subcellularLocation>
            <location evidence="24 59">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="26">Cell membrane</location>
            <topology evidence="2">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="57">Cell projection</location>
            <location evidence="57">Cilium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="57">Apical cell membrane</location>
        </subcellularLocation>
        <text evidence="1">Detected in both cell membrane and cytoplasm in neurons.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="57">Apical cell membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BYF1-1</id>
            <name>1</name>
            <name evidence="70">long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BYF1-3</id>
            <name>2</name>
            <name evidence="69">delta</name>
            <name evidence="69">dACE2</name>
            <name evidence="70">short</name>
            <sequence type="described" ref="VSP_060903"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 7 10 15 17 20 26 39 42 43 44 45 46 47 49 57">Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells (at protein level) (PubMed:15141377). Expressed in enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level) (PubMed:15141377). Expressed in the renal proximal tubule and the small intestine (at protein level) (PubMed:18424768). Expressed in heart, kidney, testis, and gastrointestinal system (at protein level) (PubMed:10924499, PubMed:10969042, PubMed:12459472, PubMed:15231706, PubMed:15671045, PubMed:32170560, PubMed:32715618). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level) (PubMed:15141377, PubMed:32170560, PubMed:32425701, PubMed:32715618, PubMed:33432184). Expressed in nasal epithelial cells (at protein level) (PubMed:32333915, PubMed:33432184). Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells (PubMed:32327758, PubMed:32358202, PubMed:32413319). Coexpressed with TMPRSS4 within mature enterocytes (PubMed:32404436).</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 2</molecule>
        <text evidence="57">Expressed in nasal and bronchial epithelial cells (at protein level).</text>
    </comment>
    <comment type="induction">
        <text evidence="11 16 20 43 46 47">Up-regulated in failing heart (PubMed:14504186, PubMed:15151696, PubMed:15671045). Expression is induced by IFNA and IFNG (PubMed:32413319, PubMed:32425701). Exposure to cigarette smoke increases expression in lungs (PubMed:32425701). Expression is decreased in nasal and bronchial epithelium of individuals with allergy after allergen challenge (PubMed:32333915). IL13 stimulation decreases expression in nasal and bronchial epithelium (PubMed:32333915).</text>
    </comment>
    <comment type="induction">
        <molecule>Isoform 1</molecule>
        <text evidence="52">Not induced by interferons such as IFNA, IFNB and IFNG.</text>
    </comment>
    <comment type="induction">
        <molecule>Isoform 2</molecule>
        <text evidence="52">Expression is induced by interferons such as IFNA, IFNB and IFNG. It seems that isoform 2 is an interferon-stimulated gene (ISG) but not isoform 1.</text>
    </comment>
    <comment type="induction">
        <text evidence="46">(Microbial infection) In airway epithelial cells, expression is increased upon influenza A virus infection (PubMed:32413319).</text>
    </comment>
    <comment type="induction">
        <molecule>Isoform 2</molecule>
        <text evidence="52 57">(Microbial infection) In airway epithelial cells, expression is induced by viruses such rhinoviruses and influenza virus.</text>
    </comment>
    <comment type="induction">
        <molecule>Isoform 2</molecule>
        <text evidence="52">(Microbial infection) Induced by human coronavirus SARS-CoV-2.</text>
    </comment>
    <comment type="domain">
        <text evidence="13">The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin.</text>
    </comment>
    <comment type="domain">
        <text evidence="80 81">The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy.</text>
    </comment>
    <comment type="PTM">
        <text evidence="6 12 13 14 28">N-glycosylation on Asn-90 may limit SARS infectivity.</text>
    </comment>
    <comment type="PTM">
        <text evidence="24 31 32 33 37 59">Proteolytic cleavage by ADAM17 generates a secreted form (PubMed:15983030, PubMed:33713620). Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1.</text>
    </comment>
    <comment type="PTM">
        <text evidence="80 81">Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains.</text>
    </comment>
    <comment type="PTM">
        <text evidence="64">Ubiquitinated. Ubiquitinated on Lys-788 via 'Lys-48'-linked ubiquitin (PubMed:36876523). 'Lys-48'-linked deubiquitinated by USP50 on the Lys-788; leading to its stabilization (PubMed:36876523).</text>
    </comment>
    <comment type="biotechnology">
        <text evidence="50">An engeneered stable, dimeric and secreted receptor with combined mutations that increase the affinity for human coronavirus SARS-CoV-2 spike protein shows potent SARS-CoV and SARS-CoV-2 neutralization in vitro.</text>
    </comment>
    <comment type="similarity">
        <text evidence="72">Belongs to the peptidase M2 family.</text>
    </comment>
    <comment type="sequence caution" evidence="72">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAQ89076" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/223/"/>
        <text>A way in - Issue 223 of March 2020</text>
    </comment>
    <dbReference type="EC" id="3.4.17.23" evidence="6 8 27"/>
    <dbReference type="EC" id="3.4.17.-" evidence="6 7 8 27 34 35 52"/>
    <dbReference type="EMBL" id="AF291820">
        <property type="protein sequence ID" value="AAF99721.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF241254">
        <property type="protein sequence ID" value="AAF78220.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY623811">
        <property type="protein sequence ID" value="AAT45083.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB193259">
        <property type="protein sequence ID" value="BAD99266.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB193260">
        <property type="protein sequence ID" value="BAD99267.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB046569">
        <property type="protein sequence ID" value="BAB40370.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="E39033">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="GQ262784">
        <property type="protein sequence ID" value="ACT66268.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="MT505392">
        <property type="protein sequence ID" value="QLP88822.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358714">
        <property type="protein sequence ID" value="AAQ89076.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY217547">
        <property type="protein sequence ID" value="AAO25651.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471074">
        <property type="protein sequence ID" value="EAW98892.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC039902">
        <property type="protein sequence ID" value="AAH39902.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC048094">
        <property type="protein sequence ID" value="AAH48094.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL110224">
        <property type="protein sequence ID" value="CAB53682.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14169.1">
        <molecule id="Q9BYF1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS94556.1">
        <molecule id="Q9BYF1-3"/>
    </dbReference>
    <dbReference type="PIR" id="T14762">
        <property type="entry name" value="T14762"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001358344.1">
        <molecule id="Q9BYF1-1"/>
        <property type="nucleotide sequence ID" value="NM_001371415.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001375381.1">
        <molecule id="Q9BYF1-3"/>
        <property type="nucleotide sequence ID" value="NM_001388452.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068576.1">
        <molecule id="Q9BYF1-1"/>
        <property type="nucleotide sequence ID" value="NM_021804.3"/>
    </dbReference>
    <dbReference type="PDB" id="1R42">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-615"/>
    </dbReference>
    <dbReference type="PDB" id="1R4L">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A=1-615"/>
    </dbReference>
    <dbReference type="PDB" id="2AJF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="3D0G">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=56-615"/>
    </dbReference>
    <dbReference type="PDB" id="3D0H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B=56-615"/>
    </dbReference>
    <dbReference type="PDB" id="3D0I">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B=56-615"/>
    </dbReference>
    <dbReference type="PDB" id="3KBH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.31 A"/>
        <property type="chains" value="A/B/C/D=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="3SCI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="3SCJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="3SCK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=83-615"/>
    </dbReference>
    <dbReference type="PDB" id="3SCL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=83-615"/>
    </dbReference>
    <dbReference type="PDB" id="6ACG">
        <property type="method" value="EM"/>
        <property type="resolution" value="5.40 A"/>
        <property type="chains" value="D=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="6ACJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.20 A"/>
        <property type="chains" value="D=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="6ACK">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.50 A"/>
        <property type="chains" value="D=19-615"/>
    </dbReference>
    <dbReference type="PDB" id="6CS2">
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    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="17"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000028570" description="Angiotensin-converting enzyme 2">
        <location>
            <begin position="18"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000292268" description="Processed angiotensin-converting enzyme 2">
        <location>
            <begin position="18"/>
            <end position="708"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="18"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="741"/>
            <end position="761"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="762"/>
            <end position="805"/>
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    </feature>
    <feature type="domain" description="Peptidase M2" evidence="4">
        <location>
            <begin position="19"/>
            <end position="607"/>
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    </feature>
    <feature type="domain" description="Collectrin-like" evidence="3">
        <location>
            <begin position="614"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with SARS-CoV spike glycoprotein" evidence="21">
        <location>
            <begin position="30"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with SARS-CoV spike glycoprotein" evidence="21">
        <location>
            <begin position="82"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with SARS-CoV spike glycoprotein" evidence="21">
        <location>
            <begin position="353"/>
            <end position="357"/>
        </location>
    </feature>
    <feature type="region of interest" description="Essential for cleavage by ADAM17" evidence="33">
        <location>
            <begin position="652"/>
            <end position="659"/>
        </location>
    </feature>
    <feature type="region of interest" description="Essential for cleavage by TMPRSS11D and TMPRSS2" evidence="33">
        <location>
            <begin position="697"/>
            <end position="716"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="772"/>
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    </feature>
    <feature type="short sequence motif" description="LIR" evidence="80 81">
        <location>
            <begin position="778"/>
            <end position="786"/>
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    </feature>
    <feature type="short sequence motif" description="SH2-binding" evidence="80 81">
        <location>
            <begin position="781"/>
            <end position="785"/>
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    </feature>
    <feature type="short sequence motif" description="Endocytic sorting signal" evidence="80 81">
        <location>
            <begin position="781"/>
            <end position="784"/>
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    </feature>
    <feature type="short sequence motif" description="PTB" evidence="80 81">
        <location>
            <begin position="792"/>
            <end position="795"/>
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    </feature>
    <feature type="short sequence motif" description="PDZ-binding" evidence="80 81">
        <location>
            <begin position="803"/>
            <end position="805"/>
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    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="789"/>
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    </feature>
    <feature type="active site" description="Proton acceptor" evidence="4 77 79">
        <location>
            <position position="375"/>
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    </feature>
    <feature type="active site" description="Proton donor" evidence="4 77">
        <location>
            <position position="505"/>
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    </feature>
    <feature type="binding site" evidence="4 13 78">
        <location>
            <position position="169"/>
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        <ligand>
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="77">
        <location>
            <position position="273"/>
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        <ligand>
            <name>substrate</name>
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    </feature>
    <feature type="binding site" evidence="77">
        <location>
            <begin position="345"/>
            <end position="346"/>
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        <ligand>
            <name>substrate</name>
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    </feature>
    <feature type="binding site" evidence="4 13">
        <location>
            <position position="374"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 13">
        <location>
            <position position="378"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 13">
        <location>
            <position position="402"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 13 78">
        <location>
            <position position="477"/>
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        <ligand>
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4 13 78">
        <location>
            <position position="481"/>
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        <ligand>
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="77">
        <location>
            <position position="515"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="80 81">
        <location>
            <position position="781"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="80 81">
        <location>
            <position position="783"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="77">
        <location>
            <position position="53"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="13 14 30">
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="13">
        <location>
            <position position="103"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="77">
        <location>
            <position position="322"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="13">
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="13 28 30">
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="690"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4 13">
        <location>
            <begin position="133"/>
            <end position="141"/>
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    </feature>
    <feature type="disulfide bond" evidence="4 13">
        <location>
            <begin position="344"/>
            <end position="361"/>
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    </feature>
    <feature type="disulfide bond" evidence="4 13">
        <location>
            <begin position="530"/>
            <end position="542"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)" evidence="64">
        <location>
            <position position="788"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_060903" description="In isoform 2.">
        <original>MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDF</original>
        <variation>MREAGWDKGG</variation>
        <location>
            <begin position="1"/>
            <end position="356"/>
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    <feature type="sequence variant" id="VAR_023082" description="In dbSNP:rs4646116." evidence="48 65">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083726" evidence="48">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="468"/>
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    </feature>
    <feature type="sequence variant" id="VAR_023083" description="In dbSNP:rs183135788." evidence="23 48">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="638"/>
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    </feature>
    <feature type="sequence variant" id="VAR_083727" evidence="48 55">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="720"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>QAK</original>
        <variation>KAE</variation>
        <location>
            <begin position="24"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Q</original>
        <variation>T</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-330 and L-386." evidence="50">
        <original>T</original>
        <variation>Y</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>K</original>
        <variation>D</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>K</original>
        <variation>Y</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="38"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>F</original>
        <variation>D</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Y</original>
        <variation>R</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>K</original>
        <variation>D</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>W</original>
        <variation>V</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>F</original>
        <variation>Y</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Q</original>
        <variation>T</variation>
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>L</original>
        <variation>T</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>MYP</original>
        <variation>NFS</variation>
        <location>
            <begin position="82"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>T</original>
        <variation>Q</variation>
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>E</original>
        <variation>P</variation>
        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>PD</original>
        <variation>SM</variation>
        <location>
            <begin position="135"/>
            <end position="136"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="About 95% loss of angiotensin I cleavage." evidence="27">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="239"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="About 95% loss of angiotensin I cleavage." evidence="27">
        <original>W</original>
        <variation>Q</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of enzyme activity. Does not affect amino acid transport activity of SLC6A19." evidence="25 29">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="273"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>K</original>
        <variation>D</variation>
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="312"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="325"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and L-386." evidence="50">
        <original>N</original>
        <variation>Y</variation>
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>NVQ</original>
        <variation>DDR</variation>
        <location>
            <begin position="338"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of enzyme activity." evidence="25">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="350"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein." evidence="50">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="351"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>K</original>
        <variation>H</variation>
        <variation>A</variation>
        <variation>D</variation>
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="357"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>L</original>
        <variation>K</variation>
        <variation>A</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>M</original>
        <variation>A</variation>
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases slightly the interaction with RBD domain of SARS-CoV-2 spike protein. In sACE2.v2.2; increases interaction with RBD domain of SARS-CoV-2 spike protein; when associated with Y-27 and Y-330." evidence="50">
        <original>A</original>
        <variation>L</variation>
        <location>
            <position position="386"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slightly inhibits interaction with SARS-CoV spike glycoprotein." evidence="21">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="389"/>
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</entry>
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            <fullName evidence="18">Acetylcholinesterase</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
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                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="9">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM H)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-546 (ISOFORMS H/R/T)</scope>
        <scope>GPI-ANCHOR AT GLY-588 (ISOFORM H)</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="10">
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            <title>Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5.</title>
            <authorList>
                <person name="Wilson M.D."/>
                <person name="Riemer C."/>
                <person name="Martindale D.W."/>
                <person name="Schnupf P."/>
                <person name="Boright A.P."/>
                <person name="Cheung T.L."/>
                <person name="Hardy D.M."/>
                <person name="Schwartz S."/>
                <person name="Scherer S.W."/>
                <person name="Tsui L.-C."/>
                <person name="Miller W."/>
                <person name="Koop B.F."/>
            </authorList>
            <dbReference type="PubMed" id="11239002"/>
            <dbReference type="DOI" id="10.1093/nar/29.6.1352"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 521-614</scope>
    </reference>
    <reference key="11">
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            <title>Purification and partial amino acid sequence analysis of human erythrocyte acetylcholinesterase.</title>
            <authorList>
                <person name="Chhajlani V."/>
                <person name="Derr D."/>
                <person name="Earles B."/>
                <person name="Schmell E."/>
                <person name="August T."/>
            </authorList>
            <dbReference type="PubMed" id="2714437"/>
            <dbReference type="DOI" id="10.1016/0014-5793(89)81352-3"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 256-273; 306-326; 396-422; 465-480 AND 528-551</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Erythrocyte</tissue>
        </source>
    </reference>
    <reference key="12">
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            <authorList>
                <person name="Velan B."/>
                <person name="Grosfeld H."/>
                <person name="Kronman C."/>
                <person name="Leitner M."/>
                <person name="Gozes Y."/>
                <person name="Lazar A."/>
                <person name="Flashner Y."/>
                <person name="Marcus D."/>
                <person name="Cohen S."/>
                <person name="Shafferman A."/>
            </authorList>
            <dbReference type="PubMed" id="1748670"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)54380-5"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF CYS-611</scope>
    </reference>
    <reference key="13">
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            <authorList>
                <person name="Shafferman A."/>
                <person name="Kronman C."/>
                <person name="Flashner Y."/>
                <person name="Leitner M."/>
                <person name="Grosfeld H."/>
                <person name="Ordentlich A."/>
                <person name="Gozes Y."/>
                <person name="Cohen S."/>
                <person name="Ariel N."/>
                <person name="Barak D."/>
            </authorList>
            <dbReference type="PubMed" id="1517212"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)37091-7"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-206; SER-234; GLU-365; ASP-435 AND HIS-478</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2002" name="Neurosci. Res." volume="42" first="261" last="268">
            <title>Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells.</title>
            <authorList>
                <person name="Yang L."/>
                <person name="He H.Y."/>
                <person name="Zhang X.J."/>
            </authorList>
            <dbReference type="PubMed" id="11985878"/>
            <dbReference type="DOI" id="10.1016/s0168-0102(02)00005-6"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1997" name="J. Mol. Graph. Model." volume="15" first="318" last="327">
            <title>External and internal electrostatic potentials of cholinesterase models.</title>
            <authorList>
                <person name="Felder C.E."/>
                <person name="Botti S.A."/>
                <person name="Lifson S."/>
                <person name="Silman I."/>
                <person name="Sussman J.L."/>
            </authorList>
            <dbReference type="PubMed" id="9640563"/>
            <dbReference type="DOI" id="10.1016/s1093-3263(98)00005-9"/>
        </citation>
        <scope>3D-STRUCTURE MODELING OF 35-574</scope>
    </reference>
    <reference evidence="21 22" key="16">
        <citation type="journal article" date="2000" name="Acta Crystallogr. D" volume="56" first="1385" last="1394">
            <title>Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.</title>
            <authorList>
                <person name="Kryger G."/>
                <person name="Harel M."/>
                <person name="Giles K."/>
                <person name="Toker L."/>
                <person name="Velan B."/>
                <person name="Lazar A."/>
                <person name="Kronman C."/>
                <person name="Barak D."/>
                <person name="Ariel N."/>
                <person name="Shafferman A."/>
                <person name="Silman I."/>
                <person name="Sussman J.L."/>
            </authorList>
            <dbReference type="PubMed" id="11053835"/>
            <dbReference type="DOI" id="10.1107/s0907444900010659"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 32-614 IN COMPLEX WITH FASCICULIN-2</scope>
        <scope>GLYCOSYLATION AT ASN-381</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference evidence="23" key="17">
        <citation type="journal article" date="2004" name="EMBO J." volume="23" first="4394" last="4405">
            <title>The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix.</title>
            <authorList>
                <person name="Dvir H."/>
                <person name="Harel M."/>
                <person name="Bon S."/>
                <person name="Liu W.-Q."/>
                <person name="Vidal M."/>
                <person name="Garbay C."/>
                <person name="Sussman J.L."/>
                <person name="Massoulie J."/>
                <person name="Silman I."/>
            </authorList>
            <dbReference type="PubMed" id="15526038"/>
            <dbReference type="DOI" id="10.1038/sj.emboj.7600425"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 575-614 IN COMPLEX WITH COLQ</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2010" name="J. Med. Chem." volume="53" first="4002" last="4008">
            <title>Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation.</title>
            <authorList>
                <person name="Carletti E."/>
                <person name="Colletier J.P."/>
                <person name="Dupeux F."/>
                <person name="Trovaslet M."/>
                <person name="Masson P."/>
                <person name="Nachon F."/>
            </authorList>
            <dbReference type="PubMed" id="20408548"/>
            <dbReference type="DOI" id="10.1021/jm901853b"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF COMPLEX WITH FASCICULIN-2</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>GLYCOSYLATION AT ASN-381</scope>
    </reference>
    <reference key="19">
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            <title>Structures of human acetylcholinesterase in complex with pharmacologically important ligands.</title>
            <authorList>
                <person name="Cheung J."/>
                <person name="Rudolph M.J."/>
                <person name="Burshteyn F."/>
                <person name="Cassidy M.S."/>
                <person name="Gary E.N."/>
                <person name="Love J."/>
                <person name="Franklin M.C."/>
                <person name="Height J.J."/>
            </authorList>
            <dbReference type="PubMed" id="23035744"/>
            <dbReference type="DOI" id="10.1021/jm300871x"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 35-573 IN COMPLEX WITH FASCICULIN-2; HUPERZINE A; GALANTAMINE AND DONEPEZIL</scope>
        <scope>GLYCOSYLATION AT ASN-296; ASN-381 AND ASN-495</scope>
        <scope>DISULFIDE BOND</scope>
    </reference>
    <reference key="20">
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            <title>Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl- and butyryl-cholinesterase.</title>
            <authorList>
                <person name="Nachon F."/>
                <person name="Carletti E."/>
                <person name="Ronco C."/>
                <person name="Trovaslet M."/>
                <person name="Nicolet Y."/>
                <person name="Jean L."/>
                <person name="Renard P.Y."/>
            </authorList>
            <dbReference type="PubMed" id="23679855"/>
            <dbReference type="DOI" id="10.1042/bj20130013"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 36-598 IN COMPLEX WITH FASCICULIN-2 AND HUPRINE W</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>GLYCOSYLATION AT ASN-381</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="1993" name="Am. J. Hum. Genet." volume="52" first="928" last="936">
            <title>Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism.</title>
            <authorList>
                <person name="Bartels C.F."/>
                <person name="Zelinski T."/>
                <person name="Lockridge O."/>
            </authorList>
            <dbReference type="PubMed" id="8488842"/>
        </citation>
        <scope>VARIANT BLOOD GROUP YT(B) ASN-353</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 8 12">Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>acetylcholine + H2O = choline + acetate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17561"/>
            <dbReference type="ChEBI" id="CHEBI:15354"/>
            <dbReference type="ChEBI" id="CHEBI:15355"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="EC" id="3.1.1.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:17562"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="1 3 7">Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers (By similarity). Isoform H generates GPI-anchored dimers; disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers. Isoform R may be monomeric.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1637793">
            <id>P22303</id>
        </interactant>
        <interactant intactId="EBI-1637847">
            <id>Q9Y215</id>
            <label>COLQ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1637793">
            <id>P22303</id>
        </interactant>
        <interactant intactId="EBI-353877">
            <id>P06733</id>
            <label>ENO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1637793">
            <id>P22303</id>
        </interactant>
        <interactant intactId="EBI-296739">
            <id>P63244</id>
            <label>RACK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 8">Synapse</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Secreted</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="1">Peripheral membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform T</molecule>
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <text>Only observed in apoptotic nuclei.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform H</molecule>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="1">Lipid-anchor</topology>
            <topology evidence="1">GPI-anchor</topology>
            <orientation evidence="1">Extracellular side</orientation>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P22303-1</id>
            <name>T</name>
            <name>ACHE-S</name>
            <name>synaptic</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P22303-2</id>
            <name>H</name>
            <name>ACHE-E</name>
            <name>erythrocytic</name>
            <name>E4-E5</name>
            <sequence type="described" ref="VSP_001457"/>
        </isoform>
        <isoform>
            <id>P22303-4</id>
            <name>R</name>
            <name>ACHE-R</name>
            <name>readthrough</name>
            <sequence type="described" ref="VSP_035569 VSP_035570"/>
        </isoform>
        <isoform>
            <id>P22303-3</id>
            <name>4</name>
            <sequence type="described" ref="VSP_035568"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="12">Isoform H is highly expressed in erythrocytes.</text>
    </comment>
    <comment type="polymorphism">
        <text>ACHE is responsible for the Yt blood group system [MIM:112100]. The molecular basis of the Yt(a)=Yt1/Yt(b)=Yt2 blood group antigens is a single variation in position 353; His-353 corresponds to Yt(a) and the rare variant with Asn-353 to Yt(b).</text>
    </comment>
    <comment type="similarity">
        <text evidence="18">Belongs to the type-B carboxylesterase/lipase family.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Acetylcholinesterase"/>
        <text>Acetylcholinesterase entry</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44317/ACHE"/>
    </comment>
    <dbReference type="EC" id="3.1.1.7" evidence="5"/>
    <dbReference type="EMBL" id="M55040">
        <property type="protein sequence ID" value="AAA68151.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S71129">
        <property type="protein sequence ID" value="AAC60618.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF334270">
        <property type="protein sequence ID" value="AAO32948.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291321">
        <property type="protein sequence ID" value="BAF84010.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223443">
        <property type="protein sequence ID" value="BAD97163.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY750146">
        <property type="protein sequence ID" value="AAU43801.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011895">
        <property type="protein sequence ID" value="AAP22364.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011895">
        <property type="protein sequence ID" value="AAP22365.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236956">
        <property type="protein sequence ID" value="EAL23812.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236956">
        <property type="protein sequence ID" value="EAL23813.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471091">
        <property type="protein sequence ID" value="EAW76461.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471091">
        <property type="protein sequence ID" value="EAW76463.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471091">
        <property type="protein sequence ID" value="EAW76462.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC036813">
        <property type="protein sequence ID" value="AAH36813.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC105060">
        <property type="protein sequence ID" value="AAI05061.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC105062">
        <property type="protein sequence ID" value="AAI05063.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143469">
        <property type="protein sequence ID" value="AAI43470.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF312032">
        <property type="protein sequence ID" value="AAK21003.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5709.1">
        <molecule id="P22303-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5710.1">
        <molecule id="P22303-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64736.1">
        <molecule id="P22303-3"/>
    </dbReference>
    <dbReference type="PIR" id="A39256">
        <property type="entry name" value="A39256"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000656.1">
        <molecule id="P22303-1"/>
        <property type="nucleotide sequence ID" value="NM_000665.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269378.1">
        <molecule id="P22303-3"/>
        <property type="nucleotide sequence ID" value="NM_001282449.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001289550.1">
        <molecule id="P22303-2"/>
        <property type="nucleotide sequence ID" value="NM_001302621.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001289551.1">
        <molecule id="P22303-1"/>
        <property type="nucleotide sequence ID" value="NM_001302622.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001354844.1">
        <molecule id="P22303-1"/>
        <property type="nucleotide sequence ID" value="NM_001367915.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001354846.1">
        <molecule id="P22303-1"/>
        <property type="nucleotide sequence ID" value="NM_001367917.1"/>
    </dbReference>
    <dbReference type="PDB" id="1B41">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.76 A"/>
        <property type="chains" value="A=36-574"/>
    </dbReference>
    <dbReference type="PDB" id="1F8U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A=32-614"/>
    </dbReference>
    <dbReference type="PDB" id="1VZJ">
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        <property type="generic name" value="Ladostigil"/>
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        <property type="generic name" value="Malathion"/>
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        <property type="generic name" value="Methanesulfonyl Fluoride"/>
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    <dbReference type="DrugBank" id="DB00940">
        <property type="generic name" value="Methantheline"/>
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    <dbReference type="DrugBank" id="DB02825">
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    <dbReference type="DrugBank" id="DB02845">
        <property type="generic name" value="Methylphosphinic Acid"/>
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    <dbReference type="DrugBank" id="DB08167">
        <property type="generic name" value="Methylthioninium"/>
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    <dbReference type="DrugBank" id="DB04021">
        <property type="generic name" value="MF268"/>
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    <dbReference type="DrugBank" id="DB00805">
        <property type="generic name" value="Minaprine"/>
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    <dbReference type="DrugBank" id="DB01805">
        <property type="generic name" value="Monoisopropylphosphorylserine"/>
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        <property type="generic name" value="N-acetyl-alpha-D-glucosamine"/>
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    <dbReference type="DrugBank" id="DB04556">
        <property type="generic name" value="NAP-226-90"/>
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    <dbReference type="DrugBank" id="DB01400">
        <property type="generic name" value="Neostigmine"/>
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        <property type="generic name" value="Obidoxime"/>
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    <dbReference type="DrugBank" id="DB13495">
        <property type="generic name" value="Paraoxon"/>
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    <dbReference type="DrugBank" id="DB04892">
        <property type="generic name" value="Phenserine"/>
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    <dbReference type="DrugBank" id="DB00981">
        <property type="generic name" value="Physostigmine"/>
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        <property type="generic name" value="Pralidoxime"/>
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        <property type="generic name" value="Ranitidine"/>
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        <property type="generic name" value="Terpinen-4-ol"/>
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        <property type="generic name" value="Tubocurarine"/>
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        <property type="antibodies" value="776 antibodies from 43 providers"/>
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        <property type="protein sequence ID" value="ENSP00000241069.5"/>
        <property type="gene ID" value="ENSG00000087085.17"/>
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        <property type="gene ID" value="ENSG00000087085.17"/>
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        <property type="protein sequence ID" value="ENSP00000404865.1"/>
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        <property type="protein sequence ID" value="ENSP00000241069.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000665.5"/>
        <property type="RefSeq protein sequence ID" value="NP_000656.1"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="project" value="YuBioLab"/>
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        <property type="project" value="Ensembl"/>
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        <property type="entry name" value="Esterase_lipase"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.40.50.1820:FF:000029">
        <property type="entry name" value="Acetylcholinesterase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050654">
        <property type="entry name" value="AChE-related_enzymes"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014788">
        <property type="entry name" value="AChE_tetra"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002018">
        <property type="entry name" value="CarbesteraseB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019826">
        <property type="entry name" value="Carboxylesterase_B_AS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019819">
        <property type="entry name" value="Carboxylesterase_B_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000997">
        <property type="entry name" value="Cholinesterase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43918">
        <property type="entry name" value="ACETYLCHOLINESTERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43918:SF11">
        <property type="entry name" value="ACETYLCHOLINESTERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08674">
        <property type="entry name" value="AChE_tetra"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00135">
        <property type="entry name" value="COesterase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00878">
        <property type="entry name" value="CHOLNESTRASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00122">
        <property type="entry name" value="CARBOXYLESTERASE_B_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00941">
        <property type="entry name" value="CARBOXYLESTERASE_B_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0095">Blood group antigen</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0336">GPI-anchor</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0531">Neurotransmitter degradation</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000008587" description="Acetylcholinesterase">
        <location>
            <begin position="32"/>
            <end position="614"/>
        </location>
    </feature>
    <feature type="active site" description="Acyl-ester intermediate">
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system">
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system">
        <location>
            <position position="478"/>
        </location>
    </feature>
    <feature type="binding site" evidence="28">
        <location>
            <position position="117"/>
        </location>
        <ligand>
            <name>galanthamine</name>
            <dbReference type="ChEBI" id="CHEBI:178021"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27">
        <location>
            <position position="117"/>
        </location>
        <ligand>
            <name>huperzine A</name>
            <dbReference type="ChEBI" id="CHEBI:178022"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="25">
        <location>
            <position position="153"/>
        </location>
        <ligand>
            <name>huprine W</name>
            <dbReference type="ChEBI" id="CHEBI:188158"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27">
        <location>
            <position position="164"/>
        </location>
        <ligand>
            <name>huperzine A</name>
            <dbReference type="ChEBI" id="CHEBI:178022"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="28">
        <location>
            <begin position="233"/>
            <end position="234"/>
        </location>
        <ligand>
            <name>galanthamine</name>
            <dbReference type="ChEBI" id="CHEBI:178021"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="25">
        <location>
            <position position="234"/>
        </location>
        <ligand>
            <name>huprine W</name>
            <dbReference type="ChEBI" id="CHEBI:188158"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="28">
        <location>
            <position position="368"/>
        </location>
        <ligand>
            <name>galanthamine</name>
            <dbReference type="ChEBI" id="CHEBI:178021"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="27">
        <location>
            <position position="368"/>
        </location>
        <ligand>
            <name>huperzine A</name>
            <dbReference type="ChEBI" id="CHEBI:178022"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="25">
        <location>
            <position position="470"/>
        </location>
        <ligand>
            <name>huprine W</name>
            <dbReference type="ChEBI" id="CHEBI:188158"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="25">
        <location>
            <position position="478"/>
        </location>
        <ligand>
            <name>huprine W</name>
            <dbReference type="ChEBI" id="CHEBI:188158"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10 26 27 28 29">
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3 9 10 11 21 22 24 25 26 27 28 29 30">
        <location>
            <position position="381"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10 30">
        <location>
            <position position="495"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="100"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="288"/>
            <end position="303"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="440"/>
            <end position="560"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain">
        <location>
            <position position="611"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035568" description="In isoform 4." evidence="17">
        <location>
            <begin position="357"/>
            <end position="444"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001457" description="In isoform H." evidence="15 16">
        <original>DTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL</original>
        <variation>ASEAPSTCPGFTHGEAAPRPGLPLPLLLLHQLLLLFLSHLRRL</variation>
        <location>
            <begin position="575"/>
            <end position="614"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035569" description="In isoform R." evidence="16">
        <original>DTLDEAERQWKAEFHRWSSYMVHWKNQFD</original>
        <variation>GMQGPAGSAGRRGVGARQCNPSLLPLASE</variation>
        <location>
            <begin position="575"/>
            <end position="603"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035570" description="In isoform R." evidence="16">
        <location>
            <begin position="604"/>
            <end position="614"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021325" description="In dbSNP:rs17881553." evidence="14">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021326" description="In dbSNP:rs17885778." evidence="14">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="135"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011934" description="In dbSNP:rs8286.">
        <original>V</original>
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        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002359" description="In Yt(b) antigen; dbSNP:rs1799805." evidence="13 14">
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        <variation>N</variation>
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Misfolding, absence of secretion." evidence="5">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="5">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="5">
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        <variation>A</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Misfolding, absence of secretion." evidence="5">
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        <location>
            <position position="435"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="5">
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        <location>
            <position position="478"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairment of interchain disulfide bridge formation." evidence="8">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="611"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; BAD97163." evidence="18" ref="5">
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        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; BAD97163." evidence="18" ref="5">
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        <variation>G</variation>
        <location>
            <position position="415"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAI43470." evidence="18" ref="9">
        <original>F</original>
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        <location>
            <position position="486"/>
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    <feature type="helix" evidence="33">
        <location>
            <begin position="37"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="40"/>
            <end position="43"/>
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    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="46"/>
            <end position="49"/>
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    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="51"/>
            <end position="53"/>
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    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="60"/>
            <end position="67"/>
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    <feature type="helix" evidence="33">
        <location>
            <begin position="74"/>
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    <feature type="strand" evidence="33">
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            <begin position="88"/>
            <end position="92"/>
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    <feature type="strand" evidence="33">
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            <begin position="99"/>
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            <begin position="123"/>
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    <feature type="strand" evidence="33">
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            <begin position="143"/>
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            <begin position="153"/>
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    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PDB" id="1B41"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PDB" id="1F8U"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
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        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
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    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PDB" id="4BDT"/>
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    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="4EY4"/>
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    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PDB" id="4EY5"/>
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    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PDB" id="4EY6"/>
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    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PDB" id="4EY7"/>
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    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PDB" id="4EY8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="31">
        <source>
            <dbReference type="PDB" id="1VZJ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="32">
        <source>
            <dbReference type="PDB" id="4EY4"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="33">
        <source>
            <dbReference type="PDB" id="4M0E"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="34">
        <source>
            <dbReference type="PDB" id="6CQW"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="35">
        <source>
            <dbReference type="PDB" id="6O5R"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="36">
        <source>
            <dbReference type="PDB" id="6O69"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="37">
        <source>
            <dbReference type="PDB" id="6WVQ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="38">
        <source>
            <dbReference type="PDB" id="6ZWE"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="39">
        <source>
            <dbReference type="PDB" id="8AEN"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="40">
        <source>
            <dbReference type="PDB" id="8AEV"/>
        </source>
    </evidence>
    <sequence length="614" mass="67796" checksum="B9AA84C77831C302" modified="1991-08-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-07-25" modified="2026-01-28" version="140" xmlns="https://uniprot.org/uniprot">
    <accession>Q5QJU3</accession>
    <accession>A2A3R8</accession>
    <accession>Q569G5</accession>
    <accession>Q5VZR7</accession>
    <accession>Q71RD2</accession>
    <name>ACER2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">Alkaline ceramidase 2</fullName>
            <shortName>AlkCDase 2</shortName>
            <shortName>Alkaline CDase 2</shortName>
            <shortName>haCER2</shortName>
            <ecNumber evidence="7 8">3.5.1.-</ecNumber>
            <ecNumber evidence="4 6 7">3.5.1.23</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acylsphingosine deacylase 3-like</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>N-acylsphingosine amidohydrolase 3-like</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="17" type="primary">ACER2</name>
        <name type="synonym">ASAH3L</name>
        <name type="ORF">PP11646</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
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        <scope>TISSUE SPECIFICITY</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
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            <dbReference type="PubMed" id="15164053"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
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            <title>Alkaline ceramidase 2 regulates beta1 integrin maturation and cell adhesion.</title>
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                <person name="Sun W."/>
                <person name="Hu W."/>
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            <dbReference type="PubMed" id="18945876"/>
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        <scope>FUNCTION</scope>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>PATHWAY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>PATHWAY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION BY 4-HPR</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION BY DNA DAMAGE</scope>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION BY TP53</scope>
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        <scope>FUNCTION</scope>
        <scope>INDUCTION BY TP53</scope>
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    <comment type="function">
        <text evidence="1 4 5 6 7 8 9 10 11 14">Golgi ceramidase that catalyzes the hydrolysis of ceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:16940153, PubMed:18945876, PubMed:20089856, PubMed:20207939). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:20207939). Has a better catalytic efficiency towards unsaturated long-chain ceramides, including C18:1-, C20:1- and C24:1-ceramides (PubMed:16940153, PubMed:18945876, PubMed:20089856, PubMed:20207939). Saturated long-chain ceramides and unsaturated very long-chain ceramides are also good substrates, whereas saturated very long-chain ceramides and short-chain ceramides are poor substrates (PubMed:20089856). Also hydrolyzes dihydroceramides to produce dihydrosphingosine (PubMed:20207939, PubMed:20628055). It is the ceramidase that controls the levels of circulating sphingosine-1-phosphate and dihydrosphingosine-1-phosphate in plasma through their production by hematopoietic cells (By similarity). Regulates cell proliferation, autophagy and apoptosis by the production of sphingosine and sphingosine-1-phosphate (PubMed:16940153, PubMed:26943039, PubMed:28294157, PubMed:29229990). As part of a p53/TP53-dependent pathway, promotes for instance autophagy and apoptosis in response to DNA damage (PubMed:26943039, PubMed:28294157, PubMed:29229990). Through the production of sphingosine, may also regulate the function of the Golgi complex and regulate the glycosylation of proteins (PubMed:18945876).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6">
            <text>N-(15Z-tetracosenoyl)-sphing-4-enine + H2O = (15Z)-tetracosenoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41267"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32392"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:74450"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:41268"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-eicosanoyl-sphing-4-enine + H2O = eicosanoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41275"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72962"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41276"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-octadecanoylsphing-4-enine + H2O = sphing-4-enine + octadecanoate</text>
            <dbReference type="Rhea" id="RHEA:41279"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72961"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41280"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6">
            <text>N-hexadecanoylsphing-4-enine + H2O = sphing-4-enine + hexadecanoate</text>
            <dbReference type="Rhea" id="RHEA:38891"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72959"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:38892"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-tetradecanoylsphing-4-enine + H2O = sphing-4-enine + tetradecanoate</text>
            <dbReference type="Rhea" id="RHEA:41287"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72957"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41288"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-dodecanoylsphing-4-enine + H2O = dodecanoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41291"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72956"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41292"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6">
            <text>N-tetracosanoyl-sphing-4-enine + H2O = tetracosanoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41283"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:31014"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:72965"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:41284"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-(hexanoyl)sphing-4-enine + H2O = hexanoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:41295"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:63867"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41296"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N-(9Z-octadecenoyl)-sphing-4-enine + H2O = sphing-4-enine + (9Z)-octadecenoate</text>
            <dbReference type="Rhea" id="RHEA:41299"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:77996"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:41300"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 6 7">
            <text>an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:20856"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:52639"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="EC" id="3.5.1.23"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:20857"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>an N-acylsphinganine + H2O = sphinganine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:33551"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:31488"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:33552"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="6 7">Specifically activated by lumenal, but not cytosolic Ca(2+). Inhibited by Zn(2+) or Cu(2+). Mg(2+) or Mn(2+) have no effect on ceramidase activity (PubMed:20089856). Inhibited by De-MAPP (PubMed:20207939).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">224 uM for D-erythro-C(6:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">134 uM for D-erythro-C(12:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">115 uM for D-erythro-C(14:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">99 uM for D-erythro-C(16:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">95 uM for D-erythro-C(18:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">77 uM for D-erythro-C(18:1)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">91 uM for D-erythro-C(20:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">72 uM for D-erythro-C(20:1)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">143 uM for D-erythro-C(24:0)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <KM evidence="6">81 uM for D-erythro-C(24:1)-ceramide (at 37 degrees Celsius and pH 9.0)</KM>
            <Vmax evidence="6">5.0 pmol/min/mg enzyme with D-erythro-C(6:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">11.0 pmol/min/mg enzyme with D-erythro-C(12:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">11.0 pmol/min/mg enzyme with D-erythro-C(14:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">24.0 pmol/min/mg enzyme with D-erythro-C(16:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">26.0 pmol/min/mg enzyme with D-erythro-C(18:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">35.0 pmol/min/mg enzyme with D-erythro-C(18:1)-ceramide as substrate</Vmax>
            <Vmax evidence="6">29.0 pmol/min/mg enzyme with D-erythro-C(20:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">38.0 pmol/min/mg enzyme with D-erythro-C(20:1)-ceramide as substrate</Vmax>
            <Vmax evidence="6">7.0 pmol/min/mg enzyme with D-erythro-C(24:0)-ceramide as substrate</Vmax>
            <Vmax evidence="6">27.0 pmol/min/mg enzyme with D-erythro-C(24:1)-ceramide as substrate</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="6">Optimum pH is 7.5-9.0.</text>
        </phDependence>
    </comment>
    <comment type="pathway">
        <text evidence="4 6 7">Lipid metabolism; sphingolipid metabolism.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13319881">
            <id>Q5QJU3-2</id>
        </interactant>
        <interactant intactId="EBI-711788">
            <id>Q00013</id>
            <label>MPP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 6">Golgi apparatus membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5QJU3-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5QJU3-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_020033"/>
        </isoform>
        <isoform>
            <id>Q5QJU3-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_020033 VSP_020034 VSP_020035"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Highly expressed in placenta.</text>
    </comment>
    <comment type="induction">
        <text evidence="4 8 9 10 11">Up-regulated upon serum deprivation (PubMed:16940153). Up-regulated by N-(4-hydroxyphenyl)retinamode/4-HPR (PubMed:20628055). Up-regulated upon DNA damage, in a p53/TP53-dependent manner, resulting in increased levels of sphingosine and sphingosine-1-phosphate (at protein level) (PubMed:26943039, PubMed:28294157, PubMed:29229990).</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the alkaline ceramidase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.-" evidence="7 8"/>
    <dbReference type="EC" id="3.5.1.23" evidence="4 6 7"/>
    <dbReference type="EMBL" id="AY312516">
        <property type="protein sequence ID" value="AAQ85132.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF370405">
        <property type="protein sequence ID" value="AAQ15241.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158206">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL391834">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC092487">
        <property type="protein sequence ID" value="AAH92487.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34992.1">
        <molecule id="Q5QJU3-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001010887.2">
        <molecule id="Q5QJU3-1"/>
        <property type="nucleotide sequence ID" value="NM_001010887.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016870183.1">
        <molecule id="Q5QJU3-2"/>
        <property type="nucleotide sequence ID" value="XM_017014694.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047279291.1">
        <molecule id="Q5QJU3-2"/>
        <property type="nucleotide sequence ID" value="XM_047423335.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054218878.1">
        <molecule id="Q5QJU3-2"/>
        <property type="nucleotide sequence ID" value="XM_054362903.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054218879.1">
        <molecule id="Q5QJU3-2"/>
        <property type="nucleotide sequence ID" value="XM_054362904.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5QJU3"/>
    <dbReference type="SMR" id="Q5QJU3"/>
    <dbReference type="BioGRID" id="131056">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5QJU3">
        <property type="interactions" value="932"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5QJU3">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000342609"/>
    <dbReference type="BindingDB" id="Q5QJU3"/>
    <dbReference type="ChEMBL" id="CHEMBL2331067"/>
    <dbReference type="SwissLipids" id="SLP:000000164"/>
    <dbReference type="GlyCosmos" id="Q5QJU3">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5QJU3">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5QJU3"/>
    <dbReference type="BioMuta" id="ACER2"/>
    <dbReference type="DMDM" id="110832756"/>
    <dbReference type="PaxDb" id="9606-ENSP00000342609"/>
    <dbReference type="PeptideAtlas" id="Q5QJU3"/>
    <dbReference type="Antibodypedia" id="2873">
        <property type="antibodies" value="65 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="340485"/>
    <dbReference type="Ensembl" id="ENST00000340967.3">
        <molecule id="Q5QJU3-1"/>
        <property type="protein sequence ID" value="ENSP00000342609.2"/>
        <property type="gene ID" value="ENSG00000177076.6"/>
    </dbReference>
    <dbReference type="GeneID" id="340485"/>
    <dbReference type="KEGG" id="hsa:340485"/>
    <dbReference type="MANE-Select" id="ENST00000340967.3">
        <property type="protein sequence ID" value="ENSP00000342609.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001010887.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001010887.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003zny.2">
        <molecule id="Q5QJU3-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23675"/>
    <dbReference type="ClinPGx" id="PA164714853"/>
    <dbReference type="CTD" id="340485"/>
    <dbReference type="DisGeNET" id="340485"/>
    <dbReference type="GeneCards" id="ACER2"/>
    <dbReference type="HGNC" id="HGNC:23675">
        <property type="gene designation" value="ACER2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000177076">
        <property type="expression patterns" value="Group enriched (stomach, urinary bladder)"/>
    </dbReference>
    <dbReference type="MIM" id="613492">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000177076"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000177076"/>
    <dbReference type="eggNOG" id="KOG2329">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00730000110920"/>
    <dbReference type="HOGENOM" id="CLU_088280_0_0_1"/>
    <dbReference type="InParanoid" id="Q5QJU3"/>
    <dbReference type="OMA" id="FWHILIF"/>
    <dbReference type="OrthoDB" id="187171at2759"/>
    <dbReference type="PAN-GO" id="Q5QJU3">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5QJU3"/>
    <dbReference type="BRENDA" id="3.5.1.23">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q5QJU3"/>
    <dbReference type="Reactome" id="R-HSA-9845614">
        <property type="pathway name" value="Sphingolipid catabolism"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q5QJU3"/>
    <dbReference type="SignaLink" id="Q5QJU3"/>
    <dbReference type="UniPathway" id="UPA00222"/>
    <dbReference type="Agora" id="ENSG00000177076"/>
    <dbReference type="BioGRID-ORCS" id="340485">
        <property type="hits" value="10 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACER2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACER2"/>
    <dbReference type="GenomeRNAi" id="340485"/>
    <dbReference type="Pharos" id="Q5QJU3">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5QJU3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5QJU3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000177076">
        <property type="expression patterns" value="Expressed in urinary bladder and 110 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000139">
        <property type="term" value="C:Golgi membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017040">
        <property type="term" value="F:N-acylsphingosine amidohydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071466">
        <property type="term" value="P:cellular response to xenobiotic stimulus"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046514">
        <property type="term" value="P:ceramide catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006974">
        <property type="term" value="P:DNA damage response"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030330">
        <property type="term" value="P:DNA damage response, signal transduction by p53 class mediator"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033629">
        <property type="term" value="P:negative regulation of cell adhesion mediated by integrin"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001953">
        <property type="term" value="P:negative regulation of cell-matrix adhesion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008284">
        <property type="term" value="P:positive regulation of cell population proliferation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042981">
        <property type="term" value="P:regulation of apoptotic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010506">
        <property type="term" value="P:regulation of autophagy"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010559">
        <property type="term" value="P:regulation of glycoprotein biosynthetic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032526">
        <property type="term" value="P:response to retinoic acid"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030149">
        <property type="term" value="P:sphingolipid catabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046512">
        <property type="term" value="P:sphingosine biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008901">
        <property type="entry name" value="ACER"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46139">
        <property type="entry name" value="ALKALINE CERAMIDASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46139:SF1">
        <property type="entry name" value="ALKALINE CERAMIDASE 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05875">
        <property type="entry name" value="Ceramidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0746">Sphingolipid metabolism</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000247748" description="Alkaline ceramidase 2">
        <location>
            <begin position="1"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="1"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="33"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="54"/>
            <end position="62"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="63"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="84"/>
            <end position="86"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="87"/>
            <end position="107"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="108"/>
            <end position="124"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="125"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="144"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="165"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="174"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="195"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="212"/>
            <end position="232"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="233"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for proper localization to the Golgi apparatus" evidence="6">
        <location>
            <begin position="1"/>
            <end position="13"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="18"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="19"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="21"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="23"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="32"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="82"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="211"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="215"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_020033" description="In isoform 2 and isoform 3." evidence="12 13">
        <location>
            <begin position="1"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_020034" description="In isoform 3." evidence="13">
        <original>CDNMRVFKLGLFSGLWWTLAL</original>
        <variation>HERNQRRRHRKGGQQGGGDKV</variation>
        <location>
            <begin position="169"/>
            <end position="189"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_020035" description="In isoform 3." evidence="13">
        <location>
            <begin position="190"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027150" description="In dbSNP:rs10964136.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of localization to the Golgi. No effect on the ceramidase activity." evidence="6">
        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAQ85132." evidence="15" ref="1">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8VD53"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9NUN7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16940153"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="18945876"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="20089856"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="20207939"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="20628055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="26943039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="28294157"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="29229990"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="15498874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="20207939"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="20089856"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="17">
        <source>
            <dbReference type="HGNC" id="HGNC:23675"/>
        </source>
    </evidence>
    <sequence length="275" mass="31309" checksum="56FD619B53C296B1" modified="2006-07-25" version="2">MGAPHWWDQLQAGSSEVDWCEDNYTIVPAIAEFYNTISNVLFFILPPICMCLFRQYATCFNSGIYLIWTLLVVVGIGSVYFHATLSFLGQMLDELAVLWVLMCALAMWFPRRYLPKIFRNDRGRFKVVVSVLSAVTTCLAFVKPAINNISLMTLGVPCTALLIAELKRCDNMRVFKLGLFSGLWWTLALFCWISDRAFCELLSSFNFPYLHCMWHILICLAAYLGCVCFAYFDAASEIPEQGPVIKFWPNEKWAFIGVPYVSLLCANKKSSVKIT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-08-14" modified="2026-01-28" version="177" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NUN7</accession>
    <accession>B2RC99</accession>
    <name>ACER3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alkaline ceramidase 3</fullName>
            <shortName>AlkCDase 3</shortName>
            <shortName>Alkaline CDase 3</shortName>
            <ecNumber evidence="2 3 4">3.5.1.-</ecNumber>
            <ecNumber evidence="3 4 5 6">3.5.1.23</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alkaline dihydroceramidase SB89</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alkaline phytoceramidase</fullName>
            <shortName>aPHC</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACER3</name>
        <name type="synonym">APHC</name>
        <name type="synonym">PHCA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="26577" last="26588">
            <title>Cloning and characterization of a novel human alkaline ceramidase. A mammalian enzyme that hydrolyzes phytoceramide.</title>
            <authorList>
                <person name="Mao C."/>
                <person name="Xu R."/>
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            </authorList>
            <dbReference type="PubMed" id="11356846"/>
            <dbReference type="DOI" id="10.1074/jbc.m102818200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2000-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Li N."/>
                <person name="Zhang W."/>
                <person name="Wan T."/>
                <person name="Chen T."/>
                <person name="Cao X."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
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                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
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                <person name="Furuya T."/>
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                <person name="Kamihara K."/>
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                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
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                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Hara H."/>
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                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
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                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
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                <person name="Moriya S."/>
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                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
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                <person name="Nakai K."/>
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                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Placenta</tissue>
            <tissue>Thalamus</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
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                <person name="Taylor T.D."/>
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                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
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                <person name="Takeda T."/>
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                <person name="Jaffe D.B."/>
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                <person name="Sougnez C."/>
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                <person name="Lander E.S."/>
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            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Eye</tissue>
        </source>
    </reference>
    <reference key="7">
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                <person name="Xu R."/>
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            <dbReference type="PubMed" id="20207939"/>
            <dbReference type="DOI" id="10.1096/fj.09-153635"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
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            <title>Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides, and its down-regulation inhibits both cell proliferation and apoptosis.</title>
            <authorList>
                <person name="Hu W."/>
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                <person name="Mao C."/>
            </authorList>
            <dbReference type="PubMed" id="20068046"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.063586"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>PATHWAY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2016" name="J. Med. Genet." volume="53" first="389" last="396">
            <title>Deficiency of the alkaline ceramidase ACER3 manifests in early childhood by progressive leukodystrophy.</title>
            <authorList>
                <person name="Edvardson S."/>
                <person name="Yi J.K."/>
                <person name="Jalas C."/>
                <person name="Xu R."/>
                <person name="Webb B.D."/>
                <person name="Snider J."/>
                <person name="Fedick A."/>
                <person name="Kleinman E."/>
                <person name="Treff N.R."/>
                <person name="Mao C."/>
                <person name="Elpeleg O."/>
            </authorList>
            <dbReference type="PubMed" id="26792856"/>
            <dbReference type="DOI" id="10.1136/jmedgenet-2015-103457"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INVOLVEMENT IN PLDECO</scope>
        <scope>VARIANT PLDECO GLY-33</scope>
        <scope>CHARACTERIZATION OF VARIANT PLDECO GLY-33</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2018" name="Nat. Commun." volume="9" first="5437" last="5437">
            <title>Structure of a human intramembrane ceramidase explains enzymatic dysfunction found in leukodystrophy.</title>
            <authorList>
                <person name="Vasiliauskaite-Brooks I."/>
                <person name="Healey R.D."/>
                <person name="Rochaix P."/>
                <person name="Saint-Paul J."/>
                <person name="Sounier R."/>
                <person name="Grison C."/>
                <person name="Waltrich-Augusto T."/>
                <person name="Fortier M."/>
                <person name="Hoh F."/>
                <person name="Saied E.M."/>
                <person name="Arenz C."/>
                <person name="Basu S."/>
                <person name="Leyrat C."/>
                <person name="Granier S."/>
            </authorList>
            <dbReference type="PubMed" id="30575723"/>
            <dbReference type="DOI" id="10.1038/s41467-018-07864-w"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 2-244 IN COMPLEX WITH CALCIUM AND ZINC IONS</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>PATHWAY</scope>
        <scope>CHARACTERIZATION OF VARIANT PLDECO GLY-33</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
        <scope>MUTAGENESIS OF ASP-19; GLU-22; ASN-24; SER-99; TYR-149 AND SER-228</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2 3 4 5 6 8">Endoplasmic reticulum and Golgi ceramidase that catalyzes the hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-ceramides, dihydroceramides and phytoceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:11356846, PubMed:20068046, PubMed:20207939, PubMed:26792856, PubMed:30575723). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:20068046). Controls the generation of sphingosine in erythrocytes, and thereby sphingosine-1-phosphate in plasma (PubMed:20207939). Through the regulation of ceramides and sphingosine-1-phosphate homeostasis in the brain may play a role in neurons survival and function (By similarity). By regulating the levels of pro-inflammatory ceramides in immune cells and tissues, may modulate the inflammatory response (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3">
            <text>an N-acyl-(4R)-4-hydroxysphinganine + H2O = (4R)-hydroxysphinganine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:33555"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:31998"/>
            <dbReference type="ChEBI" id="CHEBI:64124"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:33556"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphing-4-enine + H2O = sphing-4-enine + (5Z,8Z,11Z,14Z)-eicosatetraenoate</text>
            <dbReference type="Rhea" id="RHEA:45348"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:85198"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45349"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sphinganine + H2O = sphinganine + (5Z,8Z,11Z,14Z)-eicosatetraenoate</text>
            <dbReference type="Rhea" id="RHEA:45376"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
            <dbReference type="ChEBI" id="CHEBI:85206"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45377"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-(4R)-hydroxysphinganine + H2O = (4R)-hydroxysphinganine + (5Z,8Z,11Z,14Z)-eicosatetraenoate</text>
            <dbReference type="Rhea" id="RHEA:45380"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:64124"/>
            <dbReference type="ChEBI" id="CHEBI:85207"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45381"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(11Z-eicosenoyl)-sphing-4-enine + H2O = (11Z)-eicosenoate + sphing-4-enine</text>
            <dbReference type="Rhea" id="RHEA:45356"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32426"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:85284"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45357"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(11Z-eicosenoyl)-sphinganine + H2O = (11Z)-eicosenoate + sphinganine</text>
            <dbReference type="Rhea" id="RHEA:45360"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32426"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
            <dbReference type="ChEBI" id="CHEBI:85285"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45361"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(11Z-eicosenoyl)-(4R)-hydroxysphinganine + H2O = (11Z)-eicosenoate + (4R)-hydroxysphinganine</text>
            <dbReference type="Rhea" id="RHEA:45364"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:32426"/>
            <dbReference type="ChEBI" id="CHEBI:64124"/>
            <dbReference type="ChEBI" id="CHEBI:85286"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45365"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 5">
            <text>N-(9Z-octadecenoyl)-sphing-4-enine + H2O = sphing-4-enine + (9Z)-octadecenoate</text>
            <dbReference type="Rhea" id="RHEA:41299"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="ChEBI" id="CHEBI:77996"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:41300"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>N-(9Z-octadecenoyl)-sphinganine + H2O = sphinganine + (9Z)-octadecenoate</text>
            <dbReference type="Rhea" id="RHEA:45372"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
            <dbReference type="ChEBI" id="CHEBI:74100"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45373"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-(9Z-octadecenoyl)-(4R)-hydroxysphinganine + H2O = (4R)-hydroxysphinganine + (9Z)-octadecenoate</text>
            <dbReference type="Rhea" id="RHEA:45368"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:64124"/>
            <dbReference type="ChEBI" id="CHEBI:85204"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:45369"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4 5">
            <text>an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:20856"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:52639"/>
            <dbReference type="ChEBI" id="CHEBI:57756"/>
            <dbReference type="EC" id="3.5.1.23"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:20857"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4">
            <text>an N-acylsphinganine + H2O = sphinganine + a fatty acid</text>
            <dbReference type="Rhea" id="RHEA:33551"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:31488"/>
            <dbReference type="ChEBI" id="CHEBI:57817"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:33552"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Activated by 5 mM Ca(2+) and inhibited by 5 mM Zn(2+).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <phDependence>
            <text evidence="2">Optimum pH is 9.5.</text>
        </phDependence>
    </comment>
    <comment type="pathway">
        <text evidence="3 4 6">Lipid metabolism; sphingolipid metabolism.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Endoplasmic reticulum membrane</location>
            <topology evidence="2 6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Golgi apparatus membrane</location>
            <topology evidence="2 6">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NUN7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NUN7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_039162 VSP_039163"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 4">Ubiquitously expressed. Highly expressed in placenta (PubMed:11356846). Expressed in erythrocytes (PubMed:20207939).</text>
    </comment>
    <comment type="disease" evidence="5 6">
        <disease id="DI-05125">
            <name>Leukodystrophy, progressive, early childhood-onset</name>
            <acronym>PLDECO</acronym>
            <description>A form of leukodystrophy, a disorder of myelin production or maintenance affecting the central nervous system. PELCO features include neurological regression between 6 and 13 months of age, truncal hypotonia, appendicular spasticity, dystonia, optic disk pallor, peripheral neuropathy and neurogenic bladder. Brain imaging shows progressive diffuse abnormal white matter signals, cerebral atrophy, and thin corpus callosum. Sural nerve biopsy shows decreased myelination. PLDECO inheritance is autosomal recessive.</description>
            <dbReference type="MIM" id="617762"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the alkaline ceramidase family.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.-" evidence="2 3 4"/>
    <dbReference type="EC" id="3.5.1.23" evidence="3 4 5 6"/>
    <dbReference type="EMBL" id="AF214454">
        <property type="protein sequence ID" value="AAK71923.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF327353">
        <property type="protein sequence ID" value="AAL56013.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK002100">
        <property type="protein sequence ID" value="BAA92085.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315000">
        <property type="protein sequence ID" value="BAG37496.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP000752">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP002498">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP003119">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471076">
        <property type="protein sequence ID" value="EAW75010.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC073853">
        <property type="protein sequence ID" value="AAH73853.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8247.1">
        <molecule id="Q9NUN7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060837.3">
        <molecule id="Q9NUN7-1"/>
        <property type="nucleotide sequence ID" value="NM_018367.6"/>
    </dbReference>
    <dbReference type="PDB" id="6G7O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=2-244"/>
    </dbReference>
    <dbReference type="PDB" id="6YXH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=2-244"/>
    </dbReference>
    <dbReference type="PDBsum" id="6G7O"/>
    <dbReference type="PDBsum" id="6YXH"/>
    <dbReference type="AlphaFoldDB" id="Q9NUN7"/>
    <dbReference type="SMR" id="Q9NUN7"/>
    <dbReference type="BioGRID" id="120612">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NUN7">
        <property type="interactions" value="1008"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NUN7">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000434480"/>
    <dbReference type="SwissLipids" id="SLP:000000680"/>
    <dbReference type="GlyGen" id="Q9NUN7">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NUN7"/>
    <dbReference type="PhosphoSitePlus" id="Q9NUN7"/>
    <dbReference type="BioMuta" id="ACER3"/>
    <dbReference type="DMDM" id="296439452"/>
    <dbReference type="MassIVE" id="Q9NUN7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000434480"/>
    <dbReference type="PeptideAtlas" id="Q9NUN7"/>
    <dbReference type="ProteomicsDB" id="82700">
        <molecule id="Q9NUN7-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82701">
        <molecule id="Q9NUN7-2"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="Q9NUN7-1">
        <molecule id="Q9NUN7-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="53464">
        <property type="antibodies" value="121 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55331"/>
    <dbReference type="Ensembl" id="ENST00000532485.6">
        <molecule id="Q9NUN7-1"/>
        <property type="protein sequence ID" value="ENSP00000434480.1"/>
        <property type="gene ID" value="ENSG00000078124.14"/>
    </dbReference>
    <dbReference type="GeneID" id="55331"/>
    <dbReference type="KEGG" id="hsa:55331"/>
    <dbReference type="MANE-Select" id="ENST00000532485.6">
        <property type="protein sequence ID" value="ENSP00000434480.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018367.7"/>
        <property type="RefSeq protein sequence ID" value="NP_060837.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc009yum.2">
        <molecule id="Q9NUN7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16066"/>
    <dbReference type="ClinPGx" id="PA33256"/>
    <dbReference type="CTD" id="55331"/>
    <dbReference type="DisGeNET" id="55331"/>
    <dbReference type="GeneCards" id="ACER3"/>
    <dbReference type="HGNC" id="HGNC:16066">
        <property type="gene designation" value="ACER3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000078124">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACER3"/>
    <dbReference type="MIM" id="617036">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="617762">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000078124"/>
    <dbReference type="Orphanet" id="502444">
        <property type="disease" value="Alkaline ceramidase 3 deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000078124"/>
    <dbReference type="eggNOG" id="KOG2329">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00730000110920"/>
    <dbReference type="InParanoid" id="Q9NUN7"/>
    <dbReference type="OMA" id="IMFEPLR"/>
    <dbReference type="OrthoDB" id="187171at2759"/>
    <dbReference type="PAN-GO" id="Q9NUN7">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NUN7"/>
    <dbReference type="BRENDA" id="3.5.1.23">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NUN7"/>
    <dbReference type="Reactome" id="R-HSA-9845614">
        <property type="pathway name" value="Sphingolipid catabolism"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NUN7"/>
    <dbReference type="UniPathway" id="UPA00222"/>
    <dbReference type="Agora" id="ENSG00000078124"/>
    <dbReference type="BioGRID-ORCS" id="55331">
        <property type="hits" value="15 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACER3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACER3"/>
    <dbReference type="GenomeRNAi" id="55331"/>
    <dbReference type="Pharos" id="Q9NUN7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NUN7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NUN7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000078124">
        <property type="expression patterns" value="Expressed in endothelial cell and 195 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NUN7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000139">
        <property type="term" value="C:Golgi membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005509">
        <property type="term" value="F:calcium ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017040">
        <property type="term" value="F:N-acylsphingosine amidohydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="P:phytosphingosine biosynthetic process"/>
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        <property type="term" value="P:regulation of programmed cell death"/>
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        <property type="term" value="P:sphingosine biosynthetic process"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="InterPro" id="IPR008901">
        <property type="entry name" value="ACER"/>
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    <feature type="mutagenesis site" description="Strongly decreased enzyme activity." evidence="6">
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    <feature type="mutagenesis site" description="No effect on enzyme activity." evidence="6">
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            <position position="228"/>
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            <position position="52"/>
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    <feature type="helix" evidence="12">
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    <feature type="helix" evidence="12">
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    <feature type="helix" evidence="12">
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            <begin position="61"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="86"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="119"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="142"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="169"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="172"/>
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    <feature type="helix" evidence="12">
        <location>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="209"/>
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    </feature>
    <feature type="helix" evidence="12">
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            <begin position="216"/>
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    </feature>
    <evidence type="ECO:0000250" key="1">
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            <dbReference type="UniProtKB" id="Q9D099"/>
        </source>
    </evidence>
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        <source>
            <dbReference type="PubMed" id="11356846"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="20068046"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="20207939"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="26792856"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="30575723"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="20068046"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="20068046"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PDB" id="6G7O"/>
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    </evidence>
    <evidence type="ECO:0007829" key="12">
        <source>
            <dbReference type="PDB" id="6YXH"/>
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    </evidence>
    <sequence length="267" mass="31552" checksum="CFD2A901F12A5918" modified="2010-05-18" version="3">MAPAADREGYWGPTTSTLDWCEENYSVTWYIAEFWNTVSNLIMIIPPMFGAVQSVRDGLEKRYIASYLALTVVGMGSWCFHMTLKYEMQLLDELPMIYSCCIFVYCMFECFKIKNSVNYHLLFTLVLFSLIVTTVYLKVKEPIFHQVMYGMLVFTLVLRSIYIVTWVYPWLRGLGYTSLGIFLLGFLFWNIDNIFCESLRNFRKKVPPIIGITTQFHAWWHILTGLGSYLHILFSLYTRTLYLRYRPKVKFLFGIWPVILFEPLRKH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="246" xmlns="https://uniprot.org/uniprot">
    <accession>P02708</accession>
    <accession>B4DRV6</accession>
    <accession>D3DPE8</accession>
    <name>ACHA_HUMAN</name>
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        <recommendedName>
            <fullName evidence="17">Acetylcholine receptor subunit alpha</fullName>
        </recommendedName>
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    <gene>
        <name evidence="19" type="primary">CHRNA1</name>
        <name type="synonym">ACHRA</name>
        <name type="synonym">CHNRA</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1983" name="Nature" volume="305" first="818" last="823">
            <title>Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor.</title>
            <authorList>
                <person name="Noda M."/>
                <person name="Furutani Y."/>
                <person name="Takahashi H."/>
                <person name="Toyosato M."/>
                <person name="Tanabe T."/>
                <person name="Shimizu S."/>
                <person name="Kikyotani S."/>
                <person name="Kayano T."/>
                <person name="Hirose T."/>
                <person name="Inayama S."/>
                <person name="Numa S."/>
            </authorList>
            <dbReference type="PubMed" id="6688857"/>
            <dbReference type="DOI" id="10.1038/305818a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1988" name="FEBS Lett." volume="226" first="235" last="240">
            <title>The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA.</title>
            <authorList>
                <person name="Schoepfer R."/>
                <person name="Luther M."/>
                <person name="Lindstrom J.M."/>
            </authorList>
            <dbReference type="PubMed" id="3338555"/>
            <dbReference type="DOI" id="10.1016/0014-5793(88)81430-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1990" name="EMBO J." volume="9" first="2101" last="2106">
            <title>The human muscle nicotinic acetylcholine receptor alpha-subunit exist as two isoforms: a novel exon.</title>
            <authorList>
                <person name="Beeson D."/>
                <person name="Morris A."/>
                <person name="Vincent A."/>
                <person name="Newsom-Davis J."/>
            </authorList>
            <dbReference type="PubMed" id="1694127"/>
            <dbReference type="DOI" id="10.1002/j.1460-2075.1990.tb07378.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 2)</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1994" name="Thymus" volume="23" first="103" last="113">
            <title>Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a thymoma associated with myasthenia gravis.</title>
            <authorList>
                <person name="Gattenloehner S."/>
                <person name="Brabletz T."/>
                <person name="Schultz A."/>
                <person name="Marx A."/>
                <person name="Mueller-Hermelink H.-K."/>
                <person name="Kirchner T."/>
            </authorList>
            <dbReference type="PubMed" id="7725386"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Thymus</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Tongue</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PROTEIN SEQUENCE OF 21-457 (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-89</scope>
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        <scope>FUNCTION (ISOFORMS 1 AND 2)</scope>
        <scope>SUBUNIT (ISOFORMS 1 AND 2)</scope>
        <scope>MISCELLANEOUS (ISOFORM 2)</scope>
        <scope>MUTAGENESIS OF GLU-261</scope>
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        <scope>SUBUNIT</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF VAL-275</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 21-231</scope>
        <scope>DISULFIDE BONDS</scope>
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        </citation>
        <scope>VARIANT CMS1A SER-173</scope>
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        </citation>
        <scope>VARIANT CMS1A LYS-237</scope>
    </reference>
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            <dbReference type="PubMed" id="9158151"/>
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        </citation>
        <scope>VARIANTS CMS1A SER-173; MET-176; ILE-274 AND ILE-289</scope>
    </reference>
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        </citation>
        <scope>VARIANT CMS1A PHE-269</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS1A PHE-269</scope>
    </reference>
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        <scope>VARIANTS CMS1B VAL-253 AND ILE-305</scope>
        <scope>CHARACTERIZATION OF VARIANTS CMS1B VAL-253 AND ILE-305</scope>
    </reference>
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        <scope>ERRATUM OF PUBMED:10195214</scope>
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        </citation>
        <scope>VARIANT CMS1B LEU-152</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS1B LEU-152</scope>
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        <scope>VARIANT CMS1B LEU-276</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS1B LEU-276</scope>
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        <scope>VARIANT CMS1A TRP-438</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS1A TRP-438</scope>
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        <scope>VARIANT LMPS LEU-229</scope>
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    <comment type="function">
        <molecule>Isoform 1</molecule>
        <text evidence="10">Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="12">Non functional acetylcholine receptor alpha subunit which is not integrated into functional acetylcholine-gated cation-selective channels.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <molecule>Isoform 1</molecule>
        <text evidence="6">One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).</text>
    </comment>
    <comment type="subunit">
        <molecule>Isoform 2</molecule>
        <text evidence="12">Is able to interact with other subunits of the acetylcholine receptor but is not assembled into functional acetylcholine-gated cation-selective channels.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="18">Postsynaptic cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P02708-2</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P02708-1</id>
            <name>2</name>
            <name>P3A(+)</name>
            <name evidence="16">alpha+</name>
            <sequence type="described" ref="VSP_061499"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Isoform 1 is only expressed in skeletal muscle. Isoform 2 is constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus.</text>
    </comment>
    <comment type="disease" evidence="8">
        <disease id="DI-01895">
            <name>Multiple pterygium syndrome, lethal type</name>
            <acronym>LMPS</acronym>
            <description>Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.</description>
            <dbReference type="MIM" id="253290"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text>The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.</text>
    </comment>
    <comment type="disease" evidence="7 11 13 14 15">
        <disease id="DI-00368">
            <name>Myasthenic syndrome, congenital, 1A, slow-channel</name>
            <acronym>CMS1A</acronym>
            <description>A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.</description>
            <dbReference type="MIM" id="601462"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="3 4 5">
        <disease id="DI-00367">
            <name>Myasthenic syndrome, congenital, 1B, fast-channel</name>
            <acronym>CMS1B</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS1B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.</description>
            <dbReference type="MIM" id="608930"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="12">Acetylcholine receptors incorporating that alpha subunit do not bind alpha-bungarotoxin.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="CAA49705" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X02502">
        <property type="protein sequence ID" value="CAA26344.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X02503">
        <property type="protein sequence ID" value="CAA26344.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X02504">
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        <property type="entry name" value="Neuro_actylchol_rec"/>
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        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
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        <property type="entry name" value="LIC"/>
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        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_memb"/>
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        <property type="entry name" value="NICOTINICR"/>
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        <property type="entry name" value="NRIONCHANNEL"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
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        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
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        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1004">Congenital myasthenic syndrome</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
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    <feature type="topological domain" description="Cytoplasmic" evidence="17">
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    <feature type="topological domain" description="Extracellular" evidence="17">
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    <feature type="topological domain" description="Cytoplasmic" evidence="17">
        <location>
            <begin position="318"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
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            <begin position="428"/>
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    <feature type="topological domain" description="Extracellular" evidence="17">
        <location>
            <begin position="449"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="161"/>
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    <feature type="disulfide bond" evidence="20">
        <location>
            <begin position="148"/>
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    <feature type="disulfide bond" description="Associated with receptor activation" evidence="20">
        <location>
            <begin position="212"/>
            <end position="213"/>
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    <feature type="splice variant" id="VSP_061499" description="In isoform 2.">
        <original>Q</original>
        <variation>QGDMVDLPRPSCVTLGVPLFSHLQNE</variation>
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            <position position="78"/>
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    <feature type="sequence variant" id="VAR_038599" description="In CMS1B; mutant channel shows an approximately 30-fold decrease of ACh binding affinity for the second of 2 closed-state binding sites but only a 2-fold decrease in gating efficiency; dbSNP:rs137852807." evidence="4">
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        <location>
            <position position="152"/>
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        <location>
            <position position="173"/>
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    <feature type="sequence variant" id="VAR_000283" description="In CMS1A; dbSNP:rs137852799." evidence="14">
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    <feature type="sequence variant" id="VAR_043904" description="In LMPS; dbSNP:rs137852809." evidence="8">
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        <location>
            <position position="229"/>
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    <feature type="sequence variant" id="VAR_000284" description="In CMS1A; dbSNP:rs137852798." evidence="13">
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        <location>
            <position position="237"/>
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    <feature type="sequence variant" id="VAR_021206" description="In CMS1B; markedly reduced protein expression; dbSNP:rs137852805." evidence="3">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="253"/>
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    <feature type="sequence variant" id="VAR_021207" description="In CMS1A; causes increased channel opening in absence of ACh; prolonged opening in presence of ACh; increased affinity for ACh and enhanced desensitization; dbSNP:rs137852803." evidence="15">
        <original>V</original>
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            <position position="269"/>
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    <feature type="sequence variant" id="VAR_000285" description="In CMS1A; dbSNP:rs137852800." evidence="14">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="274"/>
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    <feature type="sequence variant" id="VAR_021208" description="In CMS1B; fewer and shorter ion channel activations with decreased channel opening rate and increased channel closing rate; dbSNP:rs137852806." evidence="5">
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        <variation>L</variation>
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    <feature type="sequence variant" id="VAR_000286" description="In CMS1A; dbSNP:rs137852802." evidence="14">
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        <variation>I</variation>
        <location>
            <position position="289"/>
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    <feature type="sequence variant" id="VAR_021209" description="In CMS1B; abnormally slow channel opening and closing resulting in abnormally brief current; dbSNP:rs137852804." evidence="3">
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        <location>
            <position position="305"/>
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    <feature type="sequence variant" id="VAR_038600" description="In dbSNP:rs6739001.">
        <original>D</original>
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        <location>
            <position position="358"/>
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    <feature type="sequence variant" id="VAR_038601" description="In CMS1A; increases the rate of channel opening and slows the rate of channel closing but has no effect on agonist binding; dbSNP:rs137852808." evidence="7">
        <original>C</original>
        <variation>W</variation>
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            <position position="438"/>
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    <feature type="mutagenesis site" description="Changed acetylcholine-gated cation-selective channel activity." evidence="12">
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        <variation>Q</variation>
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            <position position="261"/>
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    <feature type="mutagenesis site" description="Increased length of channel opening." evidence="10">
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        <variation>A</variation>
        <location>
            <position position="275"/>
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    <feature type="sequence conflict" description="In Ref. 4; AAD14247." evidence="17" ref="4">
        <original>P</original>
        <variation>F</variation>
        <location>
            <position position="390"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="23"/>
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    <feature type="strand" evidence="21">
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            <begin position="49"/>
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    <feature type="turn" evidence="22">
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            <begin position="65"/>
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    <feature type="strand" evidence="21">
        <location>
            <begin position="81"/>
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    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="89"/>
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    <feature type="strand" evidence="21">
        <location>
            <begin position="97"/>
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    <feature type="helix" evidence="22">
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            <begin position="102"/>
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    <feature type="strand" evidence="22">
        <location>
            <begin position="110"/>
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    <feature type="strand" evidence="22">
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            <begin position="115"/>
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    <feature type="strand" evidence="22">
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            <begin position="127"/>
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    <feature type="strand" evidence="22">
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            <begin position="134"/>
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    <feature type="strand" evidence="22">
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    <feature type="strand" evidence="22">
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    <feature type="strand" evidence="22">
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            <dbReference type="PubMed" id="27375219"/>
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            <dbReference type="PubMed" id="7619526"/>
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            <dbReference type="HGNC" id="HGNC:1955"/>
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    <sequence length="457" mass="51839" checksum="89480567D85C15B8" modified="2022-05-25" version="3" precursor="true">MEPWPLLLLFSLCSAGLVLGSEHETRLVAKLFKDYSSVVRPVEDHRQVVEVTVGLQLIQLINVDEVNQIVTTNVRLKQQWVDYNLKWNPDDYGGVKKIHIPSEKIWRPDLVLYNNADGDFAIVKFTKVLLQYTGHITWTPPAIFKSYCEIIVTHFPFDEQNCSMKLGTWTYDGSVVAINPESDQPDLSNFMESGEWVIKESRGWKHSVTYSCCPDTPYLDITYHFVMQRLPLYFIVNVIIPCLLFSFLTGLVFYLPTDSGEKMTLSISVLLSLTVFLLVIVELIPSTSSAVPLIGKYMLFTMVFVIASIIITVIVINTHHRSPSTHVMPNWVRKVFIDTIPNIMFFSTMKRPSREKQDKKIFTEDIDISDISGKPGPPPMGFHSPLIKHPEVKSAIEGIKYIAETMKSDQESNNAAAEWKYVAMVMDHILLGVFMLVCIIGTLAVFAGRLIELNQQG</sequence>
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    <accession>P30926</accession>
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        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit beta-4</fullName>
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        <name evidence="20" type="primary">CHRNB4</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
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    <reference key="1">
        <citation type="journal article" date="1996" name="J. Mol. Neurosci." volume="7" first="217" last="228">
            <title>Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.</title>
            <authorList>
                <person name="Elliott K.J."/>
                <person name="Ellis S.B."/>
                <person name="Berckhan K.J."/>
                <person name="Urrutia A."/>
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            </authorList>
            <dbReference type="PubMed" id="8906617"/>
            <dbReference type="DOI" id="10.1007/bf02736842"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="Mol. Pharmacol." volume="51" first="320" last="327">
            <title>'Orphan' alpha6 nicotinic AChR subunit can form a functional heteromeric acetylcholine receptor.</title>
            <authorList>
                <person name="Gerzanich V."/>
                <person name="Kuryatov A."/>
                <person name="Anand R."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="9203638"/>
            <dbReference type="DOI" id="10.1124/mol.51.2.320"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="400" first="309" last="314">
            <title>Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.</title>
            <authorList>
                <person name="Groot Kormelink P.J."/>
                <person name="Luyten W.H.M.L."/>
            </authorList>
            <dbReference type="PubMed" id="9009220"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(96)01383-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2001-03" db="EMBL/GenBank/DDBJ databases">
            <title>Characterization of the genomic structure of human nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster: identification of two novel introns in the 3' untranslated region of CHRNA3 and of a tail-to-tail overlap between CHRNA3 and CHRNA5.</title>
            <authorList>
                <person name="Duga S."/>
                <person name="Solda G."/>
                <person name="Asselta R."/>
                <person name="Bonati M.T."/>
                <person name="Dalpra L."/>
                <person name="Malcovati M."/>
                <person name="Tenchini M.L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="J. Hum. Genet." volume="46" first="362" last="366">
            <title>Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4.</title>
            <authorList>
                <person name="Lev-Lehman E."/>
                <person name="Bercovich D."/>
                <person name="Xu W."/>
                <person name="Stockton D.W."/>
                <person name="Beaudet A.L."/>
            </authorList>
            <dbReference type="PubMed" id="11450844"/>
            <dbReference type="DOI" id="10.1007/pl00010921"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
        <scope>VARIANTS TRP-136; GLY-140 AND VAL-467</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="671" last="675">
            <title>Analysis of the DNA sequence and duplication history of human chromosome 15.</title>
            <authorList>
                <person name="Zody M.C."/>
                <person name="Garber M."/>
                <person name="Sharpe T."/>
                <person name="Young S.K."/>
                <person name="Rowen L."/>
                <person name="O'Neill K."/>
                <person name="Whittaker C.A."/>
                <person name="Kamal M."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Kodira C.D."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Yang X."/>
                <person name="Abbasi N."/>
                <person name="Abouelleil A."/>
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                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Burke J."/>
                <person name="Butler J."/>
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                <person name="DeCaprio D."/>
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                <person name="Dors M."/>
                <person name="Eichler E.E."/>
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                <person name="Friedman C."/>
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                <person name="Jones C."/>
                <person name="Kamat A."/>
                <person name="Kaur A."/>
                <person name="Locke D.P."/>
                <person name="Madan A."/>
                <person name="Munson G."/>
                <person name="Jaffe D.B."/>
                <person name="Lui A."/>
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                <person name="Mauceli E."/>
                <person name="Naylor J.W."/>
                <person name="Nesbitt R."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Ratcliffe A."/>
                <person name="Rounsley S."/>
                <person name="She X."/>
                <person name="Sneddon K.M.B."/>
                <person name="Stewart S."/>
                <person name="Sougnez C."/>
                <person name="Stone S.M."/>
                <person name="Topham K."/>
                <person name="Vincent D."/>
                <person name="Wang S."/>
                <person name="Zimmer A.R."/>
                <person name="Birren B.W."/>
                <person name="Hood L."/>
                <person name="Lander E.S."/>
                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16572171"/>
            <dbReference type="DOI" id="10.1038/nature04601"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-198 (ISOFORM 2)</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="8866" last="8876">
            <title>Transcription factors NF-Y and Sp1 are important determinants of the promoter activity of the bovine and human neuronal nicotinic receptor beta 4 subunit genes.</title>
            <authorList>
                <person name="Valor L.M."/>
                <person name="Campos-Caro A."/>
                <person name="Carrasco-Serrano C."/>
                <person name="Ortiz J.A."/>
                <person name="Ballesta J.J."/>
                <person name="Criado M."/>
            </authorList>
            <dbReference type="PubMed" id="11742001"/>
            <dbReference type="DOI" id="10.1074/jbc.m110454200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1992" name="FEBS Lett." volume="312" first="66" last="70">
            <title>Neuronal-type nicotinic receptors in human neuroblastoma and small-cell lung carcinoma cell lines.</title>
            <authorList>
                <person name="Tarroni P."/>
                <person name="Rubboli F."/>
                <person name="Chini B."/>
                <person name="Zwart R."/>
                <person name="Oortgiesen M."/>
                <person name="Sher E."/>
                <person name="Clementi F."/>
            </authorList>
            <dbReference type="PubMed" id="1330682"/>
            <dbReference type="DOI" id="10.1016/0014-5793(92)81411-e"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 48-498</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1996" name="J. Biol. Chem." volume="271" first="17656" last="17665">
            <title>Assembly of human neuronal nicotinic receptor alpha5 subunits with alpha3, beta2, and beta4 subunits.</title>
            <authorList>
                <person name="Wang F."/>
                <person name="Gerzanich V."/>
                <person name="Wells G.B."/>
                <person name="Anand R."/>
                <person name="Peng X."/>
                <person name="Keyser K."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="8663494"/>
            <dbReference type="DOI" id="10.1074/jbc.271.30.17656"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2000" name="J. Physiol. (Lond.)" volume="529" first="565" last="577">
            <title>Stoichiometry of human recombinant neuronal nicotinic receptors containing the b3 subunit expressed in Xenopus oocytes.</title>
            <authorList>
                <person name="Boorman J.P."/>
                <person name="Groot-Kormelink P.J."/>
                <person name="Sivilotti L.G."/>
            </authorList>
            <dbReference type="PubMed" id="11118490"/>
            <dbReference type="DOI" id="10.1111/j.1469-7793.2000.00565.x"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>STOICHIOMETRY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF LEU-272</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="16019" last="16026">
            <title>Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes.</title>
            <authorList>
                <person name="Ellison M."/>
                <person name="Gao F."/>
                <person name="Wang H.L."/>
                <person name="Sine S.M."/>
                <person name="McIntosh J.M."/>
                <person name="Olivera B.M."/>
            </authorList>
            <dbReference type="PubMed" id="15609996"/>
            <dbReference type="DOI" id="10.1021/bi048918g"/>
        </citation>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2005" name="Mol. Pharmacol." volume="68" first="1431" last="1438">
            <title>RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells.</title>
            <authorList>
                <person name="Lansdell S.J."/>
                <person name="Gee V.J."/>
                <person name="Harkness P.C."/>
                <person name="Doward A.I."/>
                <person name="Baker E.R."/>
                <person name="Gibb A.J."/>
                <person name="Millar N.S."/>
            </authorList>
            <dbReference type="PubMed" id="16120769"/>
            <dbReference type="DOI" id="10.1124/mol.105.017459"/>
        </citation>
        <scope>INTERACTION WITH RIC3</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2011" name="Mol. Pharmacol." volume="79" first="119" last="125">
            <title>Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function.</title>
            <authorList>
                <person name="Kuryatov A."/>
                <person name="Berrettini W."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="20881005"/>
            <dbReference type="DOI" id="10.1124/mol.110.066357"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2016" name="J. Neurochem." volume="138" first="806" last="820">
            <title>Functional interaction between Lypd6 and nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Arvaniti M."/>
                <person name="Jensen M.M."/>
                <person name="Soni N."/>
                <person name="Wang H."/>
                <person name="Klein A.B."/>
                <person name="Thiriet N."/>
                <person name="Pinborg L.H."/>
                <person name="Muldoon P.P."/>
                <person name="Wienecke J."/>
                <person name="Imad Damaj M."/>
                <person name="Kohlmeier K.A."/>
                <person name="Gondre-Lewis M.C."/>
                <person name="Mikkelsen J.D."/>
                <person name="Thomsen M.S."/>
            </authorList>
            <dbReference type="PubMed" id="27344019"/>
            <dbReference type="DOI" id="10.1111/jnc.13718"/>
        </citation>
        <scope>INTERACTION WITH LYPD6</scope>
    </reference>
    <reference evidence="21 22" key="16">
        <citation type="journal article" date="2019" name="Neuron" volume="104" first="501" last="511.e6">
            <title>Agonist Selectivity and Ion Permeation in the alpha3beta4 Ganglionic Nicotinic Receptor.</title>
            <authorList>
                <person name="Gharpure A."/>
                <person name="Teng J."/>
                <person name="Zhuang Y."/>
                <person name="Noviello C.M."/>
                <person name="Walsh R.M."/>
                <person name="Cabuco R."/>
                <person name="Howard R.J."/>
                <person name="Zaveri N.T."/>
                <person name="Lindahl E."/>
                <person name="Hibbs R.E."/>
            </authorList>
            <dbReference type="PubMed" id="31488329"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2019.07.030"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.34 ANGSTROMS) OF 22-498 IN COMPLEX WITH CHRNA3 AND SODIUM</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5 8 12 14 15 16 17">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:20881005, PubMed:31488329, PubMed:8663494, PubMed:8906617, PubMed:9203638). CHRNB4 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3 and CHRNA4, as well as CHRNA5 and CHRNB3 as accesory subunits (PubMed:11118490, PubMed:20881005, PubMed:8663494). CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor (PubMed:31488329). CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo-interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction (By similarity). Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 17">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="8 10 12 14 16">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:11118490, PubMed:20881005, PubMed:31488329, PubMed:8906617). The heteropentamer CHRNA3:CHRNB4 activity is blocked by the alpha-conotoxin ImI and AuIB (PubMed:15609996).</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 11 12 13 14 15 16">Neuronal AChR is composed of two different types of subunits: alpha and beta. CHRNB4/Beta-4 subunit can be combined to CHRNA2/alpha-2, CHRNA3/alpha-3 or CHRNA4/alpha-4, CHRNA5/alpha-5 and CHRNB3/beta-3 to give rise to functional receptors (PubMed:11118490, PubMed:20881005, PubMed:31488329, PubMed:8663494, PubMed:8906617). Forms stoichiometries such as (CHRNA3)2:(CHRNB4)3 or (CHRNA3:CHRNB4)2:CHRNB3 (PubMed:11118490). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9009018">
            <id>P30926</id>
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        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Synaptic cell membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P30926-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P30926-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046674 VSP_046675"/>
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    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-4/CHRNB4 sub-subfamily.</text>
    </comment>
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        <property type="generic name" value="Succinylcholine"/>
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        <property type="glycosylation" value="4 sites, No reported glycans"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000261751"/>
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    <dbReference type="DNASU" id="1143"/>
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        <property type="gene ID" value="ENSG00000117971.13"/>
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    <dbReference type="Ensembl" id="ENST00000412074.6">
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        <property type="protein sequence ID" value="ENSP00000416386.2"/>
        <property type="gene ID" value="ENSG00000117971.13"/>
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    <dbReference type="GeneID" id="1143"/>
    <dbReference type="KEGG" id="hsa:1143"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_000750.5"/>
        <property type="RefSeq protein sequence ID" value="NP_000741.1"/>
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        <molecule id="P30926-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:1964"/>
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        <property type="gene designation" value="CHRNB4"/>
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        <property type="type" value="gene"/>
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        <property type="component" value="Chromosome 15"/>
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        <property type="project" value="Ensembl"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0034220">
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        <property type="project" value="ProtInc"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
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        <property type="entry name" value="Neur_channel"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NICOTINICR"/>
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00236">
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        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="6">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000389" description="Neuronal acetylcholine receptor subunit beta-4">
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            <begin position="22"/>
            <end position="498"/>
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        <location>
            <begin position="22"/>
            <end position="239"/>
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        <location>
            <begin position="240"/>
            <end position="255"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="6">
        <location>
            <begin position="256"/>
            <end position="261"/>
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    <feature type="transmembrane region" description="Helical" evidence="14 21 22">
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            <begin position="262"/>
            <end position="277"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="6">
        <location>
            <begin position="278"/>
            <end position="296"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="14 21 22">
        <location>
            <begin position="297"/>
            <end position="321"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="6">
        <location>
            <begin position="322"/>
            <end position="454"/>
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    <feature type="transmembrane region" description="Helical" evidence="14 21 22">
        <location>
            <begin position="455"/>
            <end position="478"/>
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    <feature type="topological domain" description="Extracellular" evidence="6">
        <location>
            <begin position="479"/>
            <end position="498"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="357"/>
            <end position="377"/>
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    </feature>
    <feature type="binding site" evidence="14 22">
        <location>
            <position position="262"/>
        </location>
        <ligand>
            <name>Na(+)</name>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </ligand>
    </feature>
    <feature type="site" description="Key residue that facilitates effective access of the conotoxin BuIA to the channel binding site" evidence="3">
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="site" description="Key residue for a low dissociation (K(off)) from the conotoxin BuIA" evidence="3">
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="36"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="138"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="14 21 22">
        <location>
            <begin position="153"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046674" description="In isoform 2." evidence="18">
        <original>NADGTYEVSVYTNLIVRSNGSVLWLPPAIYKSACKIEVKYFPFDQQNCTLKFRSWTYDHTEIDMVLMTPTASMDDFTPSGEWDIVALPGRRTVNPQDP</original>
        <variation>KSLRTGSTWLWWWTGCSCGCSCLCASWALWGSSYRPSSRPMQLLRGPTLPSVTEGPLGCGVRGCEWPGGHFAASFWVVADEALSKYVSIGHQPHQTSHSRGTGKDGGLGCPL</variation>
        <location>
            <begin position="120"/>
            <end position="217"/>
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    <feature type="splice variant" id="VSP_046675" description="In isoform 2." evidence="18">
        <location>
            <begin position="218"/>
            <end position="498"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048174" description="In dbSNP:rs12914008.">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013241" description="In dbSNP:rs141876090." evidence="9">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013242" description="In dbSNP:rs56218866." evidence="9">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013243" description="In dbSNP:rs61737502." evidence="9">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="467"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases potency of agonists." evidence="8">
        <original>L</original>
        <variation>T</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; CAA48336." evidence="19" ref="9">
        <original>EQ</original>
        <variation>DE</variation>
        <location>
            <begin position="72"/>
            <end position="73"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAC34819." evidence="19" ref="4">
        <location>
            <position position="121"/>
        </location>
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        <location>
            <begin position="26"/>
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    </feature>
    <feature type="turn" evidence="23">
        <location>
            <begin position="35"/>
            <end position="39"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="42"/>
            <end position="44"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="48"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="57"/>
            <end position="69"/>
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    </feature>
    <feature type="turn" evidence="23">
        <location>
            <begin position="70"/>
            <end position="73"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="74"/>
            <end position="86"/>
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    </feature>
    <feature type="turn" evidence="23">
        <location>
            <begin position="94"/>
            <end position="98"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="101"/>
            <end position="106"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="115"/>
            <end position="118"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="120"/>
            <end position="123"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="132"/>
            <end position="136"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
            <begin position="140"/>
            <end position="143"/>
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    </feature>
    <feature type="strand" evidence="23">
        <location>
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    <sequence length="498" mass="56380" checksum="0D48AB203F3FD03E" modified="1997-11-01" version="2" precursor="true">MRRAPSLVLFFLVALCGRGNCRVANAEEKLMDDLLNKTRYNNLIRPATSSSQLISIKLQLSLAQLISVNEREQIMTTNVWLKQEWTDYRLTWNSSRYEGVNILRIPAKRIWLPDIVLYNNADGTYEVSVYTNLIVRSNGSVLWLPPAIYKSACKIEVKYFPFDQQNCTLKFRSWTYDHTEIDMVLMTPTASMDDFTPSGEWDIVALPGRRTVNPQDPSYVDVTYDFIIKRKPLFYTINLIIPCVLTTLLAILVFYLPSDCGEKMTLCISVLLALTFFLLLISKIVPPTSLDVPLIGKYLMFTMVLVTFSIVTSVCVLNVHHRSPSTHTMAPWVKRCFLHKLPTFLFMKRPGPDSSPARAFPPSKSCVTKPEATATSTSPSNFYGNSMYFVNPASAASKSPAGSTPVAIPRDFWLRSSGRFRQDVQEALEGVSFIAQHMKNDDEDQSVVEDWKYVAMVVDRLFLWVFMFVCVLGTVGLFLPPLFQTHAASEGPYAAQRD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-07-11" modified="2026-01-28" version="198" xmlns="https://uniprot.org/uniprot">
    <accession>Q9GZZ6</accession>
    <name>ACH10_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit alpha-10</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Nicotinic acetylcholine receptor subunit alpha-10</fullName>
            <shortName>NACHR alpha-10</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">CHRNA10</name>
        <name type="synonym">NACHRA10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Mol. Pharmacol." volume="61" first="150" last="159">
            <title>A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit.</title>
            <authorList>
                <person name="Sgard F."/>
                <person name="Charpantier E."/>
                <person name="Bertrand S."/>
                <person name="Walker N."/>
                <person name="Caput D."/>
                <person name="Graham D."/>
                <person name="Bertrand D."/>
                <person name="Besnard F."/>
            </authorList>
            <dbReference type="PubMed" id="11752216"/>
            <dbReference type="DOI" id="10.1124/mol.61.1.150"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH CHRNA9</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Genomics" volume="73" first="272" last="283">
            <title>Molecular cloning and mapping of the human nicotinic acetylcholine receptor alpha10 (CHRNA10).</title>
            <authorList>
                <person name="Lustig L.R."/>
                <person name="Peng H."/>
                <person name="Hiel H."/>
                <person name="Yamamoto T."/>
                <person name="Fuchs P.A."/>
            </authorList>
            <dbReference type="PubMed" id="11350119"/>
            <dbReference type="DOI" id="10.1006/geno.2000.6503"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Inner ear</tissue>
            <tissue>Tonsil</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2000-11" db="EMBL/GenBank/DDBJ databases">
            <title>Identification and functional characterisation of a novel human neuronal nicotinic acetylcholine receptor subunit alpha 10.</title>
            <authorList>
                <person name="Vandenberk I."/>
                <person name="van der Helm L."/>
                <person name="Nieuwstraten D.M."/>
                <person name="Verfaille C."/>
                <person name="Kremer A."/>
                <person name="van der Spek P."/>
                <person name="Masure S."/>
                <person name="Hoefnagel E."/>
                <person name="Yon J."/>
                <person name="Groot Kormelink P.J."/>
                <person name="Luyten W.H."/>
                <person name="Grantham C.J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Life Sci." volume="76" first="263" last="280">
            <title>Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.</title>
            <authorList>
                <person name="Peng H."/>
                <person name="Ferris R.L."/>
                <person name="Matthews T."/>
                <person name="Hiel H."/>
                <person name="Lopez-Albaitero A."/>
                <person name="Lustig L.R."/>
            </authorList>
            <dbReference type="PubMed" id="15531379"/>
            <dbReference type="DOI" id="10.1016/j.lfs.2004.05.031"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="Neuropharmacology" volume="56" first="237" last="246">
            <title>Diversity of vertebrate nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Millar N.S."/>
                <person name="Gotti C."/>
            </authorList>
            <dbReference type="PubMed" id="18723036"/>
            <dbReference type="DOI" id="10.1016/j.neuropharm.2008.07.041"/>
        </citation>
        <scope>REVIEW ON NACHRS DIVERSITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Sci. Rep." volume="5" first="14261" last="14268">
            <title>Conotoxin alphaD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Xu S."/>
                <person name="Zhang T."/>
                <person name="Kompella S.N."/>
                <person name="Yan M."/>
                <person name="Lu A."/>
                <person name="Wang Y."/>
                <person name="Shao X."/>
                <person name="Chi C."/>
                <person name="Adams D.J."/>
                <person name="Ding J."/>
                <person name="Wang C."/>
            </authorList>
            <dbReference type="PubMed" id="26395518"/>
            <dbReference type="DOI" id="10.1038/srep14261"/>
        </citation>
        <scope>MUTAGENESIS OF LEU-31</scope>
        <scope>INTERACTION WITH THE CONOTOXIN GEXXA</scope>
    </reference>
    <comment type="function">
        <text evidence="4 7 8 11">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (Probable). Forms heteropentamers with CHRNA9. Expressed in the inner ear, in sympathetic neurons and in other non-neuronal cells, such as skin keratinocytes and lymphocytes (PubMed:11752216, PubMed:15531379). nAChR formed by CHRNA9:CHRNA10 is involved in modulation of auditory stimuli. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, mediates synaptic transmission between efferent olivocochlear fibers and hair cells of the cochlea, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing (PubMed:11752216). This may protect against acoustic trauma. May also regulate keratinocyte adhesion (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>Mg(2+)(in) = Mg(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29827"/>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="7 9">Activated by a myriad of ligands such as acetylcholine (PubMed:11752216). AChR activity is inhibited by the antagonists alpha-conotoxins RgIA and GeXXA, small disulfide-constrained peptides from cone snails (PubMed:26395518).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 7">Forms homo- or heterooligomeric channels in conjunction with CHRNA10. The native outer hair cell receptor may be composed of CHRNA9:CHRNA10 heterooligomers (PubMed:11752216). Found in the stoichiometric form (CHRNA9)2:(CHRNA10)3 (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Synaptic cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 8">Expressed in inner-ear tissue, tonsil, immortalized B-cells, cultured T-cells and peripheral blood lymphocytes.</text>
    </comment>
    <comment type="miscellaneous">
        <text>The heterooligomeric receptor composed of CHRNA9 and CHRNA10 has an atypical pharmacological profile, binding several non-nicotinic ligands including strychnine (a glycine receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist).</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-10/CHRNA10 sub-subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="CAC20435.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAG00795.2"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="development level" value="Tchem"/>
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        <property type="component" value="Chromosome 11"/>
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        <property type="expression patterns" value="Expressed in gastrocnemius and 98 other cell types or tissues"/>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="entry name" value="LGIC_TM_cation"/>
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        <property type="entry name" value="Neur_chan_lig-bd"/>
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        <property type="entry name" value="Neur_channel"/>
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        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NRIONCHANNEL"/>
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        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
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        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0107">Calcium channel</keyword>
    <keyword id="KW-0109">Calcium transport</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="5">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000376" description="Neuronal acetylcholine receptor subunit alpha-10">
        <location>
            <begin position="25"/>
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    <feature type="topological domain" description="Extracellular" evidence="5">
        <location>
            <begin position="25"/>
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            <begin position="238"/>
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    <feature type="transmembrane region" description="Helical" evidence="5">
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            <begin position="268"/>
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    <feature type="transmembrane region" description="Helical" evidence="5">
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            <begin position="302"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="5">
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            <begin position="323"/>
            <end position="428"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="429"/>
            <end position="449"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="355"/>
            <end position="380"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="154"/>
            <end position="168"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Associated with receptor activation" evidence="1">
        <location>
            <begin position="218"/>
            <end position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048172" description="In dbSNP:rs2231547.">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="11-fold increase in inhibition of the AChR composed of subunits CHRNA9 and CHRNA10 by the conotoxin GEXXA, and no change in activity on mAChR composed of subunits CHRNA9 and CHRNA10 by the competitive conotoxin Vc1A." evidence="9">
        <original>L</original>
        <variation>H</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P43144"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9JLB5"/>
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    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q9UGM1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11752216"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15531379"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="26395518"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="18723036"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:13800"/>
        </source>
    </evidence>
    <sequence length="450" mass="49705" checksum="0A1DAD32D9069870" modified="2001-03-01" version="1" precursor="true">MGLRSHHLSLGLLLLFLLPAECLGAEGRLALKLFRDLFANYTSALRPVADTDQTLNVTLEVTLSQIIDMDERNQVLTLYLWIRQEWTDAYLRWDPNAYGGLDAIRIPSSLVWRPDIVLYNKADAQPPGSASTNVVLRHDGAVRWDAPAITRSSCRVDVAAFPFDAQHCGLTFGSWTHGGHQLDVRPRGAAASLADFVENVEWRVLGMPARRRVLTYGCCSEPYPDVTFTLLLRRRAAAYVCNLLLPCVLISLLAPLAFHLPADSGEKVSLGVTVLLALTVFQLLLAESMPPAESVPLIGKYYMATMTMVTFSTALTILIMNLHYCGPSVRPVPAWARALLLGHLARGLCVRERGEPCGQSRPPELSPSPQSPEGGAGPPAGPCHEPRCLCRQEALLHHVATIANTFRSHRAAQRCHEDWKRLARVMDRFFLAIFFSMALVMSLLVLVQAL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-10-01" modified="2026-01-28" version="269" xmlns="https://uniprot.org/uniprot">
    <accession>P12821</accession>
    <accession>B0LPF0</accession>
    <accession>B4DXI3</accession>
    <accession>E7EU16</accession>
    <accession>P22966</accession>
    <accession>Q53YX9</accession>
    <accession>Q59GY8</accession>
    <accession>Q7M4L4</accession>
    <name>ACE_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="75">Angiotensin-converting enzyme</fullName>
            <shortName evidence="75">ACE</shortName>
            <ecNumber evidence="10 13 21 22 53 62">3.4.15.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="76">Dipeptidyl carboxypeptidase I</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="77">Kininase II</fullName>
        </alternativeName>
        <cdAntigenName>CD143</cdAntigenName>
        <component>
            <recommendedName>
                <fullName>Angiotensin-converting enzyme, soluble form</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="75 88" type="primary">ACE</name>
        <name type="synonym">DCP</name>
        <name type="synonym">DCP1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="Proc. Natl. Acad. Sci. U.S.A." volume="85" first="9386" last="9390">
            <title>Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning.</title>
            <authorList>
                <person name="Soubrier F."/>
                <person name="Alhenc-Gelas F."/>
                <person name="Hubert C."/>
                <person name="Allegrini J."/>
                <person name="John M."/>
                <person name="Tregear G."/>
                <person name="Corbol P."/>
            </authorList>
            <dbReference type="PubMed" id="2849100"/>
            <dbReference type="DOI" id="10.1073/pnas.85.24.9386"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC-1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1989" name="FEBS Lett." volume="252" first="99" last="104">
            <title>The testicular transcript of the angiotensin I-converting enzyme encodes for the ancestral, non-duplicated form of the enzyme.</title>
            <authorList>
                <person name="Lattion A.L."/>
                <person name="Soubrier F."/>
                <person name="Allegrini J."/>
                <person name="Hubert C."/>
                <person name="Corvol P."/>
                <person name="Alhenc-Gelas F."/>
            </authorList>
            <dbReference type="PubMed" id="2547653"/>
            <dbReference type="DOI" id="10.1016/0014-5793(89)80897-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>TISSUE SPECIFICITY (ISOFORM TESTIS-SPECIFIC)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1989" name="Proc. Natl. Acad. Sci. U.S.A." volume="86" first="7741" last="7745">
            <title>Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme.</title>
            <authorList>
                <person name="Ehlers M.R.W."/>
                <person name="Fox E.A."/>
                <person name="Strydom D.J."/>
                <person name="Riordan J.F."/>
            </authorList>
            <dbReference type="PubMed" id="2554286"/>
            <dbReference type="DOI" id="10.1073/pnas.86.20.7741"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>TISSUE SPECIFICITY (ISOFORM TESTIS-SPECIFIC)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="22" first="59" last="62">
            <title>Sequence variation in the human angiotensin converting enzyme.</title>
            <authorList>
                <person name="Rieder M.J."/>
                <person name="Taylor S.L."/>
                <person name="Clark A.G."/>
                <person name="Nickerson D.A."/>
            </authorList>
            <dbReference type="PubMed" id="10319862"/>
            <dbReference type="DOI" id="10.1038/8760"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS SER-261; TRP-561 AND SER-1286</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
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            <authorList>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1239 (ISOFORM SOMATIC-1)</scope>
        <source>
            <tissue>Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PROTEIN SEQUENCE OF 30-46</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1114-1306 (ISOFORM SOMATIC-2)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
        <source>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
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        <scope>COFACTOR</scope>
        <scope>ZINC-BINDING</scope>
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        <scope>ALTERNATIVE PROMOTER USAGE</scope>
        <scope>FUNCTION (ISOFORM TESTIS-SPECIFIC)</scope>
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        <scope>FUNCTION (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC)</scope>
    </reference>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME</scope>
        <scope>SOLUBLE FORM)</scope>
        <scope>MUTAGENESIS OF ARG-1166</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394; GLU-1016 AND ASP-1020</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394</scope>
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                <person name="Corvol P."/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME</scope>
        <scope>SOLUBLE FORM)</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>CLEAVAGE SITE</scope>
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            <authorList>
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            <dbReference type="DOI" id="10.1021/bi960243x"/>
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        <scope>DISULFIDE BONDS</scope>
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            <dbReference type="DOI" id="10.1074/jbc.271.11.6429"/>
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        <scope>SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>GLYCOSYLATION AT ASN-103; ASN-121; ASN-140; ASN-368 AND ASN-617 (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>MUTAGENESIS OF ASN-103; ASN-121; ASN-140; ASN-186 AND ASN-617 (ISOFORM TESTIS-SPECIFIC)</scope>
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                <person name="Azizi M."/>
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                <person name="Lenfant M."/>
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        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <title>Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of pro-hormone peptides by human germinal angiotensin I-converting enzyme (ACE) and the C-domain of human somatic ACE.</title>
            <authorList>
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        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
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            <dbReference type="PubMed" id="9013598"/>
            <dbReference type="DOI" id="10.1074/jbc.272.6.3511"/>
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        <scope>GLYCOSYLATION AT ASN-38; ASN-54; ASN-111; ASN-146; ASN-509; ASN-695; ASN-714; ASN-760; ASN-942 AND ASN-1191</scope>
        <scope>LACK OF GLYCOSYLATION AT ASN-1225</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
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                <person name="Isaac R.E."/>
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                <person name="Coates D."/>
                <person name="Wetsel W.C."/>
                <person name="Corvol P."/>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992</scope>
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            <title>Peptidase specificity characterization of C- and N-terminal catalytic sites of angiotensin I-converting enzyme.</title>
            <authorList>
                <person name="Araujo M.C."/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME</scope>
        <scope>SOLUBLE FORM)</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>CLEAVAGE SITE</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
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            <dbReference type="PubMed" id="10969042"/>
            <dbReference type="DOI" id="10.1161/01.res.87.5.e1"/>
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        <scope>TISSUE SPECIFICITY</scope>
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            <title>A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase.</title>
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            <dbReference type="PubMed" id="10924499"/>
            <dbReference type="DOI" id="10.1074/jbc.m002615200"/>
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        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <title>Increased shedding of angiotensin-converting enzyme by a mutation identified in the stalk region.</title>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CHARACTERIZATION OF VARIANT LEU-1228</scope>
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            <title>Arg(1098) is critical for the chloride dependence of human angiotensin I-converting enzyme C-domain catalytic activity.</title>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF ARG-529 AND ARG-1127</scope>
    </reference>
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            <title>A point mutation in the juxtamembrane stalk of human angiotensin I-converting enzyme invokes the action of a distinct secretase.</title>
            <authorList>
                <person name="Alfalah M."/>
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                <person name="Hooper N.M."/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME</scope>
        <scope>SOLUBLE FORM)</scope>
        <scope>PROTEOLYTIC CLEAVAGE</scope>
        <scope>CLEAVAGE SITE</scope>
        <scope>MUTAGENESIS OF ASN-1229</scope>
    </reference>
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            <title>Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity.</title>
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                <person name="Hu J."/>
                <person name="Igarashi A."/>
                <person name="Kamata M."/>
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        <scope>FUNCTION</scope>
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                <person name="Busse R."/>
                <person name="Fleming I."/>
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            <dbReference type="PubMed" id="12386153"/>
            <dbReference type="DOI" id="10.1161/01.res.0000038114.17939.c8"/>
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        <scope>PHOSPHORYLATION AT SER-1299</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF SER-1299</scope>
    </reference>
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            <title>Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme.</title>
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            </authorList>
            <dbReference type="PubMed" id="12459472"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(02)03640-2"/>
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        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <title>Deglycosylation, processing and crystallization of human testis angiotensin-converting enzyme.</title>
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                <person name="Schwager S.L.U."/>
                <person name="Ehlers M.R.W."/>
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                <person name="Natesh R."/>
                <person name="Acharya K.R."/>
                <person name="Sturrock E.D."/>
            </authorList>
            <dbReference type="PubMed" id="12542396"/>
            <dbReference type="DOI" id="10.1042/bj20021842"/>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CLEAVAGE SITE</scope>
    </reference>
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            <title>ACE2 gene expression is up-regulated in the human failing heart.</title>
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                <person name="Goddard M.J."/>
                <person name="Allen J.C."/>
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            </authorList>
            <dbReference type="PubMed" id="15151696"/>
            <dbReference type="DOI" id="10.1186/1741-7015-2-19"/>
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        <scope>INDUCTION</scope>
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            <title>Myocardial infarction increases ACE2 expression in rat and humans.</title>
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            <dbReference type="DOI" id="10.1093/eurheartj/ehi114"/>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
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            <title>Molecular basis of exopeptidase activity in the C-terminal domain of human angiotensin I-converting enzyme: insights into the origins of its exopeptidase activity.</title>
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        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF LYS-1116 AND TYR-1125</scope>
    </reference>
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            <title>Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor.</title>
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        <scope>FUNCTION</scope>
        <scope>ACTIVE SITES</scope>
        <scope>MUTAGENESIS OF GLU-391 AND GLU-989</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-509; ASN-695 AND ASN-714</scope>
        <source>
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            <title>Angiotensin-converting enzyme (ACE) dimerization is the initial step in the ACE inhibitor-induced ACE signaling cascade in endothelial cells.</title>
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            <dbReference type="DOI" id="10.1124/mol.105.020636"/>
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        <scope>SUBUNIT</scope>
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        <scope>FUNCTION</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVE SITES</scope>
        <scope>MUTAGENESIS OF GLU-391 AND GLU-989</scope>
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-111; ASN-445 AND ASN-714</scope>
        <source>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION AT SER-1299</scope>
        <scope>MUTAGENESIS OF SER-1299</scope>
    </reference>
    <reference evidence="89 90" key="58">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="551" last="554">
            <title>Crystal structure of the human angiotensin-converting enzyme-lisinopril complex.</title>
            <authorList>
                <person name="Natesh R."/>
                <person name="Schwager S.L.U."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="12540854"/>
            <dbReference type="DOI" id="10.1038/nature01370"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230</scope>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH CHLORIDE AND LISINOPRIL</scope>
        <scope>ACTIVE SITE</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="59">
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            <title>Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme.</title>
            <authorList>
                <person name="Natesh R."/>
                <person name="Schwager S.L.U."/>
                <person name="Evans H.R."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="15236580"/>
            <dbReference type="DOI" id="10.1021/bi049480n"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ENALAPRILAT</scope>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH CAPTOPRIL</scope>
    </reference>
    <reference key="60">
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            <title>Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design.</title>
            <authorList>
                <person name="Corradi H.R."/>
                <person name="Schwager S.L.U."/>
                <person name="Nchinda A.T."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="16476442"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2006.01.048"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 30-641 IN COMPLEX WITH LISINOPRIL; ZINC AND CHLORIDE IONS</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>GLYCOSYLATION AT ASN-54; ASN-74; ASN-146; ASN-318 AND ASN-509</scope>
    </reference>
    <reference evidence="91 93" key="61">
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            <title>The N domain of human angiotensin-I-converting enzyme: the role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407.</title>
            <authorList>
                <person name="Anthony C.S."/>
                <person name="Corradi H.R."/>
                <person name="Schwager S.L."/>
                <person name="Redelinghuys P."/>
                <person name="Georgiadis D."/>
                <person name="Dive V."/>
                <person name="Acharya K.R."/>
                <person name="Sturrock E.D."/>
            </authorList>
            <dbReference type="PubMed" id="20826823"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.167866"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 30-658 IN COMPLEX WITH ZINC</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>GLYCOSYLATION AT ASN-38; ASN-54; ASN-74; ASN-111 ASN-146; ASN-160; ASN-445 AND ASN-509</scope>
        <scope>LACK OF GLYCOSYLATION AT ASN-523</scope>
        <scope>MUTAGENESIS OF ASN-318; ASN-445 AND ASN-509</scope>
    </reference>
    <reference evidence="92" key="62">
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            <title>Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril.</title>
            <authorList>
                <person name="Akif M."/>
                <person name="Masuyer G."/>
                <person name="Schwager S.L."/>
                <person name="Bhuyan B.J."/>
                <person name="Mugesh G."/>
                <person name="Isaac R.E."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="21810173"/>
            <dbReference type="DOI" id="10.1111/j.1742-4658.2011.08276.x"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>COFACTOR</scope>
        <scope>GLYCOSYLATION AT ASN-103 AND ASN-140 (ISOFORM TESTIS-SPECIFIC)</scope>
    </reference>
    <reference evidence="94 95" key="63">
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            <title>Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides.</title>
            <authorList>
                <person name="Masuyer G."/>
                <person name="Schwager S.L."/>
                <person name="Sturrock E.D."/>
                <person name="Isaac R.E."/>
                <person name="Acharya K.R."/>
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            <dbReference type="PubMed" id="23056909"/>
            <dbReference type="DOI" id="10.1038/srep00717"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>GLYCOSYLATION AT ASN-677 AND ASN-714</scope>
    </reference>
    <reference evidence="96 97 98 99 100" key="64">
        <citation type="journal article" date="2014" name="J. Biol. Chem." volume="289" first="1798" last="1814">
            <title>Molecular and thermodynamic mechanisms of the chloride-dependent human angiotensin-I-converting enzyme (ACE).</title>
            <authorList>
                <person name="Yates C.J."/>
                <person name="Masuyer G."/>
                <person name="Schwager S.L."/>
                <person name="Akif M."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="24297181"/>
            <dbReference type="DOI" id="10.1074/jbc.m113.512335"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 69-732 IN COMPLEX WITH ZINC (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>GLYCOSYLATION AT ASN-103 AND ASN-140 (ISOFORM TESTIS-SPECIFIC)</scope>
        <scope>MUTAGENESIS OF ARG-553 (ISOFORM TESTIS-SPECIFIC)</scope>
    </reference>
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            <authorList>
                <person name="Masuyer G."/>
                <person name="Douglas R.G."/>
                <person name="Sturrock E.D."/>
                <person name="Acharya K.R."/>
            </authorList>
            <dbReference type="PubMed" id="26403559"/>
            <dbReference type="DOI" id="10.1038/srep13742"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-657 IN COMPLEX WITH ZINC</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>GLYCOSYLATION AT ASN-74; ASN-445 AND ASN-509</scope>
    </reference>
    <reference key="66">
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            <title>The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM.</title>
            <authorList>
                <person name="Vleming L.J."/>
                <person name="van der Pijl J.W."/>
                <person name="Lemkes H.H.P.J."/>
                <person name="Westendorp R.G.J."/>
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                <person name="Daha M.R."/>
                <person name="van Es L.A."/>
                <person name="van Kooten C."/>
            </authorList>
            <dbReference type="PubMed" id="10099885"/>
        </citation>
        <scope>INVOLVEMENT IN MVCD3</scope>
    </reference>
    <reference key="67">
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            <title>Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.</title>
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            <dbReference type="PubMed" id="10391210"/>
            <dbReference type="DOI" id="10.1038/10297"/>
        </citation>
        <scope>VARIANTS THR-1018; VAL-1051; GLN-1279; SER-1286 AND PRO-1296</scope>
    </reference>
    <reference key="68">
        <citation type="journal article" date="2001" name="Circulation" volume="104" first="1236" last="1240">
            <title>Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease.</title>
            <authorList>
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                <person name="van Duijn C."/>
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                <person name="Soubrier F."/>
                <person name="Adema G.J."/>
            </authorList>
            <dbReference type="PubMed" id="11551873"/>
            <dbReference type="DOI" id="10.1161/hc3601.095932"/>
        </citation>
        <scope>VARIANT LEU-1228</scope>
        <scope>ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME</scope>
    </reference>
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        <citation type="journal article" date="2003" name="Neurology" volume="61" first="1819" last="1820">
            <title>Hereditary elevation of angiotensin converting enzyme suggesting neurosarcoidosis.</title>
            <authorList>
                <person name="Linnebank M."/>
                <person name="Kesper K."/>
                <person name="Jeub M."/>
                <person name="Urbach H."/>
                <person name="Wuellner U."/>
                <person name="Klockgether T."/>
                <person name="Schmidt S."/>
            </authorList>
            <dbReference type="PubMed" id="14694062"/>
            <dbReference type="DOI" id="10.1212/01.wnl.0000098990.12845.da"/>
        </citation>
        <scope>VARIANT LEU-1228</scope>
        <scope>ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME</scope>
    </reference>
    <reference key="70">
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            <title>Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls.</title>
            <authorList>
                <person name="Casas J.P."/>
                <person name="Hingorani A.D."/>
                <person name="Bautista L.E."/>
                <person name="Sharma P."/>
            </authorList>
            <dbReference type="PubMed" id="15534175"/>
            <dbReference type="DOI" id="10.1001/archneur.61.11.1652"/>
        </citation>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR</scope>
    </reference>
    <reference key="71">
        <citation type="journal article" date="2004" name="Neurology" volume="63" first="359" last="361">
            <title>DD genotype of ACE gene is a risk factor for intracerebral hemorrhage.</title>
            <authorList>
                <person name="Slowik A."/>
                <person name="Turaj W."/>
                <person name="Dziedzic T."/>
                <person name="Haefele A."/>
                <person name="Pera J."/>
                <person name="Malecki M.T."/>
                <person name="Glodzik-Sobanska L."/>
                <person name="Szermer P."/>
                <person name="Figlewicz D.A."/>
                <person name="Szczudlik A."/>
            </authorList>
            <dbReference type="PubMed" id="15277638"/>
            <dbReference type="DOI" id="10.1212/01.wnl.0000130200.12993.0c"/>
        </citation>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO ICH</scope>
    </reference>
    <reference key="72">
        <citation type="journal article" date="2005" name="Nat. Genet." volume="37" first="964" last="968">
            <title>Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.</title>
            <authorList>
                <person name="Gribouval O."/>
                <person name="Gonzales M."/>
                <person name="Neuhaus T."/>
                <person name="Aziza J."/>
                <person name="Bieth E."/>
                <person name="Laurent N."/>
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                <person name="Feuillet F."/>
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                <person name="Joubert M."/>
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            </authorList>
            <dbReference type="PubMed" id="16116425"/>
            <dbReference type="DOI" id="10.1038/ng1623"/>
        </citation>
        <scope>INVOLVEMENT IN RTD</scope>
        <scope>VARIANT ARG-354</scope>
    </reference>
    <reference key="73">
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            <title>Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.</title>
            <authorList>
                <person name="Cromer M.K."/>
                <person name="Choi M."/>
                <person name="Nelson-Williams C."/>
                <person name="Fonseca A.L."/>
                <person name="Kunstman J.W."/>
                <person name="Korah R.M."/>
                <person name="Overton J.D."/>
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                <person name="Malchoff C.D."/>
                <person name="Stalberg P."/>
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                <person name="Westin G."/>
                <person name="Hellman P."/>
                <person name="Carling T."/>
                <person name="Bjoerklund P."/>
                <person name="Lifton R.P."/>
            </authorList>
            <dbReference type="PubMed" id="25787250"/>
            <dbReference type="DOI" id="10.1073/pnas.1503696112"/>
        </citation>
        <scope>VARIANT ASN-295</scope>
    </reference>
    <comment type="function">
        <text evidence="1 7 10 15 17 22 27 30 37 38 40 41 44 48 50 51 52 53 54 55 56 57 59 60 61 64 65 69">Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, PubMed:7523412, PubMed:7683654). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:10913258, PubMed:1320019, PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:11432860, PubMed:1851160, PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (PubMed:15615692, PubMed:2558109, PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, PubMed:656131). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:10336644, PubMed:19773553, PubMed:7876104).</text>
    </comment>
    <comment type="function">
        <molecule>Angiotensin-converting enzyme, soluble form</molecule>
        <text evidence="9 14 58 63">Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform Testis-specific</molecule>
        <text evidence="1 35 36 45">Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility (PubMed:1651327, PubMed:1668266). In contrast to somatic isoforms, only contains one catalytic domain (PubMed:1651327, PubMed:1668266). Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates (PubMed:1668266, PubMed:24297181). The identity of substrates that are needed for male fertility is unknown (By similarity). May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. The GPIase activity was reported to be essential for the egg-binding ability of the sperm (By similarity). This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 13 21 22 41 48 53 62">
            <text>Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.</text>
            <dbReference type="EC" id="3.4.15.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15 38 40 44 53 56">
            <text>angiotensin I + H2O = L-histidyl-L-leucine + angiotensin II</text>
            <dbReference type="Rhea" id="RHEA:63560"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:58506"/>
            <dbReference type="ChEBI" id="CHEBI:147350"/>
            <dbReference type="ChEBI" id="CHEBI:147392"/>
            <dbReference type="EC" id="3.4.15.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15 38 40 44 53 56">
            <dbReference type="Rhea" id="RHEA:63561"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="53 54 56 60 85">
            <text>bradykinin + H2O = L-Phe-L-Arg + bradykinin(1-7)</text>
            <dbReference type="Rhea" id="RHEA:71451"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:132988"/>
            <dbReference type="ChEBI" id="CHEBI:133147"/>
            <dbReference type="ChEBI" id="CHEBI:147352"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="53 54 56 60 85">
            <dbReference type="Rhea" id="RHEA:71452"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="55">
            <text>substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2</text>
            <dbReference type="Rhea" id="RHEA:71459"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:190692"/>
            <dbReference type="ChEBI" id="CHEBI:190693"/>
            <dbReference type="ChEBI" id="CHEBI:190700"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="55">
            <dbReference type="Rhea" id="RHEA:71460"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="55">
            <text>substance P + H2O = substance P(1-8) + Gly-L-Leu-L-Met-NH2</text>
            <dbReference type="Rhea" id="RHEA:71463"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:190692"/>
            <dbReference type="ChEBI" id="CHEBI:190694"/>
            <dbReference type="ChEBI" id="CHEBI:190699"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="55">
            <dbReference type="Rhea" id="RHEA:71464"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="55">
            <text>substance P + H2O = L-Phe-L-Phe-Gly-L-Leu-L-Met-NH2 + substance P(1-6)</text>
            <dbReference type="Rhea" id="RHEA:71471"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:190692"/>
            <dbReference type="ChEBI" id="CHEBI:190696"/>
            <dbReference type="ChEBI" id="CHEBI:190697"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="55">
            <dbReference type="Rhea" id="RHEA:71472"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="55">
            <text>neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucine</text>
            <dbReference type="Rhea" id="RHEA:71475"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:147362"/>
            <dbReference type="ChEBI" id="CHEBI:190704"/>
            <dbReference type="ChEBI" id="CHEBI:190706"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="55">
            <dbReference type="Rhea" id="RHEA:71476"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="50 61 64">
            <text>goralatide + H2O = N-acetyl-L-seryl-L-aspartate + L-lysyl-L-proline</text>
            <dbReference type="Rhea" id="RHEA:71455"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:190701"/>
            <dbReference type="ChEBI" id="CHEBI:190702"/>
            <dbReference type="ChEBI" id="CHEBI:190703"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="50 61 64">
            <dbReference type="Rhea" id="RHEA:71456"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="56 57">
            <text>Met-enkephalin + H2O = L-phenylalanyl-L-methionine + L-tyrosylglycylglycine</text>
            <dbReference type="Rhea" id="RHEA:71483"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:189868"/>
            <dbReference type="ChEBI" id="CHEBI:190708"/>
            <dbReference type="ChEBI" id="CHEBI:190709"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="56 57">
            <dbReference type="Rhea" id="RHEA:71484"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="56 57">
            <text>Leu-enkephalin + H2O = L-tyrosylglycylglycine + L-phenylalanyl-L-leucine</text>
            <dbReference type="Rhea" id="RHEA:71487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:190689"/>
            <dbReference type="ChEBI" id="CHEBI:190708"/>
            <dbReference type="ChEBI" id="CHEBI:190710"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="56 57">
            <dbReference type="Rhea" id="RHEA:71488"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Met-enkephalin-Arg-Phe + H2O = L-arginyl-L-phenylalanine + Met-enkephalin</text>
            <dbReference type="Rhea" id="RHEA:70675"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:189868"/>
            <dbReference type="ChEBI" id="CHEBI:189869"/>
            <dbReference type="ChEBI" id="CHEBI:189870"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:70676"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Testis-specific</molecule>
        <reaction evidence="36">
            <text>Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.</text>
            <dbReference type="EC" id="3.4.15.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="20 32 34 41 44 50 62">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="20 32 34">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="cofactor">
        <molecule>Isoform Testis-specific</molecule>
        <cofactor evidence="34 42 45">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="34 42 45">Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="15 20 32">
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </cofactor>
        <text evidence="20 32">Binds 3 chloride ions per subunit.</text>
    </comment>
    <comment type="cofactor">
        <molecule>Isoform Testis-specific</molecule>
        <cofactor evidence="45">
            <name>chloride</name>
            <dbReference type="ChEBI" id="CHEBI:17996"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="15 20 22 27 32 55 56 60 61 65">The dipeptidyl carboxypeptidase activity is strongly activated by chloride (PubMed:11432860, PubMed:12540854, PubMed:15615692, PubMed:16476442, PubMed:7683654). The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat (PubMed:12540854, PubMed:1320019, PubMed:16476442, PubMed:6208535, PubMed:6270633, PubMed:7876104, PubMed:8609242).</text>
    </comment>
    <comment type="activity regulation">
        <molecule>Isoform Testis-specific</molecule>
        <text evidence="36 42">Strongly inhibited by lisinopril and captopril.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="13 21">2.51 mM for Hip-His-Leu</KM>
            <KM evidence="86">30 uM for angiotensin I</KM>
            <KM evidence="38">16 uM for angiotensin I</KM>
            <KM evidence="86">1 uM for bradykinin</KM>
            <KM evidence="60">0.18 uM for bradykinin</KM>
            <KM evidence="56">1000 uM for Met-enkephalin</KM>
            <KM evidence="56">1000 uM for Leu-enkephalin</KM>
            <KM evidence="61">41 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP)</KM>
            <KM evidence="61">31 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the active site at the N-terminus</KM>
            <KM evidence="61">39 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the active site at the C-terminus</KM>
            <KM evidence="69">9 uM for GWMDFGRR peptide (Cholecystokinin-5-GRR)</KM>
            <text evidence="56 61">kcat is 500 min(-1) for angiotensin I (PubMed:6270633). kcat is 500 min(-1) for bradykinin (PubMed:6270633). kcat is 3500 min(-1) for Met-enkephalin (PubMed:6270633). kcat is 700 min(-1) for Leu-enkephalin (PubMed:6270633). kcat is 12 sec(-1) for the hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:7876104).</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="2 33">Monomer and homodimer; homodimerizes following binding to an inhibitor (PubMed:16476786). Interacts with calmodulin (CALM1, CALM2 or CALM3); interaction takes place in the cytoplasmic region and regulates phosphorylation and proteolytic cleavage (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25497695">
            <id>P12821-3</id>
        </interactant>
        <interactant intactId="EBI-703066">
            <id>P05556</id>
            <label>ITGB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="18">Cell membrane</location>
            <topology evidence="3">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">Detected in both cell membrane and cytoplasm in neurons.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Angiotensin-converting enzyme, soluble form</molecule>
        <subcellularLocation>
            <location evidence="9 14 58 63">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform Testis-specific</molecule>
        <subcellularLocation>
            <location evidence="36 66">Cell membrane</location>
            <topology evidence="3">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="36">Secreted</location>
        </subcellularLocation>
        <text evidence="36">The testis-specific isoform can be cleaved before the transmembrane region, releasing a soluble form.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative promoter"/>
        <event type="alternative splicing"/>
        <isoform>
            <id>P12821-1</id>
            <name>Somatic-1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P12821-2</id>
            <name>Somatic-2</name>
            <name>Soluble</name>
            <sequence type="described" ref="VSP_029932 VSP_029933"/>
        </isoform>
        <isoform>
            <id>P12821-3</id>
            <id>P22966-1</id>
            <name>Testis-specific</name>
            <name>ACE-T</name>
            <name evidence="78">ACEt</name>
            <name evidence="71 72">tACE</name>
            <name evidence="71">hTACE</name>
            <sequence type="described" ref="VSP_035120 VSP_035121"/>
        </isoform>
        <isoform>
            <id>P12821-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_054836 VSP_054837"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="11 12 19 28">Ubiquitously expressed, with highest levels in lung, kidney, heart, gastrointestinal system and prostate.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform Testis-specific</molecule>
        <text evidence="46 47">Specifically expressed in spermatocytes and adult testis.</text>
    </comment>
    <comment type="induction">
        <text evidence="24 28">Up-regulated in failing heart.</text>
    </comment>
    <comment type="PTM">
        <molecule>Angiotensin-converting enzyme, soluble form</molecule>
        <text evidence="9 14 58 63">Produced following proteolytic cleavage by secretase enzymes that cleave the transmembrane form in the juxtamembrane stalk region upstream of the transmembrane region (PubMed:10769174, PubMed:11274151, PubMed:7499427, PubMed:8253769). Cleavage can take place at different sites of the juxtamembrane stalk region (PubMed:10769174, PubMed:11274151, PubMed:7499427, PubMed:8253769).</text>
    </comment>
    <comment type="PTM">
        <text evidence="2 18">Phosphorylated by CK2 on Ser-1299; which allows membrane retention (PubMed:12386153). Phosphorylated on tyrosine residues on its extracellular part, promoting cleavage by secretase enzymes and formation of the soluble form (Angiotensin-converting enzyme, soluble form) (By similarity).</text>
    </comment>
    <comment type="disease" evidence="26">
        <disease id="DI-01835">
            <name>Ischemic stroke</name>
            <acronym>ISCHSTR</acronym>
            <description>A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.</description>
            <dbReference type="MIM" id="601367"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="29">
        <disease id="DI-02257">
            <name>Renal tubular dysgenesis</name>
            <acronym>RTD</acronym>
            <description>Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).</description>
            <dbReference type="MIM" id="267430"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-02756">
            <name>Microvascular complications of diabetes 3</name>
            <acronym>MVCD3</acronym>
            <description>Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.</description>
            <dbReference type="MIM" id="612624"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="25">
        <disease id="DI-03406">
            <name>Intracerebral hemorrhage</name>
            <acronym>ICH</acronym>
            <description>A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.</description>
            <dbReference type="MIM" id="614519"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform Somatic-2</molecule>
        <text evidence="80">Incomplete sequence.</text>
    </comment>
    <comment type="similarity">
        <text evidence="80">Belongs to the peptidase M2 family.</text>
    </comment>
    <comment type="sequence caution" evidence="80">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD92208" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="3.4.15.1" evidence="10 13 21 22 53 62"/>
    <dbReference type="EMBL" id="J04144">
        <property type="protein sequence ID" value="AAA51684.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M26657">
        <property type="protein sequence ID" value="AAA60611.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X16295">
        <property type="protein sequence ID" value="CAA34362.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF118569">
        <property type="protein sequence ID" value="AAD28560.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY436326">
        <property type="protein sequence ID" value="AAR03504.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301988">
        <property type="protein sequence ID" value="BAG63395.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EU332840">
        <property type="protein sequence ID" value="ABY87529.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB208971">
        <property type="protein sequence ID" value="BAD92208.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC113554">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11637.1">
        <molecule id="P12821-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45755.1">
        <molecule id="P12821-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54155.1">
        <molecule id="P12821-4"/>
    </dbReference>
    <dbReference type="PIR" id="A31759">
        <property type="entry name" value="A31759"/>
    </dbReference>
    <dbReference type="PIR" id="PW0053">
        <property type="entry name" value="PW0053"/>
    </dbReference>
    <dbReference type="PIR" id="S05238">
        <property type="entry name" value="S05238"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000780.1">
        <molecule id="P12821-1"/>
        <property type="nucleotide sequence ID" value="NM_000789.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001171528.1">
        <molecule id="P12821-4"/>
        <property type="nucleotide sequence ID" value="NM_001178057.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_690043.1">
        <molecule id="P12821-3"/>
        <property type="nucleotide sequence ID" value="NM_152830.3"/>
    </dbReference>
    <dbReference type="PDB" id="1O86">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="1O8A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="1UZE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.82 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="1UZF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="2C6F">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.01 A"/>
        <property type="chains" value="A/B=30-641"/>
    </dbReference>
    <dbReference type="PDB" id="2C6N">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=30-641"/>
    </dbReference>
    <dbReference type="PDB" id="2IUL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.01 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="2IUX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="2OC2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="2XY9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.97 A"/>
        <property type="chains" value="A=645-1228"/>
    </dbReference>
    <dbReference type="PDB" id="2XYD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="A/B=30-639"/>
    </dbReference>
    <dbReference type="PDB" id="2YDM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.44 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="3BKK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.17 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="3BKL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.18 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="3L3N">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A=642-1232"/>
    </dbReference>
    <dbReference type="PDB" id="3NXQ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.99 A"/>
        <property type="chains" value="A/B=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="4APH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.99 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4APJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4BXK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="4BZR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.84 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4BZS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="4C2N">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.59 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4C2O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4C2P">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.99 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4C2Q">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4C2R">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4CA5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A=642-1230"/>
    </dbReference>
    <dbReference type="PDB" id="4CA6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.91 A"/>
        <property type="chains" value="A/B=30-639"/>
    </dbReference>
    <dbReference type="PDB" id="4UFA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="4UFB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="5AM8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="5AM9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="5AMA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="5AMB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.55 A"/>
        <property type="chains" value="A/B=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="5AMC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.65 A"/>
        <property type="chains" value="A/B=30-658"/>
    </dbReference>
    <dbReference type="PDB" id="6EN5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.75 A"/>
        <property type="chains" value="A/B/C/D=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="6EN6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=30-657"/>
    </dbReference>
    <dbReference type="PDB" id="6F9R">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A/B=30-657"/>
    </dbReference>
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            <position position="1299"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="41 87">
        <location>
            <position position="38"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="32 41 68">
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="32 41 50 93">
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="39 41 68">
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="32 41 68">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="41">
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="32">
        <location>
            <position position="318"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="39 41 50 93">
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="31 32 41 50 68 93">
        <location>
            <position position="509"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="44 94">
        <location>
            <position position="677"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="31 68">
        <location>
            <position position="695"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="31 39 44 68 94">
        <location>
            <position position="714"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; partial" evidence="68">
        <location>
            <position position="760"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; partial" evidence="68">
        <location>
            <position position="942"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine; partial" evidence="68">
        <location>
            <position position="1191"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4 67">
        <location>
            <begin position="157"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4">
        <location>
            <begin position="359"/>
            <end position="377"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4">
        <location>
            <begin position="545"/>
            <end position="557"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4 67">
        <location>
            <begin position="757"/>
            <end position="763"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4 67">
        <location>
            <begin position="957"/>
            <end position="975"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4 67">
        <location>
            <begin position="1143"/>
            <end position="1155"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054836" description="In isoform 4." evidence="70">
        <original> </original>
        <variation>MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHGTSSQATTSSQTTTHQATAHQTSAQSPN</variation>
        <location>
            <begin position="1"/>
            <end position="641"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035120" description="In isoform Testis-specific." evidence="73 74">
        <location>
            <begin position="1"/>
            <end position="574"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035121" description="In isoform Testis-specific." evidence="73 74">
        <original>AGSSRPWQEVLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGID</original>
        <variation>MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHGTSSQATTSSQTTTHQATAHQTSAQSPN</variation>
        <location>
            <begin position="575"/>
            <end position="641"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054837" description="In isoform 4." evidence="70">
        <location>
            <begin position="1128"/>
            <end position="1168"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029932" description="In isoform Somatic-2." evidence="79">
        <original>QFHEALCQA</original>
        <variation>HPFSQHTAA</variation>
        <location>
            <begin position="1137"/>
            <end position="1145"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029933" description="In isoform Somatic-2." evidence="79">
        <location>
            <begin position="1146"/>
            <end position="1306"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029139" description="In dbSNP:rs13306087.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029140" description="In dbSNP:rs12720754.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023430" description="In dbSNP:rs3730025.">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054000" description="In dbSNP:rs147670020.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054001" description="In dbSNP:rs4303.">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011707" description="In dbSNP:rs4303." evidence="6">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="261"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_074173" description="In dbSNP:rs989500910." evidence="49">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="295"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023431" description="In dbSNP:rs2229839.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="351"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035434" description="In dbSNP:rs56394458." evidence="29">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="354"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029141" description="In dbSNP:rs13306085.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029142" description="In dbSNP:rs12720746.">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="524"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011708" description="In dbSNP:rs4314." evidence="6">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="561"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020053" description="In dbSNP:rs12709426.">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="592"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_034602" description="In dbSNP:rs13306091.">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="828"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023432" description="In dbSNP:rs3730043.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="916"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014189" description="In dbSNP:rs4976." evidence="8">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="1018"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014190" description="In dbSNP:rs4977." evidence="8">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="1051"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023433" description="In dbSNP:rs12709442.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="1187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023434" description="No effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type; dbSNP:rs121912703." evidence="13 16 23">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="1228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014191" description="In dbSNP:rs4980." evidence="8">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1279"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011709" description="In dbSNP:rs4364." evidence="6 8">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="1286"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014192" description="In dbSNP:rs4981." evidence="8">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="1296"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In Ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with D-445 and D-509. In Ndom1234569 mutant; does not affect dipeptidyl carboxypeptidase activity; when associated with D-445." evidence="41">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="318"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished dipeptidyl carboxypeptidase activity; when associated with 988-K--K-992. Abolished N-terminal active sites, leading to impaired ability to degrade the hemoregulatory peptide N-acetyl-SDKP (AcSDKP). In contrast, does not affect cleavage of other substrates, such as Cholecystokinin-5." evidence="7 22 38 60 61 62">
        <original>HEMGH</original>
        <variation>KEMGK</variation>
        <location>
            <begin position="390"/>
            <end position="394"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished peptidase activity, leading to increased levels of amyloid-beta; when associated with D-989." evidence="30 40">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="391"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In Ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with D-318 and D-445. In Ndom1234569 mutant; does not affect dipeptidyl carboxypeptidase activity; when associated with D-318." evidence="41">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="In Ndom123456 mutant; abolished dipeptidyl carboxypeptidase activity; when associated with D-318 and D-445." evidence="41">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="509"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished dependence to chloride, leading to reduced peptidyl dipeptidase activity." evidence="15">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished dipeptidyl carboxypeptidase activity; when associated with 390-K--K-394. Abolishes the second active site, preventing maturation of Cholecystokinin-5." evidence="7 22 38 60">
        <original>HEMGH</original>
        <variation>KEMGK</variation>
        <location>
            <begin position="988"/>
            <end position="992"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished peptidase activity, leading to increased levels of amyloid-beta; when associated with D-391." evidence="30 40">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="989"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strongly decreased dipeptidyl carboxypeptidase activity; when associated with 390-K--K-394." evidence="62">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="1016"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished dipeptidyl carboxypeptidase activity; when associated with 390-K--K-394." evidence="62">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="1016"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased dipeptidyl carboxypeptidase activity; when associated with 390-K--K-394." evidence="62">
        <original>D</original>
        <variation>E</variation>
        <variation>A</variation>
        <location>
            <position position="1020"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased ability to cleave substance P and bradykinin. Reduced binding to captopril inhibitor." evidence="27">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="1116"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased ability to cleave substance P and captopril inhibitor." evidence="27">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="1125"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished dependence to chloride, leading to reduced peptidyl dipeptidase activity." evidence="15">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1127"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not prevent cleavage and secretion of the soluble form, suggesting that processing can take place at different sites." evidence="63">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="1166"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased cleavage and secretion of the soluble form by generating a new cleavage site." evidence="14">
        <original>N</original>
        <variation>Q</variation>
        <location>
            <position position="1229"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes phosphorylation and decreases membrane retention." evidence="18 43">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="1299"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AA sequence." evidence="80" ref="9">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="35"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AA sequence." evidence="80" ref="9">
        <original>D</original>
        <variation>R</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="32"/>
            <end position="34"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="43"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="77"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="turn" evidence="108">
        <location>
            <begin position="106"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="109"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="115"/>
            <end position="124"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="128"/>
            <end position="131"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="134"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="155"/>
            <end position="157"/>
        </location>
    </feature>
    <feature type="strand" evidence="106">
        <location>
            <begin position="159"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="165"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="turn" evidence="108">
        <location>
            <begin position="168"/>
            <end position="170"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="171"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="182"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="turn" evidence="108">
        <location>
            <begin position="217"/>
            <end position="219"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="223"/>
            <end position="229"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="236"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="turn" evidence="108">
        <location>
            <begin position="268"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="281"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="291"/>
            <end position="293"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="294"/>
            <end position="297"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="309"/>
            <end position="314"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="319"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="340"/>
            <end position="345"/>
        </location>
    </feature>
    <feature type="strand" evidence="113">
        <location>
            <begin position="352"/>
            <end position="354"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="362"/>
            <end position="365"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="367"/>
            <end position="370"/>
        </location>
    </feature>
    <feature type="strand" evidence="108">
        <location>
            <begin position="372"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="382"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="406"/>
            <end position="408"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="414"/>
            <end position="428"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="431"/>
            <end position="436"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="447"/>
            <end position="461"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="464"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="strand" evidence="113">
        <location>
            <begin position="481"/>
            <end position="483"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="485"/>
            <end position="487"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="488"/>
            <end position="500"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="514"/>
            <end position="517"/>
        </location>
    </feature>
    <feature type="turn" evidence="108">
        <location>
            <begin position="519"/>
            <end position="524"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="528"/>
            <end position="547"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="554"/>
            <end position="556"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="563"/>
            <end position="575"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="581"/>
            <end position="589"/>
        </location>
    </feature>
    <feature type="helix" evidence="108">
        <location>
            <begin position="597"/>
            <end position="617"/>
        </location>
    </feature>
    <feature type="turn" evidence="111">
        <location>
            <begin position="634"/>
            <end position="637"/>
        </location>
    </feature>
    <feature type="helix" evidence="111">
        <location>
            <begin position="638"/>
            <end position="640"/>
        </location>
    </feature>
    <feature type="helix" evidence="107">
        <location>
            <begin position="641"/>
            <end position="643"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="646"/>
            <end position="675"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="680"/>
            <end position="704"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="709"/>
            <end position="711"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="715"/>
            <end position="724"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="728"/>
            <end position="731"/>
        </location>
    </feature>
    <feature type="helix" evidence="110">
        <location>
            <begin position="734"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="strand" evidence="110">
        <location>
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                <person name="Gaborieau V."/>
                <person name="Boffetta P."/>
                <person name="Hashibe M."/>
                <person name="Zaridze D."/>
                <person name="Mukeria A."/>
                <person name="Szeszenia-Dabrowska N."/>
                <person name="Lissowska J."/>
                <person name="Rudnai P."/>
                <person name="Fabianova E."/>
                <person name="Mates D."/>
                <person name="Bencko V."/>
                <person name="Foretova L."/>
                <person name="Janout V."/>
                <person name="Chen C."/>
                <person name="Goodman G."/>
                <person name="Field J.K."/>
                <person name="Liloglou T."/>
                <person name="Xinarianos G."/>
                <person name="Cassidy A."/>
                <person name="McLaughlin J."/>
                <person name="Liu G."/>
                <person name="Narod S."/>
                <person name="Krokan H.E."/>
                <person name="Skorpen F."/>
                <person name="Elvestad M.B."/>
                <person name="Hveem K."/>
                <person name="Vatten L."/>
                <person name="Linseisen J."/>
                <person name="Clavel-Chapelon F."/>
                <person name="Vineis P."/>
                <person name="Bueno-de-Mesquita H.B."/>
                <person name="Lund E."/>
                <person name="Martinez C."/>
                <person name="Bingham S."/>
                <person name="Rasmuson T."/>
                <person name="Hainaut P."/>
                <person name="Riboli E."/>
                <person name="Ahrens W."/>
                <person name="Benhamou S."/>
                <person name="Lagiou P."/>
                <person name="Trichopoulos D."/>
                <person name="Holcatova I."/>
                <person name="Merletti F."/>
                <person name="Kjaerheim K."/>
                <person name="Agudo A."/>
                <person name="Macfarlane G."/>
                <person name="Talamini R."/>
                <person name="Simonato L."/>
                <person name="Lowry R."/>
                <person name="Conway D.I."/>
                <person name="Znaor A."/>
                <person name="Healy C."/>
                <person name="Zelenika D."/>
                <person name="Boland A."/>
                <person name="Delepine M."/>
                <person name="Foglio M."/>
                <person name="Lechner D."/>
                <person name="Matsuda F."/>
                <person name="Blanche H."/>
                <person name="Gut I."/>
                <person name="Heath S."/>
                <person name="Lathrop M."/>
                <person name="Brennan P."/>
            </authorList>
            <dbReference type="PubMed" id="18385738"/>
            <dbReference type="DOI" id="10.1038/nature06885"/>
        </citation>
        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2008" name="Nature" volume="452" first="638" last="642">
            <title>A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.</title>
            <authorList>
                <person name="Thorgeirsson T.E."/>
                <person name="Geller F."/>
                <person name="Sulem P."/>
                <person name="Rafnar T."/>
                <person name="Wiste A."/>
                <person name="Magnusson K.P."/>
                <person name="Manolescu A."/>
                <person name="Thorleifsson G."/>
                <person name="Stefansson H."/>
                <person name="Ingason A."/>
                <person name="Stacey S.N."/>
                <person name="Bergthorsson J.T."/>
                <person name="Thorlacius S."/>
                <person name="Gudmundsson J."/>
                <person name="Jonsson T."/>
                <person name="Jakobsdottir M."/>
                <person name="Saemundsdottir J."/>
                <person name="Olafsdottir O."/>
                <person name="Gudmundsson L.J."/>
                <person name="Bjornsdottir G."/>
                <person name="Kristjansson K."/>
                <person name="Skuladottir H."/>
                <person name="Isaksson H.J."/>
                <person name="Gudbjartsson T."/>
                <person name="Jones G.T."/>
                <person name="Mueller T."/>
                <person name="Gottsaeter A."/>
                <person name="Flex A."/>
                <person name="Aben K.K.H."/>
                <person name="de Vegt F."/>
                <person name="Mulders P.F.A."/>
                <person name="Isla D."/>
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                <person name="Hansdottir I."/>
                <person name="Runarsdottir V."/>
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                <person name="Dieplinger B."/>
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                <person name="Kiemeney L.A."/>
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                <person name="Oskarsson H."/>
                <person name="Tyrfingsson T."/>
                <person name="Gudbjartsson D.F."/>
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                <person name="Thorsteinsdottir U."/>
                <person name="Kong A."/>
                <person name="Stefansson K."/>
            </authorList>
            <dbReference type="PubMed" id="18385739"/>
            <dbReference type="DOI" id="10.1038/nature06846"/>
        </citation>
        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2008" name="Nat. Genet." volume="40" first="616" last="622">
            <title>Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1.</title>
            <authorList>
                <person name="Amos C.I."/>
                <person name="Wu X."/>
                <person name="Broderick P."/>
                <person name="Gorlov I.P."/>
                <person name="Gu J."/>
                <person name="Eisen T."/>
                <person name="Dong Q."/>
                <person name="Zhang Q."/>
                <person name="Gu X."/>
                <person name="Vijayakrishnan J."/>
                <person name="Sullivan K."/>
                <person name="Matakidou A."/>
                <person name="Wang Y."/>
                <person name="Mills G."/>
                <person name="Doheny K."/>
                <person name="Tsai Y.-Y."/>
                <person name="Chen W.V."/>
                <person name="Shete S."/>
                <person name="Spitz M.R."/>
                <person name="Houlston R.S."/>
            </authorList>
            <dbReference type="PubMed" id="18385676"/>
            <dbReference type="DOI" id="10.1038/ng.109"/>
        </citation>
        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="Biochem. Pharmacol." volume="97" first="518" last="530">
            <title>UBXN2A regulates nicotinic receptor degradation by modulating the E3 ligase activity of CHIP.</title>
            <authorList>
                <person name="Teng Y."/>
                <person name="Rezvani K."/>
                <person name="De Biasi M."/>
            </authorList>
            <dbReference type="PubMed" id="26265139"/>
            <dbReference type="DOI" id="10.1016/j.bcp.2015.08.084"/>
        </citation>
        <scope>IDENTIFICATION IN A COMPLEX WITH STUB1; VCP AND UBXN2A</scope>
        <scope>INTERACTION WITH UBXN2A</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2019" name="Am. J. Hum. Genet." volume="105" first="1286" last="1293">
            <title>CAKUT and autonomic dysfunction caused by acetylcholine receptor mutations.</title>
            <authorList>
                <person name="Mann N."/>
                <person name="Kause F."/>
                <person name="Henze E.K."/>
                <person name="Gharpure A."/>
                <person name="Shril S."/>
                <person name="Connaughton D.M."/>
                <person name="Nakayama M."/>
                <person name="Klaembt V."/>
                <person name="Majmundar A.J."/>
                <person name="Wu C.W."/>
                <person name="Kolvenbach C.M."/>
                <person name="Dai R."/>
                <person name="Chen J."/>
                <person name="van der Ven A.T."/>
                <person name="Ityel H."/>
                <person name="Tooley M.J."/>
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                <person name="De Franco E."/>
                <person name="Shalaby M."/>
                <person name="Tasic V."/>
                <person name="Bauer S.B."/>
                <person name="Lee R.S."/>
                <person name="Beckel J.M."/>
                <person name="Yu W."/>
                <person name="Mane S.M."/>
                <person name="Lifton R.P."/>
                <person name="Reutter H."/>
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                <person name="Hibbs R.E."/>
                <person name="Kawate T."/>
                <person name="Hildebrandt F."/>
            </authorList>
            <dbReference type="PubMed" id="31708116"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2019.10.004"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INVOLVEMENT IN BAIPRCK</scope>
        <scope>VARIANT BAIPRCK 340-SER--ALA-505 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT BAIPRCK 340-SER--ALA-505 DEL</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 14 17 18 19">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:31488329, PubMed:31708116). CHRNA3 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, with CHRNA5, and CHRNB3 as accesory subunits (PubMed:20881005, PubMed:8663494). CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor (PubMed:31488329). CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo-interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction (By similarity). Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake (By similarity). Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through extracellular influx and basal ATP release (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="2 6 8 14 17 20">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:11118490, PubMed:20881005, PubMed:31488329, PubMed:8906617). The heteropentamer CHRNA3:CHRNB2 activity is blocked by alpha-conotoxins ImI, ImII, PnIA, GID and MII (By similarity). The heteropentamer CHRNA3:CHRNB4 activity is blocked by the alpha-conotoxin ImI and AuIB (PubMed:15609996).</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 8 9 14 15 16 17 19">Neuronal AChR is composed of two different types of subunits: alpha and beta. CHRNA3/Alpha-3 subunit can be combined to CHRNA5/alpha-5, CHRNB2/beta-2 CHRNB3/beta-3 or CHRNB4/beta-4 to give rise to functional receptors (PubMed:20881005, PubMed:31488329, PubMed:8663494). Forms stoichiometries such as (CHRNA3)2:(CHRNB4)3 or (CHRNA3:CHRNB4)2:CHRNB3 (PubMed:11118490). Part of a complex composed of STUB1/CHIP, VCP/p97, CHRNA3, and UBXN2A that modulates the ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of CHRNA3 (PubMed:26265139). Within the complex UBXN2A acts as a scaffold protein required for the interaction of CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 ubiquitination by STUB1/CHIP and subsequently ERAD (PubMed:26265139). Interacts with UBXN2A (via SEP domain), the interaction is required for the interaction of CHRNA3 in the STUB1:VCP:UBXN2A complex (PubMed:26265139). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Synaptic cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Golgi apparatus</location>
        </subcellularLocation>
        <text evidence="2">Interaction with UBXN2A/UBXD4 promotes translocation to the plasma membrane.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P32297-2</id>
            <name>2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P32297-1</id>
            <name>1</name>
            <sequence type="described" ref="VSP_037750"/>
        </isoform>
        <isoform>
            <id>P32297-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_037751"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="2">Ubiquitinated; by STUB1/CHIP and thereafter degraded by the 26S proteosome complex.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="10 11 12 13">Genetic variations in CHRNA3 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].</text>
    </comment>
    <comment type="disease" evidence="18">
        <disease id="DI-05743">
            <name>Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT</name>
            <acronym>BAIPRCK</acronym>
            <description>An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. Additional autonomic features are impaired pupillary reflex and orthostatic hypotension. The disease manifests in utero or early childhood.</description>
            <dbReference type="MIM" id="191800"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="28">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-3/CHRNA3 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M86383">
        <property type="protein sequence ID" value="AAC84176.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M37981">
        <property type="protein sequence ID" value="AAA59942.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U62432">
        <property type="protein sequence ID" value="AAB40110.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08418">
        <property type="protein sequence ID" value="CAA69695.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007783">
        <property type="protein sequence ID" value="CAA07682.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007784">
        <property type="protein sequence ID" value="CAA07682.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007785">
        <property type="protein sequence ID" value="CAA07682.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007786">
        <property type="protein sequence ID" value="CAA07682.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ007787">
        <property type="protein sequence ID" value="CAA07682.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT006646">
        <property type="protein sequence ID" value="AAP35292.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT006897">
        <property type="protein sequence ID" value="AAP35543.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC027228">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC067863">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000513">
        <property type="protein sequence ID" value="AAH00513.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001642">
        <property type="protein sequence ID" value="AAH01642.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002996">
        <property type="protein sequence ID" value="AAH02996.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006114">
        <property type="protein sequence ID" value="AAH06114.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC098443">
        <property type="protein sequence ID" value="AAH98443.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF385584">
        <property type="protein sequence ID" value="AAK68110.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X53559">
        <property type="protein sequence ID" value="CAA37625.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10305.1">
        <molecule id="P32297-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53964.1">
        <molecule id="P32297-3"/>
    </dbReference>
    <dbReference type="PIR" id="A37040">
        <property type="entry name" value="A37040"/>
    </dbReference>
    <dbReference type="PIR" id="A53956">
        <property type="entry name" value="A53956"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000734.2">
        <molecule id="P32297-2"/>
        <property type="nucleotide sequence ID" value="NM_000743.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001160166.1">
        <molecule id="P32297-3"/>
        <property type="nucleotide sequence ID" value="NM_001166694.2"/>
    </dbReference>
    <dbReference type="PDB" id="4ZK4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D/E=215-230"/>
    </dbReference>
    <dbReference type="PDB" id="5SYO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B/C/D/E=215-230"/>
    </dbReference>
    <dbReference type="PDB" id="5TVC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.93 A"/>
        <property type="chains" value="A/B/C/D/E=215-230"/>
    </dbReference>
    <dbReference type="PDB" id="6PV7">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.34 A"/>
        <property type="chains" value="A/D=32-378, A/D=434-505"/>
    </dbReference>
    <dbReference type="PDB" id="6PV8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.87 A"/>
        <property type="chains" value="A/D=32-378, A/D=434-505"/>
    </dbReference>
    <dbReference type="PDBsum" id="4ZK4"/>
    <dbReference type="PDBsum" id="5SYO"/>
    <dbReference type="PDBsum" id="5TVC"/>
    <dbReference type="PDBsum" id="6PV7"/>
    <dbReference type="PDBsum" id="6PV8"/>
    <dbReference type="AlphaFoldDB" id="P32297"/>
    <dbReference type="EMDB" id="EMD-20487"/>
    <dbReference type="EMDB" id="EMD-20488"/>
    <dbReference type="SMR" id="P32297"/>
    <dbReference type="BioGRID" id="107558">
        <property type="interactions" value="37"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-187">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-210">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-213">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2192">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2193">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-beta2"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2200">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-beta4"/>
    </dbReference>
    <dbReference type="CORUM" id="P32297"/>
    <dbReference type="FunCoup" id="P32297">
        <property type="interactions" value="745"/>
    </dbReference>
    <dbReference type="IntAct" id="P32297">
        <property type="interactions" value="50"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000315602"/>
    <dbReference type="BindingDB" id="P32297"/>
    <dbReference type="ChEMBL" id="CHEMBL3068"/>
    <dbReference type="DrugBank" id="DB15096">
        <property type="generic name" value="18-methoxycoronaridine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00915">
        <property type="generic name" value="Amantadine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01156">
        <property type="generic name" value="Bupropion"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00237">
        <property type="generic name" value="Butabarbital"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00565">
        <property type="generic name" value="Cisatracurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09028">
        <property type="generic name" value="Cytisine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00514">
        <property type="generic name" value="Dextromethorphan"/>
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    <reference key="1">
        <citation type="journal article" date="1994" name="Mol. Pharmacol." volume="45" first="546" last="554">
            <title>Human alpha 7 acetylcholine receptor: cloning of the alpha 7 subunit from the SH-SY5Y cell line and determination of pharmacological properties of native receptors and functional alpha 7 homomers expressed in Xenopus oocytes.</title>
            <authorList>
                <person name="Peng X."/>
                <person name="Katz M."/>
                <person name="Gerzanich V."/>
                <person name="Anand R."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="8145738"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <tissue>Brain</tissue>
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        <citation type="journal article" date="1998" name="Genomics" volume="52" first="173" last="185">
            <title>Genomic organization and partial duplication of the human alpha7 neuronal nicotinic acetylcholine receptor gene (CHRNA7).</title>
            <authorList>
                <person name="Gault J."/>
                <person name="Robinson M."/>
                <person name="Berger R."/>
                <person name="Drebing C."/>
                <person name="Logel J."/>
                <person name="Hopkins J."/>
                <person name="Moore T."/>
                <person name="Jacobs S."/>
                <person name="Meriwether J."/>
                <person name="Choi M.J."/>
                <person name="Kim E.J."/>
                <person name="Walton K."/>
                <person name="Buiting K."/>
                <person name="Davis A."/>
                <person name="Breese C."/>
                <person name="Freedman R."/>
                <person name="Leonard S."/>
            </authorList>
            <dbReference type="PubMed" id="9782083"/>
            <dbReference type="DOI" id="10.1006/geno.1998.5363"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
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    <reference key="3">
        <citation type="journal article" date="1996" name="J. Mol. Neurosci." volume="7" first="217" last="228">
            <title>Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.</title>
            <authorList>
                <person name="Elliott K.J."/>
                <person name="Ellis S.B."/>
                <person name="Berckhan K.J."/>
                <person name="Urrutia A."/>
                <person name="Chavez-Noriega L.E."/>
                <person name="Johnson E.C."/>
                <person name="Velicelebi G."/>
                <person name="Harpold M.M."/>
            </authorList>
            <dbReference type="PubMed" id="8906617"/>
            <dbReference type="DOI" id="10.1007/bf02736842"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="400" first="309" last="314">
            <title>Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.</title>
            <authorList>
                <person name="Groot Kormelink P.J."/>
                <person name="Luyten W.H.M.L."/>
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            <dbReference type="PubMed" id="9009220"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(96)01383-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Groot Kormelink P.J."/>
                <person name="Luyten W.H.M.L."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2001-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning cholinergic receptors in human keratinocytes.</title>
            <authorList>
                <person name="Arredondo J."/>
                <person name="Grando S.A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
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            </authorList>
            <dbReference type="PubMed" id="38382524"/>
            <dbReference type="DOI" id="10.1016/j.cell.2024.01.032"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.19 ANGSTROMS) OF 24-373 AND 413-502 IN COMPLEX WITH CA(2+); LIGAND AND ALLOSTERIC MODULATORS</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 7 9 11 12 13 16 18 19 21 22 26">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:15609996, PubMed:33735609, PubMed:8145738). CHRNA7 forms homopentameric neuronal acetylcholine receptors abundantly expressed in the central nervous system, characterized by fast desensitization and high calcium permeability (PubMed:31560909, PubMed:33735609, PubMed:38382524, PubMed:8145738). Also forms heteropentamers with CHRNB2, mainly expressed in basal forebrain cholinergic neurons. Involved in the modulation of calcium-dependent signaling pathways and influences the release of neurotransmitters, including dopamine, glutamate and GABA (PubMed:33239400). Also expressed in non-neuronal cells such as immune cells like lymphocytes, monocytes and macrophages (PubMed:12508119, PubMed:16968406, PubMed:25259522). In T cells, activation induces metabotropic signaling that results in an increase of intracellular Ca2+ concentrations, independent of ionotropic receptor functions (PubMed:17709503). In macrophages, required for acetylcholine-mediated inhibition of TNF and other inflammatory cytokine release (PubMed:12508119). Once activated by acetylcholine, nicotine or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed (PubMed:12508119, PubMed:25259522). Stimulates the cholinergic anti-inflammatory pathway, controlling inflammation by inhibiting NFKB nuclear translocation and activating the JAK2-STAT3 pathway, independently of ion channel activity (PubMed:16968406, PubMed:25259522). Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through internal stores and decreasing basal ATP release (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19 22">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>choline(out) = choline(in)</text>
            <dbReference type="Rhea" id="RHEA:32751"/>
            <dbReference type="ChEBI" id="CHEBI:15354"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>NH4(+)(in) = NH4(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:28747"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>L-arginine(in) = L-arginine(out)</text>
            <dbReference type="Rhea" id="RHEA:32143"/>
            <dbReference type="ChEBI" id="CHEBI:32682"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="19">
            <text>guanidine(out) = guanidine(in)</text>
            <dbReference type="Rhea" id="RHEA:73883"/>
            <dbReference type="ChEBI" id="CHEBI:30087"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="7 9 11 16 18 19 20 21 22">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:12508119, PubMed:16968406, PubMed:33735609, PubMed:38382524, PubMed:8145738). Oligomeric amyloid-beta protein 42 activates specifially CHRNA7:CHRNB2 nAchRs (PubMed:33239400). Activity is modulated by positive allosteric modulators (PAMs), such as flavonoids, with a wide range of chemical diversity, pharmacological sensitivity and efficacy (PubMed:31560909, PubMed:38382524). AChR activity is inhibited by the antagonists alpha-conotoxons RgIA, ImI and ImII, small disulfide-constrained peptides from cone snails (PubMed:15609996). Alpha-conotoxin PnIC selectively inhibits CHRNA7:CHRNB2 over CHRNA7 homopentamer (PubMed:38161283).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 8 9 10 14 17 18 19 20 21">Homopentamer (PubMed:33735609, PubMed:38382524). Can also form heteropentamers with CHRNB2, mainly found in basal forebrain cholinergic neurons (PubMed:33239400, PubMed:38161283). Interacts with RIC3; which is required for proper folding and assembly (PubMed:15504725, PubMed:16120769). Interacts with LYPD6 (PubMed:27344019). Interacts with CANX (PubMed:32783947).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-821758">
            <id>PRO_0000000092</id>
            <label>APP</label>
            <dbReference type="UniProtKB" id="P05067"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-10693038">
            <id>Q9NSI6-4</id>
            <label>BRWD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-20798208">
            <id>Q494W8</id>
            <label>CHRFAM7A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-372690">
            <id>Q9UBU7</id>
            <label>DBF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-12382151">
            <id>Q8N5J2-3</id>
            <label>MINDY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-620823">
            <id>Q09028</id>
            <label>RBBP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-8830896">
            <id>P55000</id>
            <label>SLURP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-79333">
            <id>P36544</id>
        </interactant>
        <interactant intactId="EBI-632715">
            <id>Q13573</id>
            <label>SNW1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Postsynaptic cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="4 15">TMEM35A/NACHO promotes its trafficking to the cell membrane (PubMed:27789755). RIC3 promotes its trafficking to the cell membrane (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P36544-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P36544-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043019"/>
        </isoform>
        <isoform>
            <id>P36544-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_058107 VSP_058108"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 22">Expressed in neuronal cells (PubMed:8145738). Expressed in macrophages (at protein level) (PubMed:12508119).</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Glycosylations at Asn-46, Asn-90 and Asn-133 are essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to the cell membrane.</text>
    </comment>
    <comment type="mass spectrometry" mass="54157.68" method="MALDI" evidence="6"/>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="25">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="25">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-7/CHRNA7 sub-subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAH37571" version="1"/>
        </conflict>
        <text>Wrong choice of frame.</text>
    </comment>
    <dbReference type="EMBL" id="X70297">
        <property type="protein sequence ID" value="CAA49778.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U40583">
        <property type="protein sequence ID" value="AAA83561.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U62436">
        <property type="protein sequence ID" value="AAB40114.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08420">
        <property type="protein sequence ID" value="CAA69697.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF385585">
        <property type="protein sequence ID" value="AAK68111.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292069">
        <property type="protein sequence ID" value="BAF84758.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK294229">
        <property type="protein sequence ID" value="BAG57531.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC004460">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009562">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012236">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC021316">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026150">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026951">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC058803">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC068448">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC079969">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC087481">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC090829">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091057">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC104266">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC104759">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC037571">
        <property type="protein sequence ID" value="AAH37571.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101345">
        <property type="protein sequence ID" value="AAI01346.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L25827">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z23141">
        <property type="protein sequence ID" value="CAA80672.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF332758">
        <property type="protein sequence ID" value="AAK19515.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10027.1">
        <molecule id="P36544-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53924.1">
        <molecule id="P36544-2"/>
    </dbReference>
    <dbReference type="PIR" id="G02259">
        <property type="entry name" value="G02259"/>
    </dbReference>
    <dbReference type="PIR" id="I37185">
        <property type="entry name" value="ACHUA7"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000737.1">
        <molecule id="P36544-1"/>
        <property type="nucleotide sequence ID" value="NM_000746.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001177384.1">
        <molecule id="P36544-2"/>
        <property type="nucleotide sequence ID" value="NM_001190455.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_683709.1">
        <property type="nucleotide sequence ID" value="NM_148911.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005254807.1">
        <property type="nucleotide sequence ID" value="XM_005254750.2"/>
    </dbReference>
    <dbReference type="PDB" id="2MAW">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=228-326, A=467-495"/>
    </dbReference>
    <dbReference type="PDB" id="5AFH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C/D/E=23-227"/>
    </dbReference>
    <dbReference type="PDB" id="5AFJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B/C/D/E=23-227"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A/B/C/D/E=23-227"/>
    </dbReference>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="A/B/C/D/E=23-227"/>
    </dbReference>
    <dbReference type="PDB" id="7EKI">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.18 A"/>
        <property type="chains" value="A/B/C/D/E=1-502"/>
    </dbReference>
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        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A/B/C/D/E=1-502"/>
    </dbReference>
    <dbReference type="PDB" id="7EKT">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.02 A"/>
        <property type="chains" value="A/B/C/D/E=1-502"/>
    </dbReference>
    <dbReference type="PDB" id="7KOO">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D/E=24-371, A/B/C/D/E=407-502"/>
    </dbReference>
    <dbReference type="PDB" id="7KOQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/B/C/D/E=24-371, A/B/C/D/E=407-502"/>
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        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B/C/D/E=24-371, A/B/C/D/E=407-502"/>
    </dbReference>
    <dbReference type="PDB" id="7RPM">
        <property type="method" value="NMR"/>
        <property type="chains" value="A/B/C/D/E=231-496"/>
    </dbReference>
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        <property type="method" value="EM"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E=24-347, A/B/C/D/E=455-502"/>
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    <dbReference type="PDB" id="8CAU">
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        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/B/C/D/E=24-502"/>
    </dbReference>
    <dbReference type="PDB" id="8CE4">
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        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B/C/D/E=24-347, A/B/C/D/E=455-502"/>
    </dbReference>
    <dbReference type="PDB" id="8CI1">
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        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D/E=24-347, A/B/C/D/E=455-502"/>
    </dbReference>
    <dbReference type="PDB" id="8CI2">
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        <property type="resolution" value="4.40 A"/>
        <property type="chains" value="A/B/C/D/E=24-347, A/B/C/D/E=455-502"/>
    </dbReference>
    <dbReference type="PDB" id="8F4V">
        <property type="method" value="NMR"/>
        <property type="chains" value="A/B/C/D/E=231-496"/>
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    <dbReference type="PDB" id="8P1H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.95 A"/>
        <property type="chains" value="A/B=361-372"/>
    </dbReference>
    <dbReference type="PDB" id="8UT1">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
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        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V80">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.34 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V82">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.61 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V86">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.47 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V88">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V89">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.53 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
    <dbReference type="PDB" id="8V8A">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.19 A"/>
        <property type="chains" value="A/B/C/D/E=24-373, A/B/C/D/E=413-502"/>
    </dbReference>
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    <feature type="sequence conflict" description="In Ref. 1; CAA49778." evidence="25" ref="1">
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    <feature type="sequence conflict" description="In Ref. 11; CAA80672." evidence="25" ref="11">
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<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
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    <accession>D3DTK6</accession>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
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            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
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    <reference key="1">
        <citation type="journal article" date="1993" name="Eur. J. Biochem." volume="215" first="229" last="238">
            <title>Primary structure of the human muscle acetylcholine receptor. cDNA cloning of the gamma and epsilon subunits.</title>
            <authorList>
                <person name="Beeson D.M.W."/>
                <person name="Brydson M."/>
                <person name="Betty M."/>
                <person name="Jeremiah S."/>
                <person name="Povey S."/>
                <person name="Vincent A."/>
                <person name="Newsom-Davis J."/>
            </authorList>
            <dbReference type="PubMed" id="7688301"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1993.tb18027.x"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <tissue>Muscle fibroblast</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="1998-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Abicht A."/>
                <person name="Stucka R."/>
                <person name="Lochmuller H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Florea L."/>
                <person name="Halpern A.L."/>
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                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="16019" last="16026">
            <title>Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes.</title>
            <authorList>
                <person name="Ellison M."/>
                <person name="Gao F."/>
                <person name="Wang H.L."/>
                <person name="Sine S.M."/>
                <person name="McIntosh J.M."/>
                <person name="Olivera B.M."/>
            </authorList>
            <dbReference type="PubMed" id="15609996"/>
            <dbReference type="DOI" id="10.1021/bi048918g"/>
        </citation>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1995" name="Neurology" volume="45" first="982" last="985">
            <title>A leucine-to-phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow-channel syndrome.</title>
            <authorList>
                <person name="Gomez C.M."/>
                <person name="Gammack J.T."/>
            </authorList>
            <dbReference type="PubMed" id="7538206"/>
            <dbReference type="DOI" id="10.1212/wnl.45.5.982"/>
        </citation>
        <scope>VARIANT CMS4A PHE-289</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1995" name="Proc. Natl. Acad. Sci. U.S.A." volume="92" first="758" last="762">
            <title>Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit.</title>
            <authorList>
                <person name="Ohno K."/>
                <person name="Hutchinson D.O."/>
                <person name="Milone M."/>
                <person name="Brengman J.M."/>
                <person name="Bouzat C."/>
                <person name="Sine S.M."/>
                <person name="Engel A.G."/>
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            <dbReference type="DOI" id="10.1073/pnas.92.3.758"/>
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        <scope>VARIANT CMS4A PRO-284</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS4A PRO-284</scope>
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    <reference key="7">
        <citation type="journal article" date="1996" name="Hum. Mol. Genet." volume="5" first="1217" last="1227">
            <title>New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.</title>
            <authorList>
                <person name="Engel A.G."/>
                <person name="Ohno K."/>
                <person name="Milone M."/>
                <person name="Wang H.-L."/>
                <person name="Nakano S."/>
                <person name="Bouzat C."/>
                <person name="Pruitt J.N. II"/>
                <person name="Hutchinson D.O."/>
                <person name="Brengman J.M."/>
                <person name="Bren N."/>
                <person name="Sieb J.P."/>
                <person name="Sine S.M."/>
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            <dbReference type="DOI" id="10.1093/hmg/5.9.1217"/>
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        <scope>VARIANT CMS4A PHE-289</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS4A PHE-289</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1996" name="Neuron" volume="17" first="157" last="170">
            <title>Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit.</title>
            <authorList>
                <person name="Ohno K."/>
                <person name="Wang H.-L."/>
                <person name="Milone M."/>
                <person name="Bren N."/>
                <person name="Brengman J.M."/>
                <person name="Nakano S."/>
                <person name="Quiram P."/>
                <person name="Pruitt J.N. II"/>
                <person name="Sine S.M."/>
                <person name="Engel A.G."/>
            </authorList>
            <dbReference type="PubMed" id="8755487"/>
            <dbReference type="DOI" id="10.1016/s0896-6273(00)80289-5"/>
        </citation>
        <scope>VARIANTS CMS4B ARG-13; LEU-141 AND LEU-163</scope>
        <scope>CHARACTERIZATION OF VARIANTS CMS4B ARG-13; LEU-141 AND LEU-163</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1997" name="Hum. Mol. Genet." volume="6" first="753" last="766">
            <title>Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations.</title>
            <authorList>
                <person name="Ohno K."/>
                <person name="Quiram P.A."/>
                <person name="Milone M."/>
                <person name="Wang H.-L."/>
                <person name="Harper M.C."/>
                <person name="Pruitt J.N. II"/>
                <person name="Brengman J.M."/>
                <person name="Pao L."/>
                <person name="Fischbeck K.H."/>
                <person name="Crawford T.O."/>
                <person name="Sine S.M."/>
                <person name="Engel A.G."/>
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            <dbReference type="PubMed" id="9158150"/>
            <dbReference type="DOI" id="10.1093/hmg/6.5.753"/>
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        <scope>VARIANTS CMS4C LEU-167; LEU-265 AND TRP-331</scope>
        <scope>CHARACTERIZATION OF VARIANTS CMS4C LEU-167; LEU-265 AND TRP-331</scope>
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    <reference key="10">
        <citation type="journal article" date="2000" name="J. Gen. Physiol." volume="116" first="449" last="462">
            <title>Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome.</title>
            <authorList>
                <person name="Wang H.-L."/>
                <person name="Ohno K."/>
                <person name="Milone M."/>
                <person name="Brengman J.M."/>
                <person name="Evoli A."/>
                <person name="Batocchi A.-P."/>
                <person name="Middleton L.T."/>
                <person name="Christodoulou K."/>
                <person name="Engel A.G."/>
                <person name="Sine S.M."/>
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            <dbReference type="PubMed" id="10962020"/>
            <dbReference type="DOI" id="10.1085/jgp.116.3.449"/>
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        <scope>VARIANT CMS4B PRO-431</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS4B PRO-431</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2002" name="Neurology" volume="59" first="162" last="168">
            <title>Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes.</title>
            <authorList>
                <person name="Croxen R."/>
                <person name="Hatton C."/>
                <person name="Shelley C."/>
                <person name="Brydson M."/>
                <person name="Chauplannaz G."/>
                <person name="Oosterhuis H."/>
                <person name="Vincent A."/>
                <person name="Newsom-Davis J."/>
                <person name="Colquhoun D."/>
                <person name="Beeson D."/>
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            <dbReference type="PubMed" id="12141316"/>
            <dbReference type="DOI" id="10.1212/wnl.59.2.162"/>
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        <scope>VARIANTS CMS4A PRO-98 AND PHE-241</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2012" name="Neurology" volume="79" first="449" last="454">
            <title>Highly fatal fast-channel syndrome caused by AChR epsilon subunit mutation at the agonist binding site.</title>
            <authorList>
                <person name="Shen X.M."/>
                <person name="Brengman J.M."/>
                <person name="Edvardson S."/>
                <person name="Sine S.M."/>
                <person name="Engel A.G."/>
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            <dbReference type="DOI" id="10.1212/wnl.0b013e31825b5bda"/>
        </citation>
        <scope>VARIANT CMS4B ARG-75</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS4B ARG-75</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2016" name="Hum. Mutat." volume="37" first="1051" last="1059">
            <title>Mutations causing slow-channel myasthenia reveal that a valine ring in the channel pore of muscle AChR is optimized for stabilizing channel gating.</title>
            <authorList>
                <person name="Shen X.M."/>
                <person name="Okuno T."/>
                <person name="Milone M."/>
                <person name="Otsuka K."/>
                <person name="Takahashi K."/>
                <person name="Komaki H."/>
                <person name="Giles E."/>
                <person name="Ohno K."/>
                <person name="Engel A.G."/>
            </authorList>
            <dbReference type="PubMed" id="27375219"/>
            <dbReference type="DOI" id="10.1002/humu.23043"/>
        </citation>
        <scope>VARIANT CMS4A ALA-285</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS4A ALA-285</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="8">After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="6">Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="disease">
        <text>The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.</text>
    </comment>
    <comment type="disease" evidence="5 8 9 10 12">
        <disease id="DI-04397">
            <name>Myasthenic syndrome, congenital, 4A, slow-channel</name>
            <acronym>CMS4A</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.</description>
            <dbReference type="MIM" id="605809"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="4 7 11">
        <disease id="DI-04396">
            <name>Myasthenic syndrome, congenital, 4B, fast-channel</name>
            <acronym>CMS4B</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.</description>
            <dbReference type="MIM" id="616324"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-00369">
            <name>Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency</name>
            <acronym>CMS4C</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.</description>
            <dbReference type="MIM" id="608931"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Epsilon/CHRNE sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X66403">
        <property type="protein sequence ID" value="CAA47030.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF105999">
        <property type="protein sequence ID" value="AAD24503.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90395.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW90396.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11058.1"/>
    <dbReference type="PIR" id="S34775">
        <property type="entry name" value="S34775"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000071.1">
        <property type="nucleotide sequence ID" value="NM_000080.4"/>
    </dbReference>
    <dbReference type="PDB" id="9DMG">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="B=1-493"/>
    </dbReference>
    <dbReference type="PDB" id="9DMH">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="B=1-493"/>
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    <dbReference type="PDB" id="9DMJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.19 A"/>
        <property type="chains" value="B=1-493"/>
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    <dbReference type="PDB" id="9DMK">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.46 A"/>
        <property type="chains" value="B=1-493"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="2.24 A"/>
        <property type="chains" value="I=1-493"/>
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    <dbReference type="PDB" id="9DMQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="B=1-493"/>
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    <dbReference type="PDB" id="9DMS">
        <property type="method" value="EM"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="B=1-493"/>
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    <dbReference type="PDB" id="9DMT">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.18 A"/>
        <property type="chains" value="B=1-493"/>
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    <dbReference type="PDB" id="9DMV">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.13 A"/>
        <property type="chains" value="B=1-493"/>
    </dbReference>
    <dbReference type="PDB" id="9GU0">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.96 A"/>
        <property type="chains" value="E=21-493"/>
    </dbReference>
    <dbReference type="PDB" id="9GU1">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.48 A"/>
        <property type="chains" value="E=21-493"/>
    </dbReference>
    <dbReference type="PDB" id="9GU2">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.73 A"/>
        <property type="chains" value="E=21-493"/>
    </dbReference>
    <dbReference type="PDB" id="9GU3">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.64 A"/>
        <property type="chains" value="E=21-493"/>
    </dbReference>
    <dbReference type="PDBsum" id="9DMG"/>
    <dbReference type="PDBsum" id="9DMH"/>
    <dbReference type="PDBsum" id="9DMJ"/>
    <dbReference type="PDBsum" id="9DMK"/>
    <dbReference type="PDBsum" id="9DML"/>
    <dbReference type="PDBsum" id="9DMQ"/>
    <dbReference type="PDBsum" id="9DMS"/>
    <dbReference type="PDBsum" id="9DMT"/>
    <dbReference type="PDBsum" id="9DMV"/>
    <dbReference type="PDBsum" id="9GU0"/>
    <dbReference type="PDBsum" id="9GU1"/>
    <dbReference type="PDBsum" id="9GU2"/>
    <dbReference type="PDBsum" id="9GU3"/>
    <dbReference type="AlphaFoldDB" id="Q04844"/>
    <dbReference type="EMDB" id="EMD-47003"/>
    <dbReference type="EMDB" id="EMD-47005"/>
    <dbReference type="EMDB" id="EMD-47007"/>
    <dbReference type="EMDB" id="EMD-47008"/>
    <dbReference type="EMDB" id="EMD-47009"/>
    <dbReference type="EMDB" id="EMD-47013"/>
    <dbReference type="EMDB" id="EMD-47014"/>
    <dbReference type="EMDB" id="EMD-47015"/>
    <dbReference type="EMDB" id="EMD-47017"/>
    <dbReference type="EMDB" id="EMD-51568"/>
    <dbReference type="EMDB" id="EMD-51569"/>
    <dbReference type="EMDB" id="EMD-51570"/>
    <dbReference type="EMDB" id="EMD-51571"/>
    <dbReference type="SMR" id="Q04844"/>
    <dbReference type="BioGRID" id="107567">
        <property type="interactions" value="35"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-255">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26535">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="CORUM" id="Q04844"/>
    <dbReference type="FunCoup" id="Q04844">
        <property type="interactions" value="396"/>
    </dbReference>
    <dbReference type="IntAct" id="Q04844">
        <property type="interactions" value="32"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000497829"/>
    <dbReference type="BindingDB" id="Q04844"/>
    <dbReference type="ChEMBL" id="CHEMBL2484"/>
    <dbReference type="DrugCentral" id="Q04844"/>
    <dbReference type="TCDB" id="1.A.9.1.1">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q04844">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q04844">
        <property type="glycosylation" value="2 sites, 3 N-linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q04844"/>
    <dbReference type="PhosphoSitePlus" id="Q04844"/>
    <dbReference type="BioMuta" id="CHRNE"/>
    <dbReference type="DMDM" id="1168301"/>
    <dbReference type="jPOST" id="Q04844"/>
    <dbReference type="PaxDb" id="9606-ENSP00000293780"/>
    <dbReference type="PeptideAtlas" id="Q04844"/>
    <dbReference type="ProteomicsDB" id="58287"/>
    <dbReference type="ABCD" id="Q04844">
        <property type="antibodies" value="1 sequenced antibody"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="11366">
        <property type="antibodies" value="176 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1145"/>
    <dbReference type="Ensembl" id="ENST00000649488.2">
        <property type="protein sequence ID" value="ENSP00000497829.1"/>
        <property type="gene ID" value="ENSG00000108556.10"/>
    </dbReference>
    <dbReference type="GeneID" id="1145"/>
    <dbReference type="KEGG" id="hsa:1145"/>
    <dbReference type="MANE-Select" id="ENST00000649488.2">
        <property type="protein sequence ID" value="ENSP00000497829.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000080.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000071.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002fzk.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1966"/>
    <dbReference type="ClinPGx" id="PA26498"/>
    <dbReference type="CTD" id="1145"/>
    <dbReference type="DisGeNET" id="1145"/>
    <dbReference type="GeneCards" id="CHRNE"/>
    <dbReference type="GeneReviews" id="CHRNE"/>
    <dbReference type="HGNC" id="HGNC:1966">
        <property type="gene designation" value="CHRNE"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000108556">
        <property type="expression patterns" value="Group enriched (heart muscle, pituitary gland)"/>
    </dbReference>
    <dbReference type="MalaCards" id="CHRNE"/>
    <dbReference type="MIM" id="100725">
        <property type="type" value="gene"/>
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        <property type="type" value="phenotype"/>
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        <property type="type" value="phenotype"/>
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    <dbReference type="MIM" id="608931">
        <property type="type" value="phenotype"/>
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        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000108556"/>
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        <property type="disease" value="Postsynaptic congenital myasthenic syndromes"/>
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    <dbReference type="VEuPathDB" id="HostDB:ENSG00000108556"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160933"/>
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    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="Q04844">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q04844"/>
    <dbReference type="PathwayCommons" id="Q04844"/>
    <dbReference type="Reactome" id="R-HSA-629587">
        <property type="pathway name" value="Highly sodium permeable postsynaptic acetylcholine nicotinic receptors"/>
    </dbReference>
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    <dbReference type="Agora" id="ENSG00000108556"/>
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        <property type="hits" value="18 hits in 1155 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="CHRNE">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CHRNE"/>
    <dbReference type="GenomeRNAi" id="1145"/>
    <dbReference type="Pharos" id="Q04844">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q04844"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
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    <dbReference type="RNAct" id="Q04844">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000108556">
        <property type="expression patterns" value="Expressed in right atrium auricular region and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q04844">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031594">
        <property type="term" value="C:neuromuscular junction"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015464">
        <property type="term" value="F:acetylcholine receptor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022848">
        <property type="term" value="F:acetylcholine-gated monoatomic cation-selective channel activity"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0008324">
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        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0095500">
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
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        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051899">
        <property type="term" value="P:membrane depolarization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006936">
        <property type="term" value="P:muscle contraction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003009">
        <property type="term" value="P:skeletal muscle contraction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0007271">
        <property type="term" value="P:synaptic transmission, cholinergic"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
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        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="LGIC_TM_nAChR"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Cholinergic receptor nicotinic epsilon subunit"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000010">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit epsilon"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="2"/>
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    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
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    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
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    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038050">
        <property type="entry name" value="Neuro_actylchol_rec"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018000">
        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002394">
        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00254">
        <property type="entry name" value="NICOTINICR"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1004">Congenital myasthenic syndrome</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide">
        <location>
            <begin position="1"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000329" description="Acetylcholine receptor subunit epsilon">
        <location>
            <begin position="21"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="21"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="240"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="265"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="273"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="292"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="307"/>
            <end position="328"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="329"/>
            <end position="456"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="457"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="481"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="148"/>
            <end position="162"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021213" description="In CMS4B; impaired association with alpha CHRNA1 subunit of AChR; dbSNP:rs372635387." evidence="11">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048170" description="In dbSNP:rs4790235.">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071629" description="In CMS4B; strongly reduces agonist affinity and gating efficiency; dbSNP:rs193919341." evidence="7">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019567" description="In CMS4A; rare example of recessive inheritance; dbSNP:rs28929768." evidence="5">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000289" description="In CMS4B; marked decrease in rate of AChR channel opening; reduction in frequency of open channel state and resistance to desensitization by ACh; dbSNP:rs121909512." evidence="11">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="141"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021214" description="In CMS4B; fails to assemble with alpha CHRNA1 subunit of AChR; dbSNP:rs121909516." evidence="11">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000290" description="In CMS4C; significantly reduced AChR expression; dbSNP:rs121909514." evidence="13">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019568" description="In CMS4A; mild form with variable penetrance; dbSNP:rs28999110." evidence="5">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000291" description="In CMS4C; prolongs burst open duration 2-fold by slowing the rate of channel closing; dbSNP:rs759226183." evidence="13">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000292" description="In CMS4A; markedly prolonged channel openings in presence of agonist; as well as opening in the absence of agonist; dbSNP:rs121909510." evidence="9">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077364" description="In CMS4A; slow-channel mutation; increases gating equilibrium constant by 25-fold, owing to increased opening rate and decreased closing rate; no effect on the choline dissociation rate constant; dbSNP:rs1597618787." evidence="8">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000293" description="In CMS4A; slows rate of AChR channel closure and increases apparent affinity for ACh; causes pathologic channel openings even in the absence of ACh resulting in a leaky channel; dbSNP:rs121909511." evidence="10 12">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000294" description="In CMS4C; shortens burst duration 2-fold by slowing the rate of channel opening and speeding the rate of ACh dissociation; has a mild fast-channel kinetic effect on the AChR by shortening the long burst and increasing the decay of the endplate current; dbSNP:rs121909515." evidence="13">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="331"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021215" description="In CMS4B; causes an increase in distributions of rates for channel opening and closing increasing the range of activation kinetics; dbSNP:rs121909517." evidence="4">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="431"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P02715"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10962020"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12141316"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15609996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22592360"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27375219"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="7531341"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="7538206"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="8755487"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="8872460"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="9158150"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:1966"/>
        </source>
    </evidence>
    <sequence length="493" mass="54697" checksum="A34AF273AF8B31FE" modified="1995-11-01" version="2" precursor="true">MARAPLGVLLLLGLLGRGVGKNEELRLYHHLFNNYDPGSRPVREPEDTVTISLKVTLTNLISLNEKEETLTTSVWIGIDWQDYRLNYSKDDFGGIETLRVPSELVWLPEIVLENNIDGQFGVAYDANVLVYEGGSVTWLPPAIYRSVCAVEVTYFPFDWQNCSLIFRSQTYNAEEVEFTFAVDNDGKTINKIDIDTEAYTENGEWAIDFCPGVIRRHHGGATDGPGETDVIYSLIIRRKPLFYVINIIVPCVLISGLVLLAYFLPAQAGGQKCTVSINVLLAQTVFLFLIAQKIPETSLSVPLLGRFLIFVMVVATLIVMNCVIVLNVSQRTPTTHAMSPRLRHVLLELLPRLLGSPPPPEAPRAASPPRRASSVGLLLRAEELILKKPRSELVFEGQRHRQGTWTAAFCQSLGAAAPEVRCCVDAVNFVAESTRDQEATGEEVSDWVRMGNALDNICFWAALVLFSVGSSLIFLGAYFNRVPDLPYAPCIQP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-07-01" modified="2026-01-28" version="243" xmlns="https://uniprot.org/uniprot">
    <accession>P11230</accession>
    <accession>B7Z5H1</accession>
    <accession>Q8IZ46</accession>
    <accession>Q96FB8</accession>
    <name>ACHB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">Acetylcholine receptor subunit beta</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="12" type="primary">CHRNB1</name>
        <name type="synonym">ACHRB</name>
        <name type="synonym">CHRNB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS GLY-32 AND TYR-124</scope>
        <source>
            <tissue>Eye</tissue>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="16019" last="16026">
            <title>Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes.</title>
            <authorList>
                <person name="Ellison M."/>
                <person name="Gao F."/>
                <person name="Wang H.L."/>
                <person name="Sine S.M."/>
                <person name="McIntosh J.M."/>
                <person name="Olivera B.M."/>
            </authorList>
            <dbReference type="PubMed" id="15609996"/>
            <dbReference type="DOI" id="10.1021/bi048918g"/>
        </citation>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1996" name="Ann. Neurol." volume="39" first="712" last="723">
            <title>A beta-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome.</title>
            <authorList>
                <person name="Gomez C.M."/>
                <person name="Maselli R."/>
                <person name="Gammack J."/>
                <person name="Lasalde J."/>
                <person name="Tamamizu S."/>
                <person name="Cornblath D.R."/>
                <person name="Lehar M."/>
                <person name="McNamee M."/>
                <person name="Kuncl R.W."/>
            </authorList>
            <dbReference type="PubMed" id="8651643"/>
            <dbReference type="DOI" id="10.1002/ana.410390607"/>
        </citation>
        <scope>VARIANT CMS2A MET-285</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1996" name="Hum. Mol. Genet." volume="5" first="1217" last="1227">
            <title>New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.</title>
            <authorList>
                <person name="Engel A.G."/>
                <person name="Ohno K."/>
                <person name="Milone M."/>
                <person name="Wang H.-L."/>
                <person name="Nakano S."/>
                <person name="Bouzat C."/>
                <person name="Pruitt J.N. II"/>
                <person name="Hutchinson D.O."/>
                <person name="Brengman J.M."/>
                <person name="Bren N."/>
                <person name="Sieb J.P."/>
                <person name="Sine S.M."/>
            </authorList>
            <dbReference type="PubMed" id="8872460"/>
            <dbReference type="DOI" id="10.1093/hmg/5.9.1217"/>
        </citation>
        <scope>VARIANT CMS2A MET-289</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1999" name="J. Clin. Invest." volume="104" first="1403" last="1410">
            <title>Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly.</title>
            <authorList>
                <person name="Quiram P.A."/>
                <person name="Ohno K."/>
                <person name="Milone M."/>
                <person name="Patterson M.C."/>
                <person name="Pruitt J.N. II"/>
                <person name="Brengman J.M."/>
                <person name="Sine S.M."/>
                <person name="Engel A.G."/>
            </authorList>
            <dbReference type="PubMed" id="10562302"/>
            <dbReference type="DOI" id="10.1172/jci8179"/>
        </citation>
        <scope>VARIANT CMS2C 449-GLU--GLU-451 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS2C 449-GLU--GLU-451 DEL</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2016" name="Hum. Mutat." volume="37" first="1051" last="1059">
            <title>Mutations causing slow-channel myasthenia reveal that a valine ring in the channel pore of muscle AChR is optimized for stabilizing channel gating.</title>
            <authorList>
                <person name="Shen X.M."/>
                <person name="Okuno T."/>
                <person name="Milone M."/>
                <person name="Otsuka K."/>
                <person name="Takahashi K."/>
                <person name="Komaki H."/>
                <person name="Giles E."/>
                <person name="Ohno K."/>
                <person name="Engel A.G."/>
            </authorList>
            <dbReference type="PubMed" id="27375219"/>
            <dbReference type="DOI" id="10.1002/humu.23043"/>
        </citation>
        <scope>VARIANT CMS2A ALA-289</scope>
        <scope>CHARACTERIZATION OF VARIANT CMS2A ALA-289</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="7">After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="6">Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-724218">
            <id>P11230</id>
        </interactant>
        <interactant intactId="EBI-6425205">
            <id>Q9NWX5</id>
            <label>ASB6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P11230-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P11230-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056675"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="7 8 9">
        <disease id="DI-04393">
            <name>Myasthenic syndrome, congenital, 2A, slow-channel</name>
            <acronym>CMS2A</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.</description>
            <dbReference type="MIM" id="616313"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-04398">
            <name>Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency</name>
            <acronym>CMS2C</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. CMS2C is clinically characterized by early-onset muscle weakness with variable severity.</description>
            <dbReference type="MIM" id="616314"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-1/CHRNB1 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X14830">
        <property type="protein sequence ID" value="CAA32939.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298938">
        <property type="protein sequence ID" value="BAH12907.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC113189">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011371">
        <property type="protein sequence ID" value="AAH11371.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC023553">
        <property type="protein sequence ID" value="AAH23553.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11106.1">
        <molecule id="P11230-1"/>
    </dbReference>
    <dbReference type="PIR" id="S04607">
        <property type="entry name" value="S04607"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000738.2">
        <molecule id="P11230-1"/>
        <property type="nucleotide sequence ID" value="NM_000747.2"/>
    </dbReference>
    <dbReference type="PDB" id="9DMG">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMH">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.19 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMK">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.46 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DML">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.24 A"/>
        <property type="chains" value="G=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMS">
        <property type="method" value="EM"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMT">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.18 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9DMV">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.13 A"/>
        <property type="chains" value="E=1-501"/>
    </dbReference>
    <dbReference type="PDB" id="9GU0">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.96 A"/>
        <property type="chains" value="B=24-501"/>
    </dbReference>
    <dbReference type="PDB" id="9GU1">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.48 A"/>
        <property type="chains" value="B=24-501"/>
    </dbReference>
    <dbReference type="PDB" id="9GU2">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.73 A"/>
        <property type="chains" value="B=24-501"/>
    </dbReference>
    <dbReference type="PDB" id="9GU3">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.64 A"/>
        <property type="chains" value="B=24-501"/>
    </dbReference>
    <dbReference type="PDBsum" id="9DMG"/>
    <dbReference type="PDBsum" id="9DMH"/>
    <dbReference type="PDBsum" id="9DMJ"/>
    <dbReference type="PDBsum" id="9DMK"/>
    <dbReference type="PDBsum" id="9DML"/>
    <dbReference type="PDBsum" id="9DMQ"/>
    <dbReference type="PDBsum" id="9DMS"/>
    <dbReference type="PDBsum" id="9DMT"/>
    <dbReference type="PDBsum" id="9DMV"/>
    <dbReference type="PDBsum" id="9GU0"/>
    <dbReference type="PDBsum" id="9GU1"/>
    <dbReference type="PDBsum" id="9GU2"/>
    <dbReference type="PDBsum" id="9GU3"/>
    <dbReference type="AlphaFoldDB" id="P11230"/>
    <dbReference type="EMDB" id="EMD-47003"/>
    <dbReference type="EMDB" id="EMD-47005"/>
    <dbReference type="EMDB" id="EMD-47007"/>
    <dbReference type="EMDB" id="EMD-47008"/>
    <dbReference type="EMDB" id="EMD-47009"/>
    <dbReference type="EMDB" id="EMD-47013"/>
    <dbReference type="EMDB" id="EMD-47014"/>
    <dbReference type="EMDB" id="EMD-47015"/>
    <dbReference type="EMDB" id="EMD-47017"/>
    <dbReference type="EMDB" id="EMD-51568"/>
    <dbReference type="EMDB" id="EMD-51569"/>
    <dbReference type="EMDB" id="EMD-51570"/>
    <dbReference type="EMDB" id="EMD-51571"/>
    <dbReference type="SMR" id="P11230"/>
    <dbReference type="BioGRID" id="107562">
        <property type="interactions" value="43"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2179">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-255">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26535">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="CORUM" id="P11230"/>
    <dbReference type="FunCoup" id="P11230">
        <property type="interactions" value="390"/>
    </dbReference>
    <dbReference type="IntAct" id="P11230">
        <property type="interactions" value="77"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000304290"/>
    <dbReference type="BindingDB" id="P11230"/>
    <dbReference type="ChEMBL" id="CHEMBL1907588"/>
    <dbReference type="ChEMBL" id="CHEMBL3885508"/>
    <dbReference type="ChEMBL" id="CHEMBL4106145"/>
    <dbReference type="DrugCentral" id="P11230"/>
    <dbReference type="TCDB" id="1.A.9.1.1">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P11230">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P11230">
        <property type="glycosylation" value="1 site, 3 N-linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P11230"/>
    <dbReference type="PhosphoSitePlus" id="P11230"/>
    <dbReference type="BioMuta" id="CHRNB1"/>
    <dbReference type="DMDM" id="21903373"/>
    <dbReference type="MassIVE" id="P11230"/>
    <dbReference type="PaxDb" id="9606-ENSP00000304290"/>
    <dbReference type="PeptideAtlas" id="P11230"/>
    <dbReference type="ProteomicsDB" id="52725">
        <molecule id="P11230-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="6694"/>
    <dbReference type="ABCD" id="P11230">
        <property type="antibodies" value="3 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="992">
        <property type="antibodies" value="256 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1140"/>
    <dbReference type="Ensembl" id="ENST00000306071.7">
        <molecule id="P11230-1"/>
        <property type="protein sequence ID" value="ENSP00000304290.2"/>
        <property type="gene ID" value="ENSG00000170175.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000536404.6">
        <molecule id="P11230-2"/>
        <property type="protein sequence ID" value="ENSP00000439209.2"/>
        <property type="gene ID" value="ENSG00000170175.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000639692.2">
        <molecule id="P11230-1"/>
        <property type="protein sequence ID" value="ENSP00000492221.1"/>
        <property type="gene ID" value="ENSG00000283946.2"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000639993.1">
        <molecule id="P11230-2"/>
        <property type="protein sequence ID" value="ENSP00000491113.1"/>
        <property type="gene ID" value="ENSG00000283946.2"/>
    </dbReference>
    <dbReference type="GeneID" id="1140"/>
    <dbReference type="KEGG" id="hsa:1140"/>
    <dbReference type="MANE-Select" id="ENST00000306071.7">
        <property type="protein sequence ID" value="ENSP00000304290.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000747.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000738.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ghb.4">
        <molecule id="P11230-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1961"/>
    <dbReference type="ClinPGx" id="PA26494"/>
    <dbReference type="CTD" id="1140"/>
    <dbReference type="DisGeNET" id="1140"/>
    <dbReference type="GeneCards" id="CHRNB1"/>
    <dbReference type="GeneReviews" id="CHRNB1"/>
    <dbReference type="HGNC" id="HGNC:1961">
        <property type="gene designation" value="CHRNB1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000170175">
        <property type="expression patterns" value="Tissue enhanced (skeletal muscle, tongue)"/>
    </dbReference>
    <dbReference type="MalaCards" id="CHRNB1"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="type" value="phenotype"/>
    </dbReference>
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        <property type="disease" value="Postsynaptic congenital myasthenic syndromes"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000170175"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158661"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_4_1"/>
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    <dbReference type="OMA" id="PCILITV"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="P11230">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P11230"/>
    <dbReference type="PathwayCommons" id="P11230"/>
    <dbReference type="SignaLink" id="P11230"/>
    <dbReference type="Agora" id="ENSG00000170175"/>
    <dbReference type="BioGRID-ORCS" id="1140">
        <property type="hits" value="14 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="3EAB04FE">
        <property type="entry name" value="Rapsn condensate"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="CHRNB1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CHRNB1"/>
    <dbReference type="GenomeRNAi" id="1140"/>
    <dbReference type="Pharos" id="P11230">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P11230"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
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    <dbReference type="RNAct" id="P11230">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000170175">
        <property type="expression patterns" value="Expressed in gastrocnemius and 99 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P11230">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031594">
        <property type="term" value="C:neuromuscular junction"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099634">
        <property type="term" value="C:postsynaptic specialization membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042166">
        <property type="term" value="F:acetylcholine binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022848">
        <property type="term" value="F:acetylcholine-gated monoatomic cation-selective channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015267">
        <property type="term" value="F:channel activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015276">
        <property type="term" value="F:ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004888">
        <property type="term" value="F:transmembrane signaling receptor activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0095500">
        <property type="term" value="P:acetylcholine receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0035095">
        <property type="term" value="P:behavioral response to nicotine"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051899">
        <property type="term" value="P:membrane depolarization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006812">
        <property type="term" value="P:monoatomic cation transport"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055001">
        <property type="term" value="P:muscle cell development"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006936">
        <property type="term" value="P:muscle contraction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050877">
        <property type="term" value="P:nervous system process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007274">
        <property type="term" value="P:neuromuscular synaptic transmission"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001941">
        <property type="term" value="P:postsynaptic membrane organization"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003009">
        <property type="term" value="P:skeletal muscle contraction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007271">
        <property type="term" value="P:synaptic transmission, cholinergic"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd19024">
        <property type="entry name" value="LGIC_ECD_nAChR_B1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19064">
        <property type="entry name" value="LGIC_TM_nAChR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000026">
        <property type="entry name" value="Cholinergic receptor nicotinic beta 1 subunit"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.70.170.10:FF:000012">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit gamma"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038050">
        <property type="entry name" value="Neuro_actylchol_rec"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018000">
        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002394">
        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR00860">
        <property type="entry name" value="LIC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00254">
        <property type="entry name" value="NICOTINICR"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1004">Congenital myasthenic syndrome</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000315" description="Acetylcholine receptor subunit beta">
        <location>
            <begin position="24"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="24"/>
            <end position="244"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="245"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="277"/>
            <end position="295"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="311"/>
            <end position="332"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="333"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="470"/>
            <end position="488"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by Tyr-kinases" evidence="1">
        <location>
            <position position="390"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="151"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_056675" description="In isoform 2." evidence="10">
        <location>
            <begin position="1"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048169" description="In dbSNP:rs17856697." evidence="5">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070842" description="In dbSNP:rs17856698." evidence="5">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000287" description="In CMS2A; dbSNP:rs137852811." evidence="8">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077363" description="In CMS2A; slow-channel mutation; increases gating equilibrium constant by 33-fold, owing to increased opening rate and decreased closing rate; no effect on the choline dissociation rate constant." evidence="7">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000288" description="In CMS2A; dbSNP:rs137852810." evidence="9">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017494" description="In CMS2C; impairs AChR assembly by disrupting a specific interaction between beta and delta subunits." evidence="4">
        <location>
            <begin position="449"/>
            <end position="451"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA32939." evidence="11" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA32939." evidence="11" ref="1">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="210"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P04758"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10562302"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15609996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="27375219"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="8651643"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="8872460"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:1961"/>
        </source>
    </evidence>
    <sequence length="501" mass="56698" checksum="365CBFA795A51394" modified="2002-07-11" version="3" precursor="true">MTPGALLMLLGALGAPLAPGVRGSEAEGRLREKLFSGYDSSVRPAREVGDRVRVSVGLILAQLISLNEKDEEMSTKVYLDLEWTDYRLSWDPAEHDGIDSLRITAESVWLPDVVLLNNNDGNFDVALDISVVVSSDGSVRWQPPGIYRSSCSIQVTYFPFDWQNCTMVFSSYSYDSSEVSLQTGLGPDGQGHQEIHIHEGTFIENGQWEIIHKPSRLIQPPGDPRGGREGQRQEVIFYLIIRRKPLFYLVNVIAPCILITLLAIFVFYLPPDAGEKMGLSIFALLTLTVFLLLLADKVPETSLSVPIIIKYLMFTMVLVTFSVILSVVVLNLHHRSPHTHQMPLWVRQIFIHKLPLYLRLKRPKPERDLMPEPPHCSSPGSGWGRGTDEYFIRKPPSDFLFPKPNRFQPELSAPDLRRFIDGPNRAVALLPELREVVSSISYIARQLQEQEDHDALKEDWQFVAMVVDRLFLWTFIIFTSVGTLVIFLDATYHLPPPDPFP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-04-27" modified="2026-01-28" version="198" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UGM1</accession>
    <accession>Q14CY7</accession>
    <accession>Q4W5A2</accession>
    <accession>Q9NYV2</accession>
    <name>ACHA9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit alpha-9</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Nicotinic acetylcholine receptor subunit alpha-9</fullName>
            <shortName>NACHR alpha-9</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">CHRNA9</name>
        <name type="synonym">NACHRA9</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT SER-442</scope>
        <source>
            <tissue>Embryo</tissue>
        </source>
    </reference>
    <reference key="2">
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-442</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2000" name="Am. J. Pathol." volume="157" first="1377" last="1391">
            <title>Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity.</title>
            <authorList>
                <person name="Nguyen V.T."/>
                <person name="Ndoye A."/>
                <person name="Grando S.A."/>
            </authorList>
            <dbReference type="PubMed" id="11021840"/>
            <dbReference type="DOI" id="10.1016/s0002-9440(10)64651-2"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 7-476</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Life Sci." volume="76" first="263" last="280">
            <title>Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.</title>
            <authorList>
                <person name="Peng H."/>
                <person name="Ferris R.L."/>
                <person name="Matthews T."/>
                <person name="Hiel H."/>
                <person name="Lopez-Albaitero A."/>
                <person name="Lustig L.R."/>
            </authorList>
            <dbReference type="PubMed" id="15531379"/>
            <dbReference type="DOI" id="10.1016/j.lfs.2004.05.031"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Neuropharmacology" volume="56" first="237" last="246">
            <title>Diversity of vertebrate nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Millar N.S."/>
                <person name="Gotti C."/>
            </authorList>
            <dbReference type="PubMed" id="18723036"/>
            <dbReference type="DOI" id="10.1016/j.neuropharm.2008.07.041"/>
        </citation>
        <scope>REVIEW ON NACHRS DIVERSITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2012" name="J. Neurochem." volume="122" first="1137" last="1144">
            <title>Molecular basis for the differential sensitivity of rat and human alpha9alpha10 nAChRs to alpha-conotoxin RgIA.</title>
            <authorList>
                <person name="Azam L."/>
                <person name="McIntosh J.M."/>
            </authorList>
            <dbReference type="PubMed" id="22774872"/>
            <dbReference type="DOI" id="10.1111/j.1471-4159.2012.07867.x"/>
        </citation>
        <scope>MUTAGENESIS OF ILE-86</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference evidence="15 16 17" key="9">
        <citation type="journal article" date="2014" name="Nat. Struct. Mol. Biol." volume="21" first="976" last="980">
            <title>Crystal structures of free and antagonist-bound states of human alpha9 nicotinic receptor extracellular domain.</title>
            <authorList>
                <person name="Zouridakis M."/>
                <person name="Giastas P."/>
                <person name="Zarkadas E."/>
                <person name="Chroni-Tzartou D."/>
                <person name="Bregestovski P."/>
                <person name="Tzartos S.J."/>
            </authorList>
            <dbReference type="PubMed" id="25282151"/>
            <dbReference type="DOI" id="10.1038/nsmb.2900"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 26-237 IN COMPLEX WITH SODIUM</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>GLYCOSYLATION</scope>
        <scope>MUTAGENESIS OF THR-172 AND THR-228</scope>
        <scope>SODIUM-BINDING</scope>
        <scope>GLYCOSYLATION AT ASN-57 AND ASN-170</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 4 8 10 11">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:11752216, PubMed:18723036, PubMed:25282151). Forms either homopentamers or heteropentamers with CHRNA10. Expressed in the inner ear, in sympathetic neurons and in other non-neuronal cells, such as skin keratinocytes and lymphocytes (PubMed:11752216, PubMed:18723036). nAChR formed by CHRNA9:CHRNA10 mediate central nervous system control of auditory and vestibular sensory processing. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane (PubMed:11752216, PubMed:25282151). In the ear, mediates synaptic transmission between efferent olivocochlear fibers and hair cells of the cochlea, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma (By similarity). May also regulate keratinocyte adhesion (PubMed:11021840, PubMed:11752216, PubMed:25282151).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>Mg(2+)(in) = Mg(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29827"/>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="9">Activated by a myriad of ligands such as acetylcholine (PubMed:22774872). AChR activity is inhibited by the antagonist alpha-conotoxins RgIA and GeXXA, small disulfide-constrained peptides from cone snails (PubMed:22774872).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4">Forms homo- or heteropentameric channels in conjunction with CHRNA10 (PubMed:11752216). The native outer hair cell receptor is composed of CHRNA9:CHRNA10 heterooligomers. Found in the stoichiometric form (CHRNA9)2:(CHRNA10)3 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008641">
            <id>Q9UGM1</id>
        </interactant>
        <interactant intactId="EBI-16123259">
            <id>P60616</id>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12">Synaptic cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 4 7">Expressed in cochlea, keratinocytes, pituitary gland, B-cells and T-cells.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10">N-glycosylated.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="13">The heterooligomeric receptor composed of CHRNA9 and CHRNA10 has an atypical pharmacological profile, binding several non-nicotinic ligands including strychnine (a glycine receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist).</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-9/CHRNA9 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="AJ243342">
        <property type="protein sequence ID" value="CAB65091.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY123244">
        <property type="protein sequence ID" value="AAM74523.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC118275">
        <property type="protein sequence ID" value="AAY40986.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC113549">
        <property type="protein sequence ID" value="AAI13550.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC113575">
        <property type="protein sequence ID" value="AAI13576.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF227732">
        <property type="protein sequence ID" value="AAF61920.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3459.1"/>
    <dbReference type="RefSeq" id="NP_060051.2">
        <property type="nucleotide sequence ID" value="NM_017581.4"/>
    </dbReference>
    <dbReference type="PDB" id="4D01">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=26-237"/>
    </dbReference>
    <dbReference type="PDB" id="4UXU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.71 A"/>
        <property type="chains" value="A/B=26-237"/>
    </dbReference>
    <dbReference type="PDB" id="4UY2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B=26-237"/>
    </dbReference>
    <dbReference type="PDB" id="6HY7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.26 A"/>
        <property type="chains" value="A=26-237"/>
    </dbReference>
    <dbReference type="PDBsum" id="4D01"/>
    <dbReference type="PDBsum" id="4UXU"/>
    <dbReference type="PDBsum" id="4UY2"/>
    <dbReference type="PDBsum" id="6HY7"/>
    <dbReference type="AlphaFoldDB" id="Q9UGM1"/>
    <dbReference type="SMR" id="Q9UGM1"/>
    <dbReference type="BioGRID" id="120731">
        <property type="interactions" value="80"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2171">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha9-alpha10"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-226">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha9"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9UGM1"/>
    <dbReference type="DIP" id="DIP-61053N"/>
    <dbReference type="FunCoup" id="Q9UGM1">
        <property type="interactions" value="550"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UGM1">
        <property type="interactions" value="50"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000312663"/>
    <dbReference type="BindingDB" id="Q9UGM1"/>
    <dbReference type="ChEMBL" id="CHEMBL2184"/>
    <dbReference type="DrugBank" id="DB05069">
        <property type="generic name" value="ATG003"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00237">
        <property type="generic name" value="Butabarbital"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00565">
        <property type="generic name" value="Cisatracurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05137">
        <property type="generic name" value="Lobeline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00184">
        <property type="generic name" value="Nicotine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05740">
        <property type="generic name" value="RPI-78M"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00202">
        <property type="generic name" value="Succinylcholine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08837">
        <property type="generic name" value="Tetraethylammonium"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="469"/>
    <dbReference type="TCDB" id="1.A.9.1.22">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9UGM1">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UGM1">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UGM1"/>
    <dbReference type="PhosphoSitePlus" id="Q9UGM1"/>
    <dbReference type="BioMuta" id="CHRNA9"/>
    <dbReference type="DMDM" id="308153406"/>
    <dbReference type="jPOST" id="Q9UGM1"/>
    <dbReference type="MassIVE" id="Q9UGM1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000312663"/>
    <dbReference type="PeptideAtlas" id="Q9UGM1"/>
    <dbReference type="ProteomicsDB" id="84234"/>
    <dbReference type="Antibodypedia" id="11757">
        <property type="antibodies" value="109 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55584"/>
    <dbReference type="Ensembl" id="ENST00000310169.3">
        <property type="protein sequence ID" value="ENSP00000312663.2"/>
        <property type="gene ID" value="ENSG00000174343.6"/>
    </dbReference>
    <dbReference type="GeneID" id="55584"/>
    <dbReference type="KEGG" id="hsa:55584"/>
    <dbReference type="MANE-Select" id="ENST00000310169.3">
        <property type="protein sequence ID" value="ENSP00000312663.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_017581.4"/>
        <property type="RefSeq protein sequence ID" value="NP_060051.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003gva.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:14079"/>
    <dbReference type="ClinPGx" id="PA26493"/>
    <dbReference type="CTD" id="55584"/>
    <dbReference type="DisGeNET" id="55584"/>
    <dbReference type="GeneCards" id="CHRNA9"/>
    <dbReference type="HGNC" id="HGNC:14079">
        <property type="gene designation" value="CHRNA9"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000174343">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="MIM" id="605116">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000174343"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000174343"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156077"/>
    <dbReference type="HOGENOM" id="CLU_018074_0_0_1"/>
    <dbReference type="InParanoid" id="Q9UGM1"/>
    <dbReference type="OMA" id="CVYDVGE"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="Q9UGM1">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UGM1"/>
    <dbReference type="PathwayCommons" id="Q9UGM1"/>
    <dbReference type="Reactome" id="R-HSA-629594">
        <property type="pathway name" value="Highly calcium permeable postsynaptic nicotinic acetylcholine receptors"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9667769">
        <property type="pathway name" value="Acetylcholine inhibits contraction of outer hair cells"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UGM1"/>
    <dbReference type="Agora" id="ENSG00000174343"/>
    <dbReference type="BioGRID-ORCS" id="55584">
        <property type="hits" value="7 hits in 1145 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="CHRNA9">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9UGM1"/>
    <dbReference type="GeneWiki" id="CHRNA9"/>
    <dbReference type="GenomeRNAi" id="55584"/>
    <dbReference type="Pharos" id="Q9UGM1">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UGM1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9UGM1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000174343">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 63 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098981">
        <property type="term" value="C:cholinergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099634">
        <property type="term" value="C:postsynaptic specialization membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902495">
        <property type="term" value="C:transmembrane transporter complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022848">
        <property type="term" value="F:acetylcholine-gated monoatomic cation-selective channel activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005262">
        <property type="term" value="F:calcium channel activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005231">
        <property type="term" value="F:excitatory extracellular ligand-gated monoatomic ion channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022850">
        <property type="term" value="F:serotonin-gated monoatomic cation channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0095500">
        <property type="term" value="P:acetylcholine receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050910">
        <property type="term" value="P:detection of mechanical stimulus involved in sensory perception of sound"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042472">
        <property type="term" value="P:inner ear morphogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051899">
        <property type="term" value="P:membrane depolarization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070373">
        <property type="term" value="P:negative regulation of ERK1 and ERK2 cascade"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007204">
        <property type="term" value="P:positive regulation of cytosolic calcium ion concentration"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042391">
        <property type="term" value="P:regulation of membrane potential"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010996">
        <property type="term" value="P:response to auditory stimulus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd19022">
        <property type="entry name" value="LGIC_ECD_nAChR_A9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19051">
        <property type="entry name" value="LGIC_TM_cation"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000009">
        <property type="entry name" value="Cholinergic receptor nicotinic alpha 9 subunit"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000044">
        <property type="entry name" value="neuronal acetylcholine receptor subunit alpha-9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.70.170.10:FF:000010">
        <property type="entry name" value="neuronal acetylcholine receptor subunit alpha-9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
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    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
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    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
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    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
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        <property type="entry name" value="Neuro_actylchol_rec"/>
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    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
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        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
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    <dbReference type="InterPro" id="IPR002394">
        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
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    <dbReference type="NCBIfam" id="TIGR00860">
        <property type="entry name" value="LIC"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00254">
        <property type="entry name" value="NICOTINICR"/>
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    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
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    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0107">Calcium channel</keyword>
    <keyword id="KW-0109">Calcium transport</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000371" description="Neuronal acetylcholine receptor subunit alpha-9">
        <location>
            <begin position="23"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="23"/>
            <end position="238"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="239"/>
            <end position="259"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="269"/>
            <end position="289"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="303"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="324"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="458"/>
            <end position="478"/>
        </location>
    </feature>
    <feature type="binding site" evidence="10 16">
        <location>
            <position position="191"/>
        </location>
        <ligand>
            <name>Na(+)</name>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 16">
        <location>
            <position position="193"/>
        </location>
        <ligand>
            <name>Na(+)</name>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </ligand>
    </feature>
    <feature type="site" description="Key residue important for potent inhibition of the CHRNA9:CHRNA10 receptor by the alpha-conotoxin RgIA (AC P0C1D0)" evidence="1">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10 15 16 17">
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="10 15 16 17">
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="10 15 16 17">
        <location>
            <begin position="155"/>
            <end position="169"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="10 15 16">
        <location>
            <begin position="219"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031151" description="In dbSNP:rs10024518.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060996" description="In dbSNP:rs55633891.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025425" description="In dbSNP:rs10009228." evidence="4 5 6">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="442"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="The CHRNA9:CHRNA10 receptor is 250-fold more potently inhibited by the alpha-conotoxin RgIA." evidence="9">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases response to acetylcholine." evidence="10">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of response to acetylcholine." evidence="10">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="helix" evidence="18">
        <location>
            <begin position="30"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="49"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="56"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="72"/>
            <end position="75"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="76"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="helix" evidence="18">
        <location>
            <begin position="96"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="99"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="104"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="helix" evidence="18">
        <location>
            <begin position="109"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="117"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="134"/>
            <end position="138"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="140"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="156"/>
            <end position="158"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="164"/>
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    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="180"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="183"/>
            <end position="191"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="201"/>
            <end position="207"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="209"/>
            <end position="217"/>
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    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="218"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="224"/>
            <end position="235"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P43144"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="11021840"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11752216"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12697997"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15531379"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="18723036"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22774872"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="25282151"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="18723036"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0000305" key="13">
        <source>
            <dbReference type="PubMed" id="11752216"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="HGNC" id="HGNC:14079"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PDB" id="4D01"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PDB" id="4UXU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PDB" id="4UY2"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="4UXU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="4UY2"/>
        </source>
    </evidence>
    <sequence length="479" mass="54807" checksum="AA6B46B559D6111D" modified="2010-10-05" version="2" precursor="true">MNWSHSCISFCWIYFAASRLRAAETADGKYAQKLFNDLFEDYSNALRPVEDTDKVLNVTLQITLSQIKDMDERNQILTAYLWIRQIWHDAYLTWDRDQYDGLDSIRIPSDLVWRPDIVLYNKADDESSEPVNTNVVLRYDGLITWDAPAITKSSCVVDVTYFPFDNQQCNLTFGSWTYNGNQVDIFNALDSGDLSDFIEDVEWEVHGMPAVKNVISYGCCSEPYPDVTFTLLLKRRSSFYIVNLLIPCVLISFLAPLSFYLPAASGEKVSLGVTILLAMTVFQLMVAEIMPASENVPLIGKYYIATMALITASTALTIMVMNIHFCGAEARPVPHWARVVILKYMSRVLFVYDVGESCLSPHHSRERDHLTKVYSKLPESNLKAARNKDLSRKKDMNKRLKNDLGCQGKNPQEAESYCAQYKVLTRNIEYIAKCLKDHKATNSKGSEWKKVAKVIDRFFMWIFFIMVFVMTILIIARAD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-10-24" modified="2026-01-28" version="240" xmlns="https://uniprot.org/uniprot">
    <accession>Q07912</accession>
    <accession>Q6ZMQ0</accession>
    <accession>Q8N6U7</accession>
    <accession>Q96H59</accession>
    <name>ACK1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Activated CDC42 kinase 1</fullName>
            <shortName>ACK-1</shortName>
            <ecNumber evidence="8 15 17 24 28">2.7.10.2</ecNumber>
            <ecNumber evidence="15 24">2.7.11.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Tyrosine kinase non-receptor protein 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">TNK2</name>
        <name type="synonym">ACK1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Nature" volume="363" first="364" last="367">
            <title>A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42.</title>
            <authorList>
                <person name="Manser E."/>
                <person name="Leung T."/>
                <person name="Salihuddin H."/>
                <person name="Tan L."/>
                <person name="Lim L."/>
            </authorList>
            <dbReference type="PubMed" id="8497321"/>
            <dbReference type="DOI" id="10.1038/363364a0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>INTERACTION WITH CDC42</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>VARIANT LEU-725</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1194" last="1198">
            <title>The DNA sequence, annotation and analysis of human chromosome 3.</title>
            <authorList>
                <person name="Muzny D.M."/>
                <person name="Scherer S.E."/>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>TISSUE SPECIFICITY</scope>
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        <scope>INTERACTION WITH NPHP1</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-881</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>INTERACTION WITH NEDD4</scope>
        <scope>UBIQUITINATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-284 AND SER-724</scope>
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        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION AT TYR-284</scope>
        <scope>DOMAIN SAM-LIKE</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANTS LEU-34; GLN-99; LYS-346 AND ILE-409</scope>
        <scope>CHARACTERIZATION OF VARIANTS LEU-34; GLN-99; LYS-346 AND ILE-409</scope>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>INTERACTION WITH AKT1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANT LYS-346</scope>
        <scope>PHOSPHORYLATION AT TYR-284</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <dbReference type="PubMed" id="20623637"/>
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        <scope>PHOSPHORYLATION AT TYR-284</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>PHOSPHORYLATION AT TYR-284</scope>
        <scope>INTERACTION WITH SRC</scope>
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            <dbReference type="PubMed" id="21169560"/>
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        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION AT TYR-284; TYR-518; TYR-827; TYR-859 AND TYR-872</scope>
    </reference>
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        <scope>REVIEW ON TUMOR GROWTH</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395</scope>
        <scope>PHOSPHORYLATION AT TYR-284</scope>
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            <dbReference type="PubMed" id="17344846"/>
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        <scope>VARIANTS LEU-34; ARG-71; GLN-99; TRP-99; MET-152; LYS-346; ILE-409; SER-507; LEU-725; GLN-748 AND HIS-1038</scope>
    </reference>
    <reference key="39">
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            <title>Mutations in TNK2 in severe autosomal recessive infantile onset epilepsy.</title>
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        <scope>VARIANT MET-638</scope>
        <scope>INTERACTION WITH NEDD4 AND NEDD4L</scope>
        <scope>CHARACTERIZATION OF VARIANT MET-638</scope>
    </reference>
    <comment type="function">
        <text evidence="8 9 14 15 17 18 21 22 26 27 28 29">Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 8 15 17 24 28">
            <text>L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10596"/>
            <dbReference type="Rhea" id="RHEA-COMP:10136"/>
            <dbReference type="Rhea" id="RHEA-COMP:20101"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:46858"/>
            <dbReference type="ChEBI" id="CHEBI:61978"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.10.2"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15 24">
            <text>L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17989"/>
            <dbReference type="Rhea" id="RHEA-COMP:9863"/>
            <dbReference type="Rhea" id="RHEA-COMP:11604"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15 24">
            <text>L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46608"/>
            <dbReference type="Rhea" id="RHEA-COMP:11060"/>
            <dbReference type="Rhea" id="RHEA-COMP:11605"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8 15 28">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="29 30">Inhibited by AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine), which suppresses activating phosphorylation at Tyr-284. Repressed by dasatinib.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 7 13 15 16 18 20 23 24 25 26 28 31 33 34 35">Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity). Homodimer. Interacts with AR, CDC42, WWASL and WWOX. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-745213">
            <id>P29972</id>
            <label>AQP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-702093">
            <id>P56945</id>
            <label>BCAR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-287394">
            <id>P60953-2</id>
            <label>CDC42</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-354967">
            <id>Q00610</id>
            <label>CLTC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-750827">
            <id>P07902</id>
            <label>GALT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-352572">
            <id>P08238</id>
            <label>HSP90AB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-389883">
            <id>P16333</id>
            <label>NCK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-740364">
            <id>Q9HC98</id>
            <label>NEK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-945833">
            <id>Q7Z3S9</id>
            <label>NOTCH2NLA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-6983382">
            <id>O60880</id>
            <label>SH2D1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-77848">
            <id>Q9Y5X1</id>
            <label>SNX9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
        </interactant>
        <interactant intactId="EBI-603457">
            <id>Q07912</id>
            <label>TNK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-3867333">
            <id>A8MQ03</id>
            <label>CYSRT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-10237931">
            <id>Q9BQC3</id>
            <label>DPH2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-750827">
            <id>P07902</id>
            <label>GALT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-79893">
            <id>Q92569</id>
            <label>PIK3R3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-6983382">
            <id>O60880</id>
            <label>SH2D1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11994780">
            <id>Q07912-2</id>
        </interactant>
        <interactant intactId="EBI-3923013">
            <id>O14796</id>
            <label>SH2D1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="28 31">Cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11 28">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="38">Cell junction</location>
            <location evidence="38">Adherens junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasmic vesicle membrane</location>
            <topology>Peripheral membrane protein</topology>
            <orientation evidence="13">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13 21">Cytoplasmic vesicle</location>
            <location evidence="13 21">Clathrin-coated vesicle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="32">Membrane</location>
            <location evidence="32">Clathrin-coated pit</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="27">Cytoplasm</location>
            <location evidence="27">Perinuclear region</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
        <text evidence="2 28">The Tyr-284 phosphorylated form is found both in the membrane and nucleus (By similarity). Co-localizes with EGFR on endosomes (PubMed:20333297). Nuclear translocation is CDC42-dependent (By similarity). Detected in long filamentous cytosolic structures where it co-localizes with CTPS1 (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q07912-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q07912-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_008655 VSP_008656"/>
        </isoform>
        <isoform>
            <id>Q07912-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_037284 VSP_037285 VSP_037286"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14 28 30">The Tyr-284 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. It also shows a significant increase in expression in prostate cancers during the progressive stages.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR.</text>
    </comment>
    <comment type="domain">
        <text evidence="31">The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation.</text>
    </comment>
    <comment type="domain">
        <text evidence="31">The UBA domain binds both poly- and mono-ubiquitin.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12 17 28 30 31 32 33">Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-518 is required for interaction with SRC and is observed during association with clathrin-coated pits.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent (By similarity).</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="38">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the protein kinase superfamily. Tyr protein kinase family.</text>
    </comment>
    <comment type="sequence caution" evidence="38">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAH08884" version="1"/>
        </conflict>
        <text>Unlikely isoform. Aberrant splice sites.</text>
    </comment>
    <comment type="sequence caution" evidence="38">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD18675" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="2.7.10.2" evidence="8 15 17 24 28"/>
    <dbReference type="EC" id="2.7.11.1" evidence="15 24"/>
    <dbReference type="EMBL" id="L13738">
        <property type="protein sequence ID" value="AAA53570.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK131539">
        <property type="protein sequence ID" value="BAD18675.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC124944">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008884">
        <property type="protein sequence ID" value="AAH08884.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC028164">
        <property type="protein sequence ID" value="AAH28164.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33927.2">
        <molecule id="Q07912-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33928.1">
        <molecule id="Q07912-1"/>
    </dbReference>
    <dbReference type="PIR" id="S33596">
        <property type="entry name" value="S33596"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001010938.2">
        <molecule id="Q07912-3"/>
        <property type="nucleotide sequence ID" value="NM_001010938.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001294975.1">
        <property type="nucleotide sequence ID" value="NM_001308046.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001374642.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="NM_001387713.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001374643.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="NM_001387714.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005772.3">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="NM_005781.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047303107.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="XM_047447151.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047303116.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="XM_047447160.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054200839.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="XM_054344864.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054200851.1">
        <molecule id="Q07912-1"/>
        <property type="nucleotide sequence ID" value="XM_054344876.1"/>
    </dbReference>
    <dbReference type="PDB" id="1CF4">
        <property type="method" value="NMR"/>
        <property type="chains" value="B=448-489"/>
    </dbReference>
    <dbReference type="PDB" id="1U46">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=109-395"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=109-395"/>
    </dbReference>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=109-395"/>
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    <dbReference type="PDB" id="3EQP">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=117-392"/>
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        <property type="resolution" value="2.50 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.31 A"/>
        <property type="chains" value="A/B=115-389"/>
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        <property type="chains" value="A/B/C/D=115-453"/>
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        <property type="resolution" value="2.87 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.79 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.78 A"/>
        <property type="chains" value="A/B/C/D=958-1038"/>
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        <property type="resolution" value="3.17 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.81 A"/>
        <property type="chains" value="B=508-519"/>
    </dbReference>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.68 A"/>
        <property type="chains" value="A=954-1038"/>
    </dbReference>
    <dbReference type="PDBsum" id="1CF4"/>
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    <dbReference type="AlphaFoldDB" id="Q07912"/>
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    <dbReference type="BioGRID" id="115485">
        <property type="interactions" value="135"/>
    </dbReference>
    <dbReference type="CORUM" id="Q07912"/>
    <dbReference type="DIP" id="DIP-33858N"/>
    <dbReference type="FunCoup" id="Q07912">
        <property type="interactions" value="728"/>
    </dbReference>
    <dbReference type="IntAct" id="Q07912">
        <property type="interactions" value="73"/>
    </dbReference>
    <dbReference type="MINT" id="Q07912"/>
    <dbReference type="STRING" id="9606.ENSP00000371341"/>
    <dbReference type="BindingDB" id="Q07912"/>
    <dbReference type="ChEMBL" id="CHEMBL4599"/>
    <dbReference type="DrugBank" id="DB18236">
        <property type="generic name" value="(R)-9b"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04367">
        <property type="generic name" value="Debromohymenialdisine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11986">
        <property type="generic name" value="Entrectinib"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB12010">
        <property type="generic name" value="Fostamatinib"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q07912"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="2246"/>
    <dbReference type="GlyCosmos" id="Q07912">
        <property type="glycosylation" value="2 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q07912">
        <property type="glycosylation" value="6 sites, 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q07912"/>
    <dbReference type="PhosphoSitePlus" id="Q07912"/>
    <dbReference type="BioMuta" id="TNK2"/>
    <dbReference type="DMDM" id="229462980"/>
    <dbReference type="CPTAC" id="CPTAC-1779"/>
    <dbReference type="CPTAC" id="CPTAC-2789"/>
    <dbReference type="jPOST" id="Q07912"/>
    <dbReference type="MassIVE" id="Q07912"/>
    <dbReference type="PaxDb" id="9606-ENSP00000371341"/>
    <dbReference type="PeptideAtlas" id="Q07912"/>
    <dbReference type="ProteomicsDB" id="58556">
        <molecule id="Q07912-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58557">
        <molecule id="Q07912-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58558">
        <molecule id="Q07912-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q07912"/>
    <dbReference type="Antibodypedia" id="4095">
        <property type="antibodies" value="764 antibodies from 40 providers"/>
    </dbReference>
    <dbReference type="CPTC" id="Q07912">
        <property type="antibodies" value="5 antibodies"/>
    </dbReference>
    <dbReference type="DNASU" id="10188"/>
    <dbReference type="Ensembl" id="ENST00000333602.14">
        <molecule id="Q07912-1"/>
        <property type="protein sequence ID" value="ENSP00000329425.6"/>
        <property type="gene ID" value="ENSG00000061938.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000439230.6">
        <molecule id="Q07912-2"/>
        <property type="protein sequence ID" value="ENSP00000395588.1"/>
        <property type="gene ID" value="ENSG00000061938.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000671753.1">
        <molecule id="Q07912-3"/>
        <property type="protein sequence ID" value="ENSP00000499858.1"/>
        <property type="gene ID" value="ENSG00000061938.22"/>
    </dbReference>
    <dbReference type="GeneID" id="10188"/>
    <dbReference type="KEGG" id="hsa:10188"/>
    <dbReference type="UCSC" id="uc003fvt.2">
        <molecule id="Q07912-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:19297"/>
    <dbReference type="ClinPGx" id="PA134909759"/>
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    <dbReference type="GeneCards" id="TNK2"/>
    <dbReference type="HGNC" id="HGNC:19297">
        <property type="gene designation" value="TNK2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000061938">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="TNK2"/>
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        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000061938"/>
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        <property type="disease" value="Infantile-onset mesial temporal lobe epilepsy with severe cognitive regression"/>
    </dbReference>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160853"/>
    <dbReference type="HOGENOM" id="CLU_000288_7_39_1"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
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        <property type="organism ID" value="2681"/>
    </dbReference>
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        <property type="pathway name" value="Signaling by LTK"/>
    </dbReference>
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        <property type="hits" value="11 hits in 1191 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="TNK2">
        <property type="organism name" value="human"/>
    </dbReference>
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        <property type="development level" value="Tclin"/>
    </dbReference>
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        <property type="component" value="Chromosome 3"/>
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        <property type="molecule type" value="protein"/>
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    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005912">
        <property type="term" value="C:adherens junction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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        <property type="project" value="Reactome"/>
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        <property type="term" value="C:endosome"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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        <property type="project" value="BHF-UCL"/>
    </dbReference>
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        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="C:perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005154">
        <property type="term" value="F:epidermal growth factor receptor binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005095">
        <property type="term" value="F:GTPase inhibitor activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004715">
        <property type="term" value="F:non-membrane spanning protein tyrosine kinase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0106310">
        <property type="term" value="F:protein serine kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004712">
        <property type="term" value="F:protein serine/threonine/tyrosine kinase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0004713">
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="F:ubiquitin protein ligase binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0050699">
        <property type="term" value="F:WW domain binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="P:cell surface receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006897">
        <property type="term" value="P:endocytosis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0016310">
        <property type="term" value="P:phosphorylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0050731">
        <property type="term" value="P:positive regulation of peptidyl-tyrosine phosphorylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000369">
        <property type="term" value="P:regulation of clathrin-dependent endocytosis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007264">
        <property type="term" value="P:small GTPase-mediated signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd05040">
        <property type="entry name" value="PTKc_Ack_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd09539">
        <property type="entry name" value="SAM_TNK-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd14274">
        <property type="entry name" value="UBA_ACK1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd14328">
        <property type="entry name" value="UBA_TNK1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="DisProt" id="DP01772"/>
    <dbReference type="FunFam" id="4.10.680.10:FF:000001">
        <property type="entry name" value="activated CDC42 kinase 1 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.510.10:FF:000080">
        <property type="entry name" value="Putative activated CDC42 kinase 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.200.20:FF:000107">
        <property type="entry name" value="Putative activated CDC42 kinase 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.680.10">
        <property type="entry name" value="Cdc42-like binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.10">
        <property type="entry name" value="DNA helicase RuvA subunit, C-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.200.20">
        <property type="entry name" value="Phosphorylase Kinase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.510.10">
        <property type="entry name" value="Transferase(Phosphotransferase) domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="IDEAL" id="IID00276"/>
    <dbReference type="InterPro" id="IPR055175">
        <property type="entry name" value="ACK/TNK-like_SAM"/>
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    <dbReference type="InterPro" id="IPR030220">
        <property type="entry name" value="Ack1_UBA_dom"/>
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    <dbReference type="InterPro" id="IPR015116">
        <property type="entry name" value="Cdc42-bd-like"/>
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    <dbReference type="InterPro" id="IPR037085">
        <property type="entry name" value="Cdc42-bd-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052112">
        <property type="entry name" value="EGFR_SigReg_Kinase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR021619">
        <property type="entry name" value="Mig-6"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000719">
        <property type="entry name" value="Prot_kinase_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017441">
        <property type="entry name" value="Protein_kinase_ATP_BS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001245">
        <property type="entry name" value="Ser-Thr/Tyr_kinase_cat_dom"/>
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    <dbReference type="InterPro" id="IPR036028">
        <property type="entry name" value="SH3-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001452">
        <property type="entry name" value="SH3_domain"/>
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    <dbReference type="InterPro" id="IPR049587">
        <property type="entry name" value="TNK-like_SAM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008266">
        <property type="entry name" value="Tyr_kinase_AS"/>
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    <dbReference type="InterPro" id="IPR020635">
        <property type="entry name" value="Tyr_kinase_cat_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14254">
        <property type="entry name" value="GENE 33 POLYPEPTIDE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14254:SF6">
        <property type="entry name" value="NON-SPECIFIC PROTEIN-TYROSINE KINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF09027">
        <property type="entry name" value="GTPase_binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF11555">
        <property type="entry name" value="Inhibitor_Mig-6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07714">
        <property type="entry name" value="PK_Tyr_Ser-Thr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF22931">
        <property type="entry name" value="SAM_TNK"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14604">
        <property type="entry name" value="SH3_9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00109">
        <property type="entry name" value="TYRKINASE"/>
    </dbReference>
    <dbReference type="SMART" id="SM00326">
        <property type="entry name" value="SH3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00219">
        <property type="entry name" value="TyrKc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50044">
        <property type="entry name" value="SH3-domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00107">
        <property type="entry name" value="PROTEIN_KINASE_ATP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50011">
        <property type="entry name" value="PROTEIN_KINASE_DOM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00109">
        <property type="entry name" value="PROTEIN_KINASE_TYR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50002">
        <property type="entry name" value="SH3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0168">Coated pit</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0254">Endocytosis</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0728">SH3 domain</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0829">Tyrosine-protein kinase</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000088058" description="Activated CDC42 kinase 1">
        <location>
            <begin position="1"/>
            <end position="1038"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase" evidence="3">
        <location>
            <begin position="126"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="domain" description="SH3" evidence="4">
        <location>
            <begin position="388"/>
            <end position="448"/>
        </location>
    </feature>
    <feature type="domain" description="CRIB">
        <location>
            <begin position="454"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="domain" description="UBA">
        <location>
            <begin position="958"/>
            <end position="996"/>
        </location>
    </feature>
    <feature type="region of interest" description="SAM-like domain">
        <location>
            <begin position="1"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="90"/>
            <end position="114"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="497"/>
            <end position="535"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with SRC" evidence="33">
        <location>
            <begin position="623"/>
            <end position="652"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with NEDD4" evidence="1">
        <location>
            <begin position="632"/>
            <end position="635"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="659"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="718"/>
            <end position="840"/>
        </location>
    </feature>
    <feature type="region of interest" description="EBD domain" evidence="1">
        <location>
            <begin position="733"/>
            <end position="876"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="917"/>
            <end position="957"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="738"/>
            <end position="749"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="772"/>
            <end position="783"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="794"/>
            <end position="805"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor">
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="132"/>
            <end position="140"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="158"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by SRC and autocatalysis" evidence="12 17 28 30 31 32 33 40">
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="32">
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="40">
        <location>
            <position position="724"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="32">
        <location>
            <position position="827"/>
        </location>
    </feature>
    <feature type="modified residue" description="Omega-N-methylarginine" evidence="2">
        <location>
            <position position="839"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="32">
        <location>
            <position position="859"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="32">
        <location>
            <position position="872"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="39">
        <location>
            <position position="881"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037284" description="In isoform 3." evidence="36">
        <original>M</original>
        <variation>MGERSAYQRLAGGEEGPQRLGGGRM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_008655" description="In isoform 2." evidence="37">
        <original>LYLGNPMDPPDLLSVELSTSRPPQHLGGVKKPTYDPVSEDQDPL</original>
        <variation>CPFSAFSPGHPPAETCGQVLWTGRREACASDPRLHPVSSRTKGL</variation>
        <location>
            <begin position="485"/>
            <end position="528"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037285" description="In isoform 3." evidence="36">
        <original>K</original>
        <variation>KREPPPRPPQPAFFTQ</variation>
        <location>
            <position position="514"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_008656" description="In isoform 2." evidence="37">
        <location>
            <begin position="529"/>
            <end position="1038"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037286" description="In isoform 3." evidence="36">
        <location>
            <begin position="965"/>
            <end position="994"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032792" description="In a lung adenocarcinoma sample; somatic mutation; increased autophosphorylation at Y-284; increased function in phosphorylation of peptide substrates; no effect on subcellular localization to perinuclear region." evidence="19 27">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032793" description="In dbSNP:rs56036945." evidence="19">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032794" description="In an ovarian mucinous carcinoma sample; somatic mutation; increased autophosphorylation at Y-284; increased function in phosphorylation of peptide substrates and WASP; no effect on subcellular localization to perinuclear region; dbSNP:rs113498671." evidence="19 27">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032795" description="In dbSNP:rs3747673." evidence="19">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032796" description="In dbSNP:rs56161912." evidence="19">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032797" description="In an ovarian endometrioid cancer sample; somatic mutation; undergoes autoactivation and causes phosphorylation on Y-284 leading to activation of AKT1; increased autophosphorylation at Y-284; increased function in phosphorylation of peptide substrates and WASP; no effect on catalytic activity itself as the purified kinase domain has activity in vitro comparable to wild-type protein; no effect on subcellular localization to perinuclear region; dbSNP:rs970946035." evidence="19 27 28">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="346"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032798" description="In a gastric adenocarcinoma sample; somatic mutation; increased autophosphorylation at Y-284; increased function in phosphorylation of peptide substrates and WASP; no effect on subcellular localization to perinuclear region." evidence="19 27">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="409"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032799" description="In dbSNP:rs35759128." evidence="19">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="507"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076966" description="Found in patients with childhood-onset epilepsy; uncertain significance; loss of interaction with NEDD4 and NEDD4L; increased protein abundance; dbSNP:rs201407161." evidence="34">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032800" description="In dbSNP:rs56260729." evidence="10 19">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="725"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032801" description="In dbSNP:rs57872314." evidence="19">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="748"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057115" description="In dbSNP:rs3749333.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="802"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032802" description="In dbSNP:rs13433937." evidence="19">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="1038"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on autophosphorylation at Y-284." evidence="27">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of autophosphorylation at Y-284." evidence="16 27">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="158"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on autophosphorylation at Y-284." evidence="27">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased autophosphorylation at Y-284." evidence="27">
        <original>V</original>
        <variation>R</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Constantly active kinase." evidence="16">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="487"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH08884." evidence="38" ref="4">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH08884." evidence="38" ref="4">
        <original>TRTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPR</original>
        <variation>PPWRDISASSSTQFPHAVPCFPTSLLAKLLLRHSVPASSREIKLVSILC</variation>
        <location>
            <begin position="304"/>
            <end position="352"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH08884." evidence="38" ref="4">
        <location>
            <begin position="353"/>
            <end position="1038"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA53570." evidence="38" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="586"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA53570." evidence="38" ref="1">
        <location>
            <position position="722"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA53570." evidence="38" ref="1">
        <original>PRA</original>
        <variation>AG</variation>
        <location>
            <begin position="838"/>
            <end position="840"/>
        </location>
    </feature>
    <feature type="strand" evidence="46">
        <location>
            <begin position="118"/>
            <end position="120"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="123"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="126"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="140"/>
            <end position="146"/>
        </location>
    </feature>
    <feature type="strand" evidence="43">
        <location>
            <begin position="148"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="152"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="turn" evidence="44">
        <location>
            <begin position="164"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="helix" evidence="45">
        <location>
            <begin position="171"/>
            <end position="181"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="192"/>
            <end position="196"/>
        </location>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <dbReference type="DOI" id="10.1124/mol.63.2.332"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>STOICHIOMETRY</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2005" name="Mol. Pharmacol." volume="68" first="1431" last="1438">
            <title>RIC-3 enhances functional expression of multiple nicotinic acetylcholine receptor subtypes in mammalian cells.</title>
            <authorList>
                <person name="Lansdell S.J."/>
                <person name="Gee V.J."/>
                <person name="Harkness P.C."/>
                <person name="Doward A.I."/>
                <person name="Baker E.R."/>
                <person name="Gibb A.J."/>
                <person name="Millar N.S."/>
            </authorList>
            <dbReference type="PubMed" id="16120769"/>
            <dbReference type="DOI" id="10.1124/mol.105.017459"/>
        </citation>
        <scope>INTERACTION WITH RIC3</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2006" name="Mol. Pharmacol." volume="70" first="1358" last="1368">
            <title>Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.</title>
            <authorList>
                <person name="Tumkosit P."/>
                <person name="Kuryatov A."/>
                <person name="Luo J."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="16835356"/>
            <dbReference type="DOI" id="10.1124/mol.106.027326"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2007" name="Mol. Pharmacol." volume="71" first="769" last="776">
            <title>Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors.</title>
            <authorList>
                <person name="Tapia L."/>
                <person name="Kuryatov A."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="17132685"/>
            <dbReference type="DOI" id="10.1124/mol.106.030445"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>STOICHIOMETRY</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF GLU-294</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2011" name="Mol. Pharmacol." volume="79" first="119" last="125">
            <title>Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function.</title>
            <authorList>
                <person name="Kuryatov A."/>
                <person name="Berrettini W."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="20881005"/>
            <dbReference type="DOI" id="10.1124/mol.110.066357"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2016" name="J. Neurochem." volume="138" first="806" last="820">
            <title>Functional interaction between Lypd6 and nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Arvaniti M."/>
                <person name="Jensen M.M."/>
                <person name="Soni N."/>
                <person name="Wang H."/>
                <person name="Klein A.B."/>
                <person name="Thiriet N."/>
                <person name="Pinborg L.H."/>
                <person name="Muldoon P.P."/>
                <person name="Wienecke J."/>
                <person name="Imad Damaj M."/>
                <person name="Kohlmeier K.A."/>
                <person name="Gondre-Lewis M.C."/>
                <person name="Mikkelsen J.D."/>
                <person name="Thomsen M.S."/>
            </authorList>
            <dbReference type="PubMed" id="27344019"/>
            <dbReference type="DOI" id="10.1111/jnc.13718"/>
        </citation>
        <scope>INTERACTION WITH LYPD6</scope>
    </reference>
    <reference evidence="24" key="15">
        <citation type="journal article" date="2012" name="Biochim. Biophys. Acta" volume="1818" first="1261" last="1268">
            <title>NMR structures of the transmembrane domains of the alpha4beta2 nAChR.</title>
            <authorList>
                <person name="Bondarenko V."/>
                <person name="Mowrey D."/>
                <person name="Tillman T."/>
                <person name="Cui T."/>
                <person name="Liu L.T."/>
                <person name="Xu Y."/>
                <person name="Tang P."/>
            </authorList>
            <dbReference type="PubMed" id="22361591"/>
            <dbReference type="DOI" id="10.1016/j.bbamem.2012.02.008"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 242-625</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference evidence="25" key="16">
        <citation type="journal article" date="2016" name="Nature" volume="538" first="411" last="415">
            <title>X-ray structure of the human alpha4beta2 nicotinic receptor.</title>
            <authorList>
                <person name="Morales-Perez C.L."/>
                <person name="Noviello C.M."/>
                <person name="Hibbs R.E."/>
            </authorList>
            <dbReference type="PubMed" id="27698419"/>
            <dbReference type="DOI" id="10.1038/nature19785"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.94 ANGSTROMS) OF 27-364 AND 586-627 IN COMPLEX WITH CHRNB2</scope>
        <scope>GLYCOSYLATION AT ASN-174</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference evidence="26 27" key="17">
        <citation type="journal article" date="2018" name="Nature" volume="557" first="261" last="265">
            <title>Structural principles of distinct assemblies of the human alpha4beta2 nicotinic receptor.</title>
            <authorList>
                <person name="Walsh R.M."/>
                <person name="Roh S.H."/>
                <person name="Gharpure A."/>
                <person name="Morales-Perez C.L."/>
                <person name="Teng J."/>
                <person name="Hibbs R.E."/>
            </authorList>
            <dbReference type="PubMed" id="29720657"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0081-7"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 27-364 AND 586-627 IN COMPLEX WITH CHRNB2</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference evidence="30 31 32 33 34 35" key="18">
        <citation type="journal article" date="2024" name="Br. J. Pharmacol." volume="181" first="1973" last="1992">
            <title>Structural bases for stoichiometry-selective calcium potentiation of a neuronal nicotinic receptor.</title>
            <authorList>
                <person name="Mazzaferro S."/>
                <person name="Kang G."/>
                <person name="Natarajan K."/>
                <person name="Hibbs R.E."/>
                <person name="Sine S.M."/>
            </authorList>
            <dbReference type="PubMed" id="38454578"/>
            <dbReference type="DOI" id="10.1111/bph.16321"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.35 ANGSTROMS) OF 27-627 IN COMPLEX WITH CHRNB2</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>MUTAGENESIS OF ASP-75; GLU-78; GLU-205; GLU-208 AND GLU-224</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="1995" name="Nat. Genet." volume="11" first="201" last="203">
            <title>A missense mutation in the neuronal nicotinic acetylcholine receptor alpha-4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy.</title>
            <authorList>
                <person name="Steinlein O.K."/>
                <person name="Mulley J.C."/>
                <person name="Propping P."/>
                <person name="Wallace R.H."/>
                <person name="Phillips H.A."/>
                <person name="Sutherland G.R."/>
                <person name="Scheffer I.E."/>
                <person name="Berkovic S.F."/>
            </authorList>
            <dbReference type="PubMed" id="7550350"/>
            <dbReference type="DOI" id="10.1038/ng1095-201"/>
        </citation>
        <scope>VARIANT ENFL1 PHE-280</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="1999" name="Neurology" volume="53" first="1749" last="1753">
            <title>A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy.</title>
            <authorList>
                <person name="Hirose S."/>
                <person name="Iwata H."/>
                <person name="Akiyoshi H."/>
                <person name="Kobayashi K."/>
                <person name="Ito M."/>
                <person name="Wada K."/>
                <person name="Kaneko S."/>
                <person name="Mitsudome A."/>
            </authorList>
            <dbReference type="PubMed" id="10563623"/>
            <dbReference type="DOI" id="10.1212/wnl.53.8.1749"/>
        </citation>
        <scope>VARIANT ENFL1 LEU-280</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2003" name="Arch. Neurol." volume="60" first="1625" last="1632">
            <title>A Korean kindred with autosomal dominant nocturnal frontal lobe epilepsy and mental retardation.</title>
            <authorList>
                <person name="Cho Y.-W."/>
                <person name="Motamedi G.K."/>
                <person name="Laufenberg I."/>
                <person name="Sohn S.-I."/>
                <person name="Lim J.-G."/>
                <person name="Lee H."/>
                <person name="Yi S.-D."/>
                <person name="Lee J.-H."/>
                <person name="Kim D.-K."/>
                <person name="Reba R."/>
                <person name="Gaillard W.D."/>
                <person name="Theodore W.H."/>
                <person name="Lesser R.P."/>
                <person name="Steinlein O.K."/>
            </authorList>
            <dbReference type="PubMed" id="14623738"/>
            <dbReference type="DOI" id="10.1001/archneur.60.11.1625"/>
        </citation>
        <scope>VARIANT ENFL1 LEU-280</scope>
    </reference>
    <comment type="function">
        <text evidence="1 11 14 16 17 18">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). CHRNA4 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, as well as CHRNA5 and CHRNB3 as accesory subunits. Is the most abundant nAChR subtype expressed in the central nervous system (PubMed:16835356, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:27698419, PubMed:29720657, PubMed:38454578). Involved in the modulation of calcium-dependent signaling pathways, influences the release of neurotransmitters, including dopamine, glutamate and GABA (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="12 13">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14 18">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="4 8 11 12 13 16 17 18">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:12527804, PubMed:16835356, PubMed:17132685, PubMed:20881005, PubMed:27698419, PubMed:29720657, PubMed:38454578). Channel potentiation by calcium is stoichiometry-selective, CHRNA4:CHRNB2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the CHRNA4 subunit and between the CHRNA4 and CHRNB2 subunits (PubMed:38454578). nAChR activity is inhibited by the antagonist alpha-conotoxins BuIA, PnIA, GID and MII, small disulfide-constrained peptides from cone snails (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4 8 10 11 12 13 14 15 16 17 18">Neuronal AChR is composed of two different types of subunits: alpha and beta (PubMed:22361591). CHRNA4 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, as well as CHRNA5 and CHRNB3 as accesory subunits (PubMed:20881005, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). Found in two major stoichiometric forms, LS (low agonist sensitivity): (CHRNA4)3:(CHRNB2)2 and HS (high agonist sensitivity): (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:12527804, PubMed:17132685, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). Cells produce predominantly an (CHRNA4)3:(CHRNB2)2 nAChR. The (CHRNA4)2:(CHRNB2)3 expression is selectively up-regulated by nicotine and has lower single channel conductance and calcium permeability (PubMed:17132685). In the striatum, also forms CHRNA4:CHRNA6:CHRNB2 complexes (By similarity). Also found in the stoichiometric form: (CHRNA4:CHRNB2)2:CHRNB3 (PubMed:16835356). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-10173507">
            <id>Q6UY14-3</id>
            <label>ADAMTSL4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-78129">
            <id>P83916</id>
            <label>CBX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-21348071">
            <id>Q6UXH1-1</id>
            <label>CRELD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-21348090">
            <id>Q6UXH1-3</id>
            <label>CRELD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-711977">
            <id>P20042</id>
            <label>EIF2S2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-1642131">
            <id>Q9NZR2</id>
            <label>LRP1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7132379">
            <id>P43681</id>
        </interactant>
        <interactant intactId="EBI-1171329">
            <id>Q92673</id>
            <label>SORL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-20716158">
            <id>P43681-1</id>
        </interactant>
        <interactant intactId="EBI-9008612">
            <id>P17787</id>
            <label>CHRNB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Synaptic cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P43681-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P43681-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054275 VSP_054276"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="7 9 19">
        <disease id="DI-00819">
            <name>Epilepsy, nocturnal frontal lobe, 1</name>
            <acronym>ENFL1</acronym>
            <description>An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.</description>
            <dbReference type="MIM" id="600513"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="22">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-4/CHRNA4 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="L35901">
        <property type="protein sequence ID" value="AAA64743.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X89741">
        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X89742">
        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X89743">
        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X89745">
        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X89746">
        <property type="protein sequence ID" value="CAA61893.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U62433">
        <property type="protein sequence ID" value="AAB40111.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08421">
        <property type="protein sequence ID" value="CAA69698.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ093071">
        <property type="protein sequence ID" value="AAY88737.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121827">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC096290">
        <property type="protein sequence ID" value="AAH96290.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC096291">
        <property type="protein sequence ID" value="AAH96291.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X87629">
        <property type="protein sequence ID" value="CAA60959.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13517.1">
        <molecule id="P43681-1"/>
    </dbReference>
    <dbReference type="PIR" id="JC4021">
        <property type="entry name" value="JC4021"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000735.1">
        <molecule id="P43681-1"/>
        <property type="nucleotide sequence ID" value="NM_000744.7"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001243502.1">
        <property type="nucleotide sequence ID" value="NM_001256573.1"/>
    </dbReference>
    <dbReference type="PDB" id="2LLY">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=240-339, A=598-626"/>
    </dbReference>
    <dbReference type="PDB" id="5KXI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.94 A"/>
        <property type="chains" value="A/D=27-364, A/D=586-627"/>
    </dbReference>
    <dbReference type="PDB" id="6CNJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/D=27-364"/>
    </dbReference>
    <dbReference type="PDB" id="6CNK">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="A/B/D=27-364"/>
    </dbReference>
    <dbReference type="PDB" id="6UR8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.71 A"/>
        <property type="chains" value="A/D=27-364, A/D=589-627"/>
    </dbReference>
    <dbReference type="PDB" id="6USF">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.87 A"/>
        <property type="chains" value="A/D=27-358, A/D=589-627"/>
    </dbReference>
    <dbReference type="PDB" id="8SSZ">
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    <keyword id="KW-0887">Epilepsy</keyword>
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    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
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        <location>
            <position position="76"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:29108"/>
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            <position position="271"/>
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            <begin position="225"/>
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<entry dataset="Swiss-Prot" created="1988-04-01" modified="2026-01-28" version="222" xmlns="https://uniprot.org/uniprot">
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            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Muscle fibroblast</tissue>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
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                <person name="Oyama M."/>
                <person name="Hata H."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Tongue</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Am. J. Hum. Genet." volume="79" first="303" last="312">
            <title>Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit.</title>
            <authorList>
                <person name="Hoffmann K."/>
                <person name="Mueller J.S."/>
                <person name="Stricker S."/>
                <person name="Megarbane A."/>
                <person name="Rajab A."/>
                <person name="Lindner T.H."/>
                <person name="Cohen M."/>
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            </authorList>
            <dbReference type="PubMed" id="16826520"/>
            <dbReference type="DOI" id="10.1086/506257"/>
        </citation>
        <scope>VARIANT EVMPS CYS-239</scope>
        <scope>VARIANT LMPS CYS-239</scope>
    </reference>
    <reference key="7">
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                <person name="Greally M.T."/>
                <person name="Tolmie J."/>
                <person name="Pasha S."/>
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                <person name="van Bokhoven H."/>
                <person name="Marton T."/>
                <person name="Al-Gazali L."/>
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                <person name="Oley C."/>
                <person name="Johnson C.A."/>
                <person name="Trembath R.C."/>
                <person name="Brunner H.G."/>
                <person name="Maher E.R."/>
            </authorList>
            <dbReference type="PubMed" id="16826531"/>
            <dbReference type="DOI" id="10.1086/506256"/>
        </citation>
        <scope>VARIANT EVMPS GLY-107</scope>
        <scope>VARIANT LMPS GLY-107</scope>
    </reference>
    <comment type="function">
        <text>After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text>Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains.</text>
    </comment>
    <comment type="interaction">
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-1043191">
            <id>Q9BYQ3</id>
            <label>KRTAP9-3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-724076">
            <id>Q99750</id>
            <label>MDFI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-748397">
            <id>P50222</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-945833">
            <id>Q7Z3S9</id>
            <label>NOTCH2NLA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-22310682">
            <id>P0DPK4</id>
            <label>NOTCH2NLC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-347996">
            <id>O43765</id>
            <label>SGTA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-2822329">
            <id>Q13596</id>
            <label>SNX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11979451">
            <id>P07510-2</id>
        </interactant>
        <interactant intactId="EBI-742487">
            <id>O43597</id>
            <label>SPRY2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P07510-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P07510-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055775"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="4 5">
        <disease id="DI-01895">
            <name>Multiple pterygium syndrome, lethal type</name>
            <acronym>LMPS</acronym>
            <description>Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.</description>
            <dbReference type="MIM" id="253290"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="4 5">
        <disease id="DI-01536">
            <name>Multiple pterygium syndrome, Escobar variant</name>
            <acronym>EVMPS</acronym>
            <description>Non-lethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis.</description>
            <dbReference type="MIM" id="265000"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Gamma/CHRNG sub-subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAY24103" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA25861" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X01715">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01716">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01717">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01718">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01719">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01720">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X01721">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X04759">
        <property type="protein sequence ID" value="CAA25861.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK125362">
        <property type="protein sequence ID" value="BAG54190.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC092165">
        <property type="protein sequence ID" value="AAY24103.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC111802">
        <property type="protein sequence ID" value="AAI11803.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33400.1">
        <molecule id="P07510-1"/>
    </dbReference>
    <dbReference type="PIR" id="A23261">
        <property type="entry name" value="A23261"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005190.4">
        <molecule id="P07510-1"/>
        <property type="nucleotide sequence ID" value="NM_005199.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P07510"/>
    <dbReference type="SMR" id="P07510"/>
    <dbReference type="BioGRID" id="107568">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2179">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma"/>
    </dbReference>
    <dbReference type="FunCoup" id="P07510">
        <property type="interactions" value="408"/>
    </dbReference>
    <dbReference type="IntAct" id="P07510">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000498757"/>
    <dbReference type="BindingDB" id="P07510"/>
    <dbReference type="ChEMBL" id="CHEMBL1907588"/>
    <dbReference type="DrugCentral" id="P07510"/>
    <dbReference type="TCDB" id="1.A.9.1.1">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P07510">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P07510">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P07510"/>
    <dbReference type="PhosphoSitePlus" id="P07510"/>
    <dbReference type="BioMuta" id="CHRNG"/>
    <dbReference type="DMDM" id="126302510"/>
    <dbReference type="jPOST" id="P07510"/>
    <dbReference type="MassIVE" id="P07510"/>
    <dbReference type="PaxDb" id="9606-ENSP00000374145"/>
    <dbReference type="PeptideAtlas" id="P07510"/>
    <dbReference type="ProteomicsDB" id="52012">
        <molecule id="P07510-1"/>
    </dbReference>
    <dbReference type="ABCD" id="P07510">
        <property type="antibodies" value="2 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="20220">
        <property type="antibodies" value="133 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1146"/>
    <dbReference type="Ensembl" id="ENST00000389492.3">
        <molecule id="P07510-2"/>
        <property type="protein sequence ID" value="ENSP00000374143.3"/>
        <property type="gene ID" value="ENSG00000196811.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000651502.1">
        <molecule id="P07510-1"/>
        <property type="protein sequence ID" value="ENSP00000498757.1"/>
        <property type="gene ID" value="ENSG00000196811.13"/>
    </dbReference>
    <dbReference type="GeneID" id="1146"/>
    <dbReference type="KEGG" id="hsa:1146"/>
    <dbReference type="MANE-Select" id="ENST00000651502.1">
        <property type="protein sequence ID" value="ENSP00000498757.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005199.5"/>
        <property type="RefSeq protein sequence ID" value="NP_005190.4"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002vsx.1">
        <molecule id="P07510-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1967"/>
    <dbReference type="ClinPGx" id="PA26499"/>
    <dbReference type="CTD" id="1146"/>
    <dbReference type="DisGeNET" id="1146"/>
    <dbReference type="GeneCards" id="CHRNG"/>
    <dbReference type="HGNC" id="HGNC:1967">
        <property type="gene designation" value="CHRNG"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000196811">
        <property type="expression patterns" value="Tissue enriched (skeletal)"/>
    </dbReference>
    <dbReference type="MalaCards" id="CHRNG"/>
    <dbReference type="MIM" id="100730">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="253290">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="265000">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000196811"/>
    <dbReference type="Orphanet" id="2990">
        <property type="disease" value="Autosomal recessive multiple pterygium syndrome"/>
    </dbReference>
    <dbReference type="Orphanet" id="33108">
        <property type="disease" value="Lethal multiple pterygium syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000196811"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160041"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_4_1"/>
    <dbReference type="InParanoid" id="P07510"/>
    <dbReference type="OMA" id="CVDACNL"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="P07510">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P07510"/>
    <dbReference type="PathwayCommons" id="P07510"/>
    <dbReference type="Reactome" id="R-HSA-629587">
        <property type="pathway name" value="Highly sodium permeable postsynaptic acetylcholine nicotinic receptors"/>
    </dbReference>
    <dbReference type="SignaLink" id="P07510"/>
    <dbReference type="Agora" id="ENSG00000196811"/>
    <dbReference type="BioGRID-ORCS" id="1146">
        <property type="hits" value="26 hits in 1149 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CHRNG"/>
    <dbReference type="GenomeRNAi" id="1146"/>
    <dbReference type="Pharos" id="P07510">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P07510"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="P07510">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000196811">
        <property type="expression patterns" value="Expressed in gastrocnemius and 49 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P07510">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015464">
        <property type="term" value="F:acetylcholine receptor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022848">
        <property type="term" value="F:acetylcholine-gated monoatomic cation-selective channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015267">
        <property type="term" value="F:channel activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0095500">
        <property type="term" value="P:acetylcholine receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051899">
        <property type="term" value="P:membrane depolarization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006936">
        <property type="term" value="P:muscle contraction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003009">
        <property type="term" value="P:skeletal muscle contraction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd19029">
        <property type="entry name" value="LGIC_ECD_nAChR_G"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19064">
        <property type="entry name" value="LGIC_TM_nAChR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000010">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit epsilon"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000036">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit gamma"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.70.170.10:FF:000012">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit gamma"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038050">
        <property type="entry name" value="Neuro_actylchol_rec"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018000">
        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002394">
        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00254">
        <property type="entry name" value="NICOTINICR"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000334" description="Acetylcholine receptor subunit gamma">
        <location>
            <begin position="23"/>
            <end position="517"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="23"/>
            <end position="240"/>
        </location>
    </feature>
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            <title>Nucleotide sequence of the human nicotinic acetylcholine receptor beta 2 subunit gene.</title>
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                <person name="Anand R."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="2">
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            <dbReference type="PubMed" id="8906617"/>
            <dbReference type="DOI" id="10.1007/bf02736842"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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    <reference key="3">
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                <person name="Groot Kormelink P.J."/>
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            <dbReference type="PubMed" id="9009220"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(96)01383-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Frontal cortex</tissue>
        </source>
    </reference>
    <reference key="4">
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                <person name="Rempel N."/>
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            </authorList>
            <dbReference type="PubMed" id="9921897"/>
            <dbReference type="DOI" id="10.1007/s004390050885"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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                <person name="Lueders K.K."/>
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            </authorList>
            <dbReference type="PubMed" id="10441742"/>
            <dbReference type="DOI" id="10.1007/s003359901111"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="7">
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            <title>Assembly of human neuronal nicotinic receptor alpha5 subunits with alpha3, beta2, and beta4 subunits.</title>
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                <person name="Wang F."/>
                <person name="Gerzanich V."/>
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                <person name="Peng X."/>
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                <person name="Lindstrom J."/>
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            <dbReference type="PubMed" id="8663494"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
    </reference>
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            <authorList>
                <person name="Boorman J.P."/>
                <person name="Groot-Kormelink P.J."/>
                <person name="Sivilotti L.G."/>
            </authorList>
            <dbReference type="PubMed" id="11118490"/>
            <dbReference type="DOI" id="10.1111/j.1469-7793.2000.00565.x"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>STOICHIOMETRY</scope>
        <scope>ACTIVITY REGULATION</scope>
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    <reference key="9">
        <citation type="journal article" date="2006" name="Mol. Pharmacol." volume="70" first="1358" last="1368">
            <title>Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.</title>
            <authorList>
                <person name="Tumkosit P."/>
                <person name="Kuryatov A."/>
                <person name="Luo J."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="16835356"/>
            <dbReference type="DOI" id="10.1124/mol.106.027326"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2003" name="Mol. Pharmacol." volume="63" first="332" last="341">
            <title>Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors.</title>
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                <person name="Nelson M.E."/>
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                <person name="Choi C.H."/>
                <person name="Zhou Y."/>
                <person name="Lindstrom J."/>
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            <dbReference type="PubMed" id="12527804"/>
            <dbReference type="DOI" id="10.1124/mol.63.2.332"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>STOICHIOMETRY</scope>
    </reference>
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            <title>Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes.</title>
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                <person name="Ellison M."/>
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            <dbReference type="PubMed" id="15609996"/>
            <dbReference type="DOI" id="10.1021/bi048918g"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SYNTHESIS OF 5-16</scope>
        <scope>3D-STRUCTURE MODELING</scope>
        <scope>ACTIVITY REGULATION</scope>
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                <person name="Lansdell S.J."/>
                <person name="Gee V.J."/>
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            <dbReference type="PubMed" id="16120769"/>
            <dbReference type="DOI" id="10.1124/mol.105.017459"/>
        </citation>
        <scope>INTERACTION WITH RIC3</scope>
    </reference>
    <reference key="13">
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            <title>Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry greatly exceeds that of (alpha4)2(beta2)3 human acetylcholine receptors.</title>
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            <dbReference type="PubMed" id="17132685"/>
            <dbReference type="DOI" id="10.1124/mol.106.030445"/>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>STOICHIOMETRY</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF LYS-285</scope>
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    <reference key="14">
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            <title>Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function.</title>
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                <person name="Kuryatov A."/>
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            <dbReference type="PubMed" id="20881005"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <title>Functional interaction between Lypd6 and nicotinic acetylcholine receptors.</title>
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                <person name="Arvaniti M."/>
                <person name="Jensen M.M."/>
                <person name="Soni N."/>
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                <person name="Klein A.B."/>
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            <dbReference type="PubMed" id="27344019"/>
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        <scope>INTERACTION WITH LYPD6</scope>
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        <scope>MUTAGENESIS OF PHE-197</scope>
        <scope>SUBUNIT</scope>
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            <dbReference type="PubMed" id="33239400"/>
            <dbReference type="DOI" id="10.1523/jneurosci.0876-20.2020"/>
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        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBUNIT</scope>
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                <person name="George A.A."/>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
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        <scope>STRUCTURE BY NMR OF 231-486</scope>
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        <scope>STRUCTURE BY NMR OF 234-484</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (3.94 ANGSTROMS) OF 26-355 AND 446-502</scope>
        <scope>GLYCOSYLATION AT ASN-168 IN COMPLEX WITH CHRNA4</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBUNIT</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 26-353 AND 446-502 IN COMPLEX WITH CHRNA4</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBUNIT</scope>
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        <scope>DISULFIDE BONDS</scope>
        <scope>SUBUNIT</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <title>The nicotinic receptor beta-2 subunit is mutant in nocturnal frontal lobe epilepsy.</title>
            <authorList>
                <person name="De Fusco M."/>
                <person name="Becchetti A."/>
                <person name="Patrignani A."/>
                <person name="Annesi G."/>
                <person name="Gambardella A."/>
                <person name="Quattrone A."/>
                <person name="Ballabio A."/>
                <person name="Wanke E."/>
                <person name="Casari G."/>
            </authorList>
            <dbReference type="PubMed" id="11062464"/>
            <dbReference type="DOI" id="10.1038/81566"/>
        </citation>
        <scope>VARIANT ENFL3 LEU-287</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2001" name="Am. J. Hum. Genet." volume="68" first="225" last="231">
            <title>CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy.</title>
            <authorList>
                <person name="Phillips H.A."/>
                <person name="Favre I."/>
                <person name="Kirkpatrick M."/>
                <person name="Zuberi S.M."/>
                <person name="Goudie D."/>
                <person name="Heron S.E."/>
                <person name="Scheffer I.E."/>
                <person name="Sutherland G.R."/>
                <person name="Berkovic S.F."/>
                <person name="Bertrand D."/>
                <person name="Mulley J.C."/>
            </authorList>
            <dbReference type="PubMed" id="11104662"/>
            <dbReference type="DOI" id="10.1086/316946"/>
        </citation>
        <scope>VARIANT ENFL3 MET-287</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2002" name="Nicotine Tob. Res." volume="4" first="115" last="125">
            <title>Genetic and functional analysis of single nucleotide polymorphisms in the beta2-neuronal nicotinic acetylcholine receptor gene (CHRNB2).</title>
            <authorList>
                <person name="Lueders K.K."/>
                <person name="Hu S."/>
                <person name="McHugh L."/>
                <person name="Myakishev M.V."/>
                <person name="Sirota L.A."/>
                <person name="Hamer D.H."/>
            </authorList>
            <dbReference type="PubMed" id="11906688"/>
            <dbReference type="DOI" id="10.1080/14622200110098419"/>
        </citation>
        <scope>VARIANT HIS-397</scope>
    </reference>
    <comment type="function">
        <text evidence="2 10 12 13 16 17 18 19 20 21">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578). CHRNB2 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3, CHRNA4 and CHRNA6, as well as CHRNA5 and CHRNB3 as accesory subunits (PubMed:16835356, PubMed:20881005, PubMed:22361591, PubMed:27698419, PubMed:29720657, PubMed:38454578, PubMed:8663494). Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation (PubMed:27698419, PubMed:29720657, PubMed:38454578). Heteropentameric channels with CHRNA6 and CHRNA4 exhibit high sensitivity to ACh and nicotine and are predominantly expressed in only a few brain areas, including dopaminergic neurons, norepirephrine neurons and cells of the visual system. nAChrs containing CHRNA6 subunits mediate endogenous cholinergic modulation of dopamine and gamma-aminobutyric acid (GABA) release in response to nicotine at nerve terminals (By similarity). Also forms functional nAChRs with other subunits such as CHRNA7:CHRNB2, mainly expressed in basal forebrain cholinergic neurons (PubMed:33239400, PubMed:38161283).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11 12">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="13 20">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="7 8 10 11 12 16 17 18 19 20">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine (PubMed:12527804, PubMed:16835356, PubMed:17132685, PubMed:20881005, PubMed:27698419, PubMed:29720657, PubMed:38454578). Channel potentiation by calcium is stoichiometry-selective, CHRNA4:CHRNB2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the CHRNA4 subunit and between the CHRNA4 and CHRNB2 subunits (PubMed:38454578). Oligomeric amyloid-beta protein 42 activates specifially CHRNA7:CHRNB2 nAchRs (PubMed:33239400). nAChR activity is inhibited by the antagonist alpha-conotoxins BuIA, PnIA, PnIC, GID and MII, small disulfide-constrained peptides from cone snails (PubMed:15609996, PubMed:38161283).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 7 9 10 11 13 14 16 17 18 19 20 23">Neuronal AChR is a heteropentamer composed of two different types of subunits: alpha and beta. CHRNB2/Beta-2 subunit can be combined to CHRNA2/alpha-2, CHRNA3/alpha-3 or CHRNA4/alpha-4, CHRNA5/alpha-5, CHRNA6/alpha-6 and CHRNB3/beta-3 to give rise to functional receptors. CHRNA2:CHRNB2 and CHRNA4:CHRNB2 nAChR complexes exist in two subtypes: LS (low agonist sensitivity) with a (CHRNA2/4)3:(CHRNB2)2 and HS (high agonist sensitivity) with a (CHRNA2/4)2:(CHRNB2)3 stoichiometry; the subtypes differ in their subunit binding interfaces which are involved in ligand binding (PubMed:12527804, PubMed:16835356, PubMed:17132685, PubMed:22361591, PubMed:27493220, PubMed:27698419, PubMed:29720657, PubMed:38454578). Cells produce predominantly an (CHRNA4)3:(CHRNB2)2 nAChR. The stoichiometric form (CHRNA4)2:(CHRNB2)3 expression is selectively up-regulated by nicotine and has lower single channel conductance and calcium permeability (PubMed:17132685). Also part of the stoichiometric forms: (CHRNA4:CHRNB2)2:CHRNB3 or (CHRNA6:CHRNB2)2:CHRNB3 (PubMed:16835356). Can form heteropentamers with CHRNA7, mainly found in basal forebrain cholinergic neurons (PubMed:33239400, PubMed:38161283). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008612">
            <id>P17787</id>
        </interactant>
        <interactant intactId="EBI-20716158">
            <id>P43681-1</id>
            <label>CHRNA4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9008612">
            <id>P17787</id>
        </interactant>
        <interactant intactId="EBI-6657490">
            <id>P30532</id>
            <label>CHRNA5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Synaptic cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="22">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="4 5">
        <disease id="DI-00820">
            <name>Epilepsy, nocturnal frontal lobe, 3</name>
            <acronym>ENFL3</acronym>
            <description>An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.</description>
            <dbReference type="MIM" id="605375"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="22">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-2/CHRNB2 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X53179">
        <property type="protein sequence ID" value="CAA37320.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U62437">
        <property type="protein sequence ID" value="AAB40115.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08415">
        <property type="protein sequence ID" value="CAA69692.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAA05108.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    </dbReference>
    <dbReference type="EMBL" id="AF077186">
        <property type="protein sequence ID" value="AAD45422.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC075040">
        <property type="protein sequence ID" value="AAH75040.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAH75041.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1070.1"/>
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        <property type="entry name" value="S10505"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="NM_000748.3"/>
    </dbReference>
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        <property type="method" value="NMR"/>
        <property type="chains" value="B=231-265"/>
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        <property type="chains" value="B=264-291"/>
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        <property type="chains" value="A=231-330, A=453-486"/>
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        <property type="chains" value="A=231-330, A=458-485"/>
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    <dbReference type="PDB" id="5KXI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.94 A"/>
        <property type="chains" value="B/C/E=26-355, B/C/E=446-502"/>
    </dbReference>
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    </dbReference>
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        <property type="resolution" value="3.70 A"/>
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    </dbReference>
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        <property type="resolution" value="3.87 A"/>
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        <property type="resolution" value="2.35 A"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
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    <keyword id="KW-0407">Ion channel</keyword>
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    <feature type="chain" id="PRO_0000000379" description="Neuronal acetylcholine receptor subunit beta-2">
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            <begin position="239"/>
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            <begin position="322"/>
            <end position="458"/>
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    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="459"/>
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    <feature type="site" description="Key residue that may interfere with effective access of the conotoxin BuIA to the channel binding site" evidence="2">
        <location>
            <position position="84"/>
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    <feature type="site" description="Key residue for a rapid dissociation (K(off)) from the conotoxin BuIA" evidence="2">
        <location>
            <position position="136"/>
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    <feature type="site" description="Key residue for a rapid dissociation (K(off)) from the conotoxin BuIA" evidence="2">
        <location>
            <position position="144"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="16 27">
        <location>
            <position position="51"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="168"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="485"/>
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    <feature type="disulfide bond" evidence="16 17 20 27 28 29 30 31 32 33 34 35">
        <location>
            <begin position="155"/>
            <end position="169"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012714" description="In ENFL3; dbSNP:rs74315291." evidence="4">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="287"/>
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    </feature>
    <feature type="sequence variant" id="VAR_012715" description="In ENFL3; approximately 10-fold increase in acetylcholine sensitivity; dbSNP:rs74315291." evidence="5">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="287"/>
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    <feature type="sequence variant" id="VAR_021564" description="In dbSNP:rs55685423." evidence="6">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="397"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces CHRNA4:CHRNB2 channel opening potentiation by divalent cations." evidence="20">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="72"/>
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    <feature type="mutagenesis site" description="Reduces CHRNA4:CHRNB2 channel opening potentiation by divalent cations." evidence="20">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="74"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of CHRNA4:CHRNB2 channel opening potentiation by divalent cations." evidence="20">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="196"/>
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    </feature>
    <feature type="mutagenesis site" description="Increases ligand activation in LS and HS nAChR subtypes." evidence="15">
        <original>F</original>
        <variation>Y</variation>
        <location>
            <position position="197"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces CHRNA4:CHRNB2 channel opening potentiation by divalent cations." evidence="20">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="202"/>
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    <feature type="mutagenesis site" description="Reduces CHRNA4:CHRNB2 channel opening potentiation by divalent cations." evidence="20">
        <original>D</original>
        <variation>A</variation>
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            <position position="218"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases Ca(2+) permeability." evidence="11">
        <original>K</original>
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            <position position="285"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAA05108." evidence="22" ref="4">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="26"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAA05108." evidence="22" ref="4">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="426"/>
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    <feature type="sequence conflict" description="In Ref. 4; CAA05108." evidence="22" ref="4">
        <original>S</original>
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            <position position="446"/>
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    <feature type="strand" evidence="39">
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    <sequence length="502" mass="57019" checksum="7EEDEF6ADFDC9F23" modified="1990-08-01" version="1" precursor="true">MARRCGPVALLLGFGLLRLCSGVWGTDTEERLVEHLLDPSRYNKLIRPATNGSELVTVQLMVSLAQLISVHEREQIMTTNVWLTQEWEDYRLTWKPEEFDNMKKVRLPSKHIWLPDVVLYNNADGMYEVSFYSNAVVSYDGSIFWLPPAIYKSACKIEVKHFPFDQQNCTMKFRSWTYDRTEIDLVLKSEVASLDDFTPSGEWDIVALPGRRNENPDDSTYVDITYDFIIRRKPLFYTINLIIPCVLITSLAILVFYLPSDCGEKMTLCISVLLALTVFLLLISKIVPPTSLDVPLVGKYLMFTMVLVTFSIVTSVCVLNVHHRSPTTHTMAPWVKVVFLEKLPALLFMQQPRHHCARQRLRLRRRQREREGAGALFFREAPGADSCTCFVNRASVQGLAGAFGAEPAPVAGPGRSGEPCGCGLREAVDGVRFIADHMRSEDDDQSVSEDWKYVAMVIDRLFLWIFVFVCVFGTIGMFLQPLFQNYTTTTFLHSDHSAPSSK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>Q15822</accession>
    <accession>A8KAX3</accession>
    <accession>B4DK19</accession>
    <accession>J3KMY9</accession>
    <accession>Q9HAQ3</accession>
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            <fullName>Neuronal acetylcholine receptor subunit alpha-2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="14">Nicotinic acetylcholine receptor subunit alpha-2</fullName>
        </alternativeName>
    </protein>
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        <name evidence="16" type="primary">CHRNA2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.</title>
            <authorList>
                <person name="Elliott K.J."/>
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            <dbReference type="PubMed" id="8906617"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-125</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
        <source>
            <tissue>Hypothalamus</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Groot Kormelink P.J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ALA-125</scope>
    </reference>
    <reference key="3">
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                <person name="Yamashita H."/>
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                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
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                <person name="Takami S."/>
                <person name="Terashima Y."/>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
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                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
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                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT ALA-125</scope>
        <source>
            <tissue>Thalamus</tissue>
        </source>
    </reference>
    <reference key="4">
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                <person name="DeCaprio D."/>
                <person name="Dooley K.T."/>
                <person name="Dorris L. III"/>
                <person name="Engels R."/>
                <person name="Gloeckner G."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hall J.L."/>
                <person name="Ishikawa S.K."/>
                <person name="Jaffe D.B."/>
                <person name="Kamat A."/>
                <person name="Kudoh J."/>
                <person name="Lehmann R."/>
                <person name="Lokitsang T."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews C.D."/>
                <person name="Mauceli E."/>
                <person name="Menzel U."/>
                <person name="Mihalev A.H."/>
                <person name="Minoshima S."/>
                <person name="Murayama Y."/>
                <person name="Naylor J.W."/>
                <person name="Nicol R."/>
                <person name="Nguyen C."/>
                <person name="O'Leary S.B."/>
                <person name="O'Neill K."/>
                <person name="Parker S.C.J."/>
                <person name="Polley A."/>
                <person name="Raymond C.K."/>
                <person name="Reichwald K."/>
                <person name="Rodriguez J."/>
                <person name="Sasaki T."/>
                <person name="Schilhabel M."/>
                <person name="Siddiqui R."/>
                <person name="Smith C.L."/>
                <person name="Sneddon T.P."/>
                <person name="Talamas J.A."/>
                <person name="Tenzin P."/>
                <person name="Topham K."/>
                <person name="Venkataraman V."/>
                <person name="Wen G."/>
                <person name="Yamazaki S."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Rosenthal A."/>
                <person name="Birren B.W."/>
                <person name="Platzer M."/>
                <person name="Shimizu N."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16421571"/>
            <dbReference type="DOI" id="10.1038/nature04406"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2009" name="Neuropharmacology" volume="56" first="237" last="246">
            <title>Diversity of vertebrate nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Millar N.S."/>
                <person name="Gotti C."/>
            </authorList>
            <dbReference type="PubMed" id="18723036"/>
            <dbReference type="DOI" id="10.1016/j.neuropharm.2008.07.041"/>
        </citation>
        <scope>REVIEW ON NACHRS DIVERSITY</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2016" name="Proc. Natl. Acad. Sci. U.S.A." volume="113" first="9635" last="9640">
            <title>Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound alpha2 homopentamer.</title>
            <authorList>
                <person name="Kouvatsos N."/>
                <person name="Giastas P."/>
                <person name="Chroni-Tzartou D."/>
                <person name="Poulopoulou C."/>
                <person name="Tzartos S.J."/>
            </authorList>
            <dbReference type="PubMed" id="27493220"/>
            <dbReference type="DOI" id="10.1073/pnas.1602619113"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 59-265</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF TRP-115 AND TYR-225</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2006" name="Am. J. Hum. Genet." volume="79" first="342" last="350">
            <title>Increased sensitivity of the neuronal nicotinic receptor alpha2 subunit causes familial epilepsy with nocturnal wandering and ictal fear.</title>
            <authorList>
                <person name="Aridon P."/>
                <person name="Marini C."/>
                <person name="Di Resta C."/>
                <person name="Brilli E."/>
                <person name="De Fusco M."/>
                <person name="Politi F."/>
                <person name="Parrini E."/>
                <person name="Manfredi I."/>
                <person name="Pisano T."/>
                <person name="Pruna D."/>
                <person name="Curia G."/>
                <person name="Cianchetti C."/>
                <person name="Pasqualetti M."/>
                <person name="Becchetti A."/>
                <person name="Guerrini R."/>
                <person name="Casari G."/>
            </authorList>
            <dbReference type="PubMed" id="16826524"/>
            <dbReference type="DOI" id="10.1086/506459"/>
        </citation>
        <scope>VARIANT ENFL4 ASN-279</scope>
        <scope>CHARACTERIZATION OF VARIANT ENFL4 ASN-279</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2014" name="Neuropharmacology" volume="79" first="715" last="725">
            <title>A signal peptide missense mutation associated with nicotine dependence alters alpha2*-nicotinic acetylcholine receptor function.</title>
            <authorList>
                <person name="Dash B."/>
                <person name="Lukas R.J."/>
                <person name="Li M.D."/>
            </authorList>
            <dbReference type="PubMed" id="24467848"/>
            <dbReference type="DOI" id="10.1016/j.neuropharm.2014.01.021"/>
        </citation>
        <scope>VARIANT ILE-22</scope>
        <scope>CHARACTERIZATION OF VARIANT ILE-22</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2015" name="Epilepsia" volume="56" first="E53" last="E57">
            <title>Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.</title>
            <authorList>
                <person name="Trivisano M."/>
                <person name="Terracciano A."/>
                <person name="Milano T."/>
                <person name="Cappelletti S."/>
                <person name="Pietrafusa N."/>
                <person name="Bertini E.S."/>
                <person name="Vigevano F."/>
                <person name="Specchio N."/>
            </authorList>
            <dbReference type="PubMed" id="25847220"/>
            <dbReference type="DOI" id="10.1111/epi.12967"/>
        </citation>
        <scope>VARIANT BFIS6 TRP-376</scope>
    </reference>
    <comment type="function">
        <text evidence="7 9 13">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:18723036). CHRNA2 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4 and plays a role in nicotine dependence (PubMed:24467848, PubMed:27493220).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="7 9">Neuronal AChR is composed of two different types of subunits: alpha and non-alpha (beta). CHRNA2/alpha-2 subunit can be combined to CHRNB2/beta-2 or CHRNB4/beta-4 to give rise to functional receptors. Both CHRNA2:CHRNB2 and CHRNA2:CHRNB4 nAChR complexes are heteropentamers with two subtypes: LS (low agonist sensitivity) with a (CHRNA2)3:(CHRNB2/4)2 and HS (high agonist sensitivity) with a (CHRNA2)2:(CHRNB2/4)3 stoichiometries; the subtypes differ in their subunit binding interfaces which are involved in ligand binding.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13">Synaptic cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q15822-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15822-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055156"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-00821">
            <name>Epilepsy, nocturnal frontal lobe, 4</name>
            <acronym>ENFL4</acronym>
            <description>An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking.</description>
            <dbReference type="MIM" id="610353"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="8">
        <disease id="DI-05284">
            <name>Seizures, benign familial infantile, 6</name>
            <acronym>BFIS6</acronym>
            <description>A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant.</description>
            <dbReference type="MIM" id="610353"/>
        </disease>
        <text>The disease may be caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-2/CHRNA2 sub-subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="15">With the use of epibatidine as high affinity ligand, an alpha-2 homopentamer has been purified and crystallized. Its physiological relevance has not been proven.</text>
    </comment>
    <dbReference type="EMBL" id="U62431">
        <property type="protein sequence ID" value="AAB40109.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y16281">
        <property type="protein sequence ID" value="CAA76154.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296348">
        <property type="protein sequence ID" value="BAG59031.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311103">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC153866">
        <property type="protein sequence ID" value="AAI53867.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6059.1">
        <molecule id="Q15822-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64856.1">
        <molecule id="Q15822-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000733.2">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="NM_000742.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269384.1">
        <molecule id="Q15822-2"/>
        <property type="nucleotide sequence ID" value="NM_001282455.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047277267.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_047421311.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047277268.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_047421312.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047277269.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_047421313.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054215658.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_054359683.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054215659.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_054359684.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054215660.1">
        <molecule id="Q15822-1"/>
        <property type="nucleotide sequence ID" value="XM_054359685.1"/>
    </dbReference>
    <dbReference type="PDB" id="5FJV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B/C/D/E=59-265"/>
    </dbReference>
    <dbReference type="PDBsum" id="5FJV"/>
    <dbReference type="AlphaFoldDB" id="Q15822"/>
    <dbReference type="SMR" id="Q15822"/>
    <dbReference type="ComplexPortal" id="CPX-2170">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha2-beta2"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2190">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha2-beta4"/>
    </dbReference>
    <dbReference type="CORUM" id="Q15822"/>
    <dbReference type="FunCoup" id="Q15822">
        <property type="interactions" value="493"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000385026"/>
    <dbReference type="BindingDB" id="Q15822"/>
    <dbReference type="ChEMBL" id="CHEMBL2109230"/>
    <dbReference type="ChEMBL" id="CHEMBL2109236"/>
    <dbReference type="DrugBank" id="DB15096">
        <property type="generic name" value="18-methoxycoronaridine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00732">
        <property type="generic name" value="Atracurium besylate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00237">
        <property type="generic name" value="Butabarbital"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00411">
        <property type="generic name" value="Carbamoylcholine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00122">
        <property type="generic name" value="Choline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00565">
        <property type="generic name" value="Cisatracurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09028">
        <property type="generic name" value="Cytisine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01245">
        <property type="generic name" value="Decamethonium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00514">
        <property type="generic name" value="Dextromethorphan"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01135">
        <property type="generic name" value="Doxacurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB07720">
        <property type="generic name" value="Epibatidine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00472">
        <property type="generic name" value="Fluoxetine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00483">
        <property type="generic name" value="Gallamine triethiodide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08960">
        <property type="generic name" value="Hexamethonium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00504">
        <property type="generic name" value="Levallorphan"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00657">
        <property type="generic name" value="Mecamylamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01336">
        <property type="generic name" value="Metocurine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00416">
        <property type="generic name" value="Metocurine iodide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01226">
        <property type="generic name" value="Mivacurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00184">
        <property type="generic name" value="Nicotine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01337">
        <property type="generic name" value="Pancuronium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01338">
        <property type="generic name" value="Pipecuronium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00721">
        <property type="generic name" value="Procaine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00728">
        <property type="generic name" value="Rocuronium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05740">
        <property type="generic name" value="RPI-78M"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00202">
        <property type="generic name" value="Succinylcholine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB06402">
        <property type="generic name" value="Telavancin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01199">
        <property type="generic name" value="Tubocurarine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01339">
        <property type="generic name" value="Vecuronium"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q15822"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="463"/>
    <dbReference type="GlyCosmos" id="Q15822">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15822">
        <property type="glycosylation" value="3 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15822"/>
    <dbReference type="PhosphoSitePlus" id="Q15822"/>
    <dbReference type="BioMuta" id="CHRNA2"/>
    <dbReference type="DMDM" id="308153405"/>
    <dbReference type="PaxDb" id="9606-ENSP00000385026"/>
    <dbReference type="PeptideAtlas" id="Q15822"/>
    <dbReference type="ProteomicsDB" id="60776">
        <molecule id="Q15822-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="10197">
        <property type="antibodies" value="165 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1135"/>
    <dbReference type="Ensembl" id="ENST00000240132.7">
        <molecule id="Q15822-2"/>
        <property type="protein sequence ID" value="ENSP00000240132.2"/>
        <property type="gene ID" value="ENSG00000120903.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000407991.3">
        <molecule id="Q15822-1"/>
        <property type="protein sequence ID" value="ENSP00000385026.1"/>
        <property type="gene ID" value="ENSG00000120903.13"/>
    </dbReference>
    <dbReference type="GeneID" id="1135"/>
    <dbReference type="KEGG" id="hsa:1135"/>
    <dbReference type="MANE-Select" id="ENST00000407991.3">
        <property type="protein sequence ID" value="ENSP00000385026.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000742.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000733.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010lur.4">
        <molecule id="Q15822-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1956"/>
    <dbReference type="ClinPGx" id="PA26489"/>
    <dbReference type="CTD" id="1135"/>
    <dbReference type="DisGeNET" id="1135"/>
    <dbReference type="GeneCards" id="CHRNA2"/>
    <dbReference type="GeneReviews" id="CHRNA2"/>
    <dbReference type="HGNC" id="HGNC:1956">
        <property type="gene designation" value="CHRNA2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000120903">
        <property type="expression patterns" value="Tissue enriched (prostate)"/>
    </dbReference>
    <dbReference type="MalaCards" id="CHRNA2"/>
    <dbReference type="MIM" id="118502">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="610353">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000120903"/>
    <dbReference type="Orphanet" id="98784">
        <property type="disease" value="Sleep-related hypermotor epilepsy"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000120903"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158299"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_0_1"/>
    <dbReference type="InParanoid" id="Q15822"/>
    <dbReference type="OMA" id="SSYHWLE"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="Q15822">
        <property type="GO annotations" value="10 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q15822"/>
    <dbReference type="PathwayCommons" id="Q15822"/>
    <dbReference type="Reactome" id="R-HSA-629594">
        <property type="pathway name" value="Highly calcium permeable postsynaptic nicotinic acetylcholine receptors"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-629597">
        <property type="pathway name" value="Highly calcium permeable nicotinic acetylcholine receptors"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q15822"/>
    <dbReference type="Agora" id="ENSG00000120903"/>
    <dbReference type="BioGRID-ORCS" id="1135">
        <property type="hits" value="15 hits in 1164 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="CHRNA2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CHRNA2"/>
    <dbReference type="GenomeRNAi" id="1135"/>
    <dbReference type="Pharos" id="Q15822">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q15822"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q15822">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000120903">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 139 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q15822">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0034703">
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        <property type="entry name" value="Neur_chan_LBD"/>
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        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NRIONCHANNEL"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
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    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
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        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
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    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
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    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <feature type="topological domain" description="Cytoplasmic">
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            <begin position="27"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="79"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="129"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
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            <begin position="183"/>
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    </feature>
    <feature type="disulfide bond" description="Associated with receptor activation" evidence="9 17">
        <location>
            <begin position="247"/>
            <end position="248"/>
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    </feature>
    <feature type="splice variant" id="VSP_055156" description="In isoform 2." evidence="12">
        <location>
            <begin position="82"/>
            <end position="96"/>
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    <feature type="sequence variant" id="VAR_027639" description="Associated with nicotine dependence; decreased response to acetylcholine and nicotine of LS nAChRs and increased response to acetylcholine and nicotine of HS nAChRs; dbSNP:rs2472553." evidence="7">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="22"/>
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    </feature>
    <feature type="sequence variant" id="VAR_027640" description="In dbSNP:rs891398." evidence="5 10 11">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027641" description="In ENFL4; markedly increases receptor sensitivity to acetylcholine; dbSNP:rs104894063." evidence="6">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076498" description="In BFIS6; uncertain significance; dbSNP:rs1018084204." evidence="8">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Changes ligand activation kinetics in a alpha-2(+):alpha-2(-) subunit interface (in LS nAChR subtype)." evidence="9">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases ligand activation in LS nAChR subtype; no effect in HS nAChR subtype." evidence="9">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="225"/>
        </location>
    </feature>
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            <begin position="61"/>
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    </feature>
    <feature type="strand" evidence="18">
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            <begin position="74"/>
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    <feature type="strand" evidence="18">
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            <begin position="78"/>
            <end position="82"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="84"/>
            <end position="99"/>
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    </feature>
    <feature type="turn" evidence="18">
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            <begin position="100"/>
            <end position="103"/>
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    </feature>
    <feature type="strand" evidence="18">
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    </feature>
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            <begin position="118"/>
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    </feature>
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        <location>
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    </feature>
    <feature type="strand" evidence="18">
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    <feature type="strand" evidence="18">
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    </feature>
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    </feature>
    <feature type="turn" evidence="18">
        <location>
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    </feature>
    <feature type="strand" evidence="18">
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    <feature type="strand" evidence="18">
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    <feature type="strand" evidence="18">
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    <feature type="strand" evidence="18">
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    </feature>
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        <location>
            <begin position="208"/>
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    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="211"/>
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    </feature>
    <feature type="turn" evidence="18">
        <location>
            <begin position="217"/>
            <end position="219"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="237"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="strand" evidence="18">
        <location>
            <begin position="248"/>
            <end position="258"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P02709"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P43681"/>
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    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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        <source>
            <dbReference type="PubMed" id="16826524"/>
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24467848"/>
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    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="25847220"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="27493220"/>
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    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="8906617"/>
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    <evidence type="ECO:0000269" key="11">
        <source ref="2"/>
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        <source>
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    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="18723036"/>
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    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="27493220"/>
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    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:1956"/>
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    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PDB" id="5FJV"/>
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    </evidence>
    <evidence type="ECO:0007829" key="18">
        <source>
            <dbReference type="PDB" id="5FJV"/>
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    <sequence length="529" mass="59765" checksum="E47062A1145E8BCC" modified="2010-10-05" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="219" xmlns="https://uniprot.org/uniprot">
    <accession>Q07001</accession>
    <accession>A8K661</accession>
    <accession>B4DT92</accession>
    <accession>Q52LH4</accession>
    <name>ACHD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">Acetylcholine receptor subunit delta</fullName>
        </recommendedName>
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    <gene>
        <name evidence="16" type="primary">CHRND</name>
        <name type="synonym">ACHRD</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="J. Neurosci." volume="9" first="1082" last="1096">
            <title>A muscle acetylcholine receptor is expressed in the human cerebellar medulloblastoma cell line TE671.</title>
            <authorList>
                <person name="Luther M.A."/>
                <person name="Schoepfer R."/>
                <person name="Whiting P."/>
                <person name="Casey B."/>
                <person name="Blatt Y."/>
                <person name="Montal M.S."/>
                <person name="Montal M."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="2564429"/>
            <dbReference type="DOI" id="10.1523/jneurosci.09-03-01082.1989"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
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    </reference>
    <comment type="function">
        <text evidence="12">After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="7">Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q07001-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q07001-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046423"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-01895">
            <name>Multiple pterygium syndrome, lethal type</name>
            <acronym>LMPS</acronym>
            <description>Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.</description>
            <dbReference type="MIM" id="253290"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-04394">
            <name>Myasthenic syndrome, congenital, 3A, slow-channel</name>
            <acronym>CMS3A</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.</description>
            <dbReference type="MIM" id="616321"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="4 6 11">
        <disease id="DI-04395">
            <name>Myasthenic syndrome, congenital, 3B, fast-channel</name>
            <acronym>CMS3B</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.</description>
            <dbReference type="MIM" id="616322"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="8 11">
        <disease id="DI-04399">
            <name>Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency</name>
            <acronym>CMS3C</acronym>
            <description>A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.</description>
            <dbReference type="MIM" id="616323"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Delta/CHRND sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X55019">
        <property type="protein sequence ID" value="CAA38759.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291526">
        <property type="protein sequence ID" value="BAF84215.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300109">
        <property type="protein sequence ID" value="BAG61904.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315297">
        <property type="protein sequence ID" value="BAG37703.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC092165">
        <property type="protein sequence ID" value="AAY24102.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471063">
        <property type="protein sequence ID" value="EAW71003.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093923">
        <property type="protein sequence ID" value="AAH93923.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093925">
        <property type="protein sequence ID" value="AAH93925.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2494.1">
        <molecule id="Q07001-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58754.1">
        <molecule id="Q07001-2"/>
    </dbReference>
    <dbReference type="PIR" id="A60916">
        <property type="entry name" value="A60916"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000742.1">
        <molecule id="Q07001-1"/>
        <property type="nucleotide sequence ID" value="NM_000751.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001243586.1">
        <molecule id="Q07001-2"/>
        <property type="nucleotide sequence ID" value="NM_001256657.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001298124.1">
        <property type="nucleotide sequence ID" value="NM_001311195.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001298125.1">
        <property type="nucleotide sequence ID" value="NM_001311196.1"/>
    </dbReference>
    <dbReference type="PDB" id="9DMG">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMH">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.19 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMK">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.46 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DML">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.24 A"/>
        <property type="chains" value="H=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMQ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.06 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMS">
        <property type="method" value="EM"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMT">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.18 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9DMV">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.13 A"/>
        <property type="chains" value="D=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="9GU0">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.96 A"/>
        <property type="chains" value="D=22-517"/>
    </dbReference>
    <dbReference type="PDB" id="9GU1">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.48 A"/>
        <property type="chains" value="D=22-517"/>
    </dbReference>
    <dbReference type="PDB" id="9GU2">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.73 A"/>
        <property type="chains" value="D=22-517"/>
    </dbReference>
    <dbReference type="PDB" id="9GU3">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.64 A"/>
        <property type="chains" value="D=22-517"/>
    </dbReference>
    <dbReference type="PDBsum" id="9DMG"/>
    <dbReference type="PDBsum" id="9DMH"/>
    <dbReference type="PDBsum" id="9DMJ"/>
    <dbReference type="PDBsum" id="9DMK"/>
    <dbReference type="PDBsum" id="9DML"/>
    <dbReference type="PDBsum" id="9DMQ"/>
    <dbReference type="PDBsum" id="9DMS"/>
    <dbReference type="PDBsum" id="9DMT"/>
    <dbReference type="PDBsum" id="9DMV"/>
    <dbReference type="PDBsum" id="9GU0"/>
    <dbReference type="PDBsum" id="9GU1"/>
    <dbReference type="PDBsum" id="9GU2"/>
    <dbReference type="PDBsum" id="9GU3"/>
    <dbReference type="AlphaFoldDB" id="Q07001"/>
    <dbReference type="EMDB" id="EMD-47003"/>
    <dbReference type="EMDB" id="EMD-47005"/>
    <dbReference type="EMDB" id="EMD-47007"/>
    <dbReference type="EMDB" id="EMD-47008"/>
    <dbReference type="EMDB" id="EMD-47009"/>
    <dbReference type="EMDB" id="EMD-47013"/>
    <dbReference type="EMDB" id="EMD-47014"/>
    <dbReference type="EMDB" id="EMD-47015"/>
    <dbReference type="EMDB" id="EMD-47017"/>
    <dbReference type="EMDB" id="EMD-51568"/>
    <dbReference type="EMDB" id="EMD-51569"/>
    <dbReference type="EMDB" id="EMD-51570"/>
    <dbReference type="EMDB" id="EMD-51571"/>
    <dbReference type="SMR" id="Q07001"/>
    <dbReference type="BioGRID" id="107566">
        <property type="interactions" value="67"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2179">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-gamma"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-255">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26535">
        <property type="entry name" value="Muscle-type nicotinic acetylcholine receptor complex, alpha1-beta1-delta-epsilon"/>
    </dbReference>
    <dbReference type="CORUM" id="Q07001"/>
    <dbReference type="FunCoup" id="Q07001">
        <property type="interactions" value="440"/>
    </dbReference>
    <dbReference type="IntAct" id="Q07001">
        <property type="interactions" value="71"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000258385"/>
    <dbReference type="BindingDB" id="Q07001"/>
    <dbReference type="ChEMBL" id="CHEMBL3011"/>
    <dbReference type="DrugCentral" id="Q07001"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="476"/>
    <dbReference type="TCDB" id="1.A.9.1.1">
        <property type="family name" value="the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q07001">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q07001">
        <property type="glycosylation" value="2 sites, 3 N-linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q07001"/>
    <dbReference type="PhosphoSitePlus" id="Q07001"/>
    <dbReference type="BioMuta" id="CHRND"/>
    <dbReference type="DMDM" id="543759"/>
    <dbReference type="jPOST" id="Q07001"/>
    <dbReference type="MassIVE" id="Q07001"/>
    <dbReference type="PaxDb" id="9606-ENSP00000258385"/>
    <dbReference type="PeptideAtlas" id="Q07001"/>
    <dbReference type="ABCD" id="Q07001">
        <property type="antibodies" value="1 sequenced antibody"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="20219">
        <property type="antibodies" value="193 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1144"/>
    <dbReference type="Ensembl" id="ENST00000258385.8">
        <molecule id="Q07001-1"/>
        <property type="protein sequence ID" value="ENSP00000258385.3"/>
        <property type="gene ID" value="ENSG00000135902.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000543200.5">
        <molecule id="Q07001-2"/>
        <property type="protein sequence ID" value="ENSP00000438380.1"/>
        <property type="gene ID" value="ENSG00000135902.11"/>
    </dbReference>
    <dbReference type="GeneID" id="1144"/>
    <dbReference type="KEGG" id="hsa:1144"/>
    <dbReference type="MANE-Select" id="ENST00000258385.8">
        <property type="protein sequence ID" value="ENSP00000258385.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000751.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000742.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002vsw.5">
        <molecule id="Q07001-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1965"/>
    <dbReference type="ClinPGx" id="PA26497"/>
    <dbReference type="CTD" id="1144"/>
    <dbReference type="DisGeNET" id="1144"/>
    <dbReference type="GeneCards" id="CHRND"/>
    <dbReference type="GeneReviews" id="CHRND"/>
    <dbReference type="HGNC" id="HGNC:1965">
        <property type="gene designation" value="CHRND"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000135902">
        <property type="expression patterns" value="Tissue enriched (skeletal)"/>
    </dbReference>
    <dbReference type="MalaCards" id="CHRND"/>
    <dbReference type="MIM" id="100720">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="253290">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="616321">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="616322">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="616323">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000135902"/>
    <dbReference type="Orphanet" id="33108">
        <property type="disease" value="Lethal multiple pterygium syndrome"/>
    </dbReference>
    <dbReference type="Orphanet" id="98913">
        <property type="disease" value="Postsynaptic congenital myasthenic syndromes"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000135902"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159794"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_4_1"/>
    <dbReference type="InParanoid" id="Q07001"/>
    <dbReference type="OMA" id="NFIVSHM"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="Q07001">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q07001"/>
    <dbReference type="PathwayCommons" id="Q07001"/>
    <dbReference type="Reactome" id="R-HSA-629587">
        <property type="pathway name" value="Highly sodium permeable postsynaptic acetylcholine nicotinic receptors"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q07001"/>
    <dbReference type="Agora" id="ENSG00000135902"/>
    <dbReference type="BioGRID-ORCS" id="1144">
        <property type="hits" value="26 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CHRND"/>
    <dbReference type="GenomeRNAi" id="1144"/>
    <dbReference type="Pharos" id="Q07001">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q07001"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q07001">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000135902">
        <property type="expression patterns" value="Expressed in gastrocnemius and 71 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q07001">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005892">
        <property type="term" value="C:acetylcholine-gated channel complex"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031594">
        <property type="term" value="C:neuromuscular junction"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043005">
        <property type="term" value="C:neuron projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045211">
        <property type="term" value="C:postsynaptic membrane"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099634">
        <property type="term" value="C:postsynaptic specialization membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045202">
        <property type="term" value="C:synapse"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042166">
        <property type="term" value="F:acetylcholine binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015464">
        <property type="term" value="F:acetylcholine receptor activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022848">
        <property type="term" value="F:acetylcholine-gated monoatomic cation-selective channel activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904315">
        <property type="term" value="F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0095500">
        <property type="term" value="P:acetylcholine receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="ComplexPortal"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007268">
        <property type="term" value="P:chemical synaptic transmission"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051899">
        <property type="term" value="P:membrane depolarization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034220">
        <property type="term" value="P:monoatomic ion transmembrane transport"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006936">
        <property type="term" value="P:muscle contraction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050881">
        <property type="term" value="P:musculoskeletal movement"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050905">
        <property type="term" value="P:neuromuscular process"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003009">
        <property type="term" value="P:skeletal muscle contraction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048630">
        <property type="term" value="P:skeletal muscle tissue growth"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd19028">
        <property type="entry name" value="LGIC_ECD_nAChR_D"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19064">
        <property type="entry name" value="LGIC_TM_nAChR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.390:FF:000029">
        <property type="entry name" value="acetylcholine receptor subunit delta isoform X1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.20.58.390:FF:000010">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit epsilon"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.70.170.10:FF:000012">
        <property type="entry name" value="Nicotinic acetylcholine receptor subunit gamma"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.70.170.10">
        <property type="entry name" value="Neurotransmitter-gated ion-channel ligand-binding domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.58.390">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane domain"/>
        <property type="match status" value="2"/>
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    <dbReference type="InterPro" id="IPR006202">
        <property type="entry name" value="Neur_chan_lig-bd"/>
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    <dbReference type="InterPro" id="IPR036734">
        <property type="entry name" value="Neur_chan_lig-bd_sf"/>
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    <dbReference type="InterPro" id="IPR006201">
        <property type="entry name" value="Neur_channel"/>
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    <dbReference type="InterPro" id="IPR036719">
        <property type="entry name" value="Neuro-gated_channel_TM_sf"/>
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    <dbReference type="InterPro" id="IPR038050">
        <property type="entry name" value="Neuro_actylchol_rec"/>
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    <dbReference type="InterPro" id="IPR006029">
        <property type="entry name" value="Neurotrans-gated_channel_TM"/>
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    <dbReference type="InterPro" id="IPR018000">
        <property type="entry name" value="Neurotransmitter_ion_chnl_CS"/>
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    <dbReference type="InterPro" id="IPR002394">
        <property type="entry name" value="Nicotinic_acetylcholine_rcpt"/>
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    <dbReference type="NCBIfam" id="TIGR00860">
        <property type="entry name" value="LIC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR18945">
        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02931">
        <property type="entry name" value="Neur_chan_LBD"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF02932">
        <property type="entry name" value="Neur_chan_memb"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00254">
        <property type="entry name" value="NICOTINICR"/>
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    <dbReference type="PRINTS" id="PR00252">
        <property type="entry name" value="NRIONCHANNEL"/>
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    <dbReference type="SUPFAM" id="SSF90112">
        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF63712">
        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00236">
        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1004">Congenital myasthenic syndrome</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0628">Postsynaptic cell membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="1">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000322" description="Acetylcholine receptor subunit delta">
        <location>
            <begin position="22"/>
            <end position="517"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="22"/>
            <end position="245"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="246"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="278"/>
            <end position="299"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="312"/>
            <end position="333"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="334"/>
            <end position="471"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="472"/>
            <end position="490"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by Tyr-kinases" evidence="1">
        <location>
            <position position="390"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="151"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046423" description="In isoform 2." evidence="14">
        <location>
            <begin position="67"/>
            <end position="81"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073691" description="In CMS3B; results in reduced gating efficiency; slows opening of the channel; decreases probability that the channel will open in response to ACh." evidence="11">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073692" description="In CMS3B; prevents expression of the AChR on the cell surface; is a null mutation; dbSNP:rs121909509." evidence="11">
        <original>I</original>
        <variation>K</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021210" description="In CMS3B; reduced adult and fetal AChR expression and a reduced probability of both adult and fetal AChR being in the open state; dbSNP:rs121909504." evidence="4">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043905" description="In LMPS; dbSNP:rs121909506." evidence="10">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073693" description="Has no appreciable kinetic effects; allows for robust AChR expression; dbSNP:rs760395222." evidence="11">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021211" description="In CMS3B; burst duration was decreased and disassociation of ACh was increased resulting in brief channel opening episodes; shows abnormal association with alpha CHRNA1 subunit resulting in a decreased number of fully assembled AChRs; dbSNP:rs121909503." evidence="6">
        <original>P</original>
        <variation>Q</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021212" description="In dbSNP:rs41265127." evidence="13">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="288"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019566" description="In CMS3A; delayed closure of AchR ion channels, increasing the propensity for open-channel block, as well as a reduced rate of channel opening; dbSNP:rs121909502." evidence="5">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036031" description="In a breast cancer sample; somatic mutation; dbSNP:rs749461400." evidence="9">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073694" description="In CMS3C; results in reduced expression of the AChR at the cell surface; impairs normal clustering of the AChR channel with RAPSN; dbSNP:rs145955590." evidence="8">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="402"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increased length of channel opening." evidence="12">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="290"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P04759"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11435464"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11782989"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12499478"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15609996"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16916845"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18252226"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18398509"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="27375219"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="8872460"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:1965"/>
        </source>
    </evidence>
    <sequence length="517" mass="58895" checksum="195CEF69358758BD" modified="1994-06-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-04-01" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>P30532</accession>
    <accession>Q15824</accession>
    <accession>Q99554</accession>
    <name>ACHA5_HUMAN</name>
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        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit alpha-5</fullName>
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        <name evidence="14" type="primary">CHRNA5</name>
        <name type="synonym">NACHRA5</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Eye</tissue>
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            <dbReference type="PubMed" id="8663494"/>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
    </reference>
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            <title>Functional interaction between Lypd6 and nicotinic acetylcholine receptors.</title>
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        <scope>INTERACTION WITH LYPD6</scope>
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            </authorList>
            <dbReference type="PubMed" id="18385720"/>
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        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
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            <dbReference type="DOI" id="10.1038/ng.109"/>
        </citation>
        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="Mol. Pharmacol." volume="79" first="119" last="125">
            <title>Acetylcholine receptor (AChR) alpha5 subunit variant associated with risk for nicotine dependence and lung cancer reduces (alpha4beta2)(2)alpha5 AChR function.</title>
            <authorList>
                <person name="Kuryatov A."/>
                <person name="Berrettini W."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="20881005"/>
            <dbReference type="DOI" id="10.1124/mol.110.066357"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>CHARACTERIZATION OF VARIANT ASN-398</scope>
        <scope>INVOLVEMENT IN SQTL3 AND LUNG CANCER</scope>
    </reference>
    <comment type="function">
        <text evidence="8 10">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:20881005, PubMed:8663494). Has an accessory rather than functional role and is only able to form functional nAChRs when co-assembled with another beta subunit (PubMed:20881005, PubMed:8663494). Participates in pentameric assemblies along with CHRNA3, CHRNA4, CHRNB2 and CHRNB4 (PubMed:20881005, PubMed:8663494). Increases receptor sensitivity to acetylcholine and nicotine when associated with CHRNA4 and CHRNB2 (PubMed:8663494). Plays a role in nicotine addiction (PubMed:20881005).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="8 10">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 9 10">Neuronal AChR that forms heteropentamers composed of two different type of subunits: alpha and non-alpha (beta). CHRNA5/alpha-5 subunit is only able to form functional nAChRs when co-assembled with another alpha subunit, can be combined to CHRNA4/alpha-4 or CHRNA3/alpha-3 and CHRNB4/beta-4 or CHRNB2/beta-2 to give rise to functional receptors (PubMed:20881005, PubMed:8663494). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6657490">
            <id>P30532</id>
        </interactant>
        <interactant intactId="EBI-9008612">
            <id>P17787</id>
            <label>CHRNB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Synaptic cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="polymorphism">
        <text evidence="5 6 7 8">Genetic variations in CHRNA5 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M83712">
        <property type="protein sequence ID" value="AAA58357.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U62434">
        <property type="protein sequence ID" value="AAB40112.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08419">
        <property type="protein sequence ID" value="CAA69696.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAC34820.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    </dbReference>
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        <property type="protein sequence ID" value="AAH33639.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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    <dbReference type="PIR" id="A38223">
        <property type="entry name" value="A38223"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="NM_000745.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P30532"/>
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    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-187">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-210">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4"/>
    </dbReference>
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    </dbReference>
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        <property type="generic name" value="Butabarbital"/>
    </dbReference>
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        <property type="generic name" value="Cisatracurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00184">
        <property type="generic name" value="Nicotine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00202">
        <property type="generic name" value="Succinylcholine"/>
    </dbReference>
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        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
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    </dbReference>
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        <property type="antibodies" value="334 antibodies from 36 providers"/>
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        <property type="protein sequence ID" value="ENSP00000299565.5"/>
        <property type="gene ID" value="ENSG00000169684.14"/>
    </dbReference>
    <dbReference type="GeneID" id="1138"/>
    <dbReference type="KEGG" id="hsa:1138"/>
    <dbReference type="MANE-Select" id="ENST00000299565.9">
        <property type="protein sequence ID" value="ENSP00000299565.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000745.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000736.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002bdy.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1959"/>
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        <property type="gene designation" value="CHRNA5"/>
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    </dbReference>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="type" value="phenotype"/>
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        <property type="hits" value="8 hits in 1155 CRISPR screens"/>
    </dbReference>
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    </dbReference>
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        <property type="component" value="Chromosome 15"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000169684">
        <property type="expression patterns" value="Expressed in ventricular zone and 108 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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    </dbReference>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
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    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="4">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000356" description="Neuronal acetylcholine receptor subunit alpha-5">
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            <begin position="23"/>
            <end position="468"/>
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        <location>
            <begin position="23"/>
            <end position="254"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="255"/>
            <end position="275"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="282"/>
            <end position="302"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="317"/>
            <end position="337"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="338"/>
            <end position="429"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="430"/>
            <end position="451"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="452"/>
            <end position="468"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="170"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Associated with receptor activation" evidence="2">
        <location>
            <begin position="234"/>
            <end position="235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_046211" description="In dbSNP:rs2229961.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_046212" description="Risk factor for lung cancer; decreased calcium permeability and fast desensitization in (CHRNA4:CHRNB2)2:CHRNA5 but not in (CHRNA3:CHRNB4)2:CHRNA5 or (CHRNA3:CHRNB24)2:CHRNA5 AChR; no effect on activation by nicotine; dbSNP:rs16969968." evidence="8 11 12">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA58357." evidence="13" ref="1">
        <original>RCGLAGAAGGAQ</original>
        <variation>ALRSSRARRAAR</variation>
        <location>
            <begin position="23"/>
            <end position="34"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA58357." evidence="13" ref="1">
        <original>V</original>
        <variation>S</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA58357." evidence="13" ref="1">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA58357." evidence="13" ref="1">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="405"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P02709"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P32297"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P43681"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="18385676"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="18385720"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="18385738"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="20881005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="27344019"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="8663494"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="8906617"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000312" key="14">
        <source>
            <dbReference type="HGNC" id="HGNC:1959"/>
        </source>
    </evidence>
    <sequence length="468" mass="53054" checksum="7FE91A2E362289C0" modified="1997-11-01" version="2" precursor="true">MAARGSGPRALRLLLLVQLVAGRCGLAGAAGGAQRGLSEPSSIAKHEDSLLKDLFQDYERWVRPVEHLNDKIKIKFGLAISQLVDVDEKNQLMTTNVWLKQEWIDVKLRWNPDDYGGIKVIRVPSDSVWTPDIVLFDNADGRFEGTSTKTVIRYNGTVTWTPPANYKSSCTIDVTFFPFDLQNCSMKFGSWTYDGSQVDIILEDQDVDKRDFFDNGEWEIVSATGSKGNRTDSCCWYPYVTYSFVIKRLPLFYTLFLIIPCIGLSFLTVLVFYLPSNEGEKICLCTSVLVSLTVFLLVIEEIIPSSSKVIPLIGEYLVFTMIFVTLSIMVTVFAINIHHRSSSTHNAMAPLVRKIFLHTLPKLLCMRSHVDRYFTQKEETESGSGPKSSRNTLEAALDSIRYITRHIMKENDVREVVEDWKFIAQVLDRMFLWTFLFVSIVGSLGLFVPVIYKWANILIPVHIGNANK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="215" xmlns="https://uniprot.org/uniprot">
    <accession>Q05901</accession>
    <accession>Q15827</accession>
    <name>ACHB3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit beta-3</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="8" type="primary">CHRNB3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Mol. Neurosci." volume="7" first="217" last="228">
            <title>Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.</title>
            <authorList>
                <person name="Elliott K.J."/>
                <person name="Ellis S.B."/>
                <person name="Berckhan K.J."/>
                <person name="Urrutia A."/>
                <person name="Chavez-Noriega L.E."/>
                <person name="Johnson E.C."/>
                <person name="Velicelebi G."/>
                <person name="Harpold M.M."/>
            </authorList>
            <dbReference type="PubMed" id="8906617"/>
            <dbReference type="DOI" id="10.1007/bf02736842"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Substantia nigra</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="FEBS Lett." volume="400" first="309" last="314">
            <title>Cloning and sequence of full-length cDNAs encoding the human neuronal nicotinic acetylcholine receptor (nAChR) subunits beta3 and beta4 and expression of seven nAChR subunits in the human neuroblastoma cell line SH-SY5Y and/or IMR-32.</title>
            <authorList>
                <person name="Groot Kormelink P.J."/>
                <person name="Luyten W.H.M.L."/>
            </authorList>
            <dbReference type="PubMed" id="9009220"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(96)01383-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Pons</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="1999-04" db="EMBL/GenBank/DDBJ databases">
            <title>Genomic structure and mutation analysis of the CHRNB3 gene.</title>
            <authorList>
                <person name="Keddache M."/>
                <person name="Durner M."/>
                <person name="Greenberg D.A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1993" name="Neurosci. Lett." volume="155" first="136" last="139">
            <title>Molecular cloning of a human neuronal nicotinic acetylcholine receptor beta 3-like subunit.</title>
            <authorList>
                <person name="Willoughby J.J."/>
                <person name="Ninkina N.N."/>
                <person name="Beech M.M."/>
                <person name="Latchman D.S."/>
                <person name="Wood J.N."/>
            </authorList>
            <dbReference type="PubMed" id="7690916"/>
            <dbReference type="DOI" id="10.1016/0304-3940(93)90691-d"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 36-458</scope>
        <source>
            <tissue>Brain stem</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2000" name="J. Physiol. (Lond.)" volume="529" first="565" last="577">
            <title>Stoichiometry of human recombinant neuronal nicotinic receptors containing the b3 subunit expressed in Xenopus oocytes.</title>
            <authorList>
                <person name="Boorman J.P."/>
                <person name="Groot-Kormelink P.J."/>
                <person name="Sivilotti L.G."/>
            </authorList>
            <dbReference type="PubMed" id="11118490"/>
            <dbReference type="DOI" id="10.1111/j.1469-7793.2000.00565.x"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>STOICHIOMETRY</scope>
        <scope>MUTAGENESIS OF VAL-273</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Mol. Pharmacol." volume="70" first="1358" last="1368">
            <title>Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.</title>
            <authorList>
                <person name="Tumkosit P."/>
                <person name="Kuryatov A."/>
                <person name="Luo J."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="16835356"/>
            <dbReference type="DOI" id="10.1124/mol.106.027326"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference evidence="9" key="8">
        <citation type="journal article" date="2022" name="Molecules" volume="27" first="4642" last="4642">
            <title>Structural Insights into the Role of beta3 nAChR Subunit in the Activation of Nicotinic Receptors.</title>
            <authorList>
                <person name="Giastas P."/>
                <person name="Papakyriakou A."/>
                <person name="Tsafaras G."/>
                <person name="Tzartos S.J."/>
                <person name="Zouridakis M."/>
            </authorList>
            <dbReference type="PubMed" id="35889515"/>
            <dbReference type="DOI" id="10.3390/molecules27144642"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 25-231</scope>
        <scope>GLYCOSYLATION AT ASN-138 AND ASN-166</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (PubMed:11118490, PubMed:16835356, PubMed:35889515). Has an accessory rather than functional role and is only able to form functional nAChRs when co-assembled with another beta subunit (PubMed:11118490, PubMed:16835356). Participates in pentameric assemblies along with CHRNA3, CHRNA4, CHRNA6, CHRNB2 and CHRNB4 (PubMed:11118490, PubMed:16835356). Modulates receptor assembly and increases receptor sensitivity to nicotine when associated with CHRNB2, CHRNA4 and/or CHRNA6 as well as CHRNA3 and CHRNB4 (PubMed:11118490, PubMed:16835356). Seems to play a role in nicotine addiction (PubMed:11118490, PubMed:16835356).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="4 5">Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 5 6">Neuronal AChR seems to be composed of two different type of subunits: alpha and beta (PubMed:11118490, PubMed:35889515). CHRNB3/beta-3 subunit is only able to form functional nAChRs when co-assembled with another beta subunit. Participates in pentameric assemblies along with CHRNA4/alpha-4 and CHRNB2/beta-2 subunits and with CHRNA6/alpha-6 as well, forming stoichiometries such as (CHRNA3:CHRNB4)2:CHRNB3, (CHRNA4:CHRNB2)2:CHRNB3 or (CHRNA6:CHRNB2)2:CHRNB3 (PubMed:11118490, PubMed:16835356).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Synaptic cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-3/CHRNB3 sub-subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="AAB40116.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y08417">
        <property type="protein sequence ID" value="CAA69694.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF140765">
        <property type="protein sequence ID" value="AAD33063.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF140760">
        <property type="protein sequence ID" value="AAD33063.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF140761">
        <property type="protein sequence ID" value="AAD33063.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH69681.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC069703">
        <property type="protein sequence ID" value="AAH69703.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC069788">
        <property type="protein sequence ID" value="AAH69788.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X67513">
        <property type="protein sequence ID" value="CAA47851.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6134.1"/>
    <dbReference type="PIR" id="I38056">
        <property type="entry name" value="I38056"/>
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    <dbReference type="RefSeq" id="NP_000740.1">
        <property type="nucleotide sequence ID" value="NM_000749.5"/>
    </dbReference>
    <dbReference type="PDB" id="8A5U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="B=25-231"/>
    </dbReference>
    <dbReference type="PDBsum" id="8A5U"/>
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    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2192">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3"/>
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    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000289957"/>
    <dbReference type="BindingDB" id="Q05901"/>
    <dbReference type="ChEMBL" id="CHEMBL2109233"/>
    <dbReference type="DrugBank" id="DB00237">
        <property type="generic name" value="Butabarbital"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00565">
        <property type="generic name" value="Cisatracurium"/>
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    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
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        <property type="generic name" value="Nicotine"/>
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    <dbReference type="DrugBank" id="DB00202">
        <property type="generic name" value="Succinylcholine"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q05901"/>
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        <property type="glycosylation" value="3 sites, No reported glycans"/>
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        <property type="glycosylation" value="3 sites"/>
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    <dbReference type="BioMuta" id="CHRNB3"/>
    <dbReference type="DMDM" id="2506128"/>
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    <dbReference type="PeptideAtlas" id="Q05901"/>
    <dbReference type="ProteomicsDB" id="58355"/>
    <dbReference type="Antibodypedia" id="11480">
        <property type="antibodies" value="171 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="1142"/>
    <dbReference type="Ensembl" id="ENST00000289957.3">
        <property type="protein sequence ID" value="ENSP00000289957.2"/>
        <property type="gene ID" value="ENSG00000147432.7"/>
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    <dbReference type="GeneID" id="1142"/>
    <dbReference type="KEGG" id="hsa:1142"/>
    <dbReference type="MANE-Select" id="ENST00000289957.3">
        <property type="protein sequence ID" value="ENSP00000289957.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000749.5"/>
        <property type="RefSeq protein sequence ID" value="NP_000740.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xpi.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1963"/>
    <dbReference type="ClinPGx" id="PA26495"/>
    <dbReference type="CTD" id="1142"/>
    <dbReference type="DisGeNET" id="1142"/>
    <dbReference type="GeneCards" id="CHRNB3"/>
    <dbReference type="HGNC" id="HGNC:1963">
        <property type="gene designation" value="CHRNB3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000147432">
        <property type="expression patterns" value="Group enriched (brain, pancreas, retina, testis)"/>
    </dbReference>
    <dbReference type="MIM" id="118508">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000147432"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000147432"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156892"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_0_1"/>
    <dbReference type="InParanoid" id="Q05901"/>
    <dbReference type="OMA" id="QMWASIV"/>
    <dbReference type="OrthoDB" id="5975154at2759"/>
    <dbReference type="PAN-GO" id="Q05901">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q05901"/>
    <dbReference type="PathwayCommons" id="Q05901"/>
    <dbReference type="Reactome" id="R-HSA-629594">
        <property type="pathway name" value="Highly calcium permeable postsynaptic nicotinic acetylcholine receptors"/>
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</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>Q15825</accession>
    <accession>B2R8V4</accession>
    <accession>B4DQH1</accession>
    <name>ACHA6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Neuronal acetylcholine receptor subunit alpha-6</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="12" type="primary">CHRNA6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Mol. Neurosci." volume="7" first="217" last="228">
            <title>Comparative structure of human neuronal alpha 2-alpha 7 and beta 2-beta 4 nicotinic acetylcholine receptor subunits and functional expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and beta 4 subunits.</title>
            <authorList>
                <person name="Elliott K.J."/>
                <person name="Ellis S.B."/>
                <person name="Berckhan K.J."/>
                <person name="Urrutia A."/>
                <person name="Chavez-Noriega L.E."/>
                <person name="Johnson E.C."/>
                <person name="Velicelebi G."/>
                <person name="Harpold M.M."/>
            </authorList>
            <dbReference type="PubMed" id="8906617"/>
            <dbReference type="DOI" id="10.1007/bf02736842"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Substantia nigra</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="1998-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Groot Kormelink P.J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-02" db="EMBL/GenBank/DDBJ databases">
            <title>Alu and other elements in the promoter of human nAChR A6 gene (CHNRA6) direct transcriptional repression.</title>
            <authorList>
                <person name="Ebihara M."/>
                <person name="Ohba H."/>
                <person name="Yoshikawa T."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
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                <person name="Ono T."/>
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                <person name="Ohmori Y."/>
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                <person name="Hikiji T."/>
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                <person name="Senba T."/>
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                <person name="Mizuno T."/>
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                <person name="Sasaki M."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
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                <person name="Nakagawa K."/>
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                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
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                <person name="Nakai K."/>
                <person name="Yada T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
    </reference>
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            <dbReference type="PubMed" id="16421571"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
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            <title>Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.</title>
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                <person name="Tumkosit P."/>
                <person name="Kuryatov A."/>
                <person name="Luo J."/>
                <person name="Lindstrom J."/>
            </authorList>
            <dbReference type="PubMed" id="16835356"/>
            <dbReference type="DOI" id="10.1124/mol.106.027326"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2016" name="J. Neurochem." volume="138" first="806" last="820">
            <title>Functional interaction between Lypd6 and nicotinic acetylcholine receptors.</title>
            <authorList>
                <person name="Arvaniti M."/>
                <person name="Jensen M.M."/>
                <person name="Soni N."/>
                <person name="Wang H."/>
                <person name="Klein A.B."/>
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                <person name="Mikkelsen J.D."/>
                <person name="Thomsen M.S."/>
            </authorList>
            <dbReference type="PubMed" id="27344019"/>
            <dbReference type="DOI" id="10.1111/jnc.13718"/>
        </citation>
        <scope>INTERACTION WITH LYPD6</scope>
    </reference>
    <comment type="function">
        <text evidence="5 7 11">Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators (Probable). CHRNA6 forms pentameric channels with CHRNB2, CHRNB3 and CHRNA4 that exhibit high sensitivity to ACh and nicotine and are predominantly expressed in only a few brain areas, including dopaminergic neurons, norepirephrine neurons and cells of the visual system (PubMed:16835356). nAChrs containing CHRNA6 subunits mediate endogenous cholinergic modulation of dopamine and gamma-aminobutyric acid (GABA) release in response to nicotine at nerve terminals.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>Ca(2+)(in) = Ca(2+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29671"/>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>K(+)(in) = K(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:29463"/>
            <dbReference type="ChEBI" id="CHEBI:29103"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>Na(+)(in) = Na(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34963"/>
            <dbReference type="ChEBI" id="CHEBI:29101"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="5 7">Activated by a myriad of ligands such as acetylcholine, cytisine and nicotine (PubMed:16835356). CHRNA6 nAChR activity is inhibited by the antagonists alpha-conotoxin MII and PIA, a small disulfide-constrained peptides from cone snails.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 7 8">Neuronal AChR is composed of two different types of subunits: alpha and non-alpha (beta). CHRNA6/alpha-6 subunit can be combined to CHRNB2/beta-2, CHRNA4/alpha-4 and CHRNB3/beta-3 to give rise to functional receptors (PubMed:16835356). Heteropentamers containing CHRNB3 have an stoichiometry of (CHRNA6:CHRNB2)2:CHRNB3 (PubMed:16835356). Interacts with LYPD6 (PubMed:27344019).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Synaptic cell membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q15825-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15825-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_042713"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-6/CHRNA6 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="U62435">
        <property type="protein sequence ID" value="AAB40113.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y16282">
        <property type="protein sequence ID" value="CAA76155.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB079251">
        <property type="protein sequence ID" value="BAC06855.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298798">
        <property type="protein sequence ID" value="BAG60933.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313521">
        <property type="protein sequence ID" value="BAG36301.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC087533">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63207.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014456">
        <property type="protein sequence ID" value="AAH14456.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56536.1">
        <molecule id="Q15825-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6135.1">
        <molecule id="Q15825-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001186208.1">
        <molecule id="Q15825-2"/>
        <property type="nucleotide sequence ID" value="NM_001199279.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004189.1">
        <molecule id="Q15825-1"/>
        <property type="nucleotide sequence ID" value="NM_004198.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047278352.1">
        <molecule id="Q15825-1"/>
        <property type="nucleotide sequence ID" value="XM_047422396.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054217429.1">
        <molecule id="Q15825-1"/>
        <property type="nucleotide sequence ID" value="XM_054361454.1"/>
    </dbReference>
    <dbReference type="PDB" id="8ZRN">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="A/C=1-374, A/C=416-494"/>
    </dbReference>
    <dbReference type="PDB" id="8ZRP">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.32 A"/>
        <property type="chains" value="A/C=1-374, A/C=416-494"/>
    </dbReference>
    <dbReference type="PDBsum" id="8ZRN"/>
    <dbReference type="PDBsum" id="8ZRP"/>
    <dbReference type="AlphaFoldDB" id="Q15825"/>
    <dbReference type="EMDB" id="EMD-60400"/>
    <dbReference type="EMDB" id="EMD-60401"/>
    <dbReference type="SMR" id="Q15825"/>
    <dbReference type="BioGRID" id="114463">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-213">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2192">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-26532">
        <property type="entry name" value="Neuronal nicotinic acetylcholine receptor complex, alpha6-beta4"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q15825">
        <property type="interactions" value="552"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15825">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000276410"/>
    <dbReference type="BindingDB" id="Q15825"/>
    <dbReference type="ChEMBL" id="CHEMBL2109233"/>
    <dbReference type="ChEMBL" id="CHEMBL2109237"/>
    <dbReference type="ChEMBL" id="CHEMBL3137285"/>
    <dbReference type="ChEMBL" id="CHEMBL4888445"/>
    <dbReference type="DrugBank" id="DB00237">
        <property type="generic name" value="Butabarbital"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00565">
        <property type="generic name" value="Cisatracurium"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09028">
        <property type="generic name" value="Cytisine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00184">
        <property type="generic name" value="Nicotine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00202">
        <property type="generic name" value="Succinylcholine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01273">
        <property type="generic name" value="Varenicline"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q15825"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="467"/>
    <dbReference type="GlyCosmos" id="Q15825">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15825">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15825"/>
    <dbReference type="PhosphoSitePlus" id="Q15825"/>
    <dbReference type="BioMuta" id="CHRNA6"/>
    <dbReference type="DMDM" id="2492620"/>
    <dbReference type="MassIVE" id="Q15825"/>
    <dbReference type="PaxDb" id="9606-ENSP00000276410"/>
    <dbReference type="PeptideAtlas" id="Q15825"/>
    <dbReference type="ProteomicsDB" id="60777">
        <molecule id="Q15825-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="60778">
        <molecule id="Q15825-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="24152">
        <property type="antibodies" value="145 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8973"/>
    <dbReference type="Ensembl" id="ENST00000276410.7">
        <molecule id="Q15825-1"/>
        <property type="protein sequence ID" value="ENSP00000276410.3"/>
        <property type="gene ID" value="ENSG00000147434.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000534622.5">
        <molecule id="Q15825-2"/>
        <property type="protein sequence ID" value="ENSP00000433871.1"/>
        <property type="gene ID" value="ENSG00000147434.9"/>
    </dbReference>
    <dbReference type="GeneID" id="8973"/>
    <dbReference type="KEGG" id="hsa:8973"/>
    <dbReference type="MANE-Select" id="ENST00000276410.7">
        <property type="protein sequence ID" value="ENSP00000276410.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004198.3"/>
        <property type="RefSeq protein sequence ID" value="NP_004189.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xpj.5">
        <molecule id="Q15825-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15963"/>
    <dbReference type="ClinPGx" id="PA26492"/>
    <dbReference type="CTD" id="8973"/>
    <dbReference type="DisGeNET" id="8973"/>
    <dbReference type="GeneCards" id="CHRNA6"/>
    <dbReference type="HGNC" id="HGNC:15963">
        <property type="gene designation" value="CHRNA6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000147434">
        <property type="expression patterns" value="Tissue enhanced (retina)"/>
    </dbReference>
    <dbReference type="MIM" id="606888">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000147434"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000147434"/>
    <dbReference type="eggNOG" id="KOG3645">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158062"/>
    <dbReference type="HOGENOM" id="CLU_018074_1_0_1"/>
    <dbReference type="InParanoid" id="Q15825"/>
    <dbReference type="OMA" id="HKDTKLH"/>
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    <dbReference type="Reactome" id="R-HSA-629594">
        <property type="pathway name" value="Highly calcium permeable postsynaptic nicotinic acetylcholine receptors"/>
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    <dbReference type="Reactome" id="R-HSA-629597">
        <property type="pathway name" value="Highly calcium permeable nicotinic acetylcholine receptors"/>
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        <property type="term" value="P:regulation of dopamine secretion"/>
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        <property type="term" value="P:synaptic transmission, cholinergic"/>
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        <property type="entry name" value="LGIC_TM_nAChR"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Neur_channel"/>
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        <property type="entry name" value="LIC"/>
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        <property type="entry name" value="NEUROTRANSMITTER GATED ION CHANNEL"/>
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        <property type="entry name" value="Neur_chan_LBD"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="NICOTINICR"/>
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        <property type="entry name" value="NRIONCHANNEL"/>
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        <property type="entry name" value="Neurotransmitter-gated ion-channel transmembrane pore"/>
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        <property type="entry name" value="Nicotinic receptor ligand binding domain-like"/>
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        <property type="entry name" value="NEUROTR_ION_CHANNEL"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0407">Ion channel</keyword>
    <keyword id="KW-0406">Ion transport</keyword>
    <keyword id="KW-1071">Ligand-gated ion channel</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="6">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000360" description="Neuronal acetylcholine receptor subunit alpha-6">
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    <feature type="transmembrane region" description="Helical" evidence="6">
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    <feature type="transmembrane region" description="Helical" evidence="6">
        <location>
            <begin position="306"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic">
        <location>
            <begin position="328"/>
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    <feature type="transmembrane region" description="Helical" evidence="6">
        <location>
            <begin position="466"/>
            <end position="484"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="401"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="54"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="171"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="158"/>
            <end position="172"/>
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    </feature>
    <feature type="disulfide bond" description="Associated with receptor activation" evidence="1">
        <location>
            <begin position="222"/>
            <end position="223"/>
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    <feature type="splice variant" id="VSP_042713" description="In isoform 2." evidence="9">
        <location>
            <begin position="74"/>
            <end position="88"/>
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    </feature>
    <feature type="sequence variant" id="VAR_048171" description="In dbSNP:rs16891583.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="447"/>
        </location>
    </feature>
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        <source>
            <dbReference type="UniProtKB" id="P02709"/>
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        <source>
            <dbReference type="UniProtKB" id="P04757"/>
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        <source>
            <dbReference type="UniProtKB" id="P43681"/>
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    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="Q9R0W9"/>
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    </evidence>
    <evidence type="ECO:0000255" key="6"/>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16835356"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27344019"/>
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    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="16835356"/>
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    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:15963"/>
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    </evidence>
    <sequence length="494" mass="56898" checksum="1A437E6DEE02ABFE" modified="1997-11-01" version="1" precursor="true">MLTSKGQGFLHGGLCLWLCVFTPFFKGCVGCATEERLFHKLFSHYNQFIRPVENVSDPVTVHFEVAITQLANVDEVNQIMETNLWLRHIWNDYKLRWDPMEYDGIETLRVPADKIWKPDIVLYNNAVGDFQVEGKTKALLKYNGMITWTPPAIFKSSCPMDITFFPFDHQNCSLKFGSWTYDKAEIDLLIIGSKVDMNDFWENSEWEIIDASGYKHDIKYNCCEEIYTDITYSFYIRRLPMFYTINLIIPCLFISFLTVLVFYLPSDCGEKVTLCISVLLSLTVFLLVITETIPSTSLVVPLVGEYLLFTMIFVTLSIVVTVFVLNIHYRTPTTHTMPRWVKTVFLKLLPQVLLMRWPLDKTRGTGSDAVPRGLARRPAKGKLASHGEPRHLKECFHCHKSNELATSKRRLSHQPLQWVVENSEHSPEVEDVINSVQFIAENMKSHNETKEVEDDWKYVAMVVDRVFLWVFIIVCVFGTAGLFLQPLLGNTGKS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-02-28" modified="2026-01-28" version="218" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKV3</accession>
    <accession>B2RTT4</accession>
    <accession>D3DS45</accession>
    <accession>O75158</accession>
    <accession>Q9UG91</accession>
    <accession>Q9UKV1</accession>
    <accession>Q9UKV2</accession>
    <name>ACINU_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Apoptotic chromatin condensation inducer in the nucleus</fullName>
            <shortName>Acinus</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACIN1</name>
        <name type="synonym">ACINUS</name>
        <name type="synonym">KIAA0670</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Nature" volume="401" first="168" last="173">
            <title>Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation.</title>
            <authorList>
                <person name="Sahara S."/>
                <person name="Aoto M."/>
                <person name="Eguchi Y."/>
                <person name="Imamoto N."/>
                <person name="Yoneda Y."/>
                <person name="Tsujimoto Y."/>
            </authorList>
            <dbReference type="PubMed" id="10490026"/>
            <dbReference type="DOI" id="10.1038/43678"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-1093</scope>
        <scope>VARIANT PRO-447</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-02" db="EMBL/GenBank/DDBJ databases">
            <title>Full-length cDNA libraries and normalization.</title>
            <authorList>
                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>VARIANT PRO-447</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
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                <person name="Aniere F."/>
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                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
                <person name="Dubois I."/>
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                <person name="Ratcliffe A."/>
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                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
                <person name="Magdelenat G."/>
                <person name="Pateau E."/>
                <person name="Petit E."/>
                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
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                <person name="Bataille E."/>
                <person name="Bluet E."/>
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                <person name="Dumont C."/>
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                <person name="Muanga J."/>
                <person name="Pellouin V."/>
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                <person name="Gauguet G."/>
                <person name="Roy A."/>
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                <person name="Verdier J."/>
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                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT PRO-447</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <scope>VARIANT PRO-447</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-1341 (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 798-813</scope>
        <source>
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        <scope>IDENTIFICATION IN THE ASAP COMPLEX</scope>
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        <scope>IDENTIFICATION IN A MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX</scope>
        <scope>INTERACTION WITH RNPS1 AND SAP18</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-328; SER-490; SER-710 AND SER-1004</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240; SER-243 AND THR-254</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT SER-1180 BY SRPK2</scope>
        <scope>INTERACTION WITH SRPK2</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434; SER-453; SER-895 AND SER-898</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] PRO-447</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-710 AND SER-1004</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>METHYLATION AT LYS-654</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-169; SER-216; SER-240; SER-243; THR-254; SER-295; SER-365; SER-384; SER-386; SER-388; THR-393; SER-410; THR-414; SER-453; SER-490; TYR-512; SER-561; SER-655; SER-657; THR-682; SER-710; THR-720; SER-838 AND SER-1004</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] PRO-447</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>INTERACTION WITH API5</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-254; THR-269; SER-400; SER-410; THR-414; SER-478; SER-490; SER-838 AND SER-990</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-717</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH SAP18 AND RNPS1</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-240; SER-243; THR-254; SER-365; SER-410; THR-414; SER-490; SER-561; SER-655; SER-657; SER-710; SER-714; SER-729; SER-838 AND SER-1004</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208; SER-210; SER-216; SER-240; SER-243; THR-326; SER-328; SER-365; SER-384; SER-386; THR-393; SER-410; SER-490; SER-655; SER-657; SER-710; SER-714; SER-729; SER-825; SER-838; SER-987 AND SER-1004</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>INTERACTION WITH RNPS1</scope>
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        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; SER-216; SER-240; SER-243; THR-254; SER-328; SER-365; SER-386; SER-388; SER-400; SER-410; THR-414; THR-420; SER-490; SER-522; SER-561; SER-655; SER-657; THR-682; SER-710; SER-714; SER-825; SER-838; THR-976; SER-987; SER-990 AND SER-1004</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] PRO-447</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; SER-169; SER-216; SER-365; SER-400; SER-410; THR-414; SER-453; SER-478; SER-490; SER-561; SER-710; SER-825; SER-838; SER-898 AND SER-1004</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825 (ISOFORM 4)</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] PRO-447</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2014" name="Nat. Struct. Mol. Biol." volume="21" first="927" last="936">
            <title>Uncovering global SUMOylation signaling networks in a site-specific manner.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="D'Souza R.C."/>
                <person name="Yang B."/>
                <person name="Verlaan-de Vries M."/>
                <person name="Mann M."/>
                <person name="Vertegaal A.C."/>
            </authorList>
            <dbReference type="PubMed" id="25218447"/>
            <dbReference type="DOI" id="10.1038/nsmb.2890"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-315 AND LYS-532</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="2014" name="Proc. Natl. Acad. Sci. U.S.A." volume="111" first="12432" last="12437">
            <title>Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.</title>
            <authorList>
                <person name="Impens F."/>
                <person name="Radoshevich L."/>
                <person name="Cossart P."/>
                <person name="Ribet D."/>
            </authorList>
            <dbReference type="PubMed" id="25114211"/>
            <dbReference type="DOI" id="10.1073/pnas.1413825111"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-268 AND LYS-532</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="2015" name="Cell Rep." volume="10" first="1778" last="1791">
            <title>SUMO-2 orchestrates chromatin modifiers in response to DNA damage.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Treffers L.W."/>
                <person name="Verlaan-de Vries M."/>
                <person name="Olsen J.V."/>
                <person name="Vertegaal A.C."/>
            </authorList>
            <dbReference type="PubMed" id="25772364"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2015.02.033"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-315 AND LYS-532</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="33">
        <citation type="journal article" date="2015" name="Mol. Cell. Proteomics" volume="14" first="1419" last="1434">
            <title>System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.</title>
            <authorList>
                <person name="Xiao Z."/>
                <person name="Chang J.G."/>
                <person name="Hendriks I.A."/>
                <person name="Sigurdsson J.O."/>
                <person name="Olsen J.V."/>
                <person name="Vertegaal A.C."/>
            </authorList>
            <dbReference type="PubMed" id="25755297"/>
            <dbReference type="DOI" id="10.1074/mcp.o114.044792"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-305 AND LYS-532</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="34">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-305; LYS-315; LYS-375; LYS-532; LYS-732; LYS-861; LYS-879; LYS-970; LYS-1047 AND LYS-1107</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="35">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] GLN-1160</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 11 14 15">Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 8 11 12 13 15">Found in a mRNA splicing-dependent exon junction complex (EJC). Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) complexes consisting of RNPS1, SAP18 and different isoforms of ACIN1; the association of SAP18 seems to require a preformed RNPS1:ACIN1 complex. Interacts with API5. Interacts with SRPK2 in a phosphorylation-dependent manner.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-740475">
            <id>P61457</id>
            <label>PCBD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-681904">
            <id>Q9H307</id>
            <label>PNN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-395959">
            <id>Q15287</id>
            <label>RNPS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-2462271">
            <id>Q15428</id>
            <label>SF3A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-593303">
            <id>P78362</id>
            <label>SRPK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-359815">
            <id>P31946</id>
            <label>YWHAB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-396258">
            <id>Q9UKV3</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-5279966">
            <id>Q9UKV3-2</id>
        </interactant>
        <interactant intactId="EBI-15972541">
            <id>Q15287-1</id>
            <label>RNPS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6976596">
            <id>Q9UKV3-3</id>
        </interactant>
        <interactant intactId="EBI-1048422">
            <id>Q9BZZ5</id>
            <label>API5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus speckle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
            <location>Nucleoplasm</location>
        </subcellularLocation>
        <text>Phosphorylation on Ser-1180 by SRPK2 redistributes it from the nuclear speckles to the nucleoplasm.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKV3-1</id>
            <name>1</name>
            <name>L</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKV3-2</id>
            <name>2</name>
            <name>S'</name>
            <sequence type="described" ref="VSP_004025 VSP_004028"/>
        </isoform>
        <isoform>
            <id>Q9UKV3-3</id>
            <name>3</name>
            <name>S</name>
            <sequence type="described" ref="VSP_004026 VSP_004029"/>
        </isoform>
        <isoform>
            <id>Q9UKV3-5</id>
            <name>4</name>
            <sequence type="described" ref="VSP_042204 VSP_042205"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Ubiquitous. The Ser-1180 phosphorylated form (by SRPK2) is highly expressed and phosphorylated in patients with myeloid hematologic malignancies.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Phosphorylation on Ser-1180 by SRPK2 up-regulates its stimulatory effect on cyclin A1.</text>
    </comment>
    <comment type="PTM">
        <text>Undergoes proteolytic cleavage; the processed form is active, contrary to the uncleaved form.</text>
    </comment>
    <comment type="caution">
        <text evidence="23">Structural and functional studies of the ASAP complex have been conducted with a chimeric complex involving a conserved fragment of Drosophila melanogaster Acinus/hkl.</text>
    </comment>
    <dbReference type="EMBL" id="AF124726">
        <property type="protein sequence ID" value="AAD56724.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF124727">
        <property type="protein sequence ID" value="AAD56725.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF124728">
        <property type="protein sequence ID" value="AAD56726.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX247975">
        <property type="protein sequence ID" value="CAD62309.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL117258">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL132780">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66187.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66188.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC140805">
        <property type="protein sequence ID" value="AAI40806.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB014570">
        <property type="protein sequence ID" value="BAA31645.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL050382">
        <property type="protein sequence ID" value="CAB43681.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53887.1">
        <molecule id="Q9UKV3-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53888.1">
        <molecule id="Q9UKV3-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55905.1">
        <molecule id="Q9UKV3-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9587.1">
        <molecule id="Q9UKV3-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001158286.2">
        <molecule id="Q9UKV3-5"/>
        <property type="nucleotide sequence ID" value="NM_001164814.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001158287.2">
        <property type="nucleotide sequence ID" value="NM_001164815.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001158288.1">
        <molecule id="Q9UKV3-2"/>
        <property type="nucleotide sequence ID" value="NM_001164816.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001158289.1">
        <molecule id="Q9UKV3-3"/>
        <property type="nucleotide sequence ID" value="NM_001164817.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055792.2">
        <molecule id="Q9UKV3-1"/>
        <property type="nucleotide sequence ID" value="NM_014977.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005267475.1">
        <molecule id="Q9UKV3-3"/>
        <property type="nucleotide sequence ID" value="XM_005267418.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054231597.1">
        <molecule id="Q9UKV3-3"/>
        <property type="nucleotide sequence ID" value="XM_054375622.1"/>
    </dbReference>
    <dbReference type="PDB" id="6G6S">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.65 A"/>
        <property type="chains" value="A/B=1008-1100"/>
    </dbReference>
    <dbReference type="PDBsum" id="6G6S"/>
    <dbReference type="AlphaFoldDB" id="Q9UKV3"/>
    <dbReference type="SMR" id="Q9UKV3"/>
    <dbReference type="BioGRID" id="116634">
        <property type="interactions" value="339"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2256">
        <property type="entry name" value="ASAP splicing-associated complex"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9UKV3"/>
    <dbReference type="DIP" id="DIP-32963N"/>
    <dbReference type="FunCoup" id="Q9UKV3">
        <property type="interactions" value="3910"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UKV3">
        <property type="interactions" value="137"/>
    </dbReference>
    <dbReference type="MINT" id="Q9UKV3"/>
    <dbReference type="STRING" id="9606.ENSP00000262710"/>
    <dbReference type="TCDB" id="3.A.18.1.1">
        <property type="family name" value="the nuclear mrna exporter (mrna-e) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9UKV3">
        <property type="glycosylation" value="3 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UKV3">
        <property type="glycosylation" value="10 sites, 1 O-linked glycan (10 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UKV3"/>
    <dbReference type="MetOSite" id="Q9UKV3"/>
    <dbReference type="PhosphoSitePlus" id="Q9UKV3"/>
    <dbReference type="SwissPalm" id="Q9UKV3"/>
    <dbReference type="BioMuta" id="ACIN1"/>
    <dbReference type="DMDM" id="308153407"/>
    <dbReference type="CPTAC" id="CPTAC-1342"/>
    <dbReference type="jPOST" id="Q9UKV3"/>
    <dbReference type="MassIVE" id="Q9UKV3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000262710"/>
    <dbReference type="PeptideAtlas" id="Q9UKV3"/>
    <dbReference type="ProteomicsDB" id="84889">
        <molecule id="Q9UKV3-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84890">
        <molecule id="Q9UKV3-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84891">
        <molecule id="Q9UKV3-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84892">
        <molecule id="Q9UKV3-5"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9UKV3"/>
    <dbReference type="Antibodypedia" id="63">
        <property type="antibodies" value="519 antibodies from 36 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="22985"/>
    <dbReference type="Ensembl" id="ENST00000262710.5">
        <molecule id="Q9UKV3-1"/>
        <property type="protein sequence ID" value="ENSP00000262710.1"/>
        <property type="gene ID" value="ENSG00000100813.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000338631.10">
        <molecule id="Q9UKV3-2"/>
        <property type="protein sequence ID" value="ENSP00000345541.6"/>
        <property type="gene ID" value="ENSG00000100813.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000357481.6">
        <molecule id="Q9UKV3-3"/>
        <property type="protein sequence ID" value="ENSP00000350073.2"/>
        <property type="gene ID" value="ENSG00000100813.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000397341.7">
        <molecule id="Q9UKV3-3"/>
        <property type="protein sequence ID" value="ENSP00000380502.3"/>
        <property type="gene ID" value="ENSG00000100813.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000555053.5">
        <molecule id="Q9UKV3-5"/>
        <property type="protein sequence ID" value="ENSP00000451328.1"/>
        <property type="gene ID" value="ENSG00000100813.16"/>
    </dbReference>
    <dbReference type="GeneID" id="22985"/>
    <dbReference type="KEGG" id="hsa:22985"/>
    <dbReference type="UCSC" id="uc001wip.5">
        <molecule id="Q9UKV3-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17066"/>
    <dbReference type="ClinPGx" id="PA134912489"/>
    <dbReference type="CTD" id="22985"/>
    <dbReference type="DisGeNET" id="22985"/>
    <dbReference type="GeneCards" id="ACIN1"/>
    <dbReference type="HGNC" id="HGNC:17066">
        <property type="gene designation" value="ACIN1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100813">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="604562">
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            <position position="305"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="37 39 40">
        <location>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="375"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="36 37 38 39 40">
        <location>
            <position position="532"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="732"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate" evidence="40">
        <location>
            <position position="861"/>
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    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="879"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="970"/>
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    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="1047"/>
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    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="40">
        <location>
            <position position="1107"/>
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    <feature type="splice variant" id="VSP_004026" description="In isoform 3." evidence="19 21">
        <location>
            <begin position="1"/>
            <end position="758"/>
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    <feature type="splice variant" id="VSP_004025" description="In isoform 2." evidence="19">
        <location>
            <begin position="1"/>
            <end position="727"/>
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    <feature type="splice variant" id="VSP_004028" description="In isoform 2." evidence="19">
        <original>GSPKKCEAEEAEPPAATQPQTSETQTSHLPESERIHHTV</original>
        <variation>MSPADRCRSANTIEPATTSSLALFLLLQRDQSSRTRGLP</variation>
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            <begin position="728"/>
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    <feature type="splice variant" id="VSP_004029" description="In isoform 3." evidence="19 21">
        <original>SERIHHTV</original>
        <variation>MLSESKEG</variation>
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            <begin position="759"/>
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            <position position="829"/>
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            <begin position="873"/>
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        <variation>K</variation>
        <location>
            <position position="257"/>
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    <feature type="sequence variant" id="VAR_022031" description="In dbSNP:rs3811182.">
        <original>I</original>
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        <location>
            <position position="311"/>
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    <feature type="sequence variant" id="VAR_061547" description="In dbSNP:rs941719." evidence="5 7 16 17 18 26 28 34 35">
        <original>A</original>
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        <location>
            <position position="447"/>
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    <feature type="sequence variant" id="VAR_022032" description="In dbSNP:rs1885097.">
        <original>S</original>
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            <position position="467"/>
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    <feature type="sequence variant" id="VAR_022033" description="In dbSNP:rs3751501.">
        <original>S</original>
        <variation>F</variation>
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            <position position="478"/>
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    <feature type="sequence variant" id="VAR_035777" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs754494408." evidence="9">
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            <position position="1160"/>
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    <feature type="mutagenesis site" description="Abolishes cleavage by CASP3 and chromatin condensation activity." evidence="5">
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            <position position="1093"/>
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    <feature type="sequence conflict" description="In Ref. 2; BAA31645." evidence="22" ref="2">
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            <position position="139"/>
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            <begin position="1012"/>
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            <begin position="1025"/>
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    <feature type="helix" evidence="41">
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    <feature type="helix" evidence="41">
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            <begin position="1089"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="35">
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            <position position="825"/>
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    <evidence type="ECO:0000250" key="1"/>
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    <evidence type="ECO:0000269" key="13">
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    <evidence type="ECO:0000269" key="14">
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    <evidence type="ECO:0000269" key="15">
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            <dbReference type="PubMed" id="19608861"/>
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            <dbReference type="PubMed" id="24275569"/>
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        <source>
            <dbReference type="PubMed" id="25114211"/>
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        <source>
            <dbReference type="PubMed" id="25218447"/>
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        <source>
            <dbReference type="PubMed" id="25755297"/>
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        <source>
            <dbReference type="PubMed" id="25772364"/>
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        <source>
            <dbReference type="PubMed" id="28112733"/>
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    <evidence type="ECO:0007829" key="41">
        <source>
            <dbReference type="PDB" id="6G6S"/>
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    <sequence length="1341" mass="151862" checksum="DCCBF310A4680691" modified="2010-10-05" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-26" modified="2026-01-28" version="151" xmlns="https://uniprot.org/uniprot">
    <accession>Q6P4H8</accession>
    <accession>B4DT41</accession>
    <accession>B4DXK2</accession>
    <accession>E9PBZ4</accession>
    <name>ACKMT_HUMAN</name>
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        <recommendedName>
            <fullName evidence="8 9">ATP synthase subunit C lysine N-methyltransferase</fullName>
            <ecNumber evidence="4 5">2.1.1.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="9">Protein N-lysine methyltransferase FAM173B</fullName>
            <shortName evidence="7">hFAM173B</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">ATPSCKMT</name>
        <name evidence="7" type="synonym">FAM173B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT MET-75</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
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                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
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                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT MET-75</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2018" name="PLoS Biol." volume="16" first="E2003452" last="E2003452">
            <title>Identification of FAM173B as a protein methyltransferase promoting chronic pain.</title>
            <authorList>
                <person name="Willemen H.L.D.M."/>
                <person name="Kavelaars A."/>
                <person name="Prado J."/>
                <person name="Maas M."/>
                <person name="Versteeg S."/>
                <person name="Nellissen L.J.J."/>
                <person name="Tromp J."/>
                <person name="Gonzalez Cano R."/>
                <person name="Zhou W."/>
                <person name="Jakobsson M.E."/>
                <person name="Malecki J."/>
                <person name="Posthuma G."/>
                <person name="Habib A.M."/>
                <person name="Heijnen C.J."/>
                <person name="Falnes P.O."/>
                <person name="Eijkelkamp N."/>
            </authorList>
            <dbReference type="PubMed" id="29444090"/>
            <dbReference type="DOI" id="10.1371/journal.pbio.2003452"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF ASP-94</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2019" name="J. Biol. Chem." volume="294" first="1128" last="1141">
            <title>Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase.</title>
            <authorList>
                <person name="Malecki J.M."/>
                <person name="Willemen H.L.D.M."/>
                <person name="Pinto R."/>
                <person name="Ho A.Y.Y."/>
                <person name="Moen A."/>
                <person name="Kjoenstad I.F."/>
                <person name="Burgering B.M.T."/>
                <person name="Zwartkruis F."/>
                <person name="Eijkelkamp N."/>
                <person name="Falnes P.O."/>
            </authorList>
            <dbReference type="PubMed" id="30530489"/>
            <dbReference type="DOI" id="10.1074/jbc.ra118.005473"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF GLU-117</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5">Mitochondrial protein-lysine N-methyltransferase that trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2. Trimethylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration (PubMed:29444090, PubMed:30530489). Promotes chronic pain (PubMed:29444090). Involved in persistent inflammatory and neuropathic pain: methyltransferase activity in the mitochondria of sensory neurons promotes chronic pain via a pathway that depends on the production of reactive oxygen species (ROS) and on the engagement of spinal cord microglia (PubMed:29444090).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5">
            <text>L-lysyl-[protein] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine + 3 H(+)</text>
            <dbReference type="Rhea" id="RHEA:54192"/>
            <dbReference type="Rhea" id="RHEA-COMP:9752"/>
            <dbReference type="Rhea" id="RHEA-COMP:13826"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29969"/>
            <dbReference type="ChEBI" id="CHEBI:57856"/>
            <dbReference type="ChEBI" id="CHEBI:59789"/>
            <dbReference type="ChEBI" id="CHEBI:61961"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4 5">
            <dbReference type="Rhea" id="RHEA:54193"/>
        </physiologicalReaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12382465">
            <id>Q6P4H8</id>
        </interactant>
        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 10">Mitochondrion membrane</location>
            <topology evidence="1">Single-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="4">Localizes to mitochondrial cristae.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6P4H8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6P4H8-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_044724"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Ubiquitously expressed.</text>
    </comment>
    <comment type="domain">
        <text evidence="5">Contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the ANT/ATPSC lysine N-methyltransferase family.</text>
    </comment>
    <dbReference type="EC" id="2.1.1.-" evidence="4 5"/>
    <dbReference type="EMBL" id="AK300042">
        <property type="protein sequence ID" value="BAG61853.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK302012">
        <property type="protein sequence ID" value="BAG63414.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012640">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC034229">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471102">
        <property type="protein sequence ID" value="EAX08074.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC063406">
        <property type="protein sequence ID" value="AAH63406.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43301.1">
        <molecule id="Q6P4H8-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58942.1">
        <molecule id="Q6P4H8-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001245317.1">
        <molecule id="Q6P4H8-2"/>
        <property type="nucleotide sequence ID" value="NM_001258388.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_954584.2">
        <molecule id="Q6P4H8-1"/>
        <property type="nucleotide sequence ID" value="NM_199133.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6P4H8"/>
    <dbReference type="SMR" id="Q6P4H8"/>
    <dbReference type="BioGRID" id="126386">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6P4H8">
        <property type="interactions" value="1347"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6P4H8">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000422338"/>
    <dbReference type="GlyGen" id="Q6P4H8">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6P4H8"/>
    <dbReference type="PhosphoSitePlus" id="Q6P4H8"/>
    <dbReference type="BioMuta" id="FAM173B"/>
    <dbReference type="DMDM" id="190360174"/>
    <dbReference type="jPOST" id="Q6P4H8"/>
    <dbReference type="MassIVE" id="Q6P4H8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000422338"/>
    <dbReference type="PeptideAtlas" id="Q6P4H8"/>
    <dbReference type="ProteomicsDB" id="19326"/>
    <dbReference type="ProteomicsDB" id="66979">
        <molecule id="Q6P4H8-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q6P4H8"/>
    <dbReference type="Antibodypedia" id="22448">
        <property type="antibodies" value="65 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="134145"/>
    <dbReference type="Ensembl" id="ENST00000510047.5">
        <molecule id="Q6P4H8-2"/>
        <property type="protein sequence ID" value="ENSP00000420876.1"/>
        <property type="gene ID" value="ENSG00000150756.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000511437.6">
        <molecule id="Q6P4H8-1"/>
        <property type="protein sequence ID" value="ENSP00000422338.1"/>
        <property type="gene ID" value="ENSG00000150756.15"/>
    </dbReference>
    <dbReference type="GeneID" id="134145"/>
    <dbReference type="KEGG" id="hsa:134145"/>
    <dbReference type="MANE-Select" id="ENST00000511437.6">
        <property type="protein sequence ID" value="ENSP00000422338.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_199133.4"/>
        <property type="RefSeq protein sequence ID" value="NP_954584.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003jeo.4">
        <molecule id="Q6P4H8-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:27029"/>
    <dbReference type="ClinPGx" id="PA162387281"/>
    <dbReference type="CTD" id="134145"/>
    <dbReference type="DisGeNET" id="134145"/>
    <dbReference type="GeneCards" id="ATPSCKMT"/>
    <dbReference type="HGNC" id="HGNC:27029">
        <property type="gene designation" value="ATPSCKMT"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000150756">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="618568">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000150756"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000150756"/>
    <dbReference type="eggNOG" id="KOG4058">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000014771"/>
    <dbReference type="HOGENOM" id="CLU_068443_4_0_1"/>
    <dbReference type="InParanoid" id="Q6P4H8"/>
    <dbReference type="OMA" id="NPWLVAY"/>
    <dbReference type="OrthoDB" id="66144at2759"/>
    <dbReference type="PAN-GO" id="Q6P4H8">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6P4H8"/>
    <dbReference type="PathwayCommons" id="Q6P4H8"/>
    <dbReference type="SignaLink" id="Q6P4H8"/>
    <dbReference type="Agora" id="ENSG00000150756"/>
    <dbReference type="BioGRID-ORCS" id="134145">
        <property type="hits" value="9 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="FAM173B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="134145"/>
    <dbReference type="Pharos" id="Q6P4H8">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6P4H8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6P4H8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000150756">
        <property type="expression patterns" value="Expressed in ileal mucosa and 169 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6P4H8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030061">
        <property type="term" value="C:mitochondrial crista"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016279">
        <property type="term" value="F:protein-lysine N-methyltransferase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018022">
        <property type="term" value="P:peptidyl-lysine methylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018023">
        <property type="term" value="P:peptidyl-lysine trimethylation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905273">
        <property type="term" value="P:positive regulation of proton-transporting ATP synthase activity, rotational mechanism"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904058">
        <property type="term" value="P:positive regulation of sensory perception of pain"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905706">
        <property type="term" value="P:regulation of mitochondrial ATP synthesis coupled proton transport"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.150:FF:000141">
        <property type="entry name" value="ATP synthase c subunit lysine N-methyltransferase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.150">
        <property type="entry name" value="Vaccinia Virus protein VP39"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026170">
        <property type="entry name" value="FAM173A/B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029063">
        <property type="entry name" value="SAM-dependent_MTases_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13610:SF8">
        <property type="entry name" value="ATP SYNTHASE SUBUNIT C LYSINE N-METHYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13610">
        <property type="entry name" value="METHYLTRANSFERASE DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53335">
        <property type="entry name" value="S-adenosyl-L-methionine-dependent methyltransferases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0489">Methyltransferase</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0949">S-adenosyl-L-methionine</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000321536" description="ATP synthase subunit C lysine N-methyltransferase">
        <location>
            <begin position="1"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="38"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for mitochondrial location" evidence="5">
        <location>
            <begin position="56"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="12">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044724" description="In isoform 2." evidence="6">
        <location>
            <begin position="149"/>
            <end position="165"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039345" description="In dbSNP:rs2438652." evidence="2 3">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039346" description="In dbSNP:rs16884350.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039347" description="In dbSNP:rs17360625.">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039348" description="In dbSNP:rs15757.">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished protein-lysine N-methyltransferase activity and ability to promote chronic pain." evidence="4">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished protein-lysine N-methyltransferase activity." evidence="5">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="29444090"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="30530489"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="29444090"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="30530489"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="29444090"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="HGNC" id="HGNC:27029"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="233" mass="26110" checksum="7F4D1F9E3AC87854" modified="2008-02-26" version="2">MEGGGGIPLETLKEESQSRHVLPASFEVNSLQKSNWGFLLTGLVGGTLVAVYAVATPFVTPALRKVCLPFVPATTKQIENVVKMLRCRRGSLVDIGSGDGRIVIAAAKKGFTAVGYELNPWLVWYSRYRAWREGVHGSAKFYISDLWKVTFSQYSNVVIFGVPQMMLQLEKKLERELEDDARVIACRFPFPHWTPDHVTGEGIDTVWAYDASTFRGREKRPCTSMHFQLPIQA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-09-19" modified="2026-01-28" version="192" xmlns="https://uniprot.org/uniprot">
    <accession>O94805</accession>
    <accession>A4D2D0</accession>
    <accession>O75421</accession>
    <name>ACL6B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Actin-like protein 6B</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>53 kDa BRG1-associated factor B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Actin-related protein Baf53b</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ArpNalpha</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>BRG1-associated factor 53B</fullName>
            <shortName>BAF53B</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="8" type="primary">ACTL6B</name>
        <name type="synonym">ACTL6</name>
        <name type="synonym">BAF53B</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <citation type="journal article" date="2019" name="Am. J. Hum. Genet." volume="104" first="815" last="834">
            <title>Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons.</title>
            <authorList>
                <person name="Bell S."/>
                <person name="Rousseau J."/>
                <person name="Peng H."/>
                <person name="Aouabed Z."/>
                <person name="Priam P."/>
                <person name="Theroux J.F."/>
                <person name="Jefri M."/>
                <person name="Tanti A."/>
                <person name="Wu H."/>
                <person name="Kolobova I."/>
                <person name="Silviera H."/>
                <person name="Manzano-Vargas K."/>
                <person name="Ehresmann S."/>
                <person name="Hamdan F.F."/>
                <person name="Hettige N."/>
                <person name="Zhang X."/>
                <person name="Antonyan L."/>
                <person name="Nassif C."/>
                <person name="Ghaloul-Gonzalez L."/>
                <person name="Sebastian J."/>
                <person name="Vockley J."/>
                <person name="Begtrup A.G."/>
                <person name="Wentzensen I.M."/>
                <person name="Crunk A."/>
                <person name="Nicholls R.D."/>
                <person name="Herman K.C."/>
                <person name="Deignan J.L."/>
                <person name="Al-Hertani W."/>
                <person name="Efthymiou S."/>
                <person name="Salpietro V."/>
                <person name="Miyake N."/>
                <person name="Makita Y."/>
                <person name="Matsumoto N."/>
                <person name="Oestern R."/>
                <person name="Houge G."/>
                <person name="Hafstroem M."/>
                <person name="Fassi E."/>
                <person name="Houlden H."/>
                <person name="Klein Wassink-Ruiter J.S."/>
                <person name="Nelson D."/>
                <person name="Goldstein A."/>
                <person name="Dabir T."/>
                <person name="van Gils J."/>
                <person name="Bourgeron T."/>
                <person name="Delorme R."/>
                <person name="Cooper G.M."/>
                <person name="Martinez J.E."/>
                <person name="Finnila C.R."/>
                <person name="Carmant L."/>
                <person name="Lortie A."/>
                <person name="Oegema R."/>
                <person name="van Gassen K."/>
                <person name="Mehta S.G."/>
                <person name="Huhle D."/>
                <person name="Abou Jamra R."/>
                <person name="Martin S."/>
                <person name="Brunner H.G."/>
                <person name="Lindhout D."/>
                <person name="Au M."/>
                <person name="Graham J.M. Jr."/>
                <person name="Coubes C."/>
                <person name="Turecki G."/>
                <person name="Gravel S."/>
                <person name="Mechawar N."/>
                <person name="Rossignol E."/>
                <person name="Michaud J.L."/>
                <person name="Lessard J."/>
                <person name="Ernst C."/>
                <person name="Campeau P.M."/>
            </authorList>
            <dbReference type="PubMed" id="31031012"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2019.03.022"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>VARIANTS DEE76 97-ARG--PRO-426 DEL; GLN-130; PHE-147 DEL; 186-GLN--PRO-426 DEL; PRO-206; 242-GLN--PRO-426 DEL; 247-TRP--PRO-426 DEL; 284-TYR--PRO-426 DEL; SER-349; 411-GLN--PRO-426 DEL AND 425-CYS-PRO-426 DEL</scope>
        <scope>VARIANTS IDDSSAD GLY-77 AND ARG-343</scope>
        <scope>CHARACTERIZATION OF VARIANT IDDSSAD ARG-343</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2019" name="Genet. Med." volume="21" first="736" last="742">
            <title>Autozygome and high throughput confirmation of disease genes candidacy.</title>
            <authorList>
                <person name="Maddirevula S."/>
                <person name="Alzahrani F."/>
                <person name="Al-Owain M."/>
                <person name="Al Muhaizea M.A."/>
                <person name="Kayyali H.R."/>
                <person name="AlHashem A."/>
                <person name="Rahbeeni Z."/>
                <person name="Al-Otaibi M."/>
                <person name="Alzaidan H.I."/>
                <person name="Balobaid A."/>
                <person name="El Khashab H.Y."/>
                <person name="Bubshait D.K."/>
                <person name="Faden M."/>
                <person name="Yamani S.A."/>
                <person name="Dabbagh O."/>
                <person name="Al-Mureikhi M."/>
                <person name="Jasser A.A."/>
                <person name="Alsaif H.S."/>
                <person name="Alluhaydan I."/>
                <person name="Seidahmed M.Z."/>
                <person name="Alabbasi B.H."/>
                <person name="Almogarri I."/>
                <person name="Kurdi W."/>
                <person name="Akleh H."/>
                <person name="Qari A."/>
                <person name="Al Tala S.M."/>
                <person name="Alhomaidi S."/>
                <person name="Kentab A.Y."/>
                <person name="Salih M.A."/>
                <person name="Chedrawi A."/>
                <person name="Alameer S."/>
                <person name="Tabarki B."/>
                <person name="Shamseldin H.E."/>
                <person name="Patel N."/>
                <person name="Ibrahim N."/>
                <person name="Abdulwahab F."/>
                <person name="Samira M."/>
                <person name="Goljan E."/>
                <person name="Abouelhoda M."/>
                <person name="Meyer B.F."/>
                <person name="Hashem M."/>
                <person name="Shaheen R."/>
                <person name="AlShahwan S."/>
                <person name="Alfadhel M."/>
                <person name="Ben-Omran T."/>
                <person name="Al-Qattan M.M."/>
                <person name="Monies D."/>
                <person name="Alkuraya F.S."/>
            </authorList>
            <dbReference type="PubMed" id="30237576"/>
            <dbReference type="DOI" id="10.1038/s41436-018-0138-x"/>
        </citation>
        <scope>VARIANT DEE76 333-CYS--PRO-426 DEL</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2019" name="Hum. Genet." volume="138" first="187" last="198">
            <title>Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epileptic encephalopathy with brain hypomyelination and cerebellar atrophy.</title>
            <authorList>
                <person name="Fichera M."/>
                <person name="Failla P."/>
                <person name="Saccuzzo L."/>
                <person name="Miceli M."/>
                <person name="Salvo E."/>
                <person name="Castiglia L."/>
                <person name="Galesi O."/>
                <person name="Grillo L."/>
                <person name="Cali F."/>
                <person name="Greco D."/>
                <person name="Amato C."/>
                <person name="Romano C."/>
                <person name="Elia M."/>
            </authorList>
            <dbReference type="PubMed" id="30656450"/>
            <dbReference type="DOI" id="10.1007/s00439-019-01972-3"/>
        </citation>
        <scope>VARIANTS DEE76 274-GLN--PRO-426 DEL AND SER-349</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 6">Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex), as such plays a role in remodeling mononucleosomes in an ATP-dependent fashion, and is required for postmitotic neural development and dendritic outgrowth. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. ACTL6B/BAF53B is not essential for assembly of the nBAF complex but is required for targeting the complex and CREST to the promoter of genes essential for dendritic growth (By similarity). Essential for neuronal maturation and dendrite development (PubMed:31031012).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 5 6">Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170 and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (PubMed:22952240, PubMed:26601204). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1 and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:22952240, PubMed:26601204). Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A or SMARCD2/BAF60B or SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (ACTB). Note that the nBAF complex is polymorphic in regard to the ATPase, SMARCA2 and SMARCA4 occupying mutually exclusive positions. May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:22952240, PubMed:26601204).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="2 3 4">
        <disease id="DI-05592">
            <name>Developmental and epileptic encephalopathy 76</name>
            <acronym>DEE76</acronym>
            <description>A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE76 is an autosomal recessive form that may result in death in childhood.</description>
            <dbReference type="MIM" id="618468"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-05593">
            <name>Intellectual developmental disorder with severe speech and ambulation defects</name>
            <acronym>IDDSSAD</acronym>
            <description>An autosomal dominant neurodevelopmental disorder with onset in infancy, and characterized by global developmental delay, intellectual disability, ambulation deficits, severe language impairment, and minor dysmorphic features including a wide mouth, diastema, and bulbous nose. Additional manifestations are spasticity, hypotonia and autistic features including stereotypies. Brain imaging show thin corpus callosum, generalized atrophy, and mild periventricular gliosis.</description>
            <dbReference type="MIM" id="618470"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the actin family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAC78795" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF053356">
        <property type="protein sequence ID" value="AAC78795.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB015906">
        <property type="protein sequence ID" value="BAA74576.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF041475">
        <property type="protein sequence ID" value="AAD54678.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314940">
        <property type="protein sequence ID" value="BAG37446.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC099394">
        <property type="protein sequence ID" value="AAP21874.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236956">
        <property type="protein sequence ID" value="EAL23823.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471091">
        <property type="protein sequence ID" value="EAW76502.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020944">
        <property type="protein sequence ID" value="AAH20944.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5702.1"/>
    <dbReference type="RefSeq" id="NP_057272.1">
        <property type="nucleotide sequence ID" value="NM_016188.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O94805"/>
    <dbReference type="SMR" id="O94805"/>
    <dbReference type="BioGRID" id="119529">
        <property type="interactions" value="110"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1196">
        <property type="entry name" value="Polybromo-associated SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1202">
        <property type="entry name" value="Neuron-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1203">
        <property type="entry name" value="Brain-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1207">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1209">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1210">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1211">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1216">
        <property type="entry name" value="Neuron-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1217">
        <property type="entry name" value="Neuron-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1218">
        <property type="entry name" value="Neuron-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1219">
        <property type="entry name" value="Brain-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1220">
        <property type="entry name" value="Brain-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1221">
        <property type="entry name" value="Brain-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1225">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1226">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1227">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1228">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6B-ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4223">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6B-BICRA-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4224">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6B-BICRAL-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4225">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6B-BICRA-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4226">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6B-BICRAL-SMARCA4 variant"/>
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    <dbReference type="CORUM" id="O94805"/>
    <dbReference type="ELM" id="O94805"/>
    <dbReference type="FunCoup" id="O94805">
        <property type="interactions" value="1188"/>
    </dbReference>
    <dbReference type="IntAct" id="O94805">
        <property type="interactions" value="79"/>
    </dbReference>
    <dbReference type="MINT" id="O94805"/>
    <dbReference type="STRING" id="9606.ENSP00000160382"/>
    <dbReference type="iPTMnet" id="O94805"/>
    <dbReference type="PhosphoSitePlus" id="O94805"/>
    <dbReference type="BioMuta" id="ACTL6B"/>
    <dbReference type="jPOST" id="O94805"/>
    <dbReference type="MassIVE" id="O94805"/>
    <dbReference type="PaxDb" id="9606-ENSP00000160382"/>
    <dbReference type="PeptideAtlas" id="O94805"/>
    <dbReference type="ProteomicsDB" id="50445"/>
    <dbReference type="ABCD" id="O94805">
        <property type="antibodies" value="1 sequenced antibody"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="30798">
        <property type="antibodies" value="201 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51412"/>
    <dbReference type="Ensembl" id="ENST00000160382.10">
        <property type="protein sequence ID" value="ENSP00000160382.5"/>
        <property type="gene ID" value="ENSG00000077080.11"/>
    </dbReference>
    <dbReference type="GeneID" id="51412"/>
    <dbReference type="KEGG" id="hsa:51412"/>
    <dbReference type="MANE-Select" id="ENST00000160382.10">
        <property type="protein sequence ID" value="ENSP00000160382.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016188.5"/>
        <property type="RefSeq protein sequence ID" value="NP_057272.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003uvy.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:160"/>
    <dbReference type="ClinPGx" id="PA24482"/>
    <dbReference type="CTD" id="51412"/>
    <dbReference type="DisGeNET" id="51412"/>
    <dbReference type="GeneCards" id="ACTL6B"/>
    <dbReference type="HGNC" id="HGNC:160">
        <property type="gene designation" value="ACTL6B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000077080">
        <property type="expression patterns" value="Group enriched (brain, pituitary gland)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACTL6B"/>
    <dbReference type="MIM" id="612458">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="618468">
        <property type="type" value="phenotype"/>
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    <dbReference type="MIM" id="618470">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000077080"/>
    <dbReference type="Orphanet" id="442835">
        <property type="disease" value="Non-specific early-onset epileptic encephalopathy"/>
    </dbReference>
    <dbReference type="Orphanet" id="528084">
        <property type="disease" value="Non-specific syndromic intellectual disability"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000077080"/>
    <dbReference type="eggNOG" id="KOG0679">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160860"/>
    <dbReference type="HOGENOM" id="CLU_027965_6_0_1"/>
    <dbReference type="InParanoid" id="O94805"/>
    <dbReference type="OMA" id="SKSWHSY"/>
    <dbReference type="OrthoDB" id="5132116at2759"/>
    <dbReference type="PAN-GO" id="O94805">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O94805"/>
    <dbReference type="PathwayCommons" id="O94805"/>
    <dbReference type="Reactome" id="R-HSA-3214858">
        <property type="pathway name" value="RMTs methylate histone arginines"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8939243">
        <property type="pathway name" value="RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9934037">
        <property type="pathway name" value="Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)"/>
    </dbReference>
    <dbReference type="SignaLink" id="O94805"/>
    <dbReference type="SIGNOR" id="O94805"/>
    <dbReference type="Agora" id="ENSG00000077080"/>
    <dbReference type="BioGRID-ORCS" id="51412">
        <property type="hits" value="15 hits in 1162 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTL6B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACTL6B"/>
    <dbReference type="GenomeRNAi" id="51412"/>
    <dbReference type="Pharos" id="O94805">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O94805"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="O94805">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000077080">
        <property type="expression patterns" value="Expressed in cortical plate and 135 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O94805">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140092">
        <property type="term" value="C:bBAF complex"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0035060">
        <property type="term" value="C:brahma complex"/>
        <property type="evidence" value="ECO:0000303"/>
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    <dbReference type="GO" id="GO:0000785">
        <property type="term" value="C:chromatin"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="C:kinetochore"/>
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        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0035267">
        <property type="term" value="C:NuA4 histone acetyltransferase complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="C:nuclear matrix"/>
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        <property type="term" value="C:nucleus"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="C:RSC-type complex"/>
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        <property type="term" value="C:SWI/SNF complex"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="term" value="F:chromatin binding"/>
        <property type="evidence" value="ECO:0000318"/>
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    <dbReference type="GO" id="GO:0005200">
        <property type="term" value="F:structural constituent of cytoskeleton"/>
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        <property type="project" value="ProtInc"/>
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        <property type="term" value="F:transcription coactivator activity"/>
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        <property type="term" value="P:chromatin organization"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006338">
        <property type="term" value="P:chromatin remodeling"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="P:dendrite development"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:negative regulation of cell differentiation"/>
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        <property type="term" value="P:nervous system development"/>
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        <property type="term" value="P:neuron maturation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0045597">
        <property type="term" value="P:positive regulation of cell differentiation"/>
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    <dbReference type="GO" id="GO:0008284">
        <property type="term" value="P:positive regulation of cell population proliferation"/>
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    <dbReference type="GO" id="GO:2000781">
        <property type="term" value="P:positive regulation of double-strand break repair"/>
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        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0045663">
        <property type="term" value="P:positive regulation of myoblast differentiation"/>
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        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="P:positive regulation of stem cell population maintenance"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="P:positive regulation of T cell differentiation"/>
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        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0070316">
        <property type="term" value="P:regulation of G0 to G1 transition"/>
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        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="P:regulation of G1/S transition of mitotic cell cycle"/>
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        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="P:regulation of mitotic metaphase/anaphase transition"/>
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        <property type="project" value="ComplexPortal"/>
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        <property type="term" value="P:regulation of nucleotide-excision repair"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="ComplexPortal"/>
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    <dbReference type="GO" id="GO:0006357">
        <property type="term" value="P:regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd13395">
        <property type="entry name" value="ASKHA_NBD_Arp4_ACTL6-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000796">
        <property type="entry name" value="Actin like 6B"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.90.640.10:FF:000009">
        <property type="entry name" value="Actin-like 6A, isoform CRA_a"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.30.36.70:FF:000005">
        <property type="entry name" value="Actin-like protein 6B"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.420.40:FF:000375">
        <property type="entry name" value="Actin-related protein 8"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.420.40:FF:000058">
        <property type="entry name" value="Putative actin-related protein 5"/>
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        <property type="match status" value="2"/>
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        <property type="entry name" value="Actin, Chain A, domain 2"/>
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        <property type="entry name" value="Actin, Chain A, domain 4"/>
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        <property type="entry name" value="Actin"/>
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        <property type="entry name" value="Actin_CS"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Actin"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ACTINS_2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0156">Chromatin regulator</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0524">Neurogenesis</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000089135" description="Actin-like protein 6B">
        <location>
            <begin position="1"/>
            <end position="426"/>
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    <feature type="region of interest" description="Essential for mediating its function in dendritic development; may contribute to neuronal-specific targeting" evidence="1">
        <location>
            <begin position="39"/>
            <end position="82"/>
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    </feature>
    <feature type="sequence variant" id="VAR_082123" description="In IDDSSAD; uncertain significance; dbSNP:rs1562851259." evidence="4">
        <original>D</original>
        <variation>G</variation>
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            <position position="77"/>
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    <feature type="sequence variant" id="VAR_082125" description="In DEE76; uncertain significance; dbSNP:rs757603505." evidence="4">
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        <variation>Q</variation>
        <location>
            <position position="130"/>
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    <feature type="sequence variant" id="VAR_082126" description="In DEE76; uncertain significance." evidence="4">
        <location>
            <position position="147"/>
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    <feature type="sequence variant" id="VAR_082127" description="In DEE76." evidence="4">
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            <begin position="186"/>
            <end position="426"/>
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    </feature>
    <feature type="sequence variant" id="VAR_082128" description="In DEE76; dbSNP:rs1562848909." evidence="4">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="206"/>
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    </feature>
    <feature type="sequence variant" id="VAR_082129" description="In DEE76." evidence="4">
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            <begin position="242"/>
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    <feature type="sequence variant" id="VAR_082130" description="In DEE76." evidence="4">
        <location>
            <begin position="247"/>
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    <feature type="sequence variant" id="VAR_082131" description="In DEE76." evidence="3">
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            <begin position="274"/>
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    <feature type="sequence variant" id="VAR_082132" description="In DEE76." evidence="4">
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            <begin position="284"/>
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            <begin position="333"/>
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    <feature type="sequence variant" id="VAR_082134" description="In IDDSSAD; probable gain-of-function mutation; dbSNP:rs1131692228." evidence="4">
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            <position position="343"/>
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    <feature type="sequence variant" id="VAR_082135" description="In DEE76; dbSNP:rs955171017." evidence="3 4">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="349"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082136" description="In DEE76." evidence="4">
        <location>
            <begin position="411"/>
            <end position="426"/>
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    <feature type="sequence variant" id="VAR_082137" description="In DEE76; uncertain significance." evidence="4">
        <location>
            <begin position="425"/>
            <end position="426"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q99MR0"/>
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    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="30237576"/>
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    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="30656450"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="31031012"/>
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    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="22952240"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="26601204"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:160"/>
        </source>
    </evidence>
    <sequence length="426" mass="46877" checksum="6E9CEBABB8C81E64" modified="1999-05-01" version="1">MSGGVYGGDEVGALVFDIGSFSVRAGYAGEDCPKADFPTTVGLLAAEEGGGLELEGDKEKKGKIFHIDTNALHVPRDGAEVMSPLKNGMIEDWECFRAILDHTYSKHVKSEPNLHPVLMSEAPWNTRAKREKLTELMFEQYNIPAFFLCKTAVLTAFANGRSTGLVLDSGATHTTAIPVHDGYVLQQGIVKSPLAGDFISMQCRELFQEMAIDIIPPYMIAAKEPVREGAPPNWKKKEKLPQVSKSWHNYMCNEVIQDFQASVLQVSDSPYDEQVAAQMPTVHYEMPNGYNTDYGAERLRIPEGLFDPSNVKGLSGNTMLGVGHVVTTSIGMCDIDIRPGLYGSVIVTGGNTLLQGFTDRLNRELSQKTPPSMRLKLIASNSTMERKFSPWIGGSILASLGTFQQMWISKQEYEEGGKQCVERKCP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NPB9</accession>
    <accession>B2R9U7</accession>
    <name>ACKR4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Atypical chemokine receptor 4</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>C-C chemokine receptor type 11</fullName>
            <shortName>C-C CKR-11</shortName>
            <shortName>CC-CKR-11</shortName>
            <shortName>CCR-11</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>CC chemokine receptor-like 1</fullName>
            <shortName>CCRL1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>CCX CKR</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACKR4</name>
        <name type="synonym">CCBP2</name>
        <name type="synonym">CCR11</name>
        <name type="synonym">CCRL1</name>
        <name type="synonym">VSHK1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Gene" volume="246" first="229" last="238">
            <title>Cloning of CCRL1, an orphan seven transmembrane receptor related to chemokine receptors, expressed abundantly in the heart.</title>
            <authorList>
                <person name="Khoja H."/>
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                <person name="Ng C.-T.L."/>
                <person name="Tucker J."/>
                <person name="Brown T."/>
                <person name="Shyamala V."/>
            </authorList>
            <dbReference type="PubMed" id="10767544"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(00)00076-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="9550" last="9556">
            <title>CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines.</title>
            <authorList>
                <person name="Schweickart V.L."/>
                <person name="Epp A."/>
                <person name="Raport C.J."/>
                <person name="Gray P.W."/>
            </authorList>
            <dbReference type="PubMed" id="10734104"/>
            <dbReference type="DOI" id="10.1074/jbc.275.13.9550"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2000" name="J. Immunol." volume="164" first="2851" last="2856">
            <title>Identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK.</title>
            <authorList>
                <person name="Gosling J."/>
                <person name="Dairaghi D.J."/>
                <person name="Wang Y."/>
                <person name="Hanley M."/>
                <person name="Talbot D."/>
                <person name="Miao Z."/>
                <person name="Schall T.J."/>
            </authorList>
            <dbReference type="PubMed" id="10706668"/>
            <dbReference type="DOI" id="10.4049/jimmunol.164.6.2851"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION IN CHEMOKINES BINDING</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
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                <person name="Fukuzumi Y."/>
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                <person name="Komiyama M."/>
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                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2002" name="Eur. J. Immunol." volume="32" first="1230" last="1241">
            <title>Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR.</title>
            <authorList>
                <person name="Townson J.R."/>
                <person name="Nibbs R.J."/>
            </authorList>
            <dbReference type="PubMed" id="11981810"/>
            <dbReference type="DOI" id="10.1002/1521-4141(200205)32:5&lt;1230::aid-immu1230&gt;3.0.co;2-l"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2010" name="Curr. Top. Microbiol. Immunol." volume="341" first="15" last="36">
            <title>Chemokine decoy receptors: structure-function and biological properties.</title>
            <authorList>
                <person name="Bonecchi R."/>
                <person name="Savino B."/>
                <person name="Borroni E.M."/>
                <person name="Mantovani A."/>
                <person name="Locati M."/>
            </authorList>
            <dbReference type="PubMed" id="20373092"/>
            <dbReference type="DOI" id="10.1007/82_2010_19"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2012" name="Immunol. Lett." volume="145" first="30" last="38">
            <title>The biochemistry and biology of the atypical chemokine receptors.</title>
            <authorList>
                <person name="Graham G.J."/>
                <person name="Locati M."/>
                <person name="Mantovani A."/>
                <person name="Rot A."/>
                <person name="Thelen M."/>
            </authorList>
            <dbReference type="PubMed" id="22698181"/>
            <dbReference type="DOI" id="10.1016/j.imlet.2012.04.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2013" name="Biochem. Soc. Trans." volume="41" first="231" last="236">
            <title>Atypical chemokine receptors: from silence to sound.</title>
            <authorList>
                <person name="Cancellieri C."/>
                <person name="Vacchini A."/>
                <person name="Locati M."/>
                <person name="Bonecchi R."/>
                <person name="Borroni E.M."/>
            </authorList>
            <dbReference type="PubMed" id="23356288"/>
            <dbReference type="DOI" id="10.1042/bst20120246"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2013" name="Br. J. Pharmacol." volume="168" first="1375" last="1387">
            <title>Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-like protein CCX-CKR.</title>
            <authorList>
                <person name="Vinet J."/>
                <person name="van Zwam M."/>
                <person name="Dijkstra I.M."/>
                <person name="Brouwer N."/>
                <person name="van Weering H.R."/>
                <person name="Watts A."/>
                <person name="Meijer M."/>
                <person name="Fokkens M.R."/>
                <person name="Kannan V."/>
                <person name="Verzijl D."/>
                <person name="Vischer H.F."/>
                <person name="Smit M.J."/>
                <person name="Leurs R."/>
                <person name="Biber K."/>
                <person name="Boddeke H.W."/>
            </authorList>
            <dbReference type="PubMed" id="23121557"/>
            <dbReference type="DOI" id="10.1111/bph.12042"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2013" name="J. Biol. Chem." volume="288" first="7169" last="7181">
            <title>Beta-arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR.</title>
            <authorList>
                <person name="Watts A.O."/>
                <person name="Verkaar F."/>
                <person name="van der Lee M.M."/>
                <person name="Timmerman C.A."/>
                <person name="Kuijer M."/>
                <person name="van Offenbeek J."/>
                <person name="van Lith L.H."/>
                <person name="Smit M.J."/>
                <person name="Leurs R."/>
                <person name="Zaman G.J."/>
                <person name="Vischer H.F."/>
            </authorList>
            <dbReference type="PubMed" id="23341447"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.406108"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH ARRB1 AND ARRB2</scope>
    </reference>
    <comment type="function">
        <text evidence="3 7 8">Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7 8">Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Recycling endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cell membrane</location>
            <topology evidence="8">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text>Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via caveolae. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5 6">Predominantly expressed in heart. Lower expression in lung, pancreas, spleen, colon, skeletal muscle and small intestine.</text>
    </comment>
    <comment type="PTM">
        <text>The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="AAF59827.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF193507">
        <property type="protein sequence ID" value="AAF61299.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF233281">
        <property type="protein sequence ID" value="AAF44751.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY221094">
        <property type="protein sequence ID" value="AAO65972.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313923">
        <property type="protein sequence ID" value="BAG36644.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC069438">
        <property type="protein sequence ID" value="AAH69438.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3075.1"/>
    <dbReference type="RefSeq" id="NP_057641.1">
        <property type="nucleotide sequence ID" value="NM_016557.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_848540.1">
        <property type="nucleotide sequence ID" value="NM_178445.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NPB9"/>
    <dbReference type="SMR" id="Q9NPB9"/>
    <dbReference type="BioGRID" id="119606">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-5918N"/>
    <dbReference type="FunCoup" id="Q9NPB9">
        <property type="interactions" value="729"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NPB9">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000249887"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="315"/>
    <dbReference type="GlyCosmos" id="Q9NPB9">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NPB9">
        <property type="glycosylation" value="3 sites"/>
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    <dbReference type="iPTMnet" id="Q9NPB9"/>
    <dbReference type="PhosphoSitePlus" id="Q9NPB9"/>
    <dbReference type="BioMuta" id="ACKR4"/>
    <dbReference type="DMDM" id="14285406"/>
    <dbReference type="MassIVE" id="Q9NPB9"/>
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    <dbReference type="PeptideAtlas" id="Q9NPB9"/>
    <dbReference type="ProteomicsDB" id="81962"/>
    <dbReference type="Antibodypedia" id="17718">
        <property type="antibodies" value="252 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51554"/>
    <dbReference type="Ensembl" id="ENST00000249887.3">
        <property type="protein sequence ID" value="ENSP00000249887.2"/>
        <property type="gene ID" value="ENSG00000129048.8"/>
    </dbReference>
    <dbReference type="GeneID" id="51554"/>
    <dbReference type="KEGG" id="hsa:51554"/>
    <dbReference type="MANE-Select" id="ENST00000249887.3">
        <property type="protein sequence ID" value="ENSP00000249887.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_016557.4"/>
        <property type="RefSeq protein sequence ID" value="NP_057641.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003eow.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1611"/>
    <dbReference type="ClinPGx" id="PA35036"/>
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    <dbReference type="DisGeNET" id="51554"/>
    <dbReference type="GeneCards" id="ACKR4"/>
    <dbReference type="HGNC" id="HGNC:1611">
        <property type="gene designation" value="ACKR4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000129048">
        <property type="expression patterns" value="Tissue enhanced (intestine)"/>
    </dbReference>
    <dbReference type="MIM" id="606065">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000129048"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000129048"/>
    <dbReference type="eggNOG" id="KOG3656">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01030000234667"/>
    <dbReference type="HOGENOM" id="CLU_009579_8_3_1"/>
    <dbReference type="InParanoid" id="Q9NPB9"/>
    <dbReference type="OMA" id="YNVVKLC"/>
    <dbReference type="OrthoDB" id="9874829at2759"/>
    <dbReference type="PAN-GO" id="Q9NPB9">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NPB9"/>
    <dbReference type="PathwayCommons" id="Q9NPB9"/>
    <dbReference type="Reactome" id="R-HSA-380108">
        <property type="pathway name" value="Chemokine receptors bind chemokines"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NPB9"/>
    <dbReference type="SIGNOR" id="Q9NPB9"/>
    <dbReference type="Agora" id="ENSG00000129048"/>
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        <property type="hits" value="19 hits in 1106 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ACKR4">
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    <dbReference type="GeneWiki" id="CCRL1"/>
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    <dbReference type="Pharos" id="Q9NPB9">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NPB9"/>
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        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NPB9">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000129048">
        <property type="expression patterns" value="Expressed in duodenum and 103 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NPB9">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005769">
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009897">
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        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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    <dbReference type="GO" id="GO:0019957">
        <property type="term" value="F:C-C chemokine binding"/>
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        <property type="term" value="F:C-C chemokine receptor activity"/>
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    <dbReference type="GO" id="GO:0004950">
        <property type="term" value="F:chemokine receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="project" value="InterPro"/>
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0060326">
        <property type="term" value="P:cell chemotaxis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="P:chemotaxis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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    <dbReference type="GO" id="GO:0007186">
        <property type="term" value="P:G protein-coupled receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006955">
        <property type="term" value="P:immune response"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007204">
        <property type="term" value="P:positive regulation of cytosolic calcium ion concentration"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd15176">
        <property type="entry name" value="7tmA_ACKR4_CCR11"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="C-C chemokine receptor type 6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.1070.10">
        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005383">
        <property type="entry name" value="ACKR4"/>
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    <dbReference type="InterPro" id="IPR050119">
        <property type="entry name" value="CCR1-9-like"/>
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    <dbReference type="InterPro" id="IPR000355">
        <property type="entry name" value="Chemokine_rcpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000276">
        <property type="entry name" value="GPCR_Rhodpsn"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017452">
        <property type="entry name" value="GPCR_Rhodpsn_7TM"/>
    </dbReference>
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        <property type="entry name" value="ATYPICAL CHEMOKINE RECEPTOR 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10489">
        <property type="entry name" value="CELL ADHESION MOLECULE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00001">
        <property type="entry name" value="7tm_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00657">
        <property type="entry name" value="CCCHEMOKINER"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01558">
        <property type="entry name" value="CHEMOKINER11"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00237">
        <property type="entry name" value="GPCRRHODOPSN"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF81321">
        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0297">G-protein coupled receptor</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0807">Transducer</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000069296" description="Atypical chemokine receptor 4">
        <location>
            <begin position="1"/>
            <end position="350"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="1"/>
            <end position="42"/>
        </location>
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        <location>
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</entry>
<entry dataset="Swiss-Prot" created="2000-12-01" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
    <accession>O15218</accession>
    <name>ACKR5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10 12">Atypical chemokine receptor 5</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>G-protein coupled receptor 182</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">ACKR5</name>
        <name evidence="11" type="synonym">ADMR</name>
        <name type="synonym">GPR182</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Biochem. Biophys. Res. Commun." volume="240" first="183" last="188">
            <title>Molecular cloning of a novel human receptor gene with homology to the rat adrenomedullin receptor and high expression in heart and immune system.</title>
            <authorList>
                <person name="Haenze J."/>
                <person name="Dittrich K."/>
                <person name="Dotsch J."/>
                <person name="Rascher W."/>
            </authorList>
            <dbReference type="PubMed" id="9367907"/>
            <dbReference type="DOI" id="10.1006/bbrc.1997.7631"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="Biochem. Biophys. Res. Commun." volume="244" first="832" last="837">
            <title>Expression of the rat adrenomedullin receptor or a putative human adrenomedullin receptor does not correlate with adrenomedullin binding or functional response.</title>
            <authorList>
                <person name="Kennedy S.P."/>
                <person name="Sun D."/>
                <person name="Oleynek J.J."/>
                <person name="Hoth C.F."/>
                <person name="Kong J."/>
                <person name="Hill R.J."/>
            </authorList>
            <dbReference type="PubMed" id="9535752"/>
            <dbReference type="DOI" id="10.1006/bbrc.1998.8349"/>
        </citation>
        <scope>CAUTION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2021" name="Proc. Natl. Acad. Sci. U.S.A." volume="118" first="0" last="0">
            <title>GPR182 is an endothelium-specific atypical chemokine receptor that maintains hematopoietic stem cell homeostasis.</title>
            <authorList>
                <person name="Le Mercier A."/>
                <person name="Bonnavion R."/>
                <person name="Yu W."/>
                <person name="Alnouri M.W."/>
                <person name="Ramas S."/>
                <person name="Zhang Y."/>
                <person name="Jaeger Y."/>
                <person name="Roquid K.A."/>
                <person name="Jeong H.W."/>
                <person name="Sivaraj K.K."/>
                <person name="Cho H."/>
                <person name="Chen X."/>
                <person name="Strilic B."/>
                <person name="Sijmonsma T."/>
                <person name="Adams R."/>
                <person name="Schroeder T."/>
                <person name="Rieger M.A."/>
                <person name="Offermanns S."/>
            </authorList>
            <dbReference type="PubMed" id="33875597"/>
            <dbReference type="DOI" id="10.1073/pnas.2021596118"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH BETA-ARRESTINS</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2022" name="Nat. Commun." volume="13" first="97" last="97">
            <title>GPR182 limits antitumor immunity via chemokine scavenging in mouse melanoma models.</title>
            <authorList>
                <person name="Torphy R.J."/>
                <person name="Sun Y."/>
                <person name="Lin R."/>
                <person name="Caffrey-Carr A."/>
                <person name="Fujiwara Y."/>
                <person name="Ho F."/>
                <person name="Miller E.N."/>
                <person name="McCarter M.D."/>
                <person name="Lyons T.R."/>
                <person name="Schulick R.D."/>
                <person name="Kedl R.M."/>
                <person name="Zhu Y."/>
            </authorList>
            <dbReference type="PubMed" id="35013216"/>
            <dbReference type="DOI" id="10.1038/s41467-021-27658-x"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2023" name="Front. Pharmacol." volume="14" first="1297596" last="1297596">
            <title>Large chemokine binding spectrum of human and mouse atypical chemokine receptor GPR182 (ACKR5).</title>
            <authorList>
                <person name="Bonnavion R."/>
                <person name="Liu S."/>
                <person name="Kawase H."/>
                <person name="Roquid K.A."/>
                <person name="Offermanns S."/>
            </authorList>
            <dbReference type="PubMed" id="38026988"/>
            <dbReference type="DOI" id="10.3389/fphar.2023.1297596"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2023" name="Front. Immunol." volume="14" first="1242531" last="1242531">
            <title>GPR182 is a broadly scavenging atypical chemokine receptor influencing T-independent immunity.</title>
            <authorList>
                <person name="Melgrati S."/>
                <person name="Gerken O.J."/>
                <person name="Artinger M."/>
                <person name="Radice E."/>
                <person name="Szpakowska M."/>
                <person name="Chevigne A."/>
                <person name="D'Uonnolo G."/>
                <person name="Antonello P."/>
                <person name="Thelen S."/>
                <person name="Pelczar P."/>
                <person name="Legler D.F."/>
                <person name="Thelen M."/>
            </authorList>
            <dbReference type="PubMed" id="37554323"/>
            <dbReference type="DOI" id="10.3389/fimmu.2023.1242531"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 6 7">Atypical chemokine receptor that regulates chemokine levels and localization through chemokine binding, independently of activating classical ligand-induced signaling pathways such as G-protein activation and Ca(2+) mobilization (PubMed:33875597, PubMed:35013216, PubMed:37554323, PubMed:38026988). Instead, it mediates chemokine sequestration, transport, or internalization to control their availability (PubMed:33875597, PubMed:35013216, PubMed:37554323, PubMed:38026988). Acts as a scavenger for a broad range of chemokines from CXC, CC and XC chemokine ligand famillies including CXCL9, CXCL10, CXCL12, CXCL13, CXCL11, CXCL14, CCL1, CCL11, CCL19, CCL25, CCL28 and XCL1 (PubMed:33875597, PubMed:35013216, PubMed:38026988). Is the only atypical receptor for chemokines CXCL13 and CCL28 (PubMed:37554323). Has a strong constitutive association with beta-arrestins, which is essential for intracellular receptor trafficking and chemokine scavenging, and occurs independently of ligand binding (PubMed:33875597, PubMed:37554323). Cooperates with ACKR3 and ACKR4 in regulating serum levels of CXCL12 and CCL19, respectively (PubMed:37554323). Acts as an important modulator of cellular immunity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 6">Strong constitutive association with beta-arrestins; leading to internalization of ACKR5 and its ligands.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Endosome membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="6">Spontaneously traffic between the plasma membrane and endosomes, in a beta-arrestin-dependent manner.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Highly expressed in heart, skeletal muscle, immune system, adrenal gland and liver.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="8 9">Was originally thought to be a receptor for adrenomedullin (PubMed:9367907). However, this function was later not confirmed (PubMed:9535752).</text>
    </comment>
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        <property type="protein sequence ID" value="CAA73910.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAP23201.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH34761.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8927.1"/>
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        <property type="entry name" value="JC5784"/>
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        <property type="nucleotide sequence ID" value="NM_007264.3"/>
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        <property type="nucleotide sequence ID" value="XM_054370944.1"/>
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        <property type="project" value="UniProtKB-KW"/>
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    </dbReference>
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    <dbReference type="InterPro" id="IPR000276">
        <property type="entry name" value="GPCR_Rhodpsn"/>
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    <dbReference type="InterPro" id="IPR017452">
        <property type="entry name" value="GPCR_Rhodpsn_7TM"/>
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    <dbReference type="InterPro" id="IPR047143">
        <property type="entry name" value="GPER1-like"/>
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    <dbReference type="PANTHER" id="PTHR24226:SF0">
        <property type="entry name" value="G-PROTEIN COUPLED RECEPTOR 182"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR24226">
        <property type="entry name" value="G-PROTEIN COUPLED RECEPTOR 182 AND ESTROGEN RECEPTOR 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00001">
        <property type="entry name" value="7tm_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00643">
        <property type="entry name" value="G10DORPHANR"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00237">
        <property type="entry name" value="GPCRRHODOPSN"/>
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    <dbReference type="SUPFAM" id="SSF81321">
        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000069112" description="Atypical chemokine receptor 5">
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            <begin position="1"/>
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    <feature type="topological domain" description="Extracellular" evidence="2">
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            <begin position="1"/>
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    <feature type="transmembrane region" description="Helical; Name=1" evidence="2">
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            <begin position="58"/>
            <end position="79"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="2">
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            <begin position="80"/>
            <end position="90"/>
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    <feature type="transmembrane region" description="Helical; Name=2" evidence="2">
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            <begin position="91"/>
            <end position="113"/>
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    <feature type="topological domain" description="Extracellular" evidence="2">
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    <feature type="transmembrane region" description="Helical; Name=7" evidence="2">
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    <feature type="sequence variant" id="VAR_033464" description="In dbSNP:rs35493121.">
        <original>C</original>
        <variation>R</variation>
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            <position position="349"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P43142"/>
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    <evidence type="ECO:0000255" key="2"/>
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            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
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            <dbReference type="PubMed" id="33875597"/>
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            <dbReference type="PubMed" id="37554323"/>
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            <dbReference type="PubMed" id="38026988"/>
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            <dbReference type="PubMed" id="9367907"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="9535752"/>
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            <dbReference type="PubMed" id="37554323"/>
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    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="9535752"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:13708"/>
        </source>
    </evidence>
    <sequence length="404" mass="45323" checksum="EF187ECFDF2DC6C1" modified="1998-01-01" version="1">MSVKPSWGPGPSEGVTAVPTSDLGEIHNWTELLDLFNHTLSECHVELSQSTKRVVLFALYLAMFVVGLVENLLVICVNWRGSGRAGLMNLYILNMAIADLGIVLSLPVWMLEVTLDYTWLWGSFSCRFTHYFYFVNMYSSIFFLVCLSVDRYVTLTSASPSWQRYQHRVRRAMCAGIWVLSAIIPLPEVVHIQLVEGPEPMCLFMAPFETYSTWALAVALSTTILGFLLPFPLITVFNVLTACRLRQPGQPKSRRHCLLLCAYVAVFVMCWLPYHVTLLLLTLHGTHISLHCHLVHLLYFFYDVIDCFSMLHCVINPILYNFLSPHFRGRLLNAVVHYLPKDQTKAGTCASSSSCSTQHSIIITKGDSQPAAAAPHPEPSLSFQAHHLLPNTSPISPTQPLTPS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>Q16570</accession>
    <accession>A8YPG5</accession>
    <accession>O75898</accession>
    <accession>Q16300</accession>
    <accession>Q8WWE3</accession>
    <accession>Q9UJP0</accession>
    <accession>Q9UKZ5</accession>
    <accession>Q9UKZ6</accession>
    <accession>Q9UQE1</accession>
    <name>ACKR1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Atypical chemokine receptor 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20 21 22 23 24 25">Duffy antigen receptor for chemokines</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Duffy antigen/chemokine receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22 27">Duffy blood group antigen</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Fy glycoprotein</fullName>
            <shortName>GpFy</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Glycoprotein D</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Plasmodium vivax receptor</fullName>
        </alternativeName>
        <cdAntigenName>CD234</cdAntigenName>
    </protein>
    <gene>
        <name type="primary">ACKR1</name>
        <name evidence="20 21 22 23 24 25" type="synonym">DARC</name>
        <name type="synonym">FY</name>
        <name type="synonym">GPD</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Proc. Natl. Acad. Sci. U.S.A." volume="90" first="10793" last="10797">
            <title>Cloning of glycoprotein D cDNA, which encodes the major subunit of the Duffy blood group system and the receptor for the Plasmodium vivax malaria parasite.</title>
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                <person name="Chaudhuri A."/>
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            </authorList>
            <dbReference type="PubMed" id="8248172"/>
            <dbReference type="DOI" id="10.1073/pnas.90.22.10793"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>VARIANT ASP-42</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1995" name="Nat. Genet." volume="10" first="224" last="228">
            <title>Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals.</title>
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                <person name="Tournamille C."/>
                <person name="Colin Y."/>
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                <person name="Le van Kim C."/>
            </authorList>
            <dbReference type="PubMed" id="7663520"/>
            <dbReference type="DOI" id="10.1038/ng0695-224"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ASP-42</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Blood" volume="85" first="622" last="626">
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                <person name="Iwamoto S."/>
                <person name="Omi T."/>
                <person name="Kajii E."/>
                <person name="Ikemoto S."/>
            </authorList>
            <dbReference type="PubMed" id="7833467"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>Arg89Cys substitution results in very low membrane expression of the Duffy antigen/receptor for chemokines in Fy(x) individuals.</title>
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                <person name="Tournamille C."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2)</scope>
        <scope>VARIANTS ASP-42; CYS-89 AND THR-100</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
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        <citation type="journal article" date="1998" name="Br. J. Haematol." volume="103" first="1184" last="1191">
            <title>The Fy(x) phenotype is associated with a missense mutation in the Fy(b) allele predicting Arg89Cys in the Duffy glycoprotein.</title>
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                <person name="Olsson M.L."/>
                <person name="Smythe J.S."/>
                <person name="Hansson C."/>
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            <dbReference type="PubMed" id="9886340"/>
            <dbReference type="DOI" id="10.1046/j.1365-2141.1998.01083.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANTS ASP-42; CYS-89 AND THR-100</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2007-09" db="EMBL/GenBank/DDBJ databases">
            <title>New polymorphisms in DARC.</title>
            <authorList>
                <person name="Doescher A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT PHE-326</scope>
        <source>
            <tissue>Peripheral blood</tissue>
        </source>
    </reference>
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            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
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                <person name="McLaren S."/>
                <person name="Milne S."/>
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                <person name="Parker A."/>
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                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
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            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT PHE-326</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
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                <person name="Zimmerman P.A."/>
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            <dbReference type="PubMed" id="10570183"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-117 (ISOFORMS 1 AND 2)</scope>
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                <person name="Miller L.H."/>
            </authorList>
            <dbReference type="PubMed" id="8879225"/>
            <dbReference type="DOI" id="10.1084/jem.184.4.1531"/>
        </citation>
        <scope>INTERACTION WITH PLASMODIUM DBPALPHA AND DBP (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="11">
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        </citation>
        <scope>INTERACTION WITH PLASMODIUM DBP (MICROBIAL INFECTION)</scope>
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            <dbReference type="PubMed" id="12956774"/>
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        </citation>
        <scope>DISULFIDE BONDS</scope>
        <scope>GLYCOSYLATION AT ASN-16</scope>
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            <dbReference type="PubMed" id="16024106"/>
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        </citation>
        <scope>INTERACTION WITH PLASMODIUM DBP (MICROBIAL INFECTION)</scope>
        <scope>DBP-BINDING REGION</scope>
        <scope>MUTAGENESIS OF GLU-9; LEU-10; SER-11; PRO-12; SER-13; GLU-15; ASN-16; SER-17; SER-18; GLN-19; LEU-20; ASP-21; PHE-22; GLU-23; ASP-24; VAL-25; TRP-26; ASN-27; SER-28; SER-29 AND TYR-30</scope>
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            <dbReference type="PubMed" id="15720551"/>
            <dbReference type="DOI" id="10.1111/j.1365-2958.2005.04484.x"/>
        </citation>
        <scope>INTERACTION WITH PLASMODIUM DBP (MICROBIAL INFECTION)</scope>
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            </authorList>
            <dbReference type="PubMed" id="17389925"/>
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        </citation>
        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN RESISTANCE TO MALARIA</scope>
    </reference>
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            <dbReference type="PubMed" id="20373092"/>
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        <scope>REVIEW</scope>
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        </citation>
        <scope>REVIEW</scope>
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        </citation>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
    </reference>
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        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
    </reference>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 14-43 IN COMPLEX WITH 211-525 OF PLASMODIUM DBP</scope>
        <scope>INTERACTION WITH PLASMODIUM DBP (MICROBIAL INFECTION)</scope>
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            <dbReference type="PubMed" id="37336887"/>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 1-60 SULFATED AT TYR-41 IN COMPLEX WITH 215-508 OF PLASMODIUM DBP AND MONOCLONAL ANTIBODY</scope>
        <scope>SULFATION (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="24">
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            <title>Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism.</title>
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        </citation>
        <scope>VARIANT ASP-42</scope>
        <source>
            <tissue>Peripheral blood</tissue>
        </source>
    </reference>
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        <scope>VARIANT CYS-89</scope>
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            <title>Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC).</title>
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            <dbReference type="DOI" id="10.1111/j.1365-2958.2004.04478.x"/>
        </citation>
        <scope>VARIANT ASP-42</scope>
        <scope>SULFATION AT TYR-30 AND TYR-41</scope>
        <scope>SULFATION (MICROBIAL INFECTION)</scope>
        <scope>MUTAGENESIS OF TYR-30 AND TYR-41</scope>
    </reference>
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            <dbReference type="PubMed" id="18179887"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2007.09.003"/>
        </citation>
        <scope>INVOLVEMENT IN WBCQ1</scope>
    </reference>
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            <authorList>
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                <person name="Tandon A."/>
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        <scope>ERRATUM OF PUBMED:18179887</scope>
    </reference>
    <comment type="function">
        <text>Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1 and TARC. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.</text>
    </comment>
    <comment type="function">
        <text evidence="11">(Microbial infection) Acts as a receptor for the malaria parasite Plasmodium vivax.</text>
    </comment>
    <comment type="function">
        <text evidence="9">(Microbial infection) Acts as a receptor for the malaria parasite Plasmodium knowlesi.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 6 7 8 15">(Microbial infection) Interacts (via N-terminal extracellular domain) with Plasmodium vivax Duffy receptor (DBP) (via PvRII region).</text>
    </comment>
    <comment type="subunit">
        <text evidence="15">(Microbial infection) Interacts (via N-terminal extracellular domain) with Plasmodium knowlesi Duffy receptor alpha form (DBPalpha) (via region II).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15935975">
            <id>Q16570-1</id>
        </interactant>
        <interactant intactId="EBI-15935953">
            <id>P22290</id>
            <label>PVDR</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21403047">
            <id>Q16570-2</id>
        </interactant>
        <interactant intactId="EBI-489374">
            <id>P51681</id>
            <label>CCR5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Recycling endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text>Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via caveolae. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q16570-1</id>
            <name>2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q16570-2</id>
            <name>1</name>
            <sequence type="described" ref="VSP_001323"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Found in adult kidney, adult spleen, bone marrow and fetal liver. In particular, it is expressed along postcapillary venules throughout the body, except in the adult liver. Erythroid cells and postcapillary venule endothelium are the principle tissues expressing duffy. Fy(-A-B) individuals do not express duffy in the bone marrow, however they do, in postcapillary venule endothelium.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5">Sulfation at Tyr-41 facilitates interaction with MGSA/CXCL1, RANTES/CCL5 and MCP-1/CCL2 but not IL8/CXCL8 (PubMed:15720550). Sulfation at Tyr-30 facilitates interaction with IL8/CXCL8 (PubMed:15720550).</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 10">(Microbial infection) Sulfation at Tyr-41 facilitates interaction with Plasmodium vivax Duffy receptor (DBP) (PubMed:15720550). Sulfation at Tyr-30/Tyr-41 and Tyr-41 alone increases binding affinity of Plasmodium vivax parasites and likely promotes invasion of red blood cells (PubMed:37336887).</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 10">(Microbial infection) Sulfation at Tyr-41 facilitates interaction with Plasmodium knowlesi Duffy receptor alpha form (DBPalpha) (PubMed:15720550). Sulfation at Tyr-30/Tyr-41 and Tyr-41 alone increases binding affinity of Plasmodium knowlesi parasites and likely promotes invasion of red blood cells (PubMed:37336887).</text>
    </comment>
    <comment type="polymorphism">
        <text>DARC is responsible for the Duffy blood group system (FY) [MIM:110700]. The molecular basis of the Fy(A)=Fy1/Fy(B)=Fy2 blood group antigens is a single variation in position 42; Gly-42 corresponds to Fy(A) and Asp-42 to Fy(B). Individuals that do not produce the Duffy antigen (FY(A-B-)) are more resistant to infection by the malarial parasite Plasmodium vivax. This allele is found predominantly in population of African origin [MIM:611162].</text>
    </comment>
    <comment type="polymorphism">
        <text>Genetic variations in DARC define the white blood cell count quantitative trait locus 1 (WBCQ1) [MIM:611862]. Peripheral white blood cell count (WBC) is a common clinical measurement, used to determine evidence of acute inflammation or infection. Peripheral WBC is the sum of several cell types including neutrophils and lymphocytes, which are the most common types of WBC, as well as less common cell types such as eosinophils, basophils, and monocytes. Elevated WBC has been associated with risk of coronary heart disease, cancer, and all-cause mortality. White blood cell levels have widespread clinical applications including assessment of patients undergoing chemotherapy and evaluation of infection.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="11">A subset of erythroblasts from genotypically Duffy-negative individuals transiently expresses ACKR1 during terminal erythroid differentiation and P.vivax merozoites can invade these ACKR1-expressing Duffy-negative erythroblasts.</text>
    </comment>
    <comment type="similarity">
        <text evidence="29">Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Duffy_antigen"/>
        <text>Duffy antigen entry</text>
    </comment>
    <dbReference type="EMBL" id="U01839">
        <property type="protein sequence ID" value="AAC50055.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X85785">
        <property type="protein sequence ID" value="CAA59770.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="S76830">
        <property type="protein sequence ID" value="AAB33239.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF055992">
        <property type="protein sequence ID" value="AAC72301.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF030521">
        <property type="protein sequence ID" value="AAD20435.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AM887935">
        <property type="protein sequence ID" value="CAP12644.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AL035403">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC017817">
        <property type="protein sequence ID" value="AAH17817.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF100634">
        <property type="protein sequence ID" value="AAF02415.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF100634">
        <property type="protein sequence ID" value="AAF02416.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="CCDS" id="CCDS1183.1">
        <molecule id="Q16570-1"/>
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        <molecule id="Q16570-2"/>
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        <property type="resolution" value="1.95 A"/>
        <property type="chains" value="C=16-43"/>
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        <property type="resolution" value="3.65 A"/>
        <property type="chains" value="A/B=46-312"/>
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        <property type="RefSeq protein sequence ID" value="NP_002027.2"/>
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    </dbReference>
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    <dbReference type="PathwayCommons" id="Q16570"/>
    <dbReference type="Reactome" id="R-HSA-375276">
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    <dbReference type="SignaLink" id="Q16570"/>
    <dbReference type="Agora" id="ENSG00000213088"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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    <dbReference type="EvolutionaryTrace" id="Q16570"/>
    <dbReference type="GeneWiki" id="Duffy_antigen_system"/>
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        <property type="development level" value="Tbio"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000213088">
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    <dbReference type="ExpressionAtlas" id="Q16570">
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        <property type="term" value="C:early endosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0038023">
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        <property type="project" value="ProtInc"/>
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    <dbReference type="GO" id="GO:0004888">
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        <property type="project" value="ProtInc"/>
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        <property type="project" value="InterPro"/>
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        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="CDD" id="cd15010">
        <property type="entry name" value="7tmA_ACKR1_DARC"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Atypical chemokine receptor 1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Duffy_chemokine_rcpt"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14181:SF1">
        <property type="entry name" value="ATYPICAL CHEMOKINE RECEPTOR 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14181">
        <property type="entry name" value="DUFFY ANTIGEN/CHEMOKINE RECEPTOR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR01559">
        <property type="entry name" value="DUFFYANTIGEN"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0095">Blood group antigen</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0297">G-protein coupled receptor</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0765">Sulfation</keyword>
    <keyword id="KW-0807">Transducer</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000152585" description="Atypical chemokine receptor 1">
        <location>
            <begin position="1"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="1"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="1">
        <location>
            <begin position="64"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="85"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="1">
        <location>
            <begin position="96"/>
            <end position="116"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="117"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="1">
        <location>
            <begin position="130"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="154"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="1">
        <location>
            <begin position="167"/>
            <end position="187"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="188"/>
            <end position="207"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="1">
        <location>
            <begin position="208"/>
            <end position="228"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="229"/>
            <end position="244"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="1">
        <location>
            <begin position="245"/>
            <end position="265"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="266"/>
            <end position="287"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="1">
        <location>
            <begin position="288"/>
            <end position="308"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="309"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mediates Plasmodium vivax Duffy receptor (DBP) binding" evidence="7">
        <location>
            <begin position="1"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="5">
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="modified residue" description="Sulfotyrosine" evidence="5">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="3">
        <location>
            <begin position="51"/>
            <end position="276"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="3">
        <location>
            <begin position="129"/>
            <end position="195"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_001323" description="In isoform 1." evidence="26 28">
        <original>MGNCLHR</original>
        <variation>MASSGYVLQ</variation>
        <location>
            <begin position="1"/>
            <end position="7"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_003480" description="Antigen Fy(b); does not affect the efficiency of sulfation of TYR-41; dbSNP:rs12075." evidence="5 12 13 14 16 18">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015068" description="Antigen Fy(x); dbSNP:rs34599082." evidence="16 17 18">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015069" description="In dbSNP:rs13962." evidence="16 18">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_044116" description="In dbSNP:rs3027020.">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_044117" description="In dbSNP:rs17851570." evidence="4 19">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="11"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="18"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Modulates the affinity of the interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>Q</original>
        <variation>A</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Modulates the affinity of the interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly reduces binding with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>W</original>
        <variation>A</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="28"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect interaction with Plasmodium vivax Duffy receptor (DBP)." evidence="7">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes sulfation. Reduces binding with IL8/CXCL8." evidence="5">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes sulfation. Reduces binding with MGSA/CXCL1, RANTES/CCL5 and MCP-1/CCL2. Reduces binding with Plasmodium vivax Duffy receptor (DBP) and Plasmodium knowlesi Duffy receptor alpha form (DBPalpha)." evidence="5">
        <original>Y</original>
        <variation>F</variation>
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            <position position="41"/>
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    <evidence type="ECO:0000269" key="12">
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            <dbReference type="PubMed" id="9731074"/>
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            <dbReference type="PubMed" id="9746760"/>
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        <source>
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        <source>
            <dbReference type="PubMed" id="16024106"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="24415938"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="28800732"/>
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    </evidence>
    <evidence type="ECO:0000303" key="25">
        <source>
            <dbReference type="PubMed" id="38056460"/>
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    </evidence>
    <evidence type="ECO:0000303" key="26">
        <source>
            <dbReference type="PubMed" id="8248172"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="8879225"/>
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        <source>
            <dbReference type="PubMed" id="9886340"/>
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    </evidence>
    <evidence type="ECO:0000305" key="29"/>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PDB" id="4NUU"/>
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    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PDB" id="4NUV"/>
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    </evidence>
    <evidence type="ECO:0007829" key="32">
        <source>
            <dbReference type="PDB" id="4NUU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="33">
        <source>
            <dbReference type="PDB" id="8A44"/>
        </source>
    </evidence>
    <sequence length="336" mass="35553" checksum="C3F2A3E71D972E2D" modified="2005-06-07" version="3">MGNCLHRAELSPSTENSSQLDFEDVWNSSYGVNDSFPDGDYGANLEAAAPCHSCNLLDDSALPFFILTSVLGILASSTVLFMLFRPLFRWQLCPGWPVLAQLAVGSALFSIVVPVLAPGLGSTRSSALCSLGYCVWYGSAFAQALLLGCHASLGHRLGAGQVPGLTLGLTVGIWGVAALLTLPVTLASGASGGLCTLIYSTELKALQATHTVACLAIFVLLPLGLFGAKGLKKALGMGPGPWMNILWAWFIFWWPHGVVLGLDFLVRSKLLLLSTCLAQQALDLLLNLAEALAILHCVATPLLLALFCHQATRTLLPSLPLPEGWSSHLDTLGSKS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-27" modified="2026-01-28" version="174" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y615</accession>
    <accession>B2RC83</accession>
    <accession>Q5JSV0</accession>
    <name>ACL7A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-like protein 7A</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Actin-like-7-alpha</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTL7A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Cloning, mapping, and expression of two novel actin genes, actin-like-7A (ACTL7A) and actin-like-7B (ACTL7B), from the familial dysautonomia candidate region on 9q31.</title>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
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                <person name="Tanaka H."/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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                <person name="Wakebe H."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Kawakami T."/>
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                <person name="Shigeta K."/>
                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
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                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="J. Biol. Chem." volume="286" first="11543" last="11554">
            <title>Molecular recognition of the Tes LIM2-3 domains by the actin-related protein Arp7A.</title>
            <authorList>
                <person name="Boeda B."/>
                <person name="Knowles P.P."/>
                <person name="Briggs D.C."/>
                <person name="Murray-Rust J."/>
                <person name="Soriano E."/>
                <person name="Garvalov B.K."/>
                <person name="McDonald N.Q."/>
                <person name="Way M."/>
            </authorList>
            <dbReference type="PubMed" id="21278383"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.171264"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 1-65 IN COMPLEX WITH ENAH AND TES</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF ALA-31 AND ALA-41</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2020" name="Sci. Adv." volume="6" first="eaaz4796" last="eaaz4796">
            <title>Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest.</title>
            <authorList>
                <person name="Xin A."/>
                <person name="Qu R."/>
                <person name="Chen G."/>
                <person name="Zhang L."/>
                <person name="Chen J."/>
                <person name="Tao C."/>
                <person name="Fu J."/>
                <person name="Tang J."/>
                <person name="Ru Y."/>
                <person name="Chen Y."/>
                <person name="Peng X."/>
                <person name="Shi H."/>
                <person name="Zhang F."/>
                <person name="Sun X."/>
            </authorList>
            <dbReference type="PubMed" id="32923619"/>
            <dbReference type="DOI" id="10.1126/sciadv.aaz4796"/>
        </citation>
        <scope>INVOLVEMENT IN SPGF86</scope>
        <scope>VARIANT SPGF86 THR-245</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2021" name="Am. J. Hum. Genet." volume="108" first="469" last="481">
            <title>Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice.</title>
            <authorList>
                <person name="Dai J."/>
                <person name="Zhang T."/>
                <person name="Guo J."/>
                <person name="Zhou Q."/>
                <person name="Gu Y."/>
                <person name="Zhang J."/>
                <person name="Hu L."/>
                <person name="Zong Y."/>
                <person name="Song J."/>
                <person name="Zhang S."/>
                <person name="Dai C."/>
                <person name="Gong F."/>
                <person name="Lu G."/>
                <person name="Zheng W."/>
                <person name="Lin G."/>
            </authorList>
            <dbReference type="PubMed" id="33626338"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2021.02.004"/>
        </citation>
        <scope>INTERACTION WITH ACTL9</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2024" name="Elife" volume="13" first="0" last="0">
            <title>Disruption in CYLC1 leads to acrosome detachment, sperm head deformity, and male in/subfertility in humans and mice.</title>
            <authorList>
                <person name="Jin H.J."/>
                <person name="Fan Y."/>
                <person name="Yang X."/>
                <person name="Dong Y."/>
                <person name="Zhang X.Z."/>
                <person name="Geng X.Y."/>
                <person name="Yan Z."/>
                <person name="Wu L."/>
                <person name="Ma M."/>
                <person name="Li B."/>
                <person name="Lyu Q."/>
                <person name="Pan Y."/>
                <person name="Liu M."/>
                <person name="Kuang Y."/>
                <person name="Chen S.R."/>
            </authorList>
            <dbReference type="PubMed" id="38573307"/>
            <dbReference type="DOI" id="10.7554/elife.95054"/>
        </citation>
        <scope>INTERACTION WITH CYLC1</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2021" name="Hum. Reprod." volume="36" first="3161" last="3169">
            <title>Novel bi-allelic variants in ACTL7A are associated with male infertility and total fertilization failure.</title>
            <authorList>
                <person name="Wang J."/>
                <person name="Zhang J."/>
                <person name="Sun X."/>
                <person name="Lin Y."/>
                <person name="Cai L."/>
                <person name="Cui Y."/>
                <person name="Liu J."/>
                <person name="Liu M."/>
                <person name="Yang X."/>
            </authorList>
            <dbReference type="PubMed" id="34727571"/>
            <dbReference type="DOI" id="10.1093/humrep/deab228"/>
        </citation>
        <scope>VARIANTS SPGF86 155-ARG--PHE-435 DEL AND ARG-362</scope>
        <scope>CHARACTERIZATION OF VARIANTS SPGF86 155-ARG--PHE-435 DEL AND ARG-362</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2023" name="Clin. Genet." volume="103" first="603" last="608">
            <title>Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure.</title>
            <authorList>
                <person name="Zhao S."/>
                <person name="Cui Y."/>
                <person name="Guo S."/>
                <person name="Liu B."/>
                <person name="Bian Y."/>
                <person name="Zhao S."/>
                <person name="Chen Z."/>
                <person name="Zhao H."/>
            </authorList>
            <dbReference type="PubMed" id="36593593"/>
            <dbReference type="DOI" id="10.1111/cge.14293"/>
        </citation>
        <scope>VARIANT SPGF86 49-SER--LYS-345 DEL</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2023" name="Hum. Reprod." volume="38" first="1213" last="1223">
            <title>ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida.</title>
            <authorList>
                <person name="Hua R."/>
                <person name="Xue R."/>
                <person name="Liu Y."/>
                <person name="Li Y."/>
                <person name="Sha X."/>
                <person name="Li K."/>
                <person name="Gao Y."/>
                <person name="Shen Q."/>
                <person name="Lv M."/>
                <person name="Xu Y."/>
                <person name="Zhang Z."/>
                <person name="He X."/>
                <person name="Cao Y."/>
                <person name="Wu H."/>
            </authorList>
            <dbReference type="PubMed" id="37004249"/>
            <dbReference type="DOI" id="10.1093/humrep/dead059"/>
        </citation>
        <scope>VARIANTS SPGF86 THR-245 AND ALA-246</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6">Essential for normal spermatogenesis and male fertility. Required for normal sperm head morphology, acroplaxome formation, acrosome attachment, and acrosome granule stability. May anchor and stabilize acrosomal adherence to the acroplaxome at least in part by facilitating the presence of F-actin in the subacrosomal space (By similarity). May play an important role in formation and fusion of Golgi-derived vesicles during acrosome biogenesis (PubMed:32923619).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 7 11">Interacts (via N-terminus) with TES (via LIM domain 2). Heterodimer with TES; the heterodimer interacts with ENAH to form a heterotrimer (PubMed:21278383). Interacts with ACTL9 (PubMed:33626338). Interacts with CYLC1; the interaction may be relevant for proper acrosome attachment to the nuclear envelope (PubMed:38573307).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Golgi apparatus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 8">Cytoplasmic vesicle</location>
            <location evidence="6 8">Secretory vesicle</location>
            <location evidence="6 8">Acrosome</location>
        </subcellularLocation>
        <text evidence="1">Detected at the Golgi apparatus during acrosome biogenesis. Detected at the subacrosomal layer in round spermatids. Detected in sperm head and tail.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Strongly expressed in testis. Also expressed in other tissues.</text>
    </comment>
    <comment type="disease" evidence="6 8 9 10">
        <disease id="DI-06755">
            <name>Spermatogenic failure 86</name>
            <acronym>SPGF86</acronym>
            <description>An autosomal recessive male infertility disorder characterized by acrosomal defects of the spermatozoa, resulting in oocyte activation deficiency and fertilization failure.</description>
            <dbReference type="MIM" id="620499"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AF113526">
        <property type="protein sequence ID" value="AAD44109.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB284520">
        <property type="protein sequence ID" value="BAF41971.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314981">
        <property type="protein sequence ID" value="BAG37480.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359692">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471105">
        <property type="protein sequence ID" value="EAW59026.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014610">
        <property type="protein sequence ID" value="AAH14610.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6772.1"/>
    <dbReference type="RefSeq" id="NP_006678.1">
        <property type="nucleotide sequence ID" value="NM_006687.4"/>
    </dbReference>
    <dbReference type="PDB" id="2XQN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.62 A"/>
        <property type="chains" value="A=1-65"/>
    </dbReference>
    <dbReference type="PDBsum" id="2XQN"/>
    <dbReference type="AlphaFoldDB" id="Q9Y615"/>
    <dbReference type="SMR" id="Q9Y615"/>
    <dbReference type="BioGRID" id="116089">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y615">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000334300"/>
    <dbReference type="iPTMnet" id="Q9Y615"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y615"/>
    <dbReference type="BioMuta" id="ACTL7A"/>
    <dbReference type="DMDM" id="27923725"/>
    <dbReference type="MassIVE" id="Q9Y615"/>
    <dbReference type="PaxDb" id="9606-ENSP00000334300"/>
    <dbReference type="PeptideAtlas" id="Q9Y615"/>
    <dbReference type="ProteomicsDB" id="86577"/>
    <dbReference type="Antibodypedia" id="14911">
        <property type="antibodies" value="161 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10881"/>
    <dbReference type="Ensembl" id="ENST00000333999.5">
        <property type="protein sequence ID" value="ENSP00000334300.3"/>
        <property type="gene ID" value="ENSG00000187003.7"/>
    </dbReference>
    <dbReference type="GeneID" id="10881"/>
    <dbReference type="KEGG" id="hsa:10881"/>
    <dbReference type="MANE-Select" id="ENST00000333999.5">
        <property type="protein sequence ID" value="ENSP00000334300.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006687.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006678.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004bdj.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:161"/>
    <dbReference type="ClinPGx" id="PA24483"/>
    <dbReference type="CTD" id="10881"/>
    <dbReference type="DisGeNET" id="10881"/>
    <dbReference type="GeneCards" id="ACTL7A"/>
    <dbReference type="HGNC" id="HGNC:161">
        <property type="gene designation" value="ACTL7A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000187003">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACTL7A"/>
    <dbReference type="MIM" id="604303">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="620499">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000187003"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000187003"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162158"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_2_1"/>
    <dbReference type="InParanoid" id="Q9Y615"/>
    <dbReference type="OMA" id="DMWEYLF"/>
    <dbReference type="OrthoDB" id="9925380at2759"/>
    <dbReference type="PAN-GO" id="Q9Y615">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y615"/>
    <dbReference type="PathwayCommons" id="Q9Y615"/>
    <dbReference type="SignaLink" id="Q9Y615"/>
    <dbReference type="Agora" id="ENSG00000187003"/>
    <dbReference type="BioGRID-ORCS" id="10881">
        <property type="hits" value="14 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTL7A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9Y615"/>
    <dbReference type="GeneWiki" id="ACTL7A"/>
    <dbReference type="GenomeRNAi" id="10881"/>
    <dbReference type="Pharos" id="Q9Y615">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y615"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y615">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000187003">
        <property type="expression patterns" value="Expressed in left testis and 66 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y615">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001669">
        <property type="term" value="C:acrosomal vesicle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005856">
        <property type="term" value="C:cytoskeleton"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001673">
        <property type="term" value="C:male germ cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031514">
        <property type="term" value="C:motile cilium"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032991">
        <property type="term" value="C:protein-containing complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005200">
        <property type="term" value="F:structural constituent of cytoskeleton"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001675">
        <property type="term" value="P:acrosome assembly"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009566">
        <property type="term" value="P:fertilization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007338">
        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007286">
        <property type="term" value="P:spermatid development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd10214">
        <property type="entry name" value="ASKHA_NBD_ACTL7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000050">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="IDEAL" id="IID00687"/>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR031769">
        <property type="entry name" value="ACTL7A_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16840">
        <property type="entry name" value="ACTL7A_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0278">Fertilization</keyword>
    <keyword id="KW-0333">Golgi apparatus</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <feature type="chain" id="PRO_0000089137" description="Actin-like protein 7A">
        <location>
            <begin position="1"/>
            <end position="435"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with TES">
        <location>
            <begin position="31"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="2">
        <location>
            <begin position="20"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="55"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031425" description="In dbSNP:rs368653764." evidence="4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088980" description="In SPGF86; likely pathogenic." evidence="9">
        <location>
            <begin position="49"/>
            <end position="435"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088981" description="In SPGF86; likely pathogenic; loss of protein expression in patient sperm." evidence="8">
        <location>
            <begin position="155"/>
            <end position="435"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033460" description="In dbSNP:rs35995497.">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085430" description="In SPGF86; uncertain significance; dbSNP:rs371671871." evidence="6 10">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088982" description="In SPGF86; uncertain significance." evidence="10">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="246"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_024362" description="In dbSNP:rs7872077." evidence="4">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="340"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060998" description="In dbSNP:rs56031956.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088983" description="In SPGF86; uncertain significance; dbSNP:rs779515458." evidence="8">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with TES." evidence="5">
        <original>A</original>
        <variation>Y</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes interaction with TES." evidence="5">
        <original>A</original>
        <variation>Y</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="42"/>
            <end position="44"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9QY84"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10373328"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="17644991"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="21278383"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="32923619"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="33626338"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="34727571"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="36593593"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="37004249"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="38573307"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="2XQN"/>
        </source>
    </evidence>
    <sequence length="435" mass="48644" checksum="FE73995971B5600C" modified="1999-11-01" version="1">MWAPPAAIMGDGPTKKVGNQAPLQTQALQTASLRDGPAKRAVWVRHTSSEPQEPTESKAAKERPKQEVTKAVVVDLGTGYCKCGFAGLPRPTHKISTTVGKPYMETAKTGDNRKETFVGQELNNTNVHLKLVNPLRHGIIVDWDTVQDIWEYLFRQEMKIAPEEHAVLVSDPPLSPHTNREKYAEMLFEAFNTPAMHIAYQSRLSMYSYGRTSGLVVEVGHGVSYVVPIYEGYPLPSITGRLDYAGSDLTAYLLGLLNSAGNEFTQDQMGIVEDIKKKCCFVALDPIEEKKVPLSEHTIRYVLPDGKEIQLCQERFLCSEMFFKPSLIKSMQLGLHTQTVSCLNKCDIALKRDLMGNILLCGGSTMLSGFPNRLQKELSSMCPNDTPQVNVLPERDSAVWTGGSILASLQGFQPLWVHRFEYEEHGPFFLYRRCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-04-18" modified="2026-01-28" version="141" xmlns="https://uniprot.org/uniprot">
    <accession>Q5JWF8</accession>
    <accession>B9EH76</accession>
    <name>ACL10_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-like protein 10</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACTL10</name>
        <name type="synonym">C20orf134</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Matthews L.H."/>
                <person name="Ashurst J.L."/>
                <person name="Burton J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Jones M."/>
                <person name="Stavrides G."/>
                <person name="Almeida J.P."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
                <person name="Beasley O.P."/>
                <person name="Bird C.P."/>
                <person name="Blakey S.E."/>
                <person name="Bridgeman A.M."/>
                <person name="Brown A.J."/>
                <person name="Buck D."/>
                <person name="Burrill W.D."/>
                <person name="Butler A.P."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clamp M."/>
                <person name="Clark G."/>
                <person name="Clark L.N."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Cobley V.E."/>
                <person name="Collier R.E."/>
                <person name="Connor R.E."/>
                <person name="Corby N.R."/>
                <person name="Coulson A."/>
                <person name="Coville G.J."/>
                <person name="Deadman R."/>
                <person name="Dhami P.D."/>
                <person name="Dunn M."/>
                <person name="Ellington A.G."/>
                <person name="Frankland J.A."/>
                <person name="Fraser A."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths M.N.D."/>
                <person name="Gwilliam R."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Heath P.D."/>
                <person name="Ho S."/>
                <person name="Holden J.L."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Jekosch K."/>
                <person name="Johnson C.M."/>
                <person name="Johnson D."/>
                <person name="Kay M.P."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lehvaeslaiho M.H."/>
                <person name="Leversha M.A."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J.D."/>
                <person name="Marsh V.L."/>
                <person name="Martin S.L."/>
                <person name="McConnachie L.J."/>
                <person name="McLay K."/>
                <person name="McMurray A.A."/>
                <person name="Milne S.A."/>
                <person name="Mistry D."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Nickerson T."/>
                <person name="Oliver K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce T.A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Prathalingam S.R."/>
                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Scott C.E."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
                <person name="Sulston J.E."/>
                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="similarity">
        <text evidence="1">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AL121906">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW76309.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137111">
        <property type="protein sequence ID" value="AAI37112.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137114">
        <property type="protein sequence ID" value="AAI37115.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33463.1"/>
    <dbReference type="RefSeq" id="NP_001019846.1">
        <property type="nucleotide sequence ID" value="NM_001024675.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5JWF8"/>
    <dbReference type="SMR" id="Q5JWF8"/>
    <dbReference type="FunCoup" id="Q5JWF8">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000329647"/>
    <dbReference type="iPTMnet" id="Q5JWF8"/>
    <dbReference type="PhosphoSitePlus" id="Q5JWF8"/>
    <dbReference type="BioMuta" id="ACTL10"/>
    <dbReference type="DMDM" id="74742586"/>
    <dbReference type="MassIVE" id="Q5JWF8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000329647"/>
    <dbReference type="PeptideAtlas" id="Q5JWF8"/>
    <dbReference type="ProteomicsDB" id="63387"/>
    <dbReference type="Antibodypedia" id="57049">
        <property type="antibodies" value="12 antibodies from 1 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="170487"/>
    <dbReference type="Ensembl" id="ENST00000677665.1">
        <property type="protein sequence ID" value="ENSP00000504425.1"/>
        <property type="gene ID" value="ENSG00000288649.2"/>
    </dbReference>
    <dbReference type="GeneID" id="170487"/>
    <dbReference type="KEGG" id="hsa:170487"/>
    <dbReference type="MANE-Select" id="ENST00000677665.1">
        <property type="protein sequence ID" value="ENSP00000504425.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001024675.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001019846.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002wzt.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16127"/>
    <dbReference type="ClinPGx" id="PA25676"/>
    <dbReference type="CTD" id="170487"/>
    <dbReference type="DisGeNET" id="170487"/>
    <dbReference type="GeneCards" id="ACTL10"/>
    <dbReference type="HGNC" id="HGNC:16127">
        <property type="gene designation" value="ACTL10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000288649">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000182584"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162922"/>
    <dbReference type="HOGENOM" id="CLU_027965_5_2_1"/>
    <dbReference type="InParanoid" id="Q5JWF8"/>
    <dbReference type="OrthoDB" id="9870582at2759"/>
    <dbReference type="PAN-GO" id="Q5JWF8">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5JWF8"/>
    <dbReference type="PathwayCommons" id="Q5JWF8"/>
    <dbReference type="SignaLink" id="Q5JWF8"/>
    <dbReference type="BioGRID-ORCS" id="170487">
        <property type="hits" value="21 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="170487"/>
    <dbReference type="Pharos" id="Q5JWF8">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5JWF8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5JWF8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000288649">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 85 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000058">
        <property type="entry name" value="Putative actin-related protein 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000232865" description="Actin-like protein 10">
        <location>
            <begin position="1"/>
            <end position="245"/>
        </location>
    </feature>
    <evidence type="ECO:0000305" key="1"/>
    <sequence length="245" mass="26751" checksum="06EC6260DF9CC2EE" modified="2005-02-15" version="1">MASTALLALCSTGAFSGLAVEAGAGVCHATPIYAGHSWHQATFRLNVAGSTLSRYLRDLLVAANPDLLQQALPRKAITHLKKRSCYVSLDFEGDLRDPARHHPASFSVGNGCCVCLSSERFRCPEPIFQPGLLGQAEQGLPALAFRALQKMPKTLRTRLADTVVLAGGSTLFPGFAERLDKELEAQCRRHGYAALRPHLVAKHGRGMAVWTGGSMVASLHSFQRRWITRAMYQECGSRLLYDVFN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-08-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P08172</accession>
    <accession>Q4VBK6</accession>
    <accession>Q9P1X9</accession>
    <name>ACM2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Muscarinic acetylcholine receptor M2</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">CHRM2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="Science" volume="237" first="527" last="532">
            <title>Identification of a family of muscarinic acetylcholine receptor genes.</title>
            <authorList>
                <person name="Bonner T.I."/>
                <person name="Buckley N.J."/>
                <person name="Young A.C."/>
                <person name="Brann M.R."/>
            </authorList>
            <dbReference type="PubMed" id="3037705"/>
            <dbReference type="DOI" id="10.1126/science.3037705"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1987" name="EMBO J." volume="6" first="3923" last="3929">
            <title>Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.</title>
            <authorList>
                <person name="Peralta E.G."/>
                <person name="Ashkenazi A."/>
                <person name="Winslow J.W."/>
                <person name="Smith D.H."/>
                <person name="Ramachandran J."/>
                <person name="Capon D.J."/>
            </authorList>
            <dbReference type="PubMed" id="3443095"/>
            <dbReference type="DOI" id="10.1002/j.1460-2075.1987.tb02733.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
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            <title>Human-specific amino acid changes found in 103 protein-coding genes.</title>
            <authorList>
                <person name="Kitano T."/>
                <person name="Liu Y.-H."/>
                <person name="Ueda S."/>
                <person name="Saitou N."/>
            </authorList>
            <dbReference type="PubMed" id="15014171"/>
            <dbReference type="DOI" id="10.1093/molbev/msh100"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-466</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1995" name="J. Biol. Chem." volume="270" first="720" last="731">
            <title>Arrestin interactions with G protein-coupled receptors. Direct binding studies of wild type and mutant arrestins with rhodopsin, beta 2-adrenergic, and m2 muscarinic cholinergic receptors.</title>
            <authorList>
                <person name="Gurevich V.V."/>
                <person name="Dion S.B."/>
                <person name="Onorato J.J."/>
                <person name="Ptasienski J."/>
                <person name="Kim C.M."/>
                <person name="Sterne-Marr R."/>
                <person name="Hosey M.M."/>
                <person name="Benovic J.L."/>
            </authorList>
            <dbReference type="PubMed" id="7822302"/>
            <dbReference type="DOI" id="10.1074/jbc.270.2.720"/>
        </citation>
        <scope>INTERACTION WITH ARRB1 AND ARRB2</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Cell. Microbiol." volume="8" first="565" last="580">
            <title>Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection.</title>
            <authorList>
                <person name="Leong W.F."/>
                <person name="Chow V.T."/>
            </authorList>
            <dbReference type="PubMed" id="16548883"/>
            <dbReference type="DOI" id="10.1111/j.1462-5822.2005.00644.x"/>
        </citation>
        <scope>INDUCTION</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Hum. Mol. Genet." volume="13" first="1903" last="1911">
            <title>Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome.</title>
            <authorList>
                <person name="Wang J.C."/>
                <person name="Hinrichs A.L."/>
                <person name="Stock H."/>
                <person name="Budde J."/>
                <person name="Allen R."/>
                <person name="Bertelsen S."/>
                <person name="Kwon J.M."/>
                <person name="Wu W."/>
                <person name="Dick D.M."/>
                <person name="Rice J."/>
                <person name="Jones K."/>
                <person name="Nurnberger J.I. Jr."/>
                <person name="Tischfield J."/>
                <person name="Porjesz B."/>
                <person name="Edenberg H.J."/>
                <person name="Hesselbrock V."/>
                <person name="Crowe R."/>
                <person name="Schuckit M."/>
                <person name="Begleiter H."/>
                <person name="Reich T."/>
                <person name="Goate A.M."/>
                <person name="Bierut L.J."/>
            </authorList>
            <dbReference type="PubMed" id="15229186"/>
            <dbReference type="DOI" id="10.1093/hmg/ddh194"/>
        </citation>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM AND MAJOR DEPRESSIVE DISORDER</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2010" name="PLoS ONE" volume="5" first="E13517" last="E13517">
            <title>RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking.</title>
            <authorList>
                <person name="Reiner C.L."/>
                <person name="McCullar J.S."/>
                <person name="Kow R.L."/>
                <person name="Le J.H."/>
                <person name="Goodlett D.R."/>
                <person name="Nathanson N.M."/>
            </authorList>
            <dbReference type="PubMed" id="20976005"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0013517"/>
        </citation>
        <scope>INTERACTION WITH RACK1</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2023" name="Mol. Cell" volume="83" first="2091" last="2107">
            <title>Structural snapshots uncover a key phosphorylation motif in GPCRs driving beta-arrestin activation.</title>
            <authorList>
                <person name="Maharana J."/>
                <person name="Sarma P."/>
                <person name="Yadav M.K."/>
                <person name="Saha S."/>
                <person name="Singh V."/>
                <person name="Saha S."/>
                <person name="Chami M."/>
                <person name="Banerjee R."/>
                <person name="Shukla A.K."/>
            </authorList>
            <dbReference type="PubMed" id="37209686"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2023.04.025"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF VAL-308</scope>
    </reference>
    <reference evidence="18" key="11">
        <citation type="journal article" date="2012" name="Nature" volume="482" first="547" last="551">
            <title>Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist.</title>
            <authorList>
                <person name="Haga K."/>
                <person name="Kruse A.C."/>
                <person name="Asada H."/>
                <person name="Yurugi-Kobayashi T."/>
                <person name="Shiroishi M."/>
                <person name="Zhang C."/>
                <person name="Weis W.I."/>
                <person name="Okada T."/>
                <person name="Kobilka B.K."/>
                <person name="Haga T."/>
                <person name="Kobayashi T."/>
            </authorList>
            <dbReference type="PubMed" id="22278061"/>
            <dbReference type="DOI" id="10.1038/nature10753"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH THE ANTAGONIST 3-QUINUCLIDINYLBENZILATE</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <reference evidence="19 20" key="12">
        <citation type="journal article" date="2013" name="Nature" volume="504" first="101" last="106">
            <title>Activation and allosteric modulation of a muscarinic acetylcholine receptor.</title>
            <authorList>
                <person name="Kruse A.C."/>
                <person name="Ring A.M."/>
                <person name="Manglik A."/>
                <person name="Hu J."/>
                <person name="Hu K."/>
                <person name="Eitel K."/>
                <person name="Hubner H."/>
                <person name="Pardon E."/>
                <person name="Valant C."/>
                <person name="Sexton P.M."/>
                <person name="Christopoulos A."/>
                <person name="Felder C.C."/>
                <person name="Gmeiner P."/>
                <person name="Steyaert J."/>
                <person name="Weis W.I."/>
                <person name="Garcia K.C."/>
                <person name="Wess J."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="24256733"/>
            <dbReference type="DOI" id="10.1038/nature12735"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) IN COMPLEXES WITH THE AGONIST IPEROXO AND THE ALLOSTERIC EFFECTOR LY2119620</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>MOTIF</scope>
        <scope>MUTAGENESIS OF ASN-58; ASP-103; TYR-206 AND ASN-404</scope>
    </reference>
    <reference evidence="28 29 30 31" key="13">
        <citation type="journal article" date="2023" name="Nat. Commun." volume="14" first="376" last="376">
            <title>Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor.</title>
            <authorList>
                <person name="Xu J."/>
                <person name="Wang Q."/>
                <person name="Hubner H."/>
                <person name="Hu Y."/>
                <person name="Niu X."/>
                <person name="Wang H."/>
                <person name="Maeda S."/>
                <person name="Inoue A."/>
                <person name="Tao Y."/>
                <person name="Gmeiner P."/>
                <person name="Du Y."/>
                <person name="Jin C."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="36690613"/>
            <dbReference type="DOI" id="10.1038/s41467-022-35726-z"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.16 ANGSTROMS) OF 4-232 AND 368-466 IN COMPLEX WITH ACETYLCHOLINE; ALLOSTERIC EFFECTOR LY2119620; GNAO1; GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <reference evidence="32 33 34" key="14">
        <citation type="journal article" date="2024" name="Science" volume="383" first="101" last="108">
            <title>Molecular insights into atypical modes of beta-arrestin interaction with seven transmembrane receptors.</title>
            <authorList>
                <person name="Maharana J."/>
                <person name="Sano F.K."/>
                <person name="Sarma P."/>
                <person name="Yadav M.K."/>
                <person name="Duan L."/>
                <person name="Stepniewski T.M."/>
                <person name="Chaturvedi M."/>
                <person name="Ranjan A."/>
                <person name="Singh V."/>
                <person name="Saha S."/>
                <person name="Mahajan G."/>
                <person name="Chami M."/>
                <person name="Shihoya W."/>
                <person name="Selent J."/>
                <person name="Chung K.Y."/>
                <person name="Banerjee R."/>
                <person name="Nureki O."/>
                <person name="Shukla A.K."/>
            </authorList>
            <dbReference type="PubMed" id="38175886"/>
            <dbReference type="DOI" id="10.1126/science.adj3347"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 300-317 IN COMPLEX WITH ARRB1 AND ARRB2</scope>
        <scope>DOMAIN</scope>
        <scope>INTERACTION WITH ARRB1 AND ARRB2</scope>
        <scope>PHOSPHORYLATION AT THR-302; THR-307; SER-309; THR-310; SER-311 AND SER-315</scope>
        <scope>MUTAGENESIS OF 307-THR--THR-310 AND 340-THR--THR-343</scope>
    </reference>
    <comment type="function">
        <text evidence="10 11 12">Muscarinic receptor for acetylcholine, a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia (PubMed:24256733, PubMed:3443095, PubMed:36690613). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:36690613). CHRM2 is coupled to G(i)/G(o) (GNAI1 or GNAO1) G proteins and mediates signaling by inhibiting adenylate cyclase activity (PubMed:36690613).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="12">Activated by allosteric modulator LY2119620.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8 14 15">Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand (PubMed:38175886, PubMed:7822302). Interacts with RACK1; the interaction regulates CHRM2 internalization (PubMed:20976005).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 10 11">Cell membrane</location>
            <topology evidence="9 10">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="16">Postsynaptic cell membrane</location>
            <topology evidence="16">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">Phosphorylation in response to agonist binding promotes receptor internalization.</text>
    </comment>
    <comment type="induction">
        <text evidence="7">Up-regulated in response to enterovirus 71 (EV71) infection.</text>
    </comment>
    <comment type="domain">
        <text evidence="13 14">The P-X-P-P motif is phosphorylated in response to ligand binding, promoting. association with beta-arrestin (ARRB1 and/or ARRB2).</text>
    </comment>
    <comment type="PTM">
        <text evidence="13 14">Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin (ARRB1 and/or ARRB2), leading to receptor desensitization and negative regulation of G-protein coupled receptor signaling.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="17">Genetic variations in CHRM2 can influence susceptibility to alcoholism [MIM:103780].</text>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-00697">
            <name>Major depressive disorder</name>
            <acronym>MDD</acronym>
            <description>A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning.</description>
            <dbReference type="MIM" id="608516"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M16404">
        <property type="protein sequence ID" value="AAA51570.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X15264">
        <property type="protein sequence ID" value="CAA33335.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF498916">
        <property type="protein sequence ID" value="AAM18939.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC095547">
        <property type="protein sequence ID" value="AAH95547.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC106741">
        <property type="protein sequence ID" value="AAI06742.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI06743.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAA94476.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="entry name" value="S10126"/>
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        <property type="nucleotide sequence ID" value="NM_000739.3"/>
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    <dbReference type="RefSeq" id="NP_001006627.1">
        <property type="nucleotide sequence ID" value="NM_001006626.3"/>
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        <property type="nucleotide sequence ID" value="NM_001006627.3"/>
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        <property type="nucleotide sequence ID" value="NM_001006628.3"/>
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    <dbReference type="RefSeq" id="NP_001006630.1">
        <property type="nucleotide sequence ID" value="NM_001006629.3"/>
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        <property type="nucleotide sequence ID" value="NM_001006630.2"/>
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        <property type="nucleotide sequence ID" value="NM_001006631.3"/>
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        <property type="nucleotide sequence ID" value="NM_001006632.3"/>
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    <dbReference type="RefSeq" id="NP_001365901.1">
        <property type="nucleotide sequence ID" value="NM_001378972.1"/>
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    <dbReference type="RefSeq" id="NP_001365902.1">
        <property type="nucleotide sequence ID" value="NM_001378973.1"/>
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    <dbReference type="RefSeq" id="XP_047275803.1">
        <property type="nucleotide sequence ID" value="XM_047419847.1"/>
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        <property type="nucleotide sequence ID" value="XM_054357179.1"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A=1-217, A=377-466"/>
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        <property type="resolution" value="3.70 A"/>
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        <property type="resolution" value="2.60 A"/>
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        <property type="resolution" value="2.95 A"/>
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        <property type="resolution" value="2.30 A"/>
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        <property type="generic name" value="Aceclidine"/>
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    <dbReference type="DrugBank" id="DB03128">
        <property type="generic name" value="Acetylcholine"/>
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        <property type="generic name" value="Aclidinium"/>
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        <property type="generic name" value="ALKS 27"/>
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    <sequence length="466" mass="51715" checksum="2FC2FD7748C22BEC" modified="1988-08-01" version="1">MNNSTNSSNNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLLIISFDRYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGECYIQFFSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSPSLVQGRIVKPNNNNMPSSDDGLEHNKIQNGKAPRDPVTENCVQGEEKESSNDSTSVSAVASNMRDDEITQDENTVSTSLGHSKDENSKQTCIRIGTKTPKSDSCTPTNTTVEVVGSSGQNGDEKQNIVARKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNTVWTIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-27" modified="2026-01-28" version="169" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y614</accession>
    <accession>B2R9Q2</accession>
    <accession>Q5JSV1</accession>
    <name>ACL7B_HUMAN</name>
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        <recommendedName>
            <fullName>Actin-like protein 7B</fullName>
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        <alternativeName>
            <fullName>Actin-like-7-beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTL7B</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Genomics" volume="58" first="302" last="309">
            <title>Cloning, mapping, and expression of two novel actin genes, actin-like-7A (ACTL7A) and actin-like-7B (ACTL7B), from the familial dysautonomia candidate region on 9q31.</title>
            <authorList>
                <person name="Chadwick B.P."/>
                <person name="Mull J."/>
                <person name="Helbling L.A."/>
                <person name="Gill S."/>
                <person name="Leyne M."/>
                <person name="Robbins C.M."/>
                <person name="Pinkett H.W."/>
                <person name="Makalowska I."/>
                <person name="Maayan C."/>
                <person name="Blumenfeld A."/>
                <person name="Axelrod F.B."/>
                <person name="Brownstein M."/>
                <person name="Gusella J.F."/>
                <person name="Slaugenhaupt S.A."/>
            </authorList>
            <dbReference type="PubMed" id="10373328"/>
            <dbReference type="DOI" id="10.1006/geno.1999.5848"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2007" name="Soc. Reprod. Fertil. Suppl." volume="65" first="531" last="534">
            <title>Single nucleotide polymorphisms: discovery of the genetic causes of male infertility.</title>
            <authorList>
                <person name="Tanaka H."/>
                <person name="Hirose M."/>
                <person name="Tokuhiro K."/>
                <person name="Matsuoka Y."/>
                <person name="Miyagawa Y."/>
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            <dbReference type="PubMed" id="17644991"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <dbReference type="PubMed" id="15164053"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Detected only in the testis and, to a lesser extent, in the prostate.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AF113527">
        <property type="protein sequence ID" value="AAD44110.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB284521">
        <property type="protein sequence ID" value="BAF41972.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313871">
        <property type="protein sequence ID" value="BAG36599.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359692">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471105">
        <property type="protein sequence ID" value="EAW59025.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033789">
        <property type="protein sequence ID" value="AAH33789.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6771.1"/>
    <dbReference type="RefSeq" id="NP_006677.1">
        <property type="nucleotide sequence ID" value="NM_006686.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9Y614"/>
    <dbReference type="SMR" id="Q9Y614"/>
    <dbReference type="BioGRID" id="116088">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y614">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000363799"/>
    <dbReference type="iPTMnet" id="Q9Y614"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y614"/>
    <dbReference type="BioMuta" id="ACTL7B"/>
    <dbReference type="DMDM" id="27923724"/>
    <dbReference type="MassIVE" id="Q9Y614"/>
    <dbReference type="PaxDb" id="9606-ENSP00000363799"/>
    <dbReference type="PeptideAtlas" id="Q9Y614"/>
    <dbReference type="ProteomicsDB" id="86576"/>
    <dbReference type="Antibodypedia" id="14908">
        <property type="antibodies" value="268 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10880"/>
    <dbReference type="Ensembl" id="ENST00000374667.5">
        <property type="protein sequence ID" value="ENSP00000363799.3"/>
        <property type="gene ID" value="ENSG00000148156.8"/>
    </dbReference>
    <dbReference type="GeneID" id="10880"/>
    <dbReference type="KEGG" id="hsa:10880"/>
    <dbReference type="MANE-Select" id="ENST00000374667.5">
        <property type="protein sequence ID" value="ENSP00000363799.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006686.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006677.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004bdi.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:162"/>
    <dbReference type="ClinPGx" id="PA24484"/>
    <dbReference type="CTD" id="10880"/>
    <dbReference type="DisGeNET" id="10880"/>
    <dbReference type="GeneCards" id="ACTL7B"/>
    <dbReference type="HGNC" id="HGNC:162">
        <property type="gene designation" value="ACTL7B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000148156">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="604304">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000148156"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000148156"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162582"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_2_1"/>
    <dbReference type="InParanoid" id="Q9Y614"/>
    <dbReference type="OMA" id="WDCVQNI"/>
    <dbReference type="OrthoDB" id="9925380at2759"/>
    <dbReference type="PAN-GO" id="Q9Y614">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y614"/>
    <dbReference type="PathwayCommons" id="Q9Y614"/>
    <dbReference type="SignaLink" id="Q9Y614"/>
    <dbReference type="Agora" id="ENSG00000148156"/>
    <dbReference type="BioGRID-ORCS" id="10880">
        <property type="hits" value="16 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTL7B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="10880"/>
    <dbReference type="Pharos" id="Q9Y614">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y614"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y614">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000148156">
        <property type="expression patterns" value="Expressed in left testis and 50 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y614">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005200">
        <property type="term" value="F:structural constituent of cytoskeleton"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd10214">
        <property type="entry name" value="ASKHA_NBD_ACTL7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000050">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089139" description="Actin-like protein 7B">
        <location>
            <begin position="1"/>
            <end position="415"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="6"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q4QR76"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10373328"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="415" mass="45234" checksum="F29F29C2101F0D8E" modified="1999-11-01" version="1">MATRNSPMPLGTAQGDPGEAGTRPGPDASLRDTGAATQLKMKPRKVHKIKAVIIDLGSQYCKCGYAGEPRPTYFISSTVGKRCPEAADAGDTRKWTLVGHELLNTEAPLKLVNPLKHGIVVDWDCVQDIWEYIFRTAMKILPEEHAVLVSDPPLSPSSNREKYAELMFETFGIPAMHVTSQSLLSIYSYGKTSGLVVESGHGVSHVVPISEGDVLPGLTSRADYAGGDLTNYLMQLLNEAGHAFTDDHLHIIEHIKKKCCYAAFLPEEELGLVPEELRVDYELPDGKLITIGQERFRCSEMLFQPSLAGSTQPGLPELTAACLGRCQDTGFKEEMAANVLLCGGCTMLDGFPERFQRELSLLCPGDSPAVAAAPERKTSVWTGGSILASLQAFQQLWVSKEEFEERGSVAIYSKC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-10-24" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TDX5</accession>
    <accession>Q3B7X3</accession>
    <accession>Q53SR5</accession>
    <accession>Q96KY2</accession>
    <name>ACMSD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="3">2-amino-3-carboxymuconate-6-semialdehyde decarboxylase</fullName>
            <ecNumber evidence="1">4.1.1.45</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="3">Picolinate carboxylase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="10" type="primary">ACMSD</name>
    </gene>
    <organism evidence="9">
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="35162" last="35167">
            <title>Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and 'quinolinate hypothesis'.</title>
            <authorList>
                <person name="Fukuoka S."/>
                <person name="Ishiguro K."/>
                <person name="Yanagihara K."/>
                <person name="Tanabe A."/>
                <person name="Egashira Y."/>
                <person name="Sanada H."/>
                <person name="Shibata K."/>
            </authorList>
            <dbReference type="PubMed" id="12140278"/>
            <dbReference type="DOI" id="10.1074/jbc.m200819200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Graves T.A."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Pepin K.H."/>
                <person name="Minx P."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
                <person name="Strong C.M."/>
                <person name="Grewal N."/>
                <person name="Goyea E."/>
                <person name="Hou S."/>
                <person name="Levy A."/>
                <person name="Martinka S."/>
                <person name="Mead K."/>
                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Shah N."/>
                <person name="Swearengen-Shahid S."/>
                <person name="Snider J."/>
                <person name="Strong J.T."/>
                <person name="Thompson J."/>
                <person name="Yoakum M."/>
                <person name="Leonard S."/>
                <person name="Pearman C."/>
                <person name="Trani L."/>
                <person name="Radionenko M."/>
                <person name="Waligorski J.E."/>
                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
                <person name="Nelson J.O."/>
                <person name="Osborne J."/>
                <person name="Ding L."/>
                <person name="Meyer R."/>
                <person name="Sabo A."/>
                <person name="Shotland Y."/>
                <person name="Sinha P."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Jones T.A."/>
                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
                <person name="Schmutz J."/>
                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
                <person name="Huang X."/>
                <person name="McPherson J.D."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Kidney</tissue>
            <tissue evidence="8">Liver</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2009" name="FEBS J." volume="276" first="6615" last="6623">
            <title>The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis.</title>
            <authorList>
                <person name="Garavaglia S."/>
                <person name="Perozzi S."/>
                <person name="Galeazzi L."/>
                <person name="Raffaelli N."/>
                <person name="Rizzi M."/>
            </authorList>
            <dbReference type="PubMed" id="19843166"/>
            <dbReference type="DOI" id="10.1111/j.1742-4658.2009.07372.x"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND DHAP</scope>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>ZINC-BINDING SITES</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2">Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS) (PubMed:12140278). ACMS can be converted non-enzymatically to quinolinate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite (PubMed:12140278). ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway (PubMed:12140278, PubMed:19843166).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>2-amino-3-carboxymuconate 6-semialdehyde + H(+) = 2-aminomuconate 6-semialdehyde + CO2</text>
            <dbReference type="Rhea" id="RHEA:16557"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16526"/>
            <dbReference type="ChEBI" id="CHEBI:77634"/>
            <dbReference type="ChEBI" id="CHEBI:77803"/>
            <dbReference type="EC" id="4.1.1.45"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:16558"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="2">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-749859">
            <id>Q8TDX5</id>
        </interactant>
        <interactant intactId="EBI-10178634">
            <id>P43364-2</id>
            <label>MAGEA11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12809094">
            <id>Q8TDX5-2</id>
        </interactant>
        <interactant intactId="EBI-347538">
            <id>Q9Y4H4</id>
            <label>GPSM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12809094">
            <id>Q8TDX5-2</id>
        </interactant>
        <interactant intactId="EBI-739895">
            <id>Q8N6Y0</id>
            <label>USHBP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8TDX5-1</id>
            <name evidence="1">1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8TDX5-2</id>
            <name evidence="5">2</name>
            <sequence type="described" ref="VSP_050622 VSP_050623"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the metallo-dependent hydrolases superfamily. ACMSD family.</text>
    </comment>
    <dbReference type="EC" id="4.1.1.45" evidence="1"/>
    <dbReference type="EMBL" id="AB071418">
        <property type="protein sequence ID" value="BAB86938.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC016725">
        <property type="protein sequence ID" value="AAY14997.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471058">
        <property type="protein sequence ID" value="EAX11650.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471058">
        <property type="protein sequence ID" value="EAX11651.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471058">
        <property type="protein sequence ID" value="EAX11652.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016018">
        <property type="protein sequence ID" value="AAH16018.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC107420">
        <property type="protein sequence ID" value="AAI07421.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2173.2">
        <molecule id="Q8TDX5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS77464.1">
        <molecule id="Q8TDX5-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001294912.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="NM_001307983.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_612199.2">
        <molecule id="Q8TDX5-1"/>
        <property type="nucleotide sequence ID" value="NM_138326.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005263645.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_005263588.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011508894.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_011510592.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016858814.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_017003325.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016858815.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_017003326.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054196474.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_054340499.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054196475.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_054340500.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054196476.1">
        <molecule id="Q8TDX5-2"/>
        <property type="nucleotide sequence ID" value="XM_054340501.1"/>
    </dbReference>
    <dbReference type="PDB" id="2WM1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.01 A"/>
        <property type="chains" value="A=1-336"/>
    </dbReference>
    <dbReference type="PDB" id="4IGM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.39 A"/>
        <property type="chains" value="A/B/C/D/E/F=1-332"/>
    </dbReference>
    <dbReference type="PDB" id="4IGN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.33 A"/>
        <property type="chains" value="A/B/C/D/E/F=1-332"/>
    </dbReference>
    <dbReference type="PDB" id="4IH3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.49 A"/>
        <property type="chains" value="A/B/C/D/E/F=1-332"/>
    </dbReference>
    <dbReference type="PDB" id="4OFC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.99 A"/>
        <property type="chains" value="A/B/C/D/E/F=1-335"/>
    </dbReference>
    <dbReference type="PDB" id="7PWY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=1-336"/>
    </dbReference>
    <dbReference type="PDBsum" id="2WM1"/>
    <dbReference type="PDBsum" id="4IGM"/>
    <dbReference type="PDBsum" id="4IGN"/>
    <dbReference type="PDBsum" id="4IH3"/>
    <dbReference type="PDBsum" id="4OFC"/>
    <dbReference type="PDBsum" id="7PWY"/>
    <dbReference type="AlphaFoldDB" id="Q8TDX5"/>
    <dbReference type="SMR" id="Q8TDX5"/>
    <dbReference type="BioGRID" id="126217">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TDX5">
        <property type="interactions" value="89"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TDX5">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000348459"/>
    <dbReference type="BindingDB" id="Q8TDX5"/>
    <dbReference type="ChEMBL" id="CHEMBL4105941"/>
    <dbReference type="DrugCentral" id="Q8TDX5"/>
    <dbReference type="iPTMnet" id="Q8TDX5"/>
    <dbReference type="PhosphoSitePlus" id="Q8TDX5"/>
    <dbReference type="BioMuta" id="ACMSD"/>
    <dbReference type="MassIVE" id="Q8TDX5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000348459"/>
    <dbReference type="PeptideAtlas" id="Q8TDX5"/>
    <dbReference type="ProteomicsDB" id="74359">
        <molecule id="Q8TDX5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74360">
        <molecule id="Q8TDX5-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2546">
        <property type="antibodies" value="115 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="130013"/>
    <dbReference type="Ensembl" id="ENST00000356140.10">
        <molecule id="Q8TDX5-1"/>
        <property type="protein sequence ID" value="ENSP00000348459.5"/>
        <property type="gene ID" value="ENSG00000153086.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000392928.5">
        <molecule id="Q8TDX5-2"/>
        <property type="protein sequence ID" value="ENSP00000376659.1"/>
        <property type="gene ID" value="ENSG00000153086.15"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="241" xmlns="https://uniprot.org/uniprot">
    <accession>P53396</accession>
    <accession>B4DIM0</accession>
    <accession>B4E3P0</accession>
    <accession>Q13037</accession>
    <accession>Q9BRL0</accession>
    <name>ACLY_HUMAN</name>
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        <recommendedName>
            <fullName>ATP-citrate synthase</fullName>
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        </recommendedName>
        <alternativeName>
            <fullName>ATP-citrate (pro-S-)-lyase</fullName>
            <shortName>ACL</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Citrate cleavage enzyme</fullName>
        </alternativeName>
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        <name type="primary">ACLY</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1992" name="Eur. J. Biochem." volume="204" first="491" last="499">
            <title>Cloning and expression of a human ATP-citrate lyase cDNA.</title>
            <authorList>
                <person name="Elshourbagy N.A."/>
                <person name="Near J.C."/>
                <person name="Kmetz P.J."/>
                <person name="Wells T.N.C."/>
                <person name="Groot P.H.E."/>
                <person name="Saxty B.A."/>
                <person name="Hughes S.A."/>
                <person name="Franklin M."/>
                <person name="Gloger I.S."/>
            </authorList>
            <dbReference type="PubMed" id="1371749"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1992.tb16659.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF HIS-760</scope>
        <scope>ACTIVE SITE</scope>
        <scope>VARIANT ASP-175</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="Protein Expr. Purif." volume="9" first="133" last="141">
            <title>Variant cDNA sequences of human ATP:citrate lyase: cloning, expression, and purification from baculovirus-infected insect cells.</title>
            <authorList>
                <person name="Lord K.A."/>
                <person name="Wang X.M."/>
                <person name="Simmons S.J."/>
                <person name="Bruckner R.C."/>
                <person name="Loscig J."/>
                <person name="O'Connor B."/>
                <person name="Bentley R."/>
                <person name="Smallwood A."/>
                <person name="Chadwick C.C."/>
                <person name="Stevis P.E."/>
                <person name="Ciccarelli R.B."/>
            </authorList>
            <dbReference type="PubMed" id="9116495"/>
            <dbReference type="DOI" id="10.1006/prep.1996.0668"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANT ASP-175</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481; THR-639; SER-663; TYR-682; SER-839 AND SER-1100</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481</scope>
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        <scope>FUNCTION</scope>
        <scope>ACETYLATION AT LYS-540; LYS-546 AND LYS-554</scope>
        <scope>UBIQUITINATION AT LYS-540; LYS-546 AND LYS-554</scope>
        <scope>MUTAGENESIS OF LYS-540; LYS-546 AND LYS-554</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455 AND SER-481</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2016" name="Genes Dev." volume="30" first="1956" last="1970">
            <title>Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression.</title>
            <authorList>
                <person name="Zhang C."/>
                <person name="Liu J."/>
                <person name="Huang G."/>
                <person name="Zhao Y."/>
                <person name="Yue X."/>
                <person name="Wu H."/>
                <person name="Li J."/>
                <person name="Zhu J."/>
                <person name="Shen Z."/>
                <person name="Haffty B.G."/>
                <person name="Hu W."/>
                <person name="Feng Z."/>
            </authorList>
            <dbReference type="PubMed" id="27664236"/>
            <dbReference type="DOI" id="10.1101/gad.283283.116"/>
        </citation>
        <scope>UBIQUITINATION AT LYS-540; LYS-546 AND LYS-554</scope>
        <scope>MUTAGENESIS OF LYS-540; LYS-546 AND LYS-554</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2018" name="Cell Metab." volume="27" first="1281" last="1293.e7">
            <title>The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.</title>
            <authorList>
                <person name="White P.J."/>
                <person name="McGarrah R.W."/>
                <person name="Grimsrud P.A."/>
                <person name="Tso S.C."/>
                <person name="Yang W.H."/>
                <person name="Haldeman J.M."/>
                <person name="Grenier-Larouche T."/>
                <person name="An J."/>
                <person name="Lapworth A.L."/>
                <person name="Astapova I."/>
                <person name="Hannou S.A."/>
                <person name="George T."/>
                <person name="Arlotto M."/>
                <person name="Olson L.B."/>
                <person name="Lai M."/>
                <person name="Zhang G.F."/>
                <person name="Ilkayeva O."/>
                <person name="Herman M.A."/>
                <person name="Wynn R.M."/>
                <person name="Chuang D.T."/>
                <person name="Newgard C.B."/>
            </authorList>
            <dbReference type="PubMed" id="29779826"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2018.04.015"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-455</scope>
        <scope>PTM</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2021" name="Elife" volume="10" first="0" last="0">
            <title>ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation.</title>
            <authorList>
                <person name="Tian M."/>
                <person name="Hao F."/>
                <person name="Jin X."/>
                <person name="Sun X."/>
                <person name="Jiang Y."/>
                <person name="Wang Y."/>
                <person name="Li D."/>
                <person name="Chang T."/>
                <person name="Zou Y."/>
                <person name="Peng P."/>
                <person name="Xia C."/>
                <person name="Liu J."/>
                <person name="Li Y."/>
                <person name="Wang P."/>
                <person name="Feng Y."/>
                <person name="Wei M."/>
            </authorList>
            <dbReference type="PubMed" id="34491895"/>
            <dbReference type="DOI" id="10.7554/elife.62394"/>
        </citation>
        <scope>UBIQUITINATION</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2024" name="IScience" volume="27" first="111176" last="111176">
            <title>SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells.</title>
            <authorList>
                <person name="Peng P."/>
                <person name="Lu Y."/>
                <person name="Ren X."/>
                <person name="Yan C."/>
                <person name="Guo X."/>
                <person name="Liu R."/>
                <person name="Song X."/>
                <person name="Huang H."/>
            </authorList>
            <dbReference type="PubMed" id="39524354"/>
            <dbReference type="DOI" id="10.1016/j.isci.2024.111176"/>
        </citation>
        <scope>BENZOYLATION AT LYS-978</scope>
        <scope>MUTAGENESIS OF LYS-978</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2025" name="EMBO J." volume="0" first="0" last="0">
            <title>SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation.</title>
            <authorList>
                <person name="Li W."/>
                <person name="Han J."/>
                <person name="Huang B."/>
                <person name="Xu T."/>
                <person name="Wan Y."/>
                <person name="Luo D."/>
                <person name="Kong W."/>
                <person name="Yu Y."/>
                <person name="Zhang L."/>
                <person name="Nian Y."/>
                <person name="Chu B."/>
                <person name="Yin C."/>
            </authorList>
            <dbReference type="PubMed" id="39881208"/>
            <dbReference type="DOI" id="10.1038/s44318-025-00369-5"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2010" name="J. Biol. Chem." volume="285" first="27418" last="27428">
            <title>Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.</title>
            <authorList>
                <person name="Sun T."/>
                <person name="Hayakawa K."/>
                <person name="Bateman K.S."/>
                <person name="Fraser M.E."/>
            </authorList>
            <dbReference type="PubMed" id="20558738"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.078667"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-425 AND 487-820 IN COMPLEX WITH CITRATE AND MAGNESIUM</scope>
        <scope>COFACTOR</scope>
        <scope>CITRATE-BINDING SITES</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2011" name="Acta Crystallogr. F" volume="67" first="1168" last="1172">
            <title>ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.</title>
            <authorList>
                <person name="Sun T."/>
                <person name="Hayakawa K."/>
                <person name="Fraser M.E."/>
            </authorList>
            <dbReference type="PubMed" id="22102020"/>
            <dbReference type="DOI" id="10.1107/s1744309111028363"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-817 IN COMPLEX WITH ADP AND MAGNESIUM</scope>
        <scope>COFACTOR</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 9 12 17 18">Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 6 9 12 18">
            <text>oxaloacetate + acetyl-CoA + ADP + phosphate = citrate + ATP + CoA</text>
            <dbReference type="Rhea" id="RHEA:21160"/>
            <dbReference type="ChEBI" id="CHEBI:16452"/>
            <dbReference type="ChEBI" id="CHEBI:16947"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.3.3.8"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="21 22 23 25 26">
            <dbReference type="Rhea" id="RHEA:21162"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9 10 11">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="5">Phosphorylation results in activation of its activity (PubMed:10653665). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (PubMed:10653665).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="18">98 uM for citrate</KM>
            <KM evidence="9">73.8 uM for citrate</KM>
            <KM evidence="5">127 uM for citrate (phosphorylated form by PKA)</KM>
            <KM evidence="5">149 uM for citrate (phosphorylated form by both PKA and GSK3)</KM>
            <KM evidence="18">14 uM for CoA</KM>
            <KM evidence="9">4 uM for CoA</KM>
            <KM evidence="5">2.59 uM for CoA (unphosphorylated form)</KM>
            <KM evidence="5">2.32 uM for CoA (unphosphorylated form in the presence of fructose 6-phosphate)</KM>
            <KM evidence="5">2.01 uM for CoA (phosphorylated form by PKA)</KM>
            <KM evidence="5">2.35 uM for CoA (phosphorylated form by PKA in the presence of fructose 6-phosphate)</KM>
            <KM evidence="5">2.28 uM for CoA (phosphorylated form by both PKA and GSK3)</KM>
            <KM evidence="5">2.09 uM for CoA (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate)</KM>
            <KM evidence="18">120 uM for ATP</KM>
            <KM evidence="9">47 uM for ATP</KM>
            <KM evidence="5">41 uM for ATP (unphosphorylated form)</KM>
            <KM evidence="5">2.89 uM for ATP (unphosphorylated form in the presence of fructose 6-phosphate)</KM>
            <KM evidence="5">41.15 uM for ATP (phosphorylated form by PKA)</KM>
            <KM evidence="5">4.79 uM for ATP (phosphorylated form by PKA in the presence of fructose 6-phosphate)</KM>
            <KM evidence="5">37.28 uM for ATP (phosphorylated form by both PKA and GSK3)</KM>
            <KM evidence="5">4.01 uM for ATP (phosphorylated form by both PKA and GSK3 in the presence of fructose 6-phosphate)</KM>
            <Vmax evidence="18">1.9 umol/h/ug enzyme</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="10 11 18">Homotetramer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="18">Cytoplasm</location>
            <location evidence="18">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P53396-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P53396-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_042201"/>
        </isoform>
        <isoform>
            <id>P53396-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_057230 VSP_042201"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="1 5 14">Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (PubMed:10653665). Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455 (By similarity). Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues (By similarity). Phosphorylated at Ser-455 by BCKDK and dephosphorylated by protein phosphatase PPM1K.</text>
    </comment>
    <comment type="PTM">
        <text evidence="8">ISGylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF (PubMed:23932781). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (PubMed:23932781). Acetylation promotes de novo lipid synthesis (PubMed:23932781). Deacetylated by SIRT2.</text>
    </comment>
    <comment type="PTM">
        <text evidence="16">Benzoylated at Lys-978 (PubMed:39524354). Debenzoylated by SIRT3; inhibiting the ATP-citrate synthase activity (PubMed:39524354).</text>
    </comment>
    <comment type="PTM">
        <text evidence="12 13 15">Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (PubMed:23932781, PubMed:27664236, PubMed:34491895). Ubiquitination is probably inhibited by acetylation at same site (PubMed:23932781). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895).</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/50486/ACLY"/>
    </comment>
    <dbReference type="EC" id="2.3.3.8" evidence="5 6 9 12 18"/>
    <dbReference type="EMBL" id="X64330">
        <property type="protein sequence ID" value="CAA45614.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U18197">
        <property type="protein sequence ID" value="AAB60340.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK295675">
        <property type="protein sequence ID" value="BAG58532.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK304802">
        <property type="protein sequence ID" value="BAG65552.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091172">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC125257">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006195">
        <property type="protein sequence ID" value="AAH06195.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11412.1">
        <molecule id="P53396-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11413.1">
        <molecule id="P53396-2"/>
    </dbReference>
    <dbReference type="PIR" id="S21173">
        <property type="entry name" value="S21173"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001087.2">
        <molecule id="P53396-1"/>
        <property type="nucleotide sequence ID" value="NM_001096.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001290203.1">
        <property type="nucleotide sequence ID" value="NM_001303274.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001290204.1">
        <property type="nucleotide sequence ID" value="NM_001303275.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_942127.1">
        <molecule id="P53396-2"/>
        <property type="nucleotide sequence ID" value="NM_198830.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005257452.1">
        <molecule id="P53396-1"/>
        <property type="nucleotide sequence ID" value="XM_005257395.2"/>
    </dbReference>
    <dbReference type="PDB" id="3MWD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=1-425, B=487-820"/>
    </dbReference>
    <dbReference type="PDB" id="3MWE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-425, B=487-821"/>
    </dbReference>
    <dbReference type="PDB" id="3PFF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A=1-817"/>
    </dbReference>
    <dbReference type="PDB" id="5TDE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="5TDF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="5TDM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="5TDZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="5TE1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="A/B=1-817"/>
    </dbReference>
    <dbReference type="PDB" id="5TEQ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=1-817"/>
    </dbReference>
    <dbReference type="PDB" id="5TES">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="5TET">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-425, B=487-810"/>
    </dbReference>
    <dbReference type="PDB" id="6HXH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=1-424, A/B/C/D/E/F/G/H=488-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6HXK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A/B/C/D=836-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6HXL">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.35 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=836-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6HXM">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.30 A"/>
        <property type="chains" value="A/B=836-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6O0H">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.67 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6POE">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6POF">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.30 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6QFB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6UI9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6UIA">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.30 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6UUW">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="6UUZ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D=1-1100"/>
    </dbReference>
    <dbReference type="PDB" id="6UV5">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A/B/C/D=1-1100"/>
    </dbReference>
    <dbReference type="PDB" id="6Z2H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=836-1101"/>
    </dbReference>
    <dbReference type="PDB" id="7LIW">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.85 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
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    <dbReference type="PDB" id="7LJ9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="7LLA">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.97 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="7RIG">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="7RKZ">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="7RMP">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
    <dbReference type="PDB" id="8G1E">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=1-1101"/>
    </dbReference>
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<entry dataset="Swiss-Prot" created="1988-08-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
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    <accession>Q4VBK7</accession>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
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    <reference key="1">
        <citation type="journal article" date="1987" name="Science" volume="237" first="527" last="532">
            <title>Identification of a family of muscarinic acetylcholine receptor genes.</title>
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                <person name="Bonner T.I."/>
                <person name="Buckley N.J."/>
                <person name="Young A.C."/>
                <person name="Brann M.R."/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <citation type="journal article" date="1988" name="Neuron" volume="1" first="403" last="410">
            <title>Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.</title>
            <authorList>
                <person name="Bonner T.I."/>
                <person name="Young A.C."/>
                <person name="Brann M.R."/>
                <person name="Buckley N.J."/>
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            <dbReference type="PubMed" id="3272174"/>
            <dbReference type="DOI" id="10.1016/0896-6273(88)90190-0"/>
        </citation>
        <scope>SEQUENCE REVISION TO 258 AND 261-266</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1987" name="EMBO J." volume="6" first="3923" last="3929">
            <title>Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.</title>
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                <person name="Peralta E.G."/>
                <person name="Ashkenazi A."/>
                <person name="Winslow J.W."/>
                <person name="Smith D.H."/>
                <person name="Ramachandran J."/>
                <person name="Capon D.J."/>
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            <dbReference type="DOI" id="10.1002/j.1460-2075.1987.tb02733.x"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Brain</tissue>
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    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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        <text>The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.</text>
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            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
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            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
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        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.</text>
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<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="201" xmlns="https://uniprot.org/uniprot">
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    <accession>Q86UN9</accession>
    <accession>Q96A02</accession>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
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            <title>Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3.</title>
            <authorList>
                <person name="Bonini J.A."/>
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            </authorList>
            <dbReference type="PubMed" id="9364936"/>
            <dbReference type="DOI" id="10.1089/dna.1997.16.1249"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Lung</tissue>
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    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="J. Biol. Chem." volume="272" first="32078" last="32083">
            <title>Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6.</title>
            <authorList>
                <person name="Nibbs R.J.B."/>
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                <person name="Landau N.R."/>
                <person name="Graham G.J."/>
            </authorList>
            <dbReference type="PubMed" id="9405404"/>
            <dbReference type="DOI" id="10.1074/jbc.272.51.32078"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-03" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
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                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
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                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Ota T."/>
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                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
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                <person name="Hosoiri T."/>
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                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
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                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
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                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
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                <person name="Arita M."/>
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                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-373</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2001" name="Am. J. Pathol." volume="158" first="867" last="877">
            <title>The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors.</title>
            <authorList>
                <person name="Nibbs R.J.B."/>
                <person name="Kriehuber E."/>
                <person name="Ponath P.D."/>
                <person name="Parent D."/>
                <person name="Qin S."/>
                <person name="Campbell J.D."/>
                <person name="Henderson A."/>
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            </authorList>
            <dbReference type="PubMed" id="11238036"/>
            <dbReference type="DOI" id="10.1016/s0002-9440(10)64035-7"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="7972" last="7982">
            <title>Multiple roles for the C-terminal tail of the chemokine scavenger D6.</title>
            <authorList>
                <person name="McCulloch C.V."/>
                <person name="Morrow V."/>
                <person name="Milasta S."/>
                <person name="Comerford I."/>
                <person name="Milligan G."/>
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            </authorList>
            <dbReference type="PubMed" id="18201974"/>
            <dbReference type="DOI" id="10.1074/jbc.m710128200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>C-TERMINAL CYTOPLASMIC TAIL</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="9">
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            <authorList>
                <person name="McCulloch C.V."/>
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                <person name="Milasta S."/>
                <person name="Comerford I."/>
                <person name="Milligan G."/>
                <person name="Graham G.J."/>
                <person name="Isaacs N.W."/>
                <person name="Nibbs R.J."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:18201974</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2010" name="Curr. Top. Microbiol. Immunol." volume="341" first="15" last="36">
            <title>Chemokine decoy receptors: structure-function and biological properties.</title>
            <authorList>
                <person name="Bonecchi R."/>
                <person name="Savino B."/>
                <person name="Borroni E.M."/>
                <person name="Mantovani A."/>
                <person name="Locati M."/>
            </authorList>
            <dbReference type="PubMed" id="20373092"/>
            <dbReference type="DOI" id="10.1007/82_2010_19"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2012" name="FASEB J." volume="26" first="3891" last="3900">
            <title>The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation.</title>
            <authorList>
                <person name="Pashover-Schallinger E."/>
                <person name="Aswad M."/>
                <person name="Schif-Zuck S."/>
                <person name="Shapiro H."/>
                <person name="Singer P."/>
                <person name="Ariel A."/>
            </authorList>
            <dbReference type="PubMed" id="22651933"/>
            <dbReference type="DOI" id="10.1096/fj.11-194894"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2012" name="Immunol. Lett." volume="145" first="30" last="38">
            <title>The biochemistry and biology of the atypical chemokine receptors.</title>
            <authorList>
                <person name="Graham G.J."/>
                <person name="Locati M."/>
                <person name="Mantovani A."/>
                <person name="Rot A."/>
                <person name="Thelen M."/>
            </authorList>
            <dbReference type="PubMed" id="22698181"/>
            <dbReference type="DOI" id="10.1016/j.imlet.2012.04.004"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2013" name="Biochem. Soc. Trans." volume="41" first="231" last="236">
            <title>Atypical chemokine receptors: from silence to sound.</title>
            <authorList>
                <person name="Cancellieri C."/>
                <person name="Vacchini A."/>
                <person name="Locati M."/>
                <person name="Bonecchi R."/>
                <person name="Borroni E.M."/>
            </authorList>
            <dbReference type="PubMed" id="23356288"/>
            <dbReference type="DOI" id="10.1042/bst20120246"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2013" name="Blood" volume="121" first="3768" last="3777">
            <title>An analysis of the function and expression of D6 on lymphatic endothelial cells.</title>
            <authorList>
                <person name="McKimmie C.S."/>
                <person name="Singh M.D."/>
                <person name="Hewit K."/>
                <person name="Lopez-Franco O."/>
                <person name="Le Brocq M."/>
                <person name="Rose-John S."/>
                <person name="Lee K.M."/>
                <person name="Baker A.H."/>
                <person name="Wheat R."/>
                <person name="Blackbourn D.J."/>
                <person name="Nibbs R.J."/>
                <person name="Graham G.J."/>
            </authorList>
            <dbReference type="PubMed" id="23479571"/>
            <dbReference type="DOI" id="10.1182/blood-2012-04-425314"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="J. Pathol." volume="229" first="168" last="175">
            <title>Regulation of the immune and inflammatory responses by the 'atypical' chemokine receptor D6.</title>
            <authorList>
                <person name="Graham G.J."/>
                <person name="Locati M."/>
            </authorList>
            <dbReference type="PubMed" id="23125030"/>
            <dbReference type="DOI" id="10.1002/path.4123"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2013" name="Mol. Immunol." volume="55" first="87" last="93">
            <title>Review: Structure-function and biological properties of the atypical chemokine receptor D6.</title>
            <authorList>
                <person name="Cancellieri C."/>
                <person name="Caronni N."/>
                <person name="Vacchini A."/>
                <person name="Savino B."/>
                <person name="Borroni E.M."/>
                <person name="Locati M."/>
                <person name="Bonecchi R."/>
            </authorList>
            <dbReference type="PubMed" id="22939232"/>
            <dbReference type="DOI" id="10.1016/j.molimm.2012.08.003"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2013" name="Sci. Signal." volume="6" first="RA30" last="RA30">
            <title>Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6.</title>
            <authorList>
                <person name="Borroni E.M."/>
                <person name="Cancellieri C."/>
                <person name="Vacchini A."/>
                <person name="Benureau Y."/>
                <person name="Lagane B."/>
                <person name="Bachelerie F."/>
                <person name="Arenzana-Seisdedos F."/>
                <person name="Mizuno K."/>
                <person name="Mantovani A."/>
                <person name="Bonecchi R."/>
                <person name="Locati M."/>
            </authorList>
            <dbReference type="PubMed" id="23633677"/>
            <dbReference type="DOI" id="10.1126/scisignal.2003627"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="14 15 16" key="18">
        <citation type="journal article" date="2024" name="Science" volume="383" first="101" last="108">
            <title>Molecular insights into atypical modes of beta-arrestin interaction with seven transmembrane receptors.</title>
            <authorList>
                <person name="Maharana J."/>
                <person name="Sano F.K."/>
                <person name="Sarma P."/>
                <person name="Yadav M.K."/>
                <person name="Duan L."/>
                <person name="Stepniewski T.M."/>
                <person name="Chaturvedi M."/>
                <person name="Ranjan A."/>
                <person name="Singh V."/>
                <person name="Saha S."/>
                <person name="Mahajan G."/>
                <person name="Chami M."/>
                <person name="Shihoya W."/>
                <person name="Selent J."/>
                <person name="Chung K.Y."/>
                <person name="Banerjee R."/>
                <person name="Nureki O."/>
                <person name="Shukla A.K."/>
            </authorList>
            <dbReference type="PubMed" id="38175886"/>
            <dbReference type="DOI" id="10.1126/science.adj3347"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.22 ANGSTROMS) OF 338-355 IN COMPLEX WITH ARRB1 AND ARRB2</scope>
        <scope>PHOSPHORYLATION AT THR-339; SER-343; SER-345; SER-346; SER-348; SER-350; SER-351 AND THR-354</scope>
    </reference>
    <comment type="function">
        <text evidence="1 7 9 10 12">Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis (PubMed:18201974, PubMed:20373092, PubMed:23479571). Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor (PubMed:18201974, PubMed:20373092, PubMed:23479571). Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3 (PubMed:18201974, PubMed:20373092, PubMed:23479571). Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway (PubMed:23633677). Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses (PubMed:23479571). Plays a major role in the immune silencing of macrophages during the resolution of inflammation (By similarity). Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs (PubMed:23479571).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
        </interactant>
        <interactant intactId="EBI-1753674">
            <id>P52803</id>
            <label>EFNA5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
        </interactant>
        <interactant intactId="EBI-17458373">
            <id>P48165</id>
            <label>GJA8</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
        </interactant>
        <interactant intactId="EBI-2808234">
            <id>P11836</id>
            <label>MS4A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
        </interactant>
        <interactant intactId="EBI-9550165">
            <id>Q0D2K0</id>
            <label>NIPAL4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
        </interactant>
        <interactant intactId="EBI-3917235">
            <id>Q9NTJ5</id>
            <label>SACM1L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
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        <interactant intactId="EBI-12808018">
            <id>Q9UKG4</id>
            <label>SLC13A4</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-13379418">
            <id>O00590</id>
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        <interactant intactId="EBI-17684533">
            <id>Q9NRX6</id>
            <label>TMEM167B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Recycling endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7 10">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="7">Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits (PubMed:18201974). Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane (PubMed:18201974).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 8 9">Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.</text>
    </comment>
    <comment type="induction">
        <text evidence="9">By interleukin-6 and interferon-gamma.</text>
    </comment>
    <comment type="domain">
        <text evidence="7">The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.</text>
    </comment>
    <comment type="PTM">
        <text evidence="7">Phosphorylated on serine residues in the C-terminal cytoplasmic tail.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="AAP20651.1"/>
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        <property type="method" value="EM"/>
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        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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        <property type="term" value="P:positive regulation of cytosolic calcium ion concentration"/>
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        <property type="entry name" value="7tmA_ACKR2_D6"/>
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        <property type="entry name" value="Atypical chemokine receptor 2"/>
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        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
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            <dbReference type="PubMed" id="20373092"/>
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        <source>
            <dbReference type="PDB" id="8GO9"/>
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            <dbReference type="PDB" id="8J8V"/>
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            <dbReference type="PDB" id="8J8Z"/>
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    </evidence>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="8J8V"/>
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    <sequence length="384" mass="43443" checksum="464C5703C1DE9A6A" modified="2002-05-02" version="2">MAATASPQPLATEDADSENSSFYYYDYLDEVAFMLCRKDAVVSFGKVFLPVFYSLIFVLGLSGNLLLLMVLLRYVPRRRMVEIYLLNLAISNLLFLVTLPFWGISVAWHWVFGSFLCKMVSTLYTINFYSGIFFISCMSLDKYLEIVHAQPYHRLRTRAKSLLLATIVWAVSLAVSIPDMVFVQTHENPKGVWNCHADFGGHGTIWKLFLRFQQNLLGFLLPLLAMIFFYSRIGCVLVRLRPAGQGRALKIAAALVVAFFVLWFPYNLTLFLHTLLDLQVFGNCEVSQHLDYALQVTESIAFLHCCFSPILYAFSSHRFRQYLKAFLAAVLGWHLAPGTAQASLSSCSESSILTAQEEMTGMNDLGERQSENYPNKEDVGNKSA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-06-06" modified="2026-01-28" version="198" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WXI4</accession>
    <accession>B1AQ22</accession>
    <accession>D3DQ50</accession>
    <accession>O75187</accession>
    <accession>Q52LP1</accession>
    <accession>Q53ER9</accession>
    <accession>Q96DI1</accession>
    <accession>Q9H883</accession>
    <name>ACO11_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">Acyl-coenzyme A thioesterase 11</fullName>
            <shortName evidence="13">Acyl-CoA thioesterase 11</shortName>
            <ecNumber evidence="6">3.1.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA thioester hydrolase 11</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adipose-associated thioesterase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Brown fat-inducible thioesterase</fullName>
            <shortName>BFIT</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">Palmitoyl-coenzyme A thioesterase</fullName>
            <ecNumber evidence="6">3.1.2.2</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT11</name>
        <name type="synonym">BFIT</name>
        <name type="synonym">KIAA0707</name>
        <name type="synonym">THEA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Biochem. J." volume="360" first="135" last="142">
            <title>BFIT, a unique acyl-CoA thioesterase induced in thermogenic brown adipose tissue: cloning, organization of the human gene and assessment of a potential link to obesity.</title>
            <authorList>
                <person name="Adams S.H."/>
                <person name="Chui C."/>
                <person name="Schilbach S.L."/>
                <person name="Yu X.X."/>
                <person name="Goddard A.D."/>
                <person name="Grimaldi J.C."/>
                <person name="Lee J."/>
                <person name="Dowd P."/>
                <person name="Colman S."/>
                <person name="Lewin D.A."/>
            </authorList>
            <dbReference type="PubMed" id="11696000"/>
            <dbReference type="DOI" id="10.1042/bj3600135"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="169" last="176">
            <title>Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</title>
            <authorList>
                <person name="Ishikawa K."/>
                <person name="Nagase T."/>
                <person name="Suyama M."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
                <person name="Nomura N."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="9734811"/>
            <dbReference type="DOI" id="10.1093/dnares/5.3.169"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Thyroid</tissue>
        </source>
    </reference>
    <reference key="4">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT ASP-202</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
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            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
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                <person name="Chen D."/>
                <person name="Latham J."/>
                <person name="Zhao H."/>
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                <person name="Dunaway-Mariano D."/>
            </authorList>
            <dbReference type="PubMed" id="22897136"/>
            <dbReference type="DOI" id="10.1021/bi3008824"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY</scope>
    </reference>
    <reference key="9">
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            <title>Comparative structural analysis of lipid binding START domains.</title>
            <authorList>
                <person name="Thorsell A.G."/>
                <person name="Lee W.H."/>
                <person name="Persson C."/>
                <person name="Siponen M.I."/>
                <person name="Nilsson M."/>
                <person name="Busam R.D."/>
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                <person name="Schuler H."/>
                <person name="Lehtio L."/>
            </authorList>
            <dbReference type="PubMed" id="21738568"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0019521"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 339-543</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Has an acyl-CoA thioesterase activity with a preference for the long chain fatty acyl-CoA thioesters hexadecanoyl-CoA/palmitoyl-CoA and tetradecanoyl-CoA/myristoyl-CoA which are the main substrates in the mitochondrial beta-oxidation pathway.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>butanoyl-CoA + H2O = butanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40111"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:40112"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <text evidence="6">kcat is 5 min(-1) for the hydrolysis of hexadecanoyl-CoA (PubMed:22897136). kcat is 3.5 min(-1) for the hydrolysis of tetradecanoyl-CoA (PubMed:22897136). kcat is 2.3 min(-1) for the hydrolysis of dodecanoyl-CoA (PubMed:22897136). kcat is 0.2 min(-1) for the hydrolysis of butanoyl-CoA (PubMed:22897136).</text>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="13">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-739879">
            <id>Q53TS8</id>
            <label>C2CD6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-10311131">
            <id>Q9NP86</id>
            <label>CABP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-371876">
            <id>Q9NQT4</id>
            <label>EXOSC5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-752301">
            <id>Q8WXD5</id>
            <label>GEMIN6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-12094670">
            <id>Q8WUI4-6</id>
            <label>HDAC7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-740220">
            <id>O14964</id>
            <label>HGS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-751857">
            <id>O15481</id>
            <label>MAGEB4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-2340269">
            <id>Q13064</id>
            <label>MKRN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-17721098">
            <id>Q8WXI4-2</id>
        </interactant>
        <interactant intactId="EBI-3921347">
            <id>P51687</id>
            <label>SUOX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion matrix</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WXI4-1</id>
            <name>1</name>
            <name>BFIT1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WXI4-2</id>
            <name>2</name>
            <name>BFIT2</name>
            <sequence type="described" ref="VSP_000160"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Isoform 1 is predominantly expressed in skeletal muscle, liver, testis, stomach, spleen, lung and brain. Isoform 2 is predominantly expressed in kidney, uterus, hibernoma and white adipose tissue.</text>
    </comment>
    <comment type="induction">
        <text>By cold exposure and repressed by heat exposure.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA31682" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="6"/>
    <dbReference type="EC" id="3.1.2.2" evidence="6"/>
    <dbReference type="EMBL" id="AF416921">
        <property type="protein sequence ID" value="AAL40937.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF416922">
        <property type="protein sequence ID" value="AAL40938.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB014607">
        <property type="protein sequence ID" value="BAA31682.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK023937">
        <property type="protein sequence ID" value="BAB14734.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223570">
        <property type="protein sequence ID" value="BAD97290.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC099796">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL590093">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471059">
        <property type="protein sequence ID" value="EAX06682.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471059">
        <property type="protein sequence ID" value="EAX06683.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471059">
        <property type="protein sequence ID" value="EAX06684.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001517">
        <property type="protein sequence ID" value="AAH01517.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093844">
        <property type="protein sequence ID" value="AAH93844.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093846">
        <property type="protein sequence ID" value="AAH93846.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS592.1">
        <molecule id="Q8WXI4-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS593.1">
        <molecule id="Q8WXI4-2"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0276">Fatty acid metabolism</keyword>
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    <keyword id="KW-0719">Serine esterase</keyword>
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            <begin position="1"/>
            <end position="13"/>
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            <end position="607"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="91"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57287"/>
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            <begin position="120"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57287"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57287"/>
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    <feature type="binding site" evidence="1">
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            <begin position="271"/>
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        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="25"/>
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    </feature>
    <feature type="splice variant" id="VSP_000160" description="In isoform 2." evidence="8 9 10 11">
        <original>CCWVRVSLTELVSASGFYSWGLESRSKGRRSDGWNGKLAGGHLSTLKAIPVAKINSRFGYLQDT</original>
        <variation>VSYYNQATPGVLNYVTTNVAGLSSEFYTTFKACEQFLLDNRNDLAPSLQTL</variation>
        <location>
            <begin position="544"/>
            <end position="607"/>
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    </feature>
    <feature type="sequence variant" id="VAR_048190" description="In dbSNP:rs34630746.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="11"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022119" description="In dbSNP:rs2304306.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="165"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022120" description="In dbSNP:rs1702003." evidence="7">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="202"/>
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    </feature>
    <feature type="sequence variant" id="VAR_022121" description="In dbSNP:rs2304305.">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="212"/>
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    </feature>
    <feature type="sequence variant" id="VAR_048191" description="In dbSNP:rs12403630.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="536"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAH01517." evidence="12" ref="7">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="255"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD97290." evidence="12" ref="4">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="348"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="347"/>
            <end position="363"/>
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    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="370"/>
            <end position="372"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="375"/>
            <end position="378"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="381"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="384"/>
            <end position="399"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="405"/>
            <end position="410"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="413"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="424"/>
            <end position="434"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="436"/>
            <end position="444"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="446"/>
            <end position="451"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="458"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="469"/>
            <end position="476"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="486"/>
            <end position="495"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="504"/>
            <end position="512"/>
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    </feature>
    <feature type="strand" evidence="15">
        <location>
            <begin position="514"/>
            <end position="516"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="522"/>
            <end position="524"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="528"/>
            <end position="538"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="541"/>
            <end position="543"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q8VHQ9"/>
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    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00197"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01106"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="22897136"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="4"/>
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    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="11696000"/>
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    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source ref="4"/>
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    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0000305" key="13">
        <source>
            <dbReference type="PubMed" id="22897136"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="3FO5"/>
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    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="6VVQ"/>
        </source>
    </evidence>
    <sequence length="607" mass="68492" checksum="12F2BCAB8AAC18EC" modified="2002-03-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-11-01" modified="2026-01-28" version="219" xmlns="https://uniprot.org/uniprot">
    <accession>P08912</accession>
    <accession>Q96RG7</accession>
    <name>ACM5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Muscarinic acetylcholine receptor M5</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">CHRM5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="Neuron" volume="1" first="403" last="410">
            <title>Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes.</title>
            <authorList>
                <person name="Bonner T.I."/>
                <person name="Young A.C."/>
                <person name="Brann M.R."/>
                <person name="Buckley N.J."/>
            </authorList>
            <dbReference type="PubMed" id="3272174"/>
            <dbReference type="DOI" id="10.1016/0896-6273(88)90190-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="1997-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Rae J.L."/>
                <person name="Shepard A.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Lens epithelium</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>Human muscarinic acetylcholine receptor 5 is localized on 15q13.1 and its expression in SH-SY5Y cells.</title>
            <authorList>
                <person name="Wang H."/>
                <person name="Yeomans J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2001-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning cholinergic receptors in human keratinocytes.</title>
            <authorList>
                <person name="Arredondo J."/>
                <person name="Grando S.A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-526</scope>
        <source>
            <tissue>Keratinocyte</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6655256">
            <id>P08912</id>
        </interactant>
        <interactant intactId="EBI-2687785">
            <id>P20309</id>
            <label>CHRM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM5 sub-subfamily.</text>
    </comment>
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                <person name="Weber S."/>
                <person name="Thiele H."/>
                <person name="Mir S."/>
                <person name="Toliat M.R."/>
                <person name="Sozeri B."/>
                <person name="Reutter H."/>
                <person name="Draaken M."/>
                <person name="Ludwig M."/>
                <person name="Altmuller J."/>
                <person name="Frommolt P."/>
                <person name="Stuart H.M."/>
                <person name="Ranjzad P."/>
                <person name="Hanley N.A."/>
                <person name="Jennings R."/>
                <person name="Newman W.G."/>
                <person name="Wilcox D.T."/>
                <person name="Thiel U."/>
                <person name="Schlingmann K.P."/>
                <person name="Beetz R."/>
                <person name="Hoyer P.F."/>
                <person name="Konrad M."/>
                <person name="Schaefer F."/>
                <person name="Nurnberg P."/>
                <person name="Woolf A.S."/>
            </authorList>
            <dbReference type="PubMed" id="22077972"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2011.10.007"/>
        </citation>
        <scope>INVOLVEMENT IN PBS</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Mol. Pharmacol." volume="79" first="251" last="261">
            <title>Regulation of M(3) muscarinic receptor expression and function by transmembrane protein 147.</title>
            <authorList>
                <person name="Rosemond E."/>
                <person name="Rossi M."/>
                <person name="McMillin S.M."/>
                <person name="Scarselli M."/>
                <person name="Donaldson J.G."/>
                <person name="Wess J."/>
            </authorList>
            <dbReference type="PubMed" id="21056967"/>
            <dbReference type="DOI" id="10.1124/mol.110.067363"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH TMEM147</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2013" name="Biochem. J." volume="452" first="303" last="312">
            <title>The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane.</title>
            <authorList>
                <person name="Patowary S."/>
                <person name="Alvarez-Curto E."/>
                <person name="Xu T.R."/>
                <person name="Holz J.D."/>
                <person name="Oliver J.A."/>
                <person name="Milligan G."/>
                <person name="Raicu V."/>
            </authorList>
            <dbReference type="PubMed" id="23521066"/>
            <dbReference type="DOI" id="10.1042/bj20121902"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2005" name="J. Biol. Chem." volume="280" first="24568" last="24575">
            <title>Identification and structural determination of the M(3) muscarinic acetylcholine receptor basolateral sorting signal.</title>
            <authorList>
                <person name="Iverson H.A."/>
                <person name="Fox D. III"/>
                <person name="Nadler L.S."/>
                <person name="Klevit R.E."/>
                <person name="Nathanson N.M."/>
            </authorList>
            <dbReference type="PubMed" id="15870063"/>
            <dbReference type="DOI" id="10.1074/jbc.m501264200"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 271-289</scope>
        <scope>MUTAGENESIS OF GLU-276; PHE-280 AND VAL-281</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="10">The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 7 9">Homodimer; the dimers can form tetramers (PubMed:23521066). Interacts with NALCN (By similarity). Interacts with TMEM147 (PubMed:21056967).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2687785">
            <id>P20309</id>
        </interactant>
        <interactant intactId="EBI-6655256">
            <id>P08912</id>
            <label>CHRM5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2687785">
            <id>P20309</id>
        </interactant>
        <interactant intactId="EBI-7085333">
            <id>Q8IZF0</id>
            <label>NALCN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Basolateral cell membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Endoplasmic reticulum membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="7">Colocalizes with TMEM147 in the endoplasmic reticulum (ER) membrane. TMEM147 impairs its trafficking to the cell membrane leading to its retention in the ER membrane.</text>
    </comment>
    <comment type="disease" evidence="8">
        <disease id="DI-03312">
            <name>Prune belly syndrome</name>
            <acronym>PBS</acronym>
            <description>A syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities.</description>
            <dbReference type="MIM" id="100100"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.</text>
    </comment>
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    <feature type="transmembrane region" description="Helical; Name=6" evidence="1">
        <location>
            <begin position="492"/>
            <end position="514"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="515"/>
            <end position="526"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="1">
        <location>
            <begin position="527"/>
            <end position="546"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="547"/>
            <end position="590"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="323"/>
            <end position="357"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Basolateral sorting signal">
        <location>
            <begin position="275"/>
            <end position="281"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="334"/>
            <end position="345"/>
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    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="385"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="5"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="4">
        <location>
            <begin position="141"/>
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    </feature>
    <feature type="disulfide bond" evidence="4">
        <location>
            <begin position="517"/>
            <end position="520"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033461" description="In dbSNP:rs2067481.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_049368" description="In dbSNP:rs16839102.">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of basolateral sorting." evidence="6">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of basolateral sorting. No effect on basolateral sorting; when associated with L-280 and L-281." evidence="6">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of basolateral sorting." evidence="6">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="280"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on basolateral sorting." evidence="6">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="280"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of basolateral sorting." evidence="6">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="281"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on basolateral sorting." evidence="6">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAG30036." evidence="11" ref="7">
        <original>KLP</original>
        <variation>RLS</variation>
        <location>
            <begin position="382"/>
            <end position="384"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="65"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="97"/>
            <end position="99"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="102"/>
            <end position="104"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="105"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="121"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="131"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="138"/>
            <end position="171"/>
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    </feature>
    <feature type="turn" evidence="15">
        <location>
            <begin position="173"/>
            <end position="175"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="176"/>
            <end position="179"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="182"/>
            <end position="210"/>
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    </feature>
    <feature type="strand" evidence="15">
        <location>
            <begin position="211"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="strand" evidence="15">
        <location>
            <begin position="224"/>
            <end position="228"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="231"/>
            <end position="239"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="241"/>
            <end position="264"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="280"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="489"/>
            <end position="502"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="505"/>
            <end position="516"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="518"/>
            <end position="521"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="523"/>
            <end position="533"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="535"/>
            <end position="544"/>
        </location>
    </feature>
    <feature type="turn" evidence="15">
        <location>
            <begin position="545"/>
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    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="549"/>
            <end position="560"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9ERZ3"/>
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    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
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    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15870063"/>
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21056967"/>
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    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="22077972"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="23521066"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="7565628"/>
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    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0007829" key="12">
        <source>
            <dbReference type="PDB" id="2CSA"/>
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    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="8E9W"/>
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    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="8E9Y"/>
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    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="8EA0"/>
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    </evidence>
    <sequence length="590" mass="66128" checksum="5CB473C57B9526E9" modified="1991-02-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-08" modified="2026-01-28" version="181" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WYK0</accession>
    <accession>B3KVK9</accession>
    <accession>Q5FWE9</accession>
    <name>ACO12_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">Acetyl-coenzyme A thioesterase</fullName>
            <ecNumber evidence="5">3.1.2.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA thioester hydrolase 12</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acyl-coenzyme A thioesterase 12</fullName>
            <shortName>Acyl-CoA thioesterase 12</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Cytoplasmic acetyl-CoA hydrolase 1</fullName>
            <shortName>CACH-1</shortName>
            <shortName>hCACH-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>START domain-containing protein 15</fullName>
            <shortName>StARD15</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT12</name>
        <name type="synonym">CACH</name>
        <name type="synonym">CACH1</name>
        <name type="synonym">STARD15</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="Acta Biochim. Pol." volume="53" first="553" last="561">
            <title>Molecular cloning and functional expression of human cytosolic acetyl-CoA hydrolase.</title>
            <authorList>
                <person name="Suematsu N."/>
                <person name="Isohashi F."/>
            </authorList>
            <dbReference type="PubMed" id="16951743"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Yamazaki M."/>
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                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
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                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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                <person name="Haydu L."/>
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                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
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                <person name="Salazar A."/>
                <person name="Thayer N."/>
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            <dbReference type="PubMed" id="15372022"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Chondrosarcoma</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="submission" date="2007-11" db="PDB data bank">
            <title>Human acyl-coenzyme A thioesterase 12.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 7-316 IN COMPLEX WITH COENZYME A</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="Nature" volume="469" first="539" last="542">
            <title>Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.</title>
            <authorList>
                <person name="Varela I."/>
                <person name="Tarpey P."/>
                <person name="Raine K."/>
                <person name="Huang D."/>
                <person name="Ong C.K."/>
                <person name="Stephens P."/>
                <person name="Davies H."/>
                <person name="Jones D."/>
                <person name="Lin M.L."/>
                <person name="Teague J."/>
                <person name="Bignell G."/>
                <person name="Butler A."/>
                <person name="Cho J."/>
                <person name="Dalgliesh G.L."/>
                <person name="Galappaththige D."/>
                <person name="Greenman C."/>
                <person name="Hardy C."/>
                <person name="Jia M."/>
                <person name="Latimer C."/>
                <person name="Lau K.W."/>
                <person name="Marshall J."/>
                <person name="McLaren S."/>
                <person name="Menzies A."/>
                <person name="Mudie L."/>
                <person name="Stebbings L."/>
                <person name="Largaespada D.A."/>
                <person name="Wessels L.F.A."/>
                <person name="Richard S."/>
                <person name="Kahnoski R.J."/>
                <person name="Anema J."/>
                <person name="Tuveson D.A."/>
                <person name="Perez-Mancera P.A."/>
                <person name="Mustonen V."/>
                <person name="Fischer A."/>
                <person name="Adams D.J."/>
                <person name="Rust A."/>
                <person name="Chan-On W."/>
                <person name="Subimerb C."/>
                <person name="Dykema K."/>
                <person name="Furge K."/>
                <person name="Campbell P.J."/>
                <person name="Teh B.T."/>
                <person name="Stratton M.R."/>
                <person name="Futreal P.A."/>
            </authorList>
            <dbReference type="PubMed" id="21248752"/>
            <dbReference type="DOI" id="10.1038/nature09639"/>
        </citation>
        <scope>VARIANT HIS-190</scope>
    </reference>
    <comment type="function">
        <text evidence="5">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16951743). Preferentially hydrolyzes acetyl-CoA (PubMed:16951743).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>acetyl-CoA + H2O = acetate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20289"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="EC" id="3.1.2.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:20290"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>butanoyl-CoA + H2O = butanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40111"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:40112"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>hexanoyl-CoA + H2O = hexanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40115"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:40116"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 5">Inhibited by ADP. Active in the presence of ATP (PubMed:16951743). Cold labile, it dissociates into inactive monomers at low temperature (By similarity).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">150 uM for acetyl-CoA</KM>
            <text evidence="5">kcat is 7000 sec(-1) for the hydrolysis of acetyl-CoA.</text>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="10">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimer or homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
            <label>ACOT12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-12007918">
            <id>O00154-4</id>
            <label>ACOT7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-2864512">
            <id>P50221</id>
            <label>MEOX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-747693">
            <id>P41227</id>
            <label>NAA10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-2585120">
            <id>Q9BSU3</id>
            <label>NAA11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-296331">
            <id>Q02548</id>
            <label>PAX5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-747278">
            <id>P26367</id>
            <label>PAX6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-10829018">
            <id>Q04864-2</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11954993">
            <id>Q8WYK0</id>
        </interactant>
        <interactant intactId="EBI-742740">
            <id>Q96BR9</id>
            <label>ZBTB8A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
            <location evidence="5">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WYK0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WYK0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055785 VSP_055786"/>
        </isoform>
    </comment>
    <dbReference type="EC" id="3.1.2.1" evidence="5"/>
    <dbReference type="EMBL" id="AB078619">
        <property type="protein sequence ID" value="BAB84022.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK122960">
        <property type="protein sequence ID" value="BAG53821.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008411">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010623">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471084">
        <property type="protein sequence ID" value="EAW95875.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC089437">
        <property type="protein sequence ID" value="AAH89437.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC075010">
        <property type="protein sequence ID" value="AAH75010.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC075011">
        <property type="protein sequence ID" value="AAH75011.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS4055.1">
        <molecule id="Q8WYK0-1"/>
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    <dbReference type="RefSeq" id="NP_570123.1">
        <molecule id="Q8WYK0-1"/>
        <property type="nucleotide sequence ID" value="NM_130767.3"/>
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    <dbReference type="PDB" id="3B7K">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B/C=7-316"/>
    </dbReference>
    <dbReference type="PDB" id="4MOB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A=7-336"/>
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    <dbReference type="PDB" id="4MOC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A=7-336"/>
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    <dbReference type="PDBsum" id="3B7K"/>
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    <dbReference type="PDBsum" id="4MOC"/>
    <dbReference type="AlphaFoldDB" id="Q8WYK0"/>
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        <property type="interactions" value="15"/>
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    <dbReference type="FunCoup" id="Q8WYK0">
        <property type="interactions" value="125"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WYK0">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000303246"/>
    <dbReference type="SwissLipids" id="SLP:000001187"/>
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        <property type="family name" value="the paai thioesterase (pte) family"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8WYK0"/>
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    <dbReference type="ProteomicsDB" id="75162">
        <molecule id="Q8WYK0-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="24697">
        <property type="antibodies" value="180 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="134526"/>
    <dbReference type="Ensembl" id="ENST00000307624.8">
        <molecule id="Q8WYK0-1"/>
        <property type="protein sequence ID" value="ENSP00000303246.3"/>
        <property type="gene ID" value="ENSG00000172497.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000513751.1">
        <molecule id="Q8WYK0-2"/>
        <property type="protein sequence ID" value="ENSP00000421628.1"/>
        <property type="gene ID" value="ENSG00000172497.10"/>
    </dbReference>
    <dbReference type="GeneID" id="134526"/>
    <dbReference type="KEGG" id="hsa:134526"/>
    <dbReference type="MANE-Select" id="ENST00000307624.8">
        <property type="protein sequence ID" value="ENSP00000303246.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_130767.3"/>
        <property type="RefSeq protein sequence ID" value="NP_570123.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003khl.5">
        <molecule id="Q8WYK0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24436"/>
    <dbReference type="ClinPGx" id="PA142672657"/>
    <dbReference type="CTD" id="134526"/>
    <dbReference type="DisGeNET" id="134526"/>
    <dbReference type="GeneCards" id="ACOT12"/>
    <dbReference type="HGNC" id="HGNC:24436">
        <property type="gene designation" value="ACOT12"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000172497">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614315">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000172497"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="Q8WYK0"/>
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        <property type="organism ID" value="2681"/>
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        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
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        <property type="hits" value="98 hits in 1142 CRISPR screens"/>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 5"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in right lobe of liver and 67 other cell types or tissues"/>
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        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0045171">
        <property type="term" value="C:intercellular bridge"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003986">
        <property type="term" value="F:acetyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008289">
        <property type="term" value="F:lipid binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006084">
        <property type="term" value="P:acetyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-UniPathway"/>
    </dbReference>
    <dbReference type="CDD" id="cd03442">
        <property type="entry name" value="BFIT_BACH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="CDD" id="cd08914">
        <property type="entry name" value="START_STARD15-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.129.10:FF:000029">
        <property type="entry name" value="Acyl-CoA thioesterase 12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.530.20:FF:000023">
        <property type="entry name" value="Acyl-CoA thioesterase 12"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Acyl-coenzyme A thioesterase 11"/>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Homo</taxon>
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    <reference key="1">
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            <title>Rapid and phosphoinositol-dependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling.</title>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
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    <reference key="2">
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            <dbReference type="PubMed" id="10380635"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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    <reference key="3">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
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        <scope>PROTEIN SEQUENCE OF 35-60; 63-76; 113-130; 154-164; 195-207; 304-315 AND 380-389</scope>
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        <scope>IDENTIFICATION IN NUA4 COMPLEX</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>IDENTIFICATION IN THE BAF COMPLEX</scope>
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        <scope>IDENTIFICATION IN THE INO80 COMPLEX</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    </reference>
    <comment type="function">
        <text evidence="1 6 14 17 18 19">Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 17 18 19">Component of numerous complexes with chromatin remodeling and histone acetyltransferase activity. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6 (PubMed:10966108, PubMed:12963728, PubMed:14966270, PubMed:15196461). The NuA4 complex interacts with MYC and the adenovirus E1A protein (PubMed:11509179). Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41 (PubMed:11509179, PubMed:14966270). Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:18765789, PubMed:9845365). In muscle cells, the BAF complex also contains DPF3. Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM/BAF190B and TRRAP/PAF400, and which may also include a HAT activity related to, but distinct from, that of KAT5 (PubMed:11839798). Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:26601204). Interacts with SMARCA4/BRG1/BAF190A (PubMed:28649782). Interacts with PHF10/BAF45A (By similarity). Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80 (PubMed:16230350, PubMed:18026119, PubMed:18922472, PubMed:21303910). Interacts with DPF2 (PubMed:28533407).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355018">
            <id>O96019</id>
        </interactant>
        <interactant intactId="EBI-2479962">
            <id>Q92526</id>
            <label>CCT6B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355018">
            <id>O96019</id>
        </interactant>
        <interactant intactId="EBI-765538">
            <id>P25490</id>
            <label>YY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O96019-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O96019-2</id>
            <name>2</name>
            <name>HArpNbeta-s</name>
            <sequence type="described" ref="VSP_000150"/>
        </isoform>
    </comment>
    <comment type="disease">
        <text evidence="13">ACTL6A mutations have been found in patients with intellectual disability of variable severity, developmental delay, dysmorphic features and digit abnormalities. Additional features may include genitourinary and cardiac defects. The disease phenotype resembles Coffin-Siris syndrome and brachymorphism-onychodysplasia-dysphalangism syndrome.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the actin family.</text>
    </comment>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH01391.1"/>
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        <property type="nucleotide sequence ID" value="NM_004301.5"/>
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        <property type="nucleotide sequence ID" value="NM_177989.4"/>
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        <property type="nucleotide sequence ID" value="NM_178042.4"/>
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        <property type="resolution" value="3.07 A"/>
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    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1164">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1194">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1195">
        <property type="entry name" value="Embryonic stem cell-specific SWI/SNF ATP-dependent chromatin remodeling complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1199">
        <property type="entry name" value="Polybromo-associated SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A variant"/>
    </dbReference>
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        <property type="entry name" value="Neural progenitor-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1204">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1205">
        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1B-SMARCA2 variant"/>
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        <property type="entry name" value="SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1B-SMARCA4 variant"/>
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    <dbReference type="ComplexPortal" id="CPX-1212">
        <property type="entry name" value="Neural progenitor-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1A-SMARCA4 variant"/>
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    <dbReference type="ComplexPortal" id="CPX-1213">
        <property type="entry name" value="Neural progenitor-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1215">
        <property type="entry name" value="Neural progenitor-specific SWI/SNF ATP-dependent chromatin remodeling complex, ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1222">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1A-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1223">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1B-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-1224">
        <property type="entry name" value="Muscle cell-specific SWI/SNF ATP-dependent chromatin remodeling complex, ACTL6A-ARID1B-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4084">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6A-BICRA-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4203">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6A-BICRAL-SMARCA2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4206">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6A-BICRA-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-4207">
        <property type="entry name" value="GBAF (SWI/SNF) ATP-dependent chromatin remodeling complex, ACTL6A-BICRAL-SMARCA4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-846">
        <property type="entry name" value="INO80 chromatin remodeling complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-974">
        <property type="entry name" value="SRCAP chromatin remodeling complex"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-978">
        <property type="entry name" value="NuA4 histone acetyltransferase complex"/>
    </dbReference>
    <dbReference type="CORUM" id="O96019"/>
    <dbReference type="DIP" id="DIP-27565N"/>
    <dbReference type="FunCoup" id="O96019">
        <property type="interactions" value="3464"/>
    </dbReference>
    <dbReference type="IntAct" id="O96019">
        <property type="interactions" value="129"/>
    </dbReference>
    <dbReference type="MINT" id="O96019"/>
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    <dbReference type="GlyGen" id="O96019">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O96019"/>
    <dbReference type="MetOSite" id="O96019"/>
    <dbReference type="PhosphoSitePlus" id="O96019"/>
    <dbReference type="SwissPalm" id="O96019"/>
    <dbReference type="BioMuta" id="ACTL6A"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000397552"/>
    <dbReference type="PeptideAtlas" id="O96019"/>
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        <molecule id="O96019-1"/>
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        <molecule id="O96019-2"/>
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    <dbReference type="Pumba" id="O96019"/>
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        <molecule id="O96019-1"/>
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        <property type="antibodies" value="379 antibodies from 39 providers"/>
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        <molecule id="O96019-2"/>
        <property type="protein sequence ID" value="ENSP00000376430.1"/>
        <property type="gene ID" value="ENSG00000136518.18"/>
    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000397552.2"/>
        <property type="gene ID" value="ENSG00000136518.18"/>
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        <property type="protein sequence ID" value="ENSP00000394014.2"/>
        <property type="gene ID" value="ENSG00000136518.18"/>
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        <property type="protein sequence ID" value="ENSP00000397552.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004301.5"/>
        <property type="RefSeq protein sequence ID" value="NP_004292.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003fjw.4">
        <molecule id="O96019-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:24124"/>
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        <property type="evidences" value="3 evidence items across 1 molecular profile"/>
    </dbReference>
    <dbReference type="ClinPGx" id="PA134914203"/>
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    <dbReference type="DisGeNET" id="86"/>
    <dbReference type="GeneCards" id="ACTL6A"/>
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        <property type="gene designation" value="ACTL6A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000136518">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACTL6A"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="disease" value="Non-specific syndromic intellectual disability"/>
    </dbReference>
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    <dbReference type="eggNOG" id="KOG0679">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
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    <dbReference type="Reactome" id="R-HSA-3214847">
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            <begin position="75"/>
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    <feature type="strand" evidence="29">
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    <feature type="strand" evidence="29">
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    <feature type="strand" evidence="29">
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    <accession>Q8NE10</accession>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
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    <reference key="2">
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    <comment type="function">
        <text evidence="4 6 7 8 9 10 11 12 13 14 15 17 20 21">Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1 (PubMed:16107333, PubMed:19255243, PubMed:19380869, PubMed:20161793, PubMed:22300987). Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway (PubMed:16940167, PubMed:18653785, PubMed:20018651). Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness (PubMed:16940167, PubMed:18653785). In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival (PubMed:16940167, PubMed:20388803). Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration (PubMed:17804806, PubMed:18653785, PubMed:19641136, PubMed:20887389). Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12 (PubMed:18653785). Required for heart valve development (PubMed:17804806). Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels (PubMed:31211835). Acts as a receptor for SHLP2, mediating its effects on activation of proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus which leads to suppression of food intake and increased energy expenditure (PubMed:37468558).</text>
    </comment>
    <comment type="function">
        <text evidence="26">(Microbial infection) Acts as a coreceptor with CXCR4 for a restricted number of HIV isolates.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10 17 18">Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2.</text>
    </comment>
    <comment type="subunit">
        <text evidence="19">(Microbial infection) Interacts with Kaposi virus protein vCCL2.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1965291">
            <id>P25106</id>
        </interactant>
        <interactant intactId="EBI-6656842">
            <id>P37288</id>
            <label>AVPR1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1965291">
            <id>P25106</id>
        </interactant>
        <interactant intactId="EBI-489411">
            <id>P61073</id>
            <label>CXCR4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>18</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="20">Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18">Early endosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18">Recycling endosome</location>
        </subcellularLocation>
        <text evidence="18">Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits in a beta-arrestin-dependent manner. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5 11 14 15 16">Expressed in monocytes, basophils, B-cells, umbilical vein endothelial cells (HUVEC) and B-lymphoblastoid cells. Lower expression detected in CD4+ T-lymphocytes and natural killer cells. In the brain, detected in endothelial cells and capillaries, and in mature neurons of the frontal cortex and hippocampus. Expressed in tubular formation in the kidney. Highly expressed in astroglial tumor endothelial, microglial and glioma cells. Expressed at low levels in normal CD34+ progenitor cells, but at very high levels in several myeloid malignant cell lines. Expressed in breast carcinomas but not in normal breast tissue (at protein level).</text>
    </comment>
    <comment type="induction">
        <text evidence="14">Up-regulated during cell differentiation in glioma cells.</text>
    </comment>
    <comment type="domain">
        <text evidence="18">The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18">The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18">Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner.</text>
    </comment>
    <comment type="disease" evidence="20">
        <disease id="DI-06034">
            <name>Oculomotor-abducens synkinesis</name>
            <acronym>OCABSN</acronym>
            <description>An autosomal recessive disorder characterized by ptosis and elevation of the eyelid on ipsilateral abduction. OCABSN features are consistent with abnormal innervation of the levator palpebrae superioris muscle, which raises the eyelid, and the lateral rectus muscle, which controls lateral eye movement.</description>
            <dbReference type="MIM" id="619215"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="25">Was originally thought to be the receptor for VIP.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/40108/CMKOR1"/>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/CXC_chemokine_receptors"/>
        <text>CXC chemokine receptors entry</text>
    </comment>
    <dbReference type="EMBL" id="M64749">
        <property type="protein sequence ID" value="AAA62370.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U73141">
        <property type="protein sequence ID" value="AAB18130.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U67784">
        <property type="protein sequence ID" value="AAB16913.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF030297">
        <property type="protein sequence ID" value="AAB94130.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="DQ822477">
        <property type="protein sequence ID" value="ABH01258.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK291659">
        <property type="protein sequence ID" value="BAF84348.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC079611">
        <property type="protein sequence ID" value="AAX93086.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471063">
        <property type="protein sequence ID" value="EAW71092.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC036661">
        <property type="protein sequence ID" value="AAH36661.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2516.1"/>
    <dbReference type="PIR" id="A39714">
        <property type="entry name" value="A39714"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_064707.1">
        <property type="nucleotide sequence ID" value="NM_020311.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005246154.1">
        <property type="nucleotide sequence ID" value="XM_005246097.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005246155.1">
        <property type="nucleotide sequence ID" value="XM_005246098.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047301091.1">
        <property type="nucleotide sequence ID" value="XM_047445135.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047301092.1">
        <property type="nucleotide sequence ID" value="XM_047445136.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054199038.1">
        <property type="nucleotide sequence ID" value="XM_054343063.1"/>
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    <dbReference type="RefSeq" id="XP_054199039.1">
        <property type="nucleotide sequence ID" value="XM_054343064.1"/>
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    <dbReference type="RefSeq" id="XP_054199040.1">
        <property type="nucleotide sequence ID" value="XM_054343065.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054199041.1">
        <property type="nucleotide sequence ID" value="XM_054343066.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054199042.1">
        <property type="nucleotide sequence ID" value="XM_054343067.1"/>
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    <dbReference type="RefSeq" id="XP_054199043.1">
        <property type="nucleotide sequence ID" value="XM_054343068.1"/>
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    <dbReference type="PDB" id="6K3F">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="U/V/W/X/Y/Z=331-345"/>
    </dbReference>
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        <property type="resolution" value="3.80 A"/>
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        <property type="resolution" value="3.30 A"/>
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        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=2-362"/>
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    <dbReference type="PDB" id="7SK9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="A=2-362"/>
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    <dbReference type="PDB" id="8TII">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="R=2-362"/>
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    <dbReference type="PDB" id="8TIL">
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        <property type="resolution" value="3.80 A"/>
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        <property type="resolution" value="3.60 A"/>
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        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="R=2-362"/>
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    <dbReference type="PDB" id="9E82">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="R=2-362"/>
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    <dbReference type="PDBsum" id="6K3F"/>
    <dbReference type="PDBsum" id="7SK3"/>
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    <dbReference type="PDBsum" id="7SK5"/>
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    <dbReference type="PDBsum" id="8TIL"/>
    <dbReference type="PDBsum" id="8TIN"/>
    <dbReference type="PDBsum" id="8TIO"/>
    <dbReference type="PDBsum" id="8VJ9"/>
    <dbReference type="PDBsum" id="9E82"/>
    <dbReference type="AlphaFoldDB" id="P25106"/>
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    <dbReference type="BioGRID" id="121321">
        <property type="interactions" value="57"/>
    </dbReference>
    <dbReference type="CORUM" id="P25106"/>
    <dbReference type="FunCoup" id="P25106">
        <property type="interactions" value="775"/>
    </dbReference>
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        <property type="interactions" value="120"/>
    </dbReference>
    <dbReference type="MINT" id="P25106"/>
    <dbReference type="STRING" id="9606.ENSP00000272928"/>
    <dbReference type="BindingDB" id="P25106"/>
    <dbReference type="ChEMBL" id="CHEMBL2010631"/>
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    <dbReference type="GlyCosmos" id="P25106">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P25106">
        <property type="glycosylation" value="4 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
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    <dbReference type="PaxDb" id="9606-ENSP00000272928"/>
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        <property type="antibodies" value="9 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="47699">
        <property type="antibodies" value="881 antibodies from 41 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="57007"/>
    <dbReference type="Ensembl" id="ENST00000272928.4">
        <property type="protein sequence ID" value="ENSP00000272928.3"/>
        <property type="gene ID" value="ENSG00000144476.7"/>
    </dbReference>
    <dbReference type="GeneID" id="57007"/>
    <dbReference type="KEGG" id="hsa:57007"/>
    <dbReference type="MANE-Select" id="ENST00000272928.4">
        <property type="protein sequence ID" value="ENSP00000272928.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_020311.3"/>
        <property type="RefSeq protein sequence ID" value="NP_064707.1"/>
    </dbReference>
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        <property type="organism name" value="human"/>
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        <property type="gene designation" value="ACKR3"/>
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        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACKR3"/>
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        <property type="type" value="gene"/>
    </dbReference>
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        <property type="type" value="phenotype"/>
    </dbReference>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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        <property type="pathway name" value="Chemokine receptors bind chemokines"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418594">
        <property type="pathway name" value="G alpha (i) signalling events"/>
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        <property type="hits" value="10 hits in 1128 CRISPR screens"/>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tchem"/>
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        <property type="component" value="Chromosome 2"/>
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    <dbReference type="RNAct" id="P25106">
        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in synovial joint and 194 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P25106">
        <property type="expression patterns" value="baseline and differential"/>
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        <property type="evidence" value="ECO:0000314"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0005905">
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    </dbReference>
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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    </dbReference>
    <dbReference type="GO" id="GO:0009897">
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    </dbReference>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
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        <property type="project" value="GO_Central"/>
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    </dbReference>
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005044">
        <property type="term" value="F:scavenger receptor activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
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        <property type="term" value="P:calcium-mediated signaling"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007155">
        <property type="term" value="P:cell adhesion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060326">
        <property type="term" value="P:cell chemotaxis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070098">
        <property type="term" value="P:chemokine-mediated signaling pathway"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006955">
        <property type="term" value="P:immune response"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008285">
        <property type="term" value="P:negative regulation of cell population proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902230">
        <property type="term" value="P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage"/>
        <property type="evidence" value="ECO:0000315"/>
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    <accession>P11229</accession>
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            <fullName>Muscarinic acetylcholine receptor M1</fullName>
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        <name type="primary">CHRM1</name>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
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    <reference key="1">
        <citation type="journal article" date="1987" name="Nucleic Acids Res." volume="15" first="10604" last="10604">
            <title>Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor.</title>
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                <person name="Allard W.J."/>
                <person name="Sigal I.S."/>
                <person name="Dixon R.A.F."/>
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            <dbReference type="DOI" id="10.1093/nar/15.24.10604"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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    <reference key="2">
        <citation type="journal article" date="1990" name="Nucleic Acids Res." volume="18" first="2191" last="2191">
            <title>Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification.</title>
            <authorList>
                <person name="Chapman C.G."/>
                <person name="Browne M.J."/>
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            <dbReference type="DOI" id="10.1093/nar/18.8.2191"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1987" name="EMBO J." volume="6" first="3923" last="3929">
            <title>Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.</title>
            <authorList>
                <person name="Peralta E.G."/>
                <person name="Ashkenazi A."/>
                <person name="Winslow J.W."/>
                <person name="Smith D.H."/>
                <person name="Ramachandran J."/>
                <person name="Capon D.J."/>
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            <dbReference type="DOI" id="10.1002/j.1460-2075.1987.tb02733.x"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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    <reference key="4">
        <citation type="submission" date="2001-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning Cholinergic Receptors in Human Keratinocytes.</title>
            <authorList>
                <person name="Arredondo J."/>
                <person name="Grando S.A."/>
            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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    <reference key="5">
        <citation type="submission" date="2002-04" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
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                <person name="Puhl H.L. III"/>
                <person name="Ikeda S.R."/>
                <person name="Aronstam R.S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
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    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="497" last="500">
            <title>Human chromosome 11 DNA sequence and analysis including novel gene identification.</title>
            <authorList>
                <person name="Taylor T.D."/>
                <person name="Noguchi H."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Kuroki Y."/>
                <person name="Dewar K."/>
                <person name="Lloyd C."/>
                <person name="Itoh T."/>
                <person name="Takeda T."/>
                <person name="Kim D.-W."/>
                <person name="She X."/>
                <person name="Barlow K.F."/>
                <person name="Bloom T."/>
                <person name="Bruford E."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Eichler E."/>
                <person name="FitzGerald M.G."/>
                <person name="Jaffe D.B."/>
                <person name="LaButti K."/>
                <person name="Nicol R."/>
                <person name="Park H.-S."/>
                <person name="Seaman C."/>
                <person name="Sougnez C."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
                <person name="Zody M.C."/>
                <person name="Birren B.W."/>
                <person name="Nusbaum C."/>
                <person name="Fujiyama A."/>
                <person name="Hattori M."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1992" name="Biochem. Biophys. Res. Commun." volume="188" first="1111" last="1115">
            <title>Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor.</title>
            <authorList>
                <person name="Arden J.R."/>
                <person name="Nagata O."/>
                <person name="Shockley M.S."/>
                <person name="Philip M."/>
                <person name="Lameh J."/>
                <person name="Sadee W."/>
            </authorList>
            <dbReference type="PubMed" id="1445347"/>
            <dbReference type="DOI" id="10.1016/0006-291x(92)91346-r"/>
        </citation>
        <scope>MUTAGENESIS</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="J. Neurochem." volume="89" first="766" last="775">
            <title>Identification of a novel family of G protein-coupled receptor associated sorting proteins.</title>
            <authorList>
                <person name="Simonin F."/>
                <person name="Karcher P."/>
                <person name="Boeuf J.J.-M."/>
                <person name="Matifas A."/>
                <person name="Kieffer B.L."/>
            </authorList>
            <dbReference type="PubMed" id="15086532"/>
            <dbReference type="DOI" id="10.1111/j.1471-4159.2004.02411.x"/>
        </citation>
        <scope>INTERACTION WITH GPRASP2</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Mol. Pharmacol." volume="79" first="251" last="261">
            <title>Regulation of M(3) muscarinic receptor expression and function by transmembrane protein 147.</title>
            <authorList>
                <person name="Rosemond E."/>
                <person name="Rossi M."/>
                <person name="McMillin S.M."/>
                <person name="Scarselli M."/>
                <person name="Donaldson J.G."/>
                <person name="Wess J."/>
            </authorList>
            <dbReference type="PubMed" id="21056967"/>
            <dbReference type="DOI" id="10.1124/mol.110.067363"/>
        </citation>
        <scope>INTERACTION WITH TMEM147</scope>
    </reference>
    <reference evidence="11" key="11">
        <citation type="journal article" date="2020" name="Science" volume="369" first="161" last="167">
            <title>Structure and selectivity engineering of the M1 muscarinic receptor toxin complex.</title>
            <authorList>
                <person name="Maeda S."/>
                <person name="Xu J."/>
                <person name="Kadji F.M.N."/>
                <person name="Clark M.J."/>
                <person name="Zhao J."/>
                <person name="Tsutsumi N."/>
                <person name="Aoki J."/>
                <person name="Sunahara R.K."/>
                <person name="Inoue A."/>
                <person name="Garcia K.C."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="32646996"/>
            <dbReference type="DOI" id="10.1126/science.aax2517"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 2-218 AND 355-460 IN COMPLEX WITH SNAKE VENOM MUSCARINIC TOXIN 7</scope>
        <scope>TOPOLOGY</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <comment type="function">
        <text>The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 7">Interacts with GPRASP2 (PubMed:15086532). Interacts with TMEM147 (PubMed:21056967).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location>Postsynaptic cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P11229-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P11229-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056651"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM1 sub-subfamily.</text>
    </comment>
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        <property type="protein sequence ID" value="CAA68560.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X52068">
        <property type="protein sequence ID" value="CAA36291.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X15263">
        <property type="protein sequence ID" value="CAA33334.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF385587">
        <property type="protein sequence ID" value="AAK68112.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AF498915">
        <property type="protein sequence ID" value="AAM18938.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC007740">
        <property type="protein sequence ID" value="AAH07740.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH22984.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="P11229-1"/>
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        <property type="entry name" value="S09508"/>
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        <property type="nucleotide sequence ID" value="NM_000738.2"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="XM_011544742.3"/>
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    <dbReference type="RefSeq" id="XP_054223541.1">
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        <property type="nucleotide sequence ID" value="XM_054367566.1"/>
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        <property type="resolution" value="2.70 A"/>
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    <dbReference type="PDB" id="6OIJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
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    <dbReference type="PDB" id="6WJC">
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    <dbReference type="PDB" id="6ZFZ">
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        <property type="resolution" value="2.17 A"/>
        <property type="chains" value="A=27-219, A=355-438"/>
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    <dbReference type="PDB" id="6ZG4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.33 A"/>
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    <dbReference type="PDB" id="6ZG9">
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    <dbReference type="PDB" id="9JEA">
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        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="A=25-412, A=414-417"/>
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        <property type="generic name" value="Aceclidine"/>
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    <dbReference type="DrugBank" id="DB03128">
        <property type="generic name" value="Acetylcholine"/>
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    <dbReference type="DrugBank" id="DB08897">
        <property type="generic name" value="Aclidinium"/>
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    <dbReference type="DrugBank" id="DB16911">
        <property type="generic name" value="AF-710B"/>
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    <dbReference type="DrugBank" id="DB05752">
        <property type="generic name" value="ALKS 27"/>
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    <dbReference type="DrugBank" id="DB00321">
        <property type="generic name" value="Amitriptyline"/>
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    <dbReference type="DrugBank" id="DB00543">
        <property type="generic name" value="Amoxapine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00517">
        <property type="generic name" value="Anisotropine methylbromide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04365">
        <property type="generic name" value="Arecoline"/>
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    <dbReference type="DrugBank" id="DB01238">
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    <dbReference type="DrugBank" id="DB14185">
        <property type="generic name" value="Aripiprazole lauroxil"/>
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    <dbReference type="DrugBank" id="DB00572">
        <property type="generic name" value="Atropine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00245">
        <property type="generic name" value="Benzatropine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00767">
        <property type="generic name" value="Benzquinamide"/>
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    <dbReference type="DrugBank" id="DB01019">
        <property type="generic name" value="Bethanechol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00810">
        <property type="generic name" value="Biperiden"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB05592">
        <property type="generic name" value="Blarcamesine"/>
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    <dbReference type="DrugBank" id="DB09128">
        <property type="generic name" value="Brexpiprazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00835">
        <property type="generic name" value="Brompheniramine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00354">
        <property type="generic name" value="Buclizine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB11504">
        <property type="generic name" value="Caramiphen"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00411">
        <property type="generic name" value="Carbamoylcholine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00185">
        <property type="generic name" value="Cevimeline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00477">
        <property type="generic name" value="Chlorpromazine"/>
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    <dbReference type="DrugBank" id="DB01239">
        <property type="generic name" value="Chlorprothixene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00568">
        <property type="generic name" value="Cinnarizine"/>
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    <dbReference type="DrugBank" id="DB00771">
        <property type="generic name" value="Clidinium"/>
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    <dbReference type="DrugBank" id="DB00363">
        <property type="generic name" value="Clozapine"/>
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    <dbReference type="DrugBank" id="DB00907">
        <property type="generic name" value="Cocaine"/>
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    <dbReference type="DrugBank" id="DB00979">
        <property type="generic name" value="Cyclopentolate"/>
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    <dbReference type="DrugBank" id="DB00942">
        <property type="generic name" value="Cycrimine"/>
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    <dbReference type="DrugBank" id="DB00434">
        <property type="generic name" value="Cyproheptadine"/>
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    <dbReference type="DrugBank" id="DB00496">
        <property type="generic name" value="Darifenacin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB06421">
        <property type="generic name" value="Declopramide"/>
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    <dbReference type="DrugBank" id="DB01151">
        <property type="generic name" value="Desipramine"/>
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    <dbReference type="DrugBank" id="DB00804">
        <property type="generic name" value="Dicyclomine"/>
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    <dbReference type="DrugBank" id="DB13720">
        <property type="generic name" value="Diphemanil"/>
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    <dbReference type="DrugBank" id="DB01231">
        <property type="generic name" value="Diphenidol"/>
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    <dbReference type="DrugBank" id="DB00280">
        <property type="generic name" value="Disopyramide"/>
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    <dbReference type="DrugBank" id="DB09167">
        <property type="generic name" value="Dosulepin"/>
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    <dbReference type="DrugBank" id="DB01142">
        <property type="generic name" value="Doxepin"/>
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    <dbReference type="DrugBank" id="DB00366">
        <property type="generic name" value="Doxylamine"/>
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    <dbReference type="DrugBank" id="DB01175">
        <property type="generic name" value="Escitalopram"/>
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    <dbReference type="DrugBank" id="DB09194">
        <property type="generic name" value="Etoperidone"/>
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    <dbReference type="DrugBank" id="DB06702">
        <property type="generic name" value="Fesoterodine"/>
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        <property type="generic name" value="Flavoxate"/>
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    <dbReference type="DrugBank" id="DB00875">
        <property type="generic name" value="Flupentixol"/>
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    <dbReference type="DrugBank" id="DB00483">
        <property type="generic name" value="Gallamine triethiodide"/>
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        <property type="generic name" value="Glycopyrronium"/>
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    <dbReference type="DrugBank" id="DB06787">
        <property type="generic name" value="Hexocyclium"/>
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    <dbReference type="DrugBank" id="DB11181">
        <property type="generic name" value="Homatropine"/>
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    <dbReference type="DrugBank" id="DB00725">
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        <property type="generic name" value="Hyoscyamine"/>
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        <property type="generic name" value="Imidafenacin"/>
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        <property type="generic name" value="Imipramine"/>
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        <property type="generic name" value="Methantheline"/>
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        <original>V</original>
        <variation>M</variation>
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<entry dataset="Swiss-Prot" created="2002-09-19" modified="2026-01-28" version="192" xmlns="https://uniprot.org/uniprot">
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            <taxon>Eutheria</taxon>
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            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
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        </source>
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            <dbReference type="PubMed" id="14574404"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Cervix</tissue>
        </source>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
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            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
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                <person name="Van Damme P."/>
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            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="11">
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            <authorList>
                <person name="Vaca Jacome A.S."/>
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            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference evidence="10" key="12">
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            <title>Crystal structure of human thioesterase superfamily member 2.</title>
            <authorList>
                <person name="Cheng Z."/>
                <person name="Song F."/>
                <person name="Shan X."/>
                <person name="Wei Z."/>
                <person name="Wang Y."/>
                <person name="Dunaway-Mariano D."/>
                <person name="Gong W."/>
            </authorList>
            <dbReference type="PubMed" id="16934754"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2006.08.025"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS)</scope>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>MUTAGENESIS OF ASP-65</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference evidence="11" key="13">
        <citation type="journal article" date="2009" name="Biochemistry" volume="48" first="1293" last="1304">
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            <authorList>
                <person name="Cao J."/>
                <person name="Xu H."/>
                <person name="Zhao H."/>
                <person name="Gong W."/>
                <person name="Dunaway-Mariano D."/>
            </authorList>
            <dbReference type="PubMed" id="19170545"/>
            <dbReference type="DOI" id="10.1021/bi801879z"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF ASN-50; HIS-56; ASP-65 AND SER-83</scope>
        <scope>SUBUNIT</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="14">
        <citation type="submission" date="2009-02" db="PDB data bank">
            <title>The crystal structure of human thioesterase superfamily member 2.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2 3">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16934754, PubMed:19170545). Has acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates (By similarity) (PubMed:16934754, PubMed:19170545). Can also hydrolyze 3-hydroxyphenylacetyl-CoA and 3,4-dihydroxyphenylacetyl-CoA (in vitro) (By similarity) (PubMed:16934754, PubMed:19170545). May play a role in controlling adaptive thermogenesis (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a fatty acyl-CoA + H2O = a fatty acid + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16781"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77636"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:16782"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>octanoyl-CoA + H2O = octanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:30144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>butanoyl-CoA + H2O = butanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40111"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40112"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>hexanoyl-CoA + H2O = hexanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40115"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40116"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40151"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:40152"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">4.9 uM for n-decanoyl-CoA</KM>
            <KM evidence="3">26 uM for n-octanoyl-CoA</KM>
            <KM evidence="3">70 uM for n-hexanoyl-CoA</KM>
            <KM evidence="3">600 uM for n-butyryl-CoA</KM>
            <KM evidence="3">220 uM for 2-butenoyl-CoA</KM>
            <KM evidence="3">120 uM for beta-methylcrotonyl-CoA</KM>
            <KM evidence="3">180 uM for crotonyl-CoA</KM>
            <KM evidence="3">250 uM for tiglyl-CoA</KM>
            <KM evidence="3">190 uM for n-propionyl-CoA</KM>
            <KM evidence="3">290 uM for acetyl-CoA</KM>
            <KM evidence="3">9.9 uM for lauroyl-CoA/dodecanoyl-CoA</KM>
            <KM evidence="3">5 uM for myristoyl-CoA/tetradecanoyl-CoA (at 25 degrees Celsius)</KM>
            <KM evidence="3">9 uM for myristoyl-CoA/tetradecanoyl-CoA (at 37 degrees Celsius)</KM>
            <KM evidence="3">16 uM for n-palmitoyl-CoA</KM>
            <KM evidence="3">9 uM for palmitoleoyl-CoA</KM>
            <KM evidence="3">20 uM for stearoyl-CoA</KM>
            <KM evidence="3">9 uM for oleoyl-CoA</KM>
            <KM evidence="3">310 uM for linoleoyl-CoA</KM>
            <KM evidence="3">20 uM for arachidonoyl-CoA/(5Z,8Z,11Z,14Z)-eicosatetraenoate</KM>
            <KM evidence="3">41 uM for 3-hydroxyphenylacetyl-CoA</KM>
            <KM evidence="3">10 uM for 3,4-dihydroxyphenylacetyl-CoA</KM>
            <KM evidence="3">25 uM for 3,5-dihydroxyphenylacetyl-CoA</KM>
            <KM evidence="3">49 uM for 4-hydroxyphenylacetyl-CoA</KM>
            <KM evidence="3">240 uM for phenylacetyl-CoA</KM>
            <KM evidence="3">32 uM for 3-hydroxybenzoyl-CoA</KM>
            <KM evidence="3">13 uM for 4-chlorobenzoyl-CoA</KM>
            <KM evidence="3">110 uM for beta-hydroxybutyryl-CoA</KM>
            <KM evidence="3">670 uM for glutaryl-CoA</KM>
            <KM evidence="3">2900 uM for 3-hydroxy-3-methylglutaryl-CoA</KM>
            <KM evidence="3">280 uM for malonyl-CoA</KM>
            <KM evidence="3">210 uM for methylmalonyl-CoA</KM>
            <text evidence="3">kcat is 0.016 sec(-1) for n-decanoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.0047 sec(-1) for n-octanoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.022 sec(-1) for n-hexanoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.047 sec(-1) for n-butyryl-CoA hydrolase activity (PubMed:19170545). kcat is 0.014 sec(-1) for 2-butenoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.023 sec(-1) for beta-methylcrotonyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.0076 sec(-1) for crotonyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.02 sec(-1) for tiglyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.036 sec(-1) for n-propionyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.054 sec(-1) for acetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.019 sec(-1) for lauroyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.02 sec(-1) for myristoyl-CoA (at 25 degrees Celsius) hydrolase activity (PubMed:19170545). kcat is 0.07 sec(-1) for myristoyl-CoA (at 37 degrees Celsius) hydrolase activity (PubMed:19170545). kcat is 0.0044 sec(-1) for n-palmitoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.017 sec(-1) for palmitoleoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.011 sec(-1) for stearoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.011 sec(-1) for oleoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.017 sec(-1) for linoleoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.022 sec(-1) for arachidonoyl-CoA hydrolase activity (PubMed:19170545). kcat is 1.4 sec(-1) for 3-hydroxyphenylacetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.19 sec(-1) for 3,4-dihydroxyphenylacetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.19 sec(-1) for 3,5-dihydroxyphenylacetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.14 sec(-1) for 4-hydroxyphenylacetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.084 sec(-1) for phenylacetyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.011 sec(-1) for 3-hydroxybenzoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.032 sec(-1) for 4-chlorobenzoyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.18 sec(-1) for beta-hydroxybutyryl-CoA hydrolase activity (PubMed:19170545). kcat is 0.05 sec(-1) for glutaryl-CoA hydrolase activity (PubMed:19170545). kcat is 0.079 sec(-1) for 3-hydroxy-3-methylglutaryl-CoA hydrolase activity (PubMed:19170545). kcat is 0.066 sec(-1) for malonyl-CoA hydrolase activity (PubMed:19170545). kcat is 0.083 sec(-1) for methylmalonyl-CoA hydrolase activity (PubMed:19170545).</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 3">Homotetramer (PubMed:16934754, PubMed:19170545). Interacts with PCTP (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-399080">
            <id>Q92993</id>
            <label>KAT5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-11742507">
            <id>Q8TAP4-4</id>
            <label>LMO3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-718622">
            <id>Q969H8</id>
            <label>MYDGF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-741158">
            <id>Q96HA8</id>
            <label>NTAQ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-9090795">
            <id>Q15047-2</id>
            <label>SETDB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-742688">
            <id>Q9NZD8</id>
            <label>SPG21</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1045357">
            <id>Q9NPJ3</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytosol</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
            <location evidence="1">Spindle</location>
        </subcellularLocation>
        <text evidence="1">During interphase, found both in the nucleus and in the cytoplasm. At mitosis, localizes to the spindle. Colocalizes with tubulin.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NPJ3-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NPJ3-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046101"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the thioesterase PaaI family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="3"/>
    <dbReference type="EC" id="3.1.2.2" evidence="3"/>
    <dbReference type="EMBL" id="AF155649">
        <property type="protein sequence ID" value="AAF67006.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF220186">
        <property type="protein sequence ID" value="AAF67651.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF274952">
        <property type="protein sequence ID" value="AAK07529.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000508">
        <property type="protein sequence ID" value="BAA91215.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK309738">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL031775">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000894">
        <property type="protein sequence ID" value="AAH00894.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4558.1">
        <molecule id="Q9NPJ3-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54972.1">
        <molecule id="Q9NPJ3-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001153566.1">
        <molecule id="Q9NPJ3-2"/>
        <property type="nucleotide sequence ID" value="NM_001160094.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060943.1">
        <molecule id="Q9NPJ3-1"/>
        <property type="nucleotide sequence ID" value="NM_018473.4"/>
    </dbReference>
    <dbReference type="PDB" id="2F0X">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=1-140"/>
    </dbReference>
    <dbReference type="PDB" id="2H4U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B/C/D=19-140"/>
    </dbReference>
    <dbReference type="PDB" id="3F5O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=1-140"/>
    </dbReference>
    <dbReference type="PDBsum" id="2F0X"/>
    <dbReference type="PDBsum" id="2H4U"/>
    <dbReference type="PDBsum" id="3F5O"/>
    <dbReference type="AlphaFoldDB" id="Q9NPJ3"/>
    <dbReference type="SMR" id="Q9NPJ3"/>
    <dbReference type="BioGRID" id="120958">
        <property type="interactions" value="55"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NPJ3">
        <property type="interactions" value="1730"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NPJ3">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000230048"/>
    <dbReference type="ChEMBL" id="CHEMBL4295957"/>
    <dbReference type="DrugBank" id="DB08688">
        <property type="generic name" value="2-Undecanone"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NPJ3"/>
    <dbReference type="PhosphoSitePlus" id="Q9NPJ3"/>
    <dbReference type="SwissPalm" id="Q9NPJ3"/>
    <dbReference type="BioMuta" id="ACOT13"/>
    <dbReference type="jPOST" id="Q9NPJ3"/>
    <dbReference type="MassIVE" id="Q9NPJ3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000230048"/>
    <dbReference type="PeptideAtlas" id="Q9NPJ3"/>
    <dbReference type="ProteomicsDB" id="26006"/>
    <dbReference type="ProteomicsDB" id="82025">
        <molecule id="Q9NPJ3-1"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9NPJ3"/>
    <dbReference type="TopDownProteomics" id="Q9NPJ3-1">
        <molecule id="Q9NPJ3-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="10661">
        <property type="antibodies" value="211 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55856"/>
    <dbReference type="Ensembl" id="ENST00000230048.5">
        <molecule id="Q9NPJ3-1"/>
        <property type="protein sequence ID" value="ENSP00000230048.3"/>
        <property type="gene ID" value="ENSG00000112304.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000537591.5">
        <molecule id="Q9NPJ3-2"/>
        <property type="protein sequence ID" value="ENSP00000445552.1"/>
        <property type="gene ID" value="ENSG00000112304.12"/>
    </dbReference>
    <dbReference type="GeneID" id="55856"/>
    <dbReference type="KEGG" id="hsa:55856"/>
    <dbReference type="MANE-Select" id="ENST00000230048.5">
        <property type="protein sequence ID" value="ENSP00000230048.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018473.4"/>
        <property type="RefSeq protein sequence ID" value="NP_060943.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003nek.4">
        <molecule id="Q9NPJ3-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:20999"/>
    <dbReference type="ClinPGx" id="PA165617655"/>
    <dbReference type="CTD" id="55856"/>
    <dbReference type="DisGeNET" id="55856"/>
    <dbReference type="GeneCards" id="ACOT13"/>
    <dbReference type="HGNC" id="HGNC:20999">
        <property type="gene designation" value="ACOT13"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000112304">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="615652">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000112304"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000112304"/>
    <dbReference type="eggNOG" id="KOG3328">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000013934"/>
    <dbReference type="HOGENOM" id="CLU_089876_12_2_1"/>
    <dbReference type="InParanoid" id="Q9NPJ3"/>
    <dbReference type="OMA" id="RDKVMVS"/>
    <dbReference type="OrthoDB" id="46529at2759"/>
    <dbReference type="PAN-GO" id="Q9NPJ3">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NPJ3"/>
    <dbReference type="BRENDA" id="3.1.2.20">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NPJ3"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9NPJ3"/>
    <dbReference type="SignaLink" id="Q9NPJ3"/>
    <dbReference type="Agora" id="ENSG00000112304"/>
    <dbReference type="BioGRID-ORCS" id="55856">
        <property type="hits" value="15 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOT13">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NPJ3"/>
    <dbReference type="GenomeRNAi" id="55856"/>
    <dbReference type="Pharos" id="Q9NPJ3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NPJ3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NPJ3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000112304">
        <property type="expression patterns" value="Expressed in right lobe of liver and 201 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005819">
        <property type="term" value="C:spindle"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047617">
        <property type="term" value="F:fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120163">
        <property type="term" value="P:negative regulation of cold-induced thermogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="YuBioLab"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051289">
        <property type="term" value="P:protein homotetramerization"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd03443">
        <property type="entry name" value="PaaI_thioesterase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.129.10:FF:000021">
        <property type="entry name" value="Acyl-coenzyme A thioesterase 13"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.10.129.10">
        <property type="entry name" value="Hotdog Thioesterase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR039298">
        <property type="entry name" value="ACOT13"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029069">
        <property type="entry name" value="HotDog_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003736">
        <property type="entry name" value="PAAI_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006683">
        <property type="entry name" value="Thioestr_dom"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR00369">
        <property type="entry name" value="unchar_dom_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR21660:SF1">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE 13"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR21660">
        <property type="entry name" value="THIOESTERASE SUPERFAMILY MEMBER-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03061">
        <property type="entry name" value="4HBT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54637">
        <property type="entry name" value="Thioesterase/thiol ester dehydrase-isomerase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000156697" description="Acyl-coenzyme A thioesterase 13">
        <location>
            <begin position="1"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="initiator methionine" description="Removed; alternate" evidence="12 13 14 15">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000424501" description="Acyl-coenzyme A thioesterase 13, N-terminally processed">
        <location>
            <begin position="2"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3 11">
        <location>
            <position position="46"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 11">
        <location>
            <position position="50"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 11">
        <location>
            <position position="81"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3 11">
        <location>
            <position position="83"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3 11">
        <location>
            <begin position="90"/>
            <end position="95"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3 11">
        <location>
            <begin position="108"/>
            <end position="113"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3 11">
        <location>
            <position position="137"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="13 14 15">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylthreonine; in Acyl-coenzyme A thioesterase 13, N-terminally processed" evidence="12 13 14 15">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="108"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="127"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046101" description="In isoform 2." evidence="4">
        <original>MTSMTQSLREVIKAMTKARNFERVLG</original>
        <variation>MVR</variation>
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced acyl-CoA hydrolase activity." evidence="3">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases affinity for substrate." evidence="3">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of acyl-CoA hydrolase activity." evidence="2 3">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced acyl-CoA hydrolase activity." evidence="2 3">
        <original>D</original>
        <variation>E</variation>
        <variation>N</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced acyl-CoA hydrolase activity." evidence="3">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="83"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="3"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="18"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="21"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="29"/>
            <end position="34"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="37"/>
            <end position="43"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="46"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="53"/>
            <end position="55"/>
        </location>
    </feature>
    <feature type="helix" evidence="16">
        <location>
            <begin position="57"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="75"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="82"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="99"/>
            <end position="109"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="111"/>
            <end position="122"/>
        </location>
    </feature>
    <feature type="turn" evidence="16">
        <location>
            <begin position="123"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="strand" evidence="16">
        <location>
            <begin position="128"/>
            <end position="137"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9CQR4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16934754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="19170545"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="16934754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="19170545"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="19170545"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:20999"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PDB" id="2F0X"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PDB" id="3F5O"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="3F5O"/>
        </source>
    </evidence>
    <sequence length="140" mass="14960" checksum="084E36EFEE715A18" modified="2000-10-01" version="1">MTSMTQSLREVIKAMTKARNFERVLGKITLVSAAPGKVICEMKVEEEHTNAIGTLHGGLTATLVDNISTMALLCTERGAPGVSVDMNITYMSPAKLGEDIVITAHVLKQGKTLAFTSVDLTNKATGKLIAQGRHTKHLGN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-12-08" modified="2026-01-28" version="180" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y305</accession>
    <accession>B3KNC9</accession>
    <accession>B7ZM94</accession>
    <name>ACOT9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A thioesterase 9, mitochondrial</fullName>
            <shortName>Acyl-CoA thioesterase 9</shortName>
            <ecNumber evidence="2">3.1.2.-</ecNumber>
            <ecNumber evidence="2">3.1.2.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA thioester hydrolase 9</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ACOT9</name>
        <name type="ORF">CGI-16</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-103</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
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                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] HIS-305</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Mitochondrial acyl-CoA thioesterase. Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoA), regulating their respective intracellular levels. Regulates both mitochondrial lipid and amino acid metabolism.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>butanoyl-CoA + H2O = butanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40111"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40112"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>propanoyl-CoA + H2O = propanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40103"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40104"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>octanoyl-CoA + H2O = octanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:30144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>4,8-dimethylnonanoyl-CoA + H2O = 4,8-dimethylnonanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40223"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77061"/>
            <dbReference type="ChEBI" id="CHEBI:77063"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40224"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>3-methylbutanoyl-CoA + H2O = 3-methylbutanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:66984"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:48942"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57345"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:66985"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>2-methylpropanoyl-CoA + H2O = 2-methylpropanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40799"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:48944"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57338"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40800"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Strongly inhibited by NADH and CoA.</text>
    </comment>
    <comment type="pathway">
        <text evidence="2">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with NYAP1, NYAP2 and MYO16.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Mitochondrion matrix</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Mitochondrion inner membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Y305-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y305-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_036419"/>
        </isoform>
        <isoform>
            <id>Q9Y305-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_036420"/>
        </isoform>
        <isoform>
            <id>Q9Y305-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_041093"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the acyl coenzyme A hydrolase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="2"/>
    <dbReference type="EC" id="3.1.2.2" evidence="2"/>
    <dbReference type="EMBL" id="AF132950">
        <property type="protein sequence ID" value="AAD27725.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK024337">
        <property type="protein sequence ID" value="BAG51291.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX648512">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093011">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC131011">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471074">
        <property type="protein sequence ID" value="EAW98998.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136671">
        <property type="protein sequence ID" value="AAI36672.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC144360">
        <property type="protein sequence ID" value="AAI44361.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS35216.1">
        <molecule id="Q9Y305-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43924.1">
        <molecule id="Q9Y305-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS83460.1">
        <molecule id="Q9Y305-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001028755.2">
        <molecule id="Q9Y305-1"/>
        <property type="nucleotide sequence ID" value="NM_001033583.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001032248.1">
        <molecule id="Q9Y305-4"/>
        <property type="nucleotide sequence ID" value="NM_001037171.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001317188.1">
        <molecule id="Q9Y305-3"/>
        <property type="nucleotide sequence ID" value="NM_001330259.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9Y305"/>
    <dbReference type="SMR" id="Q9Y305"/>
    <dbReference type="BioGRID" id="117132">
        <property type="interactions" value="191"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y305">
        <property type="interactions" value="1310"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y305"/>
    <dbReference type="STRING" id="9606.ENSP00000368605"/>
    <dbReference type="ChEMBL" id="CHEMBL4295987"/>
    <dbReference type="GlyGen" id="Q9Y305">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y305"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y305"/>
    <dbReference type="SwissPalm" id="Q9Y305"/>
    <dbReference type="BioMuta" id="ACOT9"/>
    <dbReference type="DMDM" id="224471815"/>
    <dbReference type="jPOST" id="Q9Y305"/>
    <dbReference type="MassIVE" id="Q9Y305"/>
    <dbReference type="PaxDb" id="9606-ENSP00000368605"/>
    <dbReference type="PeptideAtlas" id="Q9Y305"/>
    <dbReference type="ProteomicsDB" id="85953">
        <molecule id="Q9Y305-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="85954">
        <molecule id="Q9Y305-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="85955">
        <molecule id="Q9Y305-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="85956">
        <molecule id="Q9Y305-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9Y305"/>
    <dbReference type="Antibodypedia" id="24512">
        <property type="antibodies" value="257 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23597"/>
    <dbReference type="Ensembl" id="ENST00000336430.11">
        <molecule id="Q9Y305-1"/>
        <property type="protein sequence ID" value="ENSP00000336580.7"/>
        <property type="gene ID" value="ENSG00000123130.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000379295.5">
        <molecule id="Q9Y305-3"/>
        <property type="protein sequence ID" value="ENSP00000368597.1"/>
        <property type="gene ID" value="ENSG00000123130.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000379303.10">
        <molecule id="Q9Y305-4"/>
        <property type="protein sequence ID" value="ENSP00000368605.5"/>
        <property type="gene ID" value="ENSG00000123130.18"/>
    </dbReference>
    <dbReference type="GeneID" id="23597"/>
    <dbReference type="KEGG" id="hsa:23597"/>
    <dbReference type="MANE-Select" id="ENST00000379303.10">
        <molecule id="Q9Y305-4"/>
        <property type="protein sequence ID" value="ENSP00000368605.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001037171.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001032248.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004dao.4">
        <molecule id="Q9Y305-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17152"/>
    <dbReference type="ClinPGx" id="PA142672656"/>
    <dbReference type="CTD" id="23597"/>
    <dbReference type="DisGeNET" id="23597"/>
    <dbReference type="GeneCards" id="ACOT9"/>
    <dbReference type="HGNC" id="HGNC:17152">
        <property type="gene designation" value="ACOT9"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000123130">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACOT9"/>
    <dbReference type="MIM" id="300862">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000123130"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000123130"/>
    <dbReference type="eggNOG" id="KOG2763">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000005330"/>
    <dbReference type="InParanoid" id="Q9Y305"/>
    <dbReference type="OMA" id="QFNYTFL"/>
    <dbReference type="OrthoDB" id="331699at2759"/>
    <dbReference type="PAN-GO" id="Q9Y305">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y305"/>
    <dbReference type="BioCyc" id="MetaCyc:HS04631-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q9Y305"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9Y305"/>
    <dbReference type="UniPathway" id="UPA00199"/>
    <dbReference type="Agora" id="ENSG00000123130"/>
    <dbReference type="BioGRID-ORCS" id="23597">
        <property type="hits" value="12 hits in 783 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOT9">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="23597"/>
    <dbReference type="Pharos" id="Q9Y305">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y305"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y305">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000123130">
        <property type="expression patterns" value="Expressed in secondary oocyte and 193 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y305">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003986">
        <property type="term" value="F:acetyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047617">
        <property type="term" value="F:fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052816">
        <property type="term" value="F:long-chain fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001676">
        <property type="term" value="P:long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046459">
        <property type="term" value="P:short-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd03442">
        <property type="entry name" value="BFIT_BACH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.129.10:FF:000012">
        <property type="entry name" value="Acyl-coenzyme A thioesterase 9, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.129.10:FF:000016">
        <property type="entry name" value="Acyl-coenzyme A thioesterase 9, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.10.129.10">
        <property type="entry name" value="Hotdog Thioesterase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033120">
        <property type="entry name" value="HOTDOG_ACOT"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029069">
        <property type="entry name" value="HotDog_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006683">
        <property type="entry name" value="Thioestr_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12655">
        <property type="entry name" value="ACYL-COA THIOESTERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12655:SF0">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE 9, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03061">
        <property type="entry name" value="4HBT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54637">
        <property type="entry name" value="Thioesterase/thiol ester dehydrase-isomerase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51770">
        <property type="entry name" value="HOTDOG_ACOT"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0999">Mitochondrion inner membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000053812" description="Acyl-coenzyme A thioesterase 9, mitochondrial">
        <location>
            <begin position="22"/>
            <end position="439"/>
        </location>
    </feature>
    <feature type="domain" description="HotDog ACOT-type 1" evidence="3">
        <location>
            <begin position="84"/>
            <end position="209"/>
        </location>
    </feature>
    <feature type="domain" description="HotDog ACOT-type 2" evidence="3">
        <location>
            <begin position="289"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="10">
        <location>
            <position position="103"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_036420" description="In isoform 3." evidence="6">
        <location>
            <begin position="1"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_036419" description="In isoform 2." evidence="5">
        <original>ALRLCALGKGQLTPGRGLTQGPQNPKKQGIFHIHE</original>
        <variation>PC</variation>
        <location>
            <begin position="5"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041093" description="In isoform 4." evidence="7">
        <original>E</original>
        <variation>EACSSIHVNH</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062668" description="In a pancreatic ductal adenocarcinoma sample; somatic mutation." evidence="4">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG51291." evidence="8" ref="2">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="188"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9R0X4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01106"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="18772397"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="10810093"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:17152"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <sequence length="439" mass="49902" checksum="1CE2158D4F83D4D6" modified="2009-03-03" version="2" precursor="true">MRRAALRLCALGKGQLTPGRGLTQGPQNPKKQGIFHIHEVRDKLREIVGASTNWRDHVKAMEERKLLHSFLAKSQDGLPPRRMKDSYIEVLLPLGSEPELREKYLTVQNTVRFGRILEDLDSLGVLICYMHNKIHSAKMSPLSIVTALVDKIDMCKKSLSPEQDIKFSGHVSWVGKTSMEVKMQMFQLHGDEFCPVLDATFVMVARDSENKGPAFVNPLIPESPEEEELFRQGELNKGRRIAFSSTSLLKMAPSAEERTTIHEMFLSTLDPKTISFRSRVLPSNAVWMENSKLKSLEICHPQERNIFNRIFGGFLMRKAYELAWATACSFGGSRPFVVAVDDIMFQKPVEVGSLLFLSSQVCFTQNNYIQVRVHSEVASLQEKQHTTTNVFHFTFMSEKEVPLVFPKTYGESMLYLDGQRHFNSMSGPATLRKDYLVEP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-11-02" modified="2026-01-28" version="199" xmlns="https://uniprot.org/uniprot">
    <accession>O15254</accession>
    <accession>Q96AJ8</accession>
    <name>ACOX3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Peroxisomal acyl-coenzyme A oxidase 3</fullName>
            <ecNumber evidence="2">1.3.3.6</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Branched-chain acyl-CoA oxidase</fullName>
            <shortName>BRCACox</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Pristanoyl-CoA oxidase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOX3</name>
        <name type="synonym">BRCOX</name>
        <name type="synonym">PRCOX</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Biochem. J." volume="325" first="593" last="599">
            <title>Evidence for the existence of a pristanoyl-CoA oxidase gene in man.</title>
            <authorList>
                <person name="Vanhooren J.C.T."/>
                <person name="Marynen P."/>
                <person name="Mannaerts G.P."/>
                <person name="van Veldhoven P.P."/>
            </authorList>
            <dbReference type="PubMed" id="9271077"/>
            <dbReference type="DOI" id="10.1042/bj3250593"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2009" name="Mol. Cell. Proteomics" volume="8" first="1751" last="1764">
            <title>Large-scale proteomics analysis of the human kinome.</title>
            <authorList>
                <person name="Oppermann F.S."/>
                <person name="Gnad F."/>
                <person name="Olsen J.V."/>
                <person name="Hornberger R."/>
                <person name="Greff Z."/>
                <person name="Keri G."/>
                <person name="Mann M."/>
                <person name="Daub H."/>
            </authorList>
            <dbReference type="PubMed" id="19369195"/>
            <dbReference type="DOI" id="10.1074/mcp.m800588-mcp200"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-281</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Oxidizes the CoA-esters of 2-methyl-branched fatty acids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:38959"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:58856"/>
            <dbReference type="ChEBI" id="CHEBI:65111"/>
            <dbReference type="EC" id="1.3.3.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:38960"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(2S)-pristanoyl-CoA + O2 = (2E)-pristenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40459"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:77099"/>
            <dbReference type="ChEBI" id="CHEBI:77293"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40460"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>tetracosanoyl-CoA + O2 = (2E)-tetracosenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40319"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:74693"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40320"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40167"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40168"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanedioyl-CoA + O2 = (2E)-hexadecenedioyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40275"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:77075"/>
            <dbReference type="ChEBI" id="CHEBI:77085"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40276"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="pathway">
        <text>Lipid metabolism; peroxisomal fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Peroxisome</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O15254-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O15254-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_023355 VSP_023356"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the acyl-CoA oxidase family.</text>
    </comment>
    <dbReference type="EC" id="1.3.3.6" evidence="2"/>
    <dbReference type="EMBL" id="Y11411">
        <property type="protein sequence ID" value="CAA72214.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017053">
        <property type="protein sequence ID" value="AAH17053.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3401.1">
        <molecule id="O15254-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47017.1">
        <molecule id="O15254-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001095137.1">
        <molecule id="O15254-2"/>
        <property type="nucleotide sequence ID" value="NM_001101667.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001362712.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="NM_001375783.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001362717.1">
        <molecule id="O15254-2"/>
        <property type="nucleotide sequence ID" value="NM_001375788.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003492.2">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="NM_003501.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011511867.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_011513565.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047272185.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_047416229.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047272186.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_047416230.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206919.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_054350944.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206920.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_054350945.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206921.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_054350946.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206922.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_054350947.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054206923.1">
        <molecule id="O15254-1"/>
        <property type="nucleotide sequence ID" value="XM_054350948.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O15254"/>
    <dbReference type="SMR" id="O15254"/>
    <dbReference type="BioGRID" id="113907">
        <property type="interactions" value="88"/>
    </dbReference>
    <dbReference type="FunCoup" id="O15254">
        <property type="interactions" value="1710"/>
    </dbReference>
    <dbReference type="IntAct" id="O15254">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="MINT" id="O15254"/>
    <dbReference type="STRING" id="9606.ENSP00000348775"/>
    <dbReference type="ChEMBL" id="CHEMBL4105817"/>
    <dbReference type="DrugCentral" id="O15254"/>
    <dbReference type="GlyGen" id="O15254">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O15254"/>
    <dbReference type="PhosphoSitePlus" id="O15254"/>
    <dbReference type="SwissPalm" id="O15254"/>
    <dbReference type="BioMuta" id="ACOX3"/>
    <dbReference type="jPOST" id="O15254"/>
    <dbReference type="MassIVE" id="O15254"/>
    <dbReference type="PaxDb" id="9606-ENSP00000348775"/>
    <dbReference type="PeptideAtlas" id="O15254"/>
    <dbReference type="ProteomicsDB" id="48541">
        <molecule id="O15254-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48542">
        <molecule id="O15254-2"/>
    </dbReference>
    <dbReference type="Pumba" id="O15254"/>
    <dbReference type="Antibodypedia" id="52278">
        <property type="antibodies" value="113 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8310"/>
    <dbReference type="Ensembl" id="ENST00000356406.10">
        <molecule id="O15254-1"/>
        <property type="protein sequence ID" value="ENSP00000348775.4"/>
        <property type="gene ID" value="ENSG00000087008.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000413009.6">
        <molecule id="O15254-2"/>
        <property type="protein sequence ID" value="ENSP00000413994.2"/>
        <property type="gene ID" value="ENSG00000087008.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000503233.5">
        <molecule id="O15254-1"/>
        <property type="protein sequence ID" value="ENSP00000421625.1"/>
        <property type="gene ID" value="ENSG00000087008.17"/>
    </dbReference>
    <dbReference type="GeneID" id="8310"/>
    <dbReference type="KEGG" id="hsa:8310"/>
    <dbReference type="MANE-Select" id="ENST00000356406.10">
        <property type="protein sequence ID" value="ENSP00000348775.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003501.3"/>
        <property type="RefSeq protein sequence ID" value="NP_003492.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003glc.5">
        <molecule id="O15254-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:121"/>
    <dbReference type="ClinPGx" id="PA24445"/>
    <dbReference type="CTD" id="8310"/>
    <dbReference type="DisGeNET" id="8310"/>
    <dbReference type="GeneCards" id="ACOX3"/>
    <dbReference type="HGNC" id="HGNC:121">
        <property type="gene designation" value="ACOX3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000087008">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACOX3"/>
    <dbReference type="MIM" id="603402">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000087008"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000087008"/>
    <dbReference type="eggNOG" id="KOG0135">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159423"/>
    <dbReference type="HOGENOM" id="CLU_014629_4_2_1"/>
    <dbReference type="InParanoid" id="O15254"/>
    <dbReference type="OMA" id="SINKRFA"/>
    <dbReference type="OrthoDB" id="538336at2759"/>
    <dbReference type="PAN-GO" id="O15254">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O15254"/>
    <dbReference type="PathwayCommons" id="O15254"/>
    <dbReference type="Reactome" id="R-HSA-389887">
        <property type="pathway name" value="Beta-oxidation of pristanoyl-CoA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9033241">
        <property type="pathway name" value="Peroxisomal protein import"/>
    </dbReference>
    <dbReference type="SignaLink" id="O15254"/>
    <dbReference type="UniPathway" id="UPA00661"/>
    <dbReference type="Agora" id="ENSG00000087008"/>
    <dbReference type="BioGRID-ORCS" id="8310">
        <property type="hits" value="11 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOX3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACOX3"/>
    <dbReference type="GenomeRNAi" id="8310"/>
    <dbReference type="Pharos" id="O15254">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O15254"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="O15254">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000087008">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 150 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O15254">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005782">
        <property type="term" value="C:peroxisomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071949">
        <property type="term" value="F:FAD binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005504">
        <property type="term" value="F:fatty acid binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016402">
        <property type="term" value="F:pristanoyl-CoA oxidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033540">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA oxidase"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd01150">
        <property type="entry name" value="AXO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000010">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034171">
        <property type="entry name" value="ACO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR055060">
        <property type="entry name" value="ACOX_C_alpha1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012258">
        <property type="entry name" value="Acyl-CoA_oxidase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002655">
        <property type="entry name" value="Acyl-CoA_oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909">
        <property type="entry name" value="ELECTRON TRANSPORT OXIDOREDUCTASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909:SF390">
        <property type="entry name" value="PEROXISOMAL ACYL-COENZYME A OXIDASE 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01756">
        <property type="entry name" value="ACOX"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF22924">
        <property type="entry name" value="ACOX_C_alpha1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF000168">
        <property type="entry name" value="Acyl-CoA_oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="6 7">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000204685" description="Peroxisomal acyl-coenzyme A oxidase 3">
        <location>
            <begin position="2"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Microbody targeting signal" evidence="2">
        <location>
            <begin position="698"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="6 7">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="5">
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023355" description="In isoform 2." evidence="3">
        <original>GGYFSGEQAGEVLES</original>
        <variation>AERRCSCPGRRDRSS</variation>
        <location>
            <begin position="610"/>
            <end position="624"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_023356" description="In isoform 2." evidence="3">
        <location>
            <begin position="625"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030802" description="In dbSNP:rs12513296.">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030803" description="In dbSNP:rs13434465.">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="497"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA72214." evidence="4" ref="1">
        <original>EL</original>
        <variation>DV</variation>
        <location>
            <begin position="34"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA72214." evidence="4" ref="1">
        <original>ML</original>
        <variation>NV</variation>
        <location>
            <begin position="44"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA72214." evidence="4" ref="1">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA72214." evidence="4" ref="1">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA72214." evidence="4" ref="1">
        <original>S</original>
        <variation>K</variation>
        <location>
            <position position="601"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P07872"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q63448"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0007744" key="5">
        <source>
            <dbReference type="PubMed" id="19369195"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="700" mass="77629" checksum="40D1CD3DC6A620C1" modified="2007-02-20" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-19" modified="2026-01-28" version="168" xmlns="https://uniprot.org/uniprot">
    <accession>Q86TX2</accession>
    <accession>A1L173</accession>
    <accession>Q3I5F9</accession>
    <name>ACOT1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="5">Acyl-coenzyme A thioesterase 1</fullName>
            <shortName evidence="5">Acyl-CoA thioesterase 1</shortName>
            <ecNumber evidence="2">3.1.2.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>CTE-I</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>CTE-Ib</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Inducible cytosolic acyl-coenzyme A thioester hydrolase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Long chain acyl-CoA thioester hydrolase</fullName>
            <shortName>Long chain acyl-CoA hydrolase</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="5">Palmitoyl-coenzyme A thioesterase</fullName>
            <ecNumber evidence="2">3.1.2.2</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT1</name>
        <name type="synonym">CTE1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="FASEB J." volume="20" first="1855" last="1864">
            <title>Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.</title>
            <authorList>
                <person name="Hunt M.C."/>
                <person name="Rautanen A."/>
                <person name="Westin M.A.K."/>
                <person name="Svensson L.T."/>
                <person name="Alexson S.E.H."/>
            </authorList>
            <dbReference type="PubMed" id="16940157"/>
            <dbReference type="DOI" id="10.1096/fj.06-6042com"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
            <title>Full-length cDNA libraries and normalization.</title>
            <authorList>
                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2010-01" db="UniProtKB">
            <authorList>
                <person name="Bienvenut W.V."/>
            </authorList>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-12; 25-35 AND 223-233</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Ovarian carcinoma</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. More active towards saturated and unsaturated long chain fatty acyl-CoAs (C12-C20).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:30140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>eicosanoyl-CoA + H2O = eicosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40147"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40148"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-hexadecenoyl-CoA + H2O = (9Z)-hexadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40131"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40132"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9E)-octadecenoyl-CoA + H2O = (9E)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40723"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30825"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77537"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="5">
            <dbReference type="Rhea" id="RHEA:40724"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="2">35.8 uM for C10-acyl-CoA</KM>
            <KM evidence="2">3.6 uM for C12-acyl-CoA</KM>
            <KM evidence="2">2.8 uM for C14-acyl-CoA</KM>
            <KM evidence="2">3.6 uM for C16-acyl-CoA</KM>
            <KM evidence="2">2.4 uM for C18-acyl-CoA</KM>
            <KM evidence="2">2 uM for C20-acyl-CoA</KM>
            <KM evidence="2">2.4 uM for C16:1-acyl-CoA</KM>
            <KM evidence="2">4.1 uM for C18:1-acyl-CoA</KM>
            <KM evidence="2">2.1 uM for C18:1-trans-acyl-CoA</KM>
            <Vmax evidence="2">224.0 nmol/min/mg enzyme toward C10-acyl-CoA</Vmax>
            <Vmax evidence="2">700.0 nmol/min/mg enzyme toward C12-acyl-CoA</Vmax>
            <Vmax evidence="2">912.0 nmol/min/mg enzyme toward C14-acyl-CoA</Vmax>
            <Vmax evidence="2">691.0 nmol/min/mg enzyme toward C16-acyl-CoA</Vmax>
            <Vmax evidence="2">597.0 nmol/min/mg enzyme toward C18-acyl-CoA</Vmax>
            <Vmax evidence="2">520.0 nmol/min/mg enzyme toward C20-acyl-CoA</Vmax>
            <Vmax evidence="2">577.0 nmol/min/mg enzyme toward C16:1-acyl-CoA</Vmax>
            <Vmax evidence="2">258.0 nmol/min/mg enzyme toward C18:1-acyl-CoA</Vmax>
            <Vmax evidence="2">309.0 nmol/min/mg enzyme toward C18:1-trans-acyl-CoA</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="5">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11109648">
            <id>Q86TX2</id>
        </interactant>
        <interactant intactId="EBI-347351">
            <id>P05549</id>
            <label>TFAP2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the C/M/P thioester hydrolase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="2"/>
    <dbReference type="EC" id="3.1.2.2" evidence="2"/>
    <dbReference type="EMBL" id="DQ082754">
        <property type="protein sequence ID" value="AAZ31236.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX161396">
        <property type="protein sequence ID" value="CAD61883.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC127748">
        <property type="protein sequence ID" value="AAI27749.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132889">
        <property type="protein sequence ID" value="AAI32890.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132891">
        <property type="protein sequence ID" value="AAI32892.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143042">
        <property type="protein sequence ID" value="AAI43043.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32117.1"/>
    <dbReference type="RefSeq" id="NP_001032238.1">
        <property type="nucleotide sequence ID" value="NM_001037161.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q86TX2"/>
    <dbReference type="SMR" id="Q86TX2"/>
    <dbReference type="BioGRID" id="534965">
        <property type="interactions" value="133"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q86TX2">
        <property type="interactions" value="393"/>
    </dbReference>
    <dbReference type="IntAct" id="Q86TX2">
        <property type="interactions" value="31"/>
    </dbReference>
    <dbReference type="MINT" id="Q86TX2"/>
    <dbReference type="STRING" id="9606.ENSP00000311224"/>
    <dbReference type="ChEMBL" id="CHEMBL2189136"/>
    <dbReference type="SwissLipids" id="SLP:000000613"/>
    <dbReference type="ESTHER" id="human-ACOT1">
        <property type="family name" value="Acyl-CoA_Thioesterase"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q86TX2">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q86TX2"/>
    <dbReference type="PhosphoSitePlus" id="Q86TX2"/>
    <dbReference type="SwissPalm" id="Q86TX2"/>
    <dbReference type="BioMuta" id="ACOT1"/>
    <dbReference type="DMDM" id="50428913"/>
    <dbReference type="jPOST" id="Q86TX2"/>
    <dbReference type="MassIVE" id="Q86TX2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000311224"/>
    <dbReference type="PeptideAtlas" id="Q86TX2"/>
    <dbReference type="ProteomicsDB" id="69743"/>
    <dbReference type="Pumba" id="Q86TX2"/>
    <dbReference type="Antibodypedia" id="54875">
        <property type="antibodies" value="100 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="641371"/>
    <dbReference type="Ensembl" id="ENST00000311148.9">
        <property type="protein sequence ID" value="ENSP00000311224.4"/>
        <property type="gene ID" value="ENSG00000184227.8"/>
    </dbReference>
    <dbReference type="GeneID" id="641371"/>
    <dbReference type="KEGG" id="hsa:641371"/>
    <dbReference type="MANE-Select" id="ENST00000311148.9">
        <property type="protein sequence ID" value="ENSP00000311224.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001037161.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001032238.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xol.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:33128"/>
    <dbReference type="ClinPGx" id="PA162375318"/>
    <dbReference type="CTD" id="641371"/>
    <dbReference type="DisGeNET" id="641371"/>
    <dbReference type="GeneCards" id="ACOT1"/>
    <dbReference type="HGNC" id="HGNC:33128">
        <property type="gene designation" value="ACOT1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184227">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614313">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184227"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184227"/>
    <dbReference type="eggNOG" id="ENOG502QQ8Z">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01010000222336"/>
    <dbReference type="HOGENOM" id="CLU_029849_4_0_1"/>
    <dbReference type="InParanoid" id="Q86TX2"/>
    <dbReference type="OMA" id="LDVPYMP"/>
    <dbReference type="OrthoDB" id="6347013at2759"/>
    <dbReference type="PAN-GO" id="Q86TX2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q86TX2"/>
    <dbReference type="BioCyc" id="MetaCyc:MONOMER-14105"/>
    <dbReference type="BRENDA" id="3.1.2.2">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q86TX2"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q86TX2"/>
    <dbReference type="SignaLink" id="Q86TX2"/>
    <dbReference type="UniPathway" id="UPA00199"/>
    <dbReference type="Agora" id="ENSG00000184227">
        <property type="nominated target" value="Agora Nominated Target for Alzheimer's Disease"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="641371">
        <property type="hits" value="10 hits in 1054 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOT1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="641371"/>
    <dbReference type="Pharos" id="Q86TX2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q86TX2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="Q86TX2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184227">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 103 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q86TX2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047617">
        <property type="term" value="F:fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001676">
        <property type="term" value="P:long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000038">
        <property type="term" value="P:very long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.2240:FF:000001">
        <property type="entry name" value="acyl-coenzyme A thioesterase 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000024">
        <property type="entry name" value="acyl-coenzyme A thioesterase 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.2240">
        <property type="entry name" value="Acyl-CoA thioester hydrolase/BAAT N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016662">
        <property type="entry name" value="Acyl-CoA_thioEstase_long-chain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014940">
        <property type="entry name" value="BAAT_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006862">
        <property type="entry name" value="Thio_Ohase/aa_AcTrfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042490">
        <property type="entry name" value="Thio_Ohase/BAAT_N"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824:SF16">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE 1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08840">
        <property type="entry name" value="BAAT_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04775">
        <property type="entry name" value="Bile_Hydr_Trans"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016521">
        <property type="entry name" value="Acyl-CoA_hydro"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <feature type="initiator methionine" description="Removed" evidence="3">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000202155" description="Acyl-coenzyme A thioesterase 1">
        <location>
            <begin position="2"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059830" description="In dbSNP:rs1049568.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16940157"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000305" key="5">
        <source>
            <dbReference type="PubMed" id="16940157"/>
        </source>
    </evidence>
    <sequence length="421" mass="46277" checksum="04675F28D9D53B97" modified="2003-06-01" version="1">MAATLILEPAGRCCWDEPVRIAVRGLAPEQPVTLRASLRDEKGALFQAHARYRADTLGELDLERAPALGGSFAGLEPMGLLWALEPEKPLVRLVKRDVRTPLAVELEVLDGHDPDPGRLLCRVRHERYFLPPGVRREPVRAGRVRGTLFLPPEPGPFPGIVDMFGTGGGLLEYRASLLAGKGFAVMALAYYNYEDLPKTMETLHLEYFEEAVNYLLSHPEVKGPGVGLLGISKGGELCLSMASFLKGITAAVVINGSVANVGGTLRYKGETLPPVGVNRNRIKVTKDGYADIVDVLNSPLEGPDQKSFIPVERAESTFLFLVGQDDHNWKSEFYANEACKRLQAHGRRKPQIICYPETGHYIEPPYFPLCRASLHALVGSPIIWGGEPRAHAMAQVDAWKQLQTFFHKHLGGHEGTIPSKV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="177" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NUZ1</accession>
    <accession>A2RRB7</accession>
    <accession>B7WPB3</accession>
    <accession>B7WPP7</accession>
    <accession>E9PB20</accession>
    <accession>Q53R27</accession>
    <accession>Q53R31</accession>
    <accession>Q53SC6</accession>
    <accession>Q8TCE7</accession>
    <name>ACOXL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A oxidase-like protein</fullName>
            <shortName>Acyl-CoA oxidase-like protein</shortName>
            <ecNumber>1.3.3.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ACOXL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
            <authorList>
                <person name="Hillier L.W."/>
                <person name="Graves T.A."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Pepin K.H."/>
                <person name="Minx P."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
                <person name="Strong C.M."/>
                <person name="Grewal N."/>
                <person name="Goyea E."/>
                <person name="Hou S."/>
                <person name="Levy A."/>
                <person name="Martinka S."/>
                <person name="Mead K."/>
                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
                <person name="Shah N."/>
                <person name="Swearengen-Shahid S."/>
                <person name="Snider J."/>
                <person name="Strong J.T."/>
                <person name="Thompson J."/>
                <person name="Yoakum M."/>
                <person name="Leonard S."/>
                <person name="Pearman C."/>
                <person name="Trani L."/>
                <person name="Radionenko M."/>
                <person name="Waligorski J.E."/>
                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
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                <person name="Williams D."/>
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                <person name="She X."/>
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                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
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                <person name="Zhong F."/>
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                <person name="Reinert K."/>
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                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 163-547 (ISOFORM 2)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
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                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
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                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
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                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
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                <person name="Senoh A."/>
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                <person name="Watanabe T."/>
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                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 162-547 (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NUZ1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NUZ1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_028239"/>
        </isoform>
        <isoform>
            <id>Q9NUZ1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_028237 VSP_028238"/>
        </isoform>
        <isoform>
            <id>Q9NUZ1-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_028239 VSP_046900"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the acyl-CoA oxidase family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous translation">
            <sequence resource="EMBL-CDS" id="AAH22268" version="1"/>
        </conflict>
        <text>Wrong choice of frame.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA91970" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="1.3.3.-"/>
    <dbReference type="EMBL" id="AC096670">
        <property type="protein sequence ID" value="AAY14796.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC023131">
        <property type="protein sequence ID" value="AAY14838.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC096591">
        <property type="protein sequence ID" value="AAY24074.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC114776">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471237">
        <property type="protein sequence ID" value="EAW50357.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022268">
        <property type="protein sequence ID" value="AAH22268.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC131514">
        <property type="protein sequence ID" value="AAI31515.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001904">
        <property type="protein sequence ID" value="BAA91970.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42730.1">
        <molecule id="Q9NUZ1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46389.1">
        <molecule id="Q9NUZ1-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS92841.1">
        <molecule id="Q9NUZ1-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001136279.1">
        <molecule id="Q9NUZ1-4"/>
        <property type="nucleotide sequence ID" value="NM_001142807.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352416.1">
        <molecule id="Q9NUZ1-3"/>
        <property type="nucleotide sequence ID" value="NM_001365487.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001358183.1">
        <molecule id="Q9NUZ1-1"/>
        <property type="nucleotide sequence ID" value="NM_001371254.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011509721.1">
        <molecule id="Q9NUZ1-2"/>
        <property type="nucleotide sequence ID" value="XM_011511419.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NUZ1"/>
    <dbReference type="SMR" id="Q9NUZ1"/>
    <dbReference type="BioGRID" id="120577">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NUZ1">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NUZ1">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000407761"/>
    <dbReference type="iPTMnet" id="Q9NUZ1"/>
    <dbReference type="PhosphoSitePlus" id="Q9NUZ1"/>
    <dbReference type="BioMuta" id="ACOXL"/>
    <dbReference type="DMDM" id="205371797"/>
    <dbReference type="jPOST" id="Q9NUZ1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000407761"/>
    <dbReference type="PeptideAtlas" id="Q9NUZ1"/>
    <dbReference type="ProteomicsDB" id="19125"/>
    <dbReference type="ProteomicsDB" id="82730">
        <molecule id="Q9NUZ1-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82731">
        <molecule id="Q9NUZ1-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82732">
        <molecule id="Q9NUZ1-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="55058">
        <property type="antibodies" value="39 antibodies from 13 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55289"/>
    <dbReference type="Ensembl" id="ENST00000340561.8">
        <molecule id="Q9NUZ1-3"/>
        <property type="protein sequence ID" value="ENSP00000343717.4"/>
        <property type="gene ID" value="ENSG00000153093.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000389811.8">
        <molecule id="Q9NUZ1-1"/>
        <property type="protein sequence ID" value="ENSP00000374461.4"/>
        <property type="gene ID" value="ENSG00000153093.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000439055.6">
        <molecule id="Q9NUZ1-4"/>
        <property type="protein sequence ID" value="ENSP00000407761.1"/>
        <property type="gene ID" value="ENSG00000153093.22"/>
    </dbReference>
    <dbReference type="GeneID" id="55289"/>
    <dbReference type="KEGG" id="hsa:55289"/>
    <dbReference type="MANE-Select" id="ENST00000439055.6">
        <molecule id="Q9NUZ1-4"/>
        <property type="protein sequence ID" value="ENSP00000407761.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001142807.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001136279.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010yxk.1">
        <molecule id="Q9NUZ1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25621"/>
    <dbReference type="ClinPGx" id="PA134932567"/>
    <dbReference type="CTD" id="55289"/>
    <dbReference type="DisGeNET" id="55289"/>
    <dbReference type="GeneCards" id="ACOXL"/>
    <dbReference type="HGNC" id="HGNC:25621">
        <property type="gene designation" value="ACOXL"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000153093">
        <property type="expression patterns" value="Tissue enhanced (epididymis, lung, urinary bladder)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000153093"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000153093"/>
    <dbReference type="eggNOG" id="KOG0135">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161693"/>
    <dbReference type="HOGENOM" id="CLU_014629_4_1_1"/>
    <dbReference type="InParanoid" id="Q9NUZ1"/>
    <dbReference type="OrthoDB" id="538336at2759"/>
    <dbReference type="PAN-GO" id="Q9NUZ1">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NUZ1"/>
    <dbReference type="PathwayCommons" id="Q9NUZ1"/>
    <dbReference type="Reactome" id="R-HSA-389887">
        <property type="pathway name" value="Beta-oxidation of pristanoyl-CoA"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NUZ1"/>
    <dbReference type="Agora" id="ENSG00000153093"/>
    <dbReference type="BioGRID-ORCS" id="55289">
        <property type="hits" value="8 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOXL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="55289"/>
    <dbReference type="Pharos" id="Q9NUZ1">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NUZ1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NUZ1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000153093">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 100 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NUZ1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005782">
        <property type="term" value="C:peroxisomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003997">
        <property type="term" value="F:acyl-CoA oxidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071949">
        <property type="term" value="F:FAD binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005504">
        <property type="term" value="F:fatty acid binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033540">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA oxidase"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000033">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000034">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000019">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR055060">
        <property type="entry name" value="ACOX_C_alpha1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006091">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012258">
        <property type="entry name" value="Acyl-CoA_oxidase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002655">
        <property type="entry name" value="Acyl-CoA_oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909:SF352">
        <property type="entry name" value="ACYL-COENZYME A OXIDASE-LIKE PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909">
        <property type="entry name" value="ELECTRON TRANSPORT OXIDOREDUCTASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01756">
        <property type="entry name" value="ACOX"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF22924">
        <property type="entry name" value="ACOX_C_alpha1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02770">
        <property type="entry name" value="Acyl-CoA_dh_M"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000305100" description="Acyl-coenzyme A oxidase-like protein">
        <location>
            <begin position="1"/>
            <end position="547"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="350"/>
            <end position="355"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_028237" description="In isoform 3." evidence="2">
        <original>SRRQFGPKTKEEVKIIE</original>
        <variation>RSRIISQNCCSAPAGLY</variation>
        <location>
            <begin position="263"/>
            <end position="279"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028238" description="In isoform 3." evidence="2">
        <location>
            <begin position="280"/>
            <end position="547"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028239" description="In isoform 2 and isoform 4." evidence="2">
        <location>
            <begin position="354"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046900" description="In isoform 4." evidence="3">
        <original>QERC</original>
        <variation>QLLDLCDSVKDDARRVISTFNIPHTYLHAPIAGISNPRAAWAFYPAPLQPRPREEARSRRPKLGAKL</variation>
        <location>
            <begin position="544"/>
            <end position="547"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035164" description="In dbSNP:rs1554005.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="255"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035165" description="In dbSNP:rs17041850.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="535"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH22268." evidence="3" ref="3">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAA91970." evidence="3" ref="4">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="512"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000303" key="2">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="547" mass="61795" checksum="7F2B9B961AAE2F08" modified="2008-09-02" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-05" modified="2026-01-28" version="142" xmlns="https://uniprot.org/uniprot">
    <accession>Q6ZNF0</accession>
    <accession>B2RN68</accession>
    <name>ACP7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Acid phosphatase type 7</fullName>
            <ecNumber>3.1.3.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="3">Purple acid phosphatase long form</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ACP7</name>
        <name evidence="3" type="synonym">PAPL</name>
        <name evidence="3" type="synonym">PAPL1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
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                <person name="Sugiyama A."/>
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                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Corpus callosum</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nature" volume="428" first="529" last="535">
            <title>The DNA sequence and biology of human chromosome 19.</title>
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                <person name="Grimwood J."/>
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                <person name="Couronne O."/>
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                <person name="Dehal P."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Garcia C."/>
                <person name="Georgescu A.M."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Ho I."/>
                <person name="Huang W."/>
                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Larionov V."/>
                <person name="Leem S.-H."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Lowry S."/>
                <person name="Malfatti S."/>
                <person name="Martinez D."/>
                <person name="McCready P.M."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
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                <person name="Nolan M."/>
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                <person name="Slezak T."/>
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                <person name="Thayer N."/>
                <person name="Tice H."/>
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                <person name="Vo N."/>
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                <person name="Richardson P."/>
                <person name="Stubbs L."/>
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            </authorList>
            <dbReference type="PubMed" id="15057824"/>
            <dbReference type="DOI" id="10.1038/nature02399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Gene" volume="377" first="12" last="20">
            <title>Identification and molecular modeling of a novel, plant-like, human purple acid phosphatase.</title>
            <authorList>
                <person name="Flanagan J.U."/>
                <person name="Cassady A.I."/>
                <person name="Schenk G."/>
                <person name="Guddat L.W."/>
                <person name="Hume D.A."/>
            </authorList>
            <dbReference type="PubMed" id="16793224"/>
            <dbReference type="DOI" id="10.1016/j.gene.2006.02.031"/>
        </citation>
        <scope>IDENTIFICATION</scope>
    </reference>
    <comment type="catalytic activity">
        <reaction>
            <text>a phosphate monoester + H2O = an alcohol + phosphate</text>
            <dbReference type="Rhea" id="RHEA:15017"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30879"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:67140"/>
            <dbReference type="EC" id="3.1.3.2"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
        </cofactor>
        <text evidence="1">Binds 1 Fe cation per subunit.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.3.2"/>
    <dbReference type="EMBL" id="AK131245">
        <property type="protein sequence ID" value="BAD18425.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC011443">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136721">
        <property type="protein sequence ID" value="AAI36722.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136722">
        <property type="protein sequence ID" value="AAI36723.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33018.1"/>
    <dbReference type="RefSeq" id="NP_001004318.2">
        <property type="nucleotide sequence ID" value="NM_001004318.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011525268.1">
        <property type="nucleotide sequence ID" value="XM_011526966.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016882296.1">
        <property type="nucleotide sequence ID" value="XM_017026807.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054176976.1">
        <property type="nucleotide sequence ID" value="XM_054321001.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054176977.1">
        <property type="nucleotide sequence ID" value="XM_054321002.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054176978.1">
        <property type="nucleotide sequence ID" value="XM_054321003.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6ZNF0"/>
    <dbReference type="SMR" id="Q6ZNF0"/>
    <dbReference type="BioGRID" id="133739">
        <property type="interactions" value="52"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6ZNF0">
        <property type="interactions" value="108"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6ZNF0">
        <property type="interactions" value="20"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000327557"/>
    <dbReference type="DEPOD" id="ACP7"/>
    <dbReference type="GlyCosmos" id="Q6ZNF0">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q6ZNF0">
        <property type="glycosylation" value="3 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6ZNF0"/>
    <dbReference type="PhosphoSitePlus" id="Q6ZNF0"/>
    <dbReference type="BioMuta" id="ACP7"/>
    <dbReference type="DMDM" id="269849643"/>
    <dbReference type="jPOST" id="Q6ZNF0"/>
    <dbReference type="MassIVE" id="Q6ZNF0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000327557"/>
    <dbReference type="PeptideAtlas" id="Q6ZNF0"/>
    <dbReference type="ProteomicsDB" id="68020"/>
    <dbReference type="Antibodypedia" id="48007">
        <property type="antibodies" value="9 antibodies from 5 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="390928"/>
    <dbReference type="Ensembl" id="ENST00000331256.10">
        <property type="protein sequence ID" value="ENSP00000327557.4"/>
        <property type="gene ID" value="ENSG00000183760.12"/>
    </dbReference>
    <dbReference type="GeneID" id="390928"/>
    <dbReference type="KEGG" id="hsa:390928"/>
    <dbReference type="MANE-Select" id="ENST00000331256.10">
        <property type="protein sequence ID" value="ENSP00000327557.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001004318.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001004318.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002oki.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:33781"/>
    <dbReference type="CTD" id="390928"/>
    <dbReference type="DisGeNET" id="390928"/>
    <dbReference type="GeneCards" id="ACP7"/>
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    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
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    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000316824" description="Acid phosphatase type 7">
        <location>
            <begin position="27"/>
            <end position="438"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="141"/>
        </location>
        <ligand>
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="170"/>
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        <ligand>
            <name>Fe cation</name>
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    </feature>
    <feature type="binding site" evidence="1">
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            <position position="170"/>
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        <ligand>
            <name>Zn(2+)</name>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="173"/>
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        <ligand>
            <name>Fe cation</name>
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    </feature>
    <feature type="binding site" evidence="1">
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            <position position="205"/>
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        <ligand>
            <name>Zn(2+)</name>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="286"/>
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        <ligand>
            <name>Zn(2+)</name>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="333"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="335"/>
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        <ligand>
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="350"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAD18425." evidence="4" ref="1">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="408"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
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        <source>
            <dbReference type="PubMed" id="16793224"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:33781"/>
        </source>
    </evidence>
    <sequence length="438" mass="50480" checksum="70C5109FAAB2DDC5" modified="2009-11-24" version="2" precursor="true">MHPLPGYWSCYCLLLLFSLGVQGSLGAPSAAPEQVHLSYPGEPGSMTVTWTTWVPTRSEVQFGLQPSGPLPLRAQGTFVPFVDGGILRRKLYIHRVTLRKLLPGVQYVYRCGSAQGWSRRFRFRALKNGAHWSPRLAVFGDLGADNPKAVPRLRRDTQQGMYDAVLHVGDFAYNLDQDNARVGDRFMRLIEPVAASLPYMTCPGNHEERYNFSNYKARFSMPGDNEGLWYSWDLGPAHIISFSTEVYFFLHYGRHLVQRQFRWLESDLQKANKNRAARPWIITMGHRPMYCSNADLDDCTRHESKVRKGLQGKLYGLEDLFYKYGVDLQLWAHEHSYERLWPIYNYQVFNGSREMPYTNPRGPVHIITGSAGCEERLTPFAVFPRPWSAVRVKEYGYTRLHILNGTHIHIQQVSDDQDGKIVDDVWVVRPLFGRRMYL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="227" xmlns="https://uniprot.org/uniprot">
    <accession>Q99798</accession>
    <accession>O75809</accession>
    <accession>Q5JZ41</accession>
    <accession>Q6FHX0</accession>
    <accession>Q8TAQ6</accession>
    <name>ACON_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aconitate hydratase, mitochondrial</fullName>
            <shortName>Aconitase</shortName>
            <ecNumber evidence="2">4.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Citrate hydro-lyase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACO2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1996-12" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and structural characterization of human mitochondrial aconitase.</title>
            <authorList>
                <person name="Juang H.H."/>
                <person name="Chiou B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1998" name="Gene" volume="213" first="205" last="218">
            <title>Characterization of the human mitochondrial aconitase gene (ACO2).</title>
            <authorList>
                <person name="Mirel D.B."/>
                <person name="Marder K."/>
                <person name="Graziano J."/>
                <person name="Freyer G."/>
                <person name="Zhao Q."/>
                <person name="Mayeux R."/>
                <person name="Wilhelmsen K.C."/>
            </authorList>
            <dbReference type="PubMed" id="9630632"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(98)00188-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R84.1" last="R84.11">
            <title>A genome annotation-driven approach to cloning the human ORFeome.</title>
            <authorList>
                <person name="Collins J.E."/>
                <person name="Wright C.L."/>
                <person name="Edwards C.A."/>
                <person name="Davis M.P."/>
                <person name="Grinham J.A."/>
                <person name="Cole C.G."/>
                <person name="Goward M.E."/>
                <person name="Aguado B."/>
                <person name="Mallya M."/>
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                <person name="Huckle E.J."/>
                <person name="Beare D.M."/>
                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15461802"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-10-r84"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Halleck A."/>
                <person name="Ebert L."/>
                <person name="Mkoundinya M."/>
                <person name="Schick M."/>
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                <person name="Neubert P."/>
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                <person name="Schatten R."/>
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                <person name="Zuo D."/>
                <person name="Hu Y."/>
                <person name="LaBaer J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="Nature" volume="402" first="489" last="495">
            <title>The DNA sequence of human chromosome 22.</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>INVOLVEMENT IN OPA9</scope>
        <scope>INVOLVEMENT IN ICRD</scope>
        <scope>VARIANTS OPA9 VAL-74 AND ARG-661</scope>
        <scope>VARIANTS ICRD ASP-259 AND ASN-736</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] ASN-697</scope>
    </reference>
    <reference key="17">
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        <scope>VARIANT ICRD ARG-112</scope>
        <scope>CHARACTERIZATION OF VARIANT ICRD ARG-112</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>citrate = D-threo-isocitrate</text>
            <dbReference type="Rhea" id="RHEA:10336"/>
            <dbReference type="ChEBI" id="CHEBI:15562"/>
            <dbReference type="ChEBI" id="CHEBI:16947"/>
            <dbReference type="EC" id="4.2.1.3"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>[4Fe-4S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:49883"/>
        </cofactor>
        <text evidence="2">Binds 1 [4Fe-4S] cluster per subunit. Binding of a [3Fe-4S] cluster leads to an inactive enzyme.</text>
    </comment>
    <comment type="pathway">
        <text>Carbohydrate metabolism; tricarboxylic acid cycle; isocitrate from oxaloacetate: step 2/2.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="4">Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.</text>
    </comment>
    <comment type="disease" evidence="7 8">
        <disease id="DI-03409">
            <name>Infantile cerebellar-retinal degeneration</name>
            <acronym>ICRD</acronym>
            <description>A severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="8">
        <disease id="DI-04381">
            <name>Optic atrophy 9</name>
            <acronym>OPA9</acronym>
            <description>A condition that features progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.</description>
            <dbReference type="MIM" id="616289"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the aconitase/IPM isomerase family.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Aconitase"/>
        <text>Aconitase entry</text>
    </comment>
    <dbReference type="EC" id="4.2.1.3" evidence="2"/>
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        <property type="protein sequence ID" value="AAB38416.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAC39921.1"/>
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        <property type="protein sequence ID" value="AAC39921.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH14092.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="T52543"/>
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        <property type="nucleotide sequence ID" value="NM_001098.3"/>
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        <property type="nucleotide sequence ID" value="XM_054325660.1"/>
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        <property type="generic name" value="4-Hydroxy-Aconitate Ion"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04351">
        <property type="generic name" value="Aconitate Ion"/>
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    <dbReference type="DrugBank" id="DB04072">
        <property type="generic name" value="Alpha-Methylisocitric Acid"/>
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        <property type="generic name" value="Isocitric Acid"/>
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        <property type="generic name" value="Tricarballylic acid"/>
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        <property type="glycosylation" value="1 site, 1 glycan"/>
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        <property type="glycosylation" value="3 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site)"/>
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        <property type="antibodies" value="527 antibodies from 40 providers"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_001098.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001089.1"/>
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    <keyword id="KW-0456">Lyase</keyword>
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    <keyword id="KW-0496">Mitochondrion</keyword>
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        <location>
            <position position="549"/>
        </location>
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            <position position="559"/>
        </location>
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            <position position="573"/>
        </location>
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    </feature>
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        </location>
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    </feature>
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        </location>
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        <location>
            <position position="743"/>
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            <position position="74"/>
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        <location>
            <position position="112"/>
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    <feature type="sequence variant" id="VAR_073436" description="In ICRD; dbSNP:rs786204828." evidence="8">
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        <location>
            <position position="259"/>
        </location>
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        <location>
            <position position="661"/>
        </location>
    </feature>
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        <location>
            <position position="697"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073438" description="In ICRD; dbSNP:rs786204829." evidence="8">
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        <location>
            <position position="736"/>
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            <position position="35"/>
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            <position position="167"/>
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            <position position="517"/>
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            <position position="553"/>
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            <dbReference type="PubMed" id="22405087"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="25351951"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="780" mass="85425" checksum="58C9FFBDBDC63D5E" modified="2000-05-30" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>Q15067</accession>
    <accession>A8K6X8</accession>
    <accession>A8KAA0</accession>
    <accession>B4DK61</accession>
    <accession>F5GYQ8</accession>
    <accession>Q12863</accession>
    <accession>Q15068</accession>
    <accession>Q15101</accession>
    <accession>Q16131</accession>
    <accession>Q7Z3W5</accession>
    <accession>Q9UD31</accession>
    <name>ACOX1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="24">Peroxisomal acyl-coenzyme A oxidase 1</fullName>
            <shortName evidence="24">AOX</shortName>
            <ecNumber evidence="9 12 15 29">1.3.3.6</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="18 22">Palmitoyl-CoA oxidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal fatty acyl-CoA oxidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="19">Straight-chain acyl-CoA oxidase</fullName>
            <shortName evidence="19">SCOX</shortName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName evidence="1">Peroxisomal acyl-CoA oxidase 1, A chain</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName evidence="1">Peroxisomal acyl-CoA oxidase 1, B chain</fullName>
            </recommendedName>
        </component>
        <component>
            <recommendedName>
                <fullName evidence="1">Peroxisomal acyl-CoA oxidase 1, C chain</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="31" type="primary">ACOX1</name>
        <name type="synonym">ACOX</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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        <scope>INVOLVEMENT IN PSEUDO-NALD</scope>
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            <tissue>Liver</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>VARIANT MET-312</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT MET-312</scope>
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            <dbReference type="PubMed" id="18281296"/>
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        <scope>INTERACTION WITH LONP2</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-255; LYS-267; LYS-437; LYS-500 AND LYS-504</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORMS 1 AND 2)</scope>
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        <scope>ERRATUM OF PUBMED:20195242</scope>
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            <dbReference type="PubMed" id="33234382"/>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>VARIANT PSEUDO-NALD SER-420</scope>
        <scope>FUNCTION</scope>
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
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                <person name="Vaca Jacome A.S."/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <authorList>
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                <person name="Kamei A."/>
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                <person name="Chida S."/>
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        <scope>VARIANTS PSEUDO-NALD CYS-178 AND VAL-278</scope>
    </reference>
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            <dbReference type="DOI" id="10.1002/humu.20535"/>
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        <scope>VARIANTS PSEUDO-NALD VAL-64 DEL; CYS-178; LEU-184; VAL-231; VAL-278; ARG-309 AND PRO-310</scope>
        <scope>FUNCTION</scope>
        <scope>PATHWAY</scope>
        <scope>CATALYTIC ACTIVITY (ISOFORMS 1 AND 2)</scope>
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            <authorList>
                <consortium name="Members of Undiagnosed Diseases Network"/>
                <person name="Chung H.L."/>
                <person name="Wangler M.F."/>
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                <person name="Zuo Z."/>
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                <person name="Yamamoto S."/>
                <person name="Lee H.K."/>
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                <person name="Vogel T.P."/>
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            </authorList>
            <dbReference type="PubMed" id="32169171"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2020.02.021"/>
        </citation>
        <scope>INVOLVEMENT IN MITCH</scope>
        <scope>VARIANT MITCH SER-237</scope>
        <scope>CHARACTERIZATION OF VARIANT MITCH SER-237</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="6 8 9 13 14 15">Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids (PubMed:15060085, PubMed:17458872, PubMed:17603022, PubMed:32169171, PubMed:33234382, PubMed:7876265). Catalyzes the desaturation of fatty acyl-CoAs that have a saturated bond between C2 and C3 (2,3-saturated acyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs), and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) (PubMed:17458872, PubMed:17603022, PubMed:7876265).</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 1</molecule>
        <text evidence="9">Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="9">Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="29">
            <text>a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:38959"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:58856"/>
            <dbReference type="ChEBI" id="CHEBI:65111"/>
            <dbReference type="EC" id="1.3.3.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="29">
            <dbReference type="Rhea" id="RHEA:38960"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9 12 15">
            <text>a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:38959"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:58856"/>
            <dbReference type="ChEBI" id="CHEBI:65111"/>
            <dbReference type="EC" id="1.3.3.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27 28 30">
            <dbReference type="Rhea" id="RHEA:38960"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9 12">
            <text>a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:38959"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:58856"/>
            <dbReference type="ChEBI" id="CHEBI:65111"/>
            <dbReference type="EC" id="1.3.3.6"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27 28">
            <dbReference type="Rhea" id="RHEA:38960"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="8">
            <text>hexanoyl-CoA + O2 = (2E)-hexenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40311"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:62077"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:40312"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="8 9">
            <text>octanoyl-CoA + O2 = (2E)-octenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40175"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:62242"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27">
            <dbReference type="Rhea" id="RHEA:40176"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>octanoyl-CoA + O2 = (2E)-octenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40175"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:62242"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:40176"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="8 9">
            <text>decanoyl-CoA + O2 = (2E)-decenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40179"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:61406"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27">
            <dbReference type="Rhea" id="RHEA:40180"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>decanoyl-CoA + O2 = (2E)-decenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40179"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:61406"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:40180"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="8 9">
            <text>dodecanoyl-CoA + O2 = (2E)-dodecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40171"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57330"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27">
            <dbReference type="Rhea" id="RHEA:40172"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8 9">
            <text>dodecanoyl-CoA + O2 = (2E)-dodecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40171"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57330"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27">
            <dbReference type="Rhea" id="RHEA:40172"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8 9">
            <text>tetradecanoyl-CoA + O2 = (2E)-tetradecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40183"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:61405"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27">
            <dbReference type="Rhea" id="RHEA:40184"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="8 9 12 15">
            <text>hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40167"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8 27 28 30">
            <dbReference type="Rhea" id="RHEA:40168"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8 9 12">
            <text>hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40167"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 27 28">
            <dbReference type="Rhea" id="RHEA:40168"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8">
            <text>octadecanoyl-CoA + O2 = (2E)-octadecenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:38971"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:71412"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:38972"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8">
            <text>eicosanoyl-CoA + O2 = (2E)-eicosenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:78587"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:74691"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:78588"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8">
            <text>docosanoyl-CoA + O2 = (2E)-docosenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:78571"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:65059"/>
            <dbReference type="ChEBI" id="CHEBI:74692"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26">
            <dbReference type="Rhea" id="RHEA:78572"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8 29">
            <text>tetracosanoyl-CoA + O2 = (2E)-tetracosenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40319"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:74693"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="26 29">
            <dbReference type="Rhea" id="RHEA:40320"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="8">
            <text>hexacosanoyl-CoA + O2 = (2E)-hexacosenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:78631"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:64868"/>
            <dbReference type="ChEBI" id="CHEBI:74281"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:78632"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + O2 = (2E,5Z,8Z,11Z,14Z,17Z)-eicosahexaenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:69643"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:187901"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:69644"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + O2 = (2E,5Z,8Z,11Z,14Z,17Z)-eicosahexaenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:69643"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:187901"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:69644"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + O2 = (2E,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:39119"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:74086"/>
            <dbReference type="ChEBI" id="CHEBI:76360"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:39120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>glutaryl-CoA + O2 = (2E)-glutaconyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40315"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:57353"/>
            <dbReference type="ChEBI" id="CHEBI:57378"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:40316"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9">
            <text>hexadecanedioyl-CoA + O2 = (2E)-hexadecenedioyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40275"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:77075"/>
            <dbReference type="ChEBI" id="CHEBI:77085"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:40276"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>hexadecanedioyl-CoA + O2 = (2E)-hexadecenedioyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:40275"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:77075"/>
            <dbReference type="ChEBI" id="CHEBI:77085"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="27">
            <dbReference type="Rhea" id="RHEA:40276"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 1</molecule>
        <kinetics>
            <KM evidence="9">73 uM for hexadecanoyl-CoA (palmitoyl-CoA)</KM>
        </kinetics>
        <phDependence>
            <text evidence="9">Optimum pH is 8.5.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="9">Optimum temperature at pH 7.5 is 40 degrees Celsius with no activity at 50 degrees Celsius.</text>
        </temperatureDependence>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 2</molecule>
        <kinetics>
            <KM evidence="9">90 uM for hexadecanoyl-CoA (palmitoyl-CoA)</KM>
        </kinetics>
        <phDependence>
            <text evidence="9">Optimum pH is 7.5-8.5.</text>
        </phDependence>
        <temperatureDependence>
            <text evidence="9">Optimum temperature at pH 7.5 is 47.5 degrees Celsius with 57% activity retained at 50 degrees Celsius.</text>
        </temperatureDependence>
    </comment>
    <comment type="pathway">
        <text evidence="26 27">Lipid metabolism; peroxisomal fatty acid beta-oxidation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="11 13">Homodimer (PubMed:32169171). Interacts with LONP2 (PubMed:18281296).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13">Peroxisome</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q15067-1</id>
            <name>1</name>
            <name>ACOX1a</name>
            <name>SCOX-exon 3I</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q15067-2</id>
            <name>2</name>
            <name>ACOX1b</name>
            <name>SCOX-exon 3II</name>
            <sequence type="described" ref="VSP_000146"/>
        </isoform>
        <isoform>
            <id>Q15067-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046129 VSP_000146"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 12">Widely expressed with highest levels of isoform 1 and isoform 2 detected in testis. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 levels are higher in brain, lung, muscle, white adipose tissue and testis. Levels are almost equal in heart.</text>
    </comment>
    <comment type="disease" evidence="4 8 14 16">
        <disease id="DI-00049">
            <name>Adrenoleukodystrophy, pseudoneonatal</name>
            <acronym>Pseudo-NALD</acronym>
            <description>A peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include intellectual disability, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.</description>
            <dbReference type="MIM" id="264470"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-05884">
            <name>Mitchell syndrome</name>
            <acronym>MITCH</acronym>
            <description>A disorder characterized by episodic demyelination, sensorimotor polyneuropathy, and sensorineural hearing loss.</description>
            <dbReference type="MIM" id="618960"/>
        </disease>
        <text>The gene represented in this entry is involved in disease pathogenesis.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="28">Isoform 1 and isoform 2 can reverse the Acox1 null phenotype in mouse which is characterized by severe microvesicular hepatic steatosis, sustained activation of PPARA, spontaneous massive peroxisome proliferation and eventual development of hepatocellular carcinomas. Isoform 2 is more effective in reversal of the phenotype than isoform 1 (PubMed:20195242).</text>
    </comment>
    <comment type="similarity">
        <text evidence="25">Belongs to the acyl-CoA oxidase family.</text>
    </comment>
    <comment type="sequence caution" evidence="25">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAD97622" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="1.3.3.6" evidence="9 12 15 29"/>
    <dbReference type="EMBL" id="U03268">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03254">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03255">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03256">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03258">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03259">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03260">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03261">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03263">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03264">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03265">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03266">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03267">
        <property type="protein sequence ID" value="AAA19113.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03268">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03254">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03255">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03257">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03258">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03259">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03260">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03261">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03263">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03264">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03265">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03266">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03267">
        <property type="protein sequence ID" value="AAA19114.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U07866">
        <property type="protein sequence ID" value="AAA18595.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X71440">
        <property type="protein sequence ID" value="CAA50574.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S69189">
        <property type="protein sequence ID" value="AAB30019.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291793">
        <property type="protein sequence ID" value="BAF84482.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292965">
        <property type="protein sequence ID" value="BAF85654.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296409">
        <property type="protein sequence ID" value="BAG59073.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX537380">
        <property type="protein sequence ID" value="CAD97622.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC040980">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC087289">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471099">
        <property type="protein sequence ID" value="EAW89351.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008767">
        <property type="protein sequence ID" value="AAH08767.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010425">
        <property type="protein sequence ID" value="AAH10425.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11734.1">
        <molecule id="Q15067-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11735.1">
        <molecule id="Q15067-1"/>
    </dbReference>
    <dbReference type="PIR" id="A54942">
        <property type="entry name" value="A54942"/>
    </dbReference>
    <dbReference type="PIR" id="B54942">
        <property type="entry name" value="B54942"/>
    </dbReference>
    <dbReference type="PIR" id="I38095">
        <property type="entry name" value="I38095"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001171968.1">
        <molecule id="Q15067-3"/>
        <property type="nucleotide sequence ID" value="NM_001185039.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004026.2">
        <molecule id="Q15067-2"/>
        <property type="nucleotide sequence ID" value="NM_004035.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_009223.2">
        <molecule id="Q15067-1"/>
        <property type="nucleotide sequence ID" value="NM_007292.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q15067"/>
    <dbReference type="SMR" id="Q15067"/>
    <dbReference type="BioGRID" id="106567">
        <property type="interactions" value="124"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q15067">
        <property type="interactions" value="1801"/>
    </dbReference>
    <dbReference type="IntAct" id="Q15067">
        <property type="interactions" value="68"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000293217"/>
    <dbReference type="BindingDB" id="Q15067"/>
    <dbReference type="ChEMBL" id="CHEMBL4105748"/>
    <dbReference type="DrugBank" id="DB07930">
        <property type="generic name" value="(3R)-3-HYDROXYDODECANOIC ACID"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03147">
        <property type="generic name" value="Flavin adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09328">
        <property type="generic name" value="Vayarin"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q15067"/>
    <dbReference type="SwissLipids" id="SLP:000000536">
        <molecule id="Q15067-1"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000537">
        <molecule id="Q15067-2"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q15067">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q15067"/>
    <dbReference type="PhosphoSitePlus" id="Q15067"/>
    <dbReference type="SwissPalm" id="Q15067"/>
    <dbReference type="BioMuta" id="ACOX1"/>
    <dbReference type="DMDM" id="126302511"/>
    <dbReference type="jPOST" id="Q15067"/>
    <dbReference type="MassIVE" id="Q15067"/>
    <dbReference type="PaxDb" id="9606-ENSP00000293217"/>
    <dbReference type="PeptideAtlas" id="Q15067"/>
    <dbReference type="PRIDE" id="Q15067"/>
    <dbReference type="ProteomicsDB" id="24812"/>
    <dbReference type="ProteomicsDB" id="60421">
        <molecule id="Q15067-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="60422">
        <molecule id="Q15067-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q15067"/>
    <dbReference type="TopDownProteomics" id="Q15067-1">
        <molecule id="Q15067-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="19646">
        <property type="antibodies" value="381 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51"/>
    <dbReference type="Ensembl" id="ENST00000293217.10">
        <molecule id="Q15067-2"/>
        <property type="protein sequence ID" value="ENSP00000293217.4"/>
        <property type="gene ID" value="ENSG00000161533.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000301608.9">
        <molecule id="Q15067-1"/>
        <property type="protein sequence ID" value="ENSP00000301608.4"/>
        <property type="gene ID" value="ENSG00000161533.13"/>
    </dbReference>
    <dbReference type="GeneID" id="51"/>
    <dbReference type="KEGG" id="hsa:51"/>
    <dbReference type="MANE-Select" id="ENST00000293217.10">
        <molecule id="Q15067-2"/>
        <property type="protein sequence ID" value="ENSP00000293217.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004035.7"/>
        <property type="RefSeq protein sequence ID" value="NP_004026.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002jqe.5">
        <molecule id="Q15067-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:119"/>
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        <property type="entry name" value="Acyl-CoA_oxidase"/>
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        <property type="entry name" value="Acyl-CoA_oxidase_C"/>
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        <property type="entry name" value="AcylCo_DH-like_C"/>
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        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
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    <dbReference type="PANTHER" id="PTHR10909">
        <property type="entry name" value="ELECTRON TRANSPORT OXIDOREDUCTASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909:SF250">
        <property type="entry name" value="PEROXISOMAL ACYL-COENZYME A OXIDASE 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01756">
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF14749">
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    <dbReference type="SUPFAM" id="SSF56645">
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0622">Neuropathy</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000204677" description="Peroxisomal acyl-CoA oxidase 1, A chain">
        <location>
            <begin position="1"/>
            <end position="660"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000447500" description="Peroxisomal acyl-CoA oxidase 1, B chain" evidence="1">
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            <begin position="1"/>
            <end position="468"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000447501" description="Peroxisomal acyl-CoA oxidase 1, C chain" evidence="1">
        <location>
            <begin position="469"/>
            <end position="660"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Microbody targeting signal" evidence="3">
        <location>
            <begin position="658"/>
            <end position="660"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="421"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="139"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="178"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="site" description="Cleavage" evidence="1">
        <location>
            <begin position="468"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="32 33 35 36">
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="34">
        <location>
            <position position="255"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="34">
        <location>
            <position position="267"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="349"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="34">
        <location>
            <position position="437"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="437"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="446"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="446"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="34">
        <location>
            <position position="500"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="34">
        <location>
            <position position="504"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="512"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="512"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="542"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="637"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="637"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="643"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="649"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="651"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="654"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046129" description="In isoform 3." evidence="18">
        <location>
            <begin position="1"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000146" description="In isoform 2 and isoform 3." evidence="18 20 21 23">
        <original>KLHLVNFVEPVGLNYSMFIPTLLNQGTTAQKEKWLLSSKGLQ</original>
        <variation>NFVHRGRPEPLDLHLGMFLPTLLHQATAEQQERFFMPAWNLE</variation>
        <location>
            <begin position="90"/>
            <end position="131"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067040" description="In pseudo-NALD." evidence="8">
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048182" description="In dbSNP:rs3744032.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030619" description="In dbSNP:rs17855420." evidence="7">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025789" description="In pseudo-NALD; dbSNP:rs118204091." evidence="4 8">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067041" description="In pseudo-NALD; dbSNP:rs780887410." evidence="8">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067042" description="In pseudo-NALD." evidence="8">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083893" description="In MITCH; gain-of-function; increased dimerization; increased protein levels and peroxisomal acyl-coenzyme A oxidase function; increased levels of reactive oxygen species; no effect on VLCFA levels; no effect on peroxisome location; causes Schwann cell death and myelination defects; dbSNP:rs1567876984." evidence="13">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025790" description="In pseudo-NALD; dbSNP:rs118204090." evidence="4 8">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="278"/>
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    </feature>
    <feature type="sequence variant" id="VAR_067043" description="In pseudo-NALD; dbSNP:rs118204092." evidence="8">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="309"/>
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    <feature type="sequence variant" id="VAR_067044" description="In pseudo-NALD; dbSNP:rs758962364." evidence="8">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="310"/>
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    </feature>
    <feature type="sequence variant" id="VAR_021529" description="In dbSNP:rs1135640." evidence="5 7 10 16 17">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="312"/>
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    <feature type="sequence variant" id="VAR_085887" description="In Pseudo-NALD; uncertain significance." evidence="14">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="420"/>
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    <feature type="sequence conflict" description="In Ref. 3; CAA50574." evidence="25" ref="3">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA50574." evidence="25" ref="3">
        <original>A</original>
        <variation>R</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; CAD97622." evidence="25" ref="6">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="84"/>
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    <feature type="sequence conflict" description="In Ref. 4; AAB30019." evidence="25" ref="4">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="119"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAA18595." evidence="25" ref="2">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="200"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAA19113/AAA19114 and 2; AAA18595." evidence="25" ref="1 2">
        <original>IG</original>
        <variation>NR</variation>
        <location>
            <begin position="212"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAA19113/AAA19114 and 2; AAA18595." evidence="25" ref="1 2">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="264"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAA18595." evidence="25" ref="2">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="332"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAA18595." evidence="25" ref="2">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="449"/>
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    <feature type="sequence conflict" description="In Ref. 5; BAF85654." evidence="25" ref="5">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="490"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA19113/AAA19114 and 2; AAA18595." evidence="25" ref="1 2">
        <original>C</original>
        <variation>L</variation>
        <location>
            <position position="531"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA19113/AAA19114 and 2; AAA18595." evidence="25" ref="1 2">
        <original>VV</original>
        <variation>GL</variation>
        <location>
            <begin position="534"/>
            <end position="535"/>
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    <feature type="sequence conflict" description="In Ref. 3; CAA50574." evidence="25" ref="3">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="615"/>
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    <feature type="sequence conflict" description="In Ref. 4; AAB30019." evidence="25" ref="4">
        <original>Y</original>
        <variation>YH</variation>
        <location>
            <position position="650"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P07872"/>
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    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9R0H0"/>
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    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11815777"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15060085"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17458872"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17603022"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="17974005"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18281296"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="20195242"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="32169171"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="33234382"/>
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    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="7876265"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="8040306"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="8117268"/>
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    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="15060085"/>
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    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="17974005"/>
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    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="7876265"/>
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    </evidence>
    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="8040306"/>
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    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="8117268"/>
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    <evidence type="ECO:0000305" key="25"/>
    <evidence type="ECO:0000305" key="26">
        <source>
            <dbReference type="PubMed" id="17458872"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="27">
        <source>
            <dbReference type="PubMed" id="17603022"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="28">
        <source>
            <dbReference type="PubMed" id="20195242"/>
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    </evidence>
    <evidence type="ECO:0000305" key="29">
        <source>
            <dbReference type="PubMed" id="33234382"/>
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    </evidence>
    <evidence type="ECO:0000305" key="30">
        <source>
            <dbReference type="PubMed" id="7876265"/>
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    </evidence>
    <evidence type="ECO:0000312" key="31">
        <source>
            <dbReference type="HGNC" id="HGNC:119"/>
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    </evidence>
    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PubMed" id="17081983"/>
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    </evidence>
    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PubMed" id="19608861"/>
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    <evidence type="ECO:0007744" key="35">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007744" key="36">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="660" mass="74424" checksum="D713768A47374EA1" modified="2007-02-20" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-01-01" modified="2026-01-28" version="219" xmlns="https://uniprot.org/uniprot">
    <accession>P13798</accession>
    <accession>Q9BQ33</accession>
    <accession>Q9P0Y2</accession>
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        <recommendedName>
            <fullName>Acylamino-acid-releasing enzyme</fullName>
            <shortName>AARE</shortName>
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        <alternativeName>
            <fullName>Acyl-peptide hydrolase</fullName>
            <shortName>APH</shortName>
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        <alternativeName>
            <fullName>Acylaminoacyl-peptidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Oxidized protein hydrolase</fullName>
            <shortName>OPH</shortName>
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        <name type="primary">APEH</name>
        <name type="synonym">D3F15S2</name>
        <name type="synonym">D3S48E</name>
        <name type="synonym">DNF15S2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>The nucleotide sequence of human acylamino acid-releasing enzyme.</title>
            <authorList>
                <person name="Mitta M."/>
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            </authorList>
            <dbReference type="PubMed" id="8724851"/>
            <dbReference type="DOI" id="10.1093/dnares/3.1.31"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
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                <person name="Fujino T."/>
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                <person name="Yasuda H."/>
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            <dbReference type="PubMed" id="10719179"/>
            <dbReference type="DOI" id="10.1016/s0167-4838(00)00004-2"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1989" name="Genomics" volume="4" first="355" last="361">
            <title>The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer.</title>
            <authorList>
                <person name="Naylor S.L."/>
                <person name="Marshall A."/>
                <person name="Hensel C."/>
                <person name="Martinez P.F."/>
                <person name="Holley B."/>
                <person name="Sakaguchi A.Y."/>
            </authorList>
            <dbReference type="PubMed" id="2565880"/>
            <dbReference type="DOI" id="10.1016/0888-7543(89)90342-x"/>
        </citation>
        <scope>PRELIMINARY NUCLEOTIDE SEQUENCE OF 102-732</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="J. Protein Chem." volume="18" first="349" last="360">
            <title>Structural investigations on human erythrocyte acylpeptide hydrolase by mass spectrometric procedures.</title>
            <authorList>
                <person name="Scaloni A."/>
                <person name="Ingallinella P."/>
                <person name="Andolfo A."/>
                <person name="Jones W."/>
                <person name="Marino G."/>
                <person name="Manning J.M."/>
            </authorList>
            <dbReference type="PubMed" id="10395453"/>
            <dbReference type="DOI" id="10.1023/a:1021047730831"/>
        </citation>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>MASS SPECTROMETRY</scope>
        <scope>ACETYLATION AT MET-1</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1991" name="Oncogene" volume="6" first="1293" last="1295">
            <title>The gene from the short arm of chromosome 3, at D3F15S2, frequently deleted in renal cell carcinoma, encodes acylpeptide hydrolase.</title>
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                <person name="Erlandsson R."/>
                <person name="Boldog F."/>
                <person name="Persson B."/>
                <person name="Zabarovsky E.R."/>
                <person name="Allikmets R.L."/>
                <person name="Sumegi J."/>
                <person name="Klein G."/>
                <person name="Joernvall H."/>
            </authorList>
            <dbReference type="PubMed" id="1861871"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1991" name="Proc. Natl. Acad. Sci. U.S.A." volume="88" first="2194" last="2198">
            <title>Genetic relationship between acylpeptide hydrolase and acylase, two hydrolytic enzymes with similar binding but different catalytic specificities.</title>
            <authorList>
                <person name="Jones W.M."/>
                <person name="Scaloni A."/>
                <person name="Bossa F."/>
                <person name="Popowicz A.M."/>
                <person name="Schneewind O."/>
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            </authorList>
            <dbReference type="PubMed" id="2006156"/>
            <dbReference type="DOI" id="10.1073/pnas.88.6.2194"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1992" name="J. Biol. Chem." volume="267" first="3811" last="3818">
            <title>Acylpeptide hydrolase: inhibitors and some active site residues of the human enzyme.</title>
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                <person name="Scaloni A."/>
                <person name="Jones W.M."/>
                <person name="Barra D."/>
                <person name="Pospischil M."/>
                <person name="Sassa S."/>
                <person name="Popowicz A."/>
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            </authorList>
            <dbReference type="PubMed" id="1740429"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)50598-1"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVE SITES SER-587 AND HIS-707</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
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                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
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            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
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                <person name="Vermeulen M."/>
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                <person name="Kumar C."/>
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                <person name="Gnad F."/>
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            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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                <person name="Burkard T.R."/>
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                <person name="Kaupe I."/>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
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                <person name="Henningsen J."/>
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            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-185 AND SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1993" name="J. Mol. Biol." volume="233" first="546" last="549">
            <title>Crystallization and preliminary X-ray studies of human erythrocyte acylpeptide hydrolase.</title>
            <authorList>
                <person name="Feese M."/>
                <person name="Scaloni A."/>
                <person name="Jones W.M."/>
                <person name="Mannig J.M."/>
                <person name="Remington S.J."/>
            </authorList>
            <dbReference type="PubMed" id="8411161"/>
            <dbReference type="DOI" id="10.1006/jmbi.1993.1531"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6 7 8">Aminopeptidase involved in the degradation of N(alpha)-acylated peptides. Displays exopeptidase activity toward N-formyl and N-acetyl peptides with a preference for dipeptide substrates (By similarity). Catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (PubMed:10719179, PubMed:1740429, PubMed:2006156). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Hydrolyzes N-formylated peptides likely arising from N-terminal proteolytic cleavage of bacterial and mitochondrial proteins. May act sequentially with ACY1 in the degradation of N-acylated peptides: APEH first cleaves N-acylaminoacids from N-acylated peptides, then ACY1 further hydrolyzes the N-acylaminoacid into free aminoacid and a carboxylate (By similarity). Displays endopeptidase activity involved in the degradation of oxidized and glycated proteins (PubMed:10719179).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7 8">
            <text>Cleavage of an N-acetyl or N-formyl amino acid from the N-terminus of a polypeptide.</text>
            <dbReference type="EC" id="3.4.19.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-formyl-L-methionyl-L-leucyl-L-phenylalanine + H2O = L-leucyl-L-phenylalanine + N(alpha)-formyl-L-methionine</text>
            <dbReference type="Rhea" id="RHEA:83443"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:194314"/>
            <dbReference type="ChEBI" id="CHEBI:233080"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83444"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-formyl-L-methionyl-L-alanyl-L-serine + H2O = L-alanyl-L-serine + N(alpha)-formyl-L-methionine</text>
            <dbReference type="Rhea" id="RHEA:83495"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:233101"/>
            <dbReference type="ChEBI" id="CHEBI:233102"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83496"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-formyl-L-methionyl-L-phenylalanine + H2O = N(alpha)-formyl-L-methionine + L-phenylalanine</text>
            <dbReference type="Rhea" id="RHEA:83487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:58095"/>
            <dbReference type="ChEBI" id="CHEBI:233099"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83488"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-formyl-L-methionyl-L-alanine + H2O = N(alpha)-formyl-L-methionine + L-alanine</text>
            <dbReference type="Rhea" id="RHEA:83491"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
            <dbReference type="ChEBI" id="CHEBI:233100"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83492"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-formyl-L-methionyl-L-serine + H2O = N(alpha)-formyl-L-methionine + L-serine</text>
            <dbReference type="Rhea" id="RHEA:83499"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:33384"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:233103"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83500"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-acetyl-L-methionyl-L-alanyl-L-serine + H2O = L-alanyl-L-serine + N-acetyl-L-methionine</text>
            <dbReference type="Rhea" id="RHEA:83503"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:71670"/>
            <dbReference type="ChEBI" id="CHEBI:233101"/>
            <dbReference type="ChEBI" id="CHEBI:233104"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83504"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-acetyl-L-alanyl-L-alanyl-L-alanine + H2O = N(alpha)-acetyl-L-alanine + L-alanyl-L-alanine</text>
            <dbReference type="Rhea" id="RHEA:83511"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:133520"/>
            <dbReference type="ChEBI" id="CHEBI:195181"/>
            <dbReference type="ChEBI" id="CHEBI:233106"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83512"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>N(alpha)-acetyl-L-alanyl-L-alanine + H2O = N(alpha)-acetyl-L-alanine + L-alanine</text>
            <dbReference type="Rhea" id="RHEA:83507"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57972"/>
            <dbReference type="ChEBI" id="CHEBI:133520"/>
            <dbReference type="ChEBI" id="CHEBI:233105"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:83508"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Homotetramerization is required for activity. Tetramerization results in the formation of a gated channel which is involved in substrate selection and substrate access to the catalytic sites.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Homotetramer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-723792">
            <id>P13798</id>
        </interactant>
        <interactant intactId="EBI-723792">
            <id>P13798</id>
            <label>APEH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-723792">
            <id>P13798</id>
        </interactant>
        <interactant intactId="EBI-945994">
            <id>P53990</id>
            <label>IST1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-723792">
            <id>P13798</id>
        </interactant>
        <interactant intactId="EBI-12188567">
            <id>P53990-3</id>
            <label>IST1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-723792">
            <id>P13798</id>
        </interactant>
        <interactant intactId="EBI-740058">
            <id>O00214</id>
            <label>LGALS8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed in erythrocytes (at protein level).</text>
    </comment>
    <comment type="mass spectrometry" mass="81269.9" error="8.7" method="Electrospray" evidence="5"/>
    <comment type="similarity">
        <text evidence="9">Belongs to the peptidase S9C family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA35769" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.4.19.1" evidence="6 7 8"/>
    <dbReference type="EMBL" id="D38441">
        <property type="protein sequence ID" value="BAA07476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF141383">
        <property type="protein sequence ID" value="AAF37321.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000362">
        <property type="protein sequence ID" value="AAH00362.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001499">
        <property type="protein sequence ID" value="AAH01499.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001826">
        <property type="protein sequence ID" value="AAH01826.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03068">
        <property type="protein sequence ID" value="AAA35769.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2801.1"/>
    <dbReference type="PIR" id="JC4655">
        <property type="entry name" value="JC4655"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001631.3">
        <property type="nucleotide sequence ID" value="NM_001640.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P13798"/>
    <dbReference type="SMR" id="P13798"/>
    <dbReference type="BioGRID" id="106824">
        <property type="interactions" value="90"/>
    </dbReference>
    <dbReference type="FunCoup" id="P13798">
        <property type="interactions" value="1191"/>
    </dbReference>
    <dbReference type="IntAct" id="P13798">
        <property type="interactions" value="23"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000296456"/>
    <dbReference type="ChEMBL" id="CHEMBL1741174"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="2328"/>
    <dbReference type="ESTHER" id="human-APEH">
        <property type="family name" value="ACPH_Peptidase_S9"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.004"/>
    <dbReference type="GlyGen" id="P13798">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P13798"/>
    <dbReference type="MetOSite" id="P13798"/>
    <dbReference type="PhosphoSitePlus" id="P13798"/>
    <dbReference type="SwissPalm" id="P13798"/>
    <dbReference type="BioMuta" id="APEH"/>
    <dbReference type="DMDM" id="38258902"/>
    <dbReference type="CPTAC" id="CPTAC-21"/>
    <dbReference type="CPTAC" id="CPTAC-22"/>
    <dbReference type="jPOST" id="P13798"/>
    <dbReference type="MassIVE" id="P13798"/>
    <dbReference type="PaxDb" id="9606-ENSP00000296456"/>
    <dbReference type="PeptideAtlas" id="P13798"/>
    <dbReference type="ProteomicsDB" id="52988"/>
    <dbReference type="Pumba" id="P13798"/>
    <dbReference type="Antibodypedia" id="30567">
        <property type="antibodies" value="243 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="327"/>
    <dbReference type="Ensembl" id="ENST00000296456.10">
        <property type="protein sequence ID" value="ENSP00000296456.5"/>
        <property type="gene ID" value="ENSG00000164062.14"/>
    </dbReference>
    <dbReference type="GeneID" id="327"/>
    <dbReference type="KEGG" id="hsa:327"/>
    <dbReference type="MANE-Select" id="ENST00000296456.10">
        <property type="protein sequence ID" value="ENSP00000296456.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001640.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001631.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003cxf.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:586"/>
    <dbReference type="ClinPGx" id="PA24878"/>
    <dbReference type="CTD" id="327"/>
    <dbReference type="DisGeNET" id="327"/>
    <dbReference type="GeneCards" id="APEH"/>
    <dbReference type="HGNC" id="HGNC:586">
        <property type="gene designation" value="APEH"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164062">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="102645">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000164062"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000164062"/>
    <dbReference type="eggNOG" id="KOG2100">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000013172"/>
    <dbReference type="HOGENOM" id="CLU_014230_1_1_1"/>
    <dbReference type="InParanoid" id="P13798"/>
    <dbReference type="OrthoDB" id="416344at2759"/>
    <dbReference type="PAN-GO" id="P13798">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P13798"/>
    <dbReference type="BioCyc" id="MetaCyc:HS08997-MONOMER"/>
    <dbReference type="BRENDA" id="3.4.19.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P13798"/>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-72764">
        <property type="pathway name" value="Eukaryotic Translation Termination"/>
    </dbReference>
    <dbReference type="SignaLink" id="P13798"/>
    <dbReference type="Agora" id="ENSG00000164062"/>
    <dbReference type="BioGRID-ORCS" id="327">
        <property type="hits" value="10 hits in 1159 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="APEH">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="APEH_(gene)"/>
    <dbReference type="GenomeRNAi" id="327"/>
    <dbReference type="Pharos" id="P13798">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P13798"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="P13798">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000164062">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 191 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P13798">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904813">
        <property type="term" value="C:ficolin-1-rich granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031965">
        <property type="term" value="C:nuclear membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008242">
        <property type="term" value="F:omega peptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003723">
        <property type="term" value="F:RNA binding"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004252">
        <property type="term" value="F:serine-type endopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050435">
        <property type="term" value="P:amyloid-beta metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006415">
        <property type="term" value="P:translational termination"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="FunFam" id="2.120.10.30:FF:000047">
        <property type="entry name" value="Acylamino-acid-releasing enzyme"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000043">
        <property type="entry name" value="acylamino-acid-releasing enzyme"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.120.10.30">
        <property type="entry name" value="TolB, C-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011042">
        <property type="entry name" value="6-blade_b-propeller_TolB-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045550">
        <property type="entry name" value="AARE_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002471">
        <property type="entry name" value="Pept_S9_AS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001375">
        <property type="entry name" value="Peptidase_S9_cat"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42776:SF4">
        <property type="entry name" value="ACYLAMINO-ACID-RELEASING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR42776">
        <property type="entry name" value="SERINE PEPTIDASE S9 FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19283">
        <property type="entry name" value="APEH_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00326">
        <property type="entry name" value="Peptidase_S9"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50993">
        <property type="entry name" value="Peptidase/esterase 'gauge' domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00708">
        <property type="entry name" value="PRO_ENDOPEP_SER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000122430" description="Acylamino-acid-releasing enzyme">
        <location>
            <begin position="1"/>
            <end position="732"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="4 7">
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="4">
        <location>
            <position position="675"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="4 7">
        <location>
            <position position="707"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="5">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 14">
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 11 12 13 14 15">
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051580" description="In dbSNP:rs3816877.">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="541"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA07476." evidence="9" ref="1">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA07476." evidence="9" ref="1">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA07476." evidence="9" ref="1">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA07476." evidence="9" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF37321." evidence="9" ref="2">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="403"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P13676"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P19205"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P80227"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10084"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10395453"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10719179"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="1740429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="2006156"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="732" mass="81225" checksum="A2C370516324D851" modified="2003-11-07" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1991-05-01" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>P21399</accession>
    <accession>D3DRK7</accession>
    <accession>Q14652</accession>
    <accession>Q5VZA7</accession>
    <name>ACOHC_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="12">Cytoplasmic aconitate hydratase</fullName>
            <shortName>Aconitase</shortName>
            <ecNumber evidence="2 4 10">4.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Citrate hydro-lyase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Ferritin repressor protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Iron regulatory protein 1</fullName>
            <shortName>IRP1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Iron-responsive element-binding protein 1</fullName>
            <shortName>IRE-BP 1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACO1</name>
        <name type="synonym">IREB1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            </authorList>
            <dbReference type="PubMed" id="15164053"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Uterus</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 74-889</scope>
        <scope>RNA-BINDING</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
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            <dbReference type="PubMed" id="1903202"/>
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        <scope>SIMILARITY TO ACONITASES AND IPM ISOMERASES</scope>
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            <dbReference type="PubMed" id="1946430"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>FUNCTION</scope>
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        <scope>MUTAGENESIS OF CYS-300; CYS-437; CYS-503; CYS-506; ARG-536; ARG-541; ARG-699; SER-778 AND ARG-780</scope>
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        <scope>UBIQUITINATION</scope>
        <scope>INTERACTION WITH FBXL5</scope>
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        <scope>UBIQUITINATION</scope>
        <scope>INTERACTION WITH FBXL5</scope>
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        <scope>INTERACTION WITH FRATAXIN(81-210)</scope>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="Cell Metab." volume="18" first="187" last="198">
            <title>Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and maturation of different subsets of cytosolic-nuclear iron-sulfur proteins.</title>
            <authorList>
                <person name="Stehling O."/>
                <person name="Mascarenhas J."/>
                <person name="Vashisht A.A."/>
                <person name="Sheftel A.D."/>
                <person name="Niggemeyer B."/>
                <person name="Roesser R."/>
                <person name="Pierik A.J."/>
                <person name="Wohlschlegel J.A."/>
                <person name="Lill R."/>
            </authorList>
            <dbReference type="PubMed" id="23891004"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2013.06.015"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>RNA-BINDING</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2018" name="Cell Metab." volume="27" first="263" last="263">
            <title>Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur Proteins.</title>
            <authorList>
                <person name="Stehling O."/>
                <person name="Mascarenhas J."/>
                <person name="Vashisht A.A."/>
                <person name="Sheftel A.D."/>
                <person name="Niggemeyer B."/>
                <person name="Roesser R."/>
                <person name="Pierik A.J."/>
                <person name="Wohlschlegel J.A."/>
                <person name="Lill R."/>
            </authorList>
            <dbReference type="PubMed" id="29320706"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2017.12.009"/>
        </citation>
        <scope>ERRATUM OF PUBMED:23891004</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-628</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2006" name="Structure" volume="14" first="129" last="139">
            <title>Crystal structure of human iron regulatory protein 1 as cytosolic aconitase.</title>
            <authorList>
                <person name="Dupuy J."/>
                <person name="Volbeda A."/>
                <person name="Carpentier P."/>
                <person name="Darnault C."/>
                <person name="Moulis J.-M."/>
                <person name="Fontecilla-Camps J.C."/>
            </authorList>
            <dbReference type="PubMed" id="16407072"/>
            <dbReference type="DOI" id="10.1016/j.str.2005.09.009"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR CLUSTER</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2012" name="N. Engl. J. Med." volume="367" first="1921" last="1929">
            <title>Diagnostic exome sequencing in persons with severe intellectual disability.</title>
            <authorList>
                <person name="de Ligt J."/>
                <person name="Willemsen M.H."/>
                <person name="van Bon B.W."/>
                <person name="Kleefstra T."/>
                <person name="Yntema H.G."/>
                <person name="Kroes T."/>
                <person name="Vulto-van Silfhout A.T."/>
                <person name="Koolen D.A."/>
                <person name="de Vries P."/>
                <person name="Gilissen C."/>
                <person name="del Rosario M."/>
                <person name="Hoischen A."/>
                <person name="Scheffer H."/>
                <person name="de Vries B.B."/>
                <person name="Brunner H.G."/>
                <person name="Veltman J.A."/>
                <person name="Vissers L.E."/>
            </authorList>
            <dbReference type="PubMed" id="23033978"/>
            <dbReference type="DOI" id="10.1056/nejmoa1206524"/>
        </citation>
        <scope>VARIANT MET-318</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 9 10">Bifunctional iron sensor that switches between 2 activities depending on iron availability (PubMed:1281544, PubMed:1946430, PubMed:8041788). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788). Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1281544, PubMed:1946430, PubMed:23891004, PubMed:8041788).</text>
    </comment>
    <comment type="function">
        <text evidence="2 4 10">Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 4 10">
            <text>citrate = D-threo-isocitrate</text>
            <dbReference type="Rhea" id="RHEA:10336"/>
            <dbReference type="ChEBI" id="CHEBI:15562"/>
            <dbReference type="ChEBI" id="CHEBI:16947"/>
            <dbReference type="EC" id="4.2.1.3"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>[4Fe-4S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:49883"/>
        </cofactor>
        <text evidence="3">Binds 1 [4Fe-4S] cluster per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 5 6 7">Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2847111">
            <id>P21399</id>
        </interactant>
        <interactant intactId="EBI-365980">
            <id>P15056</id>
            <label>BRAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the aconitase/IPM isomerase family.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Aconitase"/>
        <text>Aconitase entry</text>
    </comment>
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        <property type="protein sequence ID" value="CAA77651.1"/>
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        <property type="protein sequence ID" value="ABF47095.1"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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        <property type="protein sequence ID" value="EAW58549.1"/>
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    <dbReference type="EMBL" id="CH471071">
        <property type="protein sequence ID" value="EAW58550.1"/>
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        <property type="protein sequence ID" value="EAW58552.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH18103.1"/>
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        <property type="protein sequence ID" value="AAA69900.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="S26403"/>
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        <property type="nucleotide sequence ID" value="NM_001278352.2"/>
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    <dbReference type="RefSeq" id="NP_001349769.1">
        <property type="nucleotide sequence ID" value="NM_001362840.2"/>
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        <property type="nucleotide sequence ID" value="NM_002197.3"/>
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        <property type="nucleotide sequence ID" value="XM_054363007.1"/>
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        <property type="chains" value="A=2-889"/>
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        <property type="interactions" value="1508"/>
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        <property type="generic name" value="Manganese cation"/>
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        <property type="type" value="Curated"/>
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        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
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        <property type="antibodies" value="580 antibodies from 40 providers"/>
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        <property type="hits" value="9 hits in 1155 CRISPR screens"/>
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<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="220" xmlns="https://uniprot.org/uniprot">
    <accession>P49753</accession>
    <accession>Q3I5F8</accession>
    <accession>Q53EK4</accession>
    <accession>Q9NUX4</accession>
    <name>ACOT2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A thioesterase 2, mitochondrial</fullName>
            <shortName>Acyl-CoA thioesterase 2</shortName>
            <ecNumber evidence="3 6">3.1.2.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-coenzyme A thioester hydrolase 2a</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>CTE-Ia</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA thioesterase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ZAP128</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT2</name>
        <name type="synonym">PTE2</name>
        <name type="synonym">PTE2A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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            <tissue>Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>CAUTION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-475</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-475</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="5">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-475</scope>
        <source>
            <tissue>Lung</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2000" name="Biochem. Biophys. Res. Commun." volume="275" first="233" last="240">
            <title>Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.</title>
            <authorList>
                <person name="Jones J.M."/>
                <person name="Gould S.J."/>
            </authorList>
            <dbReference type="PubMed" id="10944470"/>
            <dbReference type="DOI" id="10.1006/bbrc.2000.3285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 35-483 (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>CAUTION</scope>
        <scope>VARIANT ARG-475</scope>
    </reference>
    <reference key="7">
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            <title>Crystal structure of human mitochondrial acyl-CoA thioesterase (ACOT2).</title>
            <authorList>
                <person name="Mandel C.R."/>
                <person name="Tweel B."/>
                <person name="Tong L."/>
            </authorList>
            <dbReference type="PubMed" id="19497300"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2009.05.122"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 46-483</scope>
        <scope>ACTIVE SITE</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 6">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:10944470, PubMed:16940157). Displays higher activity toward long chain acyl CoAs (C14-C20) (PubMed:10944470, PubMed:16940157). The enzyme is involved in enhancing the hepatic fatty acid oxidation in mitochondria (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:30140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>eicosanoyl-CoA + H2O = eicosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40147"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40148"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 6">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>(9Z)-hexadecenoyl-CoA + H2O = (9Z)-hexadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40131"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40132"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>(9E)-octadecenoyl-CoA + H2O = (9E)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40723"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30825"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77537"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40724"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(9Z,12Z)-octadecadienoyl-CoA + H2O = (9Z,12Z)-octadecadienoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:40144"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">40.3 uM for C10-acyl-CoA</KM>
            <KM evidence="6">8.9 uM for C12-acyl-CoA</KM>
            <KM evidence="6">1.6 uM for C14-acyl-CoA</KM>
            <KM evidence="6">2 uM for C16-acyl-CoA</KM>
            <KM evidence="6">2.8 uM for C18-acyl-CoA</KM>
            <KM evidence="6">4.8 uM for C20-acyl-CoA</KM>
            <KM evidence="6">4.5 uM for C16:1-acyl-CoA</KM>
            <KM evidence="6">6.1 uM for C18:1-acyl-CoA</KM>
            <KM evidence="6">4.3 uM for C18:1-trans-acyl-CoA</KM>
            <Vmax evidence="6">212.0 nmol/min/mg enzyme with C10-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">681.0 nmol/min/mg enzyme with C12-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">766.0 nmol/min/mg enzyme with C14-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">656.0 nmol/min/mg enzyme with C16-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">488.0 nmol/min/mg enzyme with C18-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">408.0 nmol/min/mg enzyme with C20-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">661.0 nmol/min/mg enzyme with C16:1-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">304.0 nmol/min/mg enzyme with C18:1-acyl-CoA as substrate</Vmax>
            <Vmax evidence="6">418.0 nmol/min/mg enzyme with C18:1-trans-acyl-CoA as substrate</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="11 12">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1052865">
            <id>P49753</id>
        </interactant>
        <interactant intactId="EBI-16423037">
            <id>Q9NZ94-2</id>
            <label>NLGN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P49753-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P49753-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012225 VSP_012226"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Strongest expression in heart, liver, muscle and kidney. Weak in placenta and pancreas.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the C/M/P thioester hydrolase family.</text>
    </comment>
    <comment type="caution">
        <text evidence="11 12">Was originally (PubMed:10944470) thought to be peroxisomal but was later shown (PubMed:16940157) to be mitochondrial.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAC42007" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.1.2.2" evidence="3 6"/>
    <dbReference type="EMBL" id="L40401">
        <property type="protein sequence ID" value="AAC42007.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ082755">
        <property type="protein sequence ID" value="AAZ31237.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001939">
        <property type="protein sequence ID" value="BAA91989.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223635">
        <property type="protein sequence ID" value="BAD97355.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004436">
        <property type="protein sequence ID" value="AAH04436.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006335">
        <property type="protein sequence ID" value="AAH06335.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006500">
        <property type="protein sequence ID" value="AAH06500.4"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY005822">
        <property type="protein sequence ID" value="AAF97985.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9816.1">
        <molecule id="P49753-1"/>
    </dbReference>
    <dbReference type="PIR" id="JC7367">
        <property type="entry name" value="JC7367"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006812.3">
        <molecule id="P49753-1"/>
        <property type="nucleotide sequence ID" value="NM_006821.5"/>
    </dbReference>
    <dbReference type="PDB" id="3HLK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=46-483"/>
    </dbReference>
    <dbReference type="PDBsum" id="3HLK"/>
    <dbReference type="AlphaFoldDB" id="P49753"/>
    <dbReference type="SMR" id="P49753"/>
    <dbReference type="BioGRID" id="116164">
        <property type="interactions" value="132"/>
    </dbReference>
    <dbReference type="FunCoup" id="P49753">
        <property type="interactions" value="514"/>
    </dbReference>
    <dbReference type="IntAct" id="P49753">
        <property type="interactions" value="50"/>
    </dbReference>
    <dbReference type="MINT" id="P49753"/>
    <dbReference type="STRING" id="9606.ENSP00000238651"/>
    <dbReference type="ChEMBL" id="CHEMBL2189135"/>
    <dbReference type="SwissLipids" id="SLP:000000590"/>
    <dbReference type="ESTHER" id="human-ACOT2">
        <property type="family name" value="Acyl-CoA_Thioesterase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.942"/>
    <dbReference type="CarbonylDB" id="P49753"/>
    <dbReference type="GlyGen" id="P49753">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P49753"/>
    <dbReference type="PhosphoSitePlus" id="P49753"/>
    <dbReference type="SwissPalm" id="P49753"/>
    <dbReference type="BioMuta" id="ACOT2"/>
    <dbReference type="DMDM" id="269849771"/>
    <dbReference type="jPOST" id="P49753"/>
    <dbReference type="MassIVE" id="P49753"/>
    <dbReference type="PaxDb" id="9606-ENSP00000238651"/>
    <dbReference type="PeptideAtlas" id="P49753"/>
    <dbReference type="ProteomicsDB" id="56066">
        <molecule id="P49753-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56067">
        <molecule id="P49753-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P49753"/>
    <dbReference type="Antibodypedia" id="25399">
        <property type="antibodies" value="147 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10965"/>
    <dbReference type="Ensembl" id="ENST00000238651.10">
        <molecule id="P49753-1"/>
        <property type="protein sequence ID" value="ENSP00000238651.5"/>
        <property type="gene ID" value="ENSG00000119673.17"/>
    </dbReference>
    <dbReference type="GeneID" id="10965"/>
    <dbReference type="KEGG" id="hsa:10965"/>
    <dbReference type="MANE-Select" id="ENST00000238651.10">
        <property type="protein sequence ID" value="ENSP00000238651.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006821.6"/>
        <property type="RefSeq protein sequence ID" value="NP_006812.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xon.6">
        <molecule id="P49753-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18431"/>
    <dbReference type="ClinPGx" id="PA142672653"/>
    <dbReference type="CTD" id="10965"/>
    <dbReference type="DisGeNET" id="10965"/>
    <dbReference type="GeneCards" id="ACOT2"/>
    <dbReference type="HGNC" id="HGNC:18431">
        <property type="gene designation" value="ACOT2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000119673">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="609972">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000119673"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000119673"/>
    <dbReference type="eggNOG" id="ENOG502QQ8Z">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01010000222336"/>
    <dbReference type="InParanoid" id="P49753"/>
    <dbReference type="OrthoDB" id="6347013at2759"/>
    <dbReference type="PAN-GO" id="P49753">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P49753"/>
    <dbReference type="BioCyc" id="MetaCyc:HS04318-MONOMER"/>
    <dbReference type="BRENDA" id="3.1.2.2">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P49753"/>
    <dbReference type="Reactome" id="R-HSA-77289">
        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9033241">
        <property type="pathway name" value="Peroxisomal protein import"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9837999">
        <property type="pathway name" value="Mitochondrial protein degradation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P49753"/>
    <dbReference type="SignaLink" id="P49753"/>
    <dbReference type="SIGNOR" id="P49753"/>
    <dbReference type="UniPathway" id="UPA00199"/>
    <dbReference type="Agora" id="ENSG00000119673"/>
    <dbReference type="BioGRID-ORCS" id="10965">
        <property type="hits" value="18 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOT2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P49753"/>
    <dbReference type="GeneWiki" id="ACOT2"/>
    <dbReference type="GenomeRNAi" id="10965"/>
    <dbReference type="Pharos" id="P49753">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P49753"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="P49753">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000119673">
        <property type="expression patterns" value="Expressed in apex of heart and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P49753">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005782">
        <property type="term" value="C:peroxisomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047617">
        <property type="term" value="F:fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001676">
        <property type="term" value="P:long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000038">
        <property type="term" value="P:very long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="DisProt" id="DP03510"/>
    <dbReference type="FunFam" id="2.60.40.2240:FF:000001">
        <property type="entry name" value="acyl-coenzyme A thioesterase 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000024">
        <property type="entry name" value="acyl-coenzyme A thioesterase 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.2240">
        <property type="entry name" value="Acyl-CoA thioester hydrolase/BAAT N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016662">
        <property type="entry name" value="Acyl-CoA_thioEstase_long-chain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014940">
        <property type="entry name" value="BAAT_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006862">
        <property type="entry name" value="Thio_Ohase/aa_AcTrfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042490">
        <property type="entry name" value="Thio_Ohase/BAAT_N"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824:SF16">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE 1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08840">
        <property type="entry name" value="BAAT_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04775">
        <property type="entry name" value="Bile_Hydr_Trans"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016521">
        <property type="entry name" value="Acyl-CoA_hydro"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end status="unknown"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000202147" description="Acyl-coenzyme A thioesterase 2, mitochondrial">
        <location>
            <begin status="unknown"/>
            <end position="483"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Microbody targeting signal" evidence="2">
        <location>
            <begin position="481"/>
            <end position="483"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="388"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="8">
        <location>
            <position position="422"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="1">
        <location>
            <position position="470"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012225" description="In isoform 2." evidence="9">
        <location>
            <begin position="1"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012226" description="In isoform 2." evidence="9">
        <location>
            <begin position="53"/>
            <end position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057271" description="In dbSNP:rs11545741.">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016136" description="In dbSNP:rs7494." evidence="3 4 5 7">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="475"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAZ31237 and 3; BAA91989." evidence="10" ref="2 3">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAZ31237, 3; BAA91989, 4; BAD97355, 5; AAH04436/AAH06335/AAH06500 and 6; AAF97985." evidence="10" ref="2 3 4 5 6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH06335." evidence="10" ref="5">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="454"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="66"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="82"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="93"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="107"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="turn" evidence="13">
        <location>
            <begin position="124"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="131"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="141"/>
            <end position="144"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="147"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="164"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="181"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="197"/>
            <end position="203"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="206"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="214"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="221"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="235"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="turn" evidence="13">
        <location>
            <begin position="242"/>
            <end position="244"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="246"/>
            <end position="250"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="253"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="263"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="267"/>
            <end position="278"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="286"/>
            <end position="293"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="295"/>
            <end position="306"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="310"/>
            <end position="317"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="324"/>
            <end position="329"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="332"/>
            <end position="334"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="341"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="348"/>
            <end position="350"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="364"/>
            <end position="369"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="373"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="378"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="393"/>
            <end position="406"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="413"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="450"/>
            <end position="471"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9QYR9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10944470"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16940157"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="19497300"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="7596406"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="10944470"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="16940157"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="3HLK"/>
        </source>
    </evidence>
    <sequence length="483" mass="53218" checksum="FAEDD42BBBD935E4" modified="2009-11-24" version="6" precursor="true">MSNKLLSPHPHSVVLRSEFKMASSPAVLRASRLYQWSLKSSAQFLGSPQLRQVGQIIRVPARMAATLILEPAGRCCWDEPVRIAVRGLAPEQPVTLRASLRDEKGALFQAHARYRADTLGELDLERAPALGGSFAGLEPMGLLWALEPEKPLVRLVKRDVRTPLAVELEVLDGHDPDPGRLLCQTRHERYFLPPGVRREPVRVGRVRGTLFLPPEPGPFPGIVDMFGTGGGLLEYRASLLAGKGFAVMALAYYNYEDLPKTMETLHLEYFEEAMNYLLSHPEVKGPGVGLLGISKGGELCLSMASFLKGITAAVVINGSVANVGGTLHYKGETLPPVGVNRNRIKVTKDGYADIVDVLNSPLEGPDQKSFIPVERAESTFLFLVGQDDHNWKSEFYANEACKRLQAHGRRKPQIICYPETGHYIEPPYFPLCRASLHALVGSPIIWGGEPRAHAMAQVDAWKQLQTFFHKHLGGHEGTIPSKV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-07-19" modified="2026-01-28" version="172" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N9L9</accession>
    <accession>Q17RF4</accession>
    <accession>Q5BKT6</accession>
    <accession>Q86TX0</accession>
    <accession>Q86TX1</accession>
    <accession>Q96N88</accession>
    <name>ACOT4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">Peroxisomal succinyl-coenzyme A thioesterase</fullName>
            <ecNumber evidence="5">3.1.2.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-coenzyme A thioesterase 4</fullName>
            <shortName>Acyl-CoA thioesterase 4</shortName>
            <ecNumber evidence="5">3.1.2.2</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>PTE-2b</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal acyl coenzyme A thioester hydrolase Ib</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal long-chain acyl-CoA thioesterase Ib</fullName>
            <shortName>PTE-Ib</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT4</name>
        <name type="synonym">PTE2B</name>
        <name type="synonym">PTEIB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
            <title>Full-length cDNA libraries and normalization.</title>
            <authorList>
                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT CYS-57</scope>
        <source>
            <tissue>Colon</tissue>
            <tissue>Urinary bladder</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="FASEB J." volume="20" first="1855" last="1864">
            <title>Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.</title>
            <authorList>
                <person name="Hunt M.C."/>
                <person name="Rautanen A."/>
                <person name="Westin M.A.K."/>
                <person name="Svensson L.T."/>
                <person name="Alexson S.E.H."/>
            </authorList>
            <dbReference type="PubMed" id="16940157"/>
            <dbReference type="DOI" id="10.1096/fj.06-6042com"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MISCELLANEOUS</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2009-09" db="PDB data bank">
            <title>Human Acyl-coenzyme A thioesterase 4.</title>
            <authorList>
                <person name="Siponen M.I."/>
                <person name="Moche M."/>
                <person name="Arrowsmith C.H."/>
                <person name="Berglund H."/>
                <person name="Bountra C."/>
                <person name="Collins R."/>
                <person name="Edwards A.M."/>
                <person name="Flodin S."/>
                <person name="Flores A."/>
                <person name="Graslund S."/>
                <person name="Hammarstrom M."/>
                <person name="Johansson A."/>
                <person name="Johansson I."/>
                <person name="Kallas A."/>
                <person name="Karlberg T."/>
                <person name="Kraulis P."/>
                <person name="Kotenyova T."/>
                <person name="Kotzsch A."/>
                <person name="Markova N."/>
                <person name="Nielsen T.K."/>
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                <person name="Nyman T."/>
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                <person name="Van Den Berg S."/>
                <person name="Wahlberg E."/>
                <person name="Weigelt J."/>
                <person name="Welin M."/>
                <person name="Wisniewska M."/>
                <person name="Schuler H."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS)</scope>
    </reference>
    <comment type="function">
        <text evidence="5">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16940157). Functions as a peroxisomal succinyl-coenzyme A thioesterase that can also hydrolyze glutaryl-CoA and long chain saturated acyl-CoAs (PubMed:16940157).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>succinyl-CoA + H2O = succinate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11516"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30031"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57292"/>
            <dbReference type="EC" id="3.1.2.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:11517"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>glutaryl-CoA + H2O = glutarate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40575"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30921"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57378"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40576"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(9Z,12Z)-octadecadienoyl-CoA + H2O = (9Z,12Z)-octadecadienoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40151"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40152"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:30140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>eicosanoyl-CoA + H2O = eicosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40147"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:40148"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">14 uM for succinyl-CoA</KM>
            <KM evidence="5">147 uM for glutaryl-CoA</KM>
            <KM evidence="5">3.4 uM for C14-acyl-CoA</KM>
            <Vmax evidence="5">581.0 nmol/min/mg enzyme with succinyl-CoA as substrate</Vmax>
            <Vmax evidence="5">132.0 nmol/min/mg enzyme with glutaryl-CoA as substrate</Vmax>
            <Vmax evidence="5">137.0 nmol/min/mg enzyme with C14-acyl-CoA as substrate</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="8">Lipid metabolism; fatty acid biosynthesis.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Peroxisome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Strongest expression in liver and kidney and weaker expression in placenta, heart, and muscle.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="6">Compared to mouse peroxisomal succinyl-coenzyme A thioesterase/ACOT4, the human enzyme has a broad substrate specificity overlapping the activity of three mouse acyl-coenzyme A thioesterases, providing an explanation for the unexpectedly low number of acyl-coenzyme A thioesterase genes in the human genome.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the C/M/P thioester hydrolase family.</text>
    </comment>
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAB71017.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAD62346.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAD62354.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH31799.2"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH90945.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI17342.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI17344.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_152331.4"/>
    </dbReference>
    <dbReference type="PDB" id="3K2I">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B=1-421"/>
    </dbReference>
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        <property type="interactions" value="3"/>
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        <property type="interactions" value="46"/>
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        <property type="family name" value="Acyl-CoA_Thioesterase"/>
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        <property type="antibodies" value="85 antibodies from 22 providers"/>
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        <property type="protein sequence ID" value="ENSP00000323071.4"/>
        <property type="gene ID" value="ENSG00000177465.5"/>
    </dbReference>
    <dbReference type="GeneID" id="122970"/>
    <dbReference type="KEGG" id="hsa:122970"/>
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        <property type="RefSeq protein sequence ID" value="NP_689544.3"/>
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        <property type="organism name" value="human"/>
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        <property type="type" value="gene"/>
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        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
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        <property type="pathway name" value="Beta-oxidation of very long chain fatty acids"/>
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        <property type="pathway name" value="Peroxisomal protein import"/>
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        <property type="hits" value="8 hits in 1145 CRISPR screens"/>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 14"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000177465">
        <property type="expression patterns" value="Expressed in ileal mucosa and 117 other cell types or tissues"/>
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        <property type="evidence" value="ECO:0000304"/>
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        <property type="term" value="F:carboxylic ester hydrolase activity"/>
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        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="BAAT_C"/>
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        <property type="entry name" value="Thio_Ohase/BAAT_N"/>
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        <property type="entry name" value="PEROXISOMAL SUCCINYL-COENZYME A THIOESTERASE"/>
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        <property type="entry name" value="BAAT_C"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Bile_Hydr_Trans"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <feature type="chain" id="PRO_0000202149" description="Peroxisomal succinyl-coenzyme A thioesterase">
        <location>
            <begin position="1"/>
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            <begin position="419"/>
            <end position="421"/>
        </location>
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    <feature type="active site" description="Charge relay system" evidence="1">
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            <position position="232"/>
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    <feature type="active site" description="Charge relay system" evidence="1">
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            <position position="326"/>
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    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="360"/>
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    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="313"/>
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    </feature>
    <feature type="sequence variant" id="VAR_052300" description="In dbSNP:rs3742819." evidence="4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="57"/>
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        <original>A</original>
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        <location>
            <position position="187"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC04313." evidence="7" ref="1">
        <original>L</original>
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        <location>
            <position position="130"/>
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    <feature type="sequence conflict" description="In Ref. 1; BAC04313." evidence="7" ref="1">
        <original>ALAY</original>
        <variation>DLQS</variation>
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            <begin position="187"/>
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            <begin position="4"/>
            <end position="8"/>
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    <feature type="strand" evidence="9">
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            <begin position="20"/>
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    <feature type="strand" evidence="9">
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            <begin position="31"/>
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    <feature type="strand" evidence="9">
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    <feature type="strand" evidence="9">
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            <begin position="144"/>
            <end position="150"/>
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    <feature type="strand" evidence="9">
        <location>
            <begin position="152"/>
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    <feature type="strand" evidence="9">
        <location>
            <begin position="159"/>
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    <feature type="strand" evidence="9">
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            <dbReference type="PDB" id="3K2I"/>
        </source>
    </evidence>
    <sequence length="421" mass="46327" checksum="41BBE5AA826A9F2C" modified="2004-07-19" version="2">MSATLILEPPGRCCWNEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADARGELDLERAPALGGSFAGLEPMGLLWALEPEKPFWRFLKRDVQIPFVVELEVLDGHDPEPGRLLCQAQHERHFLPPGVRRQSVRAGRVRATLFLPPGPGPFPGIIDIFGIGGGLLEYRASLLAGHGFATLALAYYNFEDLPNNMDNISLEYFEEAVCYMLQHPQVKGPGIGLLGISLGADICLSMASFLKNVSATVSINGSGISGNTAINYKHSSIPPLGYDLRRIKVAFSGLVDIVDIRNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQTVSERLQAHGKEKPQIICYPGTGHYIEPPYFPLCPASLHRLLNKHVIWGGEPRAHSKAQEDAWKQILAFFCKHLGGTQKTAVPKL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1999-07-15" modified="2026-01-28" version="218" xmlns="https://uniprot.org/uniprot">
    <accession>O14561</accession>
    <accession>B2R4M1</accession>
    <accession>Q9UNV1</accession>
    <name>ACPM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">Acyl carrier protein, mitochondrial</fullName>
            <shortName>ACP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>CI-SDAP</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>NADH-ubiquinone oxidoreductase 9.6 kDa subunit</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">NDUFAB1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>SUBUNIT</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>FUNCTION</scope>
        <scope>COMPONENT OF THE CYSTEINE DESULFURASE COMPLEX</scope>
        <scope>PHOSPHOPANTETHEINYLATION AT SER-112</scope>
    </reference>
    <reference evidence="20 21" key="18">
        <citation type="journal article" date="2022" name="Nat. Commun." volume="13" first="929" last="929">
            <title>A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.</title>
            <authorList>
                <person name="Rebelo-Guiomar P."/>
                <person name="Pellegrino S."/>
                <person name="Dent K.C."/>
                <person name="Sas-Chen A."/>
                <person name="Miller-Fleming L."/>
                <person name="Garone C."/>
                <person name="Van Haute L."/>
                <person name="Rogan J.F."/>
                <person name="Dinan A."/>
                <person name="Firth A.E."/>
                <person name="Andrews B."/>
                <person name="Whitworth A.J."/>
                <person name="Schwartz S."/>
                <person name="Warren A.J."/>
                <person name="Minczuk M."/>
            </authorList>
            <dbReference type="PubMed" id="35177605"/>
            <dbReference type="DOI" id="10.1038/s41467-022-28503-5"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) IN COMPLEX WITH MTLSU</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 9 12">Carrier of the growing fatty acid chain in fatty acid biosynthesis (By similarity) (PubMed:27626371). Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain (PubMed:27626371). Accessory protein, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with LYRM4, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:31664822). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 7 8 10 11 12 13 15">Mammalian complex I is composed of 45 different subunits (PubMed:12611891). Interacts with ETFRF1 (PubMed:27499296). Identified in a complex composed of MALSU1, MIEF1 upstream open reading frame protein and NDUFAB1; within the trimeric complex, MIEF1 upstream open reading frame protein functions as a bridging scaffold that interacts with MALSU1 on one side, and with NDUFAB1 on the other side. The complex interacts with the mitochondrial large ribosomal subunit (PubMed:28892042, PubMed:30215512, PubMed:35177605). Interacts with alpha-1-microglobulin chain; this interaction is required for the maintenance of mitochondrial redox homeostasis. Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is a heterohexamer containing two copies of each monomer (Probable). Component of the cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the stability and cysteine desulfurase activity of NFS1 (PubMed:31664822).</text>
    </comment>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
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    </comment>
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    </comment>
    <comment type="interaction">
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    </comment>
    <comment type="interaction">
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    </comment>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 10">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="12">Phosphopantetheinylation at Ser-112 is essential for interactions with LYR motif-containing proteins.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="9">In contrast to other accessory subunits of complex I, NDUFAB1 is the only subunit that is essential for cell viability in HEK293T cells. Since knockout cells lack assembled complex I and die in galactose media, this suggests that the essential role of NDUFAB1 is independent of complex I.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the acyl carrier protein (ACP) family.</text>
    </comment>
    <comment type="sequence caution" evidence="14">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC05814" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
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    <evidence type="ECO:0007829" key="23">
        <source>
            <dbReference type="PDB" id="6ODD"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="7OF0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="7QH7"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="8QU5"/>
        </source>
    </evidence>
    <sequence length="156" mass="17417" checksum="0FCE3C3EC6D97AE2" modified="2002-07-11" version="3" precursor="true">MASRVLSAYVSRLPAAFAPLPRVRMLAVARPLSTALCSAGTQTRLGTLQPALVLAQVPGRVTQLCRQYSDMPPLTLEGIQDRVLYVLKLYDKIDPEKLSVNSHFMKDLGLDSLDQVEIIMAMEDEFGFEIPDIDAEKLMCPQEIVDYIADKKDVYE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="128" xmlns="https://uniprot.org/uniprot">
    <accession>Q3I5F7</accession>
    <accession>A0A2R8Y7H3</accession>
    <name>ACOT6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Acyl-coenzyme A thioesterase 6</fullName>
            <shortName evidence="4">Acyl-CoA thioesterase 6</shortName>
            <ecNumber evidence="2">3.1.2.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ACOT6</name>
        <name evidence="5" type="synonym">C14orf42</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="FASEB J." volume="20" first="1855" last="1864">
            <title>Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs.</title>
            <authorList>
                <person name="Hunt M.C."/>
                <person name="Rautanen A."/>
                <person name="Westin M.A.K."/>
                <person name="Svensson L.T."/>
                <person name="Alexson S.E.H."/>
            </authorList>
            <dbReference type="PubMed" id="16940157"/>
            <dbReference type="DOI" id="10.1096/fj.06-6042com"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
                <person name="Pepin K."/>
                <person name="Artiguenave F."/>
                <person name="Robert C."/>
                <person name="Cruaud C."/>
                <person name="Bruels T."/>
                <person name="Jaillon O."/>
                <person name="Friedlander L."/>
                <person name="Samson G."/>
                <person name="Brottier P."/>
                <person name="Cure S."/>
                <person name="Segurens B."/>
                <person name="Aniere F."/>
                <person name="Samain S."/>
                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
                <person name="Dubois I."/>
                <person name="Friedman C."/>
                <person name="Gouyvenoux M."/>
                <person name="James R."/>
                <person name="Madan A."/>
                <person name="Mairey-Estrada B."/>
                <person name="Mangenot S."/>
                <person name="Martins N."/>
                <person name="Menard M."/>
                <person name="Oztas S."/>
                <person name="Ratcliffe A."/>
                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
                <person name="Magdelenat G."/>
                <person name="Pateau E."/>
                <person name="Petit E."/>
                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
                <person name="Vega-Czarny N."/>
                <person name="Bataille E."/>
                <person name="Bluet E."/>
                <person name="Bordelais I."/>
                <person name="Dubois M."/>
                <person name="Dumont C."/>
                <person name="Guerin T."/>
                <person name="Haffray S."/>
                <person name="Hammadi R."/>
                <person name="Muanga J."/>
                <person name="Pellouin V."/>
                <person name="Robert D."/>
                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
                <person name="Roy A."/>
                <person name="Sainte-Marthe L."/>
                <person name="Verdier J."/>
                <person name="Verdier-Discala C."/>
                <person name="Hillier L.W."/>
                <person name="Fulton L."/>
                <person name="McPherson J."/>
                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
                <person name="Waterston R."/>
                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Catalyzes the hydrolysis of phytanoyl-CoA and pristanoyl-CoA, two methyl-branched fatty acids derived from phytol, that enter the body via the diet.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>pristanoyl-CoA + H2O = 2,6,10,14-tetramethylpentadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40415"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77250"/>
            <dbReference type="ChEBI" id="CHEBI:77268"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40416"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>phytanoyl-CoA + H2O = 3,7,11,15-tetramethylhexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40419"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:37257"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57391"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40420"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="2">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="4">Peroxisome</location>
        </subcellularLocation>
        <text evidence="4">Localization to the peroxisome is uncertain since the potential C-terminal peroxisome targeting signal found in the mouse ortholog is not perfectly conserved.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="4">Recombinant N-terminally GFP-tagged protein localizes to the cytosol.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q3I5F7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q3I5F7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_061185"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the C/M/P thioester hydrolase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.-" evidence="2"/>
    <dbReference type="EMBL" id="DQ082756">
        <property type="protein sequence ID" value="AAZ31238.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005225">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126378">
        <property type="protein sequence ID" value="AAI26379.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126380">
        <property type="protein sequence ID" value="AAI26381.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32118.1">
        <molecule id="Q3I5F7-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS91900.1">
        <molecule id="Q3I5F7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001032239.1">
        <molecule id="Q3I5F7-2"/>
        <property type="nucleotide sequence ID" value="NM_001037162.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352717.1">
        <molecule id="Q3I5F7-1"/>
        <property type="nucleotide sequence ID" value="NM_001365788.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001352718.1">
        <molecule id="Q3I5F7-2"/>
        <property type="nucleotide sequence ID" value="NM_001365789.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q3I5F7"/>
    <dbReference type="SMR" id="Q3I5F7"/>
    <dbReference type="BioGRID" id="534966">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q3I5F7">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="IntAct" id="Q3I5F7">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000370531"/>
    <dbReference type="ESTHER" id="human-ACOT6">
        <property type="family name" value="Acyl-CoA_Thioesterase"/>
    </dbReference>
    <dbReference type="MEROPS" id="S09.944"/>
    <dbReference type="iPTMnet" id="Q3I5F7"/>
    <dbReference type="PhosphoSitePlus" id="Q3I5F7"/>
    <dbReference type="BioMuta" id="ACOT6"/>
    <dbReference type="DMDM" id="121942509"/>
    <dbReference type="jPOST" id="Q3I5F7"/>
    <dbReference type="MassIVE" id="Q3I5F7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000370531"/>
    <dbReference type="PeptideAtlas" id="Q3I5F7"/>
    <dbReference type="Antibodypedia" id="63322">
        <property type="antibodies" value="45 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="641372"/>
    <dbReference type="Ensembl" id="ENST00000381139.1">
        <molecule id="Q3I5F7-2"/>
        <property type="protein sequence ID" value="ENSP00000370531.1"/>
        <property type="gene ID" value="ENSG00000205669.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000645972.2">
        <molecule id="Q3I5F7-1"/>
        <property type="protein sequence ID" value="ENSP00000496277.1"/>
        <property type="gene ID" value="ENSG00000205669.4"/>
    </dbReference>
    <dbReference type="GeneID" id="641372"/>
    <dbReference type="KEGG" id="hsa:641372"/>
    <dbReference type="MANE-Select" id="ENST00000645972.2">
        <property type="protein sequence ID" value="ENSP00000496277.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001365788.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001352717.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xop.3">
        <molecule id="Q3I5F7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:33159"/>
    <dbReference type="ClinPGx" id="PA162375329"/>
    <dbReference type="CTD" id="641372"/>
    <dbReference type="DisGeNET" id="641372"/>
    <dbReference type="GeneCards" id="ACOT6"/>
    <dbReference type="HGNC" id="HGNC:33159">
        <property type="gene designation" value="ACOT6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000205669">
        <property type="expression patterns" value="Tissue enhanced (kidney, liver, skeletal muscle)"/>
    </dbReference>
    <dbReference type="MIM" id="614267">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000205669"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000205669"/>
    <dbReference type="eggNOG" id="ENOG502QQ8Z">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT01010000222336"/>
    <dbReference type="HOGENOM" id="CLU_029849_4_1_1"/>
    <dbReference type="InParanoid" id="Q3I5F7"/>
    <dbReference type="OMA" id="GICEIPL"/>
    <dbReference type="OrthoDB" id="6347013at2759"/>
    <dbReference type="PAN-GO" id="Q3I5F7">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q3I5F7"/>
    <dbReference type="BRENDA" id="3.1.2.20">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q3I5F7"/>
    <dbReference type="SignaLink" id="Q3I5F7"/>
    <dbReference type="UniPathway" id="UPA00199"/>
    <dbReference type="Agora" id="ENSG00000205669"/>
    <dbReference type="BioGRID-ORCS" id="641372">
        <property type="hits" value="13 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOT6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="641372"/>
    <dbReference type="Pharos" id="Q3I5F7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q3I5F7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="Q3I5F7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000205669">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 75 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q3I5F7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047617">
        <property type="term" value="F:fatty acyl-CoA hydrolase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.1820:FF:000269">
        <property type="entry name" value="Acyl-CoA thioesterase 6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.40.2240:FF:000001">
        <property type="entry name" value="acyl-coenzyme A thioesterase 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.40.2240">
        <property type="entry name" value="Acyl-CoA thioester hydrolase/BAAT N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016662">
        <property type="entry name" value="Acyl-CoA_thioEstase_long-chain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014940">
        <property type="entry name" value="BAAT_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006862">
        <property type="entry name" value="Thio_Ohase/aa_AcTrfase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042490">
        <property type="entry name" value="Thio_Ohase/BAAT_N"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824:SF17">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE 6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10824">
        <property type="entry name" value="ACYL-COENZYME A THIOESTERASE-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08840">
        <property type="entry name" value="BAAT_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04775">
        <property type="entry name" value="Bile_Hydr_Trans"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016521">
        <property type="entry name" value="Acyl-CoA_hydro"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0719">Serine esterase</keyword>
    <feature type="chain" id="PRO_0000305098" description="Acyl-coenzyme A thioesterase 6">
        <location>
            <begin position="1"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Peroxisome targeting signal" evidence="3">
        <location>
            <begin position="419"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_061185" description="In isoform 2.">
        <location>
            <begin position="1"/>
            <end position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_052302" description="In dbSNP:rs17782052.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O55137"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q32Q92"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000305" key="4">
        <source>
            <dbReference type="PubMed" id="16940157"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:33159"/>
        </source>
    </evidence>
    <sequence length="421" mass="46789" checksum="CDEC8B80CAEF6F63" modified="2021-09-29" version="2">MAATLILEPAGRCCWDEPLRIAVRGLAPEQPVTLRTSLRDEEGALFRAHARYRADARDELDLERAPALGGSFAGLQPMGLLWALEPEKALVRLVKRDVRTPFAVELEVLDGHDTEPGRLLCLAQNKRDFLRPGVRREPVRAGPVRAALFLPPDEGPFPGIIDLFGSSRGLCEYRASLLAGHGFAVLALAYFRFEDLPEDLNDVHLEYFEEAVDFMLQHPKVKGPSIALLGFSKGGDLCLSMASFLKGITATVLINACVANTVAPLHYKDMIIPKLVDDLGKVKITKSGFLTFMDTWSNPLEEHNHQSLVPLEKAQVPFLFIVGMDDQSWKSEFYAQIASERLQAHGKERPQIICYPETGHCIDPPYFPPSRASVHAVLGEAIFYGGEPKAHSKAQVDAWQQIQTFFHKHLNGKKSVKHSKI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-11-02" modified="2026-01-28" version="206" xmlns="https://uniprot.org/uniprot">
    <accession>Q99424</accession>
    <accession>A6NF16</accession>
    <accession>B2R8U5</accession>
    <name>ACOX2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">Peroxisomal acyl-coenzyme A oxidase 2</fullName>
            <ecNumber evidence="7">1.17.99.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA 24-hydroxylase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="1">3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA oxidase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="3">Trihydroxycoprostanoyl-CoA oxidase</fullName>
            <shortName evidence="1">THCA-CoA oxidase</shortName>
            <shortName>THCCox</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="12" type="primary">ACOX2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="Proc. Natl. Acad. Sci. U.S.A." volume="93" first="13748" last="13753">
            <title>Molecular characterization of the human peroxisomal branched-chain acyl-CoA oxidase: cDNA cloning, chromosomal assignment, tissue distribution, and evidence for the absence of the protein in Zellweger's syndrome.</title>
            <authorList>
                <person name="Baumgart E."/>
                <person name="Vanhooren J.C.T."/>
                <person name="Fransen M."/>
                <person name="Marynen P."/>
                <person name="Puype M."/>
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                <person name="Mannaerts G.P."/>
                <person name="Van Veldhoven P.P."/>
            </authorList>
            <dbReference type="PubMed" id="8943006"/>
            <dbReference type="DOI" id="10.1073/pnas.93.24.13748"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 8-14; 271-282; 337-346; 450-468 AND 656-664</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="1997-09" db="EMBL/GenBank/DDBJ databases">
            <title>Genomic sequence of peroxisomal human branched chain acyl-CoA oxidase.</title>
            <authorList>
                <person name="Fournier B."/>
                <person name="Baumgart E."/>
                <person name="Fahimi D."/>
                <person name="Mannaerts G.P."/>
                <person name="Van Veldhoven P.P."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
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                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
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                <person name="Sudo H."/>
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                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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                <person name="Furuya T."/>
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                <person name="Murakawa K."/>
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                <person name="Kimata M."/>
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                <person name="Togiya S."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
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                <person name="Milosavljevic A."/>
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            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
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                <person name="Fasulo D."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9 AND THR-13</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2016" name="Proc. Natl. Acad. Sci. U.S.A." volume="113" first="11289" last="11293">
            <title>ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment.</title>
            <authorList>
                <person name="Vilarinho S."/>
                <person name="Sari S."/>
                <person name="Mazzacuva F."/>
                <person name="Bilguevar K."/>
                <person name="Esendagli-Yilmaz G."/>
                <person name="Jain D."/>
                <person name="Akyol G."/>
                <person name="Dalgic B."/>
                <person name="Guenel M."/>
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                <person name="Lifton R.P."/>
            </authorList>
            <dbReference type="PubMed" id="27647924"/>
            <dbReference type="DOI" id="10.1073/pnas.1613228113"/>
        </citation>
        <scope>INVOLVEMENT IN CBAS6</scope>
        <scope>VARIANT CBAS6 69-TYR--LEU-682 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT CBAS6 69-TYR--LEU-682 DEL</scope>
    </reference>
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            <authorList>
                <person name="Monte M.J."/>
                <person name="Alonso-Pena M."/>
                <person name="Briz O."/>
                <person name="Herraez E."/>
                <person name="Berasain C."/>
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                <person name="Prieto J."/>
                <person name="Marin J.J."/>
            </authorList>
            <dbReference type="PubMed" id="27884763"/>
            <dbReference type="DOI" id="10.1016/j.jhep.2016.11.005"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INVOLVEMENT IN CBAS6</scope>
        <scope>VARIANT CBAS6 TRP-225</scope>
        <scope>CHARACTERIZATION OF VARIANT CBAS6 TRP-225</scope>
    </reference>
    <comment type="function">
        <text evidence="2 7">Oxidizes the CoA esters of the bile acid intermediates di- and tri-hydroxycholestanoic acids (PubMed:27884763). Capable of oxidizing short as well as long chain 2-methyl branched fatty acids (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-CoA + A + H2O = (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-cholestan-26-oyl-CoA + AH2</text>
            <dbReference type="Rhea" id="RHEA:15733"/>
            <dbReference type="ChEBI" id="CHEBI:13193"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17499"/>
            <dbReference type="ChEBI" id="CHEBI:58677"/>
            <dbReference type="ChEBI" id="CHEBI:59807"/>
            <dbReference type="EC" id="1.17.99.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:15734"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-CoA + O2 = (24E)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-en-26-oyl-CoA + H2O2</text>
            <dbReference type="Rhea" id="RHEA:46728"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:16240"/>
            <dbReference type="ChEBI" id="CHEBI:59879"/>
            <dbReference type="ChEBI" id="CHEBI:77251"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:46729"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="2">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12026476">
            <id>Q99424</id>
        </interactant>
        <interactant intactId="EBI-1176455">
            <id>P63172</id>
            <label>DYNLT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12026476">
            <id>Q99424</id>
        </interactant>
        <interactant intactId="EBI-1053857">
            <id>Q13033</id>
            <label>STRN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 8">Peroxisome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Present in all tissues tested: heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Most abundant in heart, liver and kidney.</text>
    </comment>
    <comment type="disease" evidence="6 7">
        <disease id="DI-04924">
            <name>Congenital bile acid synthesis defect 6</name>
            <acronym>CBAS6</acronym>
            <description>An inborn error of bile acid synthesis characterized by abnormally increased liver enzymes, hypolipidemia and low cholesterol, vitamin D deficiency, elevated plasma and urinary levels of C27 intermediate bile acids 3alpha,7alpha-dihydroxy-5beta-cholestanoic acid (DHCA) and 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid (THCA). Serum levels of phytanic and pristanic acids are normal. Clinical features include liver fibrosis, mild ataxia, delayed development, and cognitive impairment. Liver histology shows many thin fibrous septa, swollen hepatocytes, glycogenated nuclei, and focal acinar transformation, consistent with hepatocellular injury and regeneration, without signs of obvious cholestasis, cholate stasis, or steatosis. CBAS6 transmission pattern is consistent with autosomal recessive inheritance.</description>
            <dbReference type="MIM" id="617308"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the acyl-CoA oxidase family.</text>
    </comment>
    <dbReference type="EC" id="1.17.99.3" evidence="7"/>
    <dbReference type="EMBL" id="X95190">
        <property type="protein sequence ID" value="CAA64489.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001541">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001542">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001543">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001544">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001545">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001546">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001547">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001548">
        <property type="protein sequence ID" value="CAB65596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313512">
        <property type="protein sequence ID" value="BAG36292.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC116036">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471055">
        <property type="protein sequence ID" value="EAW65375.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047700">
        <property type="protein sequence ID" value="AAH47700.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33775.1"/>
    <dbReference type="RefSeq" id="NP_003491.1">
        <property type="nucleotide sequence ID" value="NM_003500.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005265562.1">
        <property type="nucleotide sequence ID" value="XM_005265505.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204027.1">
        <property type="nucleotide sequence ID" value="XM_054348052.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q99424"/>
    <dbReference type="SMR" id="Q99424"/>
    <dbReference type="BioGRID" id="113906">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q99424">
        <property type="interactions" value="461"/>
    </dbReference>
    <dbReference type="IntAct" id="Q99424">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000307697"/>
    <dbReference type="GlyGen" id="Q99424">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q99424"/>
    <dbReference type="PhosphoSitePlus" id="Q99424"/>
    <dbReference type="SwissPalm" id="Q99424"/>
    <dbReference type="BioMuta" id="ACOX2"/>
    <dbReference type="DMDM" id="17366636"/>
    <dbReference type="jPOST" id="Q99424"/>
    <dbReference type="MassIVE" id="Q99424"/>
    <dbReference type="PaxDb" id="9606-ENSP00000307697"/>
    <dbReference type="PeptideAtlas" id="Q99424"/>
    <dbReference type="ProteomicsDB" id="78260"/>
    <dbReference type="Antibodypedia" id="31666">
        <property type="antibodies" value="317 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8309"/>
    <dbReference type="Ensembl" id="ENST00000302819.10">
        <property type="protein sequence ID" value="ENSP00000307697.5"/>
        <property type="gene ID" value="ENSG00000168306.14"/>
    </dbReference>
    <dbReference type="GeneID" id="8309"/>
    <dbReference type="KEGG" id="hsa:8309"/>
    <dbReference type="MANE-Select" id="ENST00000302819.10">
        <property type="protein sequence ID" value="ENSP00000307697.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003500.4"/>
        <property type="RefSeq protein sequence ID" value="NP_003491.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003dkl.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:120"/>
    <dbReference type="ClinPGx" id="PA24444"/>
    <dbReference type="CTD" id="8309"/>
    <dbReference type="DisGeNET" id="8309"/>
    <dbReference type="GeneCards" id="ACOX2"/>
    <dbReference type="HGNC" id="HGNC:120">
        <property type="gene designation" value="ACOX2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000168306">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACOX2"/>
    <dbReference type="MIM" id="601641">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="617308">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000168306"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000168306"/>
    <dbReference type="eggNOG" id="KOG0136">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160985"/>
    <dbReference type="HOGENOM" id="CLU_014629_3_1_1"/>
    <dbReference type="InParanoid" id="Q99424"/>
    <dbReference type="OMA" id="NHGVHCF"/>
    <dbReference type="OrthoDB" id="538336at2759"/>
    <dbReference type="PAN-GO" id="Q99424">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q99424"/>
    <dbReference type="BioCyc" id="MetaCyc:HS09732-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q99424"/>
    <dbReference type="Reactome" id="R-HSA-193368">
        <property type="pathway name" value="Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-389887">
        <property type="pathway name" value="Beta-oxidation of pristanoyl-CoA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9033241">
        <property type="pathway name" value="Peroxisomal protein import"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q99424"/>
    <dbReference type="Agora" id="ENSG00000168306"/>
    <dbReference type="BioGRID-ORCS" id="8309">
        <property type="hits" value="7 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACOX2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="8309"/>
    <dbReference type="Pharos" id="Q99424">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q99424"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q99424">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000168306">
        <property type="expression patterns" value="Expressed in right lobe of liver and 136 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q99424">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005782">
        <property type="term" value="C:peroxisomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033791">
        <property type="term" value="F:3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003997">
        <property type="term" value="F:acyl-CoA oxidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071949">
        <property type="term" value="F:FAD binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005504">
        <property type="term" value="F:fatty acid binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050660">
        <property type="term" value="F:flavin adenine dinucleotide binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006699">
        <property type="term" value="P:bile acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033540">
        <property type="term" value="P:fatty acid beta-oxidation using acyl-CoA oxidase"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000038">
        <property type="term" value="P:very long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.540.10:FF:000006">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.140.10:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.110.10:FF:000003">
        <property type="entry name" value="Acyl-coenzyme A oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.540.10">
        <property type="entry name" value="Acyl-CoA dehydrogenase/oxidase, N-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.110.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.140.10">
        <property type="entry name" value="Butyryl-CoA Dehydrogenase, subunit A, domain 3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR055060">
        <property type="entry name" value="ACOX_C_alpha1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029320">
        <property type="entry name" value="Acyl-CoA_ox_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR046373">
        <property type="entry name" value="Acyl-CoA_Oxase/DH_mid-dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012258">
        <property type="entry name" value="Acyl-CoA_oxidase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002655">
        <property type="entry name" value="Acyl-CoA_oxidase_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036250">
        <property type="entry name" value="AcylCo_DH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037069">
        <property type="entry name" value="AcylCoA_DH/ox_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009100">
        <property type="entry name" value="AcylCoA_DH/oxidase_NM_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909">
        <property type="entry name" value="ELECTRON TRANSPORT OXIDOREDUCTASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10909:SF344">
        <property type="entry name" value="PEROXISOMAL ACYL-COENZYME A OXIDASE 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01756">
        <property type="entry name" value="ACOX"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF22924">
        <property type="entry name" value="ACOX_C_alpha1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF14749">
        <property type="entry name" value="Acyl-CoA_ox_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF000168">
        <property type="entry name" value="Acyl-CoA_oxidase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47203">
        <property type="entry name" value="Acyl-CoA dehydrogenase C-terminal domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56645">
        <property type="entry name" value="Acyl-CoA dehydrogenase NM domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000204681" description="Peroxisomal acyl-coenzyme A oxidase 2">
        <location>
            <begin position="1"/>
            <end position="681"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Microbody targeting signal" evidence="5">
        <location>
            <begin position="679"/>
            <end position="681"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13">
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="13">
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="4">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="4">
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="4">
        <location>
            <position position="453"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="4">
        <location>
            <position position="561"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078764" description="In CBAS6; patient liver samples show absence of the protein; complete loss of fatty acid beta-oxidation activity." evidence="6">
        <location>
            <begin position="69"/>
            <end position="681"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078765" description="In CBAS6; reduces fatty acid beta-oxidation activity; does not alter subcellular location; dbSNP:rs150832314." evidence="7">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="225"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O02767"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P07872"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P97562"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q9QXD1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="27647924"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="27884763"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="8943006"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="27884763"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="12">
        <source>
            <dbReference type="HGNC" id="HGNC:120"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="681" mass="76827" checksum="7FAE9236FCBE6D4D" modified="1997-05-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="212" xmlns="https://uniprot.org/uniprot">
    <accession>O14734</accession>
    <accession>O15261</accession>
    <accession>Q17RX4</accession>
    <name>ACOT8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A thioesterase 8</fullName>
            <shortName>Acyl-CoA thioesterase 8</shortName>
            <ecNumber evidence="7 10">3.1.2.1</ecNumber>
            <ecNumber evidence="2">3.1.2.11</ecNumber>
            <ecNumber evidence="9 10">3.1.2.2</ecNumber>
            <ecNumber evidence="2">3.1.2.3</ecNumber>
            <ecNumber evidence="2">3.1.2.5</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Choloyl-coenzyme A thioesterase</fullName>
            <ecNumber evidence="10">3.1.2.27</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>HIV-Nef-associated acyl-CoA thioesterase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">Peroxisomal acyl-CoA thioesterase 2</fullName>
            <shortName evidence="12">PTE-2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal acyl-coenzyme A thioester hydrolase 1</fullName>
            <shortName>PTE-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Peroxisomal long-chain acyl-CoA thioesterase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Thioesterase II</fullName>
            <shortName>hACTE-III</shortName>
            <shortName>hACTEIII</shortName>
            <shortName>hTE</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACOT8</name>
        <name type="synonym">ACTEIII</name>
        <name evidence="11" type="synonym">PTE1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Biochem. Biophys. Res. Commun." volume="238" first="234" last="239">
            <title>A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef.</title>
            <authorList>
                <person name="Watanabe H."/>
                <person name="Shiratori T."/>
                <person name="Shoji H."/>
                <person name="Miyatake S."/>
                <person name="Okazaki Y."/>
                <person name="Ikuta K."/>
                <person name="Sato T."/>
                <person name="Saito T."/>
            </authorList>
            <dbReference type="PubMed" id="9299485"/>
            <dbReference type="DOI" id="10.1006/bbrc.1997.7217"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="J. Biol. Chem." volume="272" first="13779" last="13785">
            <title>Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation.</title>
            <authorList>
                <person name="Liu L.X."/>
                <person name="Margottin F."/>
                <person name="Le Gall S."/>
                <person name="Schwartz O."/>
                <person name="Selig L."/>
                <person name="Benarous R."/>
                <person name="Benichou S."/>
            </authorList>
            <dbReference type="PubMed" id="9153233"/>
            <dbReference type="DOI" id="10.1074/jbc.272.21.13779"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Lymphoid tissue</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="9216" last="9223">
            <title>Identification of peroxisomal acyl-CoA thioesterases in yeast and humans.</title>
            <authorList>
                <person name="Jones J.M."/>
                <person name="Nau K."/>
                <person name="Geraghty M.T."/>
                <person name="Erdmann R."/>
                <person name="Gould S.J."/>
            </authorList>
            <dbReference type="PubMed" id="10092594"/>
            <dbReference type="DOI" id="10.1074/jbc.274.14.9216"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
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                <person name="Jones M."/>
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                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
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                <person name="Phillimore B.J.C.T."/>
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                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
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                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
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                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2000" name="Biochem. Biophys. Res. Commun." volume="275" first="233" last="240">
            <title>Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase.</title>
            <authorList>
                <person name="Jones J.M."/>
                <person name="Gould S.J."/>
            </authorList>
            <dbReference type="PubMed" id="10944470"/>
            <dbReference type="DOI" id="10.1006/bbrc.2000.3285"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Exp. Cell Res." volume="297" first="127" last="141">
            <title>Overexpression of human acyl-CoA thioesterase upregulates peroxisome biogenesis.</title>
            <authorList>
                <person name="Ishizuka M."/>
                <person name="Toyama Y."/>
                <person name="Watanabe H."/>
                <person name="Fujiki Y."/>
                <person name="Takeuchi A."/>
                <person name="Yamasaki S."/>
                <person name="Yuasa S."/>
                <person name="Miyazaki M."/>
                <person name="Nakajima N."/>
                <person name="Taki S."/>
                <person name="Saito T."/>
            </authorList>
            <dbReference type="PubMed" id="15194431"/>
            <dbReference type="DOI" id="10.1016/j.yexcr.2004.02.029"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF HIS-78</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="Prog. Lipid Res." volume="41" first="99" last="130">
            <title>The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism.</title>
            <authorList>
                <person name="Hunt M.C."/>
                <person name="Alexson S.E.H."/>
            </authorList>
            <dbReference type="PubMed" id="11755680"/>
            <dbReference type="DOI" id="10.1016/s0163-7827(01)00017-0"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
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            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2 8 9 10">Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:15194431, PubMed:9153233, PubMed:9299485). Displays no strong substrate specificity with respect to the carboxylic acid moiety of Acyl-CoAs (By similarity). Hydrolyzes medium length (C2 to C20) straight-chain, saturated and unsaturated acyl-CoAS but is inactive towards substrates with longer aliphatic chains (PubMed:9153233, PubMed:9299485). Moreover, it catalyzes the hydrolysis of CoA esters of bile acids, such as choloyl-CoA and chenodeoxycholoyl-CoA and competes with bile acid CoA:amino acid N-acyltransferase (BAAT) (By similarity). Is also able to hydrolyze CoA esters of dicarboxylic acids (By similarity). It is involved in the metabolic regulation of peroxisome proliferation (PubMed:15194431).</text>
    </comment>
    <comment type="function">
        <text evidence="9">(Microbial infection) May mediate Nef-induced down-regulation of CD4 cell-surface expression (PubMed:9153233).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>choloyl-CoA + H2O = cholate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:14541"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29747"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57373"/>
            <dbReference type="EC" id="3.1.2.27"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:14542"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>chenodeoxycholoyl-CoA + H2O = chenodeoxycholate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:31511"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:36234"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62989"/>
            <dbReference type="EC" id="3.1.2.27"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:31512"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 10">
            <text>acetyl-CoA + H2O = acetate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20289"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="EC" id="3.1.2.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:20290"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 10">
            <text>butanoyl-CoA + H2O = butanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40111"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:40112"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>2-methylpropanoyl-CoA + H2O = 2-methylpropanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40799"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:48944"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57338"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:40800"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>hexanoyl-CoA + H2O = hexanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40115"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:40116"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 9 10">
            <text>octanoyl-CoA + H2O = octanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:30144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 9 10">
            <text>decanoyl-CoA + H2O = decanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40059"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:40060"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:30136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 9 10">
            <text>tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40119"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:40120"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 10">
            <text>hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16645"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="EC" id="3.1.2.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:16646"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>octadecanoyl-CoA + H2O = octadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:30139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="16">
            <dbReference type="Rhea" id="RHEA:30140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>malonyl-CoA + H2O = malonate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40219"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15792"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57384"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40220"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>acetoacetyl-CoA + H2O = acetoacetate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:15673"/>
            <dbReference type="ChEBI" id="CHEBI:13705"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57286"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="EC" id="3.1.2.11"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:15674"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>propanoyl-CoA + H2O = propanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40103"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40104"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>succinyl-CoA + H2O = succinate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11516"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30031"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57292"/>
            <dbReference type="EC" id="3.1.2.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:11517"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>glutaryl-CoA + H2O = glutarate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40575"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30921"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57378"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40576"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexanedioyl-CoA + H2O = hexanedioate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40583"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17128"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76327"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40584"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>octanedioyl-CoA + H2O = octanedioate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40587"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76282"/>
            <dbReference type="ChEBI" id="CHEBI:76317"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40588"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>decanedioyl-CoA + H2O = decanedioate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40591"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76283"/>
            <dbReference type="ChEBI" id="CHEBI:76316"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40592"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>dodecanedioyl-CoA + H2O = dodecanedioate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40595"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76273"/>
            <dbReference type="ChEBI" id="CHEBI:76315"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40596"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-tetradecenoyl-CoA + H2O = (9Z)-tetradecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40135"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32370"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65060"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40136"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-hexadecenoyl-CoA + H2O = (9Z)-hexadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40131"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40132"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z,12Z)-octadecadienoyl-CoA + H2O = (9Z,12Z)-octadecadienoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40143"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40144"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>eicosanoyl-CoA + H2O = eicosanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40147"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40148"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40151"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40152"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>4,8-dimethylnonanoyl-CoA + H2O = 4,8-dimethylnonanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40223"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77061"/>
            <dbReference type="ChEBI" id="CHEBI:77063"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:40224"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>2,6-dimethylheptanoyl-CoA + H2O = 2,6-dimethylheptanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59952"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84847"/>
            <dbReference type="ChEBI" id="CHEBI:143533"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:59953"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(3S)-3-hydroxy-3-methylglutaryl-CoA + H2O = 3-hydroxy-3-methylglutarate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:16305"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17325"/>
            <dbReference type="ChEBI" id="CHEBI:43074"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="EC" id="3.1.2.5"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:16306"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-CoA + H2O = 3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59936"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:63001"/>
            <dbReference type="ChEBI" id="CHEBI:85674"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:59937"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>2-methyloctadecanoyl-CoA + H2O = 2-methyloctadecanoate + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59940"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:143530"/>
            <dbReference type="ChEBI" id="CHEBI:143531"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:59941"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>prostaglandin F2alpha-CoA + H2O = prostaglandin F2alpha + CoA + H(+)</text>
            <dbReference type="Rhea" id="RHEA:59948"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57404"/>
            <dbReference type="ChEBI" id="CHEBI:143532"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:59949"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Inhibited by CoASH (IC(50)=10-15 uM). Also inhibited by cysteine-reactive agents.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="9">10.1 uM for decanoyl-CoA</KM>
            <Vmax evidence="9">7.1 umol/min/mg enzyme</Vmax>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="14 16">Lipid metabolism; fatty acid metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Homodimer (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10">(Microbial infection) Interacts with human immunodeficiency virus (HIV-1) Nef (via middle region); this interaction enhances ACOT8 Acyl-CoA thioesterase activity and occurs in a Nef myristoylation-independent manner (PubMed:9299485). According to a second report, the interaction with HIV-1 Nef occurs in a Nef myristoylation-independent manner but does not enhance ACOT8 Acyl-CoA thioesterase activity (PubMed:9153233).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
            <label>CFTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-6269632">
            <id>Q96BR5</id>
            <label>COA7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-3385920">
            <id>Q9Y2H9</id>
            <label>MAST1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-10181968">
            <id>Q7Z4N8</id>
            <label>P4HA3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-597835">
            <id>P50542</id>
            <label>PEX5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-1047946">
            <id>P26045</id>
            <label>PTPN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-307352">
            <id>Q04864</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-10829018">
            <id>Q04864-2</id>
            <label>REL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1237371">
            <id>O14734</id>
        </interactant>
        <interactant intactId="EBI-6164028">
            <id>P04601</id>
            <label>nef</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 8">Peroxisome matrix</location>
        </subcellularLocation>
        <text evidence="6 8">Predominantly localized in the peroxisome but a localization to the cytosol cannot be excluded.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 10">Detected in a T-cell line (at protein level). Ubiquitous (PubMed:9153233, PubMed:9299485).</text>
    </comment>
    <comment type="induction">
        <text evidence="1">Regulated by peroxisome proliferator (such as Clofibrate), via the peroxisome proliferator-activated receptors (PPARs).</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the C/M/P thioester hydrolase family.</text>
    </comment>
    <dbReference type="EC" id="3.1.2.1" evidence="7 10"/>
    <dbReference type="EC" id="3.1.2.11" evidence="2"/>
    <dbReference type="EC" id="3.1.2.2" evidence="9 10"/>
    <dbReference type="EC" id="3.1.2.3" evidence="2"/>
    <dbReference type="EC" id="3.1.2.5" evidence="2"/>
    <dbReference type="EC" id="3.1.2.27" evidence="10"/>
    <dbReference type="EMBL" id="AF014404">
        <property type="protein sequence ID" value="AAB71665.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X86032">
        <property type="protein sequence ID" value="CAA60024.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF124264">
        <property type="protein sequence ID" value="AAD27616.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL008726">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117155">
        <property type="protein sequence ID" value="AAI17156.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117157">
        <property type="protein sequence ID" value="AAI17158.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13378.1"/>
    <dbReference type="PIR" id="JC5644">
        <property type="entry name" value="JC5644"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005460.2">
        <property type="nucleotide sequence ID" value="NM_005469.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O14734"/>
    <dbReference type="SMR" id="O14734"/>
    <dbReference type="BioGRID" id="115323">
        <property type="interactions" value="74"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-38179N"/>
    <dbReference type="FunCoup" id="O14734">
        <property type="interactions" value="589"/>
    </dbReference>
    <dbReference type="IntAct" id="O14734">
        <property type="interactions" value="53"/>
    </dbReference>
    <dbReference type="MINT" id="O14734"/>
    <dbReference type="STRING" id="9606.ENSP00000217455"/>
    <dbReference type="SwissLipids" id="SLP:000000591"/>
    <dbReference type="GlyGen" id="O14734">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O14734"/>
    <dbReference type="PhosphoSitePlus" id="O14734"/>
    <dbReference type="SwissPalm" id="O14734"/>
    <dbReference type="BioMuta" id="ACOT8"/>
    <dbReference type="jPOST" id="O14734"/>
    <dbReference type="MassIVE" id="O14734"/>
    <dbReference type="PaxDb" id="9606-ENSP00000217455"/>
    <dbReference type="PeptideAtlas" id="O14734"/>
    <dbReference type="ProteomicsDB" id="48196"/>
    <dbReference type="Pumba" id="O14734"/>
    <dbReference type="Antibodypedia" id="4138">
        <property type="antibodies" value="247 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10005"/>
    <dbReference type="Ensembl" id="ENST00000217455.9">
        <property type="protein sequence ID" value="ENSP00000217455.4"/>
        <property type="gene ID" value="ENSG00000101473.18"/>
    </dbReference>
    <dbReference type="GeneID" id="10005"/>
    <dbReference type="KEGG" id="hsa:10005"/>
    <dbReference type="MANE-Select" id="ENST00000217455.9">
        <property type="protein sequence ID" value="ENSP00000217455.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005469.4"/>
        <property type="RefSeq protein sequence ID" value="NP_005460.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002xqa.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15919"/>
    <dbReference type="ClinPGx" id="PA33941"/>
    <dbReference type="CTD" id="10005"/>
    <dbReference type="DisGeNET" id="10005"/>
    <dbReference type="GeneCards" id="ACOT8"/>
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            <begin position="1"/>
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    <accession>Q6ICK2</accession>
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            <fullName>Acrosin</fullName>
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                <fullName>Acrosin light chain</fullName>
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        <component>
            <recommendedName>
                <fullName>Acrosin heavy chain</fullName>
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    <gene>
        <name type="primary">ACR</name>
        <name type="synonym">ACRS</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="FEBS Lett." volume="244" first="296" last="300">
            <title>Primary structure of human proacrosin deduced from its cDNA sequence.</title>
            <authorList>
                <person name="Baba T."/>
                <person name="Watanabe K."/>
                <person name="Kashiwabara S."/>
                <person name="Arai Y."/>
            </authorList>
            <dbReference type="PubMed" id="2493394"/>
            <dbReference type="DOI" id="10.1016/0014-5793(89)80549-6"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1990" name="Eur. J. Biochem." volume="190" first="195" last="200">
            <title>Nucleotide sequence and exon-intron organization of the human proacrosin gene.</title>
            <authorList>
                <person name="Keime S."/>
                <person name="Adham I.M."/>
                <person name="Engel W."/>
            </authorList>
            <dbReference type="PubMed" id="2114285"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1990.tb15564.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Leukocyte</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1990" name="Hum. Genet." volume="84" first="125" last="128">
            <title>Molecular cloning of human preproacrosin cDNA.</title>
            <authorList>
                <person name="Adham I.M."/>
                <person name="Klemm U."/>
                <person name="Maier W.-M."/>
                <person name="Engel W."/>
            </authorList>
            <dbReference type="PubMed" id="2298447"/>
            <dbReference type="DOI" id="10.1007/bf00208925"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1992" name="Eur. J. Biochem." volume="207" first="23" last="26">
            <title>Molecular cloning, sequencing and restriction mapping of the genomic sequence encoding human proacrosin.</title>
            <authorList>
                <person name="Vazquez-Levin M.H."/>
                <person name="Reventos J."/>
                <person name="Gordon J.W."/>
            </authorList>
            <dbReference type="PubMed" id="1628652"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1992.tb17014.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1992" name="Eur. J. Biochem." volume="207" first="27" last="28">
            <authorList>
                <person name="Adham I.M."/>
                <person name="Spitzer U."/>
                <person name="Schloesser M."/>
                <person name="Kremling H."/>
                <person name="Keime S."/>
                <person name="Engel W."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:1628652</scope>
        <scope>DISCUSSION OF PUBMED:1628652</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R84.1" last="R84.11">
            <title>A genome annotation-driven approach to cloning the human ORFeome.</title>
            <authorList>
                <person name="Collins J.E."/>
                <person name="Wright C.L."/>
                <person name="Edwards C.A."/>
                <person name="Davis M.P."/>
                <person name="Grinham J.A."/>
                <person name="Cole C.G."/>
                <person name="Goward M.E."/>
                <person name="Aguado B."/>
                <person name="Mallya M."/>
                <person name="Mokrab Y."/>
                <person name="Huckle E.J."/>
                <person name="Beare D.M."/>
                <person name="Dunham I."/>
            </authorList>
            <dbReference type="PubMed" id="15461802"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-10-r84"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1994" name="Am. J. Physiol." volume="267" first="C466" last="C472">
            <title>Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa.</title>
            <authorList>
                <person name="Zheng X."/>
                <person name="Geiger M."/>
                <person name="Ecke S."/>
                <person name="Bielek E."/>
                <person name="Donner P."/>
                <person name="Eberspacher U."/>
                <person name="Schleuning W.D."/>
                <person name="Binder B.R."/>
            </authorList>
            <dbReference type="PubMed" id="7521127"/>
            <dbReference type="DOI" id="10.1152/ajpcell.1994.267.2.c466"/>
        </citation>
        <scope>ACTIVITY REGULATION</scope>
        <scope>HETERODIMER WITH SERPINA5</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2002" name="J. Reprod. Immunol." volume="54" first="43" last="63">
            <title>Evaluation of the proacrosin/acrosin system and its mechanism of activation in human sperm extracts.</title>
            <authorList>
                <person name="Zahn A."/>
                <person name="Furlong L.I."/>
                <person name="Biancotti J.C."/>
                <person name="Ghiringhelli P.D."/>
                <person name="Marijn-Briggiler C.I."/>
                <person name="Vazquez-Levin M.H."/>
            </authorList>
            <dbReference type="PubMed" id="11839395"/>
            <dbReference type="DOI" id="10.1016/s0165-0378(01)00080-8"/>
        </citation>
        <scope>PROPEPTIDE</scope>
        <scope>ACTIVATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2023" name="Hum. Reprod." volume="38" first="1213" last="1223">
            <title>ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida.</title>
            <authorList>
                <person name="Hua R."/>
                <person name="Xue R."/>
                <person name="Liu Y."/>
                <person name="Li Y."/>
                <person name="Sha X."/>
                <person name="Li K."/>
                <person name="Gao Y."/>
                <person name="Shen Q."/>
                <person name="Lv M."/>
                <person name="Xu Y."/>
                <person name="Zhang Z."/>
                <person name="He X."/>
                <person name="Cao Y."/>
                <person name="Wu H."/>
            </authorList>
            <dbReference type="PubMed" id="37004249"/>
            <dbReference type="DOI" id="10.1093/humrep/dead059"/>
        </citation>
        <scope>INVOLVEMENT IN SPGF87</scope>
        <scope>VARIANT SPGF87 56-TRP--SER-421 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT SPGF87 56-TRP--SER-421 DEL</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Acrosin is the major protease of mammalian spermatozoa. It is a serine protease of trypsin-like cleavage specificity, it is synthesized in a zymogen form, proacrosin and stored in the acrosome.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.</text>
            <dbReference type="EC" id="3.4.21.10"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="5">Inhibited by SERPINA5.</text>
    </comment>
    <comment type="subunit">
        <text>Heavy chain (catalytic) and a light chain linked by two disulfide bonds. Forms a heterodimer with SERPINA5.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21280149">
            <id>P10323</id>
        </interactant>
        <interactant intactId="EBI-1755919">
            <id>Q05996</id>
            <label>ZP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21280149">
            <id>P10323</id>
        </interactant>
        <interactant intactId="EBI-11783624">
            <id>P21754</id>
            <label>ZP3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21280149">
            <id>P10323</id>
        </interactant>
        <interactant intactId="EBI-11783805">
            <id>Q12836</id>
            <label>ZP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-06756">
            <name>Spermatogenic failure 87</name>
            <acronym>SPGF87</acronym>
            <description>An autosomal recessive male infertility disorder characterized by inability of mutant sperm to penetrate the zona pellucida, resulting in fertilization failure.</description>
            <dbReference type="MIM" id="620500"/>
        </disease>
        <text>The disease may be caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the peptidase S1 family.</text>
    </comment>
    <dbReference type="EC" id="3.4.21.10"/>
    <dbReference type="EMBL" id="Y00970">
        <property type="protein sequence ID" value="CAA68784.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54017">
        <property type="protein sequence ID" value="CAA37964.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54018">
        <property type="protein sequence ID" value="CAA37964.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54019">
        <property type="protein sequence ID" value="CAA37964.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="X54020">
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M77378">
        <property type="protein sequence ID" value="AAA51572.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M77379">
        <property type="protein sequence ID" value="AAA51573.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M77380">
        <property type="protein sequence ID" value="AAA51574.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M77381">
        <property type="protein sequence ID" value="AAA51575.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X66188">
        <property type="protein sequence ID" value="CAA46956.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54018">
        <property type="protein sequence ID" value="CAA46956.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54019">
        <property type="protein sequence ID" value="CAA46956.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X54020">
        <property type="protein sequence ID" value="CAA46956.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456366">
        <property type="protein sequence ID" value="CAG30252.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14101.1"/>
    <dbReference type="PIR" id="S11674">
        <property type="entry name" value="S11674"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001088.2">
        <property type="nucleotide sequence ID" value="NM_001097.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P10323"/>
    <dbReference type="SMR" id="P10323"/>
    <dbReference type="BioGRID" id="106565">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="P10323">
        <property type="interactions" value="103"/>
    </dbReference>
    <dbReference type="IntAct" id="P10323">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000216139"/>
    <dbReference type="BindingDB" id="P10323"/>
    <dbReference type="ChEMBL" id="CHEMBL2738"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="2327"/>
    <dbReference type="MEROPS" id="S01.223"/>
    <dbReference type="GlyCosmos" id="P10323">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P10323">
        <property type="glycosylation" value="4 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="BioMuta" id="ACR"/>
    <dbReference type="DMDM" id="115502349"/>
    <dbReference type="jPOST" id="P10323"/>
    <dbReference type="MassIVE" id="P10323"/>
    <dbReference type="PaxDb" id="9606-ENSP00000216139"/>
    <dbReference type="PeptideAtlas" id="P10323"/>
    <dbReference type="ProteomicsDB" id="52600"/>
    <dbReference type="Antibodypedia" id="53952">
        <property type="antibodies" value="196 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="49"/>
    <dbReference type="Ensembl" id="ENST00000216139.10">
        <property type="protein sequence ID" value="ENSP00000216139.5"/>
        <property type="gene ID" value="ENSG00000100312.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000707314.1">
        <property type="protein sequence ID" value="ENSP00000516837.1"/>
        <property type="gene ID" value="ENSG00000291368.1"/>
    </dbReference>
    <dbReference type="GeneID" id="49"/>
    <dbReference type="KEGG" id="hsa:49"/>
    <dbReference type="MANE-Select" id="ENST00000216139.10">
        <property type="protein sequence ID" value="ENSP00000216139.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001097.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001088.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003bnh.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:126"/>
    <dbReference type="ClinPGx" id="PA24451"/>
    <dbReference type="CTD" id="49"/>
    <dbReference type="DisGeNET" id="49"/>
    <dbReference type="GeneCards" id="ACR"/>
    <dbReference type="HGNC" id="HGNC:126">
        <property type="gene designation" value="ACR"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000100312">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACR"/>
    <dbReference type="MIM" id="102480">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="620500">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000100312"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000100312"/>
    <dbReference type="eggNOG" id="KOG3627">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162430"/>
    <dbReference type="InParanoid" id="P10323"/>
    <dbReference type="OMA" id="LMCRDNV"/>
    <dbReference type="OrthoDB" id="6339452at2759"/>
    <dbReference type="PAN-GO" id="P10323">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P10323"/>
    <dbReference type="BRENDA" id="3.4.21.10">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P10323"/>
    <dbReference type="Reactome" id="R-HSA-1300645">
        <property type="pathway name" value="Acrosome Reaction and Sperm:Oocyte Membrane Binding"/>
    </dbReference>
    <dbReference type="SignaLink" id="P10323"/>
    <dbReference type="Agora" id="ENSG00000100312"/>
    <dbReference type="BioGRID-ORCS" id="49">
        <property type="hits" value="31 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="Acrosin"/>
    <dbReference type="GenomeRNAi" id="49"/>
    <dbReference type="Pharos" id="P10323">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P10323"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="P10323">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000100312">
        <property type="expression patterns" value="Expressed in left testis and 85 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P10323">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043159">
        <property type="term" value="C:acrosomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005798">
        <property type="term" value="C:Golgi-associated vesicle"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032991">
        <property type="term" value="C:protein-containing complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004040">
        <property type="term" value="F:amidase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005507">
        <property type="term" value="F:copper ion binding"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005537">
        <property type="term" value="F:D-mannose binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042806">
        <property type="term" value="F:fucose binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002020">
        <property type="term" value="F:protease binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004252">
        <property type="term" value="F:serine-type endopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008236">
        <property type="term" value="F:serine-type peptidase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002077">
        <property type="term" value="P:acrosome matrix dispersal"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007340">
        <property type="term" value="P:acrosome reaction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007190">
        <property type="term" value="P:activation of adenylate cyclase activity"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007339">
        <property type="term" value="P:binding of sperm to zona pellucida"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007341">
        <property type="term" value="P:penetration of zona pellucida"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048545">
        <property type="term" value="P:response to steroid hormone"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007338">
        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd00190">
        <property type="entry name" value="Tryp_SPc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.10.10:FF:000003">
        <property type="entry name" value="Transmembrane serine protease 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.10.10">
        <property type="entry name" value="Trypsin-like serine proteases"/>
        <property type="match status" value="2"/>
    </dbReference>
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        <property type="entry name" value="Pept_S1A_acrosin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009003">
        <property type="entry name" value="Peptidase_S1_PA"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043504">
        <property type="entry name" value="Peptidase_S1_PA_chymotrypsin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001314">
        <property type="entry name" value="Peptidase_S1A"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001254">
        <property type="entry name" value="Trypsin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018114">
        <property type="entry name" value="TRYPSIN_HIS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033116">
        <property type="entry name" value="TRYPSIN_SER"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24252:SF8">
        <property type="entry name" value="ACROSIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24252">
        <property type="entry name" value="ACROSIN-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00089">
        <property type="entry name" value="Trypsin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF001141">
        <property type="entry name" value="Acrosin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00722">
        <property type="entry name" value="CHYMOTRYPSIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00020">
        <property type="entry name" value="Tryp_SPc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50494">
        <property type="entry name" value="Trypsin-like serine proteases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50240">
        <property type="entry name" value="TRYPSIN_DOM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00134">
        <property type="entry name" value="TRYPSIN_HIS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00135">
        <property type="entry name" value="TRYPSIN_SER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0720">Serine protease</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000027518" description="Acrosin">
        <location>
            <begin position="20"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000027519" description="Acrosin light chain">
        <location>
            <begin position="20"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000027520" description="Acrosin heavy chain">
        <location>
            <begin position="43"/>
            <end position="343"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000027521" description="Pro-rich" evidence="6">
        <location>
            <begin position="344"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase S1" evidence="2">
        <location>
            <begin position="43"/>
            <end position="290"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="297"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="327"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="397"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="3">
        <location>
            <begin position="301"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="3">
        <location>
            <begin position="328"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="397"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="412"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="88"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="active site" description="Charge relay system" evidence="1">
        <location>
            <position position="240"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="1">
        <location>
            <position position="210"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (between light and heavy chains)" evidence="2">
        <location>
            <begin position="25"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain (between light and heavy chains)" evidence="2">
        <location>
            <begin position="29"/>
            <end position="162"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="73"/>
            <end position="89"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="177"/>
            <end position="246"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="209"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="236"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088987" description="In SPGF87; likely pathogenic; loss of protein expression in patient sperm." evidence="4">
        <location>
            <begin position="56"/>
            <end position="421"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011650" description="In dbSNP:rs1064734.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011651" description="In dbSNP:rs1064735.">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2 and 4." evidence="6" ref="2 4">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3." evidence="6" ref="3">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2 and 4." evidence="6" ref="2 4">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="268"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; CAG30252." evidence="6" ref="6">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2, 3 and 4." evidence="6" ref="2 3 4">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00274"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="37004249"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="7521127"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="421" mass="45847" checksum="7A2F7ECEC98008FA" modified="2006-10-03" version="4" precursor="true">MVEMLPTAILLVLAVSVVAKDNATCDGPCGLRFRQNPQGGVRIVGGKAAQHGAWPWMVSLQIFTYNSHRYHTCGGSLLNSRWVLTAAHCFVGKNNVHDWRLVFGAKEITYGNNKPVKAPLQERYVEKIIIHEKYNSATEGNDIALVEITPPISCGRFIGPGCLPHFKAGLPRGSQSCWVAGWGYIEEKAPRPSSILMEARVDLIDLDLCNSTQWYNGRVQPTNVCAGYPVGKIDTCQGDSGGPLMCKDSKESAYVVVGITSWGVGCARAKRPGIYTATWPYLNWIASKIGSNALRMIQSATPPPPTTRPPPIRPPFSHPISAHLPWYFQPPPRPLPPRPPAAQPRPPPSPPPPPPPPASPLPPPPPPPPPTPSSTTKLPQGLSFAKRLQQLIEVLKGKTYSDGKNHYDMETTELPELTSTS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="133" xmlns="https://uniprot.org/uniprot">
    <accession>Q08AH3</accession>
    <accession>B3KTT9</accession>
    <accession>O75202</accession>
    <name>ACS2A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM2A, mitochondrial</fullName>
            <ecNumber evidence="1">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 2A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Benzoate--CoA ligase</fullName>
            <ecNumber evidence="1">6.2.1.25</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Butyrate--CoA ligase 2A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Butyryl-coenzyme A synthetase 2A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Middle-chain acyl-CoA synthetase 2A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM2A</name>
        <name type="synonym">ACSM2</name>
        <name type="synonym">MACS2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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    </reference>
    <comment type="function">
        <text evidence="1">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (By similarity). Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>benzoate + ATP + CoA = benzoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:10132"/>
            <dbReference type="ChEBI" id="CHEBI:16150"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57369"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.25"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:10133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>hexanoate + ATP + CoA = hexanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:43740"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:43741"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46172"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:46173"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:33632"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>decanoate + ATP + CoA = decanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33627"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:33628"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6 7">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="6 7">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAC23497" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="1"/>
    <dbReference type="EC" id="6.2.1.25" evidence="1"/>
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        <property type="protein sequence ID" value="BAG53201.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC137056">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125176">
        <property type="protein sequence ID" value="AAI25177.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC003034">
        <property type="protein sequence ID" value="AAC23497.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32401.1"/>
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        <property type="nucleotide sequence ID" value="NM_001308172.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001295883.1">
        <property type="nucleotide sequence ID" value="NM_001308954.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016878412.1">
        <property type="nucleotide sequence ID" value="XM_017022923.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289547.1">
        <property type="nucleotide sequence ID" value="XM_047433591.1"/>
    </dbReference>
    <dbReference type="PDB" id="2VZE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.45 A"/>
        <property type="chains" value="A/B/C=32-577"/>
    </dbReference>
    <dbReference type="PDB" id="2WD9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B/C=32-576"/>
    </dbReference>
    <dbReference type="PDB" id="3B7W">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=32-577"/>
    </dbReference>
    <dbReference type="PDB" id="3C5E">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A=32-577"/>
    </dbReference>
    <dbReference type="PDB" id="3DAY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.95 A"/>
        <property type="chains" value="A=32-577"/>
    </dbReference>
    <dbReference type="PDB" id="3EQ6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B=32-577"/>
    </dbReference>
    <dbReference type="PDB" id="3GPC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B=32-577"/>
    </dbReference>
    <dbReference type="PDBsum" id="2VZE"/>
    <dbReference type="PDBsum" id="2WD9"/>
    <dbReference type="PDBsum" id="3B7W"/>
    <dbReference type="PDBsum" id="3C5E"/>
    <dbReference type="PDBsum" id="3DAY"/>
    <dbReference type="PDBsum" id="3EQ6"/>
    <dbReference type="PDBsum" id="3GPC"/>
    <dbReference type="AlphaFoldDB" id="Q08AH3"/>
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    <dbReference type="BioGRID" id="125840">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q08AH3">
        <property type="interactions" value="28"/>
    </dbReference>
    <dbReference type="IntAct" id="Q08AH3">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="Q08AH3"/>
    <dbReference type="STRING" id="9606.ENSP00000459451"/>
    <dbReference type="GlyGen" id="Q08AH3">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q08AH3"/>
    <dbReference type="PhosphoSitePlus" id="Q08AH3"/>
    <dbReference type="BioMuta" id="ACSM2A"/>
    <dbReference type="DMDM" id="257050995"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000459451"/>
    <dbReference type="PeptideAtlas" id="Q08AH3"/>
    <dbReference type="ProteomicsDB" id="58672"/>
    <dbReference type="Antibodypedia" id="67877">
        <property type="antibodies" value="85 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="123876"/>
    <dbReference type="Ensembl" id="ENST00000219054.10">
        <property type="protein sequence ID" value="ENSP00000219054.6"/>
        <property type="gene ID" value="ENSG00000183747.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000396104.2">
        <property type="protein sequence ID" value="ENSP00000379411.2"/>
        <property type="gene ID" value="ENSG00000183747.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000573854.6">
        <property type="protein sequence ID" value="ENSP00000459451.1"/>
        <property type="gene ID" value="ENSG00000183747.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000575690.5">
        <property type="protein sequence ID" value="ENSP00000460349.1"/>
        <property type="gene ID" value="ENSG00000183747.13"/>
    </dbReference>
    <dbReference type="GeneID" id="123876"/>
    <dbReference type="KEGG" id="hsa:123876"/>
    <dbReference type="MANE-Select" id="ENST00000573854.6">
        <property type="protein sequence ID" value="ENSP00000459451.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001308172.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001295101.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002dhf.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32017"/>
    <dbReference type="ClinPGx" id="PA162375402"/>
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    <dbReference type="GeneCards" id="ACSM2A"/>
    <dbReference type="HGNC" id="HGNC:32017">
        <property type="gene designation" value="ACSM2A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000183747">
        <property type="expression patterns" value="Group enriched (kidney, liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614358">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000183747"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000183747"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000164294"/>
    <dbReference type="InParanoid" id="Q08AH3"/>
    <dbReference type="OMA" id="MGPTRKG"/>
    <dbReference type="OrthoDB" id="6614653at2759"/>
    <dbReference type="PAN-GO" id="Q08AH3">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q08AH3"/>
    <dbReference type="PathwayCommons" id="Q08AH3"/>
    <dbReference type="Reactome" id="R-HSA-177128">
        <property type="pathway name" value="Conjugation of salicylate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9749641">
        <property type="pathway name" value="Aspirin ADME"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q08AH3"/>
    <dbReference type="Agora" id="ENSG00000183747"/>
    <dbReference type="BioGRID-ORCS" id="123876">
        <property type="hits" value="7 hits in 1097 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM2A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q08AH3"/>
    <dbReference type="GenomeRNAi" id="123876"/>
    <dbReference type="Pharos" id="Q08AH3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q08AH3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q08AH3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000183747">
        <property type="expression patterns" value="Expressed in right lobe of liver and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q08AH3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
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        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018858">
        <property type="term" value="F:benzoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0102391">
        <property type="term" value="F:decanoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031956">
        <property type="term" value="F:medium-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
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        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
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        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042593">
        <property type="term" value="P:glucose homeostasis"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036112">
        <property type="term" value="P:medium-chain fatty-acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070328">
        <property type="term" value="P:triglyceride homeostasis"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM5, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
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        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM2A, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000306093" description="Acyl-coenzyme A synthetase ACSM2A, mitochondrial">
        <location>
            <begin position="47"/>
            <end position="577"/>
        </location>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="139"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 7">
        <location>
            <begin position="221"/>
            <end position="229"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 7">
        <location>
            <begin position="359"/>
            <end position="364"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="364"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 7">
        <location>
            <position position="446"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6 7">
        <location>
            <position position="461"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <begin position="469"/>
            <end position="471"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="472"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="501"/>
        </location>
        <ligand>
            <name>CoA</name>
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            <position position="532"/>
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        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
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        <ligand>
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    <feature type="binding site" evidence="6 7">
        <location>
            <position position="557"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="513"/>
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            <position position="335"/>
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    <feature type="sequence variant" id="VAR_058694" description="In dbSNP:rs4586421.">
        <original>V</original>
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            <position position="337"/>
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    <feature type="sequence variant" id="VAR_035247" description="In dbSNP:rs1133607." evidence="3 4 5">
        <original>S</original>
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            <position position="513"/>
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    <feature type="sequence variant" id="VAR_035248" description="In dbSNP:rs1054977.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="561"/>
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    <feature type="sequence conflict" description="In Ref. 1; BAG53201, 3; AAI25177 and 4; AAC23497." evidence="8" ref="1 3 4">
        <original>N</original>
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            <position position="463"/>
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            <begin position="34"/>
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    <sequence length="577" mass="64223" checksum="16167FC69562436F" modified="2009-09-01" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-03-07" modified="2026-01-28" version="151" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NEB7</accession>
    <accession>Q9BY87</accession>
    <name>ACRBP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acrosin-binding protein</fullName>
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        <alternativeName>
            <fullName>Acrosin-binding protein, 60 kDa form</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Cancer/testis antigen 23</fullName>
            <shortName>CT23</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Cancer/testis antigen OY-TES-1</fullName>
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        <alternativeName>
            <fullName>Proacrosin-binding protein sp32</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Acrosin-binding protein, mature form</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>Acrosin-binding protein, 32 kDa form, mature form</fullName>
            </alternativeName>
        </component>
    </protein>
    <gene>
        <name evidence="8" type="primary">ACRBP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="7 9" key="1">
        <citation type="journal article" date="2001" name="Proc. Natl. Acad. Sci. U.S.A." volume="98" first="3282" last="3287">
            <title>Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.</title>
            <authorList>
                <person name="Ono T."/>
                <person name="Kurashige T."/>
                <person name="Harada N."/>
                <person name="Noguchi Y."/>
                <person name="Saika T."/>
                <person name="Niikawa N."/>
                <person name="Aoe M."/>
                <person name="Nakamura S."/>
                <person name="Higashi T."/>
                <person name="Hiraki A."/>
                <person name="Wada H."/>
                <person name="Kumon H."/>
                <person name="Old L.J."/>
                <person name="Nakayama E."/>
            </authorList>
            <dbReference type="PubMed" id="11248070"/>
            <dbReference type="DOI" id="10.1073/pnas.041625098"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue evidence="9">Testis</tissue>
        </source>
    </reference>
    <reference evidence="8" key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue evidence="8">Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <molecule>Acrosin-binding protein, mature form</molecule>
        <text evidence="2">Acrosomal protein that maintains proacrosin (pro-ACR) as an enzymatically inactive zymogen in the acrosome. Involved also in the acrosome formation.</text>
    </comment>
    <comment type="subunit">
        <molecule>Acrosin-binding protein, mature form</molecule>
        <text evidence="1">Binds proacrosin (pro-ACR). Does not bind the mature form of ACR.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Secreted</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1 2">Cytoplasmic vesicle</location>
            <location evidence="1 2">Secretory vesicle</location>
            <location evidence="1 2">Acrosome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expression restricted to testis in normal tissue. Expressed in a wide spectrum of cancers, including bladder, breast, liver, lung and colon cancers.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated on Tyr residues in capacitated sperm.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The N-terminus is blocked.</text>
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    <comment type="PTM">
        <text evidence="1">Synthesized as a 60-kDa precursor, the 32-kDa mature form is post-translationally produced by the removal of the N-terminal half of the precursor during sperm maturation in the testis and/or epididymis.</text>
    </comment>
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR21362:SF1">
        <property type="entry name" value="ACROSIN-BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07222">
        <property type="entry name" value="PBP_sp32"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF100895">
        <property type="entry name" value="Kazal-type serine protease inhibitors"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000227516" description="Acrosin-binding protein">
        <location>
            <begin position="26"/>
            <end position="543"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000449367" description="Removed in mature form" evidence="1">
        <location>
            <begin position="26"/>
            <end position="273"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000449368" description="Acrosin-binding protein, mature form">
        <location>
            <begin position="274"/>
            <end position="543"/>
        </location>
    </feature>
    <feature type="region of interest" description="Pro-ACR binding" evidence="2">
        <location>
            <begin position="26"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="185"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="region of interest" description="Pro-ACR binding" evidence="2">
        <location>
            <begin position="319"/>
            <end position="427"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="192"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="4">
        <location>
            <begin position="221"/>
            <end position="231"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="232"/>
            <end position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050633" description="In dbSNP:rs3741923.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB39388." evidence="7" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB39388." evidence="7" ref="1">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q29016"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3V140"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11248070"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="11248070"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="EMBL" id="AAH33010.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="EMBL" id="BAB39388.1"/>
        </source>
    </evidence>
    <sequence length="543" mass="61359" checksum="44D0F23583522DD9" modified="2002-10-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="153" xmlns="https://uniprot.org/uniprot">
    <accession>Q68CK6</accession>
    <accession>Q86YT1</accession>
    <name>ACS2B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM2B, mitochondrial</fullName>
            <ecNumber evidence="3">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 2B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Benzoate--CoA ligase</fullName>
            <ecNumber evidence="3 4">6.2.1.25</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Butyrate--CoA ligase 2B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Butyryl-coenzyme A synthetase 2B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Middle-chain acyl-CoA synthetase 2B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Xenobiotic/medium-chain fatty acid-CoA ligase HXM-A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM2B</name>
        <name type="synonym">ACSM2</name>
        <name type="ORF">HYST1046</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Isolation, sequencing, and expression of a cDNA for the HXM-A form of xenobiotic/medium-chain fatty acid:CoA ligase from human liver mitochondria.</title>
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                <person name="Vessey D.A."/>
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            </authorList>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 152-163 AND 483-491</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Oncogene" volume="23" first="5901" last="5911">
            <title>Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.</title>
            <authorList>
                <person name="Yamada S."/>
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                <person name="Ando H."/>
                <person name="Suita S."/>
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            </authorList>
            <dbReference type="PubMed" id="15221005"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="432" first="988" last="994">
            <title>The sequence and analysis of duplication-rich human chromosome 16.</title>
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                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Parson-Quintana B."/>
                <person name="Ramirez L."/>
                <person name="Rash S."/>
                <person name="Retterer J."/>
                <person name="Ricke D.O."/>
                <person name="Robinson D.L."/>
                <person name="Rodriguez A."/>
                <person name="Salamov A."/>
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                <person name="Scott D."/>
                <person name="Shough T."/>
                <person name="Stallings R.L."/>
                <person name="Stalvey M."/>
                <person name="Sutherland R.D."/>
                <person name="Tapia R."/>
                <person name="Tesmer J.G."/>
                <person name="Thayer N."/>
                <person name="Thompson L.S."/>
                <person name="Tice H."/>
                <person name="Torney D.C."/>
                <person name="Tran-Gyamfi M."/>
                <person name="Tsai M."/>
                <person name="Ulanovsky L.E."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="White P.S."/>
                <person name="Williams A.L."/>
                <person name="Wills P.L."/>
                <person name="Wu J.-R."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="DeJong P."/>
                <person name="Bruce D."/>
                <person name="Doggett N.A."/>
                <person name="Deaven L."/>
                <person name="Schmutz J."/>
                <person name="Grimwood J."/>
                <person name="Richardson P."/>
                <person name="Rokhsar D.S."/>
                <person name="Eichler E.E."/>
                <person name="Gilna P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
                <person name="Pennacchio L.A."/>
            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1999" name="Biochim. Biophys. Acta" volume="1428" first="455" last="462">
            <title>Characterization of the CoA ligases of human liver mitochondria catalyzing the activation of short- and medium-chain fatty acids and xenobiotic carboxylic acids.</title>
            <authorList>
                <person name="Vessey D.A."/>
                <person name="Kelley M."/>
                <person name="Warren R.S."/>
            </authorList>
            <dbReference type="PubMed" id="10434065"/>
            <dbReference type="DOI" id="10.1016/s0304-4165(99)00088-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="5">
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            <title>Comparative analyses of disease risk genes belonging to the acyl-CoA synthetase medium-chain (ACSM) family in human liver and cell lines.</title>
            <authorList>
                <person name="Boomgaarden I."/>
                <person name="Vock C."/>
                <person name="Klapper M."/>
                <person name="Doering F."/>
            </authorList>
            <dbReference type="PubMed" id="19634011"/>
            <dbReference type="DOI" id="10.1007/s10528-009-9273-z"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="6">
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-513</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="7">
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            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
            <authorList>
                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (PubMed:10434065, PubMed:12616642). Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate (PubMed:10434065, PubMed:12616642).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4">
            <text>benzoate + ATP + CoA = benzoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:10132"/>
            <dbReference type="ChEBI" id="CHEBI:16150"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57369"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.25"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8 9">
            <dbReference type="Rhea" id="RHEA:10133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>hexanoate + ATP + CoA = hexanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:43740"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:43741"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46172"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:46173"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:33632"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>decanoate + ATP + CoA = decanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33627"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:33628"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="3">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Activated by monovalent cations, such as potassium, rubidium or ammonium.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">13 uM for benzoate</KM>
            <KM evidence="3">800 uM for butyrate</KM>
            <KM evidence="3">110 uM for decanoate</KM>
            <KM evidence="3">74 uM for hexanoate</KM>
            <KM evidence="3">60 uM for laurate</KM>
            <KM evidence="3">160 uM for phenylacetate</KM>
            <KM evidence="3">7.4 uM for salicylate</KM>
            <Vmax evidence="3">103.0 nmol/min/mg enzyme for benzoate</Vmax>
            <Vmax evidence="3">27.0 nmol/min/mg enzyme for butyrate</Vmax>
            <Vmax evidence="3">15.0 nmol/min/mg enzyme for decanoate</Vmax>
            <Vmax evidence="3">88.0 nmol/min/mg enzyme for hexanoate</Vmax>
            <Vmax evidence="3">0.2 nmol/min/mg enzyme for laurate</Vmax>
            <Vmax evidence="3">29.0 nmol/min/mg enzyme for phenylacetate</Vmax>
            <Vmax evidence="3">0.7 nmol/min/mg enzyme for salicylate</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="3">Optimum pH is 8.8.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="4">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880280">
            <id>Q68CK6</id>
        </interactant>
        <interactant intactId="EBI-739552">
            <id>P43364</id>
            <label>MAGEA11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3 4 5">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 5">Detected in liver.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="3"/>
    <dbReference type="EC" id="6.2.1.25" evidence="3 4"/>
    <dbReference type="EMBL" id="AY160217">
        <property type="protein sequence ID" value="AAO17576.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB073604">
        <property type="protein sequence ID" value="BAD38642.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC141053">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC141273">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10586.1"/>
    <dbReference type="RefSeq" id="NP_001098539.1">
        <property type="nucleotide sequence ID" value="NM_001105069.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_872423.3">
        <property type="nucleotide sequence ID" value="NM_182617.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q68CK6"/>
    <dbReference type="SMR" id="Q68CK6"/>
    <dbReference type="BioGRID" id="131510">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q68CK6">
        <property type="interactions" value="27"/>
    </dbReference>
    <dbReference type="IntAct" id="Q68CK6">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000327453"/>
    <dbReference type="SwissLipids" id="SLP:000001827"/>
    <dbReference type="iPTMnet" id="Q68CK6"/>
    <dbReference type="PhosphoSitePlus" id="Q68CK6"/>
    <dbReference type="BioMuta" id="ACSM2B"/>
    <dbReference type="DMDM" id="296434397"/>
    <dbReference type="jPOST" id="Q68CK6"/>
    <dbReference type="MassIVE" id="Q68CK6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000327453"/>
    <dbReference type="PeptideAtlas" id="Q68CK6"/>
    <dbReference type="ProteomicsDB" id="66005"/>
    <dbReference type="Antibodypedia" id="55971">
        <property type="antibodies" value="3 antibodies from 3 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="348158"/>
    <dbReference type="Ensembl" id="ENST00000329697.10">
        <property type="protein sequence ID" value="ENSP00000327453.6"/>
        <property type="gene ID" value="ENSG00000066813.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000414188.6">
        <property type="protein sequence ID" value="ENSP00000390378.3"/>
        <property type="gene ID" value="ENSG00000066813.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000565232.5">
        <property type="protein sequence ID" value="ENSP00000454995.1"/>
        <property type="gene ID" value="ENSG00000066813.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000567001.5">
        <property type="protein sequence ID" value="ENSP00000456378.1"/>
        <property type="gene ID" value="ENSG00000066813.15"/>
    </dbReference>
    <dbReference type="GeneID" id="348158"/>
    <dbReference type="KEGG" id="hsa:348158"/>
    <dbReference type="MANE-Select" id="ENST00000329697.10">
        <property type="protein sequence ID" value="ENSP00000327453.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001105069.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001098539.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002dhj.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30931"/>
    <dbReference type="ClinPGx" id="PA162375437"/>
    <dbReference type="CTD" id="348158"/>
    <dbReference type="DisGeNET" id="348158"/>
    <dbReference type="GeneCards" id="ACSM2B"/>
    <dbReference type="HGNC" id="HGNC:30931">
        <property type="gene designation" value="ACSM2B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000066813">
        <property type="expression patterns" value="Group enriched (kidney, liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614359">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000066813"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000066813"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000164294"/>
    <dbReference type="InParanoid" id="Q68CK6"/>
    <dbReference type="OMA" id="GPVGCRY"/>
    <dbReference type="OrthoDB" id="6614653at2759"/>
    <dbReference type="PAN-GO" id="Q68CK6">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q68CK6"/>
    <dbReference type="PathwayCommons" id="Q68CK6"/>
    <dbReference type="Reactome" id="R-HSA-177128">
        <property type="pathway name" value="Conjugation of salicylate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-177135">
        <property type="pathway name" value="Conjugation of benzoate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-177162">
        <property type="pathway name" value="Conjugation of phenylacetate with glutamine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9749641">
        <property type="pathway name" value="Aspirin ADME"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q68CK6"/>
    <dbReference type="SignaLink" id="Q68CK6"/>
    <dbReference type="Agora" id="ENSG00000066813"/>
    <dbReference type="BioGRID-ORCS" id="348158">
        <property type="hits" value="14 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM2B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACSM2B"/>
    <dbReference type="GenomeRNAi" id="348158"/>
    <dbReference type="Pharos" id="Q68CK6">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q68CK6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q68CK6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000066813">
        <property type="expression patterns" value="Expressed in right lobe of liver and 104 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q68CK6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018858">
        <property type="term" value="F:benzoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016405">
        <property type="term" value="F:CoA-ligase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0102391">
        <property type="term" value="F:decanoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006805">
        <property type="term" value="P:xenobiotic metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM5, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605:SF3">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM2B, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000306094" description="Acyl-coenzyme A synthetase ACSM2B, mitochondrial">
        <location>
            <begin position="47"/>
            <end position="577"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="139"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="221"/>
            <end position="229"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="359"/>
            <end position="364"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="364"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="446"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="461"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="469"/>
            <end position="471"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="472"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="501"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="532"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="540"/>
            <end position="542"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="557"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10">
        <location>
            <position position="513"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAO17576." evidence="7" ref="1">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAO17576 and 2; BAD38642." evidence="7" ref="1 2">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAO17576." evidence="7" ref="1">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAO17576." evidence="7" ref="1">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAO17576." evidence="7" ref="1">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12616642"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="19634011"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="12616642"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="577" mass="64271" checksum="93A6F0581A47F222" modified="2010-05-18" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-04-23" modified="2026-01-28" version="189" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NUB1</accession>
    <accession>B3KXL2</accession>
    <accession>B4DJZ3</accession>
    <accession>D3DW48</accession>
    <accession>F5H6F4</accession>
    <accession>F8W7Y1</accession>
    <accession>Q5TF42</accession>
    <accession>Q8IV99</accession>
    <accession>Q8N234</accession>
    <accession>Q96JI1</accession>
    <accession>Q96JX6</accession>
    <accession>Q9NU28</accession>
    <name>ACS2L_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acetyl-coenzyme A synthetase 2-like, mitochondrial</fullName>
            <ecNumber evidence="6">6.2.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acetate--CoA ligase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="10">Acetyl-CoA synthetase 2</fullName>
            <shortName evidence="10">AceCS2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase short-chain family member 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Propionate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.17</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSS1</name>
        <name type="synonym">ACAS2L</name>
        <name type="synonym">KIAA1846</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
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        <scope>VARIANT MET-488</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>ACETYLATION AT LYS-642</scope>
        <scope>MUTAGENESIS OF LYS-642</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INTERACTION WITH SIRT3</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>PROTEIN SEQUENCE OF N-TERMINUS</scope>
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    <comment type="function">
        <text evidence="2 6">Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:16788062). Acetate is the preferred substrate (PubMed:16788062). Can also utilize propionate with a much lower affinity (By similarity). Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (By similarity). Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:23176"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:23177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:20373"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.17"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:20374"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="6">Inhibited by acetylation at Lys-642 and activated by deacetylation mediated by the deacetylase SIRT3.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 7">Interacts with SIRT3.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10313831">
            <id>Q9NUB1</id>
        </interactant>
        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10313831">
            <id>Q9NUB1</id>
        </interactant>
        <interactant intactId="EBI-2107455">
            <id>Q08AM6</id>
            <label>VAC14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NUB1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NUB1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_007249"/>
        </isoform>
        <isoform>
            <id>Q9NUB1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_044693 VSP_044694"/>
        </isoform>
        <isoform>
            <id>Q9NUB1-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_045546 VSP_045547"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="6">Reversibly acetylated on Lys-642 (PubMed:16788062). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylase SIRT3.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB55390" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAC03853" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="BAC03853" version="1"/>
        </conflict>
        <text>Sequencing errors.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.1" evidence="6"/>
    <dbReference type="EC" id="6.2.1.17" evidence="2"/>
    <dbReference type="EMBL" id="AK027817">
        <property type="protein sequence ID" value="BAB55390.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092295">
        <property type="protein sequence ID" value="BAC03853.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK127566">
        <property type="protein sequence ID" value="BAG54524.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296306">
        <property type="protein sequence ID" value="BAG59005.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL035661">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL080312">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471133">
        <property type="protein sequence ID" value="EAX10106.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471133">
        <property type="protein sequence ID" value="EAX10109.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC039261">
        <property type="protein sequence ID" value="AAH39261.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC044588">
        <property type="protein sequence ID" value="AAH44588.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB058749">
        <property type="protein sequence ID" value="BAB47475.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13167.1">
        <molecule id="Q9NUB1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58764.1">
        <molecule id="Q9NUB1-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58765.1">
        <molecule id="Q9NUB1-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001239604.1">
        <molecule id="Q9NUB1-2"/>
        <property type="nucleotide sequence ID" value="NM_001252675.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001239605.1">
        <molecule id="Q9NUB1-3"/>
        <property type="nucleotide sequence ID" value="NM_001252676.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001239606.1">
        <molecule id="Q9NUB1-4"/>
        <property type="nucleotide sequence ID" value="NM_001252677.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_115890.2">
        <molecule id="Q9NUB1-1"/>
        <property type="nucleotide sequence ID" value="NM_032501.3"/>
    </dbReference>
    <dbReference type="PDB" id="3GLR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="B=638-649"/>
    </dbReference>
    <dbReference type="PDB" id="3GLT">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="B=638-649"/>
    </dbReference>
    <dbReference type="PDB" id="3GLU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="B=638-649"/>
    </dbReference>
    <dbReference type="PDB" id="4BVE">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="B=638-647"/>
    </dbReference>
    <dbReference type="PDB" id="4BVF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="B=638-647"/>
    </dbReference>
    <dbReference type="PDB" id="4BVG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="B=638-647"/>
    </dbReference>
    <dbReference type="PDB" id="4C78">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="C=638-647"/>
    </dbReference>
    <dbReference type="PDB" id="5Y4H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="B=638-649"/>
    </dbReference>
    <dbReference type="PDB" id="5YTK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="G/J/K/L=638-645"/>
    </dbReference>
    <dbReference type="PDBsum" id="3GLR"/>
    <dbReference type="PDBsum" id="3GLT"/>
    <dbReference type="PDBsum" id="3GLU"/>
    <dbReference type="PDBsum" id="4BVE"/>
    <dbReference type="PDBsum" id="4BVF"/>
    <dbReference type="PDBsum" id="4BVG"/>
    <dbReference type="PDBsum" id="4C78"/>
    <dbReference type="PDBsum" id="5Y4H"/>
    <dbReference type="PDBsum" id="5YTK"/>
    <dbReference type="AlphaFoldDB" id="Q9NUB1"/>
    <dbReference type="SMR" id="Q9NUB1"/>
    <dbReference type="BioGRID" id="124122">
        <property type="interactions" value="25"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-61208N"/>
    <dbReference type="FunCoup" id="Q9NUB1">
        <property type="interactions" value="601"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NUB1">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="MINT" id="Q9NUB1"/>
    <dbReference type="STRING" id="9606.ENSP00000316924"/>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000448"/>
    <dbReference type="iPTMnet" id="Q9NUB1"/>
    <dbReference type="MetOSite" id="Q9NUB1"/>
    <dbReference type="PhosphoSitePlus" id="Q9NUB1"/>
    <dbReference type="SwissPalm" id="Q9NUB1"/>
    <dbReference type="BioMuta" id="ACSS1"/>
    <dbReference type="DMDM" id="30172968"/>
    <dbReference type="jPOST" id="Q9NUB1"/>
    <dbReference type="MassIVE" id="Q9NUB1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000316924"/>
    <dbReference type="PeptideAtlas" id="Q9NUB1"/>
    <dbReference type="ProteomicsDB" id="27173"/>
    <dbReference type="ProteomicsDB" id="30036"/>
    <dbReference type="ProteomicsDB" id="82660">
        <molecule id="Q9NUB1-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="82661">
        <molecule id="Q9NUB1-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9NUB1"/>
    <dbReference type="Antibodypedia" id="24959">
        <property type="antibodies" value="140 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84532"/>
    <dbReference type="Ensembl" id="ENST00000323482.9">
        <molecule id="Q9NUB1-1"/>
        <property type="protein sequence ID" value="ENSP00000316924.4"/>
        <property type="gene ID" value="ENSG00000154930.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000432802.6">
        <molecule id="Q9NUB1-4"/>
        <property type="protein sequence ID" value="ENSP00000388793.2"/>
        <property type="gene ID" value="ENSG00000154930.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000537502.5">
        <molecule id="Q9NUB1-3"/>
        <property type="protein sequence ID" value="ENSP00000439304.2"/>
        <property type="gene ID" value="ENSG00000154930.16"/>
    </dbReference>
    <dbReference type="GeneID" id="84532"/>
    <dbReference type="KEGG" id="hsa:84532"/>
    <dbReference type="MANE-Select" id="ENST00000323482.9">
        <property type="protein sequence ID" value="ENSP00000316924.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032501.4"/>
        <property type="RefSeq protein sequence ID" value="NP_115890.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002wub.4">
        <molecule id="Q9NUB1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16091"/>
    <dbReference type="ClinPGx" id="PA24430"/>
    <dbReference type="CTD" id="84532"/>
    <dbReference type="DisGeNET" id="84532"/>
    <dbReference type="GeneCards" id="ACSS1"/>
    <dbReference type="HGNC" id="HGNC:16091">
        <property type="gene designation" value="ACSS1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000154930">
        <property type="expression patterns" value="Tissue enhanced (choroid)"/>
    </dbReference>
    <dbReference type="MIM" id="614355">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000154930"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000154930"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158550"/>
    <dbReference type="HOGENOM" id="CLU_000022_3_0_1"/>
    <dbReference type="InParanoid" id="Q9NUB1"/>
    <dbReference type="OMA" id="AIKASWP"/>
    <dbReference type="OrthoDB" id="1706066at2759"/>
    <dbReference type="PAN-GO" id="Q9NUB1">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NUB1"/>
    <dbReference type="BRENDA" id="6.2.1.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NUB1"/>
    <dbReference type="Reactome" id="R-HSA-71384">
        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NUB1"/>
    <dbReference type="SIGNOR" id="Q9NUB1"/>
    <dbReference type="Agora" id="ENSG00000154930"/>
    <dbReference type="BioGRID-ORCS" id="84532">
        <property type="hits" value="11 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSS1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NUB1"/>
    <dbReference type="GenomeRNAi" id="84532"/>
    <dbReference type="Pharos" id="Q9NUB1">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NUB1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NUB1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000154930">
        <property type="expression patterns" value="Expressed in apex of heart and 174 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NUB1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003987">
        <property type="term" value="F:acetate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016208">
        <property type="term" value="F:AMP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050218">
        <property type="term" value="F:propionate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019413">
        <property type="term" value="P:acetate biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006085">
        <property type="term" value="P:acetyl-CoA biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019427">
        <property type="term" value="P:acetyl-CoA biosynthetic process from acetate"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006068">
        <property type="term" value="P:ethanol catabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019542">
        <property type="term" value="P:propionate biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd05966">
        <property type="entry name" value="ACS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000025">
        <property type="entry name" value="Acetyl-coenzyme A synthetase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000011">
        <property type="entry name" value="Acetyl-coenzyme A synthetase 2-like, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011904">
        <property type="entry name" value="Ac_CoA_lig"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032387">
        <property type="entry name" value="ACAS_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR02188">
        <property type="entry name" value="Ac_CoA_lig_AcsA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="NCBIfam" id="NF001208">
        <property type="entry name" value="PRK00174.1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24095">
        <property type="entry name" value="ACETYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24095:SF110">
        <property type="entry name" value="ACETYL-COENZYME A SYNTHETASE 2-LIKE, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16177">
        <property type="entry name" value="ACAS_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="6">
        <location>
            <begin position="1"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000596" description="Acetyl-coenzyme A synthetase 2-like, mitochondrial">
        <location>
            <begin position="38"/>
            <end position="689"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="17"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="32"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="224"/>
            <end position="227"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="341"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="417"/>
            <end position="419"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="441"/>
            <end position="446"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="533"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="548"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="556"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="559"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="13">
        <location>
            <position position="396"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="6">
        <location>
            <position position="642"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044693" description="In isoform 3." evidence="8">
        <original>MAARTLGRGVGRLLGSLRGLSG</original>
        <variation>MRRRKERQPWDRFHFLHFAPHG</variation>
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044694" description="In isoform 3." evidence="8">
        <location>
            <begin position="23"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_007249" description="In isoform 2." evidence="9">
        <location>
            <begin position="446"/>
            <end position="447"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045546" description="In isoform 4." evidence="8">
        <original>SGHRLGTAEIEDAIADHPAV</original>
        <variation>LQIVGFFREAIRNSGDLLEH</variation>
        <location>
            <begin position="556"/>
            <end position="575"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045547" description="In isoform 4." evidence="8">
        <location>
            <begin position="576"/>
            <end position="689"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048184" description="In dbSNP:rs6050249." evidence="4 5">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="488"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of activity." evidence="6">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="642"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAG54524." evidence="11" ref="1">
        <original>K</original>
        <variation>I</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH39261." evidence="11" ref="4">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q99NB1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16788062"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="19535340"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="16788062"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="16788062"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <sequence length="689" mass="74857" checksum="66E84E39302AD08B" modified="2003-04-23" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="163" xmlns="https://uniprot.org/uniprot">
    <accession>Q96CM8</accession>
    <accession>B4DFQ6</accession>
    <accession>B4DHT5</accession>
    <accession>B4DUF5</accession>
    <accession>Q9H7G2</accession>
    <name>ACSF2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">Medium-chain acyl-CoA ligase ACSF2, mitochondrial</fullName>
            <ecNumber evidence="6">6.2.1.2</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ACSF2</name>
        <name type="ORF">UNQ493/PRO1009</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4)</scope>
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            <tissue>Adipose tissue</tissue>
            <tissue>Amygdala</tissue>
            <tissue>Caudate nucleus</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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    <comment type="function">
        <text evidence="5 6">Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA (PubMed:17762044). Has some preference toward medium-chain substrates (PubMed:17762044). Plays a role in adipocyte differentiation (PubMed:16380219).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
        </interactant>
        <interactant intactId="EBI-741181">
            <id>Q6RW13</id>
            <label>AGTRAP</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-3936819">
            <id>Q6Q788</id>
            <label>APOA5</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-1220105">
            <id>P02654</id>
            <label>APOC1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-11343438">
            <id>Q3SXY8</id>
            <label>ARL13B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
        </interactant>
        <interactant intactId="EBI-714543">
            <id>Q15041</id>
            <label>ARL6IP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-13381098">
            <id>Q8IYJ2-2</id>
            <label>C10orf67</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-2873246">
            <id>Q8IUN9</id>
            <label>CLEC10A</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>Q96CM8</id>
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        <interactant intactId="EBI-2548702">
            <id>Q96DZ9</id>
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    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-11522780">
            <id>Q96DZ9-2</id>
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    <comment type="interaction">
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        <interactant intactId="EBI-724524">
            <id>O75208</id>
            <label>COQ9</label>
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    <comment type="interaction">
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            <id>Q96CM8</id>
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        <interactant intactId="EBI-12831978">
            <id>Q6ZPD8</id>
            <label>DGAT2L6</label>
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    <comment type="interaction">
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        <interactant intactId="EBI-13345167">
            <id>Q8TDT2</id>
            <label>GPR152</label>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
        </interactant>
        <interactant intactId="EBI-1053887">
            <id>Q5XKP0</id>
            <label>MICOS13</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-11913715">
            <id>Q8IZV5</id>
            <label>RDH10</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-17589229">
            <id>Q6NTF9-3</id>
            <label>RHBDD2</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-714881">
            <id>Q9HC62</id>
            <label>SENP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-2623095">
            <id>Q9Y371</id>
            <label>SH3GLB1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-17640454">
            <id>Q96PQ1</id>
            <label>SIGLEC12</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876502">
            <id>Q96CM8</id>
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        <interactant intactId="EBI-11321949">
            <id>O43761</id>
            <label>SYNGR3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96CM8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
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            <sequence type="described" ref="VSP_055804"/>
        </isoform>
        <isoform>
            <id>Q96CM8-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_055805"/>
        </isoform>
        <isoform>
            <id>Q96CM8-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_055803"/>
        </isoform>
    </comment>
    <comment type="induction">
        <text evidence="5">By PPARG.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="mRNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH14123.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="gene designation" value="ACSF2"/>
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        <property type="type" value="gene"/>
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        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
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        <property type="pathway name" value="Mitochondrial Fatty Acid Beta-Oxidation"/>
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    <dbReference type="Agora" id="ENSG00000167107"/>
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        <property type="hits" value="19 hits in 1161 CRISPR screens"/>
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        <property type="organism name" value="human"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 17"/>
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        <property type="molecule type" value="protein"/>
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    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="3">
        <location>
            <begin position="1"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000315793" description="Medium-chain acyl-CoA ligase ACSF2, mitochondrial">
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            <begin position="42"/>
            <end position="615"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="263"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="493"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="508"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="599"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="340"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="478"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="510"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="570"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="570"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="599"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055803" description="In isoform 4." evidence="7">
        <location>
            <begin position="1"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055804" description="In isoform 2." evidence="7">
        <original>S</original>
        <variation>SARGGMEAGRQRISVPSSFTASAAAH</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055805" description="In isoform 3." evidence="7">
        <location>
            <begin position="146"/>
            <end position="158"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038304" description="In dbSNP:rs17856448." evidence="4">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038305" description="In dbSNP:rs3744523.">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8VCW8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16380219"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17762044"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:26101"/>
        </source>
    </evidence>
    <sequence length="615" mass="68125" checksum="A3356EEA7C14730B" modified="2008-01-15" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="150" xmlns="https://uniprot.org/uniprot">
    <accession>Q4G176</accession>
    <accession>A8K4J8</accession>
    <accession>C9JQL6</accession>
    <accession>Q6INA0</accession>
    <accession>Q8N2F7</accession>
    <name>ACSF3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Malonate--CoA ligase ACSF3, mitochondrial</fullName>
            <ecNumber evidence="6">6.2.1.76</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase family member 3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="8" type="primary">ACSF3</name>
        <name type="ORF">PSEC0197</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="J. Biol. Chem." volume="286" first="33729" last="33736">
            <title>Mammalian ACSF3 protein is a malonyl-CoA synthetase that supplies the chain extender units for mitochondrial fatty acid synthesis.</title>
            <authorList>
                <person name="Witkowski A."/>
                <person name="Thweatt J."/>
                <person name="Smith S."/>
            </authorList>
            <dbReference type="PubMed" id="21846720"/>
            <dbReference type="DOI" id="10.1074/jbc.m111.291591"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ARG-354</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Nat. Genet." volume="43" first="883" last="886">
            <title>Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria.</title>
            <authorList>
                <person name="Sloan J.L."/>
                <person name="Johnston J.J."/>
                <person name="Manoli I."/>
                <person name="Chandler R.J."/>
                <person name="Krause C."/>
                <person name="Carrillo-Carrasco N."/>
                <person name="Chandrasekaran S.D."/>
                <person name="Sysol J.R."/>
                <person name="O'Brien K."/>
                <person name="Hauser N.S."/>
                <person name="Sapp J.C."/>
                <person name="Dorward H.M."/>
                <person name="Huizing M."/>
                <person name="Barshop B.A."/>
                <person name="Berry S.A."/>
                <person name="James P.M."/>
                <person name="Champaigne N.L."/>
                <person name="de Lonlay P."/>
                <person name="Valayannopoulos V."/>
                <person name="Geschwind M.D."/>
                <person name="Gavrilov D.K."/>
                <person name="Nyhan W.L."/>
                <person name="Biesecker L.G."/>
                <person name="Venditti C.P."/>
            </authorList>
            <dbReference type="PubMed" id="21841779"/>
            <dbReference type="DOI" id="10.1038/ng.908"/>
        </citation>
        <scope>VARIANTS CMAMMA ARG-198; LEU-243; ILE-358; LYS-359; THR-462; 465-GLN--GLY-470 DEL; GLN-471; TRP-471; SER-480 AND TRP-558</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6">Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester (PubMed:21841779, PubMed:21846720). May have some preference toward very-long-chain substrates (PubMed:17762044).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>tetracosanoate + ATP + CoA = tetracosanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33639"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:31014"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65052"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:33640"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>malonate + ATP + CoA = malonyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:32139"/>
            <dbReference type="ChEBI" id="CHEBI:15792"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57384"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.76"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:32140"/>
        </physiologicalReaction>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">36.8 uM for malonate</KM>
        </kinetics>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-7466542">
            <id>P43220</id>
            <label>GLP1R</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-10189448">
            <id>Q9BQ13</id>
            <label>KCTD14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-10171697">
            <id>Q6A162</id>
            <label>KRT40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-357448">
            <id>P36776</id>
            <label>LONP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-12072296">
            <id>O95460-2</id>
            <label>MATN4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-1105153">
            <id>Q96KQ4</id>
            <label>PPP1R13B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-11898753">
            <id>P51157</id>
            <label>RAB28</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10714818">
            <id>Q4G176</id>
        </interactant>
        <interactant intactId="EBI-719493">
            <id>P14373</id>
            <label>TRIM27</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-03246">
            <name>Combined malonic and methylmalonic aciduria</name>
            <acronym>CMAMMA</acronym>
            <description>A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline.</description>
            <dbReference type="MIM" id="614265"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAH72391" version="1"/>
        </conflict>
        <text>Aberrant splicing.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.76" evidence="6"/>
    <dbReference type="EMBL" id="AK075499">
        <property type="protein sequence ID" value="BAC11654.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290963">
        <property type="protein sequence ID" value="BAF83652.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009113">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC135782">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471184">
        <property type="protein sequence ID" value="EAW66744.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC028399">
        <property type="protein sequence ID" value="AAH28399.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC072391">
        <property type="protein sequence ID" value="AAH72391.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10974.1"/>
    <dbReference type="RefSeq" id="NP_001120686.1">
        <property type="nucleotide sequence ID" value="NM_001127214.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001230208.1">
        <property type="nucleotide sequence ID" value="NM_001243279.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_777577.2">
        <property type="nucleotide sequence ID" value="NM_174917.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q4G176"/>
    <dbReference type="SMR" id="Q4G176"/>
    <dbReference type="BioGRID" id="128248">
        <property type="interactions" value="87"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q4G176">
        <property type="interactions" value="1690"/>
    </dbReference>
    <dbReference type="IntAct" id="Q4G176">
        <property type="interactions" value="49"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000479130"/>
    <dbReference type="ChEMBL" id="CHEMBL4523315"/>
    <dbReference type="SwissLipids" id="SLP:000000541"/>
    <dbReference type="GlyGen" id="Q4G176">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q4G176"/>
    <dbReference type="PhosphoSitePlus" id="Q4G176"/>
    <dbReference type="SwissPalm" id="Q4G176"/>
    <dbReference type="BioMuta" id="ACSF3"/>
    <dbReference type="DMDM" id="296439438"/>
    <dbReference type="jPOST" id="Q4G176"/>
    <dbReference type="MassIVE" id="Q4G176"/>
    <dbReference type="PaxDb" id="9606-ENSP00000479130"/>
    <dbReference type="PeptideAtlas" id="Q4G176"/>
    <dbReference type="ProteomicsDB" id="62157"/>
    <dbReference type="Pumba" id="Q4G176"/>
    <dbReference type="Antibodypedia" id="2033">
        <property type="antibodies" value="108 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="197322"/>
    <dbReference type="Ensembl" id="ENST00000317447.9">
        <property type="protein sequence ID" value="ENSP00000320646.4"/>
        <property type="gene ID" value="ENSG00000176715.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000406948.7">
        <property type="protein sequence ID" value="ENSP00000384627.3"/>
        <property type="gene ID" value="ENSG00000176715.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000614302.5">
        <property type="protein sequence ID" value="ENSP00000479130.1"/>
        <property type="gene ID" value="ENSG00000176715.18"/>
    </dbReference>
    <dbReference type="GeneID" id="197322"/>
    <dbReference type="KEGG" id="hsa:197322"/>
    <dbReference type="MANE-Select" id="ENST00000614302.5">
        <property type="protein sequence ID" value="ENSP00000479130.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001243279.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001230208.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002fmp.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:27288"/>
    <dbReference type="ClinPGx" id="PA162375375"/>
    <dbReference type="CTD" id="197322"/>
    <dbReference type="DisGeNET" id="197322"/>
    <dbReference type="GeneCards" id="ACSF3"/>
    <dbReference type="HGNC" id="HGNC:27288">
        <property type="gene designation" value="ACSF3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000176715">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACSF3"/>
    <dbReference type="MIM" id="614245">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="614265">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000176715"/>
    <dbReference type="Orphanet" id="289504">
        <property type="disease" value="Combined malonic and methylmalonic acidemia"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000176715"/>
    <dbReference type="eggNOG" id="KOG1176">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157000"/>
    <dbReference type="InParanoid" id="Q4G176"/>
    <dbReference type="OMA" id="KGKWFKT"/>
    <dbReference type="OrthoDB" id="2962993at2759"/>
    <dbReference type="PAN-GO" id="Q4G176">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q4G176"/>
    <dbReference type="BioCyc" id="MetaCyc:ENSG00000176715-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q4G176"/>
    <dbReference type="Reactome" id="R-HSA-75876">
        <property type="pathway name" value="Synthesis of very long-chain fatty acyl-CoAs"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q4G176"/>
    <dbReference type="Agora" id="ENSG00000176715"/>
    <dbReference type="BioGRID-ORCS" id="197322">
        <property type="hits" value="10 hits in 1164 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSF3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACSF3"/>
    <dbReference type="GenomeRNAi" id="197322"/>
    <dbReference type="Pharos" id="Q4G176">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q4G176"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q4G176">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000176715">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 106 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q4G176">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016405">
        <property type="term" value="F:CoA-ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090409">
        <property type="term" value="F:malonyl-CoA synthetase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031957">
        <property type="term" value="F:very long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035338">
        <property type="term" value="P:long-chain fatty-acyl-CoA biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090410">
        <property type="term" value="P:malonate catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd05941">
        <property type="entry name" value="MCS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000031">
        <property type="entry name" value="Acyl-CoA synthetase family member 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000030">
        <property type="entry name" value="Acyl-CoA synthetase family member 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43201">
        <property type="entry name" value="ACYL-COA SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43201:SF8">
        <property type="entry name" value="ACYL-COA SYNTHETASE FAMILY MEMBER 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="2">
        <location>
            <begin position="1"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000315800" description="Malonate--CoA ligase ACSF3, mitochondrial">
        <location>
            <begin position="84"/>
            <end position="576"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="202"/>
            <end position="210"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="457"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="471"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="563"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_038306" description="In dbSNP:rs7188200." evidence="3">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038307" description="In dbSNP:rs11547019." evidence="3">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066504" description="In CMAMMA; dbSNP:rs387907121." evidence="5">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066505" description="In CMAMMA; dbSNP:rs140986055." evidence="5">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066506" description="In CMAMMA; dbSNP:rs387907120." evidence="5">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066507" description="In CMAMMA; dbSNP:rs150487794." evidence="5">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038308" description="In dbSNP:rs3743979." evidence="3">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066508" description="In CMAMMA; dbSNP:rs1362504214." evidence="5">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="462"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066509" description="In CMAMMA." evidence="5">
        <location>
            <begin position="465"/>
            <end position="470"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066510" description="In CMAMMA; dbSNP:rs387907119." evidence="5">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066511" description="In CMAMMA; dbSNP:rs138680796." evidence="5">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066512" description="In CMAMMA." evidence="5">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="480"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066513" description="In CMAMMA; dbSNP:rs141090143." evidence="5">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="558"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs malonyl-CoA synthase activity." evidence="6">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="354"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impairs malonyl-CoA synthase activity." evidence="6">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="354"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH28399." evidence="7" ref="5">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC11654." evidence="7" ref="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="278"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="17762044"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="21841779"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21846720"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:27288"/>
        </source>
    </evidence>
    <sequence length="576" mass="64130" checksum="60F0D5020817EF70" modified="2010-05-18" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1998-12-15" modified="2026-01-28" version="229" xmlns="https://uniprot.org/uniprot">
    <accession>O60488</accession>
    <accession>D3DUY2</accession>
    <accession>O60848</accession>
    <accession>O60849</accession>
    <accession>Q5JWV8</accession>
    <name>ACSL4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="20">Long-chain-fatty-acid--CoA ligase 4</fullName>
            <ecNumber evidence="6 7 8">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20">Arachidonate--CoA ligase</fullName>
            <ecNumber evidence="6 11">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 4</fullName>
            <shortName>LACS 4</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSL4</name>
        <name type="synonym">ACS4</name>
        <name type="synonym">FACL4</name>
        <name type="synonym">LACS4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Proneth B."/>
                <person name="Tyurina Y.Y."/>
                <person name="Panzilius E."/>
                <person name="Kobayashi S."/>
                <person name="Ingold I."/>
                <person name="Irmler M."/>
                <person name="Beckers J."/>
                <person name="Aichler M."/>
                <person name="Walch A."/>
                <person name="Prokisch H."/>
                <person name="Truembach D."/>
                <person name="Mao G."/>
                <person name="Qu F."/>
                <person name="Bayir H."/>
                <person name="Fuellekrug J."/>
                <person name="Scheel C.H."/>
                <person name="Wurst W."/>
                <person name="Schick J.A."/>
                <person name="Kagan V.E."/>
                <person name="Angeli J.P."/>
                <person name="Conrad M."/>
            </authorList>
            <dbReference type="PubMed" id="27842070"/>
            <dbReference type="DOI" id="10.1038/nchembio.2239"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2019" name="Biol. Pharm. Bull." volume="42" first="850" last="855">
            <title>Analysis on the Substrate Specificity of Recombinant Human Acyl-CoA Synthetase ACSL4 Variants.</title>
            <authorList>
                <person name="Shimbara-Matsubayashi S."/>
                <person name="Kuwata H."/>
                <person name="Tanaka N."/>
                <person name="Kato M."/>
                <person name="Hara S."/>
            </authorList>
            <dbReference type="PubMed" id="31061331"/>
            <dbReference type="DOI" id="10.1248/bpb.b19-00085"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2022" name="Nat. Cell Biol." volume="24" first="88" last="98">
            <title>PKCbetaII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis.</title>
            <authorList>
                <person name="Zhang H.L."/>
                <person name="Hu B.X."/>
                <person name="Li Z.L."/>
                <person name="Du T."/>
                <person name="Shan J.L."/>
                <person name="Ye Z.P."/>
                <person name="Peng X.D."/>
                <person name="Li X."/>
                <person name="Huang Y."/>
                <person name="Zhu X.Y."/>
                <person name="Chen Y.H."/>
                <person name="Feng G.K."/>
                <person name="Yang D."/>
                <person name="Deng R."/>
                <person name="Zhu X.F."/>
            </authorList>
            <dbReference type="PubMed" id="35027735"/>
            <dbReference type="DOI" id="10.1038/s41556-021-00818-3"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION AT THR-328</scope>
        <scope>MUTAGENESIS OF THR-328</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2024" name="Nat. Chem. Biol." volume="20" first="1341" last="1352">
            <title>Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.</title>
            <authorList>
                <person name="Li Z."/>
                <person name="Xu Z.M."/>
                <person name="Chen W.P."/>
                <person name="Du X.J."/>
                <person name="Ou C.X."/>
                <person name="Luo Z.K."/>
                <person name="Wang R."/>
                <person name="Zhang C.Q."/>
                <person name="Ge C.D."/>
                <person name="Han M."/>
                <person name="Wang F."/>
                <person name="He R.R."/>
                <person name="Sun W.Y."/>
                <person name="Ma J."/>
                <person name="Liang X.Y."/>
                <person name="Liu Z.W."/>
            </authorList>
            <dbReference type="PubMed" id="38720107"/>
            <dbReference type="DOI" id="10.1038/s41589-024-01612-6"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION AT THR-679</scope>
        <scope>MUTAGENESIS OF THR-679</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2002" name="Nat. Genet." volume="30" first="436" last="440">
            <title>FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation.</title>
            <authorList>
                <person name="Meloni I."/>
                <person name="Muscettola M."/>
                <person name="Raynaud M."/>
                <person name="Longo I."/>
                <person name="Bruttini M."/>
                <person name="Moizard M.-P."/>
                <person name="Gomot M."/>
                <person name="Chelly J."/>
                <person name="des Portes V."/>
                <person name="Fryns J.-P."/>
                <person name="Ropers H.-H."/>
                <person name="Magi B."/>
                <person name="Bellan C."/>
                <person name="Volpi N."/>
                <person name="Yntema H.G."/>
                <person name="Lewis S.E."/>
                <person name="Schaffer J.E."/>
                <person name="Renieri A."/>
            </authorList>
            <dbReference type="PubMed" id="11889465"/>
            <dbReference type="DOI" id="10.1038/ng857"/>
        </citation>
        <scope>VARIANT XLID63 SER-570</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] CYS-133</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2018" name="Am. J. Hum. Genet." volume="103" first="144" last="153">
            <title>De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.</title>
            <authorList>
                <consortium name="NIHR BioResource"/>
                <consortium name="Care4Rare Canada Consortium"/>
                <person name="Ito Y."/>
                <person name="Carss K.J."/>
                <person name="Duarte S.T."/>
                <person name="Hartley T."/>
                <person name="Keren B."/>
                <person name="Kurian M.A."/>
                <person name="Marey I."/>
                <person name="Charles P."/>
                <person name="Mendonca C."/>
                <person name="Nava C."/>
                <person name="Pfundt R."/>
                <person name="Sanchis-Juan A."/>
                <person name="van Bokhoven H."/>
                <person name="van Essen A."/>
                <person name="van Ravenswaaij-Arts C."/>
                <person name="Boycott K.M."/>
                <person name="Kernohan K.D."/>
                <person name="Dyack S."/>
                <person name="Raymond F.L."/>
            </authorList>
            <dbReference type="PubMed" id="29961568"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2018.06.001"/>
        </citation>
        <scope>VARIANT ASN-379</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6 7 8 9 11 12 13">Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233, PubMed:31061331, PubMed:38720107). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET &gt; 14,15-EET &gt; 5,6-EET &gt; 11,12-EET (PubMed:21242590). Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). Acts as an activator of ferroptosis by activating polyunsaturated fatty acids, especially arachidonate and adrenate, to their active form, generating the primary lipid-peroxidation substrates that contribute to ferroptosis (PubMed:27842070, PubMed:35027735, PubMed:38720107).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7 8">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6 7 8">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 11">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6 11">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:36140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52116"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:78832"/>
            <dbReference type="ChEBI" id="CHEBI:136409"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52117"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52112"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:90718"/>
            <dbReference type="ChEBI" id="CHEBI:136408"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52108"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65341"/>
            <dbReference type="ChEBI" id="CHEBI:136407"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52109"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 5,6-epoxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52088"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:131992"/>
            <dbReference type="ChEBI" id="CHEBI:136351"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52089"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52016"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84024"/>
            <dbReference type="ChEBI" id="CHEBI:136117"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52017"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52012"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76625"/>
            <dbReference type="ChEBI" id="CHEBI:136115"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52013"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + ATP + CoA = 8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52008"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84025"/>
            <dbReference type="ChEBI" id="CHEBI:136107"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:52009"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>(7Z,10Z,13Z,16Z)-docosatetraenoate + ATP + CoA = (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:85307"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:73856"/>
            <dbReference type="ChEBI" id="CHEBI:77225"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:85308"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:44932"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:44933"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ATP + CoA = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:67848"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:67849"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Long</molecule>
        <reaction evidence="11">
            <text>(7Z,10Z,13Z,16Z)-docosatetraenoate + ATP + CoA = (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:85307"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:73856"/>
            <dbReference type="ChEBI" id="CHEBI:77225"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:85308"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Short</molecule>
        <reaction evidence="11">
            <text>(7Z,10Z,13Z,16Z)-docosatetraenoate + ATP + CoA = (7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:85307"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:73856"/>
            <dbReference type="ChEBI" id="CHEBI:77225"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:85308"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Long</molecule>
        <reaction evidence="11">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Short</molecule>
        <reaction evidence="11">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Long</molecule>
        <reaction evidence="11">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:44932"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:44933"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Short</molecule>
        <reaction evidence="11">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:44932"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:44933"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Long</molecule>
        <reaction evidence="11">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ATP + CoA = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:67848"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:67849"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform Short</molecule>
        <reaction evidence="11">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ATP + CoA = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:67848"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:67849"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="6 9">Both triacsin C and rosiglitazone inhibit arachidonoyl-CoA ligase activity (PubMed:21242590). Specifically inhibited by thiazolidinediones, preventing ferroptosis (PubMed:27842070).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="13">Mitochondrion outer membrane</location>
            <topology evidence="20">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Endoplasmic reticulum membrane</location>
            <topology evidence="20">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cell membrane</location>
            <topology evidence="20">Single-pass type III membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O60488-1</id>
            <name>Long</name>
            <name evidence="17">V2</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O60488-2</id>
            <name>Short</name>
            <name evidence="17">V1</name>
            <sequence type="described" ref="VSP_000238"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="12 13">Phosphorylation at Thr-328 by isoform Beta-II of PRKCB promotes activation and lipid peroxidation, thereby inducing ferroptosis (PubMed:35027735). Phosphorylation at Thr-679 by PCK2 promotes ferroptosis (PubMed:38720107).</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-00734">
            <name>Intellectual developmental disorder, X-linked 63</name>
            <acronym>XLID63</acronym>
            <description>A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked intellectual disability, while syndromic forms presents with associated physical, neurological and/or psychiatric manifestations.</description>
            <dbReference type="MIM" id="300387"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="14">
        <disease id="DI-01183">
            <name>AMME complex</name>
            <acronym>ATS-MR</acronym>
            <description>An X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, intellectual disability, midface hypoplasia and elliptocytosis.</description>
            <dbReference type="MIM" id="300194"/>
        </disease>
        <text>The gene represented in this entry may be involved in disease pathogenesis.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="6 7 8"/>
    <dbReference type="EC" id="6.2.1.15" evidence="6 11"/>
    <dbReference type="EMBL" id="AF030555">
        <property type="protein sequence ID" value="AAC17493.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y12777">
        <property type="protein sequence ID" value="CAA73314.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y13058">
        <property type="protein sequence ID" value="CAA73501.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292070">
        <property type="protein sequence ID" value="BAF84759.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471120">
        <property type="protein sequence ID" value="EAX02671.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471120">
        <property type="protein sequence ID" value="EAX02672.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471120">
        <property type="protein sequence ID" value="EAX02673.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471120">
        <property type="protein sequence ID" value="EAX02674.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034959">
        <property type="protein sequence ID" value="AAH34959.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14548.1">
        <molecule id="O60488-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14549.1">
        <molecule id="O60488-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001305438.1">
        <molecule id="O60488-1"/>
        <property type="nucleotide sequence ID" value="NM_001318509.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001305439.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_001318510.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424174.1">
        <molecule id="O60488-1"/>
        <property type="nucleotide sequence ID" value="NM_001437245.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424176.1">
        <molecule id="O60488-1"/>
        <property type="nucleotide sequence ID" value="NM_001437247.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424177.1">
        <molecule id="O60488-1"/>
        <property type="nucleotide sequence ID" value="NM_001437248.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424179.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_001437250.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424180.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_001437251.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424181.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_001437252.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001424182.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_001437253.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004449.1">
        <molecule id="O60488-2"/>
        <property type="nucleotide sequence ID" value="NM_004458.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_075266.1">
        <molecule id="O60488-1"/>
        <property type="nucleotide sequence ID" value="NM_022977.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O60488"/>
    <dbReference type="SMR" id="O60488"/>
    <dbReference type="BioGRID" id="108478">
        <property type="interactions" value="192"/>
    </dbReference>
    <dbReference type="FunCoup" id="O60488">
        <property type="interactions" value="2315"/>
    </dbReference>
    <dbReference type="IntAct" id="O60488">
        <property type="interactions" value="113"/>
    </dbReference>
    <dbReference type="MINT" id="O60488"/>
    <dbReference type="STRING" id="9606.ENSP00000339787"/>
    <dbReference type="BindingDB" id="O60488"/>
    <dbReference type="ChEMBL" id="CHEMBL4680022"/>
    <dbReference type="DrugBank" id="DB00159">
        <property type="generic name" value="Icosapent"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00412">
        <property type="generic name" value="Rosiglitazone"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00197">
        <property type="generic name" value="Troglitazone"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000201"/>
    <dbReference type="SwissLipids" id="SLP:000000515">
        <molecule id="O60488-1"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000516">
        <molecule id="O60488-2"/>
    </dbReference>
    <dbReference type="TCDB" id="4.C.1.1.21">
        <property type="family name" value="the fatty acid group translocation (fat) family"/>
    </dbReference>
    <dbReference type="GlyGen" id="O60488">
        <property type="glycosylation" value="4 sites, 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O60488"/>
    <dbReference type="MetOSite" id="O60488"/>
    <dbReference type="PhosphoSitePlus" id="O60488"/>
    <dbReference type="SwissPalm" id="O60488"/>
    <dbReference type="BioMuta" id="ACSL4"/>
    <dbReference type="jPOST" id="O60488"/>
    <dbReference type="MassIVE" id="O60488"/>
    <dbReference type="PaxDb" id="9606-ENSP00000339787"/>
    <dbReference type="PeptideAtlas" id="O60488"/>
    <dbReference type="ProteomicsDB" id="49426">
        <molecule id="O60488-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="49427">
        <molecule id="O60488-2"/>
    </dbReference>
    <dbReference type="Pumba" id="O60488"/>
    <dbReference type="Antibodypedia" id="444">
        <property type="antibodies" value="357 antibodies from 36 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2182"/>
    <dbReference type="Ensembl" id="ENST00000340800.7">
        <molecule id="O60488-1"/>
        <property type="protein sequence ID" value="ENSP00000339787.2"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000348502.10">
        <molecule id="O60488-2"/>
        <property type="protein sequence ID" value="ENSP00000262835.7"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000469796.7">
        <molecule id="O60488-1"/>
        <property type="protein sequence ID" value="ENSP00000419171.2"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000502391.6">
        <molecule id="O60488-1"/>
        <property type="protein sequence ID" value="ENSP00000425408.2"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000671846.1">
        <molecule id="O60488-1"/>
        <property type="protein sequence ID" value="ENSP00000500897.1"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000672282.1">
        <molecule id="O60488-2"/>
        <property type="protein sequence ID" value="ENSP00000500678.1"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000672401.1">
        <molecule id="O60488-2"/>
        <property type="protein sequence ID" value="ENSP00000500273.1"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000673016.1">
        <molecule id="O60488-2"/>
        <property type="protein sequence ID" value="ENSP00000499969.1"/>
        <property type="gene ID" value="ENSG00000068366.22"/>
    </dbReference>
    <dbReference type="GeneID" id="2182"/>
    <dbReference type="KEGG" id="hsa:2182"/>
    <dbReference type="MANE-Select" id="ENST00000672401.1">
        <molecule id="O60488-2"/>
        <property type="protein sequence ID" value="ENSP00000500273.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001318510.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001305439.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004eoi.3">
        <molecule id="O60488-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:3571"/>
    <dbReference type="ClinPGx" id="PA27968"/>
    <dbReference type="CTD" id="2182"/>
    <dbReference type="DisGeNET" id="2182"/>
    <dbReference type="GeneCards" id="ACSL4"/>
    <dbReference type="HGNC" id="HGNC:3571">
        <property type="gene designation" value="ACSL4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000068366">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACSL4"/>
    <dbReference type="MIM" id="300157">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="300194">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="300387">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000068366"/>
    <dbReference type="Orphanet" id="86818">
        <property type="disease" value="Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome"/>
    </dbReference>
    <dbReference type="Orphanet" id="777">
        <property type="disease" value="X-linked non-syndromic intellectual disability"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000068366"/>
    <dbReference type="eggNOG" id="KOG1180">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157427"/>
    <dbReference type="HOGENOM" id="CLU_000022_45_2_1"/>
    <dbReference type="InParanoid" id="O60488"/>
    <dbReference type="OrthoDB" id="1700726at2759"/>
    <dbReference type="PAN-GO" id="O60488">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O60488"/>
    <dbReference type="BioCyc" id="MetaCyc:HS00935-MONOMER"/>
    <dbReference type="BRENDA" id="6.2.1.15">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="6.2.1.3">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O60488"/>
    <dbReference type="Reactome" id="R-HSA-434313">
        <property type="pathway name" value="Intracellular metabolism of fatty acids regulates insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-75876">
        <property type="pathway name" value="Synthesis of very long-chain fatty acyl-CoAs"/>
    </dbReference>
    <dbReference type="SignaLink" id="O60488"/>
    <dbReference type="Agora" id="ENSG00000068366"/>
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        <property type="hits" value="88 hits in 803 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSL4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACSL4"/>
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    <dbReference type="Pharos" id="O60488">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O60488"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="RNAct" id="O60488">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000068366">
        <property type="expression patterns" value="Expressed in adrenal tissue and 194 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O60488">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005811">
        <property type="term" value="C:lipid droplet"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044233">
        <property type="term" value="C:mitochondria-associated endoplasmic reticulum membrane contact site"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005741">
        <property type="term" value="C:mitochondrial outer membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005778">
        <property type="term" value="C:peroxisomal membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047676">
        <property type="term" value="F:arachidonate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004467">
        <property type="term" value="F:long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090433">
        <property type="term" value="F:palmitoyl-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031957">
        <property type="term" value="F:very long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036109">
        <property type="term" value="P:alpha-linolenic acid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0060136">
        <property type="term" value="P:embryonic process involved in female pregnancy"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0006631">
        <property type="term" value="P:fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008610">
        <property type="term" value="P:lipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006629">
        <property type="term" value="P:lipid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042759">
        <property type="term" value="P:long-chain fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001676">
        <property type="term" value="P:long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035338">
        <property type="term" value="P:long-chain fatty-acyl-CoA biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035336">
        <property type="term" value="P:long-chain fatty-acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032307">
        <property type="term" value="P:negative regulation of prostaglandin secretion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030182">
        <property type="term" value="P:neuron differentiation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0030307">
        <property type="term" value="P:positive regulation of cell growth"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0160020">
        <property type="term" value="P:positive regulation of ferroptosis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032024">
        <property type="term" value="P:positive regulation of insulin secretion"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006636">
        <property type="term" value="P:unsaturated fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd17639">
        <property type="entry name" value="LC_FACS_euk1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43272">
        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43272:SF22">
        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0023">Alport syndrome</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0250">Elliptocytosis</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0360">Hereditary hemolytic anemia</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000193109" description="Long-chain-fatty-acid--CoA ligase 4">
        <location>
            <begin position="1"/>
            <end position="711"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="3">
        <location>
            <begin position="8"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="29"/>
            <end position="711"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by PKC/PRKCB" evidence="12">
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="21">
        <location>
            <position position="447"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="13">
        <location>
            <position position="679"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_000238" description="In isoform Short." evidence="15 16 18 19">
        <location>
            <begin position="1"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036376" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs753267653." evidence="5">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083476" evidence="10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013180" description="In XLID63; dbSNP:rs122458138." evidence="4">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="570"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished phosphorylation by isoform Beta-II of PRKCB, preventing ferroptosis." evidence="12">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished phosphorylation by PCK2, preventing ferroptosis." evidence="13">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="679"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA73314." evidence="20" ref="2">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O35547"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9BEA2"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11889465"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21242590"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="24269233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="27842070"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="29961568"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="31061331"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="35027735"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="38720107"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="9480748"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="31061331"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="9480748"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="9598324"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="711" mass="79188" checksum="6483CD17FE78FE73" modified="2001-04-27" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-04-03" modified="2026-01-28" version="189" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NR19</accession>
    <accession>A6NE90</accession>
    <accession>Q5QPH2</accession>
    <accession>Q5QPH3</accession>
    <accession>Q8N238</accession>
    <accession>Q96EL0</accession>
    <accession>Q9NQP7</accession>
    <accession>Q9UJ15</accession>
    <name>ACSA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acetyl-coenzyme A synthetase, cytoplasmic</fullName>
            <ecNumber evidence="4 5 6">6.2.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acetate--CoA ligase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acetyl-CoA synthetase</fullName>
            <shortName>ACS</shortName>
            <shortName>AceCS</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Acetyl-CoA synthetase 1</fullName>
            <shortName evidence="2">AceCS1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase short-chain family member 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acyl-activating enzyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Propionate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.17</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSS2</name>
        <name type="synonym">ACAS2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>SUBUNIT</scope>
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                <person name="Tashiro H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Tongue</tissue>
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    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28; SER-30; SER-36 AND SER-267</scope>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
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            <title>Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.</title>
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                <person name="Lu Z."/>
            </authorList>
            <dbReference type="PubMed" id="28552616"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2017.04.026"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PHOSPHORYLATION AT SER-659</scope>
        <scope>MUTAGENESIS OF THR-363; SER-659 AND 664-ARG--ARG-665</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>NUCLEOLAR LOCALIZATION SIGNAL</scope>
        <scope>INTERACTION WITH PRKAA2; TFEB AND KPAN1</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 5 6">Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:10843999, PubMed:28003429, PubMed:28552616). Acetate is the preferred substrate (PubMed:10843999, PubMed:28003429). Can also utilize propionate with a much lower affinity (By similarity). Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis (PubMed:28552616). Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription (PubMed:28552616). The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival (PubMed:28552616). Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes (By similarity). Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5 6">
            <text>acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:23176"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9 10">
            <dbReference type="Rhea" id="RHEA:23177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:20373"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.17"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:20374"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 4 6">Monomer (PubMed:10843999). Interacts with TFEB (PubMed:28552616). AMPK-mediated phosphorylated form at Ser-659 interacts with KPNA1; this interaction results in nuclear translocation of ACSS2 (PubMed:28552616). Interacts with the 'Thr-172' phosphorylated form of PRKAA2 (PubMed:28552616). Interacts with CREBBP (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 5 6">Cytoplasm</location>
            <location evidence="4 5 6">Cytosol</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Nucleus</location>
        </subcellularLocation>
        <text evidence="2 6">Glucose deprivation results in its AMPK-dependent phosphorylation and subsequent nuclear translocation (PubMed:28552616). Phosphorylation at Ser-659, leads to exposure of its nuclear localization signal which is required for its interaction with KPNA1 and subsequent translocation to the nucleus (PubMed:28552616). Found in the cytoplasm in undifferentiated neurons and upon differentiation, translocates to nucleus (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NR19-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NR19-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046376"/>
        </isoform>
    </comment>
    <comment type="PTM">
        <text evidence="2">Reversibly acetylated at Lys-661 (By similarity). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3 (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="6">Glucose deprivation results in its AMPK-dependent phosphorylation at Ser-659, which leads to exposure of its nuclear localization signal, required for its interaction with KPNA1 and subsequent translocation to the nucleus.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.1" evidence="4 5 6"/>
    <dbReference type="EC" id="6.2.1.17" evidence="2"/>
    <dbReference type="EMBL" id="AF263614">
        <property type="protein sequence ID" value="AAF75064.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092281">
        <property type="protein sequence ID" value="BAC03849.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133324">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL049709">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW76248.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012172">
        <property type="protein sequence ID" value="AAH12172.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13243.1">
        <molecule id="Q9NR19-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42868.2">
        <molecule id="Q9NR19-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001070020.2">
        <molecule id="Q9NR19-2"/>
        <property type="nucleotide sequence ID" value="NM_001076552.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_061147.1">
        <molecule id="Q9NR19-1"/>
        <property type="nucleotide sequence ID" value="NM_018677.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NR19"/>
    <dbReference type="SMR" id="Q9NR19"/>
    <dbReference type="BioGRID" id="120989">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NR19">
        <property type="interactions" value="1564"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NR19">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000253382"/>
    <dbReference type="BindingDB" id="Q9NR19"/>
    <dbReference type="ChEMBL" id="CHEMBL4523467"/>
    <dbReference type="DrugBank" id="DB00131">
        <property type="generic name" value="Adenosine phosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09395">
        <property type="generic name" value="Sodium acetate"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="3128"/>
    <dbReference type="SwissLipids" id="SLP:000001167"/>
    <dbReference type="GlyGen" id="Q9NR19">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NR19"/>
    <dbReference type="PhosphoSitePlus" id="Q9NR19"/>
    <dbReference type="SwissPalm" id="Q9NR19"/>
    <dbReference type="BioMuta" id="ACSS2"/>
    <dbReference type="DMDM" id="20137525"/>
    <dbReference type="jPOST" id="Q9NR19"/>
    <dbReference type="MassIVE" id="Q9NR19"/>
    <dbReference type="PaxDb" id="9606-ENSP00000253382"/>
    <dbReference type="PeptideAtlas" id="Q9NR19"/>
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        <property type="RefSeq protein sequence ID" value="NP_061147.1"/>
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        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000208423" description="Acetyl-coenzyme A synthetase, cytoplasmic">
        <location>
            <begin position="1"/>
            <end position="701"/>
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        <location>
            <begin position="1"/>
            <end position="107"/>
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    <feature type="region of interest" description="Disordered" evidence="3">
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            <begin position="1"/>
            <end position="41"/>
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    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="6">
        <location>
            <begin position="656"/>
            <end position="668"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="219"/>
            <end position="222"/>
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            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="363"/>
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        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="439"/>
            <end position="441"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="463"/>
            <end position="468"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="552"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="567"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="575"/>
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        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="636"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="14 15">
        <location>
            <position position="28"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 14 15">
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="263"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 13 14 15">
        <location>
            <position position="267"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="12">
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by AMPK" evidence="6">
        <location>
            <position position="659"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="661"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046376" description="In isoform 2." evidence="7">
        <original>V</original>
        <variation>VQGKLKEKSKRVQP</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of catalytic activity but no effect on its nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy." evidence="6">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="363"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on catalytic activity. Loss of AMPK-mediated phosphorylation, interaction with KPNA1 and nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy." evidence="6">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="659"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on catalytic activity. Loss of interaction with KPNA1 and nuclear translocation upon glucose deprivation. Loss of ability to promote gene transcription for lysosomal biogenesis and autophagy." evidence="6">
        <original>RR</original>
        <variation>AA</variation>
        <location>
            <begin position="664"/>
            <end position="665"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC03849." evidence="8" ref="2">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH12172." evidence="8" ref="5">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="615"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC03849." evidence="8" ref="2">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="680"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9QXG4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10843999"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="28003429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="28552616"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="10843999"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="28003429"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="701" mass="78580" checksum="833580B41B73A8B4" modified="2000-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="152" xmlns="https://uniprot.org/uniprot">
    <accession>Q6NUN0</accession>
    <accession>Q96AV1</accession>
    <accession>Q96CX8</accession>
    <accession>Q9NWV3</accession>
    <name>ACSM5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM5, mitochondrial</fullName>
            <ecNumber evidence="2">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM5</name>
        <name type="synonym">MACS3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
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            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
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            <dbReference type="PubMed" id="15616553"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Kidney</tissue>
        </source>
    </reference>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
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                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
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                <person name="Mannami T."/>
                <person name="Tomoike H."/>
                <person name="Ono K."/>
                <person name="Iwanaga Y."/>
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            <dbReference type="PubMed" id="12654705"/>
            <dbReference type="DOI" id="10.1161/01.hyp.0000064944.60569.87"/>
        </citation>
        <scope>VARIANTS HIS-159; ARG-352; ARG-360 AND MET-533</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6NUN0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6NUN0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_028398"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Detected in kidney and liver.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAA91273" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="2"/>
    <dbReference type="EMBL" id="AK000588">
        <property type="protein sequence ID" value="BAA91273.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC137056">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC013753">
        <property type="protein sequence ID" value="AAH13753.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016703">
        <property type="protein sequence ID" value="AAH16703.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC068516">
        <property type="protein sequence ID" value="AAH68516.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10585.1">
        <molecule id="Q6NUN0-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81954.1">
        <molecule id="Q6NUN0-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311300.1">
        <molecule id="Q6NUN0-1"/>
        <property type="nucleotide sequence ID" value="NM_001324371.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311302.1">
        <molecule id="Q6NUN0-2"/>
        <property type="nucleotide sequence ID" value="NM_001324373.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060358.2">
        <molecule id="Q6NUN0-1"/>
        <property type="nucleotide sequence ID" value="NM_017888.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6NUN0"/>
    <dbReference type="SMR" id="Q6NUN0"/>
    <dbReference type="BioGRID" id="120323">
        <property type="interactions" value="58"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6NUN0">
        <property type="interactions" value="51"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6NUN0">
        <property type="interactions" value="54"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000327916"/>
    <dbReference type="GlyGen" id="Q6NUN0">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6NUN0"/>
    <dbReference type="PhosphoSitePlus" id="Q6NUN0"/>
    <dbReference type="BioMuta" id="ACSM5"/>
    <dbReference type="DMDM" id="269849538"/>
    <dbReference type="MassIVE" id="Q6NUN0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000327916"/>
    <dbReference type="PeptideAtlas" id="Q6NUN0"/>
    <dbReference type="ProteomicsDB" id="66692">
        <molecule id="Q6NUN0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="66693">
        <molecule id="Q6NUN0-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="25526">
        <property type="antibodies" value="112 antibodies from 18 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="54988"/>
    <dbReference type="Ensembl" id="ENST00000331849.8">
        <molecule id="Q6NUN0-1"/>
        <property type="protein sequence ID" value="ENSP00000327916.4"/>
        <property type="gene ID" value="ENSG00000183549.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000575584.5">
        <molecule id="Q6NUN0-2"/>
        <property type="protein sequence ID" value="ENSP00000460112.1"/>
        <property type="gene ID" value="ENSG00000183549.11"/>
    </dbReference>
    <dbReference type="GeneID" id="54988"/>
    <dbReference type="KEGG" id="hsa:54988"/>
    <dbReference type="MANE-Select" id="ENST00000331849.8">
        <property type="protein sequence ID" value="ENSP00000327916.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_017888.3"/>
        <property type="RefSeq protein sequence ID" value="NP_060358.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002dhd.1">
        <molecule id="Q6NUN0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:26060"/>
    <dbReference type="ClinPGx" id="PA162375501"/>
    <dbReference type="CTD" id="54988"/>
    <dbReference type="DisGeNET" id="54988"/>
    <dbReference type="GeneCards" id="ACSM5"/>
    <dbReference type="HGNC" id="HGNC:26060">
        <property type="gene designation" value="ACSM5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000183549">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614361">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000183549"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000183549"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161148"/>
    <dbReference type="HOGENOM" id="CLU_088808_0_0_1"/>
    <dbReference type="InParanoid" id="Q6NUN0"/>
    <dbReference type="OMA" id="PFNWALD"/>
    <dbReference type="OrthoDB" id="6614653at2759"/>
    <dbReference type="PAN-GO" id="Q6NUN0">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6NUN0"/>
    <dbReference type="PathwayCommons" id="Q6NUN0"/>
    <dbReference type="Reactome" id="R-HSA-177128">
        <property type="pathway name" value="Conjugation of salicylate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9749641">
        <property type="pathway name" value="Aspirin ADME"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6NUN0"/>
    <dbReference type="Agora" id="ENSG00000183549"/>
    <dbReference type="BioGRID-ORCS" id="54988">
        <property type="hits" value="10 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="54988"/>
    <dbReference type="Pharos" id="Q6NUN0">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6NUN0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6NUN0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000183549">
        <property type="expression patterns" value="Expressed in right lobe of liver and 137 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6NUN0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005525">
        <property type="term" value="F:GTP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031956">
        <property type="term" value="F:medium-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd05928">
        <property type="entry name" value="MACS_euk"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM5, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605:SF6">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM5, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0342">GTP-binding</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="5">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000306101" description="Acyl-coenzyme A synthetase ACSM5, mitochondrial">
        <location>
            <begin position="27"/>
            <end position="579"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="230"/>
            <end position="238"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="368"/>
            <end position="373"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="455"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="470"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="566"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="3">
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="3">
        <location>
            <position position="303"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028398" description="In isoform 2." evidence="7">
        <location>
            <begin position="209"/>
            <end position="579"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055495" description="In dbSNP:rs9928053.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035252" description="In dbSNP:rs559741756." evidence="6">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055496" description="In dbSNP:rs7192210.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061011" description="In dbSNP:rs59025904.">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035253" description="In dbSNP:rs8062344." evidence="6">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="352"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035254" description="In dbSNP:rs12931877." evidence="6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035255" description="In dbSNP:rs554734865." evidence="6">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="533"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH16703." evidence="8" ref="3">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA91273." evidence="8" ref="1">
        <original>SGTT</original>
        <variation>KREPP</variation>
        <location>
            <begin position="231"/>
            <end position="234"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH68516." evidence="8" ref="3">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="502"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q08AH1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8BGA8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q91VA0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="12654705"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <sequence length="579" mass="64760" checksum="9493CB853CE29CB1" modified="2009-11-24" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="127" xmlns="https://uniprot.org/uniprot">
    <accession>Q6P461</accession>
    <accession>A4FU95</accession>
    <accession>A4IF38</accession>
    <accession>Q5VZX2</accession>
    <accession>Q6ZTX1</accession>
    <name>ACSM6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM6, mitochondrial</fullName>
            <ecNumber evidence="2">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 6</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM6</name>
        <name type="synonym">C10orf129</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-415 (ISOFORM 3)</scope>
        <scope>VARIANTS GLY-19 AND SER-40</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2016" name="Expert Opin. Drug Metab. Toxicol." volume="12" first="1169" last="1179">
            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
            <authorList>
                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="3">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6P461-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6P461-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_033908 VSP_033910 VSP_033911"/>
        </isoform>
        <isoform>
            <id>Q6P461-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_033909"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAI04211" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAI04212" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAI12989" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="2"/>
    <dbReference type="EMBL" id="AK126134">
        <property type="protein sequence ID" value="BAC86458.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL157834">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC063654">
        <property type="protein sequence ID" value="AAH63654.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC104210">
        <property type="protein sequence ID" value="AAI04211.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC104211">
        <property type="protein sequence ID" value="AAI04212.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC112988">
        <property type="protein sequence ID" value="AAI12989.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7440.2">
        <molecule id="Q6P461-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_997204.2">
        <molecule id="Q6P461-1"/>
        <property type="nucleotide sequence ID" value="NM_207321.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6P461"/>
    <dbReference type="SMR" id="Q6P461"/>
    <dbReference type="FunCoup" id="Q6P461">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000340296"/>
    <dbReference type="GlyGen" id="Q6P461">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6P461"/>
    <dbReference type="PhosphoSitePlus" id="Q6P461"/>
    <dbReference type="BioMuta" id="ACSM6"/>
    <dbReference type="MassIVE" id="Q6P461"/>
    <dbReference type="PaxDb" id="9606-ENSP00000340296"/>
    <dbReference type="PeptideAtlas" id="Q6P461"/>
    <dbReference type="Antibodypedia" id="48989">
        <property type="antibodies" value="61 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="142827"/>
    <dbReference type="Ensembl" id="ENST00000394005.4">
        <molecule id="Q6P461-1"/>
        <property type="protein sequence ID" value="ENSP00000377573.3"/>
        <property type="gene ID" value="ENSG00000173124.15"/>
    </dbReference>
    <dbReference type="GeneID" id="142827"/>
    <dbReference type="KEGG" id="hsa:142827"/>
    <dbReference type="MANE-Select" id="ENST00000394005.4">
        <property type="protein sequence ID" value="ENSP00000377573.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_207321.3"/>
        <property type="RefSeq protein sequence ID" value="NP_997204.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001kke.4">
        <molecule id="Q6P461-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31665"/>
    <dbReference type="ClinPGx" id="PA134905303"/>
    <dbReference type="CTD" id="142827"/>
    <dbReference type="DisGeNET" id="142827"/>
    <dbReference type="GeneCards" id="ACSM6"/>
    <dbReference type="HGNC" id="HGNC:31665">
        <property type="gene designation" value="ACSM6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000173124">
        <property type="expression patterns" value="Tissue enhanced (lymphoid tissue, pancreas, skin, stomach)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000173124"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000173124"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000165168"/>
    <dbReference type="HOGENOM" id="CLU_000022_59_10_1"/>
    <dbReference type="InParanoid" id="Q6P461"/>
    <dbReference type="OMA" id="FGACCYP"/>
    <dbReference type="OrthoDB" id="10253869at2759"/>
    <dbReference type="PAN-GO" id="Q6P461">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6P461"/>
    <dbReference type="PathwayCommons" id="Q6P461"/>
    <dbReference type="Reactome" id="R-HSA-77352">
        <property type="pathway name" value="Beta oxidation of butanoyl-CoA to acetyl-CoA"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000173124"/>
    <dbReference type="BioGRID-ORCS" id="142827">
        <property type="hits" value="7 hits in 1138 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="142827"/>
    <dbReference type="Pharos" id="Q6P461">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6P461"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6P461">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000173124">
        <property type="expression patterns" value="Expressed in thymus and 53 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6P461">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005525">
        <property type="term" value="F:GTP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031956">
        <property type="term" value="F:medium-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605:SF1">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM6, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0342">GTP-binding</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="4">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000337112" description="Acyl-coenzyme A synthetase ACSM6, mitochondrial">
        <location>
            <begin position="22"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="226"/>
            <end position="234"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="366"/>
            <end position="371"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="453"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="468"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_033908" description="In isoform 2." evidence="6">
        <location>
            <begin position="1"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033909" description="In isoform 3." evidence="7">
        <original>D</original>
        <variation>DNGLQLHPCCCKRQDFILFHGVIFHVD</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033910" description="In isoform 2." evidence="6">
        <original>SYRFKSLKQC</original>
        <variation>RVYSVPLPKQ</variation>
        <location>
            <begin position="332"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033911" description="In isoform 2." evidence="6">
        <location>
            <begin position="342"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_063090" description="In dbSNP:rs591157." evidence="5">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_063091" description="In dbSNP:rs11188225." evidence="5">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043606" description="In dbSNP:rs7090248.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q08AH1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9BEA2"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <sequence length="480" mass="53585" checksum="E33F51846DBB8253" modified="2010-04-20" version="3" precursor="true">MLGRFQPFSLVRSFRLGFEACCYPNQKCATQTIRPPDSRCLVQAVSQNFNFAKDVLDQWSQLEKDGLRGPYPALWKVSAKGEEDKWSFERMTQLSKKAASILSDTCALSHGDRLMIILPPTPEAYWICLACVRLGITFVPGSPQLTAKKIRYQLRMSKAQCIVANEAMAPVVNSAVSDCPTLKTKLLVSDKSYDGWLDFKKLIQVAPPKQTYMRTKSQDPMAIFFTKGTTGAPKMVEYSQYGLGMGFSQASRRWMDLQPTDVLWSLGDAFGGSLSLSAVLGTWFQGACVFLCHMPTFCPETVLNVLSRFPITTLSANPEMYQELLQHKCFTSYRFKSLKQCVAAGGPISPGVIEDWKRITKLDIYEGYGQTETGLLCATSKTIKLKPSSLGKPLPPYIVQIVDENSNLLPPGEEGNIAIRIKLNQPASLYCPHMVSWEEYASARGHMLYLTGDRGIMDEDGYFWWSGRVDDVANALGQRL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-26" modified="2026-01-28" version="173" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H6R3</accession>
    <accession>Q8NC66</accession>
    <name>ACSS3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-CoA synthetase short-chain family member 3, mitochondrial</fullName>
            <ecNumber evidence="2">6.2.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acetate--CoA ligase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase short-chain family member 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Propionate--CoA ligase</fullName>
            <ecNumber evidence="5">6.2.1.17</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSS3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Hepatoma</tissue>
            <tissue>Teratocarcinoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2007" name="J. Lipid Res." volume="48" first="2736" last="2750">
            <title>Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome.</title>
            <authorList>
                <person name="Watkins P.A."/>
                <person name="Maiguel D."/>
                <person name="Jia Z."/>
                <person name="Pevsner J."/>
            </authorList>
            <dbReference type="PubMed" id="17762044"/>
            <dbReference type="DOI" id="10.1194/jlr.m700378-jlr200"/>
        </citation>
        <scope>IDENTIFICATION</scope>
        <scope>NOMENCLATURE</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2017" name="J. Biochem." volume="161" first="279" last="289">
            <title>Molecular cloning of rat acss3 and characterization of mammalian propionyl-CoA synthetase in the liver mitochondrial matrix.</title>
            <authorList>
                <person name="Yoshimura Y."/>
                <person name="Araki A."/>
                <person name="Maruta H."/>
                <person name="Takahashi Y."/>
                <person name="Yamashita H."/>
            </authorList>
            <dbReference type="PubMed" id="28003429"/>
            <dbReference type="DOI" id="10.1093/jb/mvw067"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="2 5">Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:28003429). Propionate is the preferred substrate (PubMed:28003429). Can utilize acetate and butyrate with a much lower affinity (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:23176"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:23177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:20373"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.17"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:20374"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46172"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:46173"/>
        </physiologicalReaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3921478">
            <id>Q9H6R3</id>
        </interactant>
        <interactant intactId="EBI-748974">
            <id>Q96CV9</id>
            <label>OPTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H6R3-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H6R3-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_031692"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.1" evidence="2"/>
    <dbReference type="EC" id="6.2.1.17" evidence="5"/>
    <dbReference type="EMBL" id="AK025616">
        <property type="protein sequence ID" value="BAB15190.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074938">
        <property type="protein sequence ID" value="BAC11304.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW97372.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009317">
        <property type="protein sequence ID" value="AAH09317.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015769">
        <property type="protein sequence ID" value="AAH15769.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9022.1">
        <molecule id="Q9H6R3-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001317171.1">
        <property type="nucleotide sequence ID" value="NM_001330242.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001317172.1">
        <molecule id="Q9H6R3-2"/>
        <property type="nucleotide sequence ID" value="NM_001330243.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_078836.1">
        <molecule id="Q9H6R3-1"/>
        <property type="nucleotide sequence ID" value="NM_024560.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H6R3"/>
    <dbReference type="SMR" id="Q9H6R3"/>
    <dbReference type="BioGRID" id="122745">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9H6R3">
        <property type="interactions" value="962"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H6R3">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000449535"/>
    <dbReference type="GlyGen" id="Q9H6R3">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H6R3"/>
    <dbReference type="PhosphoSitePlus" id="Q9H6R3"/>
    <dbReference type="BioMuta" id="ACSS3"/>
    <dbReference type="DMDM" id="74752698"/>
    <dbReference type="jPOST" id="Q9H6R3"/>
    <dbReference type="MassIVE" id="Q9H6R3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000449535"/>
    <dbReference type="PeptideAtlas" id="Q9H6R3"/>
    <dbReference type="ProteomicsDB" id="81014">
        <molecule id="Q9H6R3-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81015">
        <molecule id="Q9H6R3-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9H6R3"/>
    <dbReference type="TopDownProteomics" id="Q9H6R3-1">
        <molecule id="Q9H6R3-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="29817">
        <property type="antibodies" value="115 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="79611"/>
    <dbReference type="Ensembl" id="ENST00000548058.6">
        <molecule id="Q9H6R3-1"/>
        <property type="protein sequence ID" value="ENSP00000449535.1"/>
        <property type="gene ID" value="ENSG00000111058.9"/>
    </dbReference>
    <dbReference type="GeneID" id="79611"/>
    <dbReference type="KEGG" id="hsa:79611"/>
    <dbReference type="MANE-Select" id="ENST00000548058.6">
        <property type="protein sequence ID" value="ENSP00000449535.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_024560.4"/>
        <property type="RefSeq protein sequence ID" value="NP_078836.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001szl.2">
        <molecule id="Q9H6R3-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24723"/>
    <dbReference type="ClinPGx" id="PA162375534"/>
    <dbReference type="CTD" id="79611"/>
    <dbReference type="DisGeNET" id="79611"/>
    <dbReference type="GeneCards" id="ACSS3"/>
    <dbReference type="HGNC" id="HGNC:24723">
        <property type="gene designation" value="ACSS3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000111058">
        <property type="expression patterns" value="Tissue enhanced (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="614356">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000111058"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000111058"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157479"/>
    <dbReference type="HOGENOM" id="CLU_000022_3_5_1"/>
    <dbReference type="InParanoid" id="Q9H6R3"/>
    <dbReference type="OMA" id="FIMGRTD"/>
    <dbReference type="OrthoDB" id="10253869at2759"/>
    <dbReference type="PAN-GO" id="Q9H6R3">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H6R3"/>
    <dbReference type="PathwayCommons" id="Q9H6R3"/>
    <dbReference type="Reactome" id="R-HSA-77111">
        <property type="pathway name" value="Synthesis of Ketone Bodies"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9841922">
        <property type="pathway name" value="MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9H6R3"/>
    <dbReference type="SIGNOR" id="Q9H6R3"/>
    <dbReference type="Agora" id="ENSG00000111058"/>
    <dbReference type="BioGRID-ORCS" id="79611">
        <property type="hits" value="12 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSS3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="79611"/>
    <dbReference type="Pharos" id="Q9H6R3">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H6R3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H6R3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000111058">
        <property type="expression patterns" value="Expressed in germinal epithelium of ovary and 153 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9H6R3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003987">
        <property type="term" value="F:acetate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031956">
        <property type="term" value="F:medium-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050218">
        <property type="term" value="F:propionate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046951">
        <property type="term" value="P:ketone body biosynthetic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="CDD" id="cd05967">
        <property type="entry name" value="PrpE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000011">
        <property type="entry name" value="Acetyl-coenzyme A synthetase 2-like, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000017">
        <property type="entry name" value="Acyl-CoA synthetase short-chain family member 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032387">
        <property type="entry name" value="ACAS_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43347">
        <property type="entry name" value="ACYL-COA SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43347:SF3">
        <property type="entry name" value="ACYL-COA SYNTHETASE SHORT-CHAIN FAMILY MEMBER 3, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF16177">
        <property type="entry name" value="ACAS_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="4">
        <location>
            <begin position="1"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000320624" description="Acyl-CoA synthetase short-chain family member 3, mitochondrial">
        <location>
            <begin position="30"/>
            <end position="686"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="227"/>
            <end position="230"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="425"/>
            <end position="427"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="446"/>
            <end position="451"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="539"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="554"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="565"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="624"/>
        </location>
        <ligand>
            <name>CoA</name>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="524"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_031692" description="In isoform 2." evidence="6">
        <location>
            <begin position="1"/>
            <end position="318"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC11304." evidence="7" ref="1">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="428"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="A0A0G2K047"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q14DH7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="28003429"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="28003429"/>
        </source>
    </evidence>
    <sequence length="686" mass="74778" checksum="3386338C6FFFD7E8" modified="2001-03-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-04-27" modified="2026-01-28" version="208" xmlns="https://uniprot.org/uniprot">
    <accession>Q9ULC5</accession>
    <accession>A6GV77</accession>
    <accession>D3DRB3</accession>
    <accession>Q6UX44</accession>
    <accession>Q9UIU4</accession>
    <name>ACSL5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="17">Long-chain-fatty-acid--CoA ligase 5</fullName>
            <ecNumber evidence="6 9 10">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="17">Arachidonate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 5</fullName>
            <shortName>LACS 5</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="21" type="primary">ACSL5</name>
        <name evidence="16" type="synonym">ACS5</name>
        <name evidence="16" type="synonym">FACL5</name>
        <name type="ORF">UNQ633/PRO1250</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
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    <reference key="8">
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            <title>Human FACL5 (or ACS5).</title>
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                <person name="Yamashita Y."/>
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        <scope>PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2)</scope>
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            <dbReference type="PubMed" id="18691976"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32 (ISOFORM 2)</scope>
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            <dbReference type="PubMed" id="19459852"/>
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        <scope>FUNCTION</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <reference key="12">
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <dbReference type="PubMed" id="22633490"/>
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        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="14">
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                <person name="Ohkuni A."/>
                <person name="Ohno Y."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="24269233"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2013.11.036"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="15">
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
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                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
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            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] ARG-388 AND ASP-466</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2021" name="Clin. Genet." volume="99" first="376" last="383">
            <title>Deficiency of acyl-CoA synthetase 5 is associated with a severe and treatable failure to thrive of neonatal onset.</title>
            <authorList>
                <person name="Al-Thihli K."/>
                <person name="Afting C."/>
                <person name="Al-Hashmi N."/>
                <person name="Mohammed M."/>
                <person name="Sliwinski S."/>
                <person name="Al Shibli N."/>
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                <person name="Al-Kasbi G."/>
                <person name="Al-Kharusi K."/>
                <person name="Merle U."/>
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                <person name="Al-Maawali A."/>
            </authorList>
            <dbReference type="PubMed" id="33191500"/>
            <dbReference type="DOI" id="10.1111/cge.13883"/>
        </citation>
        <scope>VARIANT DIAR13 LYS-453</scope>
        <scope>CHARACTERIZATION OF VARIANT DIAR13 LYS-453</scope>
        <scope>INVOLVEMENT IN DIAR13</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6 7 8 9 10 11">Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:17681178, PubMed:22633490, PubMed:24269233, PubMed:33191500). ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 9 10">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18 19">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="19">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 19">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18 19">
            <dbReference type="Rhea" id="RHEA:36140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52116"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:78832"/>
            <dbReference type="ChEBI" id="CHEBI:136409"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52117"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52112"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:90718"/>
            <dbReference type="ChEBI" id="CHEBI:136408"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52108"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65341"/>
            <dbReference type="ChEBI" id="CHEBI:136407"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52109"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52016"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84024"/>
            <dbReference type="ChEBI" id="CHEBI:136117"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52017"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52012"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76625"/>
            <dbReference type="ChEBI" id="CHEBI:136115"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52013"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33607"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20">
            <dbReference type="Rhea" id="RHEA:33608"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 1</molecule>
        <kinetics>
            <KM evidence="6">0.11 uM for palmitic acid (at pH 7.5)</KM>
            <KM evidence="6">0.38 uM for palmitic acid (at pH 9.5)</KM>
        </kinetics>
        <phDependence>
            <text evidence="6">Optimum pH is 9.5.</text>
        </phDependence>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 3</molecule>
        <kinetics>
            <KM evidence="6">0.04 uM for palmitic acid (at pH 7.5)</KM>
            <KM evidence="6">0.15 uM for palmitic acid (at pH 8.5)</KM>
        </kinetics>
        <phDependence>
            <text evidence="6">Optimum pH is 7.5-8.5.</text>
        </phDependence>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-13059134">
            <id>Q13520</id>
            <label>AQP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-8787095">
            <id>O00559</id>
            <label>EBAG9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-594836">
            <id>O00623</id>
            <label>PEX12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-10192441">
            <id>Q86VR2</id>
            <label>RETREG3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-751012">
            <id>Q8WU57</id>
            <label>SELI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-3923031">
            <id>Q14973</id>
            <label>SLC10A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-18159983">
            <id>Q3KNW5</id>
            <label>SLC10A6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-3921243">
            <id>O60669</id>
            <label>SLC16A7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-17295964">
            <id>Q9NQQ7-3</id>
            <label>SLC35C2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-5235586">
            <id>Q8TBB6</id>
            <label>SLC7A14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2876927">
            <id>Q9ULC5</id>
        </interactant>
        <interactant intactId="EBI-8638294">
            <id>Q9NUH8</id>
            <label>TMEM14B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 11">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 10 11">Endoplasmic reticulum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Mitochondrion outer membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endoplasmic reticulum membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9ULC5-1</id>
            <name>1</name>
            <name>ACSL5b</name>
            <name>ACSL5-fl</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9ULC5-3</id>
            <name>2</name>
            <name>ACSL5a</name>
            <sequence type="described" ref="VSP_037947"/>
        </isoform>
        <isoform>
            <id>Q9ULC5-4</id>
            <name>3</name>
            <name>ACSL5delta20</name>
            <sequence type="described" ref="VSP_038233"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="11">
        <disease id="DI-06658">
            <name>Diarrhea 13</name>
            <acronym>DIAR13</acronym>
            <description>An autosomal recessive disorder characterized by neonatal onset of recurrent vomiting and diarrhea, leading to severe failure to thrive.</description>
            <dbReference type="MIM" id="620357"/>
        </disease>
        <text>The disease may be caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>Localize in mitochondrion and endoplasmic reticulum.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="17">Localize in mitochondrion and endoplasmic reticulum.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA85979" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="BAA86054" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="6 9 10"/>
    <dbReference type="EC" id="6.2.1.15" evidence="2"/>
    <dbReference type="EMBL" id="AM262166">
        <property type="protein sequence ID" value="CAK18174.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358520">
        <property type="protein sequence ID" value="AAQ88884.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000339">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK222782">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL157786">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49532.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49535.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49536.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49539.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007985">
        <property type="protein sequence ID" value="AAH07985.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB033899">
        <property type="protein sequence ID" value="BAA85979.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB033920">
        <property type="protein sequence ID" value="BAA86054.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7572.1">
        <molecule id="Q9ULC5-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7573.1">
        <molecule id="Q9ULC5-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_057318.2">
        <molecule id="Q9ULC5-3"/>
        <property type="nucleotide sequence ID" value="NM_016234.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_976313.1">
        <molecule id="Q9ULC5-1"/>
        <property type="nucleotide sequence ID" value="NM_203379.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_976314.1">
        <molecule id="Q9ULC5-1"/>
        <property type="nucleotide sequence ID" value="NM_203380.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9ULC5"/>
    <dbReference type="SMR" id="Q9ULC5"/>
    <dbReference type="BioGRID" id="119687">
        <property type="interactions" value="32"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9ULC5">
        <property type="interactions" value="1562"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9ULC5">
        <property type="interactions" value="29"/>
    </dbReference>
    <dbReference type="MINT" id="Q9ULC5"/>
    <dbReference type="STRING" id="9606.ENSP00000348429"/>
    <dbReference type="BindingDB" id="Q9ULC5"/>
    <dbReference type="ChEMBL" id="CHEMBL4105818"/>
    <dbReference type="DrugCentral" id="Q9ULC5"/>
    <dbReference type="SwissLipids" id="SLP:000000202"/>
    <dbReference type="SwissLipids" id="SLP:000000517">
        <molecule id="Q9ULC5-3"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000000518">
        <molecule id="Q9ULC5-1"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9ULC5">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9ULC5">
        <property type="glycosylation" value="4 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9ULC5"/>
    <dbReference type="PhosphoSitePlus" id="Q9ULC5"/>
    <dbReference type="SwissPalm" id="Q9ULC5"/>
    <dbReference type="BioMuta" id="ACSL5"/>
    <dbReference type="DMDM" id="13431659"/>
    <dbReference type="jPOST" id="Q9ULC5"/>
    <dbReference type="MassIVE" id="Q9ULC5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000348429"/>
    <dbReference type="PeptideAtlas" id="Q9ULC5"/>
    <dbReference type="ProteomicsDB" id="84979">
        <molecule id="Q9ULC5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84980">
        <molecule id="Q9ULC5-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84981">
        <molecule id="Q9ULC5-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9ULC5"/>
    <dbReference type="Antibodypedia" id="31809">
        <property type="antibodies" value="279 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51703"/>
    <dbReference type="Ensembl" id="ENST00000354655.9">
        <molecule id="Q9ULC5-1"/>
        <property type="protein sequence ID" value="ENSP00000346680.4"/>
        <property type="gene ID" value="ENSG00000197142.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000356116.6">
        <molecule id="Q9ULC5-3"/>
        <property type="protein sequence ID" value="ENSP00000348429.1"/>
        <property type="gene ID" value="ENSG00000197142.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000393081.6">
        <molecule id="Q9ULC5-1"/>
        <property type="protein sequence ID" value="ENSP00000376796.1"/>
        <property type="gene ID" value="ENSG00000197142.12"/>
    </dbReference>
    <dbReference type="GeneID" id="51703"/>
    <dbReference type="KEGG" id="hsa:51703"/>
    <dbReference type="MANE-Select" id="ENST00000354655.9">
        <property type="protein sequence ID" value="ENSP00000346680.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_203379.2"/>
        <property type="RefSeq protein sequence ID" value="NP_976313.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001kzs.4">
        <molecule id="Q9ULC5-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16526"/>
    <dbReference type="ClinPGx" id="PA27969"/>
    <dbReference type="CTD" id="51703"/>
    <dbReference type="DisGeNET" id="51703"/>
    <dbReference type="GeneCards" id="ACSL5"/>
    <dbReference type="HGNC" id="HGNC:16526">
        <property type="gene designation" value="ACSL5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000197142">
        <property type="expression patterns" value="Tissue enhanced (epididymis, intestine, liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACSL5"/>
    <dbReference type="MIM" id="605677">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="620357">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000197142"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000197142"/>
    <dbReference type="eggNOG" id="KOG1256">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156651"/>
    <dbReference type="HOGENOM" id="CLU_000022_45_4_1"/>
    <dbReference type="InParanoid" id="Q9ULC5"/>
    <dbReference type="OMA" id="IWHSYER"/>
    <dbReference type="OrthoDB" id="1700726at2759"/>
    <dbReference type="PAN-GO" id="Q9ULC5">
        <property type="GO annotations" value="8 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9ULC5"/>
    <dbReference type="BioCyc" id="MetaCyc:HS01349-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q9ULC5"/>
    <dbReference type="Reactome" id="R-HSA-75876">
        <property type="pathway name" value="Synthesis of very long-chain fatty acyl-CoAs"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9ULC5"/>
    <dbReference type="SignaLink" id="Q9ULC5"/>
    <dbReference type="SIGNOR" id="Q9ULC5"/>
    <dbReference type="Agora" id="ENSG00000197142"/>
    <dbReference type="BioGRID-ORCS" id="51703">
        <property type="hits" value="23 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSL5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACSL5"/>
    <dbReference type="GenomeRNAi" id="51703"/>
    <dbReference type="Pharos" id="Q9ULC5">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9ULC5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9ULC5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000197142">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 181 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005741">
        <property type="term" value="C:mitochondrial outer membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0047676">
        <property type="term" value="F:arachidonate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004467">
        <property type="term" value="F:long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090434">
        <property type="term" value="F:oleoyl-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001676">
        <property type="term" value="P:long-chain fatty acid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035338">
        <property type="term" value="P:long-chain fatty-acyl-CoA biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010747">
        <property type="term" value="P:positive regulation of long-chain fatty acid import across plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:2001236">
        <property type="term" value="P:regulation of extrinsic apoptotic signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd05927">
        <property type="entry name" value="LC-FACS_euk"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000006">
        <property type="entry name" value="long-chain-fatty-acid--CoA ligase 6 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045311">
        <property type="entry name" value="LC-FACS_euk"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43272">
        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43272:SF107">
        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000193112" description="Long-chain-fatty-acid--CoA ligase 5">
        <location>
            <begin position="1"/>
            <end position="683"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="4">
        <location>
            <begin position="12"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="33"/>
            <end position="683"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="361"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037947" description="In isoform 2." evidence="12 13 15">
        <original>M</original>
        <variation>MDALKPPCLWRNHERGKKDRDSCGRKNSEPGSPHSLEALRDAAPSQGLNFLLLFTKM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_038233" description="In isoform 3." evidence="14">
        <location>
            <begin position="614"/>
            <end position="637"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022117" description="In dbSNP:rs3736946.">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036377" description="In a colorectal cancer sample; somatic mutation." evidence="5">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="388"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088452" description="In DIAR13; loss of oleoyl-CoA ligase activity; does not affect localization to mitochondrion; does not affect localization to endoplasmic reticulum." evidence="11">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="453"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036378" description="In a colorectal cancer sample; somatic mutation." evidence="5">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="466"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048240" description="In dbSNP:rs12254915.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="486"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="22">
        <location sequence="Q9ULC5-3">
            <position position="32"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="O88813"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8JZR0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17681178"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="18806831"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="19459852"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="24269233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="33191500"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="12975309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="17681178"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0000305" key="18">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="24269233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="20">
        <source>
            <dbReference type="PubMed" id="33191500"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="21">
        <source>
            <dbReference type="HGNC" id="HGNC:16526"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <sequence length="683" mass="75991" checksum="781AFE1A7A78C286" modified="2000-05-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-10-01" modified="2026-01-28" version="218" xmlns="https://uniprot.org/uniprot">
    <accession>P33121</accession>
    <accession>B7Z452</accession>
    <accession>D3DP57</accession>
    <accession>P41215</accession>
    <accession>Q8N8V7</accession>
    <accession>Q8TA99</accession>
    <name>ACSL1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">Long-chain-fatty-acid--CoA ligase 1</fullName>
            <ecNumber evidence="7 8">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase 1</fullName>
            <shortName>ACS1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Arachidonate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 1</fullName>
            <shortName>LACS 1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 2</fullName>
            <shortName>LACS 2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain fatty acid-CoA ligase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Palmitoyl-CoA ligase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Palmitoyl-CoA ligase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Phytanate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.24</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15" type="primary">ACSL1</name>
        <name type="synonym">FACL1</name>
        <name type="synonym">FACL2</name>
        <name type="synonym">LACS</name>
        <name type="synonym">LACS1</name>
        <name type="synonym">LACS2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 395-698 (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PROTEIN SEQUENCE OF 1-8; 12-19; 341-349; 377-386; 562-572; 633-640 AND 655-675</scope>
        <scope>ACETYLATION AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>B-cell lymphoma</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1999" name="Biochem. J." volume="344" first="135" last="143">
            <title>Identification and molecular characterization of acyl-CoA synthetase in human red cells and erythroid precursor.</title>
            <authorList>
                <person name="Malhotra K.T."/>
                <person name="Malhotra K."/>
                <person name="Lubin B.H."/>
                <person name="Kuypers F.A."/>
            </authorList>
            <dbReference type="PubMed" id="10548543"/>
            <dbReference type="DOI" id="10.1042/bj3440135"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="J. Lipid Res." volume="52" first="782" last="793">
            <title>Long-chain acyl-CoA synthetase 4 modulates prostaglandin E(2) release from human arterial smooth muscle cells.</title>
            <authorList>
                <person name="Golej D.L."/>
                <person name="Askari B."/>
                <person name="Kramer F."/>
                <person name="Barnhart S."/>
                <person name="Vivekanandan-Giri A."/>
                <person name="Pennathur S."/>
                <person name="Bornfeldt K.E."/>
            </authorList>
            <dbReference type="PubMed" id="21242590"/>
            <dbReference type="DOI" id="10.1194/jlr.m013292"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2012" name="Mol. Cell" volume="46" first="461" last="471">
            <title>The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.</title>
            <authorList>
                <person name="Nakahara K."/>
                <person name="Ohkuni A."/>
                <person name="Kitamura T."/>
                <person name="Abe K."/>
                <person name="Naganuma T."/>
                <person name="Ohno Y."/>
                <person name="Zoeller R.A."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="22633490"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2012.04.033"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2013" name="Biochem. Biophys. Res. Commun." volume="442" first="195" last="201">
            <title>Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway.</title>
            <authorList>
                <person name="Ohkuni A."/>
                <person name="Ohno Y."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="24269233"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2013.11.036"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-620</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2 6 7 8">Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:21242590, PubMed:22633490, PubMed:24269233). Preferentially uses palmitoleate, oleate and linoleate (PubMed:24269233). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs) (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13 14">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>3,7,11,15-tetramethylhexadecanoate + ATP + CoA = phytanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:21380"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:37257"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57391"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.24"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:21381"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 8">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12 14">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13 14">
            <dbReference type="Rhea" id="RHEA:36140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>2,6,10,14-tetramethylpentadecanoate + ATP + CoA = pristanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:47264"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77250"/>
            <dbReference type="ChEBI" id="CHEBI:77268"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:47265"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52016"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84024"/>
            <dbReference type="ChEBI" id="CHEBI:136117"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52017"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52108"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65341"/>
            <dbReference type="ChEBI" id="CHEBI:136407"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52109"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52112"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:90718"/>
            <dbReference type="ChEBI" id="CHEBI:136408"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52116"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:78832"/>
            <dbReference type="ChEBI" id="CHEBI:136409"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52117"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33607"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:33608"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Inhibited at high temperature and by arachidonate.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion outer membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Peroxisome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Microsome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Endoplasmic reticulum membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P33121-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P33121-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009604"/>
        </isoform>
        <isoform>
            <id>P33121-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_054391"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Highly expressed in liver, heart, skeletal muscle, kidney and erythroid cells, and to a lesser extent in brain, lung, placenta and pancreas.</text>
    </comment>
    <comment type="developmental stage">
        <text>Expressed during the early stages of erythroid development while expression is very low in reticulocytes and young erythrocytes.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="11">May be due to a competing acceptor splice site.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAC04704" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="7 8"/>
    <dbReference type="EC" id="6.2.1.15" evidence="2"/>
    <dbReference type="EC" id="6.2.1.24" evidence="2"/>
    <dbReference type="EMBL" id="D10040">
        <property type="protein sequence ID" value="BAA00931.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L09229">
        <property type="protein sequence ID" value="AAB00959.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK096117">
        <property type="protein sequence ID" value="BAC04704.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK296826">
        <property type="protein sequence ID" value="BAH12438.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC079257">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC084871">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX04662.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX04663.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX04665.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC026290">
        <property type="protein sequence ID" value="AAH26290.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC050073">
        <property type="protein sequence ID" value="AAH50073.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3839.1">
        <molecule id="P33121-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS68826.1">
        <molecule id="P33121-3"/>
    </dbReference>
    <dbReference type="PIR" id="JX0202">
        <property type="entry name" value="JX0202"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273637.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001286708.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273639.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="NM_001286710.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273640.1">
        <property type="nucleotide sequence ID" value="NM_001286711.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368806.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381877.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368807.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381878.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368808.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381879.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368809.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381880.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368810.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381881.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368811.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381882.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368812.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001381883.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368813.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="NM_001381884.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368814.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="NM_001381885.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368815.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="NM_001381886.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001368816.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="NM_001381887.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001986.2">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="NM_001995.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016863376.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="XM_017007887.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047305775.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="XM_047449819.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054205230.1">
        <molecule id="P33121-3"/>
        <property type="nucleotide sequence ID" value="XM_054349255.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054205231.1">
        <molecule id="P33121-1"/>
        <property type="nucleotide sequence ID" value="XM_054349256.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P33121"/>
    <dbReference type="SMR" id="P33121"/>
    <dbReference type="BioGRID" id="108476">
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        <property type="antibodies" value="308 antibodies from 35 providers"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_001995.5"/>
        <property type="RefSeq protein sequence ID" value="NP_001986.2"/>
    </dbReference>
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        <property type="type" value="gene"/>
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        <property type="project" value="RHEA"/>
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        <property type="project" value="ARUK-UCL"/>
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="project" value="YuBioLab"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AMP-binding_CS"/>
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        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
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        <property type="entry name" value="ANL_N_sf"/>
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        <property type="entry name" value="LC-FACS_euk"/>
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        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE 1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0492">Microsome</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0944">Nitration</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000193104" description="Long-chain-fatty-acid--CoA ligase 1">
        <location>
            <begin position="1"/>
            <end position="698"/>
        </location>
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    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="4">
        <location>
            <begin position="25"/>
            <end position="45"/>
        </location>
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    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="46"/>
            <end position="698"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="9">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="3'-nitrotyrosine" evidence="2">
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
        <location>
            <position position="386"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="16">
        <location>
            <position position="620"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="632"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GlcNAc) serine" evidence="1">
        <location>
            <position position="135"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054391" description="In isoform 3." evidence="10">
        <original>NTVNPCPDDTLISFLPLAHMFERVVE</original>
        <variation>KALPLSASDTHISYLPLAHIYEQLLK</variation>
        <location>
            <begin position="306"/>
            <end position="331"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009604" description="In isoform 2." evidence="10">
        <location>
            <begin position="508"/>
            <end position="517"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>YVR</original>
        <variation>CV</variation>
        <location>
            <begin position="21"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>AA</original>
        <variation>SRR</variation>
        <location>
            <begin position="37"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>YATR</original>
        <variation>RPRH</variation>
        <location>
            <begin position="44"/>
            <end position="47"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>CD</original>
        <variation>WH</variation>
        <location>
            <begin position="55"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="385"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>EL</original>
        <variation>DV</variation>
        <location>
            <begin position="400"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="477"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>VDV</original>
        <variation>GWQL</variation>
        <location>
            <begin position="492"/>
            <end position="494"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="502"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB00959." evidence="11" ref="2">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="695"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P18163"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P41216"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10548543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21242590"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="24269233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="21242590"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="24269233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:3569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="698" mass="77943" checksum="FD6669453589D362" modified="1993-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="147" xmlns="https://uniprot.org/uniprot">
    <accession>Q4L235</accession>
    <accession>A5D8V3</accession>
    <accession>A5PL22</accession>
    <accession>Q63HK2</accession>
    <accession>Q63HR7</accession>
    <accession>Q6IPP8</accession>
    <accession>Q6TFZ6</accession>
    <accession>Q7Z5Y3</accession>
    <accession>Q96BW4</accession>
    <accession>Q9P064</accession>
    <name>ACSF4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="2">Beta-alanine-activating enzyme</fullName>
            <ecNumber>6.2.1.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase family member 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein NRPS998</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AASDH</name>
        <name type="synonym">ACSF4</name>
        <name type="synonym">U26</name>
        <name type="ORF">HSPC318</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2005" name="Mol. Biol. Rep." volume="32" first="47" last="53">
            <title>Cloning and characterization of a novel human homolog of mouse U26, a putative PQQ-dependent AAS dehydrogenase.</title>
            <authorList>
                <person name="Wang L."/>
                <person name="Jil C."/>
                <person name="Xu Y."/>
                <person name="Xu J."/>
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            </authorList>
            <dbReference type="PubMed" id="15865210"/>
            <dbReference type="DOI" id="10.1007/s11033-003-2716-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT ASP-1030</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2003-09" db="EMBL/GenBank/DDBJ databases">
            <title>Identification and preliminary characterization of a human protein with similarity to microbial peptide synthetases.</title>
            <authorList>
                <person name="Paliga K."/>
                <person name="Bauer K."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT VAL-747</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
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                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
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                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
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            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 96-1098</scope>
        <source>
            <tissue>Liver</tissue>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
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                <person name="Hillier L.W."/>
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                <person name="Cotton M."/>
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                <person name="Erb T."/>
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                <person name="Gaige T."/>
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                <person name="Strong C.M."/>
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                <person name="Kozlowicz-Reilly A."/>
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                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
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                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
                <person name="Nelson J.O."/>
                <person name="Osborne J."/>
                <person name="Ding L."/>
                <person name="Meyer R."/>
                <person name="Sabo A."/>
                <person name="Shotland Y."/>
                <person name="Sinha P."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Jones T.A."/>
                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
                <person name="Schmutz J."/>
                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
                <person name="Huang X."/>
                <person name="McPherson J.D."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4)</scope>
        <scope>VARIANT VAL-747</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2000" name="Genome Res." volume="10" first="1546" last="1560">
            <title>Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells.</title>
            <authorList>
                <person name="Zhang Q.-H."/>
                <person name="Ye M."/>
                <person name="Wu X.-Y."/>
                <person name="Ren S.-X."/>
                <person name="Zhao M."/>
                <person name="Zhao C.-J."/>
                <person name="Fu G."/>
                <person name="Shen Y."/>
                <person name="Fan H.-Y."/>
                <person name="Lu G."/>
                <person name="Zhong M."/>
                <person name="Xu X.-R."/>
                <person name="Han Z.-G."/>
                <person name="Zhang J.-W."/>
                <person name="Tao J."/>
                <person name="Huang Q.-H."/>
                <person name="Zhou J."/>
                <person name="Hu G.-X."/>
                <person name="Gu J."/>
                <person name="Chen S.-J."/>
                <person name="Chen Z."/>
            </authorList>
            <dbReference type="PubMed" id="11042152"/>
            <dbReference type="DOI" id="10.1101/gr.140200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-164</scope>
        <scope>VARIANTS VAL-61 AND ARG-93</scope>
        <source>
            <tissue>Umbilical cord blood</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649 AND SER-724</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">Covalently binds beta-alanine in an ATP-dependent manner to form a thioester bond with its phosphopantetheine group and transfers it to an, as yet, unknown acceptor. May be required for a post-translational protein modification or for post-transcriptional modification of an RNA.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q4L235-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q4L235-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_030707"/>
        </isoform>
        <isoform>
            <id>Q4L235-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_030711 VSP_030712"/>
        </isoform>
        <isoform>
            <id>Q4L235-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_030710 VSP_030713"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Ubiquitously expressed in adult tissues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="11">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAH56482" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.-"/>
    <dbReference type="EMBL" id="AY314787">
        <property type="protein sequence ID" value="AAQ83120.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF516672">
        <property type="protein sequence ID" value="AAP76519.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY422212">
        <property type="protein sequence ID" value="AAR31184.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX640635">
        <property type="protein sequence ID" value="CAH56482.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Transcribed_RNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX648853">
        <property type="protein sequence ID" value="CAH56130.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC068620">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC071815">
        <property type="protein sequence ID" value="AAH71815.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC141824">
        <property type="protein sequence ID" value="AAI41825.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC142709">
        <property type="protein sequence ID" value="AAI42710.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF161436">
        <property type="protein sequence ID" value="AAF28996.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3504.1">
        <molecule id="Q4L235-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS68705.1">
        <molecule id="Q4L235-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS68706.1">
        <molecule id="Q4L235-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS75127.1">
        <molecule id="Q4L235-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273597.1">
        <molecule id="Q4L235-2"/>
        <property type="nucleotide sequence ID" value="NM_001286668.2"/>
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    <dbReference type="RefSeq" id="NP_001273598.1">
        <property type="nucleotide sequence ID" value="NM_001286669.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273599.1">
        <property type="nucleotide sequence ID" value="NM_001286670.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273600.1">
        <molecule id="Q4L235-4"/>
        <property type="nucleotide sequence ID" value="NM_001286671.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273601.1">
        <molecule id="Q4L235-3"/>
        <property type="nucleotide sequence ID" value="NM_001286672.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001310819.1">
        <property type="nucleotide sequence ID" value="NM_001323890.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001310821.1">
        <property type="nucleotide sequence ID" value="NM_001323892.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001310822.1">
        <property type="nucleotide sequence ID" value="NM_001323893.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001310828.1">
        <property type="nucleotide sequence ID" value="NM_001323899.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_861522.2">
        <molecule id="Q4L235-1"/>
        <property type="nucleotide sequence ID" value="NM_181806.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q4L235"/>
    <dbReference type="SMR" id="Q4L235"/>
    <dbReference type="BioGRID" id="126342">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q4L235">
        <property type="interactions" value="2187"/>
    </dbReference>
    <dbReference type="IntAct" id="Q4L235">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000205214"/>
    <dbReference type="iPTMnet" id="Q4L235"/>
    <dbReference type="PhosphoSitePlus" id="Q4L235"/>
    <dbReference type="BioMuta" id="AASDH"/>
    <dbReference type="DMDM" id="269849683"/>
    <dbReference type="jPOST" id="Q4L235"/>
    <dbReference type="MassIVE" id="Q4L235"/>
    <dbReference type="PaxDb" id="9606-ENSP00000205214"/>
    <dbReference type="PeptideAtlas" id="Q4L235"/>
    <dbReference type="ProteomicsDB" id="62225">
        <molecule id="Q4L235-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62226">
        <molecule id="Q4L235-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62227">
        <molecule id="Q4L235-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62228">
        <molecule id="Q4L235-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q4L235"/>
    <dbReference type="Antibodypedia" id="24007">
        <property type="antibodies" value="56 antibodies from 15 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="132949"/>
    <dbReference type="Ensembl" id="ENST00000205214.11">
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        <property type="gene ID" value="ENSG00000157426.15"/>
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        <property type="protein sequence ID" value="ENSP00000421171.1"/>
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    <dbReference type="Ensembl" id="ENST00000513376.5">
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        <property type="gene ID" value="ENSG00000157426.15"/>
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        <property type="protein sequence ID" value="ENSP00000205214.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_181806.4"/>
        <property type="RefSeq protein sequence ID" value="NP_861522.2"/>
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    <dbReference type="UCSC" id="uc003hbn.5">
        <molecule id="Q4L235-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:23993"/>
    <dbReference type="ClinPGx" id="PA162375178"/>
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    <dbReference type="HGNC" id="HGNC:23993">
        <property type="gene designation" value="AASDH"/>
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    <dbReference type="HPA" id="ENSG00000157426">
        <property type="expression patterns" value="Low tissue specificity"/>
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    <dbReference type="MIM" id="614365">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000157426"/>
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    <dbReference type="eggNOG" id="KOG1178">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="eggNOG" id="KOG4649">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00440000033811"/>
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    <dbReference type="OMA" id="NGNVICC"/>
    <dbReference type="OrthoDB" id="408177at2759"/>
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        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="Q4L235"/>
    <dbReference type="BRENDA" id="1.2.1.31">
        <property type="organism ID" value="2681"/>
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    <dbReference type="PathwayCommons" id="Q4L235"/>
    <dbReference type="SignaLink" id="Q4L235"/>
    <dbReference type="Agora" id="ENSG00000157426"/>
    <dbReference type="BioGRID-ORCS" id="132949">
        <property type="hits" value="3 hits in 1153 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="AASDH">
        <property type="organism name" value="human"/>
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    <dbReference type="GenomeRNAi" id="132949"/>
    <dbReference type="Pharos" id="Q4L235">
        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:Q4L235"/>
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        <property type="component" value="Chromosome 4"/>
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    <dbReference type="RNAct" id="Q4L235">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000157426">
        <property type="expression patterns" value="Expressed in kidney epithelium and 188 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016874">
        <property type="term" value="F:ligase activity"/>
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        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0043041">
        <property type="term" value="P:amino acid activation for nonribosomal peptide biosynthetic process"/>
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        <property type="term" value="P:fatty acid metabolic process"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="CDD" id="cd17654">
        <property type="entry name" value="A_NRPS_acs4"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="AASDH isoform 4"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="acyl-CoA synthetase family member 4"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Beta-alanine-activating enzyme"/>
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    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="YVTN repeat-like/Quinoprotein amine dehydrogenase"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="AASDH_AMP"/>
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    <dbReference type="InterPro" id="IPR036736">
        <property type="entry name" value="ACP-like_sf"/>
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    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
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    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
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    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
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    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
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    <dbReference type="InterPro" id="IPR052091">
        <property type="entry name" value="Beta-ala_Activ/Resist"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009081">
        <property type="entry name" value="PP-bd_ACP"/>
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    <dbReference type="InterPro" id="IPR018391">
        <property type="entry name" value="PQQ_b-propeller_rpt"/>
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    <dbReference type="InterPro" id="IPR002372">
        <property type="entry name" value="PQQ_rpt_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011047">
        <property type="entry name" value="Quinoprotein_ADH-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR015943">
        <property type="entry name" value="WD40/YVTN_repeat-like_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR44394">
        <property type="entry name" value="BETA-ALANINE-ACTIVATING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR44394:SF1">
        <property type="entry name" value="BETA-ALANINE-ACTIVATING ENZYME"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13570">
        <property type="entry name" value="Beta-prop_ACSF4"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00550">
        <property type="entry name" value="PP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00564">
        <property type="entry name" value="PQQ"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47336">
        <property type="entry name" value="ACP-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50998">
        <property type="entry name" value="Quinoprotein alcohol dehydrogenase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50075">
        <property type="entry name" value="CARRIER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0596">Phosphopantetheine</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000315803" description="Beta-alanine-activating enzyme">
        <location>
            <begin position="1"/>
            <end position="1098"/>
        </location>
    </feature>
    <feature type="domain" description="Carrier" evidence="3">
        <location>
            <begin position="553"/>
            <end position="630"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="198"/>
            <end position="206"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="428"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="442"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="527"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="O-(pantetheine 4'-phosphoryl)serine" evidence="3">
        <location>
            <position position="589"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12 13">
        <location>
            <position position="649"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13">
        <location>
            <position position="724"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030707" description="In isoform 2." evidence="10">
        <location>
            <begin position="1"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030710" description="In isoform 4." evidence="8">
        <original>CYNGLVYVLKSNSGEKYWMFTTEDAVK</original>
        <variation>LAVLYQWTNLFIPVYLTIRAKNIFWFP</variation>
        <location>
            <begin position="831"/>
            <end position="857"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030711" description="In isoform 3." evidence="8 9">
        <original>CYNGLVYVLKS</original>
        <variation>KFLNLRFVELN</variation>
        <location>
            <begin position="831"/>
            <end position="841"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030712" description="In isoform 3." evidence="8 9">
        <location>
            <begin position="842"/>
            <end position="1098"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_030713" description="In isoform 4." evidence="8">
        <location>
            <begin position="858"/>
            <end position="1098"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061008" description="In dbSNP:rs34543011." evidence="4">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="61"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061009" description="In dbSNP:rs34228795." evidence="4">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038309" description="In dbSNP:rs3796543.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038310" description="In dbSNP:rs3796544." evidence="5 7">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="747"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038311" description="In dbSNP:rs3796545.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="774"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038312" description="In dbSNP:rs12498340.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="865"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038313" description="In dbSNP:rs8340." evidence="6">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="1030"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAI41825/AAI42710." evidence="11" ref="5">
        <original>I</original>
        <variation>R</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAH56130." evidence="11" ref="3">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAQ83120 and 3; CAH56482." evidence="11" ref="1 3">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="428"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAH56482." evidence="11" ref="3">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="470"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAH56482." evidence="11" ref="3">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="489"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAH56482." evidence="11" ref="3">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="498"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q80WC9"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00258"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11042152"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15865210"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="1098" mass="122597" checksum="067ACB7C020AD4F1" modified="2009-11-24" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-04-27" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>O95573</accession>
    <accession>Q60I92</accession>
    <accession>Q8IUM9</accession>
    <name>ACSL3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="8">Fatty acid CoA ligase Acsl3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="2">Arachidonate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 3</fullName>
            <shortName>LACS 3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="8">Long-chain-fatty-acid--CoA ligase 3</fullName>
            <ecNumber evidence="6">6.2.1.3</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="2">Medium-chain acyl-CoA ligase Acsl3</fullName>
            <ecNumber evidence="2">6.2.1.2</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="10" type="primary">ACSL3</name>
        <name type="synonym">ACS3</name>
        <name type="synonym">FACL3</name>
        <name type="synonym">LACS3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Genomics" volume="42" first="180" last="181">
            <title>Human acyl-coenzyme A synthetase 3 cDNA and localization of its gene (ACS3) to chromosome band 2q34-q35.</title>
            <authorList>
                <person name="Minekura H."/>
                <person name="Fujino T."/>
                <person name="Kang M.-J."/>
                <person name="Fujita T."/>
                <person name="Endo Y."/>
                <person name="Yamamoto T.T."/>
            </authorList>
            <dbReference type="PubMed" id="9177793"/>
            <dbReference type="DOI" id="10.1006/geno.1997.4710"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT SER-551</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Gene" volume="278" first="185" last="192">
            <title>Genomic organization and transcription units of the human acyl-CoA synthetase 3 gene.</title>
            <authorList>
                <person name="Minekura H."/>
                <person name="Kang M.-J."/>
                <person name="Inagaki Y."/>
                <person name="Suzuki H."/>
                <person name="Sato H."/>
                <person name="Fujino T."/>
                <person name="Yamamoto T.T."/>
            </authorList>
            <dbReference type="PubMed" id="11707336"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(01)00714-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
        <scope>VARIANT SER-551</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="849" last="854">
            <title>Long chain acyl-CoA synthetase 3-mediated phosphatidylcholine synthesis is required for assembly of very low density lipoproteins in human hepatoma Huh7 cells.</title>
            <authorList>
                <person name="Yao H."/>
                <person name="Ye J."/>
            </authorList>
            <dbReference type="PubMed" id="18003621"/>
            <dbReference type="DOI" id="10.1074/jbc.m706160200"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2008" name="Mol. Cell" volume="31" first="438" last="448">
            <title>Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.</title>
            <authorList>
                <person name="Daub H."/>
                <person name="Olsen J.V."/>
                <person name="Bairlein M."/>
                <person name="Gnad F."/>
                <person name="Oppermann F.S."/>
                <person name="Korner R."/>
                <person name="Greff Z."/>
                <person name="Keri G."/>
                <person name="Stemmann O."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="18691976"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2008.07.007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2012" name="Mol. Cell" volume="46" first="461" last="471">
            <title>The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.</title>
            <authorList>
                <person name="Nakahara K."/>
                <person name="Ohkuni A."/>
                <person name="Kitamura T."/>
                <person name="Abe K."/>
                <person name="Naganuma T."/>
                <person name="Ohno Y."/>
                <person name="Zoeller R.A."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="22633490"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2012.04.033"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-683</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="2 5 6">Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins) (PubMed:18003621). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:36140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52116"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:78832"/>
            <dbReference type="ChEBI" id="CHEBI:136409"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52117"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52112"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:90718"/>
            <dbReference type="ChEBI" id="CHEBI:136408"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52108"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65341"/>
            <dbReference type="ChEBI" id="CHEBI:136407"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52109"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + ATP + CoA = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52016"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:84024"/>
            <dbReference type="ChEBI" id="CHEBI:136117"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52017"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoate + ATP + CoA = 11,12-epoxy-(5Z,8Z,14Z)-eicosatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52012"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:76625"/>
            <dbReference type="ChEBI" id="CHEBI:136115"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52013"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>tetradecanoate + ATP + CoA = tetradecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33619"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33620"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33623"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33624"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>octadecanoate + ATP + CoA = octadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33615"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57394"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33616"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>eicosanoate + ATP + CoA = eicosanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46208"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32360"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57380"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:46209"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-octadecenoate + ATP + CoA = (9Z)-octadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33607"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57387"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33608"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z)-hexadecenoate + ATP + CoA = (9Z)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33647"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61540"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33648"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z,12Z)-octadecadienoate + ATP + CoA = (9Z,12Z)-octadecadienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33651"/>
            <dbReference type="ChEBI" id="CHEBI:30245"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57383"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(9Z,12Z,15Z)-octadecatrienoate + ATP + CoA = (9Z,12Z,15Z)-octadecatrienoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:44936"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32387"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74034"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:44937"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + ATP + CoA = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:44932"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:74298"/>
            <dbReference type="ChEBI" id="CHEBI:77016"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:44933"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + ATP + CoA = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:67848"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58562"/>
            <dbReference type="ChEBI" id="CHEBI:73862"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:67849"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>a fatty acid + ATP + CoA = a fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:38883"/>
            <dbReference type="ChEBI" id="CHEBI:28868"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:77636"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:38884"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1190822">
            <id>O95573</id>
        </interactant>
        <interactant intactId="EBI-2797775">
            <id>P56962</id>
            <label>STX17</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion outer membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Peroxisome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Microsome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Endoplasmic reticulum membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.15" evidence="2"/>
    <dbReference type="EC" id="6.2.1.3" evidence="6"/>
    <dbReference type="EC" id="6.2.1.2" evidence="2"/>
    <dbReference type="EMBL" id="D89053">
        <property type="protein sequence ID" value="BAA37142.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB061712">
        <property type="protein sequence ID" value="BAB72074.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB061436">
        <property type="protein sequence ID" value="BAB72139.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041692">
        <property type="protein sequence ID" value="AAH41692.1"/>
        <property type="molecule type" value="mRNA"/>
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    </dbReference>
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        <property type="entry name" value="LC_FACS_euk1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
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    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
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        <property type="entry name" value="ANL_N_sf"/>
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    <dbReference type="PANTHER" id="PTHR43272:SF13">
        <property type="entry name" value="FATTY ACID COA LIGASE ACSL3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43272">
        <property type="entry name" value="LONG-CHAIN-FATTY-ACID--COA LIGASE"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0492">Microsome</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000193107" description="Fatty acid CoA ligase Acsl3">
        <location>
            <begin position="1"/>
            <end position="720"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="3">
        <location>
            <begin position="21"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="42"/>
            <end position="720"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="11 12">
        <location>
            <position position="683"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026716" description="In dbSNP:rs1046032." evidence="4 7">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="551"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA37142 and 2; BAB72074/BAB72139." evidence="8" ref="1 2">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="246"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q63151"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="11707336"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="18003621"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="9177793"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000305" key="9">
        <source>
            <dbReference type="PubMed" id="22633490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="HGNC" id="HGNC:3570"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="720" mass="80420" checksum="AAC4B0B4543EC8DD" modified="2006-10-03" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-04-27" modified="2026-01-28" version="206" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKU0</accession>
    <accession>J3KPG3</accession>
    <accession>O94924</accession>
    <accession>O95829</accession>
    <accession>Q108M9</accession>
    <accession>Q108N0</accession>
    <accession>Q4G191</accession>
    <accession>Q86TN7</accession>
    <name>ACSL6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">Long-chain-fatty-acid--CoA ligase 6</fullName>
            <ecNumber evidence="6 7">6.2.1.3</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="13">Arachidonate--CoA ligase</fullName>
            <ecNumber evidence="2">6.2.1.15</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Long-chain acyl-CoA synthetase 6</fullName>
            <shortName>LACS 6</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">ACSL6</name>
        <name type="synonym">ACS2</name>
        <name type="synonym">FACL6</name>
        <name type="synonym">KIAA0837</name>
        <name type="synonym">LACS5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Biochem. J." volume="344" first="135" last="143">
            <title>Identification and molecular characterization of acyl-CoA synthetase in human red cells and erythroid precursor.</title>
            <authorList>
                <person name="Malhotra K.T."/>
                <person name="Malhotra K."/>
                <person name="Lubin B.H."/>
                <person name="Kuypers F.A."/>
            </authorList>
            <dbReference type="PubMed" id="10548543"/>
            <dbReference type="DOI" id="10.1042/bj3440135"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Genes Chromosomes Cancer" volume="26" first="192" last="202">
            <title>Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).</title>
            <authorList>
                <person name="Yagasaki F."/>
                <person name="Jinnai I."/>
                <person name="Yoshida S."/>
                <person name="Yokoyama Y."/>
                <person name="Matsuda A."/>
                <person name="Kusumoto S."/>
                <person name="Kobayashi H."/>
                <person name="Terasaki H."/>
                <person name="Ohyashiki K."/>
                <person name="Asou N."/>
                <person name="Murohashi I."/>
                <person name="Bessho M."/>
                <person name="Hirashima K."/>
            </authorList>
            <dbReference type="PubMed" id="10502316"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-2264(199911)26:3&lt;192::aid-gcc2&gt;3.0.co;2-e"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH ETV6</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="BMC Mol. Biol." volume="7" first="21" last="21">
            <title>Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains.</title>
            <authorList>
                <person name="Soupene E."/>
                <person name="Kuypers F.A."/>
            </authorList>
            <dbReference type="PubMed" id="16834775"/>
            <dbReference type="DOI" id="10.1186/1471-2199-7-21"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6)</scope>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 253-374 (ISOFORM 5)</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 8)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="355" last="364">
            <title>Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
                <person name="Suyama M."/>
                <person name="Kikuno R."/>
                <person name="Hirosawa M."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
                <person name="Nomura N."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="10048485"/>
            <dbReference type="DOI" id="10.1093/dnares/5.6.355"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2004-07" db="EMBL/GenBank/DDBJ databases">
            <title>Full-length cDNA libraries and normalization.</title>
            <authorList>
                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Nature" volume="431" first="268" last="274">
            <title>The DNA sequence and comparative analysis of human chromosome 5.</title>
            <authorList>
                <person name="Schmutz J."/>
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                <person name="Terry A."/>
                <person name="Couronne O."/>
                <person name="Grimwood J."/>
                <person name="Lowry S."/>
                <person name="Gordon L.A."/>
                <person name="Scott D."/>
                <person name="Xie G."/>
                <person name="Huang W."/>
                <person name="Hellsten U."/>
                <person name="Tran-Gyamfi M."/>
                <person name="She X."/>
                <person name="Prabhakar S."/>
                <person name="Aerts A."/>
                <person name="Altherr M."/>
                <person name="Bajorek E."/>
                <person name="Black S."/>
                <person name="Branscomb E."/>
                <person name="Caoile C."/>
                <person name="Challacombe J.F."/>
                <person name="Chan Y.M."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Goodstein D."/>
                <person name="Grigoriev I."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Israni S."/>
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                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Martinez D."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nandkeshwar R."/>
                <person name="Noonan J.P."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
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                <person name="Ramirez L."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
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            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 8)</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 9)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2012" name="Mol. Cell" volume="46" first="461" last="471">
            <title>The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.</title>
            <authorList>
                <person name="Nakahara K."/>
                <person name="Ohkuni A."/>
                <person name="Kitamura T."/>
                <person name="Abe K."/>
                <person name="Naganuma T."/>
                <person name="Ohno Y."/>
                <person name="Zoeller R.A."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="22633490"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2012.04.033"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2013" name="Biochem. Biophys. Res. Commun." volume="442" first="195" last="201">
            <title>Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway.</title>
            <authorList>
                <person name="Ohkuni A."/>
                <person name="Ohno Y."/>
                <person name="Kihara A."/>
            </authorList>
            <dbReference type="PubMed" id="24269233"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2013.11.036"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7">Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490, PubMed:24269233). Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7">
            <text>a long-chain fatty acid + ATP + CoA = a long-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15421"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:83139"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.3"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14 15">
            <dbReference type="Rhea" id="RHEA:15422"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>(5Z,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:19713"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:32395"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57368"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:19714"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7">
            <text>(E)-hexadec-2-enoate + ATP + CoA = (2E)-hexadecenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:36139"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61526"/>
            <dbReference type="ChEBI" id="CHEBI:72745"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14 15">
            <dbReference type="Rhea" id="RHEA:36140"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + ATP + CoA = 15-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52116"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:78832"/>
            <dbReference type="ChEBI" id="CHEBI:136409"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52117"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + ATP + CoA = 12-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52112"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:90718"/>
            <dbReference type="ChEBI" id="CHEBI:136408"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + ATP + CoA = 5-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:52108"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:65341"/>
            <dbReference type="ChEBI" id="CHEBI:136407"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:52109"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12883224">
            <id>Q9UKU0-7</id>
        </interactant>
        <interactant intactId="EBI-6309018">
            <id>Q9NV79</id>
            <label>PCMTD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12883224">
            <id>Q9UKU0-7</id>
        </interactant>
        <interactant intactId="EBI-625509">
            <id>Q8N720</id>
            <label>ZNF655</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion outer membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Peroxisome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Microsome membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Endoplasmic reticulum membrane</location>
            <topology evidence="1">Single-pass type III membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKU0-4</id>
            <name>4</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-1</id>
            <name>1</name>
            <name>Long</name>
            <name>v2</name>
            <sequence type="described" ref="VSP_037819"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-2</id>
            <name>2</name>
            <name>Short</name>
            <sequence type="described" ref="VSP_021024 VSP_000241"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_021024"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-5</id>
            <name>5</name>
            <name>v4</name>
            <sequence type="described" ref="VSP_037823"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-6</id>
            <name>6</name>
            <name>v5</name>
            <sequence type="described" ref="VSP_037821"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-7</id>
            <name>7</name>
            <name>v3</name>
            <sequence type="described" ref="VSP_037820 VSP_037822"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-8</id>
            <name>8</name>
            <name>v1</name>
            <sequence type="described" ref="VSP_037819 VSP_021024"/>
        </isoform>
        <isoform>
            <id>Q9UKU0-9</id>
            <name>9</name>
            <sequence type="described" ref="VSP_046954"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expressed predominantly in erythrocyte precursors, in particular in reticulocytes, fetal blood cells derived from fetal liver, hemopoietic stem cells from cord blood, bone marrow and brain.</text>
    </comment>
    <comment type="developmental stage">
        <text>Expression is low at earlier stages of erythroid development but is very high in reticulocytes.</text>
    </comment>
    <comment type="disease">
        <text evidence="4">A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;12)(q31;p13) with ETV6.</text>
    </comment>
    <comment type="disease">
        <text evidence="4">A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;12)(q31;p13) with ETV6.</text>
    </comment>
    <comment type="disease">
        <text evidence="4">A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ETV6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="AAH26161" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA74860" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.3" evidence="6 7"/>
    <dbReference type="EC" id="6.2.1.15" evidence="2"/>
    <dbReference type="EMBL" id="AF129166">
        <property type="protein sequence ID" value="AAD47199.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF099740">
        <property type="protein sequence ID" value="AAD17853.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ083030">
        <property type="protein sequence ID" value="AAZ30713.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ083031">
        <property type="protein sequence ID" value="AAZ30714.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB020644">
        <property type="protein sequence ID" value="BAA74860.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR606980">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025772">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026398">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC034228">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC026161">
        <property type="protein sequence ID" value="AAH26161.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047453">
        <property type="protein sequence ID" value="AAH47453.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34228.1">
        <molecule id="Q9UKU0-8"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34229.1">
        <molecule id="Q9UKU0-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56381.1">
        <molecule id="Q9UKU0-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56382.1">
        <molecule id="Q9UKU0-7"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56383.1">
        <molecule id="Q9UKU0-9"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001009185.1">
        <molecule id="Q9UKU0-1"/>
        <property type="nucleotide sequence ID" value="NM_001009185.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001192176.1">
        <property type="nucleotide sequence ID" value="NM_001205247.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001192177.1">
        <molecule id="Q9UKU0-3"/>
        <property type="nucleotide sequence ID" value="NM_001205248.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001192179.1">
        <molecule id="Q9UKU0-9"/>
        <property type="nucleotide sequence ID" value="NM_001205250.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001192180.1">
        <molecule id="Q9UKU0-7"/>
        <property type="nucleotide sequence ID" value="NM_001205251.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392408.1">
        <molecule id="Q9UKU0-4"/>
        <property type="nucleotide sequence ID" value="NM_001405479.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392409.1">
        <molecule id="Q9UKU0-4"/>
        <property type="nucleotide sequence ID" value="NM_001405480.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392410.1">
        <molecule id="Q9UKU0-3"/>
        <property type="nucleotide sequence ID" value="NM_001405481.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392411.1">
        <molecule id="Q9UKU0-4"/>
        <property type="nucleotide sequence ID" value="NM_001405482.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392412.1">
        <molecule id="Q9UKU0-4"/>
        <property type="nucleotide sequence ID" value="NM_001405483.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392413.1">
        <molecule id="Q9UKU0-3"/>
        <property type="nucleotide sequence ID" value="NM_001405484.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001392419.1">
        <molecule id="Q9UKU0-7"/>
        <property type="nucleotide sequence ID" value="NM_001405490.1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
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    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0492">Microsome</keyword>
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    <keyword id="KW-1000">Mitochondrion outer membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000193115" description="Long-chain-fatty-acid--CoA ligase 6">
        <location>
            <begin position="1"/>
            <end position="697"/>
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    <feature type="transmembrane region" description="Helical; Signal-anchor for type III membrane protein" evidence="3">
        <location>
            <begin position="25"/>
            <end position="45"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="46"/>
            <end position="697"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037819" description="In isoform 1 and isoform 8." evidence="8">
        <original>M</original>
        <variation>MLTFFLVSGGSLWLFVEFVLSLLEKM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046954" description="In isoform 9." evidence="11">
        <original>M</original>
        <variation>MPEFVLSLLEKM</variation>
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037820" description="In isoform 7." evidence="11">
        <location>
            <begin position="31"/>
            <end position="65"/>
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    <feature type="splice variant" id="VSP_037821" description="In isoform 6." evidence="12">
        <original>T</original>
        <variation>TGLSCQEGASATASTQ</variation>
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037822" description="In isoform 7." evidence="11">
        <location>
            <begin position="306"/>
            <end position="345"/>
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    </feature>
    <feature type="splice variant" id="VSP_021024" description="In isoform 3, isoform 2 and isoform 8." evidence="9 10">
        <original>KVIFPRQDDVLISFLPLAHMFERVI</original>
        <variation>SQWAPTCADVHISYLPLAHMFERMV</variation>
        <location>
            <begin position="306"/>
            <end position="330"/>
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    </feature>
    <feature type="splice variant" id="VSP_037823" description="In isoform 5." evidence="12">
        <location>
            <begin position="306"/>
            <end position="312"/>
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    <feature type="splice variant" id="VSP_000241" description="In isoform 2." evidence="9">
        <original>VKAIHIHSDMFSVQNGLLTPTLKAKRPELREYFKKQIEELYSISM</original>
        <variation>DLPQCLIQIKVFSKY</variation>
        <location>
            <begin position="653"/>
            <end position="697"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD47199." evidence="13" ref="1">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="19"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD47199." evidence="13" ref="1">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="46"/>
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    <feature type="sequence conflict" description="In Ref. 7; AAH47453." evidence="13" ref="7">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="257"/>
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    <feature type="sequence conflict" description="In Ref. 7; AAH26161." evidence="13" ref="7">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="260"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAZ30714." evidence="13" ref="3">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="356"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAD47199 and 3; AAZ30714." evidence="13" ref="1 3">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="696"/>
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    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="P33124"/>
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    <evidence type="ECO:0000255" key="3"/>
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        <source>
            <dbReference type="PubMed" id="10502316"/>
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        <source>
            <dbReference type="PubMed" id="10548543"/>
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        <source>
            <dbReference type="PubMed" id="22633490"/>
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        <source>
            <dbReference type="PubMed" id="24269233"/>
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        <source>
            <dbReference type="PubMed" id="10502316"/>
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        <source>
            <dbReference type="PubMed" id="10548543"/>
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        <source>
            <dbReference type="PubMed" id="15489334"/>
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    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="16834775"/>
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    </evidence>
    <evidence type="ECO:0000305" key="13"/>
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        <source>
            <dbReference type="PubMed" id="22633490"/>
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        <source>
            <dbReference type="PubMed" id="24269233"/>
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    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:16496"/>
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    </evidence>
    <sequence length="697" mass="77752" checksum="AC566177B47D0975" modified="2007-03-06" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="140" xmlns="https://uniprot.org/uniprot">
    <accession>Q08AH1</accession>
    <accession>Q08AH2</accession>
    <accession>Q96A20</accession>
    <name>ACSM1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM1, mitochondrial</fullName>
            <ecNumber evidence="4">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Benzoate--CoA ligase</fullName>
            <ecNumber evidence="4">6.2.1.25</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Butyrate--CoA ligase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Butyryl-coenzyme A synthetase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="3">Lipoate-activating enzyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Middle-chain acyl-CoA synthetase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="5">Xenobiotic/medium-chain fatty acid-CoA ligase HXM-B</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM1</name>
        <name type="synonym">BUCS1</name>
        <name evidence="3" type="synonym">LAE</name>
        <name type="synonym">MACS1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="35961" last="35966">
            <title>Molecular identification and characterization of two medium-chain acyl-CoA synthetases, MACS1 and the Sa gene product.</title>
            <authorList>
                <person name="Fujino T."/>
                <person name="Takei Y.A."/>
                <person name="Sone H."/>
                <person name="Ioka R.X."/>
                <person name="Kamataki A."/>
                <person name="Magoori K."/>
                <person name="Takahashi S."/>
                <person name="Sakai J."/>
                <person name="Yamamoto T.T."/>
            </authorList>
            <dbReference type="PubMed" id="11470804"/>
            <dbReference type="DOI" id="10.1074/jbc.m106651200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="Biochim. Biophys. Acta" volume="1428" first="455" last="462">
            <title>Characterization of the CoA ligases of human liver mitochondria catalyzing the activation of short- and medium-chain fatty acids and xenobiotic carboxylic acids.</title>
            <authorList>
                <person name="Vessey D.A."/>
                <person name="Kelley M."/>
                <person name="Warren R.S."/>
            </authorList>
            <dbReference type="PubMed" id="10434065"/>
            <dbReference type="DOI" id="10.1016/s0304-4165(99)00088-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2016" name="Expert Opin. Drug Metab. Toxicol." volume="12" first="1169" last="1179">
            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
            <authorList>
                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="3 4">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (PubMed:10434065). Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate (PubMed:10434065). Also catalyzes the activation of lipoate to lipoyl-nucleoside monophosphate (By similarity). Activates lipoate with GTP at a 1000-fold higher rate than with ATP and activates both (R)- and (S)-lipoate to the respective lipoyl-GMP, with a preference for (R)-lipoate (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>benzoate + ATP + CoA = benzoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:10132"/>
            <dbReference type="ChEBI" id="CHEBI:16150"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57369"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.25"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4">
            <dbReference type="Rhea" id="RHEA:10133"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>(R)-lipoate + GTP + H(+) = (R)-lipoyl-GMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46700"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
            <dbReference type="ChEBI" id="CHEBI:83088"/>
            <dbReference type="ChEBI" id="CHEBI:86460"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:46701"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33632"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>decanoate + ATP + CoA = decanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33627"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:33628"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33623"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33624"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>tetradecanoate + ATP + CoA = tetradecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33619"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:30807"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57385"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:33620"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>hexanoate + ATP + CoA = hexanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:43740"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:43741"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8">
            <text>butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46172"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:46173"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>hexadecanoate + ATP + CoA = hexadecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:30751"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57379"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:30752"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="4">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="4">Activated by monovalent cations, such as potassium, rubidium or ammonium.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">21 uM for benzoate</KM>
            <KM evidence="4">570 uM for butyrate</KM>
            <KM evidence="4">20 uM for decanoate</KM>
            <KM evidence="4">34 uM for hexanoate</KM>
            <KM evidence="4">24 uM for laurate</KM>
            <KM evidence="4">143 uM for phenylacetate</KM>
            <KM evidence="4">25 uM for salicylate</KM>
            <Vmax evidence="4">9.0 nmol/min/mg enzyme for benzoate</Vmax>
            <Vmax evidence="4">24.0 nmol/min/mg enzyme for butyrate</Vmax>
            <Vmax evidence="4">8.0 nmol/min/mg enzyme for decanoate</Vmax>
            <Vmax evidence="4">118.0 nmol/min/mg enzyme for hexanoate</Vmax>
            <Vmax evidence="4">0.15 nmol/min/mg enzyme for laurate</Vmax>
            <Vmax evidence="4">2.0 nmol/min/mg enzyme for phenylacetate</Vmax>
        </kinetics>
        <phDependence>
            <text evidence="4">Optimum pH is 8.8.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="3">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818055">
            <id>Q08AH1</id>
        </interactant>
        <interactant intactId="EBI-11522780">
            <id>Q96DZ9-2</id>
            <label>CMTM5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818055">
            <id>Q08AH1</id>
        </interactant>
        <interactant intactId="EBI-5650739">
            <id>P43356</id>
            <label>MAGEA2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818055">
            <id>Q08AH1</id>
        </interactant>
        <interactant intactId="EBI-11522433">
            <id>Q5JR59-3</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818055">
            <id>Q08AH1</id>
        </interactant>
        <interactant intactId="EBI-1051317">
            <id>Q9H4L5</id>
            <label>OSBPL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2818055">
            <id>Q08AH1</id>
        </interactant>
        <interactant intactId="EBI-741137">
            <id>O43663</id>
            <label>PRC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Mitochondrion matrix</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q08AH1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q08AH1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_028391"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="4"/>
    <dbReference type="EC" id="6.2.1.25" evidence="4"/>
    <dbReference type="EMBL" id="AB059429">
        <property type="protein sequence ID" value="BAB64535.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB062503">
        <property type="protein sequence ID" value="BAB68363.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125177">
        <property type="protein sequence ID" value="AAI25178.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125178">
        <property type="protein sequence ID" value="AAI25179.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10587.1">
        <molecule id="Q08AH1-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001305819.1">
        <molecule id="Q08AH1-1"/>
        <property type="nucleotide sequence ID" value="NM_001318890.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_443188.2">
        <molecule id="Q08AH1-1"/>
        <property type="nucleotide sequence ID" value="NM_052956.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q08AH1"/>
    <dbReference type="SMR" id="Q08AH1"/>
    <dbReference type="BioGRID" id="125496">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q08AH1">
        <property type="interactions" value="81"/>
    </dbReference>
    <dbReference type="IntAct" id="Q08AH1">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000301956"/>
    <dbReference type="SwissLipids" id="SLP:000000449"/>
    <dbReference type="GlyGen" id="Q08AH1">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q08AH1"/>
    <dbReference type="PhosphoSitePlus" id="Q08AH1"/>
    <dbReference type="BioMuta" id="ACSM1"/>
    <dbReference type="DMDM" id="121940002"/>
    <dbReference type="MassIVE" id="Q08AH1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000301956"/>
    <dbReference type="PeptideAtlas" id="Q08AH1"/>
    <dbReference type="ProteomicsDB" id="58670">
        <molecule id="Q08AH1-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="58671">
        <molecule id="Q08AH1-2"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="Q08AH1-1">
        <molecule id="Q08AH1-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="49877">
        <property type="antibodies" value="70 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="116285"/>
    <dbReference type="Ensembl" id="ENST00000307493.8">
        <molecule id="Q08AH1-1"/>
        <property type="protein sequence ID" value="ENSP00000301956.3"/>
        <property type="gene ID" value="ENSG00000166743.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000519745.5">
        <molecule id="Q08AH1-2"/>
        <property type="protein sequence ID" value="ENSP00000428650.1"/>
        <property type="gene ID" value="ENSG00000166743.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000520010.6">
        <molecule id="Q08AH1-1"/>
        <property type="protein sequence ID" value="ENSP00000428047.1"/>
        <property type="gene ID" value="ENSG00000166743.11"/>
    </dbReference>
    <dbReference type="GeneID" id="116285"/>
    <dbReference type="KEGG" id="hsa:116285"/>
    <dbReference type="MANE-Select" id="ENST00000520010.6">
        <property type="protein sequence ID" value="ENSP00000428047.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001318890.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001305819.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002dhm.1">
        <molecule id="Q08AH1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18049"/>
    <dbReference type="ClinPGx" id="PA25468"/>
    <dbReference type="CTD" id="116285"/>
    <dbReference type="DisGeNET" id="116285"/>
    <dbReference type="GeneCards" id="ACSM1"/>
    <dbReference type="HGNC" id="HGNC:18049">
        <property type="gene designation" value="ACSM1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000166743">
        <property type="expression patterns" value="Tissue enriched (breast)"/>
    </dbReference>
    <dbReference type="MIM" id="614357">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000166743"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000166743"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161138"/>
    <dbReference type="HOGENOM" id="CLU_000022_59_10_1"/>
    <dbReference type="InParanoid" id="Q08AH1"/>
    <dbReference type="OMA" id="KTMDPMV"/>
    <dbReference type="OrthoDB" id="6614653at2759"/>
    <dbReference type="PAN-GO" id="Q08AH1">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q08AH1"/>
    <dbReference type="BioCyc" id="MetaCyc:HS09445-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q08AH1"/>
    <dbReference type="Reactome" id="R-HSA-177135">
        <property type="pathway name" value="Conjugation of benzoate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-177162">
        <property type="pathway name" value="Conjugation of phenylacetate with glutamine"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q08AH1"/>
    <dbReference type="Agora" id="ENSG00000166743"/>
    <dbReference type="BioGRID-ORCS" id="116285">
        <property type="hits" value="15 hits in 1149 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="116285"/>
    <dbReference type="Pharos" id="Q08AH1">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q08AH1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q08AH1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000166743">
        <property type="expression patterns" value="Expressed in left ovary and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q08AH1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0072562">
        <property type="term" value="C:blood microparticle"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
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    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018858">
        <property type="term" value="F:benzoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016405">
        <property type="term" value="F:CoA-ligase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0102391">
        <property type="term" value="F:decanoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0005525">
        <property type="term" value="F:GTP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004467">
        <property type="term" value="F:long-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031956">
        <property type="term" value="F:medium-chain fatty acid-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0018874">
        <property type="term" value="P:benzoate metabolic process"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019605">
        <property type="term" value="P:butyrate metabolic process"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042632">
        <property type="term" value="P:cholesterol homeostasis"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015980">
        <property type="term" value="P:energy derivation by oxidation of organic compounds"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019395">
        <property type="term" value="P:fatty acid oxidation"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006805">
        <property type="term" value="P:xenobiotic metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="CDD" id="cd05928">
        <property type="entry name" value="MACS_euk"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM5, mitochondrial"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
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    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
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    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
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    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
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        <property type="entry name" value="ANL_N_sf"/>
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    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
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        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
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        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM1, MITOCHONDRIAL"/>
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    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0342">GTP-binding</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000306091" description="Acyl-coenzyme A synthetase ACSM1, mitochondrial">
        <location>
            <begin position="32"/>
            <end position="577"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="226"/>
            <end position="234"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="452"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="467"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="563"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="85"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="204"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="204"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="391"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="391"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="531"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="538"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="538"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="549"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_028391" description="In isoform 2." evidence="6">
        <location>
            <begin position="205"/>
            <end position="577"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048238" description="In dbSNP:rs16970511.">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035245" description="In dbSNP:rs8056709.">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="479"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035246" description="In dbSNP:rs16970453.">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="515"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB64535/BAB68363." evidence="7" ref="1">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="549"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q91VA0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9BEA2"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="10434065"/>
        </source>
    </evidence>
    <sequence length="577" mass="65273" checksum="380BF4B8944B0E34" modified="2006-10-31" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-02-26" modified="2026-01-28" version="155" xmlns="https://uniprot.org/uniprot">
    <accession>Q562R1</accession>
    <accession>B2RPJ1</accession>
    <accession>Q562R2</accession>
    <accession>Q562S9</accession>
    <accession>Q562X8</accession>
    <name>ACTBL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Beta-actin-like protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Kappa-actin</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTBL2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Endometrial tumor</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Hepatol. Res." volume="36" first="33" last="39">
            <title>Identification of a novel actin isoform in hepatocellular carcinoma.</title>
            <authorList>
                <person name="Chang K.-W."/>
                <person name="Yang P.-Y."/>
                <person name="Lai H.-Y."/>
                <person name="Yeh T.-S."/>
                <person name="Chen T.-C."/>
                <person name="Yeh C.-T."/>
            </authorList>
            <dbReference type="PubMed" id="16824795"/>
            <dbReference type="DOI" id="10.1016/j.hepres.2006.05.003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-187</scope>
        <scope>INTERACTION WITH PFN1 AND PFDN1</scope>
        <source>
            <tissue>Hepatoma</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others (By similarity). Interacts with PFN1 and PFDN1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1773495">
            <id>Q562R1</id>
        </interactant>
        <interactant intactId="EBI-1566210">
            <id>Q8IW35</id>
            <label>CEP97</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1773495">
            <id>Q562R1</id>
        </interactant>
        <interactant intactId="EBI-21889552">
            <id>P18405</id>
            <label>SRD5A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="1">Oxidation of Met-45 and Met-48 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Monomethylation at Lys-85 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (By similarity).</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the actin family.</text>
    </comment>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_001017992.4"/>
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    <dbReference type="AlphaFoldDB" id="Q562R1"/>
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    </dbReference>
    <dbReference type="iPTMnet" id="Q562R1"/>
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        <property type="antibodies" value="69 antibodies from 18 providers"/>
    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000416706.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001017992.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001017992.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003jrm.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:17780"/>
    <dbReference type="ClinPGx" id="PA142672651"/>
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        <property type="gene designation" value="ACTBL2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000169067">
        <property type="expression patterns" value="Not detected"/>
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="10 GO annotations based on evolutionary models"/>
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        <property type="hits" value="15 hits in 1150 CRISPR screens"/>
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    <dbReference type="CD-CODE" id="232F8A39">
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        <property type="entry name" value="Stress granule"/>
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        <property type="component" value="Chromosome 5"/>
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        <property type="term" value="C:NuA4 histone acetyltransferase complex"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0019901">
        <property type="term" value="F:protein kinase binding"/>
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    <dbReference type="GO" id="GO:0098973">
        <property type="term" value="F:structural constituent of postsynaptic actin cytoskeleton"/>
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    <dbReference type="GO" id="GO:0007409">
        <property type="term" value="P:axonogenesis"/>
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        <property type="term" value="P:cell motility"/>
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        <property type="entry name" value="ASKHA_NBD_actin"/>
        <property type="match status" value="1"/>
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    </dbReference>
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        <property type="entry name" value="Actin_CS"/>
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        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00406">
        <property type="entry name" value="ACTINS_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000318849" description="Beta-actin-like protein 2">
        <location>
            <begin position="1"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="1">
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="1">
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAX82242." evidence="3" ref="4">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAX82260." evidence="3" ref="4">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="135"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAX82259." evidence="3" ref="4">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAX82193." evidence="3" ref="4">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16824795"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="376" mass="42003" checksum="6095D374964D71DA" modified="2008-02-26" version="2">MTDNELSALVVDNGSGMCKAGFGGDDAPRAVFPSMIGRPRHQGVMVGMGQKDCYVGDEAQSKRGVLTLKYPIEHGVVTNWDDMEKIWYHTFYNELRVAPDEHPILLTEAPLNPKINREKMTQIMFEAFNTPAMYVAIQAVLSLYASGRTTGIVMDSGDGVTHIVPIYEGYALPHAILRLDLAGRDLTDYLMKILTERGYNFTTTAEREIVRDVKEKLCYVALDFEQEMVRAAASSSPERSYELPDGQVITIGNERFRCPEAIFQPSFLGIESSGIHETTFNSIMKCDVDIRKDLYANTVLSGGSTMYPGIADRMQKEIITLAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQEYDEAGPPIVHRKCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-23" modified="2026-01-28" version="142" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BYX7</accession>
    <accession>Q562N5</accession>
    <name>ACTBM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative beta-actin-like protein 3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Kappa-actin</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>POTE ankyrin domain family member K</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">POTEKP</name>
        <name type="synonym">ACTBL3</name>
        <name type="ORF">FKSG30</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2000-11" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and characterization of FKSG30, a novel gene encoding a protein similar to ACTG1.</title>
            <authorList>
                <person name="Wang Y.-G."/>
                <person name="Gong L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Hepatol. Res." volume="36" first="33" last="39">
            <title>Identification of a novel actin isoform in hepatocellular carcinoma.</title>
            <authorList>
                <person name="Chang K.-W."/>
                <person name="Yang P.-Y."/>
                <person name="Lai H.-Y."/>
                <person name="Yeh T.-S."/>
                <person name="Chen T.-C."/>
                <person name="Yeh C.-T."/>
            </authorList>
            <dbReference type="PubMed" id="16824795"/>
            <dbReference type="DOI" id="10.1016/j.hepres.2006.05.003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-186</scope>
        <scope>INTERACTION WITH PFN1 AND PFDN1</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2013" name="Nat. Commun." volume="4" first="1832" last="1832">
            <title>ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.</title>
            <authorList>
                <person name="Li M.M."/>
                <person name="Nilsen A."/>
                <person name="Shi Y."/>
                <person name="Fusser M."/>
                <person name="Ding Y.H."/>
                <person name="Fu Y."/>
                <person name="Liu B."/>
                <person name="Niu Y."/>
                <person name="Wu Y.S."/>
                <person name="Huang C.M."/>
                <person name="Olofsson M."/>
                <person name="Jin K.X."/>
                <person name="Lv Y."/>
                <person name="Xu X.Z."/>
                <person name="He C."/>
                <person name="Dong M.Q."/>
                <person name="Rendtlew Danielsen J.M."/>
                <person name="Klungland A."/>
                <person name="Yang Y.G."/>
            </authorList>
            <dbReference type="PubMed" id="23673617"/>
            <dbReference type="DOI" id="10.1038/ncomms2863"/>
        </citation>
        <scope>METHYLATION AT LYS-84</scope>
        <scope>DEMETHYLATION BY ALKBH4</scope>
    </reference>
    <comment type="subunit">
        <text evidence="2">Interacts with PFN1 and PFDN1. Does not interact with PFN2.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2">Expressed in some hepatocellular carcinomas.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text>Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the actin family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="AY014272">
        <property type="protein sequence ID" value="AAG50355.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY970480">
        <property type="protein sequence ID" value="AAX82286.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BYX7"/>
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        <property type="interactions" value="346"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BYX7">
        <property type="interactions" value="44"/>
    </dbReference>
    <dbReference type="MINT" id="Q9BYX7"/>
    <dbReference type="GlyGen" id="Q9BYX7">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9BYX7"/>
    <dbReference type="PhosphoSitePlus" id="Q9BYX7"/>
    <dbReference type="SwissPalm" id="Q9BYX7"/>
    <dbReference type="BioMuta" id="HGNC:30182"/>
    <dbReference type="DMDM" id="74739412"/>
    <dbReference type="jPOST" id="Q9BYX7"/>
    <dbReference type="MassIVE" id="Q9BYX7"/>
    <dbReference type="ProteomicsDB" id="79742"/>
    <dbReference type="TopDownProteomics" id="Q9BYX7"/>
    <dbReference type="AGR" id="HGNC:30182"/>
    <dbReference type="GeneCards" id="POTEKP"/>
    <dbReference type="HGNC" id="HGNC:30182">
        <property type="gene designation" value="POTEKP"/>
    </dbReference>
    <dbReference type="MIM" id="611266">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q9BYX7"/>
    <dbReference type="PAN-GO" id="Q9BYX7">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9BYX7"/>
    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9BYX7"/>
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        <property type="development level" value="Tdark"/>
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        <property type="term" value="F:ATP binding"/>
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        <property type="term" value="F:structural constituent of postsynaptic actin cytoskeleton"/>
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        <property type="term" value="P:cell motility"/>
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    </dbReference>
    <dbReference type="CDD" id="cd10224">
        <property type="entry name" value="ASKHA_NBD_actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000291">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Major actin"/>
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    <dbReference type="FunFam" id="3.30.420.40:FF:000058">
        <property type="entry name" value="Putative actin-related protein 5"/>
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        <property type="match status" value="2"/>
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    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
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    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
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    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
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    <dbReference type="InterPro" id="IPR004001">
        <property type="entry name" value="Actin_CS"/>
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    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000307865" description="Putative beta-actin-like protein 3">
        <location>
            <begin position="1"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="1">
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="1">
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-methyllysine" evidence="3">
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAX82286." evidence="4" ref="2">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAX82286." evidence="4" ref="2">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="16824795"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="23673617"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="375" mass="42016" checksum="98127B88A9983B7D" modified="2001-06-01" version="1">MDDDTAVLVIDNGSGMCKAGFAGDDAPQAVFPSIVGRPRHQGMMEGMHQKESYVGKEAQSKRGMLTLKYPMEHGIITNWDDMEKIWHHTFYNELRVAPEEHPILLTEAPLNPKANREKMTQIMFETFNTPAMYVAIQAVLSLYTSGRTTGIVMDSGDGFTHTVPIYEGNALPHATLRLDLAGRELTDYLMKILTERGYRFTTTAEQEIVRDIKEKLCYVALDSEQEMAMAASSSSVEKSYELPDGQVITIGNERFRCPEALFQPCFLGMESCGIHKTTFNSIVKSDVDIRKDLYTNTVLSGGTTMYPGIAHRMQKEITALAPSIMKIKIIAPPKRKYSVWVGGSILASLSTFQQMWISKQEYDESGPSIVHRKCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="217" xmlns="https://uniprot.org/uniprot">
    <accession>P60709</accession>
    <accession>P02570</accession>
    <accession>P70514</accession>
    <accession>P99021</accession>
    <accession>Q11211</accession>
    <accession>Q64316</accession>
    <accession>Q75MN2</accession>
    <accession>Q96B34</accession>
    <accession>Q96HG5</accession>
    <name>ACTB_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin, cytoplasmic 1</fullName>
            <ecNumber evidence="3">3.6.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Beta-actin</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Actin, cytoplasmic 1, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">ACTB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA.</title>
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                <person name="Ponte P."/>
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            <dbReference type="PubMed" id="6322116"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
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            <dbReference type="PubMed" id="2994062"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
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                <person name="Ohmori H."/>
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            </authorList>
            <dbReference type="PubMed" id="1734024"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="12853948"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Eye</tissue>
            <tissue>Kidney</tissue>
            <tissue>Muscle</tissue>
            <tissue>Pancreas</tissue>
            <tissue>Placenta</tissue>
            <tissue>Skin</tissue>
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            <dbReference type="DOI" id="10.1038/nbt810"/>
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        <scope>PROTEIN SEQUENCE OF 2-28</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
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        <citation type="submission" date="2005-06" db="UniProtKB">
            <authorList>
                <person name="Bienvenut W.V."/>
            </authorList>
        </citation>
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        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT ASP-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>B-cell lymphoma</tissue>
        </source>
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                <person name="Afjehi-Sadat L."/>
                <person name="Chen W.-Q."/>
                <person name="Sun Y."/>
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        <scope>PROTEIN SEQUENCE OF 19-62; 85-113; 184-191; 197-206; 216-254; 291-312; 316-326 AND 360-372</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Cajal-Retzius cell</tissue>
            <tissue>Fetal brain cortex</tissue>
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                <person name="Hanukoglu I."/>
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            <dbReference type="DOI" id="10.1016/0022-2836(83)90117-1"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 252-375</scope>
    </reference>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH DHX9</scope>
    </reference>
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        <scope>IDENTIFICATION IN A COMPLEX WITH RAN; XPO6 AND PFN1</scope>
        <scope>INTERACTION WITH XPO6</scope>
    </reference>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Lymphoblast</tissue>
        </source>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 66-80 IN COMPLEX WITH SETD3</scope>
        <scope>METHYLATION AT HIS-73</scope>
        <scope>MUTAGENESIS OF HIS-73</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 66-88 IN COMPLEX WITH SETD3</scope>
        <scope>MUTAGENESIS OF HIS-73</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) OF 66-88 IN COMPLEX WITH SETD3</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.57 ANGSTROMS) IN COMPLEX WITH MZT1; MZT2A; CDK5RAP2 AND THE GAMMA-TUBULIN RING COMPLEX</scope>
        <scope>FUNCTION</scope>
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            <dbReference type="PubMed" id="38609661"/>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (7.00 ANGSTROMS) IN COMPLEXES WITH MZT1; TUBA1B; TUBB3 AND THE GAMMA-TUBULIN RING COMPLEX</scope>
        <scope>FUNCTION</scope>
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        <scope>VARIANT THC8 LYS-364</scope>
        <scope>INVOLVEMENT IN THC8</scope>
        <scope>INTERACTION WITH PFN1</scope>
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        <scope>VARIANT DDS1 TRP-183</scope>
        <scope>CHARACTERIZATION OF VARIANT DDS1 TRP-183</scope>
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        <scope>VARIANTS BRWS1 ASP-12; VAL-65; CYS-196 AND HIS-196</scope>
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        <scope>CHARACTERIZATION OF VARIANT DDS1 TRP-183</scope>
        <scope>CHARACTERIZATION OF VARIANT THC8 LYS-364</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
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        <scope>VARIANT DDS1 TRP-183</scope>
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        <scope>VARIANT BNS CYS-147</scope>
        <scope>VARIANT SER-147</scope>
        <scope>INVOLVEMENT IN BNS</scope>
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        <scope>VARIANT DDS1 TRP-183</scope>
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        <scope>VARIANTS THC8 ARG-313 AND 338-SER--ILE-341 DEL</scope>
        <scope>INVOLVEMENT IN THC8</scope>
    </reference>
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        <scope>VARIANT BRWS1 ALA-70</scope>
        <scope>VARIANT THC8 PHE-171</scope>
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        <scope>VARIANTS CSMH ASP-111; HIS-137; ALA-146; VAL-146; ASP-146; SER-146; SER-147 AND CYS-147</scope>
        <scope>INVOLVEMENT IN CSMH</scope>
    </reference>
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        <scope>VARIANT DDS1 TRP-183</scope>
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    <comment type="function">
        <text evidence="4 21 26 28 40 41">Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="21">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 4 5 6 8 9 11 12 13 14 16 17 21 24 40 41">Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (PubMed:16685646, PubMed:28604741). Each actin can bind to 4 others (PubMed:16685646, PubMed:28604741). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:18765789). In muscle cells, the BAF complex also contains DPF3 (PubMed:18765789). Found in a complex with XPO6, Ran, ACTB and PFN1 (PubMed:14592989). Interacts with PFN1 (PubMed:10411937, PubMed:25255767). Interacts with XPO6 and EMD (PubMed:15328537). Interacts with ERBB2 (PubMed:21555369). Interacts with GCSAM (PubMed:17823310). Interacts with TBC1D21 (By similarity). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (By similarity). Interacts with DHX9 (via C-terminus); this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (PubMed:11687588). Interacts with FAM107A (PubMed:21969592, PubMed:28604741). Associates with the gamma-tubulin ring complex (gTuRC) consisting of TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 and gamma-tubulin TUBG1 or TUBG2; within the complex, interacts with TUBGCP3 and TUBGCP6 to form a luminal bridge with MZT1 that stabilizes the initial structure during complex assembly (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The filament contains 8 copies of ACTR1A and 1 ACTB (By similarity). Interacts with TPRN which forms ring-like structures in the stereocilium taper region; the interaction may stabilize stereocilia in inner ear hair cells (By similarity). Interacts with AMOTL2 (via N-terminus), the interaction facilitates binding of cell junction complexes to actin fibers in endothelial cells (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-353944">
            <id>P60709</id>
            <label>ACTB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-351292">
            <id>P63261</id>
            <label>ACTG1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-525456">
            <id>Q9UQB8</id>
            <label>BAIAP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-1051165">
            <id>P40123</id>
            <label>CAP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-295634">
            <id>Q16543</id>
            <label>CDC37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-352733">
            <id>P23528</id>
            <label>CFL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-10201319">
            <id>Q549N0</id>
            <label>CFL2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-351218">
            <id>Q9Y281</id>
            <label>CFL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-349854">
            <id>P13569</id>
            <label>CFTR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-745191">
            <id>P60981</id>
            <label>DSTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-8654968">
            <id>Q8WTR2</id>
            <label>DUSP19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2339219">
            <id>Q08426</id>
            <label>EHHADH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-489887">
            <id>P50402</id>
            <label>EMD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-641062">
            <id>P04626</id>
            <label>ERBB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
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        <interactant intactId="EBI-6264551">
            <id>Q8TCJ0-2</id>
            <label>FBXO25</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-351896">
            <id>P11142</id>
            <label>HSPA8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2867394">
            <id>P83110</id>
            <label>HTRA3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-1642165">
            <id>O14950</id>
            <label>MYL12B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-395044">
            <id>P14598</id>
            <label>NCF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-1391623">
            <id>P29474</id>
            <label>NOS3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2947053">
            <id>Q92636</id>
            <label>NSMAF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-741158">
            <id>Q96HA8</id>
            <label>NTAQ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-713780">
            <id>P07737</id>
            <label>PFN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2340927">
            <id>P78317</id>
            <label>RNF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-347161">
            <id>P84022</id>
            <label>SMAD3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-1056740">
            <id>P37802</id>
            <label>TAGLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
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        <interactant intactId="EBI-717399">
            <id>Q9BSI4</id>
            <label>TINF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-1783169">
            <id>P13693</id>
            <label>TPT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-10180829">
            <id>Q7KZS0</id>
            <label>UBE2I</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
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        <interactant intactId="EBI-11141397">
            <id>Q9UBQ0-2</id>
            <label>VPS29</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-351917">
            <id>O75083</id>
            <label>WDR1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2169">
            <id>P60010</id>
            <label>ACT1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-2406">
            <id>P46680</id>
            <label>AIP1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-916155">
            <id>P08413</id>
            <label>Camk2b</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-79525">
            <id>Q9PTD7</id>
            <label>cgn</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-8291665">
            <id>Q8K4J6</id>
            <label>Mrtfa</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-1797">
            <id>Q02821</id>
            <label>SRP1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-353944">
            <id>P60709</id>
        </interactant>
        <interactant intactId="EBI-21116">
            <id>P38340</id>
            <label>TAE1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 12">Cytoplasm</location>
            <location evidence="6 12">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 28">Nucleus</location>
        </subcellularLocation>
        <text evidence="12">Localized in cytoplasmic mRNP granules containing untranslated mRNAs.</text>
    </comment>
    <comment type="PTM">
        <text evidence="10">ISGylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="25">Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <text evidence="19">Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes (PubMed:23673617). Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (PubMed:23673617).</text>
    </comment>
    <comment type="PTM">
        <text evidence="2 31 32 34 35">Methylated at His-73 by SETD3 (PubMed:30526847, PubMed:30626964, PubMed:30785395, PubMed:31388018). Methylation at His-73 is required for smooth muscle contraction of the laboring uterus during delivery (By similarity).</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, cytoplasmic 1</molecule>
        <text evidence="39">N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, cytoplasmic 1, N-terminally processed</molecule>
        <text evidence="26">N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins (PubMed:29581253). In contrast, filament nucleation by the Arp2/3 complex is not affected (PubMed:29581253).</text>
    </comment>
    <comment type="PTM">
        <text evidence="44 45">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
    <comment type="disease" evidence="11 21 23 27 38">
        <disease id="DI-00412">
            <name>Dystonia-deafness syndrome 1</name>
            <acronym>DDS1</acronym>
            <description>An autosomal dominant form of dystonia with juvenile onset, associated with congenital or childhood-onset sensorineural deafness. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. Some DDS1 patients have dysmorphic features, skeletal anomalies, and/or mild developmental delay with impaired intellectual development.</description>
            <dbReference type="MIM" id="607371"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="18 33">
        <disease id="DI-03416">
            <name>Baraitser-Winter syndrome 1</name>
            <acronym>BRWS1</acronym>
            <description>A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.</description>
            <dbReference type="MIM" id="243310"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="5 21 30 33">
        <disease id="DI-06744">
            <name>Thrombocytopenia 8, with dysmorphic features and developmental delay</name>
            <acronym>THC8</acronym>
            <description>A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC8 is an autosomal dominant form characterized by early-childhood onset of thrombocytopenia with platelet anisotropy. Affected individuals also have dysmorphic facial features and variable developmental delay with speech delay and mildly impaired intellectual development.</description>
            <dbReference type="MIM" id="620475"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="22">
        <disease id="DI-06747">
            <name>Becker nevus syndrome</name>
            <acronym>BNS</acronym>
            <description>A syndrome characterized by the association of Becker nevi with musculoskeletal abnormalities, unilateral breast hypoplasia, intellectual disability, developmental delay, and cardiomyopathy. Becker nevus is a cutaneous hamartoma that appears in childhood as a unilateral tan patch and increases in thickness, pigmentation, and hair growth during adolescence. Histologically, epidermal acanthosis is accompanied by irregularly dispersed ectopic smooth muscle bundles and increased terminal hair follicles. Most cases are sporadic.</description>
            <dbReference type="MIM" id="604919"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="36">
        <disease id="DI-06743">
            <name>Congenital smooth muscle hamartoma, with or without hemihypertrophy</name>
            <acronym>CSMH</acronym>
            <description>A benign skin lesion that usually presents as an indurated, slightly pigmented or flesh-colored plaque with perifollicular papules or coarse hair. Histopathologically, there is excessive proliferation of ectopic smooth muscle within the dermis. Hair follicles are normal in number and hyperkeratosis, acanthosis and hyperpigmentation of the basal cell layer can sometimes be seen. Rarely, CSMH is associated with hemihypertrophy.</description>
            <dbReference type="MIM" id="620470"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="43">In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="43">Belongs to the actin family.</text>
    </comment>
    <comment type="caution">
        <text evidence="15 20">Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/42959/ACTB"/>
    </comment>
    <comment type="online information" name="Mendelian genes actin, beta (ACTB)">
        <link uri="https://databases.lovd.nl/shared/genes/ACTB"/>
        <text>Leiden Open Variation Database (LOVD)</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/208/"/>
        <text>On mar and motion - Issue 208 of November 2018</text>
    </comment>
    <dbReference type="EC" id="3.6.4.-" evidence="3"/>
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        <property type="protein sequence ID" value="CAA25099.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="M10277">
        <property type="protein sequence ID" value="AAA51567.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X63432">
        <property type="protein sequence ID" value="CAA45026.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AY582799">
        <property type="protein sequence ID" value="AAS79319.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006483">
        <property type="protein sequence ID" value="AAP22343.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001301">
        <property type="protein sequence ID" value="AAH01301.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002409">
        <property type="protein sequence ID" value="AAH02409.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004251">
        <property type="protein sequence ID" value="AAH04251.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008633">
        <property type="protein sequence ID" value="AAH08633.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012854">
        <property type="protein sequence ID" value="AAH12854.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC013380">
        <property type="protein sequence ID" value="AAH13380.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014861">
        <property type="protein sequence ID" value="AAH14861.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016045">
        <property type="protein sequence ID" value="AAH16045.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="V00478">
        <property type="protein sequence ID" value="CAA23745.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5341.1"/>
    <dbReference type="PIR" id="A25168">
        <property type="entry name" value="ATHUB"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001092.1">
        <property type="nucleotide sequence ID" value="NM_001101.5"/>
    </dbReference>
    <dbReference type="PDB" id="3BYH">
        <property type="method" value="EM"/>
        <property type="resolution" value="12.00 A"/>
        <property type="chains" value="A=2-375"/>
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    <dbReference type="PDB" id="3D2U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.21 A"/>
        <property type="chains" value="C/G=170-178"/>
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    <dbReference type="PDB" id="3J82">
        <property type="method" value="EM"/>
        <property type="resolution" value="7.70 A"/>
        <property type="chains" value="B/C/D=2-375"/>
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    <dbReference type="PDB" id="3LUE">
        <property type="method" value="EM"/>
        <property type="chains" value="A/B/C/D/E/F/G/H/I/J=2-375"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="7.00 A"/>
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    <dbReference type="PDB" id="6ICT">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.95 A"/>
        <property type="chains" value="E/G/H/I=66-88"/>
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    <dbReference type="PDB" id="6ICV">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="C/D=66-88"/>
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    <dbReference type="PDB" id="6LTJ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.70 A"/>
        <property type="chains" value="K=1-375"/>
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    <dbReference type="PDB" id="6MBJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.78 A"/>
        <property type="chains" value="Y/Z=66-80"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.69 A"/>
        <property type="chains" value="Y/Z=66-80"/>
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        <property type="evidence" value="ECO:0007007"/>
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        <property type="entry name" value="Actin/actin-like_CS"/>
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        <property type="entry name" value="Actin_CS"/>
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        <property type="entry name" value="ATPase_NBD"/>
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    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
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    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
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    <dbReference type="PROSITE" id="PS00406">
        <property type="entry name" value="ACTINS_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1023">Dystonia</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000367073" description="Actin, cytoplasmic 1">
        <location>
            <begin position="1"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="initiator methionine" description="Removed; alternate" evidence="7 39 42 61 62 63 64">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000771" description="Actin, cytoplasmic 1, N-terminally processed" evidence="46">
        <location>
            <begin position="2"/>
            <end position="375"/>
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    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="39 63">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylaspartate; in Actin, cytoplasmic 1, N-terminally processed" evidence="26 29 42 61 62 63 64">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="25">
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="25">
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="modified residue" description="Tele-methylhistidine" evidence="31 32 34 35 37">
        <location>
            <position position="73"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-methyllysine" evidence="19">
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-270); by Vibrio toxins RtxA and VgrG1" evidence="44">
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="cross-link" description="(Microbial infection) Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-50); by Vibrio toxins RtxA and VgrG1" evidence="44">
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067810" description="In BRWS1; dbSNP:rs281875331." evidence="18">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067811" description="In BRWS1; dbSNP:rs281875332." evidence="18">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088861" description="In BRWS1; likely pathogenic." evidence="33">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088862" description="In CSMH; uncertain significance; somatic variant." evidence="36">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088863" description="In CSMH; uncertain significance; somatic variant." evidence="36">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088864" description="In CSMH; somatic variant." evidence="36">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088865" description="In CSMH; somatic variant." evidence="36">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088866" description="In CSMH; somatic variant." evidence="36">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088867" description="In CSMH; somatic variant." evidence="36">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088868" description="In BNS and CSMH; also found in isolated non-syndromic Becker nevi; somatic variant." evidence="22 36">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088869" description="In CSMH; also found in isolated non-syndromic Becker nevi; somatic variant." evidence="22 36">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088870" description="In THC8; likely pathogenic." evidence="33">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="171"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030026" description="In DDS1; likely pathogenic; results in reduced actin polymerization rate and increased depolymerization; results in higher ATP hydrolysis compared to the wild type; does not affect thermal stability; modifies cell response to latrunculin A; dbSNP:rs104894003." evidence="11 21 23 27 38">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067812" description="In BRWS1; dbSNP:rs281875333." evidence="18">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067813" description="In BRWS1; dbSNP:rs281875334." evidence="18">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048185" description="In dbSNP:rs11546899.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088871" description="In THC8; uncertain significance." evidence="30">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088872" description="In THC8; likely pathogenic." evidence="30">
        <location>
            <begin position="338"/>
            <end position="341"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088873" description="In THC8; uncertain significance; results in reduced actin polymerization rate without affecting depolymerization; has no effect on ATP hydrolysis rate; does not affect thermal stability." evidence="5 21">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased interaction with SETD3." evidence="34">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="69"/>
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        <citation type="journal article" date="1989" name="Nucleic Acids Res." volume="17" first="1767" last="1767">
            <title>The nucleotide sequence of a human smooth muscle alpha-actin (aortic type) cDNA.</title>
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                <person name="Kakunaga T."/>
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            <dbReference type="PubMed" id="30626964"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0821-8"/>
        </citation>
        <scope>METHYLATION AT HIS-75</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2007" name="Nat. Genet." volume="39" first="1488" last="1493">
            <title>Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections.</title>
            <authorList>
                <person name="Guo D.-C."/>
                <person name="Pannu H."/>
                <person name="Tran-Fadulu V."/>
                <person name="Papke C.L."/>
                <person name="Yu R.K."/>
                <person name="Avidan N."/>
                <person name="Bourgeois S."/>
                <person name="Estrera A.L."/>
                <person name="Safi H.J."/>
                <person name="Sparks E."/>
                <person name="Amor D."/>
                <person name="Ades L."/>
                <person name="McConnell V."/>
                <person name="Willoughby C.E."/>
                <person name="Abuelo D."/>
                <person name="Willing M."/>
                <person name="Lewis R.A."/>
                <person name="Kim D.H."/>
                <person name="Scherer S."/>
                <person name="Tung P.P."/>
                <person name="Ahn C."/>
                <person name="Buja L.M."/>
                <person name="Raman C.S."/>
                <person name="Shete S.S."/>
                <person name="Milewicz D.M."/>
            </authorList>
            <dbReference type="PubMed" id="17994018"/>
            <dbReference type="DOI" id="10.1038/ng.2007.6"/>
        </citation>
        <scope>VARIANTS AAT6 THR-117; GLN-118; HIS-135; CYS-149; ALA-154; CYS-258; HIS-258; GLY-292 AND ASN-353</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2009" name="Am. J. Hum. Genet." volume="84" first="617" last="627">
            <title>Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease.</title>
            <authorList>
                <person name="Guo D.-C."/>
                <person name="Papke C.L."/>
                <person name="Tran-Fadulu V."/>
                <person name="Regalado E.S."/>
                <person name="Avidan N."/>
                <person name="Johnson R.J."/>
                <person name="Kim D.H."/>
                <person name="Pannu H."/>
                <person name="Willing M.C."/>
                <person name="Sparks E."/>
                <person name="Pyeritz R.E."/>
                <person name="Singh M.N."/>
                <person name="Dalman R.L."/>
                <person name="Grotta J.C."/>
                <person name="Marian A.J."/>
                <person name="Boerwinkle E.A."/>
                <person name="Frazier L.Q."/>
                <person name="LeMaire S.A."/>
                <person name="Coselli J.S."/>
                <person name="Estrera A.L."/>
                <person name="Safi H.J."/>
                <person name="Veeraraghavan S."/>
                <person name="Muzny D.M."/>
                <person name="Wheeler D.A."/>
                <person name="Willerson J.T."/>
                <person name="Yu R.K."/>
                <person name="Shete S.S."/>
                <person name="Scherer S.E."/>
                <person name="Raman C.S."/>
                <person name="Buja L.M."/>
                <person name="Milewicz D.M."/>
            </authorList>
            <dbReference type="PubMed" id="19409525"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2009.04.007"/>
        </citation>
        <scope>VARIANTS AAT6 HIS-39; THR-117; GLN-118; CYS-149; ALA-154; GLN-185; GLN-212; HIS-258; CYS-258; ASN-326 AND ASN-353</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2009" name="Hum. Mutat." volume="30" first="1406" last="1411">
            <title>Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD).</title>
            <authorList>
                <person name="Morisaki H."/>
                <person name="Akutsu K."/>
                <person name="Ogino H."/>
                <person name="Kondo N."/>
                <person name="Yamanaka I."/>
                <person name="Tsutsumi Y."/>
                <person name="Yoshimuta T."/>
                <person name="Okajima T."/>
                <person name="Matsuda H."/>
                <person name="Minatoya K."/>
                <person name="Sasaki H."/>
                <person name="Tanaka H."/>
                <person name="Ishibashi-Ueda H."/>
                <person name="Morisaki T."/>
            </authorList>
            <dbReference type="PubMed" id="19639654"/>
            <dbReference type="DOI" id="10.1002/humu.21081"/>
        </citation>
        <scope>VARIANTS AAT6 CYS-145; CYS-149 AND GLN-212</scope>
        <scope>PREDISPOSITION TO A VARIETY OF VASCULAR DISEASES</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2010" name="Am. J. Med. Genet. A" volume="152" first="2437" last="2443">
            <title>De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction.</title>
            <authorList>
                <person name="Milewicz D.M."/>
                <person name="Ostergaard J.R."/>
                <person name="Ala-Kokko L.M."/>
                <person name="Khan N."/>
                <person name="Grange D.K."/>
                <person name="Mendoza-Londono R."/>
                <person name="Bradley T.J."/>
                <person name="Olney A.H."/>
                <person name="Ades L."/>
                <person name="Maher J.F."/>
                <person name="Guo D."/>
                <person name="Buja L.M."/>
                <person name="Kim D."/>
                <person name="Hyland J.C."/>
                <person name="Regalado E.S."/>
            </authorList>
            <dbReference type="PubMed" id="20734336"/>
            <dbReference type="DOI" id="10.1002/ajmg.a.33657"/>
        </citation>
        <scope>VARIANT SMDYS HIS-179</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2011" name="Eur. J. Paediatr. Neurol." volume="15" first="117" last="122">
            <title>Analysis of ACTA2 in European Moyamoya disease patients.</title>
            <authorList>
                <person name="Roder C."/>
                <person name="Peters V."/>
                <person name="Kasuya H."/>
                <person name="Nishizawa T."/>
                <person name="Wakita S."/>
                <person name="Berg D."/>
                <person name="Schulte C."/>
                <person name="Khan N."/>
                <person name="Tatagiba M."/>
                <person name="Krischek B."/>
            </authorList>
            <dbReference type="PubMed" id="20970362"/>
            <dbReference type="DOI" id="10.1016/j.ejpn.2010.09.002"/>
        </citation>
        <scope>VARIANT MYMY5 HIS-179</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2016" name="Am. J. Med. Genet. A" volume="170" first="2965" last="2974">
            <title>Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</title>
            <authorList>
                <person name="Moreno C.A."/>
                <person name="Metze K."/>
                <person name="Lomazi E.A."/>
                <person name="Bertola D.R."/>
                <person name="Barbosa R.H."/>
                <person name="Cosentino V."/>
                <person name="Sobreira N."/>
                <person name="Cavalcanti D.P."/>
            </authorList>
            <dbReference type="PubMed" id="27481187"/>
            <dbReference type="DOI" id="10.1002/ajmg.a.37857"/>
        </citation>
        <scope>VARIANT SMDYS CYS-179</scope>
    </reference>
    <comment type="function">
        <text>Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text>Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-698810">
            <id>P62736</id>
        </interactant>
        <interactant intactId="EBI-3046641">
            <id>P17900</id>
            <label>GM2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-698810">
            <id>P62736</id>
        </interactant>
        <interactant intactId="EBI-2603996">
            <id>Q9BXW4</id>
            <label>MAP1LC3C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-698810">
            <id>P62736</id>
        </interactant>
        <interactant intactId="EBI-7797649">
            <id>P11684</id>
            <label>SCGB1A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-698810">
            <id>P62736</id>
        </interactant>
        <interactant intactId="EBI-11897462">
            <id>Q8N4U5</id>
            <label>TCP11L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-698810">
            <id>P62736</id>
        </interactant>
        <interactant intactId="EBI-751204">
            <id>Q9BWQ6</id>
            <label>YIPF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="induction">
        <text evidence="5">Up-regulated in response to enterovirus 71 (EV71) infection.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Methylated at His-75 by SETD3.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, aortic smooth muscle, intermediate form</molecule>
        <text evidence="2">N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14 15">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
    <comment type="disease">
        <text evidence="7">ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, premature onset coronary artery disease (CAD), premature ischemic strokes and Moyamoya disease.</text>
    </comment>
    <comment type="disease" evidence="6 7 8">
        <disease id="DI-00130">
            <name>Aortic aneurysm, familial thoracic 6</name>
            <acronym>AAT6</acronym>
            <description>A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.</description>
            <dbReference type="MIM" id="611788"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-03141">
            <name>Moyamoya disease 5</name>
            <acronym>MYMY5</acronym>
            <description>A progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults.</description>
            <dbReference type="MIM" id="614042"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 11">
        <disease id="DI-03109">
            <name>Smooth muscle dysfunction syndrome</name>
            <acronym>SMDYS</acronym>
            <description>An autosomal dominant syndrome characterized by dysfunction of smooth muscle cells throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.</description>
            <dbReference type="MIM" id="613834"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.-" evidence="4"/>
    <dbReference type="EMBL" id="X13839">
        <property type="protein sequence ID" value="CAA32064.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J05192">
        <property type="protein sequence ID" value="AAA51577.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY692464">
        <property type="protein sequence ID" value="AAW29811.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR536518">
        <property type="protein sequence ID" value="CAG38756.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313294">
        <property type="protein sequence ID" value="BAG36101.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL157394">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW50153.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017554">
        <property type="protein sequence ID" value="AAH17554.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC093052">
        <property type="protein sequence ID" value="AAH93052.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="K01741">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="K01742">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="K01743">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M33216">
        <property type="protein sequence ID" value="AAA60560.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7392.1"/>
    <dbReference type="PIR" id="A35020">
        <property type="entry name" value="ATHUSM"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001135417.1">
        <property type="nucleotide sequence ID" value="NM_001141945.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307784.1">
        <property type="nucleotide sequence ID" value="NM_001320855.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393391.1">
        <property type="nucleotide sequence ID" value="NM_001406462.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393392.1">
        <property type="nucleotide sequence ID" value="NM_001406463.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393393.1">
        <property type="nucleotide sequence ID" value="NM_001406464.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001604.1">
        <property type="nucleotide sequence ID" value="NM_001613.4"/>
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    <dbReference type="AlphaFoldDB" id="P62736"/>
    <dbReference type="EMDB" id="EMD-35888"/>
    <dbReference type="SMR" id="P62736"/>
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        <property type="interactions" value="564"/>
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    <dbReference type="CORUM" id="P62736"/>
    <dbReference type="ELM" id="P62736"/>
    <dbReference type="FunCoup" id="P62736">
        <property type="interactions" value="597"/>
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    <dbReference type="IntAct" id="P62736">
        <property type="interactions" value="233"/>
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    <dbReference type="MINT" id="P62736"/>
    <dbReference type="STRING" id="9606.ENSP00000224784"/>
    <dbReference type="DrugBank" id="DB12695">
        <property type="generic name" value="Phenethyl Isothiocyanate"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P62736">
        <property type="glycosylation" value="1 site, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P62736">
        <property type="glycosylation" value="4 sites, 1 N-linked glycan (1 site), 2 O-linked glycans (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P62736"/>
    <dbReference type="MetOSite" id="P62736"/>
    <dbReference type="PhosphoSitePlus" id="P62736"/>
    <dbReference type="SwissPalm" id="P62736"/>
    <dbReference type="BioMuta" id="ACTA2"/>
    <dbReference type="DMDM" id="51316972"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00008603"/>
    <dbReference type="jPOST" id="P62736"/>
    <dbReference type="MassIVE" id="P62736"/>
    <dbReference type="PaxDb" id="9606-ENSP00000402373"/>
    <dbReference type="PeptideAtlas" id="P62736"/>
    <dbReference type="PRIDE" id="P62736"/>
    <dbReference type="ProteomicsDB" id="57419"/>
    <dbReference type="Pumba" id="P62736"/>
    <dbReference type="TopDownProteomics" id="P62736"/>
    <dbReference type="Antibodypedia" id="30207">
        <property type="antibodies" value="1563 antibodies from 53 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="59"/>
    <dbReference type="Ensembl" id="ENST00000224784.10">
        <property type="protein sequence ID" value="ENSP00000224784.6"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000415557.2">
        <property type="protein sequence ID" value="ENSP00000396730.2"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
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    <dbReference type="Ensembl" id="ENST00000458159.6">
        <property type="protein sequence ID" value="ENSP00000398239.2"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
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    <dbReference type="Ensembl" id="ENST00000713597.1">
        <property type="protein sequence ID" value="ENSP00000518893.1"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
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    <dbReference type="Ensembl" id="ENST00000713599.1">
        <property type="protein sequence ID" value="ENSP00000518895.1"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
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    <dbReference type="Ensembl" id="ENST00000713602.1">
        <property type="protein sequence ID" value="ENSP00000518898.1"/>
        <property type="gene ID" value="ENSG00000107796.15"/>
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    <dbReference type="GeneID" id="59"/>
    <dbReference type="KEGG" id="hsa:59"/>
    <dbReference type="MANE-Select" id="ENST00000224784.10">
        <property type="protein sequence ID" value="ENSP00000224784.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001613.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001604.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001kfp.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:130"/>
    <dbReference type="ClinPGx" id="PA24456"/>
    <dbReference type="CTD" id="59"/>
    <dbReference type="DisGeNET" id="59"/>
    <dbReference type="GeneCards" id="ACTA2"/>
    <dbReference type="GeneReviews" id="ACTA2"/>
    <dbReference type="HGNC" id="HGNC:130">
        <property type="gene designation" value="ACTA2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000107796">
        <property type="expression patterns" value="Tissue enhanced (endometrium, seminal vesicle, smooth muscle)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACTA2"/>
    <dbReference type="MIM" id="102620">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="611788">
        <property type="type" value="phenotype"/>
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    <dbReference type="MIM" id="613834">
        <property type="type" value="phenotype"/>
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    <dbReference type="MIM" id="614042">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000107796"/>
    <dbReference type="Orphanet" id="91387">
        <property type="disease" value="Familial thoracic aortic aneurysm and aortic dissection"/>
    </dbReference>
    <dbReference type="Orphanet" id="2573">
        <property type="disease" value="Moyamoya disease"/>
    </dbReference>
    <dbReference type="Orphanet" id="404463">
        <property type="disease" value="Multisystemic smooth muscle dysfunction syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000107796"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000154148"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_2_1"/>
    <dbReference type="InParanoid" id="P62736"/>
    <dbReference type="OMA" id="THNTIHA"/>
    <dbReference type="OrthoDB" id="9816491at2759"/>
    <dbReference type="PAN-GO" id="P62736">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="P62736"/>
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        <property type="pathway name" value="Smooth Muscle Contraction"/>
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        <property type="pathway name" value="NOTCH4 Intracellular Domain Regulates Transcription"/>
    </dbReference>
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        <property type="pathway name" value="Regulation of CDH1 Function"/>
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    <dbReference type="Reactome" id="R-HSA-9913351">
        <property type="pathway name" value="Formation of the dystrophin-glycoprotein complex (DGC)"/>
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        <property type="organism name" value="human"/>
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        <property type="component" value="Chromosome 10"/>
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        <property type="expression patterns" value="baseline and differential"/>
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        <property type="entry name" value="ASKHA_NBD_actin"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ATPase_NBD"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ACTINS_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0993">Aortic aneurysm</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0514">Muscle protein</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000442603" description="Actin, aortic smooth muscle, intermediate form" evidence="2">
        <location>
            <begin position="2"/>
            <end position="377"/>
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            <begin position="3"/>
            <end position="377"/>
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    <feature type="modified residue" description="N-acetylcysteine; in intermediate form" evidence="2">
        <location>
            <position position="2"/>
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    <feature type="modified residue" description="N-acetylglutamate; in Actin, aortic smooth muscle" evidence="16">
        <location>
            <position position="3"/>
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    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="2">
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="2">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="modified residue" description="Tele-methylhistidine" evidence="12">
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-methyllysine" evidence="3">
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-52); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062577" description="In AAT6; dbSNP:rs794728021." evidence="7">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045915" description="In AAT6." evidence="6 7">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045916" description="In AAT6; dbSNP:rs112602953." evidence="6 7">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045917" description="In AAT6; dbSNP:rs751300489." evidence="6">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="135"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062578" description="In AAT6." evidence="8">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="145"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045918" description="In AAT6; dbSNP:rs121434526." evidence="6 7 8">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045919" description="In AAT6; dbSNP:rs1554841298." evidence="6 7">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085865" description="In SMDYS; dbSNP:rs886039303." evidence="11">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_064516" description="In MYMY5 and SMDYS; disease phenotype include smooth muscle cells dysfunction in organs throughout the body with decreased contractile function in the iris, bladder and gastrointestinal tract; dbSNP:rs387906592." evidence="9 10">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062579" description="In AAT6; dbSNP:rs1057521105." evidence="7">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011944" description="In dbSNP:rs1803028.">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062580" description="In AAT6; dbSNP:rs397516685." evidence="7 8">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045920" description="In AAT6; dbSNP:rs121434528." evidence="6 7">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045921" description="In AAT6; dbSNP:rs121434527." evidence="6 7">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045922" description="In AAT6." evidence="6">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="292"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011945" description="In dbSNP:rs1803027.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062581" description="In AAT6; dbSNP:rs777832794." evidence="7">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045923" description="In AAT6." evidence="6 7">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011946" description="In dbSNP:rs1062398.">
        <original>H</original>
        <variation>P</variation>
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAA51577." evidence="13" ref="2">
        <original>S</original>
        <variation>W</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P60709"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P62737"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P68032"/>
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    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P68137"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16548883"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17994018"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="19409525"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="19639654"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="20734336"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="20970362"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="27481187"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="30626964"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="19015515"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="26228148"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <sequence length="377" mass="42009" checksum="2D0543262DB35CA5" modified="2004-08-16" version="1" precursor="true">MCEEEDSTALVCDNGSGLCKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIITNWDDMEKIWHHSFYNELRVAPEEHPTLLTEAPLNPKANREKMTQIMFETFNVPAMYVAIQAVLSLYASGRTTGIVLDSGDGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERGYSFVTTAEREIVRDIKEKLCYVALDFENEMATAASSSSLEKSYELPDGQVITIGNERFRCPETLFQPSFIGMESAGIHETTYNSIMKCDIDIRKDLYANNVLSGGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQEYDEAGPSIVHRKCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-10-02" modified="2026-01-28" version="151" xmlns="https://uniprot.org/uniprot">
    <accession>Q53FZ2</accession>
    <accession>O60363</accession>
    <accession>Q13732</accession>
    <accession>Q15425</accession>
    <accession>Q7KYM6</accession>
    <accession>Q9BUA2</accession>
    <name>ACSM3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM3, mitochondrial</fullName>
            <ecNumber evidence="5">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Butyrate--CoA ligase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Butyryl-coenzyme A synthetase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Middle-chain acyl-CoA synthetase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Propionate--CoA ligase</fullName>
            <ecNumber evidence="3">6.2.1.17</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Protein SA homolog</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM3</name>
        <name type="synonym">SAH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Hypertension" volume="23" first="375" last="380">
            <title>Human SA gene locus as a candidate locus for essential hypertension.</title>
            <authorList>
                <person name="Iwai N."/>
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                <person name="Kinoshita M."/>
            </authorList>
            <dbReference type="PubMed" id="7907320"/>
            <dbReference type="DOI" id="10.1161/01.hyp.23.3.375"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1995" name="Hypertension" volume="25" first="6" last="13">
            <title>Evaluation of the SA locus in human hypertension.</title>
            <authorList>
                <person name="Nabika T."/>
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                <person name="Soubrier F."/>
            </authorList>
            <dbReference type="PubMed" id="7843754"/>
            <dbReference type="DOI" id="10.1161/01.hyp.25.1.6"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>LACK OF INVOLVEMENT IN HEREDITARY HYPERTENSION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="Genomics" volume="60" first="295" last="308">
            <title>Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.</title>
            <authorList>
                <person name="Loftus B.J."/>
                <person name="Kim U.-J."/>
                <person name="Sneddon V.P."/>
                <person name="Kalush F."/>
                <person name="Brandon R."/>
                <person name="Fuhrmann J."/>
                <person name="Mason T."/>
                <person name="Crosby M.L."/>
                <person name="Barnstead M."/>
                <person name="Cronin L."/>
                <person name="Mays A.D."/>
                <person name="Cao Y."/>
                <person name="Xu R.X."/>
                <person name="Kang H.-L."/>
                <person name="Mitchell S."/>
                <person name="Eichler E.E."/>
                <person name="Harris P.C."/>
                <person name="Venter J.C."/>
                <person name="Adams M.D."/>
            </authorList>
            <dbReference type="PubMed" id="10493829"/>
            <dbReference type="DOI" id="10.1006/geno.1999.5927"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Suzuki Y."/>
                <person name="Sugano S."/>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
                <person name="Takeda T."/>
                <person name="Sakaki Y."/>
                <person name="Tanaka A."/>
                <person name="Yokoyama S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ASN-367</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2016" name="Expert Opin. Drug Metab. Toxicol." volume="12" first="1169" last="1179">
            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
            <authorList>
                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2002" name="Circulation" volume="105" first="41" last="47">
            <title>Association between SAH, an acyl-CoA synthetase gene, and hypertriglyceridemia, obesity, and hypertension.</title>
            <authorList>
                <person name="Iwai N."/>
                <person name="Katsuya T."/>
                <person name="Mannami T."/>
                <person name="Higaki J."/>
                <person name="Ogihara T."/>
                <person name="Kokame K."/>
                <person name="Ogata J."/>
                <person name="Baba S."/>
            </authorList>
            <dbReference type="PubMed" id="11772874"/>
            <dbReference type="DOI" id="10.1161/hc0102.101780"/>
        </citation>
        <scope>VARIANT ASN-367</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2007" name="J. Hypertens." volume="25" first="557" last="564">
            <title>SAH gene variants are associated with obesity-related hypertension in Caucasians: the PEGASE Study.</title>
            <authorList>
                <person name="Telgmann R."/>
                <person name="Brand E."/>
                <person name="Nicaud V."/>
                <person name="Hagedorn C."/>
                <person name="Beining K."/>
                <person name="Schoenfelder J."/>
                <person name="Brink-Spalink V."/>
                <person name="Schmidt-Petersen K."/>
                <person name="Matanis T."/>
                <person name="Vischer P."/>
                <person name="Nofer J.-R."/>
                <person name="Hasenkamp S."/>
                <person name="Plouin P.-F."/>
                <person name="Drouet L."/>
                <person name="Cambien F."/>
                <person name="Paul M."/>
                <person name="Tiret L."/>
                <person name="Brand-Herrmann S.-M."/>
            </authorList>
            <dbReference type="PubMed" id="17278971"/>
            <dbReference type="DOI" id="10.1097/hjh.0b013e3280144779"/>
        </citation>
        <scope>VARIANT ASN-367</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (PubMed:11772874). Capable of activating medium-chain fatty acids with a preference for isobutyrate among fatty acids with 2-6 carbon atoms (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>propanoate + ATP + CoA = propanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:20373"/>
            <dbReference type="ChEBI" id="CHEBI:17272"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57392"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.17"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:20374"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>butanoate + ATP + CoA = butanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46172"/>
            <dbReference type="ChEBI" id="CHEBI:17968"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57371"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:46173"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>2-methylpropanoate + ATP + CoA = 2-methylpropanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46176"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:48944"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57338"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:46177"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>2-methylbutanoate + ATP + CoA = 2-methylbutanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:46180"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:48946"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57336"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:46181"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:33632"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25887341">
            <id>Q53FZ2-2</id>
        </interactant>
        <interactant intactId="EBI-2432309">
            <id>Q92876</id>
            <label>KLK6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q53FZ2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q53FZ2-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_028395 VSP_028396"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <comment type="caution">
        <text evidence="10">It is uncertain whether Met-1 or Met-9 is the initiator.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC31667" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA03853" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA56369" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="5"/>
    <dbReference type="EC" id="6.2.1.17" evidence="3"/>
    <dbReference type="EMBL" id="D16350">
        <property type="protein sequence ID" value="BAA03853.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X80062">
        <property type="protein sequence ID" value="CAA56369.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC004381">
        <property type="protein sequence ID" value="AAC31667.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223139">
        <property type="protein sequence ID" value="BAD96859.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002790">
        <property type="protein sequence ID" value="AAH02790.3"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10589.1">
        <molecule id="Q53FZ2-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45435.1">
        <molecule id="Q53FZ2-2"/>
    </dbReference>
    <dbReference type="PIR" id="I54401">
        <property type="entry name" value="I54401"/>
    </dbReference>
    <dbReference type="PIR" id="S69913">
        <property type="entry name" value="S69913"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005613.2">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="NM_005622.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_973729.1">
        <molecule id="Q53FZ2-2"/>
        <property type="nucleotide sequence ID" value="NM_202000.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024306138.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_024450370.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290391.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434435.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290392.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434436.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290393.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434437.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290394.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434438.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290395.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434439.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290396.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_047434440.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047290397.1">
        <molecule id="Q53FZ2-2"/>
        <property type="nucleotide sequence ID" value="XM_047434441.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169556.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313581.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169557.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313582.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169558.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313583.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169559.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313584.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169560.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313585.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169561.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313586.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054169562.1">
        <molecule id="Q53FZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054313587.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q53FZ2"/>
    <dbReference type="SMR" id="Q53FZ2"/>
    <dbReference type="BioGRID" id="112203">
        <property type="interactions" value="23"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q53FZ2">
        <property type="interactions" value="289"/>
    </dbReference>
    <dbReference type="IntAct" id="Q53FZ2">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000289416"/>
    <dbReference type="SwissLipids" id="SLP:000001189"/>
    <dbReference type="iPTMnet" id="Q53FZ2"/>
    <dbReference type="PhosphoSitePlus" id="Q53FZ2"/>
    <dbReference type="SwissPalm" id="Q53FZ2"/>
    <dbReference type="BioMuta" id="ACSM3"/>
    <dbReference type="DMDM" id="158706483"/>
    <dbReference type="jPOST" id="Q53FZ2"/>
    <dbReference type="MassIVE" id="Q53FZ2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000289416"/>
    <dbReference type="PeptideAtlas" id="Q53FZ2"/>
    <dbReference type="ProteomicsDB" id="62470">
        <molecule id="Q53FZ2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="62471">
        <molecule id="Q53FZ2-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q53FZ2"/>
    <dbReference type="Antibodypedia" id="25607">
        <property type="antibodies" value="154 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="6296"/>
    <dbReference type="Ensembl" id="ENST00000289416.10">
        <molecule id="Q53FZ2-1"/>
        <property type="protein sequence ID" value="ENSP00000289416.5"/>
        <property type="gene ID" value="ENSG00000005187.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000440284.6">
        <molecule id="Q53FZ2-2"/>
        <property type="protein sequence ID" value="ENSP00000394565.2"/>
        <property type="gene ID" value="ENSG00000005187.13"/>
    </dbReference>
    <dbReference type="GeneID" id="6296"/>
    <dbReference type="KEGG" id="hsa:6296"/>
    <dbReference type="MANE-Select" id="ENST00000289416.10">
        <property type="protein sequence ID" value="ENSP00000289416.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005622.4"/>
        <property type="RefSeq protein sequence ID" value="NP_005613.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002dhq.4">
        <molecule id="Q53FZ2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:10522"/>
    <dbReference type="ClinPGx" id="PA34930"/>
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    <keyword id="KW-0460">Magnesium</keyword>
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    <keyword id="KW-0547">Nucleotide-binding</keyword>
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            <begin position="1"/>
            <end position="27"/>
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            <position position="106"/>
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    <feature type="modified residue" description="N6-acetyllysine" evidence="3">
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            <position position="157"/>
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            <end position="438"/>
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    <feature type="sequence variant" id="VAR_035249" description="In dbSNP:rs5713.">
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        <location>
            <position position="100"/>
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    </feature>
    <feature type="sequence variant" id="VAR_048239" description="In dbSNP:rs13306603.">
        <original>D</original>
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        <location>
            <position position="270"/>
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        <original>P</original>
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        <location>
            <position position="308"/>
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    </feature>
    <feature type="sequence variant" id="VAR_035251" description="In dbSNP:rs5716." evidence="5 6 7">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="367"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA03853." evidence="10" ref="1">
        <original>E</original>
        <variation>R</variation>
        <location>
            <position position="132"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA03853." evidence="10" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA03853." evidence="10" ref="1">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAD96859." evidence="10" ref="4">
        <original>V</original>
        <variation>D</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA03853." evidence="10" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="463"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA03853." evidence="10" ref="1">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="569"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q08AH1"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q3UNX5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11772874"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="17278971"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="7843754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="11772874"/>
        </source>
    </evidence>
    <sequence length="586" mass="66153" checksum="329967C751F11F1D" modified="2007-10-02" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1993-07-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
    <accession>Q01718</accession>
    <accession>A8K016</accession>
    <accession>Q3MI45</accession>
    <accession>Q504X6</accession>
    <name>ACTHR_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adrenocorticotropic hormone receptor</fullName>
            <shortName evidence="19">ACTH receptor</shortName>
            <shortName>ACTH-R</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="20">Adrenocorticotropin receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Melanocortin receptor 2</fullName>
            <shortName>MC2-R</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="22" type="primary">MC2R</name>
        <name type="synonym">ACTHR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1992" name="Science" volume="257" first="1248" last="1251">
            <title>The cloning of a family of genes that encode the melanocortin receptors.</title>
            <authorList>
                <person name="Mountjoy K.G."/>
                <person name="Robbins L.S."/>
                <person name="Mortrud M."/>
                <person name="Cone R.D."/>
            </authorList>
            <dbReference type="PubMed" id="1325670"/>
            <dbReference type="DOI" id="10.1126/science.1325670"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2001-07" db="EMBL/GenBank/DDBJ databases">
            <title>Genome-wide discovery and analysis of human seven transmembrane helix receptor genes.</title>
            <authorList>
                <person name="Suwa M."/>
                <person name="Sato T."/>
                <person name="Okouchi I."/>
                <person name="Arita M."/>
                <person name="Futami K."/>
                <person name="Matsumoto S."/>
                <person name="Tsutsumi S."/>
                <person name="Aburatani H."/>
                <person name="Asai K."/>
                <person name="Akiyama Y."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-01" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
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                <person name="Shiratori A."/>
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                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
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                <person name="Furuya T."/>
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                <person name="Omura Y."/>
                <person name="Abe K."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
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                <person name="Watanabe S."/>
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                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Okitani R."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
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                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
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                <person name="Nakagawa K."/>
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                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
    <reference key="5">
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            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1993" name="J. Biol. Chem." volume="268" first="8246" last="8250">
            <title>Molecular cloning of a novel melanocortin receptor.</title>
            <authorList>
                <person name="Gantz I."/>
                <person name="Konda Y."/>
                <person name="Tashiro T."/>
                <person name="Shimoto Y."/>
                <person name="Miwa H."/>
                <person name="Munzert G."/>
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                <person name="Delvalle J."/>
                <person name="Yamada T."/>
            </authorList>
            <dbReference type="PubMed" id="8463333"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)53088-x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-293</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2005" name="Nat. Genet." volume="37" first="166" last="170">
            <title>Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2.</title>
            <authorList>
                <person name="Metherell L.A."/>
                <person name="Chapple J.P."/>
                <person name="Cooray S."/>
                <person name="David A."/>
                <person name="Becker C."/>
                <person name="Rueschendorf F."/>
                <person name="Naville D."/>
                <person name="Begeot M."/>
                <person name="Khoo B."/>
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                <person name="Huebner A."/>
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                <person name="Clark A.J.L."/>
            </authorList>
            <dbReference type="PubMed" id="15654338"/>
            <dbReference type="DOI" id="10.1038/ng1501"/>
        </citation>
        <scope>INTERACTION WITH MRAP</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2007" name="Am. J. Physiol." volume="293" first="R1120" last="R1126">
            <title>Structural insights into the role of the ACTH receptor cysteine residues on receptor function.</title>
            <authorList>
                <person name="Yang Y."/>
                <person name="Chen M."/>
                <person name="Kesterson R.A. Jr."/>
                <person name="Harmon C.M."/>
            </authorList>
            <dbReference type="PubMed" id="17596328"/>
            <dbReference type="DOI" id="10.1152/ajpregu.00240.2007"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF CYS-21; CYS-245; CYS-251 AND CYS-253</scope>
        <scope>INTERACTION WITH ACTH</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2009" name="Proc. Natl. Acad. Sci. U.S.A." volume="106" first="6146" last="6151">
            <title>MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family.</title>
            <authorList>
                <person name="Chan L.F."/>
                <person name="Webb T.R."/>
                <person name="Chung T.T."/>
                <person name="Meimaridou E."/>
                <person name="Cooray S.N."/>
                <person name="Guasti L."/>
                <person name="Chapple J.P."/>
                <person name="Egertova M."/>
                <person name="Elphick M.R."/>
                <person name="Cheetham M.E."/>
                <person name="Metherell L.A."/>
                <person name="Clark A.J."/>
            </authorList>
            <dbReference type="PubMed" id="19329486"/>
            <dbReference type="DOI" id="10.1073/pnas.0809918106"/>
        </citation>
        <scope>INTERACTION WITH MRAP AND MRAP2</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2009" name="J. Biol. Chem." volume="284" first="22641" last="22648">
            <title>Opposite effects of the melanocortin-2 (MC2) receptor accessory protein MRAP on MC2 and MC5 receptor dimerization and trafficking.</title>
            <authorList>
                <person name="Sebag J.A."/>
                <person name="Hinkle P.M."/>
            </authorList>
            <dbReference type="PubMed" id="19535343"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.022400"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>INTERACTION WITH MRAP</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA28" last="RA28">
            <title>Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2.</title>
            <authorList>
                <person name="Sebag J.A."/>
                <person name="Hinkle P.M."/>
            </authorList>
            <dbReference type="PubMed" id="20371771"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000593"/>
        </citation>
        <scope>INTERACTION WITH MRAP AND MRAP2</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2011" name="Endocrinology" volume="152" first="4224" last="4231">
            <title>The E3 ubiquitin ligase Mahogunin ubiquitinates the melanocortin 2 receptor.</title>
            <authorList>
                <person name="Cooray S.N."/>
                <person name="Guasti L."/>
                <person name="Clark A.J."/>
            </authorList>
            <dbReference type="PubMed" id="21862608"/>
            <dbReference type="DOI" id="10.1210/en.2011-0147"/>
        </citation>
        <scope>UBIQUITINATION BY MGRN1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="23" key="14">
        <citation type="journal article" date="2023" name="Cell Res." volume="33" first="46" last="54">
            <title>Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.</title>
            <authorList>
                <person name="Luo P."/>
                <person name="Feng W."/>
                <person name="Ma S."/>
                <person name="Dai A."/>
                <person name="Wu K."/>
                <person name="Chen X."/>
                <person name="Yuan Q."/>
                <person name="Cai X."/>
                <person name="Yang D."/>
                <person name="Wang M.W."/>
                <person name="Eric Xu H."/>
                <person name="Jiang Y."/>
            </authorList>
            <dbReference type="PubMed" id="36588120"/>
            <dbReference type="DOI" id="10.1038/s41422-022-00751-6"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) OF 2-297 IN COMPLEX WITH G PROTEIN; MRAP AND CALCIUM</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ACTH</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1993" name="Lancet" volume="341" first="461" last="462">
            <title>Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor.</title>
            <authorList>
                <person name="Clark A.J.L."/>
                <person name="McLoughlin L."/>
                <person name="Grossman A."/>
            </authorList>
            <dbReference type="PubMed" id="8094489"/>
            <dbReference type="DOI" id="10.1016/0140-6736(93)90208-x"/>
        </citation>
        <scope>VARIANT GCCD1 ILE-74</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1993" name="J. Clin. Invest." volume="92" first="2458" last="2461">
            <title>Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene.</title>
            <authorList>
                <person name="Tsigos C."/>
                <person name="Arai K."/>
                <person name="Hung W."/>
                <person name="Chrousos G.P."/>
            </authorList>
            <dbReference type="PubMed" id="8227361"/>
            <dbReference type="DOI" id="10.1172/jci116853"/>
        </citation>
        <scope>VARIANT GCCD1 ARG-120</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="1994" name="Trends Endocrinol. Metab." volume="5" first="209" last="214">
            <title>Molecular insights into inherited ACTH resistance syndromes.</title>
            <authorList>
                <person name="Clark A.J.L."/>
                <person name="Weber A."/>
            </authorList>
        </citation>
        <scope>VARIANTS GCCD1 CYS-128 AND HIS-146</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="1996" name="J. Clin. Endocrinol. Metab." volume="81" first="1442" last="1448">
            <title>Demonstration by transfection studies that mutations in the adrenocorticotropin receptor gene are one cause of the hereditary syndrome of glucocorticoid deficiency.</title>
            <authorList>
                <person name="Naville D."/>
                <person name="Barjhoux L."/>
                <person name="Jaillard C."/>
                <person name="Faury D."/>
                <person name="Despert F."/>
                <person name="Esteva B."/>
                <person name="Durand P."/>
                <person name="Saez J.M."/>
                <person name="Begeot M."/>
            </authorList>
            <dbReference type="PubMed" id="8636348"/>
            <dbReference type="DOI" id="10.1210/jcem.81.4.8636348"/>
        </citation>
        <scope>VARIANTS GCCD1 ASN-107 AND PHE-251</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="19">
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            <title>Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH.</title>
            <authorList>
                <person name="Ishii T."/>
                <person name="Ogata T."/>
                <person name="Sasaki G."/>
                <person name="Sato S."/>
                <person name="Kinoshita E.I."/>
                <person name="Matsuo N."/>
            </authorList>
            <dbReference type="PubMed" id="10971458"/>
            <dbReference type="DOI" id="10.1046/j.1365-2265.2000.01040.x"/>
        </citation>
        <scope>VARIANTS GCCD1 ASN-103 AND TRP-137</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2002" name="J. Clin. Endocrinol. Metab." volume="87" first="4318" last="4323">
            <title>Clinical, genetic, and functional characterization of adrenocorticotropin receptor mutations using a novel receptor assay.</title>
            <authorList>
                <person name="Fluck C.E."/>
                <person name="Martens J.W.M."/>
                <person name="Conte F.A."/>
                <person name="Miller W.L."/>
            </authorList>
            <dbReference type="PubMed" id="12213892"/>
            <dbReference type="DOI" id="10.1210/jc.2002-020501"/>
        </citation>
        <scope>VARIANTS GCCD1 ILE-74; TRP-137 AND CYS-254</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2010" name="Hum. Genet." volume="127" first="112" last="112">
            <title>Novel human pathological mutations. Gene symbol: MC2R. Disease: Glucocorticoid deficiency.</title>
            <authorList>
                <person name="Mueller O.T."/>
                <person name="Coovadia A."/>
            </authorList>
            <dbReference type="PubMed" id="20108423"/>
        </citation>
        <scope>VARIANT PRO-137</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 6 8 14 17">G protein-coupled receptor for corticotropin/ACTH, primarily expressed in adrenal cortex where it plays a key role in the regulation of adrenocortical function (PubMed:1325670, PubMed:17596328, PubMed:36588120). Upon activation, couples to G(s) protein, stimulating adenylate cyclase and activating the cAMP-dependent signaling pathway, the MAPK cascade as well as the PKA pathway, leading to steroidogenic factor 1/NR5A1-mediated transcriptional activation (PubMed:1325670). Activation by ACTH facilitates the release of adrenal glucocorticoids, including cortisol and corticosterone (PubMed:12213892, PubMed:8636348). In addition, MC2R is required for fetal and neonatal adrenal gland development (By similarity).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="14">
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="7 8 9 10 12 14">Homodimer (PubMed:19535343). Interacts with corticotropin/ACTH (PubMed:17596328, PubMed:36588120). Interacts with MRAP; this interaction targets MC2R to the plasma membrane (PubMed:15654338, PubMed:19535343). Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of ACTH (PubMed:19329486, PubMed:20371771).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9537171">
            <id>Q01718</id>
        </interactant>
        <interactant intactId="EBI-9538727">
            <id>Q8TCY5</id>
            <label>MRAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9537171">
            <id>Q01718</id>
        </interactant>
        <interactant intactId="EBI-21991233">
            <id>Q8TCY5-1</id>
            <label>MRAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9537171">
            <id>Q01718</id>
        </interactant>
        <interactant intactId="EBI-9537218">
            <id>Q96G30</id>
            <label>MRAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10 13">Cell membrane</location>
            <topology evidence="14">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Melanocytes and corticoadrenal tissue.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13">Ubiquitinated by MGRN1 that may be involved in post-endocytic trafficking and/or degradation of internalized receptor.</text>
    </comment>
    <comment type="disease" evidence="4 5 15 16 17">
        <disease id="DI-01669">
            <name>Glucocorticoid deficiency 1</name>
            <acronym>GCCD1</acronym>
            <description>A form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.</description>
            <dbReference type="MIM" id="202200"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family.</text>
    </comment>
    <dbReference type="EMBL" id="X65633">
        <property type="protein sequence ID" value="CAA46587.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB065915">
        <property type="protein sequence ID" value="BAC06130.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK289381">
        <property type="protein sequence ID" value="BAF82070.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315319">
        <property type="protein sequence ID" value="BAG37722.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471113">
        <property type="protein sequence ID" value="EAX01503.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC069074">
        <property type="protein sequence ID" value="AAH69074.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC094710">
        <property type="protein sequence ID" value="AAH94710.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC104169">
        <property type="protein sequence ID" value="AAI04170.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC104170">
        <property type="protein sequence ID" value="AAI04171.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY225229">
        <property type="protein sequence ID" value="AAO67714.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11869.1"/>
    <dbReference type="PIR" id="C43265">
        <property type="entry name" value="C43265"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000520.1">
        <property type="nucleotide sequence ID" value="NM_000529.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001278840.1">
        <property type="nucleotide sequence ID" value="NM_001291911.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016881270.1">
        <property type="nucleotide sequence ID" value="XM_017025781.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047293493.1">
        <property type="nucleotide sequence ID" value="XM_047437537.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054174631.1">
        <property type="nucleotide sequence ID" value="XM_054318656.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054174632.1">
        <property type="nucleotide sequence ID" value="XM_054318657.1"/>
    </dbReference>
    <dbReference type="PDB" id="8GY7">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="R=2-297"/>
    </dbReference>
    <dbReference type="PDB" id="9K3L">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.01 A"/>
        <property type="chains" value="R=1-297"/>
    </dbReference>
    <dbReference type="PDBsum" id="8GY7"/>
    <dbReference type="PDBsum" id="9K3L"/>
    <dbReference type="AlphaFoldDB" id="Q01718"/>
    <dbReference type="EMDB" id="EMD-34371"/>
    <dbReference type="EMDB" id="EMD-62018"/>
    <dbReference type="SMR" id="Q01718"/>
    <dbReference type="BioGRID" id="110328">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="CORUM" id="Q01718"/>
    <dbReference type="DIP" id="DIP-29949N"/>
    <dbReference type="FunCoup" id="Q01718">
        <property type="interactions" value="849"/>
    </dbReference>
    <dbReference type="IntAct" id="Q01718">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="Q01718"/>
    <dbReference type="STRING" id="9606.ENSP00000333821"/>
    <dbReference type="BindingDB" id="Q01718"/>
    <dbReference type="ChEMBL" id="CHEMBL1965"/>
    <dbReference type="DrugBank" id="DB11653">
        <property type="generic name" value="Bremelanotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01285">
        <property type="generic name" value="Corticotropin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09334">
        <property type="generic name" value="Seractide acetate"/>
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    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:6930"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PDB" id="8GY7"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="8GY7"/>
        </source>
    </evidence>
    <sequence length="297" mass="33927" checksum="66EE31961ABB8773" modified="1993-07-01" version="1">MKHIINSYENINNTARNNSDCPRVVLPEEIFFTISIVGVLENLIVLLAVFKNKNLQAPMYFFICSLAISDMLGSLYKILENILIILRNMGYLKPRGSFETTADDIIDSLFVLSLLGSIFSLSVIAADRYITIFHALRYHSIVTMRRTVVVLTVIWTFCTGTGITMVIFSHHVPTVITFTSLFPLMLVFILCLYVHMFLLARSHTRKISTLPRANMKGAITLTILLGVFIFCWAPFVLHVLLMTFCPSNPYCACYMSLFQVNGMLIMCNAVIDPFIYAFRSPELRDAFKKMIFCSRYW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1987-03-20" modified="2026-01-28" version="186" xmlns="https://uniprot.org/uniprot">
    <accession>P68032</accession>
    <accession>P04270</accession>
    <name>ACTC_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin, alpha cardiac muscle 1</fullName>
            <ecNumber evidence="5">3.6.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-cardiac actin</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Actin, alpha cardiac muscle 1, intermediate form</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">ACTC1</name>
        <name type="synonym">ACTC</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1982" name="Proc. Natl. Acad. Sci. U.S.A." volume="79" first="5901" last="5905">
            <title>Molecular structure and evolutionary origin of human cardiac muscle actin gene.</title>
            <authorList>
                <person name="Hamada H."/>
                <person name="Petrino M.G."/>
                <person name="Kakunaga T."/>
            </authorList>
            <dbReference type="PubMed" id="6310553"/>
            <dbReference type="DOI" id="10.1073/pnas.79.19.5901"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="18537" last="18542">
            <title>Connecting actin monomers by iso-peptide bond is a toxicity mechanism of the Vibrio cholerae MARTX toxin.</title>
            <authorList>
                <person name="Kudryashov D.S."/>
                <person name="Durer Z.A."/>
                <person name="Ytterberg A.J."/>
                <person name="Sawaya M.R."/>
                <person name="Pashkov I."/>
                <person name="Prochazkova K."/>
                <person name="Yeates T.O."/>
                <person name="Loo R.R."/>
                <person name="Loo J.A."/>
                <person name="Satchell K.J."/>
                <person name="Reisler E."/>
            </authorList>
            <dbReference type="PubMed" id="19015515"/>
            <dbReference type="DOI" id="10.1073/pnas.0808082105"/>
        </citation>
        <scope>CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2013" name="Nat. Commun." volume="4" first="1832" last="1832">
            <title>ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.</title>
            <authorList>
                <person name="Li M.M."/>
                <person name="Nilsen A."/>
                <person name="Shi Y."/>
                <person name="Fusser M."/>
                <person name="Ding Y.H."/>
                <person name="Fu Y."/>
                <person name="Liu B."/>
                <person name="Niu Y."/>
                <person name="Wu Y.S."/>
                <person name="Huang C.M."/>
                <person name="Olofsson M."/>
                <person name="Jin K.X."/>
                <person name="Lv Y."/>
                <person name="Xu X.Z."/>
                <person name="He C."/>
                <person name="Dong M.Q."/>
                <person name="Rendtlew Danielsen J.M."/>
                <person name="Klungland A."/>
                <person name="Yang Y.G."/>
            </authorList>
            <dbReference type="PubMed" id="23673617"/>
            <dbReference type="DOI" id="10.1038/ncomms2863"/>
        </citation>
        <scope>METHYLATION AT LYS-86</scope>
        <scope>DEMETHYLATION BY ALKBH4</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2015" name="Science" volume="349" first="535" last="539">
            <title>ACD toxin-produced actin oligomers poison formin-controlled actin polymerization.</title>
            <authorList>
                <person name="Heisler D.B."/>
                <person name="Kudryashova E."/>
                <person name="Grinevich D.O."/>
                <person name="Suarez C."/>
                <person name="Winkelman J.D."/>
                <person name="Birukov K.G."/>
                <person name="Kotha S.R."/>
                <person name="Parinandi N.L."/>
                <person name="Vavylonis D."/>
                <person name="Kovar D.R."/>
                <person name="Kudryashov D.S."/>
            </authorList>
            <dbReference type="PubMed" id="26228148"/>
            <dbReference type="DOI" id="10.1126/science.aab4090"/>
        </citation>
        <scope>CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2019" name="Nature" volume="565" first="372" last="376">
            <title>SETD3 is an actin histidine methyltransferase that prevents primary dystocia.</title>
            <authorList>
                <person name="Wilkinson A.W."/>
                <person name="Diep J."/>
                <person name="Dai S."/>
                <person name="Liu S."/>
                <person name="Ooi Y.S."/>
                <person name="Song D."/>
                <person name="Li T.M."/>
                <person name="Horton J.R."/>
                <person name="Zhang X."/>
                <person name="Liu C."/>
                <person name="Trivedi D.V."/>
                <person name="Ruppel K.M."/>
                <person name="Vilches-Moure J.G."/>
                <person name="Casey K.M."/>
                <person name="Mak J."/>
                <person name="Cowan T."/>
                <person name="Elias J.E."/>
                <person name="Nagamine C.M."/>
                <person name="Spudich J.A."/>
                <person name="Cheng X."/>
                <person name="Carette J.E."/>
                <person name="Gozani O."/>
            </authorList>
            <dbReference type="PubMed" id="30626964"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0821-8"/>
        </citation>
        <scope>METHYLATION AT HIS-75</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1998" name="Science" volume="280" first="750" last="752">
            <title>Actin mutations in dilated cardiomyopathy, a heritable form of heart failure.</title>
            <authorList>
                <person name="Olson T.M."/>
                <person name="Michels V.V."/>
                <person name="Thibodeau S.N."/>
                <person name="Tai Y.-S."/>
                <person name="Keating M.T."/>
            </authorList>
            <dbReference type="PubMed" id="9563954"/>
            <dbReference type="DOI" id="10.1126/science.280.5364.750"/>
        </citation>
        <scope>VARIANTS CMD1R HIS-314 AND GLY-363</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1999" name="J. Clin. Invest." volume="103" first="R39" last="R43">
            <title>Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.</title>
            <authorList>
                <person name="Mogensen J."/>
                <person name="Klausen I.C."/>
                <person name="Pedersen A.K."/>
                <person name="Egeblad H."/>
                <person name="Bross P."/>
                <person name="Kruse T.A."/>
                <person name="Gregersen N."/>
                <person name="Hansen P.S."/>
                <person name="Baandrup U."/>
                <person name="Boerglum A.D."/>
            </authorList>
            <dbReference type="PubMed" id="10330430"/>
            <dbReference type="DOI" id="10.1172/jci6460"/>
        </citation>
        <scope>VARIANT CMH11 SER-297</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2000" name="J. Mol. Cell. Cardiol." volume="32" first="1687" last="1694">
            <title>Inherited and de novo mutations in the cardiac actin gene cause hypertrophic cardiomyopathy.</title>
            <authorList>
                <person name="Olson T.M."/>
                <person name="Doan T.P."/>
                <person name="Kishimoto N.Y."/>
                <person name="Whitby F.G."/>
                <person name="Ackerman M.J."/>
                <person name="Fananapazir L."/>
            </authorList>
            <dbReference type="PubMed" id="10966831"/>
            <dbReference type="DOI" id="10.1006/jmcc.2000.1204"/>
        </citation>
        <scope>VARIANTS CMH11 LYS-101; ALA-166 AND PRO-333</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2004" name="J. Med. Genet." volume="41" first="E10" last="E10">
            <title>Clinical and genetic characteristics of alpha cardiac actin gene mutations in hypertrophic cardiomyopathy.</title>
            <authorList>
                <person name="Mogensen J."/>
                <person name="Perrot A."/>
                <person name="Andersen P.S."/>
                <person name="Havndrup O."/>
                <person name="Klausen I.C."/>
                <person name="Christiansen M."/>
                <person name="Bross P."/>
                <person name="Egeblad H."/>
                <person name="Bundgaard H."/>
                <person name="Osterziel K.J."/>
                <person name="Haltern G."/>
                <person name="Lapp H."/>
                <person name="Reinecke P."/>
                <person name="Gregersen N."/>
                <person name="Borglum A.D."/>
            </authorList>
            <dbReference type="PubMed" id="14729850"/>
            <dbReference type="DOI" id="10.1136/jmg.2003.010447"/>
        </citation>
        <scope>VARIANTS CMH11 CYS-168 AND LEU-307</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2008" name="Hum. Mol. Genet." volume="17" first="256" last="265">
            <title>Alpha-cardiac actin mutations produce atrial septal defects.</title>
            <authorList>
                <person name="Matsson H."/>
                <person name="Eason J."/>
                <person name="Bookwalter C.S."/>
                <person name="Klar J."/>
                <person name="Gustavsson P."/>
                <person name="Sunnegardh J."/>
                <person name="Enell H."/>
                <person name="Jonzon A."/>
                <person name="Vikkula M."/>
                <person name="Gutierrez I."/>
                <person name="Granados-Riveron J."/>
                <person name="Pope M."/>
                <person name="Bu'Lock F."/>
                <person name="Cox J."/>
                <person name="Robinson T.E."/>
                <person name="Song F."/>
                <person name="Brook D.J."/>
                <person name="Marston S."/>
                <person name="Trybus K.M."/>
                <person name="Dahl N."/>
            </authorList>
            <dbReference type="PubMed" id="17947298"/>
            <dbReference type="DOI" id="10.1093/hmg/ddm302"/>
        </citation>
        <scope>VARIANT ASD5 VAL-125</scope>
        <scope>CHARACTERIZATION OF VARIANT ASD5 VAL-125</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2008" name="N. Engl. J. Med." volume="358" first="1899" last="1908">
            <title>Shared genetic causes of cardiac hypertrophy in children and adults.</title>
            <authorList>
                <person name="Morita H."/>
                <person name="Rehm H.L."/>
                <person name="Menesses A."/>
                <person name="McDonough B."/>
                <person name="Roberts A.E."/>
                <person name="Kucherlapati R."/>
                <person name="Towbin J.A."/>
                <person name="Seidman J.G."/>
                <person name="Seidman C.E."/>
            </authorList>
            <dbReference type="PubMed" id="18403758"/>
            <dbReference type="DOI" id="10.1056/nejmoa075463"/>
        </citation>
        <scope>VARIANTS CMH11 TYR-90 AND CYS-97</scope>
    </reference>
    <comment type="function">
        <text>Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text>Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-352273">
            <id>P68032</id>
        </interactant>
        <interactant intactId="EBI-352733">
            <id>P23528</id>
            <label>CFL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="3">Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Monomethylation at Lys-86 (K86me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, alpha cardiac muscle 1, intermediate form</molecule>
        <text evidence="3">N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12">Methylated at His-75 by SETD3.</text>
    </comment>
    <comment type="PTM">
        <text evidence="15 16">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-00223">
            <name>Cardiomyopathy, dilated, 1R</name>
            <acronym>CMD1R</acronym>
            <description>A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.</description>
            <dbReference type="MIM" id="613424"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 10">
        <disease id="DI-00241">
            <name>Cardiomyopathy, familial hypertrophic, 11</name>
            <acronym>CMH11</acronym>
            <description>A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.</description>
            <dbReference type="MIM" id="612098"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9">
        <disease id="DI-02497">
            <name>Atrial septal defect 5</name>
            <acronym>ASD5</acronym>
            <description>A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.</description>
            <dbReference type="MIM" id="612794"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.-" evidence="5"/>
    <dbReference type="EMBL" id="J00073">
        <property type="protein sequence ID" value="AAB59619.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00070">
        <property type="protein sequence ID" value="AAB59619.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00071">
        <property type="protein sequence ID" value="AAB59619.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J00072">
        <property type="protein sequence ID" value="AAB59619.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR541795">
        <property type="protein sequence ID" value="CAG46594.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009978">
        <property type="protein sequence ID" value="AAH09978.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10041.1"/>
    <dbReference type="PIR" id="A02998">
        <property type="entry name" value="ATHUC"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393411.1">
        <property type="nucleotide sequence ID" value="NM_001406482.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393412.1">
        <property type="nucleotide sequence ID" value="NM_001406483.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005150.1">
        <property type="nucleotide sequence ID" value="NM_005159.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288935.1">
        <property type="nucleotide sequence ID" value="XM_047432979.1"/>
    </dbReference>
    <dbReference type="PDB" id="8GSU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GSW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GT1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.35 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GT2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GT3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GT4">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.55 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8GT5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="A=3-377"/>
    </dbReference>
    <dbReference type="PDB" id="8ZB7">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.19 A"/>
        <property type="chains" value="A/B/C/D/E/F=7-377"/>
    </dbReference>
    <dbReference type="PDB" id="8ZI9">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.08 A"/>
        <property type="chains" value="F=7-377"/>
    </dbReference>
    <dbReference type="PDB" id="8ZJ1">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.25 A"/>
        <property type="chains" value="A/C/D/E/F=7-377"/>
    </dbReference>
    <dbReference type="PDB" id="9B3Q">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A/D/E=1-377"/>
    </dbReference>
    <dbReference type="PDB" id="9B3R">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="A/D/E=1-377"/>
    </dbReference>
    <dbReference type="PDB" id="9BPH">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.12 A"/>
        <property type="chains" value="A/B/C/D=3-377"/>
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    <dbReference type="PDB" id="9BPM">
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        <property type="entry name" value="ACTINS_ACT_LIKE"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0976">Atrial septal defect</keyword>
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    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0514">Muscle protein</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed">
        <location>
            <position position="1"/>
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    </feature>
    <feature type="chain" id="PRO_0000442998" description="Actin, alpha cardiac muscle 1, intermediate form" evidence="2">
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            <begin position="2"/>
            <end position="377"/>
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            <end position="377"/>
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            <position position="2"/>
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    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="46"/>
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    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="49"/>
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    </feature>
    <feature type="modified residue" description="Tele-methylhistidine" evidence="12">
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-methyllysine" evidence="11">
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-52); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045924" description="In CMH11; dbSNP:rs121912676." evidence="10">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_045925" description="In CMH11; dbSNP:rs759495229." evidence="10">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012857" description="In CMH11; dbSNP:rs193922680." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_046502" description="In ASD5; reduced affinity for myosin; normal actin filament polymerization ability; normal actomyosin motor function; dbSNP:rs121912677." evidence="9">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012858" description="In CMH11; dbSNP:rs267606628." evidence="7">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_046503" description="In CMH11; dbSNP:rs2140430974." evidence="8">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012859" description="In CMH11; dbSNP:rs121912675." evidence="6">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="297"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_046504" description="In CMH11; dbSNP:rs2140429593." evidence="8">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012860" description="In CMD1R; dbSNP:rs121912673." evidence="13">
        <original>R</original>
        <variation>H</variation>
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    <sequence length="377" mass="42019" checksum="E5C10FA19730CAD2" modified="1987-03-20" version="1" precursor="true">MCDDEETTALVCDNGSGLVKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIITNWDDMEKIWHHTFYNELRVAPEEHPTLLTEAPLNPKANREKMTQIMFETFNVPAMYVAIQAVLSLYASGRTTGIVLDSGDGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERGYSFVTTAEREIVRDIKEKLCYVALDFENEMATAASSSSLEKSYELPDGQVITIGNERFRCPETLFQPSFIGMESAGIHETTYNSIMKCDIDIRKDLYANNVLSGGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWISKQEYDEAGPSIVHRKCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-01" modified="2026-01-28" version="163" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H568</accession>
    <accession>Q13104</accession>
    <accession>Q96M75</accession>
    <name>ACTL8_HUMAN</name>
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        <recommendedName>
            <fullName>Actin-like protein 8</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Cancer/testis antigen 57</fullName>
            <shortName>CT57</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTL8</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
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    </reference>
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                <person name="Sato K."/>
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                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
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                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
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                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-3</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
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                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-3</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2005" name="Proc. Natl. Acad. Sci. U.S.A." volume="102" first="7940" last="7945">
            <title>Identification of cancer/testis-antigen genes by massively parallel signature sequencing.</title>
            <authorList>
                <person name="Chen Y.-T."/>
                <person name="Scanlan M.J."/>
                <person name="Venditti C.A."/>
                <person name="Chua R."/>
                <person name="Theiler G."/>
                <person name="Stevenson B.J."/>
                <person name="Iseli C."/>
                <person name="Gure A.O."/>
                <person name="Vasicek T."/>
                <person name="Strausberg R.L."/>
                <person name="Jongeneel C.V."/>
                <person name="Old L.J."/>
                <person name="Simpson A.J.G."/>
            </authorList>
            <dbReference type="PubMed" id="15905330"/>
            <dbReference type="DOI" id="10.1073/pnas.0502583102"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="interaction">
        <interactant intactId="EBI-10306917">
            <id>Q9H568</id>
        </interactant>
        <interactant intactId="EBI-739994">
            <id>Q9Y5P4</id>
            <label>CERT1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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            <id>Q9H568</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Strongly expressed in testis and pancreas. Weak expression in placenta.</text>
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    <comment type="similarity">
        <text evidence="5">Belongs to the actin family.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA62476" version="1"/>
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    <dbReference type="CCDS" id="CCDS183.1"/>
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        <property type="nucleotide sequence ID" value="NM_030812.3"/>
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        <property type="nucleotide sequence ID" value="XM_011542212.3"/>
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        <property type="antibodies" value="149 antibodies from 25 providers"/>
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        <property type="protein sequence ID" value="ENSP00000364555.1"/>
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        <property type="component" value="Chromosome 1"/>
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        <property type="term" value="P:epithelial cell differentiation"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
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        <property type="entry name" value="Actin like 8"/>
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        <property type="entry name" value="ATPase_NBD"/>
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        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Actin"/>
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    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000286171" description="Actin-like protein 8">
        <location>
            <begin position="1"/>
            <end position="366"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032079" description="In dbSNP:rs694214." evidence="2 3">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032080" description="In dbSNP:rs3795322.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="PubMed" id="14702039"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <source>
            <dbReference type="PubMed" id="15905330"/>
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    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="366" mass="41360" checksum="BCCFC1E5CDC1C8FB" modified="2001-03-01" version="1">MAARTVIIDHGSGFLKAGTAGWNEPQMVFPNIVNYLPCKENPGPSYARRRVSLGIDICHPDTFSYPIERGRILNWEGVQYLWSFVLENHRREQEVPPVIITETPLREPADRKKMLEILFELLHVPSVLLADQLQMSLYASGLLTGVVVDSGYGLTRVQPFHQGRPLPASGKTLEFAGQDLSAYLLKSLFKEDCDRRCLFQLETVAVTQMNKCYVPQNLGEALDFRERQQSALDESNTYQLPDGSRVELTPMQRVAPEMFFSPQVFEQPGPSIPRAIVESVESCEISLRPLLVSHVMACGGNTLYPGFTKRLFRELMGDHVSSTKATVWEGSNRNFSVWLGASVVAHLSTYQSEWMSREEYGEHMRM</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-06-10" modified="2026-01-28" version="110" xmlns="https://uniprot.org/uniprot">
    <accession>P0C7M7</accession>
    <accession>A8MTI6</accession>
    <name>ACSM4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acyl-coenzyme A synthetase ACSM4, mitochondrial</fullName>
            <ecNumber evidence="3">6.2.1.2</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acyl-CoA synthetase medium-chain family member 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACSM4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="346" last="351">
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            <authorList>
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                <person name="Escotto M."/>
                <person name="Flagg N."/>
                <person name="Forbes L.D."/>
                <person name="Gabisi A.M."/>
                <person name="Garza M."/>
                <person name="Hamilton C."/>
                <person name="Henderson N."/>
                <person name="Hernandez O."/>
                <person name="Hines S."/>
                <person name="Hogues M.E."/>
                <person name="Huang M."/>
                <person name="Idlebird D.G."/>
                <person name="Johnson R."/>
                <person name="Jolivet A."/>
                <person name="Jones S."/>
                <person name="Kagan R."/>
                <person name="King L.M."/>
                <person name="Leal B."/>
                <person name="Lebow H."/>
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                <person name="LeVan J.M."/>
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                <person name="Lucier A."/>
                <person name="Lucier R.L."/>
                <person name="Ma J."/>
                <person name="Madu R.C."/>
                <person name="Mapua P."/>
                <person name="Martindale A.D."/>
                <person name="Martinez E."/>
                <person name="Massey E."/>
                <person name="Mawhiney S."/>
                <person name="Meador M.G."/>
                <person name="Mendez S."/>
                <person name="Mercado C."/>
                <person name="Mercado I.C."/>
                <person name="Merritt C.E."/>
                <person name="Miner Z.L."/>
                <person name="Minja E."/>
                <person name="Mitchell T."/>
                <person name="Mohabbat F."/>
                <person name="Mohabbat K."/>
                <person name="Montgomery B."/>
                <person name="Moore N."/>
                <person name="Morris S."/>
                <person name="Munidasa M."/>
                <person name="Ngo R.N."/>
                <person name="Nguyen N.B."/>
                <person name="Nickerson E."/>
                <person name="Nwaokelemeh O.O."/>
                <person name="Nwokenkwo S."/>
                <person name="Obregon M."/>
                <person name="Oguh M."/>
                <person name="Oragunye N."/>
                <person name="Oviedo R.J."/>
                <person name="Parish B.J."/>
                <person name="Parker D.N."/>
                <person name="Parrish J."/>
                <person name="Parks K.L."/>
                <person name="Paul H.A."/>
                <person name="Payton B.A."/>
                <person name="Perez A."/>
                <person name="Perrin W."/>
                <person name="Pickens A."/>
                <person name="Primus E.L."/>
                <person name="Pu L.-L."/>
                <person name="Puazo M."/>
                <person name="Quiles M.M."/>
                <person name="Quiroz J.B."/>
                <person name="Rabata D."/>
                <person name="Reeves K."/>
                <person name="Ruiz S.J."/>
                <person name="Shao H."/>
                <person name="Sisson I."/>
                <person name="Sonaike T."/>
                <person name="Sorelle R.P."/>
                <person name="Sutton A.E."/>
                <person name="Svatek A.F."/>
                <person name="Svetz L.A."/>
                <person name="Tamerisa K.S."/>
                <person name="Taylor T.R."/>
                <person name="Teague B."/>
                <person name="Thomas N."/>
                <person name="Thorn R.D."/>
                <person name="Trejos Z.Y."/>
                <person name="Trevino B.K."/>
                <person name="Ukegbu O.N."/>
                <person name="Urban J.B."/>
                <person name="Vasquez L.I."/>
                <person name="Vera V.A."/>
                <person name="Villasana D.M."/>
                <person name="Wang L."/>
                <person name="Ward-Moore S."/>
                <person name="Warren J.T."/>
                <person name="Wei X."/>
                <person name="White F."/>
                <person name="Williamson A.L."/>
                <person name="Wleczyk R."/>
                <person name="Wooden H.S."/>
                <person name="Wooden S.H."/>
                <person name="Yen J."/>
                <person name="Yoon L."/>
                <person name="Yoon V."/>
                <person name="Zorrilla S.E."/>
                <person name="Nelson D."/>
                <person name="Kucherlapati R."/>
                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16541075"/>
            <dbReference type="DOI" id="10.1038/nature04569"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2006-03" db="EMBL/GenBank/DDBJ databases">
            <title>Exhaustive RT-PCR and sequencing of all novel TWINSCAN predictions in human.</title>
            <authorList>
                <person name="Stevens M."/>
                <person name="Wei C."/>
                <person name="Gross S.S."/>
                <person name="McPherson J."/>
                <person name="Brent M.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 330-474</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2007" name="J. Lipid Res." volume="48" first="2736" last="2750">
            <title>Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome.</title>
            <authorList>
                <person name="Watkins P.A."/>
                <person name="Maiguel D."/>
                <person name="Jia Z."/>
                <person name="Pevsner J."/>
            </authorList>
            <dbReference type="PubMed" id="17762044"/>
            <dbReference type="DOI" id="10.1194/jlr.m700378-jlr200"/>
        </citation>
        <scope>IDENTIFICATION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2016" name="Expert Opin. Drug Metab. Toxicol." volume="12" first="1169" last="1179">
            <title>Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.</title>
            <authorList>
                <person name="van der Sluis R."/>
                <person name="Erasmus E."/>
            </authorList>
            <dbReference type="PubMed" id="27351777"/>
            <dbReference type="DOI" id="10.1080/17425255.2016.1206888"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (By similarity). Capable of activating medium-chain fatty acids with a preference for C6-12 fatty acids (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a medium-chain fatty acid + ATP + CoA = a medium-chain fatty acyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:48340"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:59558"/>
            <dbReference type="ChEBI" id="CHEBI:90546"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="6.2.1.2"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:48341"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>hexanoate + ATP + CoA = hexanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:43740"/>
            <dbReference type="ChEBI" id="CHEBI:17120"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:62620"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:43741"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>octanoate + ATP + CoA = octanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33631"/>
            <dbReference type="ChEBI" id="CHEBI:25646"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57386"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:33632"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>decanoate + ATP + CoA = decanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33627"/>
            <dbReference type="ChEBI" id="CHEBI:27689"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:61430"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:33628"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>dodecanoate + ATP + CoA = dodecanoyl-CoA + AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:33623"/>
            <dbReference type="ChEBI" id="CHEBI:18262"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:57375"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:33624"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the ATP-dependent AMP-binding enzyme family.</text>
    </comment>
    <dbReference type="EC" id="6.2.1.2" evidence="3"/>
    <dbReference type="EMBL" id="AC131205">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DY654856">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44825.1"/>
    <dbReference type="RefSeq" id="NP_001073923.1">
        <property type="nucleotide sequence ID" value="NM_001080454.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P0C7M7"/>
    <dbReference type="SMR" id="P0C7M7"/>
    <dbReference type="BioGRID" id="131135">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="P0C7M7">
        <property type="interactions" value="27"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000382349"/>
    <dbReference type="GlyGen" id="P0C7M7">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P0C7M7"/>
    <dbReference type="PhosphoSitePlus" id="P0C7M7"/>
    <dbReference type="BioMuta" id="ACSM4"/>
    <dbReference type="DMDM" id="190358135"/>
    <dbReference type="jPOST" id="P0C7M7"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000382349"/>
    <dbReference type="PeptideAtlas" id="P0C7M7"/>
    <dbReference type="ProteomicsDB" id="52346"/>
    <dbReference type="Antibodypedia" id="59210">
        <property type="antibodies" value="55 antibodies from 12 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="341392"/>
    <dbReference type="Ensembl" id="ENST00000399422.5">
        <property type="protein sequence ID" value="ENSP00000382349.4"/>
        <property type="gene ID" value="ENSG00000215009.6"/>
    </dbReference>
    <dbReference type="GeneID" id="341392"/>
    <dbReference type="KEGG" id="hsa:341392"/>
    <dbReference type="MANE-Select" id="ENST00000399422.5">
        <property type="protein sequence ID" value="ENSP00000382349.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001080454.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001073923.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001qsx.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32016"/>
    <dbReference type="ClinPGx" id="PA162375472"/>
    <dbReference type="CTD" id="341392"/>
    <dbReference type="GeneCards" id="ACSM4"/>
    <dbReference type="HGNC" id="HGNC:32016">
        <property type="gene designation" value="ACSM4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000215009">
        <property type="expression patterns" value="Not detected"/>
    </dbReference>
    <dbReference type="MIM" id="614360">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000215009"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000215009"/>
    <dbReference type="eggNOG" id="KOG1175">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162316"/>
    <dbReference type="HOGENOM" id="CLU_000022_59_10_1"/>
    <dbReference type="InParanoid" id="P0C7M7"/>
    <dbReference type="OMA" id="QLWTPLT"/>
    <dbReference type="OrthoDB" id="6614653at2759"/>
    <dbReference type="PAN-GO" id="P0C7M7">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P0C7M7"/>
    <dbReference type="PathwayCommons" id="P0C7M7"/>
    <dbReference type="Reactome" id="R-HSA-177128">
        <property type="pathway name" value="Conjugation of salicylate with glycine"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9749641">
        <property type="pathway name" value="Aspirin ADME"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000215009"/>
    <dbReference type="BioGRID-ORCS" id="341392">
        <property type="hits" value="15 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACSM4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="341392"/>
    <dbReference type="Pharos" id="P0C7M7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P0C7M7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="P0C7M7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000215009">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 58 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0102391">
        <property type="term" value="F:decanoate-CoA ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015645">
        <property type="term" value="F:fatty acid ligase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004321">
        <property type="term" value="F:fatty-acyl-CoA synthase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006637">
        <property type="term" value="P:acyl-CoA metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006633">
        <property type="term" value="P:fatty acid biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd05928">
        <property type="entry name" value="MACS_euk"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.12780:FF:000007">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM2A, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.30:FF:000005">
        <property type="entry name" value="Acyl-coenzyme A synthetase ACSM5, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.12780">
        <property type="entry name" value="N-terminal domain of ligase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025110">
        <property type="entry name" value="AMP-bd_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045851">
        <property type="entry name" value="AMP-bd_C_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020845">
        <property type="entry name" value="AMP-binding_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000873">
        <property type="entry name" value="AMP-dep_synth/lig_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR042099">
        <property type="entry name" value="ANL_N_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051087">
        <property type="entry name" value="Mitochondrial_ACSM"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43605:SF8">
        <property type="entry name" value="ACYL-COENZYME A SYNTHETASE ACSM4, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00501">
        <property type="entry name" value="AMP-binding"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13193">
        <property type="entry name" value="AMP-binding_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56801">
        <property type="entry name" value="Acetyl-CoA synthetase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00455">
        <property type="entry name" value="AMP_BINDING"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0276">Fatty acid metabolism</keyword>
    <keyword id="KW-0436">Ligase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="4">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000339384" description="Acyl-coenzyme A synthetase ACSM4, mitochondrial">
        <location>
            <begin position="23"/>
            <end position="580"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="229"/>
            <end position="237"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="368"/>
            <end position="373"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="455"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="470"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="566"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_061010" description="In dbSNP:rs61584783.">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="481"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q08AH1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q7TN78"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="580" mass="65703" checksum="217EF355B93BACC0" modified="2008-06-10" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="248" xmlns="https://uniprot.org/uniprot">
    <accession>P35609</accession>
    <accession>B1ANE4</accession>
    <accession>B2RCS5</accession>
    <accession>Q86TF4</accession>
    <accession>Q86TI8</accession>
    <name>ACTN2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-actinin-2</fullName>
        </recommendedName>
        <alternativeName>
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    <gene>
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            <taxon>Vertebrata</taxon>
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            <taxon>Mammalia</taxon>
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            <dbReference type="DOI" id="10.1074/jbc.m603244200"/>
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        <scope>INTERACTION WITH XIRP2</scope>
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    <reference key="14">
        <citation type="journal article" date="2010" name="Eur. J. Cell Biol." volume="89" first="681" last="692">
            <title>The sarcomeric Z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin.</title>
            <authorList>
                <person name="Linnemann A."/>
                <person name="van der Ven P.F."/>
                <person name="Vakeel P."/>
                <person name="Albinus B."/>
                <person name="Simonis D."/>
                <person name="Bendas G."/>
                <person name="Schenk J.A."/>
                <person name="Micheel B."/>
                <person name="Kley R.A."/>
                <person name="Fuerst D.O."/>
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            <dbReference type="DOI" id="10.1016/j.ejcb.2010.04.004"/>
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        <scope>INTERACTION WITH SYNPO2</scope>
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    <reference key="15">
        <citation type="journal article" date="2010" name="Exp. Cell Res." volume="316" first="297" last="313">
            <title>BPAG1 isoform-b: complex distribution pattern in striated and heart muscle and association with plectin and alpha-actinin.</title>
            <authorList>
                <person name="Steiner-Champliaud M.F."/>
                <person name="Schneider Y."/>
                <person name="Favre B."/>
                <person name="Paulhe F."/>
                <person name="Praetzel-Wunder S."/>
                <person name="Faulkner G."/>
                <person name="Konieczny P."/>
                <person name="Raith M."/>
                <person name="Wiche G."/>
                <person name="Adebola A."/>
                <person name="Liem R.K."/>
                <person name="Langbein L."/>
                <person name="Sonnenberg A."/>
                <person name="Fontao L."/>
                <person name="Borradori L."/>
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            <dbReference type="PubMed" id="19932097"/>
            <dbReference type="DOI" id="10.1016/j.yexcr.2009.11.010"/>
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        <scope>INTERACTION WITH DST</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2012" name="Circ. Res." volume="111" first="1504" last="1516">
            <title>F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo.</title>
            <authorList>
                <person name="Spaich S."/>
                <person name="Will R.D."/>
                <person name="Just S."/>
                <person name="Spaich S."/>
                <person name="Kuhn C."/>
                <person name="Frank D."/>
                <person name="Berger I.M."/>
                <person name="Wiemann S."/>
                <person name="Korn B."/>
                <person name="Koegl M."/>
                <person name="Backs J."/>
                <person name="Katus H.A."/>
                <person name="Rottbauer W."/>
                <person name="Frey N."/>
            </authorList>
            <dbReference type="PubMed" id="22972877"/>
            <dbReference type="DOI" id="10.1161/circresaha.112.271007"/>
        </citation>
        <scope>UBIQUITINATION BY FBXL22</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="1999" name="Cell" volume="98" first="537" last="546">
            <title>Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments.</title>
            <authorList>
                <person name="Djinovic-Carugo K."/>
                <person name="Young P."/>
                <person name="Gautel M."/>
                <person name="Saraste M."/>
            </authorList>
            <dbReference type="PubMed" id="10481917"/>
            <dbReference type="DOI" id="10.1016/s0092-8674(00)81981-9"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 391-637</scope>
    </reference>
    <reference key="18">
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            <title>Ca2+-independent binding of an EF-hand domain to a novel motif in the alpha-actinin-titin complex.</title>
            <authorList>
                <person name="Atkinson R.A."/>
                <person name="Joseph C."/>
                <person name="Kelly G."/>
                <person name="Muskett F.W."/>
                <person name="Frenkiel T.A."/>
                <person name="Nietlispach D."/>
                <person name="Pastore A."/>
            </authorList>
            <dbReference type="PubMed" id="11573089"/>
            <dbReference type="DOI" id="10.1038/nsb1001-853"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 823-894 IN COMPLEX WITH A TITIN Z-REPEAT</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2001" name="Structure" volume="9" first="597" last="604">
            <title>Crystal structure of the alpha-actinin rod reveals an extensive torsional twist.</title>
            <authorList>
                <person name="Ylanne J."/>
                <person name="Scheffzek K."/>
                <person name="Young P."/>
                <person name="Saraste M."/>
            </authorList>
            <dbReference type="PubMed" id="11470434"/>
            <dbReference type="DOI" id="10.1016/s0969-2126(01)00619-0"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 274-746</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2003" name="Mol. Genet. Metab." volume="80" first="207" last="215">
            <title>Mutations in the muscle LIM protein and alpha-actinin-2 genes in dilated cardiomyopathy and endocardial fibroelastosis.</title>
            <authorList>
                <person name="Mohapatra B."/>
                <person name="Jimenez S."/>
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            </authorList>
            <dbReference type="PubMed" id="14567970"/>
            <dbReference type="DOI" id="10.1016/s1096-7192(03)00142-2"/>
        </citation>
        <scope>VARIANT CMD1AA ARG-9</scope>
        <scope>VARIANT VAL-604</scope>
    </reference>
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        <citation type="journal article" date="2010" name="J. Am. Coll. Cardiol." volume="55" first="1127" last="1135">
            <title>Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis.</title>
            <authorList>
                <person name="Chiu C."/>
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                <person name="Yeates L."/>
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                <person name="Jormakka M."/>
                <person name="Lind J.M."/>
                <person name="Semsarian C."/>
            </authorList>
            <dbReference type="PubMed" id="20022194"/>
            <dbReference type="DOI" id="10.1016/j.jacc.2009.11.016"/>
        </citation>
        <scope>VARIANTS CMH23 THR-119; MET-495; ALA-583 AND GLY-628</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2014" name="BMC Med. Genet." volume="15" first="99" last="99">
            <title>Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death.</title>
            <authorList>
                <person name="Bagnall R.D."/>
                <person name="Molloy L.K."/>
                <person name="Kalman J.M."/>
                <person name="Semsarian C."/>
            </authorList>
            <dbReference type="PubMed" id="25224718"/>
            <dbReference type="DOI" id="10.1186/s12881-014-0099-0"/>
        </citation>
        <scope>VARIANT CMD1AA THR-119</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2014" name="Circ. Cardiovasc. Genet." volume="7" first="741" last="750">
            <title>Novel alpha-actinin 2 variant associated with familial hypertrophic cardiomyopathy and juvenile atrial arrhythmias: a massively parallel sequencing study.</title>
            <authorList>
                <person name="Girolami F."/>
                <person name="Iascone M."/>
                <person name="Tomberli B."/>
                <person name="Bardi S."/>
                <person name="Benelli M."/>
                <person name="Marseglia G."/>
                <person name="Pescucci C."/>
                <person name="Pezzoli L."/>
                <person name="Sana M.E."/>
                <person name="Basso C."/>
                <person name="Marziliano N."/>
                <person name="Merlini P.A."/>
                <person name="Fornaro A."/>
                <person name="Cecchi F."/>
                <person name="Torricelli F."/>
                <person name="Olivotto I."/>
            </authorList>
            <dbReference type="PubMed" id="25173926"/>
            <dbReference type="DOI" id="10.1161/circgenetics.113.000486"/>
        </citation>
        <scope>VARIANT CMH23 THR-228</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2019" name="Acta Neuropathol." volume="137" first="501" last="519">
            <title>ACTN2 mutations cause 'Multiple structured Core Disease' (MsCD).</title>
            <authorList>
                <person name="Lornage X."/>
                <person name="Romero N.B."/>
                <person name="Grosgogeat C.A."/>
                <person name="Malfatti E."/>
                <person name="Donkervoort S."/>
                <person name="Marchetti M.M."/>
                <person name="Neuhaus S.B."/>
                <person name="Foley A.R."/>
                <person name="Labasse C."/>
                <person name="Schneider R."/>
                <person name="Carlier R.Y."/>
                <person name="Chao K.R."/>
                <person name="Medne L."/>
                <person name="Deleuze J.F."/>
                <person name="Orlikowski D."/>
                <person name="Boennemann C.G."/>
                <person name="Gupta V.A."/>
                <person name="Fardeau M."/>
                <person name="Boehm J."/>
                <person name="Laporte J."/>
            </authorList>
            <dbReference type="PubMed" id="30701273"/>
            <dbReference type="DOI" id="10.1007/s00401-019-01963-8"/>
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        <scope>VARIANTS CMYO8 ARG-727 AND 732-ALA--ILE-742 DEL</scope>
        <scope>INVOLVEMENT IN CMYO8</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2019" name="Ann. Neurol." volume="85" first="899" last="906">
            <title>Actininopathy: A new muscular dystrophy caused by ACTN2 dominant mutations.</title>
            <authorList>
                <person name="Savarese M."/>
                <person name="Palmio J."/>
                <person name="Poza J.J."/>
                <person name="Weinberg J."/>
                <person name="Olive M."/>
                <person name="Cobo A.M."/>
                <person name="Vihola A."/>
                <person name="Jonson P.H."/>
                <person name="Sarparanta J."/>
                <person name="Garcia-Bragado F."/>
                <person name="Urtizberea J.A."/>
                <person name="Hackman P."/>
                <person name="Udd B."/>
            </authorList>
            <dbReference type="PubMed" id="30900782"/>
            <dbReference type="DOI" id="10.1002/ana.25470"/>
        </citation>
        <scope>VARIANTS MPD6 PRO-131 AND ARG-487</scope>
        <scope>INVOLVEMENT IN MPD6</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2024" name="Ann. Clin. Transl. Neurol." volume="11" first="629" last="640">
            <title>Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.</title>
            <authorList>
                <consortium name="Undiagnosed Diseases Network"/>
                <person name="Donkervoort S."/>
                <person name="Mohassel P."/>
                <person name="O'Leary M."/>
                <person name="Bonner D.E."/>
                <person name="Hartley T."/>
                <person name="Acquaye N."/>
                <person name="Brull A."/>
                <person name="Mozaffar T."/>
                <person name="Saporta M.A."/>
                <person name="Dyment D.A."/>
                <person name="Sampson J.B."/>
                <person name="Pajusalu S."/>
                <person name="Austin-Tse C."/>
                <person name="Hurth K."/>
                <person name="Cohen J.S."/>
                <person name="McWalter K."/>
                <person name="Warman-Chardon J."/>
                <person name="Crunk A."/>
                <person name="Foley A.R."/>
                <person name="Mammen A.L."/>
                <person name="Wheeler M.T."/>
                <person name="O'Donnell-Luria A."/>
                <person name="Boennemann C.G."/>
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            <dbReference type="PubMed" id="38311799"/>
            <dbReference type="DOI" id="10.1002/acn3.51983"/>
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        <scope>VARIANT GLY-506</scope>
        <scope>INVOLVEMENT IN AUTOSOMAL RECESSIVE MYOPATHY</scope>
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    <comment type="function">
        <text>F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 5 6 7 8 10 11 12">Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-terminal region with the LDB3 PDZ domain. Interacts with XIRP2. Interacts with DST isoform 1 (via N-terminus). Interacts with PARVB. Interacts with SYNPO2.</text>
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        <interactant intactId="EBI-493777">
            <id>Q6P0Q8</id>
            <label>MAST2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-14086479">
            <id>Q8IVT4</id>
            <label>MGC50722</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-2555563">
            <id>Q8IY33</id>
            <label>MICALL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-1757866">
            <id>P00540</id>
            <label>MOS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-723524">
            <id>Q7Z7H8</id>
            <label>MRPL10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-16430371">
            <id>A0A0S2Z4Y0</id>
            <label>MYOT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-296701">
            <id>Q9UBF9</id>
            <label>MYOT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-744402">
            <id>Q9NP98</id>
            <label>MYOZ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-746712">
            <id>Q9NPC6</id>
            <label>MYOZ2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-3920396">
            <id>Q6ZUT1</id>
            <label>NKAPD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-5660292">
            <id>Q86VF7</id>
            <label>NRAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-741158">
            <id>Q96HA8</id>
            <label>NTAQ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-724897">
            <id>O00151</id>
            <label>PDLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-5658852">
            <id>Q53GG5</id>
            <label>PDLIM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-12702438">
            <id>Q53GG5-2</id>
            <label>PDLIM3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-352350">
            <id>P62140</id>
            <label>PPP1CB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-359352">
            <id>P25786</id>
            <label>PSMA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-347462">
            <id>P47897</id>
            <label>QARS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-296739">
            <id>P63244</id>
            <label>RACK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-366542">
            <id>O95059</id>
            <label>RPP14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-10217913">
            <id>Q14D33</id>
            <label>RTP5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-3957636">
            <id>Q8IYX7</id>
            <label>SAXO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-1045459">
            <id>O95863</id>
            <label>SNAI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-751145">
            <id>P23497</id>
            <label>SP100</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-6589365">
            <id>P23497-2</id>
            <label>SP100</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-1377865">
            <id>Q15506</id>
            <label>SPA17</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-350743">
            <id>P49458</id>
            <label>SRP9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-12082116">
            <id>Q9H987-2</id>
            <label>SYNPO2L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-74615">
            <id>Q9H0E2</id>
            <label>TOLLIP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-681210">
            <id>Q8WZ42</id>
            <label>TTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-743272">
            <id>O75604</id>
            <label>USP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-11990572">
            <id>J3KMY6</id>
            <label>ZC2HC1C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-14104088">
            <id>Q53FD0-2</id>
            <label>ZC2HC1C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-741415">
            <id>O60232</id>
            <label>ZNRD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77797">
            <id>P35609</id>
        </interactant>
        <interactant intactId="EBI-77785">
            <id>Q61824</id>
            <label>Adam12</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 12 17">Cytoplasm</location>
            <location evidence="7 12 17">Myofibril</location>
            <location evidence="7 12 17">Sarcomere</location>
            <location evidence="7 12 17">Z line</location>
        </subcellularLocation>
        <text>Colocalizes with MYOZ1 and FLNC at the Z-lines of skeletal muscle.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P35609-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P35609-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054923"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in both skeletal and cardiac muscle.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14">Ubiquitinated by FBXL22, leading to proteasomal degradation.</text>
    </comment>
    <comment type="disease" evidence="13 15">
        <disease id="DI-04440">
            <name>Cardiomyopathy, familial hypertrophic, 23, with or without left ventricular non-compaction</name>
            <acronym>CMH23</acronym>
            <description>A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.</description>
            <dbReference type="MIM" id="612158"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9 16">
        <disease id="DI-00211">
            <name>Cardiomyopathy, dilated, 1AA, with or without left ventricular non-compaction</name>
            <acronym>CMD1AA</acronym>
            <description>A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.</description>
            <dbReference type="MIM" id="612158"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="17">
        <disease id="DI-05700">
            <name>Congenital myopathy 8</name>
            <acronym>CMYO8</acronym>
            <description>An autosomal dominant muscular disorder characterized by progressive early-onset muscle weakness, gait difficulties, loss of ambulation, and respiratory insufficiency. Morphological and ultrastructural analyses of muscle biopsies reveal type 1 fiber predominance, multiple structured cores forming a circular arrangement beneath the sarcolemma, and jagged Z-lines.</description>
            <dbReference type="MIM" id="618654"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="18">
        <disease id="DI-05701">
            <name>Myopathy, distal, 6, adult onset, autosomal dominant</name>
            <acronym>MPD6</acronym>
            <description>An autosomal dominant muscular disorder characterized by adult onset of asymmetric distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles.</description>
            <dbReference type="MIM" id="618655"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text evidence="19">Defects in ACTN2 may be the cause of an autosomal recessive myopathy characterized by asymmetric, progressive muscle weakness predominantly affecting the lower extremities. Patients do not manifest cardiomyopathy or respiratory insufficiency. Muscle biopsy reveals disruption of the inter-myofibrillar architecture, type I fiber predominance and atrophy.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the alpha-actinin family.</text>
    </comment>
    <dbReference type="EMBL" id="M86406">
        <property type="protein sequence ID" value="AAA51583.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M86804">
        <property type="protein sequence ID" value="AAA51584.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249756">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249757">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249758">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249759">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249760">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ249761">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AJ249762">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249772">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249775">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ249776">
        <property type="protein sequence ID" value="CAB61269.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315250">
        <property type="protein sequence ID" value="BAG37672.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359185">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359921">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471098">
        <property type="protein sequence ID" value="EAW70064.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471098">
        <property type="protein sequence ID" value="EAW70065.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC047901">
        <property type="protein sequence ID" value="AAH47901.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051770">
        <property type="protein sequence ID" value="AAH51770.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1613.1">
        <molecule id="P35609-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS60455.1">
        <molecule id="P35609-2"/>
    </dbReference>
    <dbReference type="PIR" id="A40199">
        <property type="entry name" value="FAHUA2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001094.1">
        <molecule id="P35609-1"/>
        <property type="nucleotide sequence ID" value="NM_001103.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001265272.1">
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        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd00176">
        <property type="entry name" value="SPEC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.238.10:FF:000004">
        <property type="entry name" value="Actinin alpha 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.418.10:FF:000001">
        <property type="entry name" value="Actinin alpha 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.20.58.60:FF:000004">
        <property type="entry name" value="Actinin alpha 1"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.58.60">
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        <property type="entry name" value="Calponin-like domain"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="EF-hand"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001589">
        <property type="entry name" value="Actinin_actin-bd_CS"/>
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        <property type="entry name" value="CH_dom"/>
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        <property type="entry name" value="CH_dom_sf"/>
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        <property type="entry name" value="EF-hand-dom_pair"/>
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        <property type="entry name" value="EF-hand_Ca_insen"/>
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    <dbReference type="InterPro" id="IPR002048">
        <property type="entry name" value="EF_hand_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018159">
        <property type="entry name" value="Spectrin/alpha-actinin"/>
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    <dbReference type="InterPro" id="IPR002017">
        <property type="entry name" value="Spectrin_repeat"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11915">
        <property type="entry name" value="SPECTRIN/FILAMIN RELATED CYTOSKELETAL PROTEIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00307">
        <property type="entry name" value="CH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13499">
        <property type="entry name" value="EF-hand_7"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF08726">
        <property type="entry name" value="EFhand_Ca_insen"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00435">
        <property type="entry name" value="Spectrin"/>
        <property type="match status" value="4"/>
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    <dbReference type="SMART" id="SM00033">
        <property type="entry name" value="CH"/>
        <property type="match status" value="2"/>
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    <dbReference type="SMART" id="SM00054">
        <property type="entry name" value="EFh"/>
        <property type="match status" value="2"/>
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    <dbReference type="SMART" id="SM01184">
        <property type="entry name" value="efhand_Ca_insen"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="SPEC"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF47576">
        <property type="entry name" value="Calponin-homology domain, CH-domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF47473">
        <property type="entry name" value="EF-hand"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF46966">
        <property type="entry name" value="Spectrin repeat"/>
        <property type="match status" value="4"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00019">
        <property type="entry name" value="ACTININ_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00020">
        <property type="entry name" value="ACTININ_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="CH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50222">
        <property type="entry name" value="EF_HAND_2"/>
        <property type="match status" value="2"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0009">Actin-binding</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0122">Cardiomyopathy</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000073435" description="Alpha-actinin-2">
        <location>
            <begin position="1"/>
            <end position="894"/>
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    </feature>
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            <end position="257"/>
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            <begin position="281"/>
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    </feature>
    <feature type="repeat" description="Spectrin 2">
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            <begin position="401"/>
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    <feature type="repeat" description="Spectrin 3">
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            <begin position="516"/>
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    <feature type="repeat" description="Spectrin 4">
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    <feature type="domain" description="EF-hand 1" evidence="3">
        <location>
            <begin position="753"/>
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    <feature type="domain" description="EF-hand 2" evidence="3">
        <location>
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            <end position="824"/>
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    </feature>
    <feature type="region of interest" description="Actin-binding">
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            <begin position="1"/>
            <end position="254"/>
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    <feature type="binding site" evidence="21">
        <location>
            <position position="766"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>1</label>
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    </feature>
    <feature type="binding site" evidence="21">
        <location>
            <position position="770"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21">
        <location>
            <position position="777"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21">
        <location>
            <position position="802"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21">
        <location>
            <position position="804"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="21">
        <location>
            <position position="808"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="237"/>
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    </feature>
    <feature type="splice variant" id="VSP_054923" description="In isoform 2." evidence="20">
        <original>IVNTPKPDERAIMTYVSCFYHAFAGAEQ</original>
        <variation>LVYTARPDERAIMTYVSCYYHAFAGAQK</variation>
        <location>
            <begin position="234"/>
            <end position="261"/>
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    </feature>
    <feature type="sequence variant" id="VAR_054628" description="In CMD1AA; dbSNP:rs121434525." evidence="9">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="9"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071970" description="In CMH23 and CMD1AA; dbSNP:rs727502886." evidence="13 16">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083364" description="In MPD6; uncertain significance; dbSNP:rs1572114611." evidence="18">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_074292" description="In CMH23; dbSNP:rs786205144." evidence="15">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083365" description="In MPD6; dbSNP:rs1572140109." evidence="18">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="487"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071971" description="In CMH23; dbSNP:rs200248944." evidence="13">
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        <variation>M</variation>
        <location>
            <position position="495"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089760" description="Found in patients with autosomal recessive myopathy and asymmetric muscle weakness without significant cardiac or respiratory involvement; likely pathogenic; dbSNP:rs794728967." evidence="19">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="506"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071972" description="In CMH23; dbSNP:rs200631005." evidence="13">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033487" description="In dbSNP:rs35997569." evidence="9">
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        <variation>V</variation>
        <location>
            <position position="604"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071973" description="In CMH23; dbSNP:rs786204951." evidence="13">
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        <location>
            <position position="628"/>
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    </feature>
    <feature type="sequence variant" id="VAR_083366" description="In CMYO8; dbSNP:rs1572148902." evidence="17">
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        <location>
            <position position="727"/>
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            <begin position="732"/>
            <end position="742"/>
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        <location>
            <begin position="21"/>
            <end position="29"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="32"/>
            <end position="52"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="53"/>
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    </feature>
    <feature type="turn" evidence="26">
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            <begin position="62"/>
            <end position="68"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="70"/>
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    </feature>
    <feature type="strand" evidence="25">
        <location>
            <begin position="90"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="93"/>
            <end position="109"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="119"/>
            <end position="123"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="127"/>
            <end position="142"/>
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    <feature type="turn" evidence="26">
        <location>
            <begin position="143"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="153"/>
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    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="175"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="178"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="184"/>
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            <begin position="195"/>
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            <begin position="200"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="30701273"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="30900782"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="38311799"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21"/>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="1HCI"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="23">
        <source>
            <dbReference type="PDB" id="1QUU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="4D1E"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="5A36"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="6SWT"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="6TS3"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="7A8T"/>
        </source>
    </evidence>
    <sequence length="894" mass="103854" checksum="7F612C1C3B3E2299" modified="1994-06-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-04-29" modified="2026-01-28" version="141" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TC94</accession>
    <accession>A8K893</accession>
    <accession>Q6X960</accession>
    <name>ACTL9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-like protein 9</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="7" type="primary">ACTL9</name>
        <name type="synonym">ACTL7C</name>
        <name type="ORF">HSD21</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT HIS-227</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS PHE-37; VAL-51 AND HIS-227</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] ASP-42 AND THR-332</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2021" name="Am. J. Hum. Genet." volume="108" first="469" last="481">
            <title>Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice.</title>
            <authorList>
                <person name="Dai J."/>
                <person name="Zhang T."/>
                <person name="Guo J."/>
                <person name="Zhou Q."/>
                <person name="Gu Y."/>
                <person name="Zhang J."/>
                <person name="Hu L."/>
                <person name="Zong Y."/>
                <person name="Song J."/>
                <person name="Zhang S."/>
                <person name="Dai C."/>
                <person name="Gong F."/>
                <person name="Lu G."/>
                <person name="Zheng W."/>
                <person name="Lin G."/>
            </authorList>
            <dbReference type="PubMed" id="33626338"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2021.02.004"/>
        </citation>
        <scope>INVOLVEMENT IN SPGF53</scope>
        <scope>VARIANTS SPGF53 LEU-345; LEU-380 AND 403-TYR--TYR-416 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANTS SPGF53 LEU-345; LEU-380 AND 403-TYR--TYR-416 DEL</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH ACTL7A</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Testis-specic protein that plays an important role in fusion of proacrosomal vesicles and perinuclear theca formation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Interacts with ACTL7A.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasmic vesicle</location>
            <location evidence="4">Secretory vesicle</location>
            <location evidence="4">Acrosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
            <location evidence="4">Cytoskeleton</location>
            <location evidence="4">Perinuclear theca</location>
        </subcellularLocation>
        <text evidence="4">Localizes predominantly in the equatorial segment of the sperm head and neck regions, with some localization in the acrosomal segment of the head. Colocalizes in the acrosomal and equatorial segments of sperm with ACTL7A. Colocalizes with PLCZ1 in the equatorial segment of the head of capacitated sperm.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Testis-specific.</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-06072">
            <name>Spermatogenic failure 53</name>
            <acronym>SPGF53</acronym>
            <description>An autosomal recessive infertility disorder characterized by impaired oocyte fertilization due to oocyte activation failure, in association with structural anomalies in sperm heads.</description>
            <dbReference type="MIM" id="619258"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AY248901">
        <property type="protein sequence ID" value="AAP20052.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292258">
        <property type="protein sequence ID" value="BAF84947.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093230">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC024028">
        <property type="protein sequence ID" value="AAH24028.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC045752">
        <property type="protein sequence ID" value="AAH45752.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12207.1"/>
    <dbReference type="RefSeq" id="NP_848620.3">
        <property type="nucleotide sequence ID" value="NM_178525.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TC94"/>
    <dbReference type="SMR" id="Q8TC94"/>
    <dbReference type="BioGRID" id="129853">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TC94">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TC94">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000316674"/>
    <dbReference type="iPTMnet" id="Q8TC94"/>
    <dbReference type="PhosphoSitePlus" id="Q8TC94"/>
    <dbReference type="BioMuta" id="ACTL9"/>
    <dbReference type="DMDM" id="308153636"/>
    <dbReference type="jPOST" id="Q8TC94"/>
    <dbReference type="MassIVE" id="Q8TC94"/>
    <dbReference type="PaxDb" id="9606-ENSP00000316674"/>
    <dbReference type="PeptideAtlas" id="Q8TC94"/>
    <dbReference type="ProteomicsDB" id="74103"/>
    <dbReference type="Antibodypedia" id="12540">
        <property type="antibodies" value="112 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="284382"/>
    <dbReference type="Ensembl" id="ENST00000324436.5">
        <property type="protein sequence ID" value="ENSP00000316674.3"/>
        <property type="gene ID" value="ENSG00000181786.6"/>
    </dbReference>
    <dbReference type="GeneID" id="284382"/>
    <dbReference type="KEGG" id="hsa:284382"/>
    <dbReference type="MANE-Select" id="ENST00000324436.5">
        <property type="protein sequence ID" value="ENSP00000316674.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_178525.5"/>
        <property type="RefSeq protein sequence ID" value="NP_848620.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc032hly.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28494"/>
    <dbReference type="ClinPGx" id="PA165392996"/>
    <dbReference type="CTD" id="284382"/>
    <dbReference type="DisGeNET" id="284382"/>
    <dbReference type="GeneCards" id="ACTL9"/>
    <dbReference type="HGNC" id="HGNC:28494">
        <property type="gene designation" value="ACTL9"/>
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    <dbReference type="HPA" id="ENSG00000181786">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
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    <dbReference type="MalaCards" id="ACTL9"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000181786"/>
    <dbReference type="Orphanet" id="276234">
        <property type="disease" value="Non-syndromic male infertility due to sperm motility disorder"/>
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    <dbReference type="VEuPathDB" id="HostDB:ENSG00000181786"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
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        <property type="hits" value="14 hits in 1136 CRISPR screens"/>
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        <property type="development level" value="Tdark"/>
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        <property type="component" value="Chromosome 19"/>
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        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 36 other cell types or tissues"/>
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        <property type="term" value="C:acrosomal vesicle"/>
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        <property type="term" value="C:actin cytoskeleton"/>
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        <property type="term" value="C:perinuclear theca"/>
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        <property type="term" value="C:sperm head"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="term" value="P:acrosome assembly"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:fertilization"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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        <property type="entry name" value="ASKHA_NBD_ACTL7"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Actin, alpha skeletal muscle"/>
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    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
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    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
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    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
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        <property type="entry name" value="ACTIN"/>
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        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0278">Fertilization</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000332297" description="Actin-like protein 9">
        <location>
            <begin position="1"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043000" description="In dbSNP:rs2340550." evidence="2">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043001" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs2146191770." evidence="3">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043002" description="In dbSNP:rs10410943." evidence="2">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043003" description="In dbSNP:rs4804079." evidence="2 5">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043004" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs782721280." evidence="3">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="332"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085431" description="In SPGF53; uncertain significance; reduces interaction with ACTL7A; dbSNP:rs1478948010." evidence="4">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085432" description="In SPGF53; uncertain significance; reduces interaction with ACTL7A; dbSNP:rs532021673." evidence="4">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085433" description="In SPGF53; uncertain significance; abolishes interaction with ACTL7A." evidence="4">
        <location>
            <begin position="403"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP20052." evidence="6" ref="1">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="33626338"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:28494"/>
        </source>
    </evidence>
    <sequence length="416" mass="45516" checksum="B4CE3043F99E2195" modified="2022-02-23" version="4">MDASRPKSSESQSSLEAPRPGPNPSPNVVNKPLQRDSPGMVADRLPPKTGAVVIDMGTGTCKVGFAGQASPTYTVATILGCQPKKPATSGQSGLQTFIGEAARVLPELTLVQPLRSGIVVDWDAAELIWRHLLEHDLRVATHDHPLLFSDPPFSPATNREKLVEVAFESLRSPAMYVASQSVLSVYAHGRVSGLVVDTGHGVTYTVPVFQGYNLLHATERLDLAGNNLTAFLAEMLLQAGLPLGQQDLDLVENIKHHYCYVASDFQKEQARPEQEYKRTLKLPDGRTVTLGKELFQCPELLFNPPEVPGLSPVGLSTMAKQSLRKLSLEMRADLAQNVLLCGGSSLFTGFEGRFRAELLRALPAETHVVVAAQPTRNFSVWIGGSILASLRAFQSCWVLREQYEEQGPYIVYRKCY</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-02-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
    <accession>Q08043</accession>
    <accession>A6NP77</accession>
    <accession>Q4KKV2</accession>
    <name>ACTN3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-actinin-3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-actinin skeletal muscle isoform 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>F-actin cross-linking protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTN3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11.</title>
            <authorList>
                <person name="Beggs A.H."/>
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            </authorList>
            <dbReference type="PubMed" id="1339456"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(19)50420-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANTS GLN-523; ARG-628 AND ARG-776</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="2">
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                <person name="Sakaki Y."/>
            </authorList>
            <dbReference type="PubMed" id="16554811"/>
            <dbReference type="DOI" id="10.1038/nature04632"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS GLN-523; ARG-628 AND ARG-776</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="Hum. Mol. Genet." volume="10" first="1335" last="1346">
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                <person name="Mills M."/>
                <person name="Yang N."/>
                <person name="Weinberger R."/>
                <person name="Vander Woude D.L."/>
                <person name="Beggs A.H."/>
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                <person name="North K.N."/>
            </authorList>
            <dbReference type="PubMed" id="11440986"/>
            <dbReference type="DOI" id="10.1093/hmg/10.13.1335"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="Proc. Natl. Acad. Sci. U.S.A." volume="98" first="1595" last="1600">
            <title>Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines.</title>
            <authorList>
                <person name="Takada F."/>
                <person name="Vander Woude D.L."/>
                <person name="Tong H.-Q."/>
                <person name="Thompson T.G."/>
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            </authorList>
            <dbReference type="PubMed" id="11171996"/>
            <dbReference type="DOI" id="10.1073/pnas.98.4.1595"/>
        </citation>
        <scope>INTERACTION WITH MYOZ1</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="Am. J. Hum. Genet." volume="73" first="627" last="631">
            <title>ACTN3 genotype is associated with human elite athletic performance.</title>
            <authorList>
                <person name="Yang N."/>
                <person name="MacArthur D.G."/>
                <person name="Gulbin J.P."/>
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                <person name="Beggs A.H."/>
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                <person name="North K."/>
            </authorList>
            <dbReference type="PubMed" id="12879365"/>
            <dbReference type="DOI" id="10.1086/377590"/>
        </citation>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2005" name="Eur. J. Hum. Genet." volume="13" first="965" last="969">
            <title>Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes.</title>
            <authorList>
                <person name="Niemi A.K."/>
                <person name="Majamaa K."/>
            </authorList>
            <dbReference type="PubMed" id="15886711"/>
            <dbReference type="DOI" id="10.1038/sj.ejhg.5201438"/>
        </citation>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="Eur. J. Hum. Genet." volume="16" first="391" last="394">
            <title>The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes.</title>
            <authorList>
                <person name="Roth S.M."/>
                <person name="Walsh S."/>
                <person name="Liu D."/>
                <person name="Metter E.J."/>
                <person name="Ferrucci L."/>
                <person name="Hurley B.F."/>
            </authorList>
            <dbReference type="PubMed" id="18043716"/>
            <dbReference type="DOI" id="10.1038/sj.ejhg.5201964"/>
        </citation>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2012" name="Mol. Cell. Proteomics" volume="11" first="M111.015131" last="M111.015131">
            <title>Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.</title>
            <authorList>
                <person name="Bienvenut W.V."/>
                <person name="Sumpton D."/>
                <person name="Martinez A."/>
                <person name="Lilla S."/>
                <person name="Espagne C."/>
                <person name="Meinnel T."/>
                <person name="Giglione C."/>
            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2018" name="Am. J. Hum. Genet." volume="102" first="845" last="857">
            <title>The effect of ACTN3 gene doping on skeletal muscle performance.</title>
            <authorList>
                <person name="Garton F.C."/>
                <person name="Houweling P.J."/>
                <person name="Vukcevic D."/>
                <person name="Meehan L.R."/>
                <person name="Lee F.X.Z."/>
                <person name="Lek M."/>
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                <person name="Head S.I."/>
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            <dbReference type="PubMed" id="29706347"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2018.03.009"/>
        </citation>
        <scope>POLYMORPHISM</scope>
    </reference>
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            <title>The crystal structure of the actin binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alpha-actinin.</title>
            <authorList>
                <person name="Franzot G."/>
                <person name="Sjoblom B."/>
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                <person name="Djinovic Carugo K."/>
            </authorList>
            <dbReference type="PubMed" id="15808860"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2005.01.002"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 26-273</scope>
    </reference>
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            <dbReference type="PubMed" id="10192379"/>
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        </citation>
        <scope>VARIANTS GLN-523 AND 577-ARG--LEU-901 DEL</scope>
        <scope>POLYMORPHISM</scope>
        <scope>TISSUE SPECIFICITY</scope>
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    <reference key="13">
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                <person name="Wyckelsma V.L."/>
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            <dbReference type="PubMed" id="33600773"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2021.01.013"/>
        </citation>
        <scope>VARIANT 577-ARG--LEU-901 DEL</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <comment type="function">
        <text>F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4">Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
        </interactant>
        <interactant intactId="EBI-351710">
            <id>P12814</id>
            <label>ACTN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
        </interactant>
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
            <label>ACTN3</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-351526">
            <id>O43707</id>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-745641">
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-12811889">
            <id>Q9Y6H3</id>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-739879">
            <id>Q53TS8</id>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-10179719">
            <id>A2RRN7</id>
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        <interactant intactId="EBI-12010090">
            <id>A8MYP8</id>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-12155483">
            <id>Q9H1P6</id>
            <label>CIMIP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
        </interactant>
        <interactant intactId="EBI-1188472">
            <id>P78358</id>
            <label>CTAG1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-751587">
            <id>Q9GZU7</id>
            <label>CTDSP1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
        </interactant>
        <interactant intactId="EBI-12175919">
            <id>P42830</id>
            <label>CXCL5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-749139">
            <id>O95865</id>
            <label>DDAH2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-947964">
            <id>Q16610</id>
            <label>ECM1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-6658203">
            <id>Q86YD7</id>
            <label>FAM90A1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-7251368">
            <id>Q9BZE0</id>
            <label>GLIS2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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            <id>O14964</id>
            <label>HGS</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-17244356">
            <id>P35452-2</id>
            <label>HOXD12</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-7116203">
            <id>O75031</id>
            <label>HSF2BP</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-2866408">
            <id>P26440</id>
            <label>IVD</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-2564105">
            <id>P48668</id>
            <label>KRT6C</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-12039345">
            <id>Q9UBR4-2</id>
            <label>LHX3</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-739832">
            <id>Q8TBB1</id>
            <label>LNX1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
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        <interactant intactId="EBI-1045155">
            <id>P43360</id>
            <label>MAGEA6</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-2555563">
            <id>Q8IY33</id>
            <label>MICALL2</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-296701">
            <id>Q9UBF9</id>
            <label>MYOT</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-744402">
            <id>Q9NP98</id>
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        <organismsDiffer>false</organismsDiffer>
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        <organismsDiffer>false</organismsDiffer>
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            <label>PCCB</label>
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    <comment type="interaction">
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <label>PTK6</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-1045459">
            <id>O95863</id>
            <label>SNAI1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q08043</id>
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        <interactant intactId="EBI-12288855">
            <id>Q5JUK2</id>
            <label>SOHLH1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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            <id>Q6P1L6</id>
            <label>ZNF343</label>
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    <comment type="interaction">
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            <label>ZNF426</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="tissue specificity">
        <text evidence="3 5">Expression restricted to fast (type 2) skeletal muscle fibers (at protein level).</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="3 5 6 9 10 11 12">A common variant at position 577 creates a stop codon at position 577, leading to ACTN3 deficiency (PubMed:10192379). The presence of this variant is not associated with any disease phenotype [MIM:617749] (PubMed:11440986). It has a global frequency of almost 44% in the human population according to the Genome Aggregation Database (gnomAD v4.1.0). It is thought that the variant p.Arg577Ter became more frequent as humans migrated out of Africa into the colder climates of central and northern Europe, as individuals carrying this variant are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis (PubMed:33600773). The variant p.Arg577Ter at the homozygous state is underrepresented in elite sprint/power athletes and overrepresented in endurance athletes, suggesting that ACT3 deficiency increases muscle endurance at the cost of power generation (PubMed:12879365, PubMed:15886711, PubMed:18043716, PubMed:29706347).</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the alpha-actinin family.</text>
    </comment>
    <comment type="online information" name="Protein Spotlight">
        <link uri="https://www.proteinspotlight.org/back_issues/273/"/>
        <text>Shift - Issue 273 of October 2024</text>
    </comment>
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        <property type="chains" value="A=26-273"/>
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        <source>
            <dbReference type="PubMed" id="11171996"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11440986"/>
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        <source>
            <dbReference type="PubMed" id="12879365"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="1339456"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15886711"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18043716"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="29706347"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="33600773"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="1TJT"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="16">
        <source>
            <dbReference type="PDB" id="1WKU"/>
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    </evidence>
    <sequence length="901" mass="103241" checksum="C49B7885E7E1EDA7" modified="2008-11-25" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-10-11" modified="2026-01-28" version="174" xmlns="https://uniprot.org/uniprot">
    <accession>P63267</accession>
    <accession>B2R7E7</accession>
    <accession>B4E315</accession>
    <accession>D6W5H8</accession>
    <accession>E9PG30</accession>
    <accession>P12718</accession>
    <accession>Q504R1</accession>
    <accession>Q6FI22</accession>
    <name>ACTH_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin, gamma-enteric smooth muscle</fullName>
            <ecNumber evidence="5">3.6.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-actin-3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Gamma-2-actin</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Smooth muscle gamma-actin</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Actin, gamma-enteric smooth muscle, intermediate form</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">ACTG2</name>
        <name type="synonym">ACTA3</name>
        <name type="synonym">ACTL3</name>
        <name type="synonym">ACTSG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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                <person name="Wilkinson A.W."/>
                <person name="Diep J."/>
                <person name="Dai S."/>
                <person name="Liu S."/>
                <person name="Ooi Y.S."/>
                <person name="Song D."/>
                <person name="Li T.M."/>
                <person name="Horton J.R."/>
                <person name="Zhang X."/>
                <person name="Liu C."/>
                <person name="Trivedi D.V."/>
                <person name="Ruppel K.M."/>
                <person name="Vilches-Moure J.G."/>
                <person name="Casey K.M."/>
                <person name="Mak J."/>
                <person name="Cowan T."/>
                <person name="Elias J.E."/>
                <person name="Nagamine C.M."/>
                <person name="Spudich J.A."/>
                <person name="Cheng X."/>
                <person name="Carette J.E."/>
                <person name="Gozani O."/>
            </authorList>
            <dbReference type="PubMed" id="30626964"/>
            <dbReference type="DOI" id="10.1038/s41586-018-0821-8"/>
        </citation>
        <scope>METHYLATION AT HIS-74</scope>
    </reference>
    <reference evidence="22" key="12">
        <citation type="journal article" date="2020" name="Cell Discov." volume="6" first="3" last="3">
            <title>Molecular basis for histidine N3-specific methylation of actin H73 by SETD3.</title>
            <authorList>
                <person name="Zheng Y."/>
                <person name="Zhang X."/>
                <person name="Li H."/>
            </authorList>
            <dbReference type="PubMed" id="31993215"/>
            <dbReference type="DOI" id="10.1038/s41421-019-0135-5"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 61-82 IN COMPLEX WITH SETD3</scope>
        <scope>METHYLATION AT HIS-74</scope>
        <scope>MUTAGENESIS OF ILE-72</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2012" name="Gastroenterology" volume="143" first="1482" last="1491">
            <title>Segregation of a missense variant in enteric smooth muscle actin gamma-2 with autosomal dominant familial visceral myopathy.</title>
            <authorList>
                <person name="Lehtonen H.J."/>
                <person name="Sipponen T."/>
                <person name="Tojkander S."/>
                <person name="Karikoski R."/>
                <person name="Jarvinen H."/>
                <person name="Laing N.G."/>
                <person name="Lappalainen P."/>
                <person name="Aaltonen L.A."/>
                <person name="Tuupanen S."/>
            </authorList>
            <dbReference type="PubMed" id="22960657"/>
            <dbReference type="DOI" id="10.1053/j.gastro.2012.08.045"/>
        </citation>
        <scope>VARIANT VSCM1 SER-148</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2014" name="Endoscopy" volume="46" first="533" last="537">
            <title>Familial visceral myopathy diagnosed by exome sequencing of a patient with chronic intestinal pseudo-obstruction.</title>
            <authorList>
                <person name="Holla O.L."/>
                <person name="Bock G."/>
                <person name="Busk O.L."/>
                <person name="Isfoss B.L."/>
            </authorList>
            <dbReference type="PubMed" id="24777424"/>
            <dbReference type="DOI" id="10.1055/s-0034-1365142"/>
        </citation>
        <scope>VARIANT VSCM1 SER-148</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2014" name="Hum. Genet." volume="133" first="737" last="742">
            <title>De novo ACTG2 mutations cause congenital distended bladder, microcolon, and intestinal hypoperistalsis.</title>
            <authorList>
                <person name="Thorson W."/>
                <person name="Diaz-Horta O."/>
                <person name="Foster J. II"/>
                <person name="Spiliopoulos M."/>
                <person name="Quintero R."/>
                <person name="Farooq A."/>
                <person name="Blanton S."/>
                <person name="Tekin M."/>
            </authorList>
            <dbReference type="PubMed" id="24337657"/>
            <dbReference type="DOI" id="10.1007/s00439-013-1406-0"/>
        </citation>
        <scope>VARIANTS MMIHS5 CYS-178 AND LEU-178</scope>
        <scope>CHARACTERIZATION OF VARIANTS MMIHS5 CYS-178 AND LEU-178</scope>
        <scope>INVOLVEMENT IN MMIHS5</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2014" name="PLoS Genet." volume="10" first="E1004258" last="E1004258">
            <title>Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome.</title>
            <authorList>
                <consortium name="Baylor-Hopkins Center for Mendelian Genomics"/>
                <person name="Wangler M.F."/>
                <person name="Gonzaga-Jauregui C."/>
                <person name="Gambin T."/>
                <person name="Penney S."/>
                <person name="Moss T."/>
                <person name="Chopra A."/>
                <person name="Probst F.J."/>
                <person name="Xia F."/>
                <person name="Yang Y."/>
                <person name="Werlin S."/>
                <person name="Eglite I."/>
                <person name="Kornejeva L."/>
                <person name="Bacino C.A."/>
                <person name="Baldridge D."/>
                <person name="Neul J."/>
                <person name="Lehman E.L."/>
                <person name="Larson A."/>
                <person name="Beuten J."/>
                <person name="Muzny D.M."/>
                <person name="Jhangiani S."/>
                <person name="Gibbs R.A."/>
                <person name="Lupski J.R."/>
                <person name="Beaudet A."/>
            </authorList>
            <dbReference type="PubMed" id="24676022"/>
            <dbReference type="DOI" id="10.1371/journal.pgen.1004258"/>
        </citation>
        <scope>VARIANTS MMIHS5 CYS-40; HIS-40; ASN-134; CYS-178; HIS-178 AND CYS-257</scope>
        <scope>VARIANTS VSCM1 HIS-40; THR-45; GLY-63; LEU-110 AND ASP-198</scope>
        <scope>INVOLVEMENT IN MMIHS5</scope>
        <scope>INVOLVEMENT IN VSCM1</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2016" name="Am. J. Med. Genet. A" volume="170" first="2965" last="2974">
            <title>Visceral myopathy: Clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes.</title>
            <authorList>
                <person name="Moreno C.A."/>
                <person name="Metze K."/>
                <person name="Lomazi E.A."/>
                <person name="Bertola D.R."/>
                <person name="Barbosa R.H."/>
                <person name="Cosentino V."/>
                <person name="Sobreira N."/>
                <person name="Cavalcanti D.P."/>
            </authorList>
            <dbReference type="PubMed" id="27481187"/>
            <dbReference type="DOI" id="10.1002/ajmg.a.37857"/>
        </citation>
        <scope>VARIANTS MMIHS5 CYS-178; LEU-178 AND HIS-257</scope>
        <scope>VARIANT VSCM1 ILE-195</scope>
        <scope>INVOLVEMENT IN MMIHS5</scope>
        <scope>INVOLVEMENT IN VSCM1</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2016" name="Hum. Mol. Genet." volume="25" first="571" last="583">
            <title>ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome.</title>
            <authorList>
                <person name="Halim D."/>
                <person name="Hofstra R.M."/>
                <person name="Signorile L."/>
                <person name="Verdijk R.M."/>
                <person name="van der Werf C.S."/>
                <person name="Sribudiani Y."/>
                <person name="Brouwer R.W."/>
                <person name="van Ijcken W.F."/>
                <person name="Dahl N."/>
                <person name="Verheij J.B."/>
                <person name="Baumann C."/>
                <person name="Kerner J."/>
                <person name="van Bever Y."/>
                <person name="Galjart N."/>
                <person name="Wijnen R.M."/>
                <person name="Tibboel D."/>
                <person name="Burns A.J."/>
                <person name="Muller F."/>
                <person name="Brooks A.S."/>
                <person name="Alves M.M."/>
            </authorList>
            <dbReference type="PubMed" id="26647307"/>
            <dbReference type="DOI" id="10.1093/hmg/ddv497"/>
        </citation>
        <scope>VARIANTS MMIHS5 CYS-40; GLN-63; CYS-178; HIS-178 AND LEU-178</scope>
        <scope>INVOLVEMENT IN MMIHS5</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>CHARACTERIZATION OF VARIANTS MMIHS5 CYS-40; GLN-63; CYS-178; HIS-178 AND LEU-178</scope>
        <scope>CHARACTERIZATION OF VARIANT VSCM1 SER-148</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2017" name="J. Pediatr. Gastroenterol. Nutr." volume="65" first="384" last="387">
            <title>Diagnosis of chronic intestinal pseudo-obstruction and megacystis by sequencing the ACTG2 gene.</title>
            <authorList>
                <person name="Milunsky A."/>
                <person name="Baldwin C."/>
                <person name="Zhang X."/>
                <person name="Primack D."/>
                <person name="Curnow A."/>
                <person name="Milunsky J."/>
            </authorList>
            <dbReference type="PubMed" id="28422808"/>
            <dbReference type="DOI" id="10.1097/mpg.0000000000001608"/>
        </citation>
        <scope>VARIANTS MMIHS5 HIS-40 AND CYS-257</scope>
        <scope>INVOLVEMENT IN MMIHS5</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2018" name="Neurogastroenterol. Motil." volume="30" first="e13371" last="e13371">
            <title>Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.</title>
            <authorList>
                <person name="Ravenscroft G."/>
                <person name="Pannell S."/>
                <person name="O'Grady G."/>
                <person name="Ong R."/>
                <person name="Ee H.C."/>
                <person name="Faiz F."/>
                <person name="Marns L."/>
                <person name="Goel H."/>
                <person name="Kumarasinghe P."/>
                <person name="Sollis E."/>
                <person name="Sivadorai P."/>
                <person name="Wilson M."/>
                <person name="Magoffin A."/>
                <person name="Nightingale S."/>
                <person name="Freckmann M.L."/>
                <person name="Kirk E.P."/>
                <person name="Sachdev R."/>
                <person name="Lemberg D.A."/>
                <person name="Delatycki M.B."/>
                <person name="Kamm M.A."/>
                <person name="Basnayake C."/>
                <person name="Lamont P.J."/>
                <person name="Amor D.J."/>
                <person name="Jones K."/>
                <person name="Schilperoort J."/>
                <person name="Davis M.R."/>
                <person name="Laing N.G."/>
            </authorList>
            <dbReference type="PubMed" id="29781137"/>
            <dbReference type="DOI" id="10.1111/nmo.13371"/>
        </citation>
        <scope>VARIANTS VSCM1 HIS-40; LEU-148 AND CYS-257</scope>
        <scope>VARIANT MMIHS5 CYS-40</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2021" name="Clin. Genet." volume="99" first="430" last="436">
            <title>Novel ACTG2 variants disclose allelic heterogeneity and bi-allelic inheritance in pediatric chronic intestinal pseudo-obstruction.</title>
            <authorList>
                <person name="Matera I."/>
                <person name="Bordo D."/>
                <person name="Di Duca M."/>
                <person name="Lerone M."/>
                <person name="Santamaria G."/>
                <person name="Pongiglione M."/>
                <person name="Lezo A."/>
                <person name="Diamanti A."/>
                <person name="Spagnuolo M.I."/>
                <person name="Pini Prato A."/>
                <person name="Alberti D."/>
                <person name="Mattioli G."/>
                <person name="Gandullia P."/>
                <person name="Ceccherini I."/>
            </authorList>
            <dbReference type="PubMed" id="33294969"/>
            <dbReference type="DOI" id="10.1111/cge.13895"/>
        </citation>
        <scope>VARIANT MMIHS5 HIS-40</scope>
        <scope>VARIANTS VSCM1 GLN-41; PHE-143; ARG-149; ASP-196 AND CYS-257</scope>
        <scope>VARIANT TRP-336</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2021" name="Transl. Pediatr." volume="10" first="679" last="685">
            <title>Visceral myopathy diagnosed by a de novo ACTG2 mutation in a patient with chronic intestinal pseudo-obstruction-a case report.</title>
            <authorList>
                <person name="Xiong X."/>
                <person name="Li J."/>
                <person name="Liu C."/>
                <person name="Xu F."/>
            </authorList>
            <dbReference type="PubMed" id="33880338"/>
            <dbReference type="DOI" id="10.21037/tp-20-316"/>
        </citation>
        <scope>VARIANT VSCM1 ASP-196</scope>
    </reference>
    <comment type="function">
        <text>Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text>Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P63267-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P63267-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_045861"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">In the intestine, abundantly expressed in smooth muscle cells of muscularis mucosa and muscularis propria. Also detected in intestinal vascular smooth muscle cells.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Oxidation of Met-45 and Met-48 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, gamma-enteric smooth muscle, intermediate form</molecule>
        <text evidence="2">N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">Monomethylation at Lys-85 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14 15">Methylated at His-74 by SETD3.</text>
    </comment>
    <comment type="PTM">
        <text evidence="20 21">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-51 of one monomer and Glu-271 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
    <comment type="disease" evidence="6 8 9 10 11 13 16 17">
        <disease id="DI-04078">
            <name>Visceral myopathy 1</name>
            <acronym>VSCM1</acronym>
            <description>An autosomal dominant form of myopathic pseudo-obstruction characterized by impaired function of enteric smooth muscle cells, resulting in abnormal intestinal motility, severe abdominal pain, malnutrition, and even death. The disease shows inter- and intrafamilial variability. Most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and dependence on total parenteral nutrition and urinary catheterization.</description>
            <dbReference type="MIM" id="155310"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="7 8 10 11 12 13 16">
        <disease id="DI-06166">
            <name>Megacystis-microcolon-intestinal hypoperistalsis syndrome 5</name>
            <acronym>MMIHS5</acronym>
            <description>A form of megacystis-microcolon-intestinal hypoperistalsis syndrome, a congenital visceral myopathy primarily affecting females, and characterized by loss of smooth muscle contraction in the bladder and intestine. Affected individuals present at birth with functional obstruction of intestine, microcolon, dilation of bladder, and secondary hydronephrosis. The majority of cases have a fatal outcome due to malnutrition and sepsis, followed by multiorgan failure. MMIHS5 is an autosomal dominant form with significant inter- and intrafamilial variability.</description>
            <dbReference type="MIM" id="619431"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.-" evidence="5"/>
    <dbReference type="EMBL" id="X16940">
        <property type="protein sequence ID" value="CAA34814.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D00654">
        <property type="protein sequence ID" value="BAA00546.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK304523">
        <property type="protein sequence ID" value="BAG65327.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312955">
        <property type="protein sequence ID" value="BAG35794.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR536515">
        <property type="protein sequence ID" value="CAG38753.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR541794">
        <property type="protein sequence ID" value="CAG46593.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073046">
        <property type="protein sequence ID" value="AAX88909.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAW99713.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC012617">
        <property type="protein sequence ID" value="AAH12617.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC094877">
        <property type="protein sequence ID" value="AAH94877.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="P63267-2"/>
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    <dbReference type="PIR" id="A40261">
        <property type="entry name" value="A40261"/>
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    <dbReference type="RefSeq" id="NP_001186822.1">
        <molecule id="P63267-2"/>
        <property type="nucleotide sequence ID" value="NM_001199893.2"/>
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    <dbReference type="RefSeq" id="NP_001606.1">
        <molecule id="P63267-1"/>
        <property type="nucleotide sequence ID" value="NM_001615.4"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.71 A"/>
        <property type="chains" value="B/D=61-82"/>
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    <dbReference type="PDB" id="8V2O">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.45 A"/>
        <property type="chains" value="A/B/C/D/E=1-376"/>
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    <dbReference type="PDB" id="8V2Z">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.72 A"/>
        <property type="chains" value="A/B/C/D/E=1-376"/>
    </dbReference>
    <dbReference type="PDB" id="8V30">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.54 A"/>
        <property type="chains" value="A/B/C/D/E=1-376"/>
    </dbReference>
    <dbReference type="PDBsum" id="6JAT"/>
    <dbReference type="PDBsum" id="8V2O"/>
    <dbReference type="PDBsum" id="8V2Z"/>
    <dbReference type="PDBsum" id="8V30"/>
    <dbReference type="AlphaFoldDB" id="P63267"/>
    <dbReference type="EMDB" id="EMD-42918"/>
    <dbReference type="EMDB" id="EMD-42938"/>
    <dbReference type="EMDB" id="EMD-42939"/>
    <dbReference type="SMR" id="P63267"/>
    <dbReference type="BioGRID" id="106587">
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    <dbReference type="CORUM" id="P63267"/>
    <dbReference type="FunCoup" id="P63267">
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    </dbReference>
    <dbReference type="IntAct" id="P63267">
        <property type="interactions" value="27"/>
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    <dbReference type="MINT" id="P63267"/>
    <dbReference type="STRING" id="9606.ENSP00000386857"/>
    <dbReference type="GlyGen" id="P63267">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P63267"/>
    <dbReference type="MetOSite" id="P63267"/>
    <dbReference type="PhosphoSitePlus" id="P63267"/>
    <dbReference type="SwissPalm" id="P63267"/>
    <dbReference type="BioMuta" id="ACTG2"/>
    <dbReference type="DMDM" id="54036679"/>
    <dbReference type="OGP" id="P12718"/>
    <dbReference type="jPOST" id="P63267"/>
    <dbReference type="MassIVE" id="P63267"/>
    <dbReference type="PaxDb" id="9606-ENSP00000386857"/>
    <dbReference type="PeptideAtlas" id="P63267"/>
    <dbReference type="PRIDE" id="P63267"/>
    <dbReference type="ProteomicsDB" id="20231"/>
    <dbReference type="ProteomicsDB" id="57515">
        <molecule id="P63267-1"/>
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    <dbReference type="Pumba" id="P63267"/>
    <dbReference type="Antibodypedia" id="3526">
        <property type="antibodies" value="321 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="72"/>
    <dbReference type="Ensembl" id="ENST00000345517.8">
        <molecule id="P63267-1"/>
        <property type="protein sequence ID" value="ENSP00000295137.3"/>
        <property type="gene ID" value="ENSG00000163017.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409624.1">
        <molecule id="P63267-1"/>
        <property type="protein sequence ID" value="ENSP00000386857.1"/>
        <property type="gene ID" value="ENSG00000163017.15"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
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    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0514">Muscle protein</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000442949" description="Actin, gamma-enteric smooth muscle, intermediate form" evidence="2">
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            <begin position="2"/>
            <end position="376"/>
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            <position position="2"/>
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        <location>
            <position position="3"/>
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    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="45"/>
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    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="48"/>
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    </feature>
    <feature type="modified residue" description="Tele-methylhistidine" evidence="14 15">
        <location>
            <position position="74"/>
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    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-271); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-51); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_045861" description="In isoform 2." evidence="18">
        <location>
            <begin position="43"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071279" description="In MMIHS5; interferes with proper polymerization into thin filaments; dbSNP:rs587777385." evidence="8 10 13">
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        <variation>C</variation>
        <location>
            <position position="40"/>
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    </feature>
    <feature type="sequence variant" id="VAR_071280" description="In VSCM1 and MMIHS5; dbSNP:rs587777386." evidence="8 12 13 16">
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        <location>
            <position position="40"/>
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    </feature>
    <feature type="sequence variant" id="VAR_085866" description="In VSCM1; uncertain significance." evidence="16">
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        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071281" description="In VSCM1; dbSNP:rs864309490." evidence="8">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071282" description="In VSCM1; dbSNP:rs864309491." evidence="8">
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        <variation>G</variation>
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085867" description="In MMIHS5; interferes with proper polymerization into thin filaments." evidence="10">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071283" description="In VSCM1." evidence="8">
        <original>P</original>
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        <location>
            <position position="110"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071284" description="In MMIHS5; dbSNP:rs587777388." evidence="8">
        <original>Y</original>
        <variation>N</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085868" description="In VSCM1." evidence="16">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085869" description="In VSCM1." evidence="13">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071285" description="In VSCM1; interferes with proper polymerization into thin filaments; dbSNP:rs587777383." evidence="6 9 10">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085870" description="In VSCM1." evidence="16">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071286" description="In MMIHS5; interferes with proper polymerization into thin filaments leading to impaired contractility of the smooth muscle; dbSNP:rs78001248." evidence="7 8 10 11">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071287" description="In MMIHS5; interferes with proper polymerization into thin filaments; dbSNP:rs587777384." evidence="8 10">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071288" description="In MMIHS5; interferes with proper polymerization into thin filaments leading to impaired contractility of the smooth muscle; dbSNP:rs587777384." evidence="7 10 11">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085871" description="In VSCM1." evidence="11">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="195"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085872" description="In VSCM1." evidence="16 17">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071289" description="In VSCM1; dbSNP:rs864309492." evidence="8">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071290" description="In MMIHS5 and VSCM1; dbSNP:rs587777387." evidence="8 12 13 16">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="257"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085873" description="In MMIHS5." evidence="11">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="257"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085874" description="Found in a severe infantile gastrointestinal motility disorder; uncertain significance." evidence="16">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="336"/>
        </location>
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    <feature type="mutagenesis site" description="Abolished methylation by SETD3." evidence="15">
        <original>I</original>
        <variation>A</variation>
        <variation>D</variation>
        <variation>K</variation>
        <location>
            <position position="72"/>
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    <feature type="mutagenesis site" description="Slightly decreased methylation by SETD3." evidence="15">
        <original>I</original>
        <variation>L</variation>
        <variation>M</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAG38753." evidence="19" ref="4">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAG65327." evidence="19" ref="3">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="157"/>
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    <feature type="strand" evidence="24">
        <location>
            <begin position="9"/>
            <end position="13"/>
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    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="15"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="29"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="36"/>
            <end position="39"/>
        </location>
    </feature>
    <feature type="strand" evidence="25">
        <location>
            <begin position="46"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="57"/>
            <end position="61"/>
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    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="63"/>
            <end position="65"/>
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    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="66"/>
            <end position="69"/>
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    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="71"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="80"/>
            <end position="91"/>
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    </feature>
    <feature type="turn" evidence="24">
        <location>
            <begin position="92"/>
            <end position="95"/>
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    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="99"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="104"/>
            <end position="108"/>
        </location>
    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="114"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="131"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="helix" evidence="24">
        <location>
            <begin position="138"/>
            <end position="146"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="151"/>
            <end position="156"/>
        </location>
    </feature>
    <feature type="strand" evidence="24">
        <location>
            <begin position="161"/>
            <end position="167"/>
        </location>
    </feature>
    <feature type="helix" evidence="24">
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Lung</tissue>
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            </authorList>
            <dbReference type="PubMed" id="15057824"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Melanoma</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2022" name="Science" volume="377" first="1533" last="1537">
            <title>Actin maturation requires the ACTMAP/C19orf54 protease.</title>
            <authorList>
                <person name="Haahr P."/>
                <person name="Galli R.A."/>
                <person name="van den Hengel L.G."/>
                <person name="Bleijerveld O.B."/>
                <person name="Kazokaite-Adomaitiene J."/>
                <person name="Song J.Y."/>
                <person name="Kroese L.J."/>
                <person name="Krimpenfort P."/>
                <person name="Baltissen M.P."/>
                <person name="Vermeulen M."/>
                <person name="Ottenheijm C.A.C."/>
                <person name="Brummelkamp T.R."/>
            </authorList>
            <dbReference type="PubMed" id="36173861"/>
            <dbReference type="DOI" id="10.1126/science.abq5082"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH PFN1 AND PFN2 ISOFORMS IIA AND IIB</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF CYS-132</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3">Actin maturation protease that specifically mediates the cleavage of immature acetylated N-terminal actin, thereby contributing to actin maturation (PubMed:36173861). Cleaves N-terminal acetylated methionine of immature cytoplasmic beta- and gamma-actins ACTB and ACTG1 after translation (PubMed:36173861). Cleaves N-terminal acetylated cysteine of muscle alpha-actins ACTA1, ACTC1 and ACTA2 after canonical removal of N-terminal methionine (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <molecule>Actin maturation protease</molecule>
        <reaction evidence="3">
            <text>N-terminal N(alpha)-acetyl-L-methionyl-L-aspartyl-[protein] + H2O = N-terminal L-aspartyl-[protein] + N-acetyl-L-methionine</text>
            <dbReference type="Rhea" id="RHEA:74571"/>
            <dbReference type="Rhea" id="RHEA-COMP:12669"/>
            <dbReference type="Rhea" id="RHEA-COMP:12693"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:64720"/>
            <dbReference type="ChEBI" id="CHEBI:71670"/>
            <dbReference type="ChEBI" id="CHEBI:133063"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:74572"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Actin maturation protease</molecule>
        <reaction evidence="3">
            <text>N-terminal N(alpha)-acetyl-L-methionyl-L-glutamyl-[protein] + H2O = N-terminal L-glutamyl-[protein] + N-acetyl-L-methionine</text>
            <dbReference type="Rhea" id="RHEA:74575"/>
            <dbReference type="Rhea" id="RHEA-COMP:12668"/>
            <dbReference type="Rhea" id="RHEA-COMP:12697"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:64721"/>
            <dbReference type="ChEBI" id="CHEBI:71670"/>
            <dbReference type="ChEBI" id="CHEBI:133360"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:74576"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Actin maturation protease</molecule>
        <reaction evidence="1">
            <text>N-terminal N(alpha)-acetyl-L-cysteinyl-L-aspartyl-[protein] + H2O = N-terminal L-aspartyl-[protein] + N-acetyl-L-cysteine</text>
            <dbReference type="Rhea" id="RHEA:74579"/>
            <dbReference type="Rhea" id="RHEA-COMP:12669"/>
            <dbReference type="Rhea" id="RHEA-COMP:18395"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:64720"/>
            <dbReference type="ChEBI" id="CHEBI:78236"/>
            <dbReference type="ChEBI" id="CHEBI:193599"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:74580"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Actin maturation protease</molecule>
        <reaction evidence="1">
            <text>N-terminal N(alpha)-acetyl-L-cysteinyl-L-glutamyl-[protein] + H2O = N-terminal L-glutamyl-[protein] + N-acetyl-L-cysteine</text>
            <dbReference type="Rhea" id="RHEA:74583"/>
            <dbReference type="Rhea" id="RHEA-COMP:12668"/>
            <dbReference type="Rhea" id="RHEA-COMP:18396"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:64721"/>
            <dbReference type="ChEBI" id="CHEBI:78236"/>
            <dbReference type="ChEBI" id="CHEBI:193601"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:74584"/>
        </physiologicalReaction>
    </comment>
    <comment type="subunit">
        <text evidence="3">Interacts (via N-terminus) with PFN2 isoforms IIa and IIb; the interactions may facilitate efficient cleavage of the acetylated N-terminus of immature actin (PubMed:36173861). Interacts with PFN1 (PubMed:36173861).</text>
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            <label>A1CF</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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        <interactant intactId="EBI-11096309">
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        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-2824328">
            <id>O95947</id>
            <label>TBX6</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-954089">
            <id>O15273</id>
            <label>TCAP</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-11746252">
            <id>Q9NQB0-10</id>
            <label>TCF7L2</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-10239812">
            <id>Q96M29</id>
            <label>TEKT5</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-357061">
            <id>Q92734</id>
            <label>TFG</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-11741437">
            <id>Q08117-2</id>
            <label>TLE5</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-3939165">
            <id>O43711</id>
            <label>TLX3</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-74615">
            <id>Q9H0E2</id>
            <label>TOLLIP</label>
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    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-3650647">
            <id>Q9BUZ4</id>
            <label>TRAF4</label>
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    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-358993">
            <id>Q15645</id>
            <label>TRIP13</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-2349743">
            <id>Q12815</id>
            <label>TROAP</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-2107455">
            <id>Q08AM6</id>
            <label>VAC14</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-10191303">
            <id>O95231</id>
            <label>VENTX</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
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        <interactant intactId="EBI-12032042">
            <id>Q64LD2-2</id>
            <label>WDR25</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-12040603">
            <id>Q9NZC7-5</id>
            <label>WWOX</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-14104088">
            <id>Q53FD0-2</id>
            <label>ZC2HC1C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-742550">
            <id>Q96K80</id>
            <label>ZC3H10</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-746595">
            <id>Q96E35</id>
            <label>ZMYND19</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11976299">
            <id>Q5BKX5-3</id>
        </interactant>
        <interactant intactId="EBI-750454">
            <id>Q96EJ4</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5BKX5-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5BKX5-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_039884 VSP_039885"/>
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        <isoform>
            <id>Q5BKX5-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_039884"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="3">The N-terminal proline-rich disordered region contributes to the interaction with PFN2.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ACTMAP family.</text>
    </comment>
    <dbReference type="EC" id="3.4.11.-" evidence="3"/>
    <dbReference type="EMBL" id="AK298068">
        <property type="protein sequence ID" value="BAG60359.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC020945">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC020262">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC090894">
        <property type="protein sequence ID" value="AAH90894.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS12564.2">
        <molecule id="Q5BKX5-1"/>
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    <dbReference type="RefSeq" id="NP_001340734.1">
        <molecule id="Q5BKX5-3"/>
        <property type="nucleotide sequence ID" value="NM_001353805.2"/>
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    <dbReference type="RefSeq" id="NP_940878.3">
        <molecule id="Q5BKX5-1"/>
        <property type="nucleotide sequence ID" value="NM_198476.5"/>
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    <dbReference type="AlphaFoldDB" id="Q5BKX5"/>
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        <property type="interactions" value="82"/>
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    <dbReference type="FunCoup" id="Q5BKX5">
        <property type="interactions" value="94"/>
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    <dbReference type="IntAct" id="Q5BKX5">
        <property type="interactions" value="70"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000367564"/>
    <dbReference type="GlyGen" id="Q5BKX5">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5BKX5"/>
    <dbReference type="PhosphoSitePlus" id="Q5BKX5"/>
    <dbReference type="BioMuta" id="C19orf54"/>
    <dbReference type="DMDM" id="308153429"/>
    <dbReference type="jPOST" id="Q5BKX5"/>
    <dbReference type="MassIVE" id="Q5BKX5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000367564"/>
    <dbReference type="PeptideAtlas" id="Q5BKX5"/>
    <dbReference type="ProteomicsDB" id="62702">
        <molecule id="Q5BKX5-1"/>
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    <dbReference type="ProteomicsDB" id="62703">
        <molecule id="Q5BKX5-2"/>
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    <dbReference type="ProteomicsDB" id="62704">
        <molecule id="Q5BKX5-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q5BKX5"/>
    <dbReference type="Antibodypedia" id="45214">
        <property type="antibodies" value="62 antibodies from 14 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="284325"/>
    <dbReference type="Ensembl" id="ENST00000378313.7">
        <molecule id="Q5BKX5-1"/>
        <property type="protein sequence ID" value="ENSP00000367564.2"/>
        <property type="gene ID" value="ENSG00000188493.16"/>
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    <dbReference type="GeneID" id="284325"/>
    <dbReference type="KEGG" id="hsa:284325"/>
    <dbReference type="MANE-Select" id="ENST00000378313.7">
        <property type="protein sequence ID" value="ENSP00000367564.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_198476.5"/>
        <property type="RefSeq protein sequence ID" value="NP_940878.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002oou.1">
        <molecule id="Q5BKX5-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24758"/>
    <dbReference type="ClinPGx" id="PA147358417"/>
    <dbReference type="CTD" id="284325"/>
    <dbReference type="DisGeNET" id="284325"/>
    <dbReference type="GeneCards" id="ACTMAP"/>
    <dbReference type="HGNC" id="HGNC:24758">
        <property type="gene designation" value="ACTMAP"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000188493">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="620093">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000188493"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000188493"/>
    <dbReference type="eggNOG" id="ENOG502QQQD">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012368"/>
    <dbReference type="HOGENOM" id="CLU_077492_1_0_1"/>
    <dbReference type="InParanoid" id="Q5BKX5"/>
    <dbReference type="OMA" id="QLWDYEQ"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5BKX5"/>
    <dbReference type="PathwayCommons" id="Q5BKX5"/>
    <dbReference type="SignaLink" id="Q5BKX5"/>
    <dbReference type="Agora" id="ENSG00000188493"/>
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        <property type="hits" value="15 hits in 1126 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="284325"/>
    <dbReference type="Pharos" id="Q5BKX5">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5BKX5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
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        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000188493">
        <property type="expression patterns" value="Expressed in pancreatic ductal cell and 186 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5BKX5">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070005">
        <property type="term" value="F:cysteine-type aminopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004239">
        <property type="term" value="F:initiator methionyl aminopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016485">
        <property type="term" value="P:protein processing"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR040043">
        <property type="entry name" value="ACTMAP"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR28631:SF1">
        <property type="entry name" value="ACTIN MATURATION PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR28631">
        <property type="entry name" value="UPF0692 PROTEIN C19ORF54"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF21646">
        <property type="entry name" value="ACTMAP-like_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0031">Aminopeptidase</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000297659" description="Actin maturation protease">
        <location>
            <begin position="1"/>
            <end position="351"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="region of interest" description="Peptidase C39-like" evidence="6">
        <location>
            <begin position="124"/>
            <end position="244"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="2">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="2">
        <location>
            <begin position="36"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="2">
        <location>
            <begin position="51"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="active site" evidence="8">
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="10 11 12">
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039884" description="In isoform 2 and isoform 3." evidence="4 5">
        <original>MTSPCSPPLKPPISPPKTPVPQASSIPSPPLPPSPLDFSALPSPPWSQQTPVPPPLPLPPPPAATGPAPRHVFGLEKSQLLKEAFDKAGPVPKGREDVKRLLKLHKDRFRGDLRWILFCADLPSLIQEGPQCGLVALWMAGTLLSPPSGVPLERLIRVATERGYTAQGEMFSVADMGRLAQEVLGCQAKLLSGGLGGPNRDLVLQHLVTGHPLLIP</original>
        <variation>MRAGGLVDGRYSPVAPQWRPPGETHTGGHGKRLHGPGRDVLSTS</variation>
        <location>
            <begin position="1"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039885" description="In isoform 2." evidence="4">
        <original>VRESNLQLTDFSPSRATDGRVYVVPVGGVRAGLCGQALLLTPQDCSH</original>
        <variation>GPPLSSH</variation>
        <location>
            <begin position="305"/>
            <end position="351"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Catalytically inactive, disrupts N-terminal cleavage of immature actin." evidence="3">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="132"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BC020262." evidence="7" ref="3">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="J3QPC3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="36173861"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="36173861"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000305" key="8">
        <source>
            <dbReference type="PubMed" id="36173861"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:24758"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="351" mass="37779" checksum="B1CE78515DC3A553" modified="2010-10-05" version="2">MTSPCSPPLKPPISPPKTPVPQASSIPSPPLPPSPLDFSALPSPPWSQQTPVPPPLPLPPPPAATGPAPRHVFGLEKSQLLKEAFDKAGPVPKGREDVKRLLKLHKDRFRGDLRWILFCADLPSLIQEGPQCGLVALWMAGTLLSPPSGVPLERLIRVATERGYTAQGEMFSVADMGRLAQEVLGCQAKLLSGGLGGPNRDLVLQHLVTGHPLLIPYDEDFNHEPCQRKGHKAHWAVSAGVLLGVRAVPSLGYTEDPELPGLFHPVLGTPCQPPSLPEEGSPGAVYLLSKQGKSWHYQLWDYDQVRESNLQLTDFSPSRATDGRVYVVPVGGVRAGLCGQALLLTPQDCSH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-31" modified="2026-01-28" version="146" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TDG2</accession>
    <accession>Q6X7C1</accession>
    <accession>Q96L10</accession>
    <name>ACTT1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="5">Actin-related protein T1</fullName>
            <shortName evidence="3 4">ARP-T1</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="7" type="primary">ACTRT1</name>
        <name evidence="4" type="synonym">ARPT1</name>
        <name type="ORF">HSD27</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Exp. Cell Res." volume="279" first="177" last="187">
            <title>Novel actin-related proteins Arp-T1 and Arp-T2 as components of the cytoskeletal calyx of the mammalian sperm head.</title>
            <authorList>
                <person name="Heid H.W."/>
                <person name="Figge U."/>
                <person name="Winter S."/>
                <person name="Kuhn C."/>
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            <dbReference type="PubMed" id="12243744"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <dbReference type="PubMed" id="15772651"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANTS LYS-124 AND 217-GLU--PHE-376 DEL</scope>
        <scope>INVOLVEMENT IN DISEASE</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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    <comment type="function">
        <text evidence="1">Negatively regulates the Hedgehog (SHH) signaling. Binds to the promoter of the SHH signaling mediator, GLI1, and inhibits its expression.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
            <location evidence="6">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasmic vesicle</location>
            <location evidence="2">Secretory vesicle</location>
            <location evidence="2">Acrosome</location>
        </subcellularLocation>
        <text evidence="1">Both detected in the nucleus and cytoplasm, localizes to the nucleus where it binds chromatin upon stimulation of the Hedgehog pathway.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="1">In skin, expressed in the basal, spinous and granular layers of the epidermis. Also expressed in hair follicles, sebaceaous glands, eccrine sweat glands and semen.</text>
    </comment>
    <comment type="disease">
        <text evidence="1">Mutations and insertions in the coding sequence or in regulatory non-coding elements of this gene may be associated with Bazex syndrome; a cancer-prone genodermatosis with an X-linked dominant inheritance pattern.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AF440739">
        <property type="protein sequence ID" value="AAM00432.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY251532">
        <property type="protein sequence ID" value="AAP20055.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z74696">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014597">
        <property type="protein sequence ID" value="AAH14597.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14611.1"/>
    <dbReference type="RefSeq" id="NP_612146.1">
        <property type="nucleotide sequence ID" value="NM_138289.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TDG2"/>
    <dbReference type="SMR" id="Q8TDG2"/>
    <dbReference type="BioGRID" id="126584">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TDG2">
        <property type="interactions" value="94"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TDG2">
        <property type="interactions" value="16"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000360165"/>
    <dbReference type="GlyGen" id="Q8TDG2">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8TDG2"/>
    <dbReference type="PhosphoSitePlus" id="Q8TDG2"/>
    <dbReference type="BioMuta" id="ACTRT1"/>
    <dbReference type="DMDM" id="118586151"/>
    <dbReference type="jPOST" id="Q8TDG2"/>
    <dbReference type="MassIVE" id="Q8TDG2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000360165"/>
    <dbReference type="PeptideAtlas" id="Q8TDG2"/>
    <dbReference type="ProteomicsDB" id="74282"/>
    <dbReference type="Antibodypedia" id="511">
        <property type="antibodies" value="114 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="139741"/>
    <dbReference type="Ensembl" id="ENST00000371124.5">
        <property type="protein sequence ID" value="ENSP00000360165.3"/>
        <property type="gene ID" value="ENSG00000123165.9"/>
    </dbReference>
    <dbReference type="GeneID" id="139741"/>
    <dbReference type="KEGG" id="hsa:139741"/>
    <dbReference type="MANE-Select" id="ENST00000371124.5">
        <property type="protein sequence ID" value="ENSP00000360165.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_138289.4"/>
        <property type="RefSeq protein sequence ID" value="NP_612146.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004eum.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24027"/>
    <dbReference type="ClinPGx" id="PA142672646"/>
    <dbReference type="CTD" id="139741"/>
    <dbReference type="DisGeNET" id="139741"/>
    <dbReference type="GeneCards" id="ACTRT1"/>
    <dbReference type="HGNC" id="HGNC:24027">
        <property type="gene designation" value="ACTRT1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000123165">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="300487">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000123165"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000123165"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162451"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_2_1"/>
    <dbReference type="InParanoid" id="Q8TDG2"/>
    <dbReference type="OMA" id="RWFSAWI"/>
    <dbReference type="OrthoDB" id="10053773at2759"/>
    <dbReference type="PAN-GO" id="Q8TDG2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8TDG2"/>
    <dbReference type="PathwayCommons" id="Q8TDG2"/>
    <dbReference type="SignaLink" id="Q8TDG2"/>
    <dbReference type="Agora" id="ENSG00000123165"/>
    <dbReference type="BioGRID-ORCS" id="139741">
        <property type="hits" value="9 hits in 763 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="139741"/>
    <dbReference type="Pharos" id="Q8TDG2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8TDG2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TDG2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000123165">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 2 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001669">
        <property type="term" value="C:acrosomal vesicle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003682">
        <property type="term" value="F:chromatin binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0045892">
        <property type="term" value="P:negative regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006355">
        <property type="term" value="P:regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008589">
        <property type="term" value="P:regulation of smoothened signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd13397">
        <property type="entry name" value="ASKHA_NBD_actin_Arp-T1-3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000018">
        <property type="entry name" value="Actin-like protein (Centractin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="chain" id="PRO_0000255656" description="Actin-related protein T1">
        <location>
            <begin position="1"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080907" description="Found in a patient with Bazex syndrome; uncertain significance; dbSNP:rs1927774523." evidence="1">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080908" description="Found in a patient with Bazex syndrome; uncertain significance." evidence="1">
        <location>
            <begin position="217"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAP20055." evidence="5" ref="2">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAP20055." evidence="5" ref="2">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00432." evidence="5" ref="1">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="28869610"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="31429579"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="12243744"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="28869610"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0000305" key="6">
        <source>
            <dbReference type="PubMed" id="28869610"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:24027"/>
        </source>
    </evidence>
    <sequence length="376" mass="41696" checksum="4E633B7869017508" modified="2006-10-31" version="2">MFNPHALDVPAVIFDNGSGLCKAGLSGEIGPRHVISSVLGHCKFNVPLARLNQKYFVGQEALYKYEALHLHYPIERGLVTGWDDMEKLWKHLFERELGVKPSQQPVLMTEPSLNPREIREKLAEMMFETFSVPGFYLSNHAVAALYASACVTGLVVDSGDGVTCTVPIFEGYSLPHAVTKLCMAGRDITEHLTRLLFASGFNFPCILNKAVVNNIKEKLCYIALEPEKELRKSRGEVLGAYRLPDGHVIHFGDELYQVPEVLFAPDQLGIHSPGLSKMVSSSIMKCDTDIQNKLYADIVLSGGTTLLPGLEERLMKEVEQLASKGTPIKITASPDRCFSAWIGASIMTSMSSFKQMWVTSADFKEYGTSVVQRRCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>P63261</accession>
    <accession>A8K7C2</accession>
    <accession>P02571</accession>
    <accession>P14104</accession>
    <accession>P99022</accession>
    <accession>Q5U032</accession>
    <accession>Q96E67</accession>
    <name>ACTG_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin, cytoplasmic 2</fullName>
            <ecNumber evidence="2">3.6.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Gamma-actin</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Actin, cytoplasmic 2, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">ACTG1</name>
        <name type="synonym">ACTG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>B-cell</tissue>
            <tissue>Eye</tissue>
            <tissue>Lung</tissue>
            <tissue>Ovary</tissue>
            <tissue>Placenta</tissue>
            <tissue>Skin</tissue>
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        <scope>CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION)</scope>
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        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND GLU-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
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        <scope>DEMETHYLATION BY ALKBH4</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT GLU-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION)</scope>
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        <scope>ACETYLATION AT GLU-2</scope>
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            <dbReference type="PubMed" id="29581253"/>
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        <scope>FUNCTION</scope>
        <scope>ACETYLATION AT GLU-2</scope>
    </reference>
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        <scope>METHYLATION AT HIS-73</scope>
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            <dbReference type="PubMed" id="36173861"/>
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        <scope>PROTEOLYTIC CLEAVAGE BY ACTMAP</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT MET-1</scope>
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            <dbReference type="PubMed" id="13680526"/>
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        </citation>
        <scope>VARIANTS DFNA20 ILE-89; MET-118; LEU-264 AND ALA-332</scope>
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            <dbReference type="PubMed" id="14684684"/>
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        <scope>VARIANT DFNA20 ILE-278</scope>
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        <scope>VARIANT DFNA20 ALA-370</scope>
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        <scope>VARIANT DFNA20 VAL-122</scope>
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        <scope>VARIANTS DFNA20 ASN-118 AND LYS-241</scope>
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            <dbReference type="PubMed" id="22366783"/>
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        <scope>VARIANTS BRWS2 ILE-120; VAL-135; PHE-155; LYS-203; TRP-254 AND TRP-256</scope>
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            <dbReference type="DOI" id="10.1186/1750-1172-7-60"/>
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        <scope>VARIANT DFNA20 HIS-187</scope>
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            <dbReference type="PubMed" id="25388789"/>
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        <scope>VARIANT DFNA20 LYS-316</scope>
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                <consortium name="UK10K"/>
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            <dbReference type="PubMed" id="28493397"/>
            <dbReference type="DOI" id="10.1002/humu.23246"/>
        </citation>
        <scope>VARIANT LEU-70</scope>
        <scope>CHARACTERIZATION OF VARIANT LEU-70</scope>
        <scope>INTERACTION WITH CAPZB; TWF1; COFILIN AND PROFILIN</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 24">Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="13">Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin (PubMed:28493397).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-353944">
            <id>P60709</id>
            <label>ACTB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-351292">
            <id>P63261</id>
            <label>ACTG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-1051165">
            <id>P40123</id>
            <label>CAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>13</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-3943153">
            <id>O60826</id>
            <label>CCDC22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-295634">
            <id>Q16543</id>
            <label>CDC37</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-352733">
            <id>P23528</id>
            <label>CFL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-10201319">
            <id>Q549N0</id>
            <label>CFL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-351218">
            <id>Q9Y281</id>
            <label>CFL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>10</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-745191">
            <id>P60981</id>
            <label>DSTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
        </interactant>
        <interactant intactId="EBI-2339219">
            <id>Q08426</id>
            <label>EHHADH</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
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            <id>P42858</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P63261</id>
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    <comment type="interaction">
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
        <interactant intactId="EBI-351292">
            <id>P63261</id>
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            <id>Q96HA8</id>
            <label>NTAQ1</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P63261</id>
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    <comment type="interaction">
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            <id>P63261</id>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P63261</id>
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            <id>P60010</id>
            <label>ACT1</label>
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    <comment type="interaction">
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            <label>AIP1</label>
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    <comment type="interaction">
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            <id>P63261</id>
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    <comment type="interaction">
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        <subcellularLocation>
            <location evidence="13">Cytoplasm</location>
            <location evidence="13">Cytoskeleton</location>
        </subcellularLocation>
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    <comment type="PTM">
        <text evidence="1">Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, cytoplasmic 2</molecule>
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    <comment type="PTM">
        <molecule>Actin, cytoplasmic 2, N-terminally processed</molecule>
        <text evidence="14">N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins (PubMed:29581253). In contrast, filament nucleation by the Arp2/3 complex is not affected (PubMed:29581253).</text>
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    <comment type="PTM">
        <text evidence="16">Methylated at His-73 by SETD3.</text>
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    <comment type="PTM">
        <text evidence="22 23">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
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        <disease id="DI-00846">
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            <acronym>DFNA20</acronym>
            <description>A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="9">
        <disease id="DI-03417">
            <name>Baraitser-Winter syndrome 2</name>
            <acronym>BRWS2</acronym>
            <description>A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease">
        <text evidence="13">Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="21">Belongs to the actin family.</text>
    </comment>
    <comment type="online information" name="Mendelian genes actin, gamma 1 (ACTG1)">
        <link uri="https://databases.lovd.nl/shared/genes/ACTG1"/>
        <text>Leiden Open Variation Database (LOVD)</text>
    </comment>
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        <property type="protein sequence ID" value="CAA27723.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAA51579.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="BAF84626.1"/>
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        <property type="molecule type" value="mRNA"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <reference key="1">
        <citation type="journal article" date="2000" name="Oncogene" volume="19" first="380" last="386">
            <title>The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells.</title>
            <authorList>
                <person name="Nikolopoulos S.N."/>
                <person name="Spengler B.A."/>
                <person name="Kisselbach K."/>
                <person name="Evans A.E."/>
                <person name="Biedler J.L."/>
                <person name="Ross R.A."/>
            </authorList>
            <dbReference type="PubMed" id="10656685"/>
            <dbReference type="DOI" id="10.1038/sj.onc.1203310"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2012" name="Tsitologiia" volume="54" first="25" last="32">
            <title>Novel splicing isoform of actin-binding protein alpha-actinin 4 in epidermoid carcinoma cells A431.</title>
            <authorList>
                <person name="Aksenova V.I.U."/>
                <person name="Khotin M.G."/>
                <person name="Turoverova L.V."/>
                <person name="Iudintseva N.M."/>
                <person name="Magnusson K.E."/>
                <person name="Pinaev G.P."/>
                <person name="Tentler D.G."/>
            </authorList>
            <dbReference type="PubMed" id="22567897"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ACTN4ISO)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2006-03" db="EMBL/GenBank/DDBJ databases">
            <title>Actinin alpha4, an actin binding protein, is a transcriptional coactivator that antagonizes class II HDAC activity.</title>
            <authorList>
                <person name="Chakraborty S."/>
                <person name="Cheng X."/>
                <person name="Lam M."/>
                <person name="Reineke E.L."/>
                <person name="Li X."/>
                <person name="Liu Y."/>
                <person name="Gao C."/>
                <person name="Khurana S."/>
                <person name="Kao H.-Y."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nature" volume="428" first="529" last="535">
            <title>The DNA sequence and biology of human chromosome 19.</title>
            <authorList>
                <person name="Grimwood J."/>
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                <person name="Schmutz J."/>
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                <person name="Couronne O."/>
                <person name="Tran-Gyamfi M."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224 (ISOFORM 1)</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>INTERACTION WITH MAGI1</scope>
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        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE CART COMPLEX</scope>
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        <scope>IDENTIFICATION IN A MRNP GRANULE COMPLEX</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-114; LYS-592 AND LYS-625</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH IGSF8</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-249</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="33228246"/>
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        <scope>INTERACTION WITH SEPTIN14</scope>
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            <title>Solution structure of the third spectrin repeat of alpha-actinin-4.</title>
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        <scope>STRUCTURE BY NMR OF 519-645</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 734-757 IN COMPLEX WITH VCL</scope>
        <scope>INTERACTION WITH VCL</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 47-271</scope>
        <scope>CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262</scope>
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        <scope>CHARACTERIZATION OF VARIANTS FSGS1 GLU-255; ILE-259 AND PRO-262</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH PPARG AND RARA</scope>
        <scope>MUTAGENESIS OF 87-LEU-LEU-88</scope>
        <scope>DOMAIN</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>VARIANT FSGS1 PHE-262</scope>
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        <scope>VARIANTS FSGS1 THR-427 AND ASP-748</scope>
        <scope>VARIANTS VAL-784; ARG-786; LEU-787; SER-787; TYR-793; ASP-798 AND MET-801</scope>
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        <scope>VARIANTS FSGS1 ARG-59; GLN-72; LEU-153; GLU-255; ILE-259 AND PRO-262</scope>
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    <comment type="function">
        <text evidence="2 10 15 17 27">F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3 9 10 11 12 15 17 21">Homodimer; antiparallel. Binds TRIM3 at the N-terminus (PubMed:15772161). Interacts with MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation (By similarity). Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (PubMed:15772161). Interacts with MAGI1 (PubMed:12042308). Interacts with PDLIM2 (By similarity). Interacts with PPARG and RARA (PubMed:22351778). Binds to VCL; this interaction triggers VCL conformational changes (PubMed:15988023). Interacts with SEPTIN14 (PubMed:33228246). Interacts with IGSF8 (PubMed:22689882).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-2880652">
            <id>Q08043</id>
            <label>ACTN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-10174327">
            <id>A8K571</id>
            <label>BMP7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-725606">
            <id>Q9NWQ9</id>
            <label>C14orf119</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-491549">
            <id>P35222</id>
            <label>CTNNB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-297509">
            <id>P46940</id>
            <label>IQGAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-11023122">
            <id>O60294</id>
            <label>LCMT2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-739832">
            <id>Q8TBB1</id>
            <label>LNX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-748397">
            <id>P50222</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-2555563">
            <id>Q8IY33</id>
            <label>MICALL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-746712">
            <id>Q9NPC6</id>
            <label>MYOZ2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-724897">
            <id>O00151</id>
            <label>PDLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-12037893">
            <id>O94875-10</id>
            <label>SORBS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-79553">
            <id>Q07157</id>
            <label>TJP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-10175581">
            <id>B2R8Y4</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-2547640">
            <id>P03466</id>
            <label>NP</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351526">
            <id>O43707</id>
        </interactant>
        <interactant intactId="EBI-9512099">
            <id>Q5L4H4</id>
            <label>NP</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-15971664">
            <id>O43707-1</id>
        </interactant>
        <interactant intactId="EBI-413374">
            <id>P10276</id>
            <label>RARA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="15 22">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15 22">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="22">Cytoplasm</location>
            <location evidence="22">Cytoskeleton</location>
            <location evidence="22">Stress fiber</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Perinuclear region</location>
        </subcellularLocation>
        <text evidence="2 12 22">Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Expressed in the perinuclear rim and manchette structure in early elongating spermatids during spermiogenesis (By similarity). Nuclear translocation can be induced by the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively localized in the nucleus in a limited number of cell lines (breast cancer cell line MCF-7, oral floor cancer IMC-2, and bladder cancer KU-7).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O43707-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O43707-2</id>
            <name>ACTN4ISO</name>
            <sequence type="described" ref="VSP_047733"/>
        </isoform>
        <isoform>
            <id>O43707-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_053401"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="22">Widely expressed.</text>
    </comment>
    <comment type="domain">
        <text evidence="15">Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.</text>
    </comment>
    <comment type="disease" evidence="8 13 14 15 18 19 20">
        <disease id="DI-01620">
            <name>Focal segmental glomerulosclerosis 1</name>
            <acronym>FSGS1</acronym>
            <description>A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.</description>
            <dbReference type="MIM" id="603278"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform ACTN4ISO</molecule>
        <text evidence="16">Does not colocalize with actin cytoskeleton structures.</text>
    </comment>
    <comment type="similarity">
        <text evidence="26">Belongs to the alpha-actinin family.</text>
    </comment>
    <comment type="sequence caution" evidence="26">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAC17470" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="26">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA24447" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="U48734">
        <property type="protein sequence ID" value="AAC17470.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="GU987085">
        <property type="protein sequence ID" value="ADG03678.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ431186">
        <property type="protein sequence ID" value="ABD96103.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008649">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC022144">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC005033">
        <property type="protein sequence ID" value="AAH05033.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL047603">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AU118403">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D89980">
        <property type="protein sequence ID" value="BAA24447.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS12518.1">
        <molecule id="O43707-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004915.2">
        <molecule id="O43707-1"/>
        <property type="nucleotide sequence ID" value="NM_004924.5"/>
    </dbReference>
    <dbReference type="PDB" id="1WLX">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=519-645"/>
    </dbReference>
    <dbReference type="PDB" id="1YDI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="B=734-757"/>
    </dbReference>
    <dbReference type="PDB" id="2R0O">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=47-271"/>
    </dbReference>
    <dbReference type="PDB" id="6O31">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.51 A"/>
        <property type="chains" value="A=47-271"/>
    </dbReference>
    <dbReference type="PDB" id="6OA6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.37 A"/>
        <property type="chains" value="A=47-271"/>
    </dbReference>
    <dbReference type="PDBsum" id="1WLX"/>
    <dbReference type="PDBsum" id="1YDI"/>
    <dbReference type="PDBsum" id="2R0O"/>
    <dbReference type="PDBsum" id="6O31"/>
    <dbReference type="PDBsum" id="6OA6"/>
    <dbReference type="AlphaFoldDB" id="O43707"/>
    <dbReference type="BMRB" id="O43707"/>
    <dbReference type="SMR" id="O43707"/>
    <dbReference type="BioGRID" id="106596">
        <property type="interactions" value="424"/>
    </dbReference>
    <dbReference type="CORUM" id="O43707"/>
    <dbReference type="DIP" id="DIP-33179N"/>
    <dbReference type="FunCoup" id="O43707">
        <property type="interactions" value="1162"/>
    </dbReference>
    <dbReference type="IntAct" id="O43707">
        <property type="interactions" value="162"/>
    </dbReference>
    <dbReference type="MINT" id="O43707"/>
    <dbReference type="STRING" id="9606.ENSP00000252699"/>
    <dbReference type="CarbonylDB" id="O43707"/>
    <dbReference type="GlyGen" id="O43707">
        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O43707"/>
    <dbReference type="MetOSite" id="O43707"/>
    <dbReference type="PhosphoSitePlus" id="O43707"/>
    <dbReference type="SwissPalm" id="O43707"/>
    <dbReference type="BioMuta" id="ACTN4"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="O43707"/>
    <dbReference type="CPTAC" id="CPTAC-7"/>
    <dbReference type="CPTAC" id="CPTAC-8"/>
    <dbReference type="jPOST" id="O43707"/>
    <dbReference type="MassIVE" id="O43707"/>
    <dbReference type="PaxDb" id="9606-ENSP00000252699"/>
    <dbReference type="PeptideAtlas" id="O43707"/>
    <dbReference type="PRIDE" id="O43707"/>
    <dbReference type="ProteomicsDB" id="12838"/>
    <dbReference type="ProteomicsDB" id="49125">
        <molecule id="O43707-1"/>
    </dbReference>
    <dbReference type="Pumba" id="O43707"/>
    <dbReference type="Antibodypedia" id="974">
        <property type="antibodies" value="492 antibodies from 45 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="81"/>
    <dbReference type="Ensembl" id="ENST00000252699.7">
        <molecule id="O43707-1"/>
        <property type="protein sequence ID" value="ENSP00000252699.2"/>
        <property type="gene ID" value="ENSG00000130402.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000390009.7">
        <molecule id="O43707-2"/>
        <property type="protein sequence ID" value="ENSP00000439497.1"/>
        <property type="gene ID" value="ENSG00000130402.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000634692.1">
        <molecule id="O43707-2"/>
        <property type="protein sequence ID" value="ENSP00000488962.1"/>
        <property type="gene ID" value="ENSG00000282844.2"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000634960.2">
        <molecule id="O43707-1"/>
        <property type="protein sequence ID" value="ENSP00000489220.1"/>
        <property type="gene ID" value="ENSG00000282844.2"/>
    </dbReference>
    <dbReference type="GeneID" id="81"/>
    <dbReference type="KEGG" id="hsa:81"/>
    <dbReference type="MANE-Select" id="ENST00000252699.7">
        <property type="protein sequence ID" value="ENSP00000252699.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004924.6"/>
        <property type="RefSeq protein sequence ID" value="NP_004915.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002oja.3">
        <molecule id="O43707-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:166"/>
    <dbReference type="ClinPGx" id="PA23"/>
    <dbReference type="CTD" id="81"/>
    <dbReference type="DisGeNET" id="81"/>
    <dbReference type="GeneCards" id="ACTN4"/>
    <dbReference type="HGNC" id="HGNC:166">
        <property type="gene designation" value="ACTN4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000130402">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACTN4"/>
    <dbReference type="MIM" id="603278">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="604638">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000130402"/>
    <dbReference type="Orphanet" id="656">
        <property type="disease" value="Hereditary steroid-resistant nephrotic syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000130402"/>
    <dbReference type="eggNOG" id="KOG0035">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159343"/>
    <dbReference type="HOGENOM" id="CLU_005217_1_1_1"/>
    <dbReference type="InParanoid" id="O43707"/>
    <dbReference type="OMA" id="KIADYNH"/>
    <dbReference type="OrthoDB" id="10017054at2759"/>
    <dbReference type="PAN-GO" id="O43707">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O43707"/>
    <dbReference type="PathwayCommons" id="O43707"/>
    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-373753">
        <property type="pathway name" value="Nephrin family interactions"/>
    </dbReference>
    <dbReference type="SignaLink" id="O43707"/>
    <dbReference type="SIGNOR" id="O43707"/>
    <dbReference type="Agora" id="ENSG00000130402"/>
    <dbReference type="BioGRID-ORCS" id="81">
        <property type="hits" value="24 hits in 1168 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="F85A2E29">
        <property type="entry name" value="IMP1 RNP granule"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTN4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="O43707"/>
    <dbReference type="GeneWiki" id="Actinin_alpha_4"/>
    <dbReference type="GenomeRNAi" id="81"/>
    <dbReference type="Pharos" id="O43707">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O43707"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="O43707">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000130402">
        <property type="expression patterns" value="Expressed in popliteal artery and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O43707">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030054">
        <property type="term" value="C:cell junction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042995">
        <property type="term" value="C:cell projection"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030864">
        <property type="term" value="C:cortical actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005925">
        <property type="term" value="C:focal adhesion"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048471">
        <property type="term" value="C:perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031093">
        <property type="term" value="C:platelet alpha granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098871">
        <property type="term" value="C:postsynaptic actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="SynGO"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032991">
        <property type="term" value="C:protein-containing complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031143">
        <property type="term" value="C:pseudopodium"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990904">
        <property type="term" value="C:ribonucleoprotein complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001725">
        <property type="term" value="C:stress fiber"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030018">
        <property type="term" value="C:Z disc"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003779">
        <property type="term" value="F:actin binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051015">
        <property type="term" value="F:actin filament binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005509">
        <property type="term" value="F:calcium ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031490">
        <property type="term" value="F:chromatin DNA binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005178">
        <property type="term" value="F:integrin binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016922">
        <property type="term" value="F:nuclear receptor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042974">
        <property type="term" value="F:nuclear retinoic acid receptor binding"/>
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        <property type="term" value="P:vesicle transport along actin filament"/>
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        <property type="entry name" value="Actinin alpha 1"/>
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        <property type="entry name" value="Actinin_actin-bd_CS"/>
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        <property type="entry name" value="Spectrin/alpha-actinin"/>
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    <dbReference type="InterPro" id="IPR002017">
        <property type="entry name" value="Spectrin_repeat"/>
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    <dbReference type="Pfam" id="PF00307">
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        <property type="match status" value="2"/>
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    <dbReference type="SUPFAM" id="SSF47576">
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="2"/>
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    </dbReference>
    <dbReference type="PROSITE" id="PS50222">
        <property type="entry name" value="EF_HAND_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0009">Actin-binding</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0106">Calcium</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000073440" description="Alpha-actinin-4">
        <location>
            <begin position="1"/>
            <end position="911"/>
        </location>
    </feature>
    <feature type="domain" description="Calponin-homology (CH) 1" evidence="6">
        <location>
            <begin position="50"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="domain" description="Calponin-homology (CH) 2" evidence="6">
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            <begin position="163"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="repeat" description="Spectrin 1" evidence="5">
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            <begin position="293"/>
            <end position="403"/>
        </location>
    </feature>
    <feature type="repeat" description="Spectrin 2" evidence="5">
        <location>
            <begin position="413"/>
            <end position="518"/>
        </location>
    </feature>
    <feature type="repeat" description="Spectrin 3" evidence="5">
        <location>
            <begin position="528"/>
            <end position="639"/>
        </location>
    </feature>
    <feature type="repeat" description="Spectrin 4" evidence="5">
        <location>
            <begin position="649"/>
            <end position="752"/>
        </location>
    </feature>
    <feature type="domain" description="EF-hand 1" evidence="7">
        <location>
            <begin position="765"/>
            <end position="800"/>
        </location>
    </feature>
    <feature type="domain" description="EF-hand 2" evidence="7">
        <location>
            <begin position="806"/>
            <end position="841"/>
        </location>
    </feature>
    <feature type="region of interest" description="Actin-binding">
        <location>
            <begin position="1"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with VCL" evidence="11 29">
        <location>
            <begin position="12"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with VCL" evidence="11 29">
        <location>
            <begin position="40"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with VCL" evidence="11 29">
        <location>
            <begin position="108"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="region of interest" description="Polyphosphoinositide (PIP2)-binding" evidence="5">
        <location>
            <begin position="177"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mediates interaction with MICALL2" evidence="2">
        <location>
            <begin position="736"/>
            <end position="911"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="LXXLL motif" evidence="15">
        <location>
            <begin position="84"/>
            <end position="88"/>
        </location>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="778"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="780"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="7">
        <location>
            <position position="789"/>
        </location>
        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="1">
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="30">
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="31">
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="30">
        <location>
            <position position="592"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="30">
        <location>
            <position position="625"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="696"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="779"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="2">
        <location>
            <position position="859"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="4">
        <location>
            <position position="909"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_047733" description="In isoform ACTN4ISO." evidence="24">
        <location>
            <begin position="54"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_053401" description="In isoform 3." evidence="25">
        <location>
            <begin position="89"/>
            <end position="478"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079797" description="In FSGS1." evidence="19">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079798" description="In FSGS1." evidence="19">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079799" description="In FSGS1; uncertain significance." evidence="19">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010378" description="In FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coactivator activity; dominant negative effect on nuclear receptors-mediated transcription; increased actin-binding affinity; dbSNP:rs121908415." evidence="8 13 15 19">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="255"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010379" description="In FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coactivator activity; dominant negative effect on nuclear receptors-mediated transcription; increased actin-binding affinity; dbSNP:rs121908416." evidence="8 13 15 19">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072115" description="In FSGS1." evidence="14">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_010380" description="In FSGS1; no effect on protein abundance; no effect on homodimerization; loss of localization to the nucleus; prevents nuclear localization of the wild-type protein; decreased interaction with PPARG and RARA; loss of transcriptional coactivator activity; dominant negative effect on nuclear receptors-mediated transcription; increased actin-binding affinity; dbSNP:rs121908417." evidence="8 13 15 19">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079800" description="In FSGS1; uncertain significance; dbSNP:rs112545413." evidence="18">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="310"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072116" description="In FSGS1; dbSNP:rs201128110." evidence="20">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072117" description="In FSGS1." evidence="20">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="748"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072118" description="Found in patients with IgA nephropathy; uncertain significance; dbSNP:rs771421233." evidence="20">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="784"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072119" evidence="20">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="786"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072120" evidence="20">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="787"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072121" evidence="20">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="787"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072122" description="Found in patients with IgA nephropathy; uncertain significance." evidence="20">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="793"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072123" description="Found in patients with IgA nephropathy; uncertain significance." evidence="20">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="798"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072124" description="In dbSNP:rs141727248." evidence="20">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="801"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduced interaction with RARA. Loss of the transcriptional coac tivator activity toward RARA." evidence="15">
        <original>LL</original>
        <variation>AA</variation>
        <location>
            <begin position="87"/>
            <end position="88"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC17470." evidence="26" ref="1">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AL047603." evidence="26" ref="6">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AU118403." evidence="26" ref="7">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="221"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC17470." evidence="26" ref="1">
        <original>T</original>
        <variation>TET</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC17470." evidence="26" ref="1">
        <original>EHL</original>
        <variation>CSTS</variation>
        <location>
            <begin position="292"/>
            <end position="294"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC17470." evidence="26" ref="1">
        <original>TL</original>
        <variation>SV</variation>
        <location>
            <begin position="359"/>
            <end position="360"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC17470." evidence="26" ref="1">
        <original>I</original>
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        <location>
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</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="151" xmlns="https://uniprot.org/uniprot">
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    <accession>B1AN52</accession>
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            <taxon>Vertebrata</taxon>
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    <reference key="1">
        <citation type="journal article" date="2001" name="Biochim. Biophys. Acta" volume="1522" first="130" last="133">
            <title>Identification of two cDNAs for human actin-related proteins (Arps) that have remarkable similarity to conventional actin.</title>
            <authorList>
                <person name="Harata M."/>
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            </authorList>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="Exp. Cell Res." volume="279" first="177" last="187">
            <title>Novel actin-related proteins Arp-T1 and Arp-T2 as components of the cytoskeletal calyx of the mammalian sperm head.</title>
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                <person name="Heid H.W."/>
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            </authorList>
            <dbReference type="PubMed" id="12243744"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
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                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
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                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
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                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
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            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
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                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
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                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
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                <person name="Remington K.A."/>
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                <person name="Eichler E.E."/>
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                <person name="Hunkapiller M.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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        <interactant intactId="EBI-54800759">
            <id>Q8TDY3</id>
        </interactant>
        <interactant intactId="EBI-2555126">
            <id>Q9H2J4</id>
            <label>PDCL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the actin family.</text>
    </comment>
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        <property type="nucleotide sequence ID" value="NM_080431.4"/>
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        <property type="interactions" value="13"/>
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        <property type="antibodies" value="131 antibodies from 25 providers"/>
    </dbReference>
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        <property type="protein sequence ID" value="ENSP00000367658.2"/>
        <property type="gene ID" value="ENSG00000169717.7"/>
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        <property type="protein sequence ID" value="ENSP00000367658.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_080431.5"/>
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    <dbReference type="UCSC" id="uc001ajz.4">
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:24026"/>
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        <property type="gene designation" value="ACTRT2"/>
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        <property type="expression patterns" value="Tissue enriched (testis)"/>
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        <property type="type" value="gene"/>
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    <dbReference type="OrthoDB" id="10053773at2759"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
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        <property type="hits" value="8 hits in 1141 CRISPR screens"/>
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    <dbReference type="GenomeRNAi" id="140625"/>
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        <property type="development level" value="Tdark"/>
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    <dbReference type="PRO" id="PR:Q8TDY3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TDY3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000169717">
        <property type="expression patterns" value="Expressed in left testis and 46 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd13397">
        <property type="entry name" value="ASKHA_NBD_actin_Arp-T1-3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000018">
        <property type="entry name" value="Actin-like protein (Centractin)"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089144" description="Actin-related protein T2">
        <location>
            <begin position="1"/>
            <end position="377"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020416" description="In dbSNP:rs3795263.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH29499." evidence="2" ref="5">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB85862." evidence="2" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000305" key="2"/>
    <sequence length="377" mass="41702" checksum="73272DE854B48FEB" modified="2004-05-10" version="2">MFNPHALDSPAVIFDNGSGFCKAGLSGEFGPRHMVSSIVGHLKFQAPSAEANQKKYFVGEEALYKQEALQLHSPFERGLITGWDDVERLWKHLFEWELGVKPSDQPLLATEPSLNPRENREKMAEVMFENFGVPAFYLSDQAVLALYASACVTGLVVDSGDAVTCTVPIFEGYSLPHAVTKLHVAGRDITELLMQLLLASGHTFPCQLDKGLVDDIKKKLCYVALEPEKELSRRPEEVLREYKLPDGNIISLGDPLHQAPEALFVPQQLGSQSPGLSNMVSSSITKCDTDIQKILFGEIVLSGGTTLFHGLDDRLLKELEQLASKDTPIKITAPPDRWFSTWIGASIVTSLSSFKQMWVTAADFKEFGTSVVQRRCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-10-01" modified="2026-01-28" version="265" xmlns="https://uniprot.org/uniprot">
    <accession>P12814</accession>
    <accession>B3V8S3</accession>
    <accession>B4DHH3</accession>
    <accession>B7TY16</accession>
    <accession>Q1HE25</accession>
    <accession>Q9BTN1</accession>
    <name>ACTN1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-actinin-1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-actinin cytoskeletal isoform</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>F-actin cross-linking protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Non-muscle alpha-actinin-1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTN1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <tissue>Placenta</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
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            <tissue>Skin</tissue>
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        <scope>PROTEIN SEQUENCE OF 1-21</scope>
        <source>
            <tissue>Platelet</tissue>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>INTERACTION WITH TTID</scope>
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        <scope>INTERACTION WITH MYOZ2</scope>
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        <scope>PHOSPHORYLATION AT TYR-12</scope>
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        <scope>INTERACTION WITH LPP</scope>
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        <scope>INTERACTION WITH DDN</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-95; LYS-195 AND LYS-676</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="22689882"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH IGSF8</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471 AND SER-677</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 30-253</scope>
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        <scope>VARIANTS BDPLT15 LYS-32; GLN-46; ILE-105; LYS-225; TRP-738 AND GLN-752</scope>
        <scope>VARIANT TRP-197</scope>
        <scope>CHARACTERIZATION OF VARIANTS BDPLT15 LYS-32 AND ILE-105</scope>
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        <scope>VARIANT BDPLT15 GLN-46</scope>
        <scope>CHARACTERIZATION OF VARIANT BDPLT15 GLN-46</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <comment type="function">
        <text evidence="10">F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 5 6 8 9 10">Homodimer; antiparallel. Interacts with MYOZ2, TTID and LPP (PubMed:10369880, PubMed:11114196, PubMed:12615977). Interacts with DDN (PubMed:16464232). Interacts with PSD. Interacts with MICALL2 (By similarity). Interacts with DNM2 and CTTN. Interacts with PDLIM1. Interacts with PDLIM2. Interacts with PDLIM4 (via PDZ domain) (By similarity). Interacts with IGSF8 (PubMed:22689882).</text>
    </comment>
    <comment type="interaction">
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            <id>P12814</id>
        </interactant>
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            <id>P35609</id>
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        <organismsDiffer>false</organismsDiffer>
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            <id>Q13936</id>
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            <id>Q7L775</id>
            <label>EPM2AIP1</label>
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            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-448202">
            <id>O95257</id>
            <label>GADD45G</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-4291090">
            <id>Q9Y223</id>
            <label>GNE</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-2511344">
            <id>Q8NC69</id>
            <label>KCTD6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-739832">
            <id>Q8TBB1</id>
            <label>LNX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-2555563">
            <id>Q8IY33</id>
            <label>MICALL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-16430371">
            <id>A0A0S2Z4Y0</id>
            <label>MYOT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-744402">
            <id>Q9NP98</id>
            <label>MYOZ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-746712">
            <id>Q9NPC6</id>
            <label>MYOZ2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-3920396">
            <id>Q6ZUT1</id>
            <label>NKAPD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-3932815">
            <id>P00973</id>
            <label>OAS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
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        <interactant intactId="EBI-12081862">
            <id>P00973-2</id>
            <label>OAS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-372861">
            <id>P50479</id>
            <label>PDLIM4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-1752330">
            <id>Q9BYB0</id>
            <label>SHANK3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-352936">
            <id>Q8N3V7</id>
            <label>SYNPO</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-12082116">
            <id>Q9H987-2</id>
            <label>SYNPO2L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-681210">
            <id>Q8WZ42</id>
            <label>TTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-594644">
            <id>P10599</id>
            <label>TXN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-743272">
            <id>O75604</id>
            <label>USP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-10175581">
            <id>B2R8Y4</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-6654049">
            <id>Q8VC66</id>
            <label>Ssx2ip</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-351710">
            <id>P12814</id>
        </interactant>
        <interactant intactId="EBI-6904388">
            <id>PRO_0000037577</id>
            <dbReference type="UniProtKB" id="P27958"/>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12 13">Cytoplasm</location>
            <location evidence="12 13">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Cytoplasm</location>
            <location evidence="13">Myofibril</location>
            <location evidence="13">Sarcomere</location>
            <location evidence="13">Z line</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Ruffle</location>
        </subcellularLocation>
        <text evidence="1">Colocalizes with MYOZ2 and PPP3CA at the Z-line of heart and skeletal muscle. Colocalizes with PSD in membrane ruffles and central reticular structures.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P12814-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P12814-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041264"/>
        </isoform>
        <isoform>
            <id>P12814-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043525"/>
        </isoform>
        <isoform>
            <id>P12814-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_041264 VSP_047763"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="11 12">
        <disease id="DI-03753">
            <name>Bleeding disorder, platelet-type, 15</name>
            <acronym>BDPLT15</acronym>
            <description>An autosomal dominant form of macrothrombocytopenia. Affected individuals usually have no or only mild bleeding tendency, such as epistaxis. Laboratory studies show decreased numbers of large platelets and anisocytosis, but the platelets show no in vitro functional abnormalities.</description>
            <dbReference type="MIM" id="615193"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="18">Belongs to the alpha-actinin family.</text>
    </comment>
    <dbReference type="EMBL" id="X15804">
        <property type="protein sequence ID" value="CAA33803.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="M95178">
        <property type="protein sequence ID" value="AAA51582.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="EU716325">
        <property type="protein sequence ID" value="ACE62922.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="DQ496098">
        <property type="protein sequence ID" value="ABF50047.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="FJ410030">
        <property type="protein sequence ID" value="ACJ24535.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BT007207">
        <property type="protein sequence ID" value="AAP35871.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK295099">
        <property type="protein sequence ID" value="BAG58135.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL117694">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471061">
        <property type="protein sequence ID" value="EAW80975.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC003576">
        <property type="protein sequence ID" value="AAH03576.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC015766">
        <property type="protein sequence ID" value="AAH15766.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="X55187">
        <property type="protein sequence ID" value="CAA38970.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS45129.1">
        <molecule id="P12814-2"/>
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    <dbReference type="CCDS" id="CCDS9792.1">
        <molecule id="P12814-1"/>
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    <dbReference type="PIR" id="S05503">
        <property type="entry name" value="FAHUAA"/>
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    <dbReference type="RefSeq" id="NP_001093.1">
        <molecule id="P12814-1"/>
        <property type="nucleotide sequence ID" value="NM_001102.4"/>
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    <dbReference type="RefSeq" id="NP_001123476.1">
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        <property type="nucleotide sequence ID" value="NM_001130004.2"/>
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    <dbReference type="RefSeq" id="NP_001123477.1">
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        <property type="nucleotide sequence ID" value="NM_001130005.2"/>
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    <dbReference type="RefSeq" id="NP_001410943.1">
        <molecule id="P12814-4"/>
        <property type="nucleotide sequence ID" value="NM_001424014.1"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A=30-253"/>
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    <dbReference type="PDB" id="2EYN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=30-253"/>
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    <dbReference type="PDB" id="2N8Y">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=743-892"/>
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    <dbReference type="PDB" id="2N8Z">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=743-892"/>
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    <dbReference type="PDBsum" id="2EYI"/>
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        <property type="interactions" value="342"/>
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    <dbReference type="CORUM" id="P12814"/>
    <dbReference type="DIP" id="DIP-33184N"/>
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        <property type="interactions" value="1036"/>
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        <property type="interactions" value="141"/>
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    <dbReference type="MINT" id="P12814"/>
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        <property type="generic name" value="Copper"/>
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        <property type="generic name" value="Human calcitonin"/>
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        <property type="glycosylation" value="1 site, 2 glycans"/>
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        <property type="glycosylation" value="1 site, 2 O-linked glycans (1 site)"/>
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    <dbReference type="ProteomicsDB" id="6259"/>
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        <property type="antibodies" value="481 antibodies from 39 providers"/>
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    <dbReference type="DNASU" id="87"/>
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        <property type="protein sequence ID" value="ENSP00000193403.6"/>
        <property type="gene ID" value="ENSG00000072110.18"/>
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    <dbReference type="Ensembl" id="ENST00000394419.9">
        <molecule id="P12814-3"/>
        <property type="protein sequence ID" value="ENSP00000377941.4"/>
        <property type="gene ID" value="ENSG00000072110.18"/>
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    <dbReference type="Ensembl" id="ENST00000438964.6">
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        <property type="protein sequence ID" value="ENSP00000414272.2"/>
        <property type="gene ID" value="ENSG00000072110.18"/>
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    <dbReference type="Ensembl" id="ENST00000538545.6">
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        <property type="protein sequence ID" value="ENSP00000439828.2"/>
        <property type="gene ID" value="ENSG00000072110.18"/>
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    <dbReference type="GeneID" id="87"/>
    <dbReference type="KEGG" id="hsa:87"/>
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        <property type="protein sequence ID" value="ENSP00000377941.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001130004.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001123476.1"/>
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        <property type="gene designation" value="ACTN1"/>
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        <property type="expression patterns" value="Tissue enhanced (smooth)"/>
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    <dbReference type="MalaCards" id="ACTN1"/>
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        <property type="type" value="gene"/>
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        <property type="type" value="phenotype"/>
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    <dbReference type="OpenTargets" id="ENSG00000072110"/>
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        <property type="disease" value="Autosomal dominant macrothrombocytopenia"/>
    </dbReference>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="HOGENOM" id="CLU_005217_1_1_1"/>
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        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
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    <dbReference type="Reactome" id="R-HSA-114608">
        <property type="pathway name" value="Platelet degranulation"/>
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    <dbReference type="Reactome" id="R-HSA-3000170">
        <property type="pathway name" value="Syndecan interactions"/>
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        <property type="pathway name" value="Nephrin family interactions"/>
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        <property type="pathway name" value="Regulation of cytoskeletal remodeling and cell spreading by IPP complex components"/>
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    <dbReference type="Reactome" id="R-HSA-9013405">
        <property type="pathway name" value="RHOD GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9013418">
        <property type="pathway name" value="RHOBTB2 GTPase cycle"/>
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    <dbReference type="Reactome" id="R-HSA-9035034">
        <property type="pathway name" value="RHOF GTPase cycle"/>
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    <dbReference type="SignaLink" id="P12814"/>
    <dbReference type="SIGNOR" id="P12814"/>
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        <property type="nominated target" value="Agora Nominated Target for Alzheimer's Disease"/>
    </dbReference>
    <dbReference type="BioGRID-ORCS" id="87">
        <property type="hits" value="17 hits in 1163 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="3EAB04FE">
        <property type="entry name" value="Rapsn condensate"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTN1">
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P12814"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
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    <dbReference type="RNAct" id="P12814">
        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in blood vessel layer and 207 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:brush border"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
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        <property type="term" value="C:cell junction"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042995">
        <property type="term" value="C:cell projection"/>
        <property type="evidence" value="ECO:0000314"/>
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    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000073431" description="Alpha-actinin-1">
        <location>
            <begin position="1"/>
            <end position="892"/>
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            <end position="135"/>
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            <end position="250"/>
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    </feature>
    <feature type="repeat" description="Spectrin 3">
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            <end position="620"/>
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            <end position="733"/>
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            <end position="781"/>
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    </feature>
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        <location>
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            <end position="822"/>
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    </feature>
    <feature type="region of interest" description="Actin-binding">
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            <begin position="1"/>
            <end position="247"/>
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    </feature>
    <feature type="region of interest" description="Interaction with DDN" evidence="9">
        <location>
            <begin position="274"/>
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    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="759"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="761"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
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    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="763"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="765"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="770"/>
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        <ligand>
            <name>Ca(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29108"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="20">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20">
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by FAK1" evidence="7">
        <location>
            <position position="12"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="19">
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="19">
        <location>
            <position position="195"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="21">
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="19">
        <location>
            <position position="676"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="21">
        <location>
            <position position="677"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="890"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041264" description="In isoform 2 and isoform 4." evidence="14 15 17">
        <original>DHSGTLGPEEFKACLISLGYDIGNDPQ</original>
        <variation>KKTGMMDTDDFRACLISMGYNM</variation>
        <location>
            <begin position="761"/>
            <end position="787"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043525" description="In isoform 3." evidence="16">
        <original>Q</original>
        <variation>QKKTGMMDTDDFRACLISMGYNM</variation>
        <location>
            <position position="787"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_047763" description="In isoform 4." evidence="17">
        <original>K</original>
        <variation>KLQEGGKMQTAHAAFTPPGFAAVSGRAALRLLDFAAFLTTLSSQ</variation>
        <location>
            <position position="840"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069910" description="In BDPLT15; the mutation dominantly affects the actin filament assembly likely resulting in abnormal cytoskeletal organization; dbSNP:rs387907346." evidence="11">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069911" description="In BDPLT15; disorganization of the actin and alpha-actinin 1 filaments; dbSNP:rs387907348." evidence="11 12">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069912" description="In BDPLT15; the mutation dominantly affects the actin filament assembly likely resulting in abnormal cytoskeletal organization; dbSNP:rs387907345." evidence="11">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069913" description="In dbSNP:rs904887313." evidence="11">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069914" description="In BDPLT15; dbSNP:rs387907350." evidence="11">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="225"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_053883" description="In dbSNP:rs7157661.">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="707"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069915" description="In BDPLT15; dbSNP:rs387907349." evidence="11">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="738"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069916" description="In BDPLT15; dbSNP:rs387907347." evidence="11">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="752"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_053884" description="In dbSNP:rs11557769.">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="868"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; CAA38970." evidence="18" ref="11">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="317"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; BAG58135." evidence="18" ref="7">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; BAG58135." evidence="18" ref="7">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="424"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; CAA38970." evidence="18" ref="11">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="477"/>
        </location>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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    <comment type="function">
        <text>Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367493">
            <id>P42025</id>
        </interactant>
        <interactant intactId="EBI-724352">
            <id>Q14203</id>
            <label>DCTN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367493">
            <id>P42025</id>
        </interactant>
        <interactant intactId="EBI-715074">
            <id>Q13561</id>
            <label>DCTN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367493">
            <id>P42025</id>
        </interactant>
        <interactant intactId="EBI-466029">
            <id>P42858</id>
            <label>HTT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367493">
            <id>P42025</id>
        </interactant>
        <interactant intactId="EBI-367600">
            <id>Q9QZB7</id>
            <label>Actr10</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
            <location>Microtubule organizing center</location>
            <location>Centrosome</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the actin family. ARP1 subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X82207">
        <property type="protein sequence ID" value="CAA57691.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC017099">
        <property type="protein sequence ID" value="AAY24280.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01924.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01927.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC004374">
        <property type="protein sequence ID" value="AAH04374.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006372">
        <property type="protein sequence ID" value="AAH06372.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010090">
        <property type="protein sequence ID" value="AAH10090.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2033.1"/>
    <dbReference type="RefSeq" id="NP_005726.1">
        <property type="nucleotide sequence ID" value="NM_005735.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P42025"/>
    <dbReference type="SMR" id="P42025"/>
    <dbReference type="BioGRID" id="115424">
        <property type="interactions" value="134"/>
    </dbReference>
    <dbReference type="FunCoup" id="P42025">
        <property type="interactions" value="1977"/>
    </dbReference>
    <dbReference type="IntAct" id="P42025">
        <property type="interactions" value="76"/>
    </dbReference>
    <dbReference type="MINT" id="P42025"/>
    <dbReference type="STRING" id="9606.ENSP00000289228"/>
    <dbReference type="GlyGen" id="P42025">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P42025"/>
    <dbReference type="MetOSite" id="P42025"/>
    <dbReference type="PhosphoSitePlus" id="P42025"/>
    <dbReference type="SwissPalm" id="P42025"/>
    <dbReference type="BioMuta" id="ACTR1B"/>
    <dbReference type="DMDM" id="1168333"/>
    <dbReference type="OGP" id="P42025"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00029469"/>
    <dbReference type="jPOST" id="P42025"/>
    <dbReference type="MassIVE" id="P42025"/>
    <dbReference type="PaxDb" id="9606-ENSP00000289228"/>
    <dbReference type="PeptideAtlas" id="P42025"/>
    <dbReference type="ProteomicsDB" id="55480"/>
    <dbReference type="Pumba" id="P42025"/>
    <dbReference type="Antibodypedia" id="32643">
        <property type="antibodies" value="158 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10120"/>
    <dbReference type="Ensembl" id="ENST00000289228.7">
        <property type="protein sequence ID" value="ENSP00000289228.5"/>
        <property type="gene ID" value="ENSG00000115073.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000708081.1">
        <property type="protein sequence ID" value="ENSP00000517084.1"/>
        <property type="gene ID" value="ENSG00000291597.1"/>
    </dbReference>
    <dbReference type="GeneID" id="10120"/>
    <dbReference type="KEGG" id="hsa:10120"/>
    <dbReference type="MANE-Select" id="ENST00000289228.7">
        <property type="protein sequence ID" value="ENSP00000289228.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005735.4"/>
        <property type="RefSeq protein sequence ID" value="NP_005726.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002syb.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:168"/>
    <dbReference type="ClinPGx" id="PA24487"/>
    <dbReference type="CTD" id="10120"/>
    <dbReference type="DisGeNET" id="10120"/>
    <dbReference type="GeneCards" id="ACTR1B"/>
    <dbReference type="HGNC" id="HGNC:168">
        <property type="gene designation" value="ACTR1B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000115073">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="605144">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000115073"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000115073"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161587"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_1_1"/>
    <dbReference type="InParanoid" id="P42025"/>
    <dbReference type="OMA" id="YTTWTGG"/>
    <dbReference type="OrthoDB" id="5132116at2759"/>
    <dbReference type="PAN-GO" id="P42025">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P42025"/>
    <dbReference type="PathwayCommons" id="P42025"/>
    <dbReference type="Reactome" id="R-HSA-2132295">
        <property type="pathway name" value="MHC class II antigen presentation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P42025"/>
    <dbReference type="Agora" id="ENSG00000115073"/>
    <dbReference type="BioGRID-ORCS" id="10120">
        <property type="hits" value="197 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="8C2F96ED">
        <property type="entry name" value="Centrosome"/>
    </dbReference>
    <dbReference type="CD-CODE" id="DEE660B4">
        <property type="entry name" value="Stress granule"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACTR1B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACTR1B"/>
    <dbReference type="GenomeRNAi" id="10120"/>
    <dbReference type="Pharos" id="P42025">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P42025"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="P42025">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000115073">
        <property type="expression patterns" value="Expressed in right frontal lobe and 210 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005813">
        <property type="term" value="C:centrosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="LIFEdb"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005869">
        <property type="term" value="C:dynactin complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904813">
        <property type="term" value="C:ficolin-1-rich granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034774">
        <property type="term" value="C:secretory granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd10216">
        <property type="entry name" value="ASKHA_NBD_Arp1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000188">
        <property type="entry name" value="Actin like 6B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000205">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000018">
        <property type="entry name" value="Actin-like protein (Centractin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000008">
        <property type="entry name" value="alpha-centractin isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004001">
        <property type="entry name" value="Actin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0944">Nitration</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089060" description="Beta-centractin">
        <location>
            <begin position="1"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="4 5">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="3'-nitrotyrosine" evidence="1">
        <location>
            <position position="4"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025315" description="In dbSNP:rs11547231." evidence="2">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048187" description="In dbSNP:rs11692435.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8R5C5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0007744" key="4">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="5">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <sequence length="376" mass="42293" checksum="24C24ECEE18B83BD" modified="1995-11-01" version="1">MESYDIIANQPVVIDNGSGVIKAGFAGDQIPKYCFPNYVGRPKHMRVMAGALEGDLFIGPKAEEHRGLLTIRYPMEHGVVRDWNDMERIWQYVYSKDQLQTFSEEHPVLLTEAPLNPSKNREKAAEVFFETFNVPALFISMQAVLSLYATGRTTGVVLDSGDGVTHAVPIYEGFAMPHSIMRVDIAGRDVSRYLRLLLRKEGVDFHTSAEFEVVRTIKERACYLSINPQKDEALETEKVQYTLPDGSTLDVGPARFRAPELLFQPDLVGDESEGLHEVVAFAIHKSDMDLRRTLFANIVLSGGSTLFKGFGDRLLSEVKKLAPKDIKIKISAPQERLYSTWIGGSILASLDTFKKMWVSKKEYEEDGSRAIHRKTF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="148" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BYD9</accession>
    <accession>Q96IS0</accession>
    <accession>Q96NJ0</accession>
    <name>ACTT3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin-related protein T3</fullName>
            <shortName>ARP-T3</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Actin-related protein M1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACTRT3</name>
        <name type="synonym">ARPM1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Biochim. Biophys. Acta" volume="1522" first="130" last="133">
            <title>Identification of two cDNAs for human actin-related proteins (Arps) that have remarkable similarity to conventional actin.</title>
            <authorList>
                <person name="Harata M."/>
                <person name="Nishimori K."/>
                <person name="Hatta S."/>
            </authorList>
            <dbReference type="PubMed" id="11750065"/>
            <dbReference type="DOI" id="10.1016/s0167-4781(01)00315-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Okitani R."/>
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                <person name="Itoh T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
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                <person name="Togashi T."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
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                <person name="Hu S."/>
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                <person name="Zhang J."/>
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                <person name="Zhou J."/>
                <person name="Zhou Y."/>
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                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <comment type="subunit">
        <text evidence="1">Interacts with PFN3.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-54800784">
            <id>Q9BYD9</id>
        </interactant>
        <interactant intactId="EBI-2555126">
            <id>Q9H2J4</id>
            <label>PDCL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2">Ubiquitously expressed.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EMBL" id="AB049117">
        <property type="protein sequence ID" value="BAB39481.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK055346">
        <property type="protein sequence ID" value="BAB70906.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC078802">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007289">
        <property type="protein sequence ID" value="AAH07289.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3206.1"/>
    <dbReference type="RefSeq" id="NP_115876.3">
        <property type="nucleotide sequence ID" value="NM_032487.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BYD9"/>
    <dbReference type="SMR" id="Q9BYD9"/>
    <dbReference type="BioGRID" id="124111">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BYD9">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BYD9">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000333037"/>
    <dbReference type="BioMuta" id="ACTRT3"/>
    <dbReference type="DMDM" id="47116738"/>
    <dbReference type="MassIVE" id="Q9BYD9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000333037"/>
    <dbReference type="PeptideAtlas" id="Q9BYD9"/>
    <dbReference type="ProteomicsDB" id="79622"/>
    <dbReference type="Antibodypedia" id="33699">
        <property type="antibodies" value="132 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84517"/>
    <dbReference type="Ensembl" id="ENST00000330368.3">
        <property type="protein sequence ID" value="ENSP00000333037.1"/>
        <property type="gene ID" value="ENSG00000184378.4"/>
    </dbReference>
    <dbReference type="GeneID" id="84517"/>
    <dbReference type="KEGG" id="hsa:84517"/>
    <dbReference type="MANE-Select" id="ENST00000330368.3">
        <property type="protein sequence ID" value="ENSP00000333037.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032487.5"/>
        <property type="RefSeq protein sequence ID" value="NP_115876.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ffs.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24022"/>
    <dbReference type="CTD" id="84517"/>
    <dbReference type="DisGeNET" id="84517"/>
    <dbReference type="GeneCards" id="ACTRT3"/>
    <dbReference type="HGNC" id="HGNC:24022">
        <property type="gene designation" value="ACTRT3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184378">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="608534">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184378"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184378"/>
    <dbReference type="eggNOG" id="KOG0676">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162209"/>
    <dbReference type="HOGENOM" id="CLU_027965_0_2_1"/>
    <dbReference type="InParanoid" id="Q9BYD9"/>
    <dbReference type="OMA" id="WEDMEIM"/>
    <dbReference type="OrthoDB" id="6953074at2759"/>
    <dbReference type="PAN-GO" id="Q9BYD9">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BYD9"/>
    <dbReference type="PathwayCommons" id="Q9BYD9"/>
    <dbReference type="SignaLink" id="Q9BYD9"/>
    <dbReference type="Agora" id="ENSG00000184378"/>
    <dbReference type="BioGRID-ORCS" id="84517">
        <property type="hits" value="30 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84517"/>
    <dbReference type="Pharos" id="Q9BYD9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BYD9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BYD9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184378">
        <property type="expression patterns" value="Expressed in sperm and 107 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015629">
        <property type="term" value="C:actin cytoskeleton"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001673">
        <property type="term" value="C:male germ cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd13397">
        <property type="entry name" value="ASKHA_NBD_actin_Arp-T1-3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.640.10:FF:000007">
        <property type="entry name" value="Actin like 7B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000050">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.40">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089142" description="Actin-related protein T3">
        <location>
            <begin position="1"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055483" description="In dbSNP:rs2068178.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH07289." evidence="3" ref="3">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB70906." evidence="3" ref="2">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="282"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="11750065"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="372" mass="41008" checksum="56413BCF02AA4794" modified="2001-06-01" version="1">MNHCQLPVVIDNGSGMIKAGVAGCREPQFIYPNIIGRAKGQSRAAQGGLELCVGDQAQDWRSSLFISYPVERGLITSWEDMEIMWKHIYDYNLKLKPCDGPVLITEPALNPLANRQQITEMFFEHLGVPAFYMSIQAVLALFAAGFTTGLVLNSGAGVTQSVPIFEGYCLPHGVQQLDLAGLDLTNYLMVLMKNHGIMLLSASDRKIVEDIKESFCYVAMNYEEEMAKKPDCLEKVYQLPDGKVIQLHDQLFSCPEALFSPCHMNLEAPGIDKICFSSIMKCDTGLRNSFFSNIILAGGSTSFPGLDKRLVKDIAKVAPANTAVQVIAPPERKISVWMGGSILASLSAFQDMWITAAEFKEVGPNIVHQRCF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="189" xmlns="https://uniprot.org/uniprot">
    <accession>P61163</accession>
    <accession>B2R6B0</accession>
    <accession>P42024</accession>
    <name>ACTZ_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alpha-centractin</fullName>
            <shortName>Centractin</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>ARP1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Actin-RPV</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Centrosome-associated actin homolog</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="7" type="primary">ACTR1A</name>
        <name type="synonym">CTRN1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Beta-centractin: characterization and distribution of a new member of the centractin family of actin-related proteins.</title>
            <authorList>
                <person name="Clark S.W."/>
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            </authorList>
            <dbReference type="PubMed" id="7696711"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1992" name="Nature" volume="359" first="244" last="246">
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            </authorList>
            <dbReference type="PubMed" id="1528266"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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    <comment type="function">
        <text evidence="1">Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 5">Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The filament contains 8 copies of ACTR1A and 1 ACTB. Interacts with dynein and adapters such as BICD2 (By similarity). Interacts with BCCIP (isoform 2/alpha) (PubMed:28394342).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-774234">
            <id>P61163</id>
        </interactant>
        <interactant intactId="EBI-724352">
            <id>Q14203</id>
            <label>DCTN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-774234">
            <id>P61163</id>
        </interactant>
        <interactant intactId="EBI-715074">
            <id>Q13561</id>
            <label>DCTN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
            <location evidence="3">Cytoskeleton</location>
            <location evidence="3">Microtubule organizing center</location>
            <location evidence="3">Centrosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
            <location evidence="4">Cell cortex</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the actin family. ARP1 subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="X82206">
        <property type="protein sequence ID" value="CAA57690.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z14978">
        <property type="protein sequence ID" value="CAA78701.1"/>
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    </dbReference>
    <dbReference type="EMBL" id="AK312506">
        <property type="protein sequence ID" value="BAG35407.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AL121928">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49685.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC000693">
        <property type="protein sequence ID" value="AAH00693.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC026016">
        <property type="protein sequence ID" value="AAH26016.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7536.1"/>
    <dbReference type="PIR" id="S29089">
        <property type="entry name" value="S29089"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005727.1">
        <property type="nucleotide sequence ID" value="NM_005736.4"/>
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    <dbReference type="PDB" id="9B7J">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.49 A"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.47 A"/>
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        <property type="pathway name" value="AURKA Activation by TPX2"/>
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        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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    <dbReference type="ChiTaRS" id="ACTR1A">
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    <dbReference type="GeneWiki" id="ACTR1A"/>
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    <dbReference type="PRO" id="PR:P61163"/>
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        <property type="component" value="Chromosome 10"/>
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    <dbReference type="Bgee" id="ENSG00000138107">
        <property type="expression patterns" value="Expressed in cortical plate and 212 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P61163">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
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        <property type="term" value="C:cell cortex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005813">
        <property type="term" value="C:centrosome"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="evidence" value="ECO:0000318"/>
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    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
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        <property type="term" value="C:microtubule associated complex"/>
        <property type="evidence" value="ECO:0000304"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016192">
        <property type="term" value="P:vesicle-mediated transport"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd10216">
        <property type="entry name" value="ASKHA_NBD_Arp1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.40:FF:000188">
        <property type="entry name" value="Actin like 6B"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="alpha-centractin isoform X1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
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    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
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    <dbReference type="InterPro" id="IPR004001">
        <property type="entry name" value="Actin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11937">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000089058" description="Alpha-centractin">
        <location>
            <begin position="1"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="8 9">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="F2Z5G5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P85515"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="14654843"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="22327364"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="28394342"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:167"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <sequence length="376" mass="42614" checksum="4A978E7AB3739436" modified="2004-05-10" version="1">MESYDVIANQPVVIDNGSGVIKAGFAGDQIPKYCFPNYVGRPKHVRVMAGALEGDIFIGPKAEEHRGLLSIRYPMEHGIVKDWNDMERIWQYVYSKDQLQTFSEEHPVLLTEAPLNPRKNRERAAEVFFETFNVPALFISMQAVLSLYATGRTTGVVLDSGDGVTHAVPIYEGFAMPHSIMRIDIAGRDVSRFLRLYLRKEGYDFHSSSEFEIVKAIKERACYLSINPQKDETLETEKAQYYLPDGSTIEIGPSRFRAPELLFRPDLIGEESEGIHEVLVFAIQKSDMDLRRTLFSNIVLSGGSTLFKGFGDRLLSEVKKLAPKDVKIRISAPQERLYSTWIGGSILASLDTFKKMWVSKKEYEEDGARSIHRKTF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="198" xmlns="https://uniprot.org/uniprot">
    <accession>P68133</accession>
    <accession>P02568</accession>
    <accession>P99020</accession>
    <accession>Q5T8M9</accession>
    <name>ACTS_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Actin, alpha skeletal muscle</fullName>
            <ecNumber evidence="5">3.6.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-actin-1</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Actin, alpha skeletal muscle, intermediate form</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name type="primary">ACTA1</name>
        <name type="synonym">ACTA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1983" name="Nucleic Acids Res." volume="11" first="3503" last="3516">
            <title>Isolation and characterization of cDNA clones for human skeletal muscle alpha actin.</title>
            <authorList>
                <person name="Hanauer A."/>
                <person name="Levin M."/>
                <person name="Heilig R."/>
                <person name="Daegelen D."/>
                <person name="Kahn A."/>
                <person name="Mandel J.-L."/>
            </authorList>
            <dbReference type="PubMed" id="6190133"/>
            <dbReference type="DOI" id="10.1093/nar/11.11.3503"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Skeletal muscle</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1988" name="Genomics" volume="3" first="323" last="336">
            <title>Nucleotide sequence and expression of the human skeletal alpha-actin gene: evolution of functional regulatory domains.</title>
            <authorList>
                <person name="Taylor A."/>
                <person name="Erba H.P."/>
                <person name="Muscat G.E.O."/>
                <person name="Kedes L."/>
            </authorList>
            <dbReference type="PubMed" id="2907503"/>
            <dbReference type="DOI" id="10.1016/0888-7543(88)90123-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="23" first="208" last="212">
            <title>Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.</title>
            <authorList>
                <person name="Nowak K.J."/>
                <person name="Wattanasirichaigoon D."/>
                <person name="Goebel H.H."/>
                <person name="Wilce M."/>
                <person name="Pelin K."/>
                <person name="Donner K."/>
                <person name="Jacob R.L."/>
                <person name="Hubner C."/>
                <person name="Oexle K."/>
                <person name="Anderson J.R."/>
                <person name="Verity C.M."/>
                <person name="North K.N."/>
            </authorList>
            <dbReference type="PubMed" id="10508519"/>
            <dbReference type="DOI" id="10.1038/13837"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS CMYO2A ARG-17; TYR-42; SER-117; VAL-134; LEU-165; ASP-184; CYS-185; HIS-258; LEU-265; LYS-282; GLY-288 AND PHE-372</scope>
        <scope>VARIANTS CMYO2B PRO-96 AND VAL-261</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
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                <person name="Lloyd C."/>
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                <person name="Almeida J.P."/>
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                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
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                <person name="King A."/>
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            <dbReference type="PubMed" id="17705262"/>
            <dbReference type="DOI" id="10.1002/ana.21200"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT CMYO2A MET-165</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2012" name="Neurology" volume="78" first="1100" last="1103">
            <title>Nemaline myopathy with stiffness and hypertonia associated with an ACTA1 mutation.</title>
            <authorList>
                <person name="Jain R.K."/>
                <person name="Jayawant S."/>
                <person name="Squier W."/>
                <person name="Muntoni F."/>
                <person name="Sewry C.A."/>
                <person name="Manzur A."/>
                <person name="Quinlivan R."/>
                <person name="Lillis S."/>
                <person name="Jungbluth H."/>
                <person name="Sparrow J.C."/>
                <person name="Ravenscroft G."/>
                <person name="Nowak K.J."/>
                <person name="Memo M."/>
                <person name="Marston S.B."/>
                <person name="Laing N.G."/>
            </authorList>
            <dbReference type="PubMed" id="22442437"/>
            <dbReference type="DOI" id="10.1212/wnl.0b013e31824e8ebe"/>
        </citation>
        <scope>VARIANT CMYO2A ASN-328</scope>
        <scope>CHARACTERIZATION OF VARIANT CMYO2A ASN-328</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2013" name="Pediatrics" volume="131" first="E1986" last="E1990">
            <title>Nemaline myopathy with dilated cardiomyopathy in childhood.</title>
            <authorList>
                <person name="Gatayama R."/>
                <person name="Ueno K."/>
                <person name="Nakamura H."/>
                <person name="Yanagi S."/>
                <person name="Ueda H."/>
                <person name="Yamagishi H."/>
                <person name="Yasui S."/>
            </authorList>
            <dbReference type="PubMed" id="23650303"/>
            <dbReference type="DOI" id="10.1542/peds.2012-1139"/>
        </citation>
        <scope>VARIANT CMYO2A CYS-358</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2015" name="JAMA Neurol." volume="72" first="689" last="698">
            <title>Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family.</title>
            <authorList>
                <person name="Zukosky K."/>
                <person name="Meilleur K."/>
                <person name="Traynor B.J."/>
                <person name="Dastgir J."/>
                <person name="Medne L."/>
                <person name="Devoto M."/>
                <person name="Collins J."/>
                <person name="Rooney J."/>
                <person name="Zou Y."/>
                <person name="Yang M.L."/>
                <person name="Gibbs J.R."/>
                <person name="Meier M."/>
                <person name="Stetefeld J."/>
                <person name="Finkel R.S."/>
                <person name="Schessl J."/>
                <person name="Elman L."/>
                <person name="Felice K."/>
                <person name="Ferguson T.A."/>
                <person name="Ceyhan-Birsoy O."/>
                <person name="Beggs A.H."/>
                <person name="Tennekoon G."/>
                <person name="Johnson J.O."/>
                <person name="Boennemann C.G."/>
            </authorList>
            <dbReference type="PubMed" id="25938801"/>
            <dbReference type="DOI" id="10.1001/jamaneurol.2015.37"/>
        </citation>
        <scope>INVOLVEMENT IN SHPM</scope>
        <scope>VARIANT SHPM ASP-197</scope>
        <scope>CHARACTERIZATION OF VARIANT SHPM ASP-197</scope>
        <scope>CHARACTERIZATION OF VARIANT CMYO2A GLY-288</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2015" name="J. Med. Genet." volume="52" first="208" last="216">
            <title>Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders.</title>
            <authorList>
                <person name="Chae J.H."/>
                <person name="Vasta V."/>
                <person name="Cho A."/>
                <person name="Lim B.C."/>
                <person name="Zhang Q."/>
                <person name="Eun S.H."/>
                <person name="Hahn S.H."/>
            </authorList>
            <dbReference type="PubMed" id="25635128"/>
            <dbReference type="DOI" id="10.1136/jmedgenet-2014-102819"/>
        </citation>
        <scope>VARIANTS CMYO2A ARG-72 AND VAL-116</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="2018" name="Am. J. Med. Genet. A" volume="176" first="359" last="367">
            <title>Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.</title>
            <authorList>
                <person name="Ahmed A.A."/>
                <person name="Skaria P."/>
                <person name="Safina N.P."/>
                <person name="Thiffault I."/>
                <person name="Kats A."/>
                <person name="Taboada E."/>
                <person name="Habeebu S."/>
                <person name="Saunders C."/>
            </authorList>
            <dbReference type="PubMed" id="29274205"/>
            <dbReference type="DOI" id="10.1002/ajmg.a.38577"/>
        </citation>
        <scope>VARIANT CMYO2A SER-17</scope>
    </reference>
    <comment type="function">
        <text>Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 17">Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with alpha-actinin (By similarity). Identified in a complex composed of ACTA1, COBL, GSN AND TMSB4X (By similarity). Interacts with TTID (PubMed:10958653). Interacts (via its C-terminus) with USP25; the interaction occurs for all USP25 isoforms but is strongest for isoform USP25m in muscle differentiating cells (PubMed:16501887).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
        </interactant>
        <interactant intactId="EBI-2556915">
            <id>P13928</id>
            <label>ANXA8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
        </interactant>
        <interactant intactId="EBI-10254793">
            <id>Q6XD76</id>
            <label>ASCL4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
        </interactant>
        <interactant intactId="EBI-1383687">
            <id>Q9UQM7</id>
            <label>CAMK2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
        </interactant>
        <interactant intactId="EBI-6509505">
            <id>Q0VD86</id>
            <label>INCA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-25830459">
            <id>Q6ZQX7-4</id>
            <label>LIAT1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-10171633">
            <id>Q96PV4</id>
            <label>PNMA5</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
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        <interactant intactId="EBI-11285923">
            <id>Q9H7C4</id>
            <label>SYNC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-367510">
            <id>P68133</id>
        </interactant>
        <interactant intactId="EBI-717634">
            <id>P17024</id>
            <label>ZNF20</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="3">Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.</text>
    </comment>
    <comment type="PTM">
        <text evidence="24">Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.</text>
    </comment>
    <comment type="PTM">
        <molecule>Actin, alpha skeletal muscle, intermediate form</molecule>
        <text evidence="3">N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.</text>
    </comment>
    <comment type="PTM">
        <text evidence="28">Methylated at His-75 by SETD3.</text>
    </comment>
    <comment type="PTM">
        <text evidence="30 31">(Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).</text>
    </comment>
    <comment type="disease" evidence="6 8 9 11 12 13 15 16 18 20 22 23 25 26 27">
        <disease id="DI-02034">
            <name>Congenital myopathy 2A, typical, autosomal dominant</name>
            <acronym>CMYO2A</acronym>
            <description>A muscular disorder characterized by generalized muscle weakness, delayed motor milestones, hypotonia, and muscle fiber abnormalities on histologic examination. Histologic findings include abnormal thread- or rod-like structures (nemaline rods), intranuclear rods, clumped filaments, cores, or fiber-type disproportion. The spectrum of clinical phenotypes ranges from severe neonatal presentations to onset of a milder disorder in childhood.</description>
            <dbReference type="MIM" id="161800"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="6 10">
        <disease id="DI-06621">
            <name>Congenital myopathy 2B, severe infantile, autosomal recessive</name>
            <acronym>CMYO2B</acronym>
            <description>An autosomal recessive skeletal muscle disorder characterized by severe hypotonia with lack of spontaneous movements and respiratory insufficiency, usually leading to death in infancy or early childhood. Longer survival has been reported.</description>
            <dbReference type="MIM" id="620265"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="14 19">
        <disease id="DI-06622">
            <name>Congenital myopathy 2C, severe infantile, autosomal dominant</name>
            <acronym>CMYO2C</acronym>
            <description>An autosomal dominant skeletal muscle disorder characterized by severe congenital weakness usually resulting in death from respiratory failure in the first year or so of life. Patients present at birth with hypotonia, lack of antigravity movements, poor head control, and difficulties feeding or breathing, often requiring tube-feeding and mechanical ventilation. Decreased fetal movements may be observed in some cases.</description>
            <dbReference type="MIM" id="620278"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="26">
        <disease id="DI-04672">
            <name>Myopathy, scapulohumeroperoneal</name>
            <acronym>SHPM</acronym>
            <description>An autosomal dominant muscular disorder characterized by progressive muscle weakness with initial scapulo-humeral-peroneal and distal distribution. Over time, muscle weakness progresses to proximal muscle groups. Clinical characteristics include scapular winging, mild lower facial weakness, foot drop due to foot eversion and dorsiflexion weakness, and selective muscle atrophy. Age at onset and disease progression are variable.</description>
            <dbReference type="MIM" id="616852"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.</text>
    </comment>
    <comment type="similarity">
        <text evidence="29">Belongs to the actin family.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.-" evidence="5"/>
    <dbReference type="EMBL" id="J00068">
        <property type="protein sequence ID" value="AAB59376.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="M20543">
        <property type="protein sequence ID" value="AAA60296.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF182035">
        <property type="protein sequence ID" value="AAF02694.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CR536516">
        <property type="protein sequence ID" value="CAG38754.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAG46595.1"/>
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        <property type="protein sequence ID" value="EAW69898.1"/>
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        <property type="protein sequence ID" value="AAH12597.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.15 A"/>
        <property type="chains" value="B=52-60"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
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        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
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        <property type="generic name" value="1-Methylhistidine"/>
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        <property type="generic name" value="Aplyronine A"/>
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        <property type="generic name" value="Jaspisamide A"/>
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        <property type="generic name" value="Kabiramide C"/>
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        <property type="generic name" value="Latrunculin A"/>
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        <property type="generic name" value="Reidispongiolide A"/>
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        <property type="gene ID" value="ENSG00000143632.16"/>
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        <property type="RefSeq protein sequence ID" value="NP_001091.1"/>
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        <property type="gene designation" value="ACTA1"/>
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        <property type="disease" value="Congenital fiber-type disproportion myopathy"/>
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        <property type="disease" value="Congenital myopathy with excess of thin filaments"/>
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        <property type="disease" value="Intermediate nemaline myopathy"/>
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        <property type="disease" value="Progressive scapulohumeroperoneal distal myopathy"/>
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    <dbReference type="Orphanet" id="97244">
        <property type="disease" value="Rigid spine syndrome"/>
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        <property type="disease" value="Severe congenital nemaline myopathy"/>
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        <property type="disease" value="Typical nemaline myopathy"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="pathway name" value="Regulation of CDH1 Function"/>
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        <property type="organism name" value="human"/>
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    <dbReference type="GO" id="GO:0030240">
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        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="CDD" id="cd10224">
        <property type="entry name" value="ASKHA_NBD_actin"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.420.40:FF:000291">
        <property type="entry name" value="Actin, alpha skeletal muscle"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.90.640.10:FF:000047">
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        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.420.40:FF:000058">
        <property type="entry name" value="Putative actin-related protein 5"/>
        <property type="match status" value="1"/>
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    </dbReference>
    <dbReference type="Gene3D" id="3.90.640.10">
        <property type="entry name" value="Actin, Chain A, domain 4"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR004000">
        <property type="entry name" value="Actin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020902">
        <property type="entry name" value="Actin/actin-like_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004001">
        <property type="entry name" value="Actin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043129">
        <property type="entry name" value="ATPase_NBD"/>
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00022">
        <property type="entry name" value="Actin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00190">
        <property type="entry name" value="ACTIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00268">
        <property type="entry name" value="ACTIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53067">
        <property type="entry name" value="Actin-like ATPase domain"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00406">
        <property type="entry name" value="ACTINS_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00432">
        <property type="entry name" value="ACTINS_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01132">
        <property type="entry name" value="ACTINS_ACT_LIKE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0514">Muscle protein</keyword>
    <keyword id="KW-1057">Nemaline myopathy</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0558">Oxidation</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000442803" description="Actin, alpha skeletal muscle, intermediate form" evidence="2">
        <location>
            <begin position="2"/>
            <end position="377"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000442804" description="Actin, alpha skeletal muscle" evidence="4">
        <location>
            <begin position="3"/>
            <end position="377"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with alpha-actinin" evidence="4">
        <location>
            <begin position="112"/>
            <end position="125"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with alpha-actinin" evidence="4">
        <location>
            <begin position="360"/>
            <end position="372"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylcysteine; in intermediate form" evidence="3">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="modified residue" description="Methionine (R)-sulfoxide" evidence="3">
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-malonyllysine" evidence="21">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="modified residue" description="Tele-methylhistidine" evidence="28">
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-methyllysine" evidence="24">
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-272); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="cross-link" description="Isoglutamyl lysine isopeptide (Glu-Lys) (interchain with K-52); by Vibrio toxins RtxA and VgrG1" evidence="1">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062424" description="In CMYO2A; some patients have core lesions on muscle biopsy; dbSNP:rs121909527." evidence="15">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011680" description="In CMYO2A; dbSNP:rs121909521." evidence="6">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085717" description="In CMYO2A; dbSNP:rs121909521." evidence="27">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062425" description="In CMYO2A." evidence="10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062426" description="In CMYO2A; dbSNP:rs1553255521." evidence="10 12">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062427" description="In CMYO2A." evidence="10 12">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015579" description="In CMYO2A; dbSNP:rs2102736554." evidence="6 10 12">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062428" description="In CMYO2A; dbSNP:rs1659984269." evidence="10 12">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062429" description="In CMYO2A; dbSNP:rs1558082125." evidence="10">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062430" description="In CMYO2A; dbSNP:rs398123562." evidence="10">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062431" description="In CMYO2A; dbSNP:rs1553255502." evidence="10 12">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062432" description="In CMYO2A." evidence="11">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083589" description="In CMYO2A; dbSNP:rs1659978909." evidence="25">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062433" description="In CMYO2A." evidence="11">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062434" description="In CMYO2A." evidence="10 12">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062435" description="In CMYO2A." evidence="10 12">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062436" description="In CMYO2A." evidence="12">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062437" description="In CMYO2A." evidence="10 12">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062438" description="In CMYO2A." evidence="12">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="85"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011681" description="In CMYO2B; dbSNP:rs121909519." evidence="6 10">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062439" description="In CMYO2A; dbSNP:rs1659975786." evidence="10">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_083590" description="In CMYO2A; dbSNP:rs1659975747." evidence="25">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011682" description="In CMYO2A; dbSNP:rs121909520." evidence="6 9 10 11">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062440" description="In CMYO2A." evidence="10">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062441" description="In CMYO2A." evidence="10">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013470" description="In CMYO2A; dbSNP:rs1659974377." evidence="6 8 10">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062442" description="In CMYO2A." evidence="10 12">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011683" description="In CMYO2A; dbSNP:rs121909526." evidence="9 10 11">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062443" description="In CMYO2A." evidence="10">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062444" description="In CMYO2A; dbSNP:rs1553255482." evidence="10">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062445" description="In CMYO2A." evidence="10 12">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062446" description="In CMYO2A." evidence="10">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062447" description="In CMYO2A." evidence="10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011684" description="In CMYO2A; dbSNP:rs121909522." evidence="6 10 11">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="165"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062448" description="In CMYO2A; results in sequestration of sarcomeric and Z line proteins into intranuclear aggregates; there is some evidence of muscle regeneration suggesting a compensatory effect; dbSNP:rs121909522." evidence="10 11 16 20">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="165"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062449" description="In CMYO2A." evidence="10">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062450" description="In CMYO2A." evidence="12">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062451" description="In CMYO2A." evidence="10">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062452" description="In CMYO2A." evidence="10">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015580" description="In CMYO2A." evidence="6 10 12">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015582" description="In CMYO2A; dbSNP:rs1064794287." evidence="6 10">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062453" description="In CMYO2A; requires 2 nucleotide substitutions.">
        <original>R</original>
        <variation>D</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015581" description="In CMYO2A." evidence="9 10 11 12">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062454" description="In CMYO2A; dbSNP:rs1064794287." evidence="10">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076426" description="In SHPM; no effect on cytoskeleton structure; dbSNP:rs869312739." evidence="26">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062455" description="In CMYO2A." evidence="10">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062456" description="In CMYO2A." evidence="12">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="199"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032917" description="In CMYO2C; dbSNP:rs121909530." evidence="14">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="223"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062457" description="In CMYO2A." evidence="10 12">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062458" description="In CMYO2A; dbSNP:rs1057521118." evidence="10">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062459" description="In CMYO2A; requires 2 nucleotide substitutions.">
        <original>N</original>
        <variation>V</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062460" description="In CMYO2A." evidence="10 12">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062461" description="In CMYO2A." evidence="10">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062462" description="In CMYO2A; dbSNP:rs794727714." evidence="10 12">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062463" description="In CMYO2A; dbSNP:rs367543051." evidence="10">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062464" description="In CMYO2A; dbSNP:rs1659954634." evidence="10">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062465" description="In CMYO2A." evidence="10 12">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062466" description="In CMYO2A." evidence="10 12">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015583" description="In CMYO2A; dbSNP:rs1659953887." evidence="6 10">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062467" description="In CMYO2A." evidence="10">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011685" description="In CMYO2B; dbSNP:rs121909523." evidence="6 10">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="261"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015584" description="In CMYO2A." evidence="6 10">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011686" description="In CMYO2A; dbSNP:rs121909525." evidence="9 10 11 12">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062468" description="In CMYO2A; dbSNP:rs1553255362." evidence="13">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062469" description="In CMYO2A; dbSNP:rs121909525." evidence="10">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013471" description="In CMYO2A; dbSNP:rs1553255360." evidence="8 10">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062470" description="In CMYO2A; dbSNP:rs1553255357." evidence="10">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062471" description="In CMYO2A; dbSNP:rs2102735278." evidence="10 12">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015585" description="In CMYO2A; dbSNP:rs2102735270." evidence="6 10 12">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="282"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062472" description="In CMYO2A." evidence="10">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_015586" description="In CMYO2A; formation of rod-like structure." evidence="6 10 12 26">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="288"/>
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    </feature>
    <feature type="sequence variant" id="VAR_032918" description="In CMYO2C; results in decreased motility due to abnormal interactions between actin and tropomyosin with tropomyosin stabilized in the 'off' position; the mutant protein incorporates into actin filaments and does not result in increased actin aggregation or disruption of the sarcomere; dbSNP:rs121909529." evidence="14 19">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="294"/>
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    <feature type="sequence variant" id="VAR_076427" description="In CMYO2A; no effect on actin structure; higher sensitivity to calcium; dbSNP:rs398122936." evidence="22">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="328"/>
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    <feature type="sequence variant" id="VAR_032919" description="In CMYO2C; dbSNP:rs121909531." evidence="14">
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        <location>
            <position position="334"/>
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    <feature type="sequence variant" id="VAR_062473" description="In CMYO2A; dbSNP:rs121909528." evidence="15">
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        <location>
            <position position="336"/>
        </location>
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        <location>
            <position position="338"/>
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    </feature>
    <feature type="sequence variant" id="VAR_062475" description="In CMYO2A." evidence="10">
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        <location>
            <position position="338"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062476" description="In CMYO2A; dbSNP:rs2102735031." evidence="10">
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        <location>
            <position position="350"/>
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    </feature>
    <feature type="sequence variant" id="VAR_076428" description="In CMYO2A; found in a patient with a rare combination of CMYO2A and dilated cardiomyopathy; dbSNP:rs587777354." evidence="23">
        <original>W</original>
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        <location>
            <position position="358"/>
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    <feature type="sequence variant" id="VAR_015587" description="In CMYO2A; dbSNP:rs121909524." evidence="9 10 11">
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        <location>
            <position position="359"/>
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    <feature type="sequence variant" id="VAR_011687" description="In CMYO2A." evidence="6 10">
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        <location>
            <position position="372"/>
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    </feature>
    <feature type="sequence variant" id="VAR_062477" description="In CMYO2A." evidence="10">
        <original>R</original>
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        <location>
            <position position="374"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062478" description="In CMYO2A; dbSNP:rs1571892209." evidence="13">
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        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062479" description="In CMYO2A." evidence="10 12">
        <original>K</original>
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        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="strand" evidence="34">
        <location>
            <begin position="10"/>
            <end position="14"/>
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    </feature>
    <feature type="strand" evidence="34">
        <location>
            <begin position="16"/>
            <end position="23"/>
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    </feature>
    <feature type="strand" evidence="34">
        <location>
            <begin position="30"/>
            <end position="34"/>
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    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="42"/>
            <end position="44"/>
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    </feature>
    <feature type="strand" evidence="34">
        <location>
            <begin position="46"/>
            <end position="49"/>
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    </feature>
    <feature type="strand" evidence="32">
        <location>
            <begin position="53"/>
            <end position="55"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="58"/>
            <end position="62"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="64"/>
            <end position="66"/>
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    </feature>
    <feature type="strand" evidence="34">
        <location>
            <begin position="72"/>
            <end position="74"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="81"/>
            <end position="94"/>
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    <feature type="turn" evidence="34">
        <location>
            <begin position="100"/>
            <end position="102"/>
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    <feature type="strand" evidence="34">
        <location>
            <begin position="105"/>
            <end position="109"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="115"/>
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    <feature type="strand" evidence="34">
        <location>
            <begin position="132"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="139"/>
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    <feature type="strand" evidence="34">
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            <begin position="150"/>
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    <feature type="strand" evidence="34">
        <location>
            <begin position="162"/>
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    <feature type="strand" evidence="34">
        <location>
            <begin position="178"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="184"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="196"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="205"/>
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    <feature type="helix" evidence="34">
        <location>
            <begin position="225"/>
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    <feature type="strand" evidence="34">
        <location>
            <begin position="240"/>
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    <feature type="strand" evidence="34">
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            <begin position="245"/>
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    <feature type="strand" evidence="34">
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    <sequence length="377" mass="42051" checksum="DF2A3A046346A179" modified="1986-07-21" version="1" precursor="true">MCDEDETTALVCDNGSGLVKAGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQSKRGILTLKYPIEHGIITNWDDMEKIWHHTFYNELRVAPEEHPTLLTEAPLNPKANREKMTQIMFETFNVPAMYVAIQAVLSLYASGRTTGIVLDSGDGVTHNVPIYEGYALPHAIMRLDLAGRDLTDYLMKILTERGYSFVTTAEREIVRDIKEKLCYVALDFENEMATAASSSSLEKSYELPDGQVITIGNERFRCPETLFQPSFIGMESAGIHETTYNSIMKCDIDIRKDLYANNVMSGGTTMYPGIADRMQKEITALAPSTMKIKIIAPPERKYSVWIGGSILASLSTFQQMWITKQEYDEAGPSIVHRKCF</sequence>
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<entry dataset="Swiss-Prot" created="2005-10-25" modified="2026-01-28" version="185" xmlns="https://uniprot.org/uniprot">
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF LYS-222</scope>
        <source>
            <tissue evidence="9">Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue evidence="17">Placenta</tissue>
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            <dbReference type="PubMed" id="15815621"/>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue evidence="16">Brain</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15531507"/>
            <dbReference type="DOI" id="10.1210/jc.2004-0893"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF THR-194 AND LYS-222</scope>
    </reference>
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        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF LYS-222</scope>
    </reference>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] THR-195; ARG-216; ARG-267; VAL-355 AND VAL-482</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 9 11 12">Serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consists of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. Receptor for activin AB, activin B, activin E and NODAL. Upon NODAL binding, activation results in increased apoptosis and reduced proliferation through suppression of AKT signaling and the activation of Smad2-dependent signaling pathway in pancreatic beta-cells, trophoblasts, epithelial or neuronal cells (PubMed:15531507, PubMed:15150278). Acts as a positive regulator for macrophage activation partially through down-regulation of PPARG expression (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44880"/>
            <dbReference type="Rhea" id="RHEA-COMP:11024"/>
            <dbReference type="Rhea" id="RHEA-COMP:11025"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:18673"/>
            <dbReference type="Rhea" id="RHEA-COMP:11022"/>
            <dbReference type="Rhea" id="RHEA-COMP:11023"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="15">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="15">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="1">Binds the type 2 receptor protein ACVR2A.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Membrane</location>
            <topology evidence="10">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NER5-1</id>
            <name evidence="10">1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NER5-2</id>
            <name evidence="10">2</name>
            <name evidence="14">B</name>
            <name evidence="14">soluble B</name>
            <sequence type="described" ref="VSP_051841"/>
        </isoform>
        <isoform>
            <id>Q8NER5-3</id>
            <name evidence="10">3</name>
            <name evidence="14">A</name>
            <name evidence="14">soluble A</name>
            <sequence type="described" ref="VSP_051842"/>
        </isoform>
        <isoform>
            <id>Q8NER5-4</id>
            <name evidence="10">4</name>
            <name evidence="14">Truncated</name>
            <sequence type="described" ref="VSP_051840"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 10">Present in pancreas, heart, colon, small intestine, ovary and the hippocampus, medulla oblongata and putamen of the brain. Isoform 1, isoform 2, isoform 3 and isoform 4 are all expressed in the placenta throughout pregnancy.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.</text>
    </comment>
    <dbReference type="EC" id="2.7.11.30"/>
    <dbReference type="EMBL" id="AY127050">
        <property type="protein sequence ID" value="AAM93495.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF525679">
        <property type="protein sequence ID" value="AAP21993.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF525680">
        <property type="protein sequence ID" value="AAP21994.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF525681">
        <property type="protein sequence ID" value="AAP21995.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC019186">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC079750">
        <property type="protein sequence ID" value="AAX88951.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022530">
        <property type="protein sequence ID" value="AAH22530.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2205.1">
        <molecule id="Q8NER5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46432.1">
        <molecule id="Q8NER5-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46433.1">
        <molecule id="Q8NER5-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46434.1">
        <molecule id="Q8NER5-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001104501.1">
        <molecule id="Q8NER5-4"/>
        <property type="nucleotide sequence ID" value="NM_001111031.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001104502.1">
        <molecule id="Q8NER5-3"/>
        <property type="nucleotide sequence ID" value="NM_001111032.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001104503.1">
        <molecule id="Q8NER5-2"/>
        <property type="nucleotide sequence ID" value="NM_001111033.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_660302.2">
        <molecule id="Q8NER5-1"/>
        <property type="nucleotide sequence ID" value="NM_145259.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8NER5"/>
    <dbReference type="SMR" id="Q8NER5"/>
    <dbReference type="BioGRID" id="126232">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="CORUM" id="Q8NER5"/>
    <dbReference type="FunCoup" id="Q8NER5">
        <property type="interactions" value="744"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8NER5">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000243349"/>
    <dbReference type="ChEMBL" id="CHEMBL5642"/>
    <dbReference type="iPTMnet" id="Q8NER5"/>
    <dbReference type="PhosphoSitePlus" id="Q8NER5"/>
    <dbReference type="BioMuta" id="ACVR1C"/>
    <dbReference type="DMDM" id="74762565"/>
    <dbReference type="jPOST" id="Q8NER5"/>
    <dbReference type="MassIVE" id="Q8NER5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000243349"/>
    <dbReference type="PeptideAtlas" id="Q8NER5"/>
    <dbReference type="ProteomicsDB" id="73204">
        <molecule id="Q8NER5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73205">
        <molecule id="Q8NER5-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73206">
        <molecule id="Q8NER5-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="73207">
        <molecule id="Q8NER5-4"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2075">
        <property type="antibodies" value="419 antibodies from 35 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="130399"/>
    <dbReference type="Ensembl" id="ENST00000243349.13">
        <molecule id="Q8NER5-1"/>
        <property type="protein sequence ID" value="ENSP00000243349.7"/>
        <property type="gene ID" value="ENSG00000123612.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000335450.7">
        <molecule id="Q8NER5-3"/>
        <property type="protein sequence ID" value="ENSP00000335178.7"/>
        <property type="gene ID" value="ENSG00000123612.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000348328.9">
        <molecule id="Q8NER5-2"/>
        <property type="protein sequence ID" value="ENSP00000335139.6"/>
        <property type="gene ID" value="ENSG00000123612.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409680.7">
        <molecule id="Q8NER5-4"/>
        <property type="protein sequence ID" value="ENSP00000387168.3"/>
        <property type="gene ID" value="ENSG00000123612.17"/>
    </dbReference>
    <dbReference type="GeneID" id="130399"/>
    <dbReference type="KEGG" id="hsa:130399"/>
    <dbReference type="MANE-Select" id="ENST00000243349.13">
        <property type="protein sequence ID" value="ENSP00000243349.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_145259.3"/>
        <property type="RefSeq protein sequence ID" value="NP_660302.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002tzk.5">
        <molecule id="Q8NER5-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18123"/>
    <dbReference type="ClinPGx" id="PA134908988"/>
    <dbReference type="CTD" id="130399"/>
    <dbReference type="DisGeNET" id="130399"/>
    <dbReference type="GeneCards" id="ACVR1C"/>
    <dbReference type="HGNC" id="HGNC:18123">
        <property type="gene designation" value="ACVR1C"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000123612">
        <property type="expression patterns" value="Tissue enriched (adipose)"/>
    </dbReference>
    <dbReference type="MIM" id="608981">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000123612"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000123612"/>
    <dbReference type="eggNOG" id="KOG2052">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158842"/>
    <dbReference type="HOGENOM" id="CLU_000288_8_1_1"/>
    <dbReference type="InParanoid" id="Q8NER5"/>
    <dbReference type="OMA" id="TCQGRQC"/>
    <dbReference type="OrthoDB" id="69842at2759"/>
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        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NER5"/>
    <dbReference type="BRENDA" id="2.7.11.30">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q8NER5"/>
    <dbReference type="Reactome" id="R-HSA-1181150">
        <property type="pathway name" value="Signaling by NODAL"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-1433617">
        <property type="pathway name" value="Regulation of signaling by NODAL"/>
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    <dbReference type="Reactome" id="R-HSA-1502540">
        <property type="pathway name" value="Signaling by Activin"/>
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    <dbReference type="SIGNOR" id="Q8NER5"/>
    <dbReference type="Agora" id="ENSG00000123612"/>
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        <property type="hits" value="8 hits in 1185 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACVR1C">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ACVR1C"/>
    <dbReference type="GenomeRNAi" id="130399"/>
    <dbReference type="Pharos" id="Q8NER5">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NER5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NER5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000123612">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 130 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048179">
        <property type="term" value="C:activin receptor complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="F:activin receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ARUK-UCL"/>
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    <dbReference type="GO" id="GO:0016361">
        <property type="term" value="F:activin receptor activity, type I"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0019838">
        <property type="term" value="F:growth factor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0000305"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0038100">
        <property type="term" value="F:nodal binding"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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        <property type="term" value="P:activin receptor signaling pathway"/>
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    <dbReference type="GO" id="GO:0030262">
        <property type="term" value="P:apoptotic nuclear changes"/>
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    <dbReference type="GO" id="GO:0097190">
        <property type="term" value="P:apoptotic signaling pathway"/>
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        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
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        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0071363">
        <property type="term" value="P:cellular response to growth factor stimulus"/>
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    <dbReference type="GO" id="GO:0030073">
        <property type="term" value="P:insulin secretion"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0019915">
        <property type="term" value="P:lipid storage"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:negative regulation of chorionic trophoblast cell proliferation"/>
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        <property type="term" value="P:negative regulation of insulin secretion"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:negative regulation of trophoblast cell migration"/>
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    <dbReference type="GO" id="GO:0007399">
        <property type="term" value="P:nervous system development"/>
        <property type="evidence" value="ECO:0000318"/>
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        <property type="term" value="P:nodal signaling pathway"/>
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    <dbReference type="GO" id="GO:0043065">
        <property type="term" value="P:positive regulation of apoptotic process"/>
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        <property type="project" value="MGI"/>
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    <dbReference type="GO" id="GO:0006468">
        <property type="term" value="P:protein phosphorylation"/>
        <property type="evidence" value="ECO:0000305"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:response to dietary excess"/>
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        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0009749">
        <property type="term" value="P:response to glucose"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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        <property type="term" value="P:response to insulin"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0001834">
        <property type="term" value="P:trophectodermal cell proliferation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="CDD" id="cd14143">
        <property type="entry name" value="STKc_TGFbR1_ACVR1b_ACVR1c"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd23540">
        <property type="entry name" value="TFP_LU_ECD_ALK7"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.510.10:FF:000045">
        <property type="entry name" value="Receptor protein serine/threonine kinase"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.10.60.10:FF:000007">
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        <property type="entry name" value="CD59"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.200.20">
        <property type="entry name" value="Phosphorylase Kinase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.510.10">
        <property type="entry name" value="Transferase(Phosphotransferase) domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000472">
        <property type="entry name" value="Activin_recp"/>
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    <dbReference type="InterPro" id="IPR003605">
        <property type="entry name" value="GS_dom"/>
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    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
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    <dbReference type="InterPro" id="IPR000719">
        <property type="entry name" value="Prot_kinase_dom"/>
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    <dbReference type="InterPro" id="IPR017441">
        <property type="entry name" value="Protein_kinase_ATP_BS"/>
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    <dbReference type="InterPro" id="IPR001245">
        <property type="entry name" value="Ser-Thr/Tyr_kinase_cat_dom"/>
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        <property type="entry name" value="Ser/Thr_kinase_AS"/>
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    <dbReference type="InterPro" id="IPR045860">
        <property type="entry name" value="Snake_toxin-like_sf"/>
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    <dbReference type="InterPro" id="IPR000333">
        <property type="entry name" value="TGFB_receptor"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23255:SF58">
        <property type="entry name" value="ACTIVIN RECEPTOR TYPE-1C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23255">
        <property type="entry name" value="TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01064">
        <property type="entry name" value="Activin_recp"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF07714">
        <property type="entry name" value="PK_Tyr_Ser-Thr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08515">
        <property type="entry name" value="TGF_beta_GS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00467">
        <property type="entry name" value="GS"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00220">
        <property type="entry name" value="S_TKc"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF57302">
        <property type="entry name" value="Snake toxin-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="GS"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS00107">
        <property type="entry name" value="PROTEIN_KINASE_ATP"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50011">
        <property type="entry name" value="PROTEIN_KINASE_DOM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00108">
        <property type="entry name" value="PROTEIN_KINASE_ST"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="5">
        <location>
            <begin position="1"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000042628" description="Activin receptor type-1C">
        <location>
            <begin position="21"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="5">
        <location>
            <begin position="22"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="5">
        <location>
            <begin position="114"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="5">
        <location>
            <begin position="135"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="domain" description="GS" evidence="7">
        <location>
            <begin position="165"/>
            <end position="194"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase" evidence="6">
        <location>
            <begin position="195"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="3 6 8">
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3 6">
        <location>
            <begin position="201"/>
            <end position="209"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3 6">
        <location>
            <position position="222"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_051840" description="In isoform 4." evidence="14">
        <location>
            <begin position="1"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051841" description="In isoform 2." evidence="14">
        <location>
            <begin position="102"/>
            <end position="258"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_051842" description="In isoform 3." evidence="14">
        <location>
            <begin position="102"/>
            <end position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041407" description="In dbSNP:rs56188432." evidence="13">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="195"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041408" description="In dbSNP:rs34742924." evidence="13">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041409" description="In a lung squamous cell carcinoma sample; somatic mutation." evidence="13">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="267"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041410" description="In dbSNP:rs35500979." evidence="13">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="355"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041411" description="In dbSNP:rs7594480." evidence="13">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Pro-apoptotic." evidence="12">
        <original>T</original>
        <variation>D</variation>
        <location>
            <position position="194"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of response to NODAL and SMAD2 phosphorylation." evidence="9 11 12">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH22530." evidence="15" ref="4">
        <original>S</original>
        <variation>Y</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAH22530." evidence="15" ref="4">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P70539"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q04771"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q8K348"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00159"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="7">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00585"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="8">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10027"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12063393"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12606401"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="15150278"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="15531507"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="17344846"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="12606401"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="EMBL" id="AAH22530.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="17">
        <source>
            <dbReference type="EMBL" id="AAM93495.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="18">
        <source>
            <dbReference type="EMBL" id="AAP21994.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="19">
        <source>
            <dbReference type="EMBL" id="AAX88951.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="20">
        <source>
            <dbReference type="HGNC" id="HGNC:18123"/>
        </source>
    </evidence>
    <sequence length="493" mass="54871" checksum="5A10F259679204CB" modified="2002-10-01" version="1" precursor="true">MTRALCSALRQALLLLAAAAELSPGLKCVCLLCDSSNFTCQTEGACWASVMLTNGKEQVIKSCVSLPELNAQVFCHSSNNVTKTECCFTDFCNNITLHLPTASPNAPKLGPMELAIIITVPVCLLSIAAMLTVWACQGRQCSYRKKKRPNVEEPLSECNLVNAGKTLKDLIYDVTASGSGSGLPLLVQRTIARTIVLQEIVGKGRFGEVWHGRWCGEDVAVKIFSSRDERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSEYHEQGSLYDYLNRNIVTVAGMIKLALSIASGLAHLHMEIVGTQGKPAIAHRDIKSKNILVKKCETCAIADLGLAVKHDSILNTIDIPQNPKVGTKRYMAPEMLDDTMNVNIFESFKRADIYSVGLVYWEIARRCSVGGIVEEYQLPYYDMVPSDPSIEEMRKVVCDQKFRPSIPNQWQSCEALRVMGRIMRECWYANGAARLTALRIKKTISQLCVKEDCKA</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-08-29" modified="2026-01-28" version="171" xmlns="https://uniprot.org/uniprot">
    <accession>Q96HD9</accession>
    <name>ACY3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming)</fullName>
            <ecNumber>3.5.1.114</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acylase III</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Aminoacylase-3</fullName>
            <shortName>ACY-3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Aspartoacylase-2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Hepatitis C virus core-binding protein 1</fullName>
            <shortName>HCBP1</shortName>
            <shortName>HCV core-binding protein 1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACY3</name>
        <name type="synonym">ASPA2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2001-06" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of a novel aspartoacylase homolog (ACY-3) in human and mouse kidneys.</title>
            <authorList>
                <person name="Huang C.-H."/>
                <person name="Chen H."/>
                <person name="Peng J."/>
                <person name="Chen Y."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2002-10" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Pushkin A."/>
                <person name="Carpenito G."/>
                <person name="Abuladze N."/>
                <person name="Newman D."/>
                <person name="Kurtz I."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Colon</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2009" name="J. Gastroenterol. Hepatol." volume="24" first="1300" last="1304">
            <title>Identification of a novel protein binding to hepatitis C virus core protein.</title>
            <authorList>
                <person name="Chen Y.R."/>
                <person name="Chen T.Y."/>
                <person name="Zhang S.L."/>
                <person name="Lin S.M."/>
                <person name="Zhao Y.R."/>
                <person name="Ye F."/>
                <person name="Zhang X."/>
                <person name="Shi L."/>
                <person name="Dang S.S."/>
                <person name="Liu M."/>
            </authorList>
            <dbReference type="PubMed" id="19486448"/>
            <dbReference type="DOI" id="10.1111/j.1440-1746.2009.05846.x"/>
        </citation>
        <scope>INTERACTION WITH HCV CORE PROTEIN (MICROBIAL INFECTION)</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>an N-acyl-aromatic L-alpha-amino acid + H2O = an aromatic L-alpha-amino acid + a carboxylate</text>
            <dbReference type="Rhea" id="RHEA:54184"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:29067"/>
            <dbReference type="ChEBI" id="CHEBI:84824"/>
            <dbReference type="ChEBI" id="CHEBI:138093"/>
            <dbReference type="EC" id="3.5.1.114"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>an N-acetyl-L-cysteine-S-conjugate + H2O = an S-substituted L-cysteine + acetate</text>
            <dbReference type="Rhea" id="RHEA:36855"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:58717"/>
            <dbReference type="ChEBI" id="CHEBI:58718"/>
            <dbReference type="EC" id="3.5.1.114"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Exists as a mixture of homodimers and homotetramer, both catalytically active.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">(Microbial infection) Interacts with hepatitis C virus/HCV core protein.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-10308705">
            <id>Q9H7C9</id>
            <label>AAMDC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-4289908">
            <id>P84085</id>
            <label>ARF5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-750475">
            <id>P45381</id>
            <label>ASPA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-3867333">
            <id>A8MQ03</id>
            <label>CYSRT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-742054">
            <id>Q96D03</id>
            <label>DDIT4L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-739467">
            <id>Q9H8Y8</id>
            <label>GORASP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-6509505">
            <id>Q0VD86</id>
            <label>INCA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-11992140">
            <id>Q3LI76</id>
            <label>KRTAP15-1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-3957672">
            <id>Q6PEX3</id>
            <label>KRTAP26-1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-739832">
            <id>Q8TBB1</id>
            <label>LNX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-945833">
            <id>Q7Z3S9</id>
            <label>NOTCH2NLA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-348555">
            <id>O75928</id>
            <label>PIAS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-742388">
            <id>Q9H8W4</id>
            <label>PLEKHF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-10182608">
            <id>O15305</id>
            <label>PMM2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
        </interactant>
        <interactant intactId="EBI-6260">
            <id>P32502</id>
            <label>GCD7</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Apical cell membrane</location>
            <topology evidence="3">Peripheral membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <text>Predominantly localized in the apical membrane of cells in the S1 segment. In the proximal straight tubules (S2 and S3 segments) is expressed diffusely throughout the cytoplasm.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the AspA/AstE family. Aspartoacylase subfamily.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.114"/>
    <dbReference type="EMBL" id="AY040761">
        <property type="protein sequence ID" value="AAK94770.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY169233">
        <property type="protein sequence ID" value="AAN87896.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008689">
        <property type="protein sequence ID" value="AAH08689.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8175.1"/>
    <dbReference type="RefSeq" id="NP_542389.1">
        <property type="nucleotide sequence ID" value="NM_080658.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96HD9"/>
    <dbReference type="SMR" id="Q96HD9"/>
    <dbReference type="BioGRID" id="124869">
        <property type="interactions" value="28"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96HD9">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96HD9">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="MINT" id="Q96HD9"/>
    <dbReference type="STRING" id="9606.ENSP00000255082"/>
    <dbReference type="iPTMnet" id="Q96HD9"/>
    <dbReference type="PhosphoSitePlus" id="Q96HD9"/>
    <dbReference type="BioMuta" id="ACY3"/>
    <dbReference type="DMDM" id="34395507"/>
    <dbReference type="jPOST" id="Q96HD9"/>
    <dbReference type="MassIVE" id="Q96HD9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000255082"/>
    <dbReference type="PeptideAtlas" id="Q96HD9"/>
    <dbReference type="ProteomicsDB" id="76736"/>
    <dbReference type="Antibodypedia" id="30490">
        <property type="antibodies" value="302 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="91703"/>
    <dbReference type="Ensembl" id="ENST00000255082.8">
        <property type="protein sequence ID" value="ENSP00000255082.3"/>
        <property type="gene ID" value="ENSG00000132744.9"/>
    </dbReference>
    <dbReference type="GeneID" id="91703"/>
    <dbReference type="KEGG" id="hsa:91703"/>
    <dbReference type="MANE-Select" id="ENST00000255082.8">
        <property type="protein sequence ID" value="ENSP00000255082.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_080658.2"/>
        <property type="RefSeq protein sequence ID" value="NP_542389.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001omq.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24104"/>
    <dbReference type="ClinPGx" id="PA134936640"/>
    <dbReference type="CTD" id="91703"/>
    <dbReference type="DisGeNET" id="91703"/>
    <dbReference type="GeneCards" id="ACY3"/>
    <dbReference type="HGNC" id="HGNC:24104">
        <property type="gene designation" value="ACY3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000132744">
        <property type="expression patterns" value="Group enriched (intestine, kidney, liver, pancreas)"/>
    </dbReference>
    <dbReference type="MIM" id="614413">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000132744"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000132744"/>
    <dbReference type="eggNOG" id="ENOG502QRAK">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000001189"/>
    <dbReference type="HOGENOM" id="CLU_083292_0_0_1"/>
    <dbReference type="InParanoid" id="Q96HD9"/>
    <dbReference type="OMA" id="AMHLCHH"/>
    <dbReference type="OrthoDB" id="8300214at2759"/>
    <dbReference type="PAN-GO" id="Q96HD9">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96HD9"/>
    <dbReference type="BioCyc" id="MetaCyc:HS13441-MONOMER"/>
    <dbReference type="BRENDA" id="3.5.1.114">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q96HD9"/>
    <dbReference type="Reactome" id="R-HSA-5423646">
        <property type="pathway name" value="Aflatoxin activation and detoxification"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q96HD9"/>
    <dbReference type="Agora" id="ENSG00000132744"/>
    <dbReference type="BioGRID-ORCS" id="91703">
        <property type="hits" value="27 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="91703"/>
    <dbReference type="Pharos" id="Q96HD9">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96HD9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96HD9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000132744">
        <property type="expression patterns" value="Expressed in ileal mucosa and 120 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96HD9">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016324">
        <property type="term" value="C:apical plasma membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004046">
        <property type="term" value="F:aminoacylase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016788">
        <property type="term" value="F:hydrolase activity, acting on ester bonds"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd06909">
        <property type="entry name" value="M14_ASPA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.20.25.160:FF:000001">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.630.10:FF:000025">
        <property type="entry name" value="aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.20.25.160">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.630.10">
        <property type="entry name" value="Zn peptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_00704">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050178">
        <property type="entry name" value="AspA/AstE_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016708">
        <property type="entry name" value="Aspartoacylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR055438">
        <property type="entry name" value="AstE_AspA_cat"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007036">
        <property type="entry name" value="Aste_AspA_hybrid_dom"/>
    </dbReference>
    <dbReference type="NCBIfam" id="NF002601">
        <property type="entry name" value="PRK02259.1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15162">
        <property type="entry name" value="ASPARTOACYLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15162:SF5">
        <property type="entry name" value="N-ACYL-AROMATIC-L-AMINO ACID AMIDOHYDROLASE (CARBOXYLATE-FORMING)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF24827">
        <property type="entry name" value="AstE_AspA_cat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04952">
        <property type="entry name" value="AstE_AspA_hybrid"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF018001">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53187">
        <property type="entry name" value="Zn-dependent exopeptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000216875" description="N-acyl-aromatic-L-amino acid amidohydrolase (carboxylate-forming)">
        <location>
            <begin position="1"/>
            <end position="319"/>
        </location>
    </feature>
    <feature type="region of interest" description="Hydrolytic domain" evidence="1">
        <location>
            <begin position="1"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="region of interest" description="Shielding domain" evidence="1">
        <location>
            <begin position="211"/>
            <end position="318"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="21"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="24"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="63"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="70"/>
            <end position="71"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="116"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="178"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="288"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_048341" description="In dbSNP:rs948445.">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048342" description="In dbSNP:rs2290959.">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="281"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q91XE4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="19486448"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="319" mass="35241" checksum="2595358AC8B5BEFB" modified="2001-12-01" version="1">MCSLPVPREPLRRVAVTGGTHGNEMSGVYLARHWLHAPAELQRASFSAVPVLANPAATSGCRRYVDHDLNRTFTSSFLNSRPTPDDPYEVTRARELNQLLGPKASGQAFDFVLDLHNTTANMGTCLIAKSSHEVFAMHLCRHLQLQYPELSCQVFLYQRSGEESYNLDSVAKNGLGLELGPQPQGVLRADIFSRMRTLVATVLDFIELFNQGTAFPAFEMEAYRPVGVVDFPRTEAGHLAGTVHPQLQDRDFQPLQPGAPIFQMFSGEDLLYEGESTVYPVFINEAAYYEKGVAFVQTEKFTFTVPAMPALTPAPSPAS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="223" xmlns="https://uniprot.org/uniprot">
    <accession>Q03154</accession>
    <accession>C9J6I6</accession>
    <accession>C9J9D8</accession>
    <accession>C9JWD4</accession>
    <name>ACY1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aminoacylase-1</fullName>
            <shortName>ACY-1</shortName>
            <ecNumber evidence="4">3.5.1.14</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>N-acyl-L-amino-acid amidohydrolase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACY1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Biochim. Biophys. Acta" volume="1174" first="201" last="203">
            <title>The nucleotide sequence of human aminoacylase-1.</title>
            <authorList>
                <person name="Mitta M."/>
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            <dbReference type="PubMed" id="8357837"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
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            <title>Human aminoacylase-1. Cloning, sequence, and expression analysis of a chromosome 3p21 gene inactivated in small cell lung cancer.</title>
            <authorList>
                <person name="Cook R.M."/>
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                <person name="Buchhagen D.L."/>
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            </authorList>
            <dbReference type="PubMed" id="8394326"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="1993-06" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Iwaki K."/>
                <person name="Tanaka Y."/>
                <person name="Ohta T."/>
                <person name="Fukuda S."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1194" last="1198">
            <title>The DNA sequence, annotation and analysis of human chromosome 3.</title>
            <authorList>
                <person name="Muzny D.M."/>
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                <person name="Milosavljevic A."/>
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                <person name="Gonzalez-Garay M.L."/>
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                <person name="Hu S."/>
                <person name="Huang W."/>
                <person name="Jackson L.R."/>
                <person name="Jacob L.S."/>
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                <person name="Liu B."/>
                <person name="Liu J."/>
                <person name="Liu W."/>
                <person name="Lu J."/>
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                <person name="Plopper F.J."/>
                <person name="Qiang B."/>
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                <person name="Rodriguez R."/>
                <person name="Saenphimmachak C."/>
                <person name="Santibanez J."/>
                <person name="Shen H."/>
                <person name="Shen Y."/>
                <person name="Subramanian S."/>
                <person name="Tabor P.E."/>
                <person name="Verduzco D."/>
                <person name="Waldron L."/>
                <person name="Wang J."/>
                <person name="Wang J."/>
                <person name="Wang Q."/>
                <person name="Williams G.A."/>
                <person name="Wong G.K.-S."/>
                <person name="Yao Z."/>
                <person name="Zhang J."/>
                <person name="Zhang X."/>
                <person name="Zhao G."/>
                <person name="Zhou J."/>
                <person name="Zhou Y."/>
                <person name="Nelson D."/>
                <person name="Lehrach H."/>
                <person name="Reinhardt R."/>
                <person name="Naylor S.L."/>
                <person name="Yang H."/>
                <person name="Olson M."/>
                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="44496" last="44504">
            <title>Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family.</title>
            <authorList>
                <person name="Lindner H.A."/>
                <person name="Lunin V.V."/>
                <person name="Alary A."/>
                <person name="Hecker R."/>
                <person name="Cygler M."/>
                <person name="Menard R."/>
            </authorList>
            <dbReference type="PubMed" id="12933810"/>
            <dbReference type="DOI" id="10.1074/jbc.m304233200"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ZINC IONS</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF HIS-80; ASP-113; GLU-147; GLU-148; GLU-175; HIS-206 AND HIS-373</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2005" name="Biochem. Biophys. Res. Commun." volume="338" first="1322" last="1326">
            <title>Aminoacylase I deficiency: a novel inborn error of metabolism.</title>
            <authorList>
                <person name="Van Coster R.N."/>
                <person name="Gerlo E.A."/>
                <person name="Giardina T.G."/>
                <person name="Engelke U.F."/>
                <person name="Smet J.E."/>
                <person name="De Praeter C.M."/>
                <person name="Meersschaut V.A."/>
                <person name="De Meirleir L.J."/>
                <person name="Seneca S.H."/>
                <person name="Devreese B."/>
                <person name="Leroy J.G."/>
                <person name="Herga S."/>
                <person name="Perrier J.P."/>
                <person name="Wevers R.A."/>
                <person name="Lissens W."/>
            </authorList>
            <dbReference type="PubMed" id="16274666"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2005.10.126"/>
        </citation>
        <scope>VARIANT ACY1D CYS-353</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2006" name="Am. J. Hum. Genet." volume="78" first="401" last="409">
            <title>Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism.</title>
            <authorList>
                <person name="Sass J.O."/>
                <person name="Mohr V."/>
                <person name="Olbrich H."/>
                <person name="Engelke U."/>
                <person name="Horvath J."/>
                <person name="Fliegauf M."/>
                <person name="Loges N.T."/>
                <person name="Schweitzer-Krantz S."/>
                <person name="Moebus R."/>
                <person name="Weiler P."/>
                <person name="Kispert A."/>
                <person name="Superti-Furga A."/>
                <person name="Wevers R.A."/>
                <person name="Omran H."/>
            </authorList>
            <dbReference type="PubMed" id="16465618"/>
            <dbReference type="DOI" id="10.1086/500563"/>
        </citation>
        <scope>VARIANTS ACY1D ASP-233 AND CYS-353</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
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                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
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                <person name="Willson J.K.V."/>
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                <person name="Wu L."/>
                <person name="Liu C."/>
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                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] ASP-381</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2007" name="Neurology" volume="68" first="2151" last="2153">
            <title>Neurological findings in aminoacylase 1 deficiency.</title>
            <authorList>
                <person name="Sass J.O."/>
                <person name="Olbrich H."/>
                <person name="Mohr V."/>
                <person name="Hart C."/>
                <person name="Woldseth B."/>
                <person name="Krywawych S."/>
                <person name="Bjurulf B."/>
                <person name="Lakhani P.K."/>
                <person name="Buchdahl R.M."/>
                <person name="Omran H."/>
            </authorList>
            <dbReference type="PubMed" id="17562838"/>
            <dbReference type="DOI" id="10.1212/01.wnl.0000264933.56204.e8"/>
        </citation>
        <scope>VARIANTS ACY1D TRP-197; CYS-353 AND HIS-393</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="Biochim. Biophys. Acta" volume="1812" first="685" last="690">
            <title>The molecular basis of aminoacylase 1 deficiency.</title>
            <authorList>
                <person name="Sommer A."/>
                <person name="Christensen E."/>
                <person name="Schwenger S."/>
                <person name="Seul R."/>
                <person name="Haas D."/>
                <person name="Olbrich H."/>
                <person name="Omran H."/>
                <person name="Sass J.O."/>
            </authorList>
            <dbReference type="PubMed" id="21414403"/>
            <dbReference type="DOI" id="10.1016/j.bbadis.2011.03.005"/>
        </citation>
        <scope>VARIANTS ACY1D GLN-378; TRP-378 AND CYS-386</scope>
        <scope>CHARACTERIZATION OF VARIANTS ACY1D TRP-197; ASP-233; CYS-353; TRP-378 AND CYS-386</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">Aminoacylase involved in the hydrolysis of N-acetylated and N-formylated amino acids. May act sequentially with APEH in the degradation of N-acylated peptides: APEH first cleaves N-acylaminoacids from N-acylated peptides, then ACY1 further hydrolyzes the N-acylaminoacid into free aminoacid and a carboxylate.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>an N-acyl-L-amino acid + H2O = an L-alpha-amino acid + a carboxylate</text>
            <dbReference type="Rhea" id="RHEA:15565"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:29067"/>
            <dbReference type="ChEBI" id="CHEBI:59869"/>
            <dbReference type="ChEBI" id="CHEBI:59874"/>
            <dbReference type="EC" id="3.5.1.14"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:15566"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>N-acetyl-L-methionine + H2O = L-methionine + acetate</text>
            <dbReference type="Rhea" id="RHEA:67440"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
            <dbReference type="ChEBI" id="CHEBI:71670"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:67441"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>N-acetyl-L-glutamine + H2O = L-glutamine + acetate</text>
            <dbReference type="Rhea" id="RHEA:67368"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:58359"/>
            <dbReference type="ChEBI" id="CHEBI:143879"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:67369"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>N(alpha)-formyl-L-methionine + H2O = formate + L-methionine</text>
            <dbReference type="Rhea" id="RHEA:17781"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15740"/>
            <dbReference type="ChEBI" id="CHEBI:57809"/>
            <dbReference type="ChEBI" id="CHEBI:57844"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:17782"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="4">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimer. Interacts with SPHK1 (By similarity).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
            <label>ACY1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-1050106">
            <id>O75934</id>
            <label>BCAS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-741158">
            <id>Q96HA8</id>
            <label>NTAQ1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-1048967">
            <id>P36639</id>
            <label>NUDT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-12380931">
            <id>P36639-2</id>
            <label>NUDT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-14017370">
            <id>Q8TCT1</id>
            <label>PHOSPHO1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-11986293">
            <id>P0CG20</id>
            <label>PRR35</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-752030">
            <id>Q96A09</id>
            <label>TENT5B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-710997">
            <id>P54274</id>
            <label>TERF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-3939165">
            <id>O43711</id>
            <label>TLX3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-2214398">
            <id>Q9UPN9</id>
            <label>TRIM33</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-742064">
            <id>Q03154</id>
        </interactant>
        <interactant intactId="EBI-12040603">
            <id>Q9NZC7-5</id>
            <label>WWOX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q03154-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q03154-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046877"/>
        </isoform>
        <isoform>
            <id>Q03154-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046878"/>
        </isoform>
        <isoform>
            <id>Q03154-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046876"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expression is highest in kidney, strong in brain and weaker in placenta and spleen.</text>
    </comment>
    <comment type="disease" evidence="5 6 8 9">
        <disease id="DI-00095">
            <name>Aminoacylase-1 deficiency</name>
            <acronym>ACY1D</acronym>
            <description>An enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.</description>
            <dbReference type="MIM" id="609924"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the peptidase M20A family.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.14" evidence="4"/>
    <dbReference type="EMBL" id="L07548">
        <property type="protein sequence ID" value="AAA02852.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D14524">
        <property type="protein sequence ID" value="BAA03397.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D16307">
        <property type="protein sequence ID" value="BAA03814.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC115284">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000545">
        <property type="protein sequence ID" value="AAH00545.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC003023">
        <property type="protein sequence ID" value="AAH03023.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014112">
        <property type="protein sequence ID" value="AAH14112.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2844.1">
        <molecule id="Q03154-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56261.1">
        <molecule id="Q03154-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56262.1">
        <molecule id="Q03154-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56263.1">
        <molecule id="Q03154-4"/>
    </dbReference>
    <dbReference type="PIR" id="A47488">
        <property type="entry name" value="A47488"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000657.1">
        <molecule id="Q03154-1"/>
        <property type="nucleotide sequence ID" value="NM_000666.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185824.1">
        <molecule id="Q03154-1"/>
        <property type="nucleotide sequence ID" value="NM_001198895.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185825.1">
        <molecule id="Q03154-2"/>
        <property type="nucleotide sequence ID" value="NM_001198896.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185826.1">
        <molecule id="Q03154-3"/>
        <property type="nucleotide sequence ID" value="NM_001198897.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185827.1">
        <molecule id="Q03154-4"/>
        <property type="nucleotide sequence ID" value="NM_001198898.2"/>
    </dbReference>
    <dbReference type="PDB" id="1Q7L">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.40 A"/>
        <property type="chains" value="A/C=1-198, B/D=321-408"/>
    </dbReference>
    <dbReference type="PDBsum" id="1Q7L"/>
    <dbReference type="AlphaFoldDB" id="Q03154"/>
    <dbReference type="SMR" id="Q03154"/>
    <dbReference type="BioGRID" id="106610">
        <property type="interactions" value="69"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q03154">
        <property type="interactions" value="338"/>
    </dbReference>
    <dbReference type="IntAct" id="Q03154">
        <property type="interactions" value="39"/>
    </dbReference>
    <dbReference type="MINT" id="Q03154"/>
    <dbReference type="STRING" id="9606.ENSP00000384296"/>
    <dbReference type="DrugBank" id="DB06151">
        <property type="generic name" value="Acetylcysteine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00128">
        <property type="generic name" value="Aspartic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09130">
        <property type="generic name" value="Copper"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q03154"/>
    <dbReference type="MEROPS" id="M20.973"/>
    <dbReference type="GlyGen" id="Q03154">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q03154"/>
    <dbReference type="PhosphoSitePlus" id="Q03154"/>
    <dbReference type="BioMuta" id="ACY1"/>
    <dbReference type="DMDM" id="461466"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00009268"/>
    <dbReference type="jPOST" id="Q03154"/>
    <dbReference type="MassIVE" id="Q03154"/>
    <dbReference type="PaxDb" id="9606-ENSP00000384296"/>
    <dbReference type="PeptideAtlas" id="Q03154"/>
    <dbReference type="ProteomicsDB" id="11969"/>
    <dbReference type="ProteomicsDB" id="58194">
        <molecule id="Q03154-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="8777"/>
    <dbReference type="ProteomicsDB" id="9178"/>
    <dbReference type="Pumba" id="Q03154"/>
    <dbReference type="Antibodypedia" id="34911">
        <property type="antibodies" value="524 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="95"/>
    <dbReference type="Ensembl" id="ENST00000404366.7">
        <molecule id="Q03154-1"/>
        <property type="protein sequence ID" value="ENSP00000384296.2"/>
        <property type="gene ID" value="ENSG00000243989.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000476351.5">
        <molecule id="Q03154-4"/>
        <property type="protein sequence ID" value="ENSP00000417056.1"/>
        <property type="gene ID" value="ENSG00000243989.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000476854.5">
        <molecule id="Q03154-3"/>
        <property type="protein sequence ID" value="ENSP00000419262.1"/>
        <property type="gene ID" value="ENSG00000243989.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000494103.5">
        <molecule id="Q03154-2"/>
        <property type="protein sequence ID" value="ENSP00000417618.1"/>
        <property type="gene ID" value="ENSG00000243989.10"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000636358.2">
        <molecule id="Q03154-1"/>
        <property type="protein sequence ID" value="ENSP00000490149.1"/>
        <property type="gene ID" value="ENSG00000243989.10"/>
    </dbReference>
    <dbReference type="GeneID" id="95"/>
    <dbReference type="KEGG" id="hsa:95"/>
    <dbReference type="MANE-Select" id="ENST00000636358.2">
        <property type="protein sequence ID" value="ENSP00000490149.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000666.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000657.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc021wzb.2">
        <molecule id="Q03154-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:177"/>
    <dbReference type="ClinPGx" id="PA24497"/>
    <dbReference type="CTD" id="95"/>
    <dbReference type="DisGeNET" id="95"/>
    <dbReference type="GeneCards" id="ACY1"/>
    <dbReference type="HGNC" id="HGNC:177">
        <property type="gene designation" value="ACY1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000243989">
        <property type="expression patterns" value="Group enriched (intestine, kidney, liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACY1"/>
    <dbReference type="MIM" id="104620">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="609924">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000243989"/>
    <dbReference type="Orphanet" id="137754">
        <property type="disease" value="Aminoacylase 1 deficiency"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000243989"/>
    <dbReference type="eggNOG" id="KOG2275">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155631"/>
    <dbReference type="HOGENOM" id="CLU_021802_5_0_1"/>
    <dbReference type="InParanoid" id="Q03154"/>
    <dbReference type="OMA" id="FYGERAQ"/>
    <dbReference type="OrthoDB" id="3064516at2759"/>
    <dbReference type="PAN-GO" id="Q03154">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q03154"/>
    <dbReference type="BioCyc" id="MetaCyc:HS03800-MONOMER"/>
    <dbReference type="BRENDA" id="3.5.1.14">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q03154"/>
    <dbReference type="Reactome" id="R-HSA-5423646">
        <property type="pathway name" value="Aflatoxin activation and detoxification"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5579007">
        <property type="pathway name" value="Defective ACY1 causes encephalopathy"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9753281">
        <property type="pathway name" value="Paracetamol ADME"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q03154"/>
    <dbReference type="SignaLink" id="Q03154"/>
    <dbReference type="Agora" id="ENSG00000243989"/>
    <dbReference type="BioGRID-ORCS" id="95">
        <property type="hits" value="12 hits in 1161 CRISPR screens"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q03154"/>
    <dbReference type="GeneWiki" id="ACY1"/>
    <dbReference type="GenomeRNAi" id="95"/>
    <dbReference type="Pharos" id="Q03154">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q03154"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q03154">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000243989">
        <property type="expression patterns" value="Expressed in duodenum and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q03154">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004046">
        <property type="term" value="F:aminoacylase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006520">
        <property type="term" value="P:amino acid metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="CDD" id="cd05646">
        <property type="entry name" value="M20_AcylaseI_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.630.10:FF:000019">
        <property type="entry name" value="Aminoacylase 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.150.900:FF:000001">
        <property type="entry name" value="Aminoacylase-1, putative"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.360:FF:000005">
        <property type="entry name" value="Putative Aminoacylase-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.150.900">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.360">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.630.10">
        <property type="entry name" value="Zn peptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052083">
        <property type="entry name" value="Aminoacylase-1_M20A"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001261">
        <property type="entry name" value="ArgE/DapE_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036264">
        <property type="entry name" value="Bact_exopeptidase_dim_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR010159">
        <property type="entry name" value="N-acyl_aa_amidohydrolase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002933">
        <property type="entry name" value="Peptidase_M20"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011650">
        <property type="entry name" value="Peptidase_M20_dimer"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01880">
        <property type="entry name" value="Ac-peptdase-euk"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45892">
        <property type="entry name" value="AMINOACYLASE-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45892:SF1">
        <property type="entry name" value="AMINOACYLASE-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07687">
        <property type="entry name" value="M20_dimer"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01546">
        <property type="entry name" value="Peptidase_M20"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF036696">
        <property type="entry name" value="ACY-1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55031">
        <property type="entry name" value="Bacterial exopeptidase dimerisation domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53187">
        <property type="entry name" value="Zn-dependent exopeptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00758">
        <property type="entry name" value="ARGE_DAPE_CPG2_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00759">
        <property type="entry name" value="ARGE_DAPE_CPG2_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000185236" description="Aminoacylase-1">
        <location>
            <begin position="1"/>
            <end position="408"/>
        </location>
    </feature>
    <feature type="active site" evidence="1">
        <location>
            <position position="82"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="4">
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="80"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="113"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="113"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="148"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="175"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="373"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_046876" description="In isoform 4." evidence="10">
        <location>
            <begin position="32"/>
            <end position="66"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046877" description="In isoform 2." evidence="10">
        <location>
            <begin position="103"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046878" description="In isoform 3." evidence="10">
        <location>
            <begin position="220"/>
            <end position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051805" description="In dbSNP:rs887540.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043113" description="In ACY1D; loss of activity; dbSNP:rs121912700." evidence="8 9">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026104" description="In ACY1D; loss of activity; dbSNP:rs121912699." evidence="6 9">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026105" description="In ACY1D; loss of activity; dbSNP:rs121912698." evidence="5 6 8 9">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_065562" description="In ACY1D; dbSNP:rs150480963." evidence="9">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_065563" description="In ACY1D; slightly reduced activity; dbSNP:rs148346337." evidence="9">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036076" description="In a breast cancer sample; somatic mutation." evidence="7">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="381"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_020452" description="In ACY1D; loss of activity; dbSNP:rs2229152." evidence="9">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="386"/>
        </location>
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    <feature type="sequence variant" id="VAR_043114" description="In ACY1D; dbSNP:rs121912701." evidence="8">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="393"/>
        </location>
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    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>E</original>
        <variation>A</variation>
        <variation>Q</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreased protein stability. Loss of enzyme activity." evidence="4">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="175"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>H</original>
        <variation>N</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost abolishes enzyme activity." evidence="4">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="373"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="11"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="31"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="48"/>
            <end position="55"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="58"/>
            <end position="65"/>
        </location>
    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="74"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="88"/>
            <end position="90"/>
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    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="95"/>
            <end position="97"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="104"/>
            <end position="107"/>
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    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="109"/>
            <end position="114"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="115"/>
            <end position="130"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="139"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="147"/>
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    </feature>
    <feature type="turn" evidence="12">
        <location>
            <begin position="152"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="155"/>
            <end position="158"/>
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    </feature>
    <feature type="helix" evidence="12">
        <location>
            <begin position="162"/>
            <end position="165"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="169"/>
            <end position="174"/>
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    </feature>
    <feature type="strand" evidence="12">
        <location>
            <begin position="180"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="194"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="322"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="338"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="348"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="359"/>
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    <feature type="strand" evidence="12">
        <location>
            <begin position="378"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="381"/>
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    <feature type="helix" evidence="12">
        <location>
            <begin position="405"/>
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    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q6AYS7"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q99JW2"/>
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    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12933810"/>
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        <source>
            <dbReference type="PubMed" id="16274666"/>
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        <source>
            <dbReference type="PubMed" id="12933810"/>
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            <dbReference type="PDB" id="1Q7L"/>
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    <sequence length="408" mass="45885" checksum="293350CD7759826C" modified="1994-02-01" version="1">MTSKGPEEEHPSVTLFRQYLRIRTVQPKPDYGAAVAFFEETARQLGLGCQKVEVAPGYVVTVLTWPGTNPTLSSILLNSHTDVVPVFKEHWSHDPFEAFKDSEGYIYARGAQDMKCVSIQYLEAVRRLKVEGHRFPRTIHMTFVPDEEVGGHQGMELFVQRPEFHALRAGFALDEGIANPTDAFTVFYSERSPWWVRVTSTGRPGHASRFMEDTAAEKLHKVVNSILAFREKEWQRLQSNPHLKEGSVTSVNLTKLEGGVAYNVIPATMSASFDFRVAPDVDFKAFEEQLQSWCQAAGEGVTLEFAQKWMHPQVTPTDDSNPWWAAFSRVCKDMNLTLEPEIMPAATDNRYIRAVGVPALGFSPMNRTPVLLHDHDERLHEAVFLRGVDIYTRLLPALASVPALPSDS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-04-01" modified="2026-01-28" version="195" xmlns="https://uniprot.org/uniprot">
    <accession>P14621</accession>
    <name>ACYP2_HUMAN</name>
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        <recommendedName>
            <fullName>Acylphosphatase-2</fullName>
            <ecNumber>3.6.1.7</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acylphosphatase, muscle type isozyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acylphosphate phosphohydrolase 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACYP2</name>
        <name type="synonym">ACYP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Ovary</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1984" name="Mol. Biol. Med." volume="2" first="369" last="378">
            <title>Human skeletal muscle acylphosphatase: the primary structure.</title>
            <authorList>
                <person name="Manao G."/>
                <person name="Camici G."/>
                <person name="Modesti A."/>
                <person name="Liguri G."/>
                <person name="Berti A."/>
                <person name="Setfani M."/>
                <person name="Cappugi G."/>
                <person name="Ramponi G."/>
            </authorList>
            <dbReference type="PubMed" id="6100723"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-99</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="FEBS Lett." volume="367" first="145" last="148">
            <title>Cloning and expression of the cDNA coding for the erythrocyte isoenzyme of human acylphosphatase.</title>
            <authorList>
                <person name="Fiaschi T."/>
                <person name="Raugei G."/>
                <person name="Marzocchini R."/>
                <person name="Chiarugi P."/>
                <person name="Cirri P."/>
                <person name="Ramponi G."/>
            </authorList>
            <dbReference type="PubMed" id="7796909"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)00553-l"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 22-99</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>Its physiological role is not yet clear.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>an acyl phosphate + H2O = a carboxylate + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:14965"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29067"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:59918"/>
            <dbReference type="EC" id="3.6.1.7"/>
        </reaction>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10198377">
            <id>P14621</id>
        </interactant>
        <interactant intactId="EBI-10198377">
            <id>P14621</id>
            <label>ACYP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10198377">
            <id>P14621</id>
        </interactant>
        <interactant intactId="EBI-632965">
            <id>Q9NS37</id>
            <label>CREBZF</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10198377">
            <id>P14621</id>
        </interactant>
        <interactant intactId="EBI-749441">
            <id>O00204</id>
            <label>SULT2B1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the acylphosphatase family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAH12290.1"/>
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        <property type="protein sequence ID" value="CAA58988.1"/>
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        <property type="nucleotide sequence ID" value="NM_138448.4"/>
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    <dbReference type="DIP" id="DIP-48449N"/>
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        <property type="generic name" value="Formic acid"/>
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    <dbReference type="MassIVE" id="P14621"/>
    <dbReference type="PaxDb" id="9606-ENSP00000378161"/>
    <dbReference type="PeptideAtlas" id="P14621"/>
    <dbReference type="ProteomicsDB" id="53066"/>
    <dbReference type="Pumba" id="P14621"/>
    <dbReference type="Antibodypedia" id="30250">
        <property type="antibodies" value="110 antibodies from 22 providers"/>
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    <dbReference type="Ensembl" id="ENST00000394666.9">
        <property type="protein sequence ID" value="ENSP00000378161.3"/>
        <property type="gene ID" value="ENSG00000170634.13"/>
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    <dbReference type="GeneID" id="98"/>
    <dbReference type="KEGG" id="hsa:98"/>
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        <property type="protein sequence ID" value="ENSP00000378161.3"/>
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        <property type="RefSeq protein sequence ID" value="NP_612457.1"/>
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    <dbReference type="AGR" id="HGNC:180"/>
    <dbReference type="ClinPGx" id="PA24500"/>
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    <dbReference type="HGNC" id="HGNC:180">
        <property type="gene designation" value="ACYP2"/>
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        <property type="expression patterns" value="Tissue enhanced (brain, skeletal muscle, tongue)"/>
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    <dbReference type="MalaCards" id="ACYP2"/>
    <dbReference type="MIM" id="102595">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000170634"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000170634"/>
    <dbReference type="eggNOG" id="KOG3360">
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    <dbReference type="GeneTree" id="ENSGT00390000011103"/>
    <dbReference type="HOGENOM" id="CLU_141932_0_1_1"/>
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    <dbReference type="OMA" id="HAIMAEN"/>
    <dbReference type="OrthoDB" id="7961613at2759"/>
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    <dbReference type="PhylomeDB" id="P14621"/>
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        <property type="organism ID" value="2681"/>
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    <dbReference type="PathwayCommons" id="P14621"/>
    <dbReference type="SABIO-RK" id="P14621"/>
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        <property type="hits" value="14 hits in 1161 CRISPR screens"/>
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    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
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    <dbReference type="GeneWiki" id="ACYP2"/>
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    <dbReference type="Pharos" id="P14621">
        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:P14621"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
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    <dbReference type="RNAct" id="P14621">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000170634">
        <property type="expression patterns" value="Expressed in pons and 200 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P14621">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003998">
        <property type="term" value="F:acylphosphatase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006796">
        <property type="term" value="P:phosphate-containing compound metabolic process"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.100:FF:000011">
        <property type="entry name" value="Acylphosphatase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.100">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020456">
        <property type="entry name" value="Acylphosphatase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001792">
        <property type="entry name" value="Acylphosphatase-like_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036046">
        <property type="entry name" value="Acylphosphatase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017968">
        <property type="entry name" value="Acylphosphatase_CS"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10029">
        <property type="entry name" value="ACYLPHOSPHATASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10029:SF20">
        <property type="entry name" value="ACYLPHOSPHATASE-2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00708">
        <property type="entry name" value="Acylphosphatase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00112">
        <property type="entry name" value="ACYLPHPHTASE"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54975">
        <property type="entry name" value="Acylphosphatase/BLUF domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00150">
        <property type="entry name" value="ACYLPHOSPHATASE_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00151">
        <property type="entry name" value="ACYLPHOSPHATASE_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51160">
        <property type="entry name" value="ACYLPHOSPHATASE_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="3 5">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000158542" description="Acylphosphatase-2">
        <location>
            <begin position="2"/>
            <end position="99"/>
        </location>
    </feature>
    <feature type="domain" description="Acylphosphatase-like" evidence="2">
        <location>
            <begin position="9"/>
            <end position="99"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylserine" evidence="5">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="93"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P35745"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00520"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="6100723"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0007744" key="5">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="99" mass="11140" checksum="AEDE40E45B6207A0" modified="2007-01-23" version="2">MSTAQSLKSVDYEVFGRVQGVCFRMYTEDEARKIGVVGWVKNTSKGTVTGQVQGPEDKVNSMKSWLSKVGSPSSRIDRTNFSNEKTISKLEYSNFSIRY</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
    <accession>P45381</accession>
    <name>ACY2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">Aspartoacylase</fullName>
            <ecNumber evidence="7 11 12 16">3.5.1.15</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Aminoacylase-2</fullName>
            <shortName>ACY-2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="25" type="primary">ASPA</name>
        <name type="synonym">ACY2</name>
        <name evidence="19" type="synonym">ASP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Nat. Genet." volume="5" first="118" last="123">
            <title>Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease.</title>
            <authorList>
                <person name="Kaul R."/>
                <person name="Gao G.P."/>
                <person name="Balamurugan K."/>
                <person name="Matalon R."/>
            </authorList>
            <dbReference type="PubMed" id="8252036"/>
            <dbReference type="DOI" id="10.1038/ng1093-118"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT CAND ALA-285</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Arch. Biochem. Biophys." volume="413" first="1" last="8">
            <title>Purification and preliminary characterization of brain aspartoacylase.</title>
            <authorList>
                <person name="Moore R.A."/>
                <person name="Le Coq J."/>
                <person name="Faehnle C.R."/>
                <person name="Viola R.E."/>
            </authorList>
            <dbReference type="PubMed" id="12706335"/>
            <dbReference type="DOI" id="10.1016/s0003-9861(03)00055-9"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CHARACTERIZATION</scope>
        <scope>CHARACTERIZATION OF VARIANT CAND ALA-285</scope>
        <scope>MUTAGENESIS OF GLU-285</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="FEBS Lett." volume="580" first="5899" last="5904">
            <title>Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease.</title>
            <authorList>
                <person name="Herga S."/>
                <person name="Berrin J.G."/>
                <person name="Perrier J."/>
                <person name="Puigserver A."/>
                <person name="Giardina T."/>
            </authorList>
            <dbReference type="PubMed" id="17027983"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2006.09.056"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ZINC-BINDING SITES</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF GLU-178</scope>
    </reference>
    <reference evidence="26 27" key="5">
        <citation type="journal article" date="2008" name="Biochemistry" volume="47" first="3484" last="3492">
            <title>Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue.</title>
            <authorList>
                <person name="Le Coq J."/>
                <person name="Pavlovsky A."/>
                <person name="Malik R."/>
                <person name="Sanishvili R."/>
                <person name="Xu C."/>
                <person name="Viola R.E."/>
            </authorList>
            <dbReference type="PubMed" id="18293939"/>
            <dbReference type="DOI" id="10.1021/bi702400x"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEXES WITH ZINC IONS; PHOSPHATE AND N-PHOSPHONOMETHYL-L-ASPARTATE</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>SUBUNIT</scope>
        <scope>ACTIVE SITE</scope>
        <scope>REACTION MECHANISM</scope>
        <scope>MUTAGENESIS OF ARG-71; TYR-164; ARG-168; GLU-178 AND TYR-288</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="Proc. Natl. Acad. Sci. U.S.A." volume="104" first="456" last="461">
            <title>Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.</title>
            <authorList>
                <person name="Bitto E."/>
                <person name="Bingman C.A."/>
                <person name="Wesenberg G.E."/>
                <person name="McCoy J.G."/>
                <person name="Phillips G.N. Jr."/>
            </authorList>
            <dbReference type="PubMed" id="17194761"/>
            <dbReference type="DOI" id="10.1073/pnas.0607817104"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH ZINC IONS</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1994" name="Am. J. Hum. Genet." volume="55" first="34" last="41">
            <title>Canavan disease: mutations among Jewish and non-Jewish patients.</title>
            <authorList>
                <person name="Kaul R."/>
                <person name="Gao G.P."/>
                <person name="Aloya M."/>
                <person name="Balamurugan K."/>
                <person name="Petrosky A."/>
                <person name="Michals K."/>
                <person name="Matalon R."/>
            </authorList>
            <dbReference type="PubMed" id="8023850"/>
        </citation>
        <scope>VARIANTS CAND ALA-285 AND GLU-305</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1995" name="Am. J. Hum. Genet." volume="57" first="572" last="580">
            <title>The molecular basis of canavan (aspartoacylase deficiency) disease in European non-Jewish patients.</title>
            <authorList>
                <person name="Shaag A."/>
                <person name="Anikster Y."/>
                <person name="Christensen E."/>
                <person name="Glustein J.Z."/>
                <person name="Fois A."/>
                <person name="Michelakakis H."/>
                <person name="Nigro F."/>
                <person name="Pronicka E."/>
                <person name="Ribes A."/>
                <person name="Zabot M.-T."/>
                <person name="Elpeleg O.N."/>
            </authorList>
            <dbReference type="PubMed" id="7668285"/>
        </citation>
        <scope>VARIANTS CAND 176-GLY-ILE-177 DEL; ARG-274; SER-295 AND GLU-305</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1995" name="Hum. Mutat." volume="5" first="269" last="271">
            <title>Novel (Cys152 &gt; Arg) missense mutation in an Arab patient with Canavan disease.</title>
            <authorList>
                <person name="Kaul R."/>
                <person name="Gao G.P."/>
                <person name="Michals K."/>
                <person name="Whelan D.T."/>
                <person name="Levin S."/>
                <person name="Matalon R."/>
            </authorList>
            <dbReference type="PubMed" id="7599639"/>
            <dbReference type="DOI" id="10.1002/humu.1380050313"/>
        </citation>
        <scope>VARIANT CAND ARG-152</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1996" name="Am. J. Hum. Genet." volume="59" first="95" last="102">
            <title>Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease.</title>
            <authorList>
                <person name="Kaul R."/>
                <person name="Gao G.P."/>
                <person name="Matalon R."/>
                <person name="Aloya M."/>
                <person name="Su Q."/>
                <person name="Jin M."/>
                <person name="Johnson A.B."/>
                <person name="Schutgens R.B.H."/>
                <person name="Clarke J.T.R."/>
            </authorList>
            <dbReference type="PubMed" id="8659549"/>
        </citation>
        <scope>VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152; CYS-168; ALA-285 AND GLU-305</scope>
        <scope>VARIANT GLY-310</scope>
        <scope>CHARACTERIZATION OF VARIANTS CAND THR-16; ARG-27; GLU-114; GLU-123; TYR-152 AND CYS-168</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1998" name="Hum. Mutat. Suppl." volume="1" first="S308" last="S309">
            <title>Missense mutation (I143T) in a Japanese patient with Canavan disease.</title>
            <authorList>
                <person name="Kobayashi K."/>
                <person name="Tsujino S."/>
                <person name="Ezoe T."/>
                <person name="Hamaguchi H."/>
                <person name="Nihei K."/>
                <person name="Sakuragawa N."/>
            </authorList>
            <dbReference type="PubMed" id="9452117"/>
            <dbReference type="DOI" id="10.1002/humu.1380110196"/>
        </citation>
        <scope>VARIANT CAND THR-143</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1999" name="Am. J. Med. Genet." volume="87" first="273" last="275">
            <title>Novel missense mutation (Y231C) in a Turkish patient with Canavan disease.</title>
            <authorList>
                <person name="Rady P.L."/>
                <person name="Vargas T."/>
                <person name="Tyring S.K."/>
                <person name="Matalon R."/>
                <person name="Langenbeck U."/>
            </authorList>
            <dbReference type="PubMed" id="10564886"/>
            <dbReference type="DOI" id="10.1002/(sici)1096-8628(19991126)87:3&lt;273::aid-ajmg17&gt;3.0.co;2-o"/>
        </citation>
        <scope>VARIANT CAND CYS-231</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1999" name="J. Inherit. Metab. Dis." volume="22" first="531" last="534">
            <title>The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients.</title>
            <authorList>
                <person name="Elpeleg O.N."/>
                <person name="Shaag A."/>
            </authorList>
            <dbReference type="PubMed" id="10407784"/>
            <dbReference type="DOI" id="10.1023/a:1005512524957"/>
        </citation>
        <scope>VARIANTS CAND THR-16; ARG-27; HIS-183; PHE-186; ARG-195; ARG-274; SER-280; LEU-280; THR-287; SER-295 AND GLU-305</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2000" name="Eur. J. Hum. Genet." volume="8" first="557" last="560">
            <title>Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population.</title>
            <authorList>
                <person name="Sistermans E.A."/>
                <person name="de Coo R.F."/>
                <person name="van Beerendonk H.M."/>
                <person name="Poll-The B.T."/>
                <person name="Kleijer W.J."/>
                <person name="van Oost B.A."/>
            </authorList>
            <dbReference type="PubMed" id="10909858"/>
            <dbReference type="DOI" id="10.1038/sj.ejhg.5200477"/>
        </citation>
        <scope>VARIANTS CAND PRO-21; THR-57; HIS-168 AND THR-181</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2002" name="J. Inherit. Metab. Dis." volume="25" first="557" last="570">
            <title>Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease.</title>
            <authorList>
                <person name="Zeng B.J."/>
                <person name="Wang Z.H."/>
                <person name="Ribeiro L.A."/>
                <person name="Leone P."/>
                <person name="De Gasperi R."/>
                <person name="Kim S.J."/>
                <person name="Raghavan S."/>
                <person name="Ong E."/>
                <person name="Pastores G.M."/>
                <person name="Kolodny E.H."/>
            </authorList>
            <dbReference type="PubMed" id="12638939"/>
            <dbReference type="DOI" id="10.1023/a:1022091223498"/>
        </citation>
        <scope>VARIANTS CAND GLY-24; ALA-68; TRP-152; ARG-244 AND VAL-249</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2002" name="J. Med. Genet." volume="39" first="E55" last="E55">
            <title>Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease.</title>
            <authorList>
                <person name="Olsen T.R."/>
                <person name="Tranebjaerg L."/>
                <person name="Kvittingen E.A."/>
                <person name="Hagenfeldt L."/>
                <person name="Moller C."/>
                <person name="Nilssen O."/>
            </authorList>
            <dbReference type="PubMed" id="12205125"/>
            <dbReference type="DOI" id="10.1136/jmg.39.9.e55"/>
        </citation>
        <scope>VARIANTS CAND TYR-114 AND VAL-249</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2013" name="Clin. Biochem." volume="46" first="1902" last="1904">
            <title>New T530C mutation in the aspartoacylase gene caused Canavan disease with no correlation between severity and N-acetylaspartate excretion.</title>
            <authorList>
                <person name="Di Pietro V."/>
                <person name="Cavallari U."/>
                <person name="Amorini A.M."/>
                <person name="Lazzarino G."/>
                <person name="Longo S."/>
                <person name="Poggiani C."/>
                <person name="Cavalli P."/>
                <person name="Tavazzi B."/>
            </authorList>
            <dbReference type="PubMed" id="24036223"/>
            <dbReference type="DOI" id="10.1016/j.clinbiochem.2013.09.004"/>
        </citation>
        <scope>VARIANT CAND THR-177</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2017" name="Hum. Mutat." volume="38" first="524" last="531">
            <title>Clinically distinct phenotypes of Canavan disease correlate with residual aspartoacylase enzyme activity.</title>
            <authorList>
                <person name="Mendes M.I."/>
                <person name="Smith D.E."/>
                <person name="Pop A."/>
                <person name="Lennertz P."/>
                <person name="Fernandez Ojeda M.R."/>
                <person name="Kanhai W.A."/>
                <person name="van Dooren S.J."/>
                <person name="Anikster Y."/>
                <person name="Baric I."/>
                <person name="Boelen C."/>
                <person name="Campistol J."/>
                <person name="de Boer L."/>
                <person name="Kariminejad A."/>
                <person name="Kayserili H."/>
                <person name="Roubertie A."/>
                <person name="Verbruggen K.T."/>
                <person name="Vianey-Saban C."/>
                <person name="Williams M."/>
                <person name="Salomons G.S."/>
            </authorList>
            <dbReference type="PubMed" id="28101991"/>
            <dbReference type="DOI" id="10.1002/humu.23181"/>
        </citation>
        <scope>VARIANTS CAND LYS-24; PRO-30; VAL-57; THR-63; ARG-69; VAL-101; LYS-129; THR-170; VAL-180; HIS-204; ARG-248 AND ASP-286</scope>
        <scope>CHARACTERIZATION OF VARIANTS CAND LYS-24; PRO-30; VAL-57; THR-63; ARG-69; VAL-101; LYS-129; THR-170; VAL-180; HIS-204; ARG-248; ALA-285 AND ASP-286</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <comment type="function">
        <text evidence="8 11 16">Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter. In other tissues it acts as a scavenger of NAA from body fluids.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 10 11 12 16">
            <text>an N-acyl-L-aspartate + H2O = a carboxylate + L-aspartate</text>
            <dbReference type="Rhea" id="RHEA:10872"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:29067"/>
            <dbReference type="ChEBI" id="CHEBI:29991"/>
            <dbReference type="ChEBI" id="CHEBI:58497"/>
            <dbReference type="EC" id="3.5.1.15"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:10873"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 10 11 16">
            <text>N-acetyl-L-aspartate + H2O = L-aspartate + acetate</text>
            <dbReference type="Rhea" id="RHEA:59408"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
            <dbReference type="ChEBI" id="CHEBI:29991"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="24">
            <dbReference type="Rhea" id="RHEA:59409"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9 10">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="9 10">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <Vmax evidence="12">1.2 nmol/h/mg enzyme</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="22 23">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-3916242">
            <id>Q96HD9</id>
            <label>ACY3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>15</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-750475">
            <id>P45381</id>
            <label>ASPA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-350590">
            <id>Q9UNS2</id>
            <label>COPS3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-1054321">
            <id>Q68J44</id>
            <label>DUSP29</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-751001">
            <id>Q14145</id>
            <label>KEAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-629434">
            <id>O75925</id>
            <label>PIAS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-947187">
            <id>Q9UHD9</id>
            <label>UBQLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-25832660">
            <id>Q9H347</id>
            <label>UBQLN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-750475">
            <id>P45381</id>
        </interactant>
        <interactant intactId="EBI-12295223">
            <id>Q8IYU4</id>
            <label>UBQLNL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="16">Brain white matter, skeletal muscle, kidney, adrenal glands, lung and liver.</text>
    </comment>
    <comment type="disease" evidence="2 3 4 5 6 7 11 12 13 14 15 16 17 18">
        <disease id="DI-00208">
            <name>Canavan disease</name>
            <acronym>CAND</acronym>
            <description>A rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demyelination that gives rise to a spongy appearance. The clinical features are onset in early infancy, atonia of neck muscles, hypotonia, hyperextension of legs and flexion of arms, blindness, severe mental defect, megalocephaly, and death by 18 months on the average.</description>
            <dbReference type="MIM" id="271900"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the AspA/AstE family. Aspartoacylase subfamily.</text>
    </comment>
    <dbReference type="EC" id="3.5.1.15" evidence="7 11 12 16"/>
    <dbReference type="EMBL" id="S67156">
        <property type="protein sequence ID" value="AAB29190.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC029128">
        <property type="protein sequence ID" value="AAH29128.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11028.1"/>
    <dbReference type="PIR" id="S38538">
        <property type="entry name" value="S38538"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000040.1">
        <property type="nucleotide sequence ID" value="NM_000049.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001121557.1">
        <property type="nucleotide sequence ID" value="NM_001128085.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016880150.1">
        <property type="nucleotide sequence ID" value="XM_017024661.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054172172.1">
        <property type="nucleotide sequence ID" value="XM_054316197.1"/>
    </dbReference>
    <dbReference type="PDB" id="2I3C">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=2-313"/>
    </dbReference>
    <dbReference type="PDB" id="2O4H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDB" id="2O53">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDB" id="2Q51">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=2-313"/>
    </dbReference>
    <dbReference type="PDB" id="4MRI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDB" id="4MXU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDB" id="4NFR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDB" id="4TNU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="A/B=1-313"/>
    </dbReference>
    <dbReference type="PDBsum" id="2I3C"/>
    <dbReference type="PDBsum" id="2O4H"/>
    <dbReference type="PDBsum" id="2O53"/>
    <dbReference type="PDBsum" id="2Q51"/>
    <dbReference type="PDBsum" id="4MRI"/>
    <dbReference type="PDBsum" id="4MXU"/>
    <dbReference type="PDBsum" id="4NFR"/>
    <dbReference type="PDBsum" id="4TNU"/>
    <dbReference type="AlphaFoldDB" id="P45381"/>
    <dbReference type="SMR" id="P45381"/>
    <dbReference type="BioGRID" id="106935">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-60793N"/>
    <dbReference type="FunCoup" id="P45381">
        <property type="interactions" value="383"/>
    </dbReference>
    <dbReference type="IntAct" id="P45381">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000263080"/>
    <dbReference type="DrugBank" id="DB00128">
        <property type="generic name" value="Aspartic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01593">
        <property type="generic name" value="Zinc"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14487">
        <property type="generic name" value="Zinc acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14533">
        <property type="generic name" value="Zinc chloride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14548">
        <property type="generic name" value="Zinc sulfate, unspecified form"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P45381"/>
    <dbReference type="iPTMnet" id="P45381"/>
    <dbReference type="PhosphoSitePlus" id="P45381"/>
    <dbReference type="BioMuta" id="ASPA"/>
    <dbReference type="jPOST" id="P45381"/>
    <dbReference type="MassIVE" id="P45381"/>
    <dbReference type="PaxDb" id="9606-ENSP00000263080"/>
    <dbReference type="PeptideAtlas" id="P45381"/>
    <dbReference type="ProteomicsDB" id="55676"/>
    <dbReference type="Antibodypedia" id="10844">
        <property type="antibodies" value="294 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="443"/>
    <dbReference type="Ensembl" id="ENST00000263080.3">
        <property type="protein sequence ID" value="ENSP00000263080.2"/>
        <property type="gene ID" value="ENSG00000108381.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000456349.6">
        <property type="protein sequence ID" value="ENSP00000409976.2"/>
        <property type="gene ID" value="ENSG00000108381.12"/>
    </dbReference>
    <dbReference type="GeneID" id="443"/>
    <dbReference type="KEGG" id="hsa:443"/>
    <dbReference type="MANE-Select" id="ENST00000263080.3">
        <property type="protein sequence ID" value="ENSP00000263080.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000049.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000040.1"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:756"/>
    <dbReference type="ClinPGx" id="PA25055"/>
    <dbReference type="CTD" id="443"/>
    <dbReference type="DisGeNET" id="443"/>
    <dbReference type="GeneCards" id="ASPA"/>
    <dbReference type="GeneReviews" id="ASPA"/>
    <dbReference type="HGNC" id="HGNC:756">
        <property type="gene designation" value="ASPA"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000108381">
        <property type="expression patterns" value="Tissue enhanced (brain, kidney)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ASPA"/>
    <dbReference type="MIM" id="271900">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="608034">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000108381"/>
    <dbReference type="Orphanet" id="314918">
        <property type="disease" value="Mild Canavan disease"/>
    </dbReference>
    <dbReference type="Orphanet" id="314911">
        <property type="disease" value="Severe Canavan disease"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000108381"/>
    <dbReference type="eggNOG" id="ENOG502QRAK">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000001189"/>
    <dbReference type="HOGENOM" id="CLU_083292_0_0_1"/>
    <dbReference type="InParanoid" id="P45381"/>
    <dbReference type="OMA" id="THGNEIN"/>
    <dbReference type="OrthoDB" id="8300214at2759"/>
    <dbReference type="PAN-GO" id="P45381">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P45381"/>
    <dbReference type="BioCyc" id="MetaCyc:HS03094-MONOMER"/>
    <dbReference type="BRENDA" id="3.5.1.15">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P45381"/>
    <dbReference type="Reactome" id="R-HSA-8963693">
        <property type="pathway name" value="Aspartate and asparagine metabolism"/>
    </dbReference>
    <dbReference type="SignaLink" id="P45381"/>
    <dbReference type="SIGNOR" id="P45381"/>
    <dbReference type="Agora" id="ENSG00000108381"/>
    <dbReference type="BioGRID-ORCS" id="443">
        <property type="hits" value="5 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ASPA">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P45381"/>
    <dbReference type="GenomeRNAi" id="443"/>
    <dbReference type="Pharos" id="P45381">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P45381"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="P45381">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000108381">
        <property type="expression patterns" value="Expressed in corpus callosum and 166 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P45381">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019807">
        <property type="term" value="F:aspartoacylase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016811">
        <property type="term" value="F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016788">
        <property type="term" value="F:hydrolase activity, acting on ester bonds"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006083">
        <property type="term" value="P:acetate metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006531">
        <property type="term" value="P:aspartate metabolic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd06909">
        <property type="entry name" value="M14_ASPA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.20.25.160:FF:000001">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.630.10:FF:000025">
        <property type="entry name" value="aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.20.25.160">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.630.10">
        <property type="entry name" value="Zn peptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_00704">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050178">
        <property type="entry name" value="AspA/AstE_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016708">
        <property type="entry name" value="Aspartoacylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR055438">
        <property type="entry name" value="AstE_AspA_cat"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007036">
        <property type="entry name" value="Aste_AspA_hybrid_dom"/>
    </dbReference>
    <dbReference type="NCBIfam" id="NF002601">
        <property type="entry name" value="PRK02259.1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15162">
        <property type="entry name" value="ASPARTOACYLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15162:SF9">
        <property type="entry name" value="ASPARTOACYLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF24827">
        <property type="entry name" value="AstE_AspA_cat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04952">
        <property type="entry name" value="AstE_AspA_hybrid"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF018001">
        <property type="entry name" value="Aspartoacylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53187">
        <property type="entry name" value="Zn-dependent exopeptidases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1026">Leukodystrophy</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000216871" description="Aspartoacylase">
        <location>
            <begin position="1"/>
            <end position="313"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor/acceptor" evidence="21 23 26">
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="binding site" evidence="8 10 26 27">
        <location>
            <position position="21"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 10 26 27">
        <location>
            <position position="24"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26">
        <location>
            <position position="63"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26">
        <location>
            <position position="70"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26 27">
        <location>
            <position position="71"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 10 26 27">
        <location>
            <position position="116"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26">
        <location>
            <position position="164"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26">
        <location>
            <position position="168"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="10 26">
        <location>
            <position position="288"/>
        </location>
        <ligand>
            <name>N-acetyl-L-aspartate</name>
            <dbReference type="ChEBI" id="CHEBI:16953"/>
        </ligand>
    </feature>
    <feature type="site" description="Transition state stabilizer" evidence="21 23 26">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039079" description="In CAND; &lt;0.5% residual enzyme activity; dbSNP:rs769653717." evidence="2 17">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016778" description="In CAND." evidence="4">
        <original>H</original>
        <variation>P</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016782" description="In CAND; dbSNP:rs104894551." evidence="6">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078086" description="In CAND; &lt;1% residual enzyme activity." evidence="12">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039080" description="In CAND; 3% residual enzyme activity; dbSNP:rs766328537." evidence="2 17">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078087" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs1555538144." evidence="12">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016779" description="In CAND." evidence="4">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078088" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs1555538148." evidence="12">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="57"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078089" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs1555538151." evidence="12">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016783" description="In CAND." evidence="6">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078090" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs776777887." evidence="12">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078091" description="In CAND; &lt;1% residual enzyme activity." evidence="12">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039081" description="In CAND; &lt;0.5% residual enzyme activity." evidence="17">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016784" description="In CAND; dbSNP:rs1446467099." evidence="5">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039082" description="In CAND; about 25% residual enzyme activity; dbSNP:rs1057521115." evidence="17">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="123"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078092" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs773049803." evidence="12">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_004995" description="In CAND; dbSNP:rs777936704." evidence="18">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_004996" description="In CAND; loss of activity; dbSNP:rs104894548." evidence="13">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016785" description="In CAND." evidence="6">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039083" description="In CAND; &lt;0.5% residual enzyme activity." evidence="17">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039084" description="In CAND; undetectable enzyme activity; dbSNP:rs937670540." evidence="17">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016780" description="In CAND; dbSNP:rs770706390." evidence="4">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078093" description="In CAND; 5.5% residual enzyme activity; dbSNP:rs144321760." evidence="12">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_004997" description="In CAND." evidence="14">
        <location>
            <begin position="176"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078094" description="In CAND; Loss of catalytic activity." evidence="11">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078095" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs1014551540." evidence="12">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="180"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016781" description="In CAND; dbSNP:rs786204572." evidence="4">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039085" description="In CAND; dbSNP:rs1555539857." evidence="2">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039086" description="In CAND." evidence="2">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039087" description="In CAND." evidence="2">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="195"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078096" description="In CAND; 12% residual enzyme activity." evidence="12">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="204"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016786" description="In CAND; dbSNP:rs104894550." evidence="3">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016787" description="In CAND; dbSNP:rs1057516995." evidence="6">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078097" description="In CAND; &lt;1% residual enzyme activity." evidence="12">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_016788" description="In CAND; dbSNP:rs104894552." evidence="5 6">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_004998" description="In CAND; dbSNP:rs761064915." evidence="2 14">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039088" description="In CAND; dbSNP:rs1555541310." evidence="2">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039089" description="In CAND; dbSNP:rs750505963." evidence="2">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_004999" description="In CAND; predominant mutation in Ashkenazi Jewish population; 99% loss of activity; dbSNP:rs28940279." evidence="7 12 15 16 17">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="285"/>
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    <feature type="sequence variant" id="VAR_078098" description="In CAND; &lt;1% residual enzyme activity; dbSNP:rs1414684396." evidence="12">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="286"/>
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    </feature>
    <feature type="sequence variant" id="VAR_039090" description="In CAND; dbSNP:rs774323189." evidence="2">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_005000" description="In CAND." evidence="2 14">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="295"/>
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    </feature>
    <feature type="sequence variant" id="VAR_005001" description="In CAND; pan-European origin; most prevalent among non-Jewish CAND patients; probably the most ancient mutation; loss of activity; dbSNP:rs28940574." evidence="2 14 15 17">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="305"/>
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    <feature type="sequence variant" id="VAR_039091" description="In dbSNP:rs376854191." evidence="17">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="310"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 99%." evidence="10">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="71"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 99%." evidence="10">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 99%." evidence="10">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces activity by 99%." evidence="8 10">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="178"/>
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    </feature>
    <feature type="mutagenesis site" description="Abolishes enzymatic activity." evidence="8 10">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="178"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes enzymatic activity." evidence="8 10">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="178"/>
        </location>
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    <feature type="mutagenesis site" description="5-fold decrease in activity." evidence="7">
        <original>E</original>
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        <location>
            <position position="285"/>
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    <feature type="mutagenesis site" description="Reduces activity by 99%." evidence="10">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="288"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="14"/>
            <end position="18"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="25"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="39"/>
            <end position="41"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="48"/>
            <end position="53"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="55"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="65"/>
            <end position="67"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="69"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="75"/>
            <end position="78"/>
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    <feature type="strand" evidence="31">
        <location>
            <begin position="84"/>
            <end position="86"/>
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    <feature type="helix" evidence="30">
        <location>
            <begin position="88"/>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="105"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="110"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="119"/>
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    <feature type="strand" evidence="30">
        <location>
            <begin position="123"/>
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    <feature type="helix" evidence="30">
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            <begin position="134"/>
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    <feature type="strand" evidence="30">
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            <begin position="152"/>
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    <feature type="strand" evidence="28">
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<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="247" xmlns="https://uniprot.org/uniprot">
    <accession>P36896</accession>
    <accession>B7Z5L8</accession>
    <accession>B7Z5W5</accession>
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    <accession>Q15480</accession>
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            <fullName>Serine/threonine-protein kinase receptor R2</fullName>
            <shortName>SKR2</shortName>
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        <name type="primary">ACVR1B</name>
        <name type="synonym">ACVRLK4</name>
        <name type="synonym">ALK4</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
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            <dbReference type="PubMed" id="12364468"/>
            <dbReference type="DOI" id="10.1210/jc.2002-020527"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
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            <title>Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells.</title>
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            <dbReference type="PubMed" id="11909953"/>
            <dbReference type="DOI" id="10.1128/mcb.22.8.2586-2597.2002"/>
        </citation>
        <scope>INTERACTION WITH CRIPTO</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
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            <dbReference type="PubMed" id="12112843"/>
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        <scope>PHOSPHORYLATION AT TYR-380</scope>
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            <dbReference type="PubMed" id="12639945"/>
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        <scope>FUNCTION</scope>
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            </authorList>
            <dbReference type="PubMed" id="12665502"/>
            <dbReference type="DOI" id="10.1074/jbc.m302015200"/>
        </citation>
        <scope>MUTAGENESIS OF LEU-40; ILE-70; VAL-73; LEU-75 AND PRO-77</scope>
        <scope>ACTIVIN-BINDING</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="16720724"/>
            <dbReference type="DOI" id="10.1677/jme.1.01966"/>
        </citation>
        <scope>INTERACTION WITH FKBP1A AND SMAD7</scope>
        <scope>UBIQUITINATION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="18039968"/>
            <dbReference type="DOI" id="10.1242/dev.000026"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>AUTOPHOSPHORYLATION</scope>
    </reference>
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                <person name="Kobayashi T."/>
                <person name="Funatsu O."/>
                <person name="Morita A."/>
                <person name="Ikekita M."/>
            </authorList>
            <dbReference type="PubMed" id="20226172"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2010.03.039"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
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            <dbReference type="PubMed" id="20596523"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0011332"/>
        </citation>
        <scope>UBIQUITINATION</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="21791611"/>
            <dbReference type="DOI" id="10.1128/mcb.05448-11"/>
        </citation>
        <scope>INTERACTION WITH TSC22D1</scope>
    </reference>
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            <title>Activation of the activin A-ALK-Smad pathway in systemic sclerosis.</title>
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            <dbReference type="PubMed" id="21377836"/>
            <dbReference type="DOI" id="10.1016/j.jaut.2010.09.004"/>
        </citation>
        <scope>INVOLVEMENT IN SYSTEMIC SCLEROSIS</scope>
    </reference>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] LEU-146</scope>
        <scope>VARIANT [LARGE SCALE ANALYSIS] HIS-478 (ISOFORM 3)</scope>
    </reference>
    <comment type="function">
        <text evidence="11 12 16 17 20 22 23">Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44880"/>
            <dbReference type="Rhea" id="RHEA-COMP:11024"/>
            <dbReference type="Rhea" id="RHEA-COMP:11025"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:18673"/>
            <dbReference type="Rhea" id="RHEA-COMP:11022"/>
            <dbReference type="Rhea" id="RHEA-COMP:11023"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="1">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="activity regulation">
        <text evidence="7 8">Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 7 8 9 14 19 20 21 22 23">Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B) (PubMed:8196624, PubMed:8622651, PubMed:9032295). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). Interacts with SMAD2 and SMAD3 (PubMed:9892009). Interacts with SMAD7 (PubMed:12023024, PubMed:16720724, PubMed:9892009). Interacts with FKBP1A (PubMed:16720724). Interacts with IGSF1 (PubMed:11266516). Interacts with CRIPTO (PubMed:11909953). Interacts with TDP2 (By similarity). Interacts with TSC22D1/TSC-22 (PubMed:21791611).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384128">
            <id>P36896</id>
        </interactant>
        <interactant intactId="EBI-1027571">
            <id>P62942</id>
            <label>FKBP1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384128">
            <id>P36896</id>
        </interactant>
        <interactant intactId="EBI-352572">
            <id>P08238</id>
            <label>HSP90AB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384128">
            <id>P36896</id>
        </interactant>
        <interactant intactId="EBI-347263">
            <id>Q13485</id>
            <label>SMAD4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384128">
            <id>P36896</id>
        </interactant>
        <interactant intactId="EBI-3861591">
            <id>O15105</id>
            <label>SMAD7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384128">
            <id>P36896</id>
        </interactant>
        <interactant intactId="EBI-8571194">
            <id>P27040</id>
            <label>Acvr2b</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P36896-1</id>
            <name>1</name>
            <name>SKR2-1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P36896-2</id>
            <name>2</name>
            <name>SKR2-2</name>
            <sequence type="described" ref="VSP_004954"/>
        </isoform>
        <isoform>
            <id>P36896-3</id>
            <name>3</name>
            <name>SKR2-3</name>
            <sequence type="described" ref="VSP_004953"/>
        </isoform>
        <isoform>
            <id>P36896-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_041842"/>
        </isoform>
        <isoform>
            <id>P36896-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_041841"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in many tissues, most strongly in kidney, pancreas, brain, lung, and liver.</text>
    </comment>
    <comment type="domain">
        <text evidence="21">The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9 10 11 21">Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7.</text>
    </comment>
    <comment type="PTM">
        <text>Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex.</text>
    </comment>
    <comment type="PTM">
        <text>Ubiquitinated.</text>
    </comment>
    <comment type="disease">
        <text evidence="18">ACVRIB is abundantly expressed in systemic sclerosis patient fibroblasts and production of collagen is also induced by activin-A/INHBA. This suggests that the activin/ACRV1B signaling mechanism is involved in systemic sclerosis.</text>
    </comment>
    <comment type="similarity">
        <text evidence="26">Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.</text>
    </comment>
    <dbReference type="EC" id="2.7.11.30"/>
    <dbReference type="EMBL" id="Z22536">
        <property type="protein sequence ID" value="CAA80258.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U14722">
        <property type="protein sequence ID" value="AAA50246.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L10125">
        <property type="protein sequence ID" value="AAA60555.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L10126">
        <property type="protein sequence ID" value="AAA60556.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L31848">
        <property type="protein sequence ID" value="AAA53349.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L31848">
        <property type="protein sequence ID" value="AAA53350.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L31848">
        <property type="protein sequence ID" value="AAA53351.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT007072">
        <property type="protein sequence ID" value="AAP35735.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299120">
        <property type="protein sequence ID" value="BAH12954.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK299496">
        <property type="protein sequence ID" value="BAH13051.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025259">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000254">
        <property type="protein sequence ID" value="AAH00254.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC040531">
        <property type="protein sequence ID" value="AAH40531.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44893.2">
        <molecule id="P36896-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44894.2">
        <molecule id="P36896-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8816.1">
        <molecule id="P36896-1"/>
    </dbReference>
    <dbReference type="PIR" id="I38859">
        <property type="entry name" value="I38859"/>
    </dbReference>
    <dbReference type="PIR" id="I80182">
        <property type="entry name" value="I80182"/>
    </dbReference>
    <dbReference type="PIR" id="I80183">
        <property type="entry name" value="I80183"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399707.1">
        <molecule id="P36896-5"/>
        <property type="nucleotide sequence ID" value="NM_001412778.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399708.1">
        <molecule id="P36896-5"/>
        <property type="nucleotide sequence ID" value="NM_001412779.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399709.1">
        <molecule id="P36896-5"/>
        <property type="nucleotide sequence ID" value="NM_001412780.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399710.1">
        <molecule id="P36896-5"/>
        <property type="nucleotide sequence ID" value="NM_001412781.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004293.1">
        <molecule id="P36896-1"/>
        <property type="nucleotide sequence ID" value="NM_004302.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_064732.3">
        <molecule id="P36896-5"/>
        <property type="nucleotide sequence ID" value="NM_020327.3"/>
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    <dbReference type="RefSeq" id="NP_064733.3">
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            <begin position="24"/>
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    <feature type="active site" description="Proton acceptor" evidence="4 6">
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        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="213"/>
            <end position="221"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="234"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="10">
        <location>
            <position position="380"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041841" description="In isoform 5." evidence="24">
        <location>
            <begin position="1"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041842" description="In isoform 4." evidence="24">
        <original>D</original>
        <variation>ADCSFLTLPWEVVMVSAAPKLRSLRLQYKGGRGRARFLFPLN</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_004953" description="In isoform 3." evidence="25">
        <original>VHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQEDVKI</original>
        <variation>TFLFCLCSYLPFQDAGSPKAVLLPPFFLQPVGCLLPEPESSFKVAIKGVEVAVLRVRLFFRDQFVE</variation>
        <location>
            <begin position="422"/>
            <end position="505"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_004954" description="In isoform 2." evidence="25">
        <original>ALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQEDVKI</original>
        <variation>VRSWPPAAFPSA</variation>
        <location>
            <begin position="465"/>
            <end position="505"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041406" description="In dbSNP:rs34488074." evidence="15">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011716" description="In dbSNP:rs928906.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="408"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases binding to activin." evidence="13">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases binding to activin." evidence="13">
        <original>I</original>
        <variation>A</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Increases binding to activin." evidence="13">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="73"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases binding to activin." evidence="13">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="75"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Decreases binding to activin." evidence="13">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Leads to constitutive activation." evidence="21">
        <original>T</original>
        <variation>V</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAA60555/AAA60556." evidence="26" ref="3">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAA60555/AAA60556." evidence="26" ref="3">
        <original>WR</original>
        <variation>MA</variation>
        <location>
            <begin position="222"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="32"/>
            <end position="34"/>
        </location>
    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="40"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="49"/>
            <end position="55"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="60"/>
            <end position="62"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="66"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="turn" evidence="27">
        <location>
            <begin position="72"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="77"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="82"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="turn" evidence="28">
        <location>
            <begin position="88"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="94"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_082894" description="In dbSNP:rs34050429." evidence="26">
        <original>R</original>
        <variation>H</variation>
        <location sequence="P36896-3">
            <position position="478"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q61271"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00159"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00585"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10027"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11266516"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="11909953"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12023024"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12112843"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="12364468"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="12639945"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="12665502"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="16720724"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="17344846"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="18039968"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="20226172"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="21377836"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="21791611"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="8196624"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="8622651"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="9032295"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="9892009"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="25">
        <source>
            <dbReference type="PubMed" id="8058741"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="26"/>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="7MRZ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="7OLY"/>
        </source>
    </evidence>
    <sequence length="505" mass="56807" checksum="40A6C65CAA4C7573" modified="1994-06-01" version="1" precursor="true">MAESAGASSFFPLVVLLLAGSGGSGPRGVQALLCACTSCLQANYTCETDGACMVSIFNLDGMEHHVRTCIPKVELVPAGKPFYCLSSEDLRNTHCCYTDYCNRIDLRVPSGHLKEPEHPSMWGPVELVGIIAGPVFLLFLIIIIVFLVINYHQRVYHNRQRLDMEDPSCEMCLSKDKTLQDLVYDLSTSGSGSGLPLFVQRTVARTIVLQEIIGKGRFGEVWRGRWRGGDVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTIEGMIKLALSAASGLAHLHMEIVGTQGKPGIAHRDLKSKNILVKKNGMCAIADLGLAVRHDAVTDTIDIAPNQRVGTKRYMAPEVLDETINMKHFDSFKCADIYALGLVYWEIARRCNSGGVHEEYQLPYYDLVPSDPSIEEMRKVVCDQKLRPNIPNWWQSYEALRVMGKMMRECWYANGAARLTALRIKKTLSQLSVQEDVKI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="245" xmlns="https://uniprot.org/uniprot">
    <accession>P37023</accession>
    <accession>A6NGA8</accession>
    <name>ACVL1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="24">Activin receptor type-1-like</fullName>
            <ecNumber>2.7.11.30</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Activin receptor-like kinase 1</fullName>
            <shortName>ALK-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Serine/threonine-protein kinase receptor R3</fullName>
            <shortName>SKR3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>TGF-B superfamily receptor type I</fullName>
            <shortName>TSR-I</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACVRL1</name>
        <name type="synonym">ACVRLK1</name>
        <name type="synonym">ALK1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Oncogene" volume="8" first="2879" last="2887">
            <title>Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.</title>
            <authorList>
                <person name="ten Dijke P."/>
                <person name="Ichijo H."/>
                <person name="Franzen P."/>
                <person name="Schulz P."/>
                <person name="Saras J."/>
                <person name="Toyoshima H."/>
                <person name="Heldin C.-H."/>
                <person name="Miyazono K."/>
            </authorList>
            <dbReference type="PubMed" id="8397373"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="Cell" volume="75" first="671" last="680">
            <title>Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors.</title>
            <authorList>
                <person name="Attisano L."/>
                <person name="Carcamo J."/>
                <person name="Ventura F."/>
                <person name="Weis F.M."/>
                <person name="Massague J."/>
                <person name="Wrana J.L."/>
            </authorList>
            <dbReference type="PubMed" id="8242742"/>
            <dbReference type="DOI" id="10.1016/0092-8674(93)90488-c"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="Am. J. Hum. Genet." volume="61" first="60" last="67">
            <title>The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.</title>
            <authorList>
                <person name="Berg J.N."/>
                <person name="Gallione C.J."/>
                <person name="Stenzel T.T."/>
                <person name="Johnson D.W."/>
                <person name="Allen W.P."/>
                <person name="Schwartz C.E."/>
                <person name="Jackson C.E."/>
                <person name="Porteous M.E.M."/>
                <person name="Marchuk D.A."/>
            </authorList>
            <dbReference type="PubMed" id="9245985"/>
            <dbReference type="DOI" id="10.1086/513903"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS HHT2 CYS-50; GLN-67; ILE-333; TRP-374 AND THR-424</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="346" last="351">
            <title>The finished DNA sequence of human chromosome 12.</title>
            <authorList>
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                <person name="Morgan M.B."/>
                <person name="Nazareth L.V."/>
                <person name="Scott G."/>
                <person name="Sodergren E."/>
                <person name="Song X.-Z."/>
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                <person name="Dang M."/>
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                <person name="Forbes L.D."/>
                <person name="Gabisi A.M."/>
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                <person name="Hines S."/>
                <person name="Hogues M.E."/>
                <person name="Huang M."/>
                <person name="Idlebird D.G."/>
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                <person name="Leal B."/>
                <person name="Lebow H."/>
                <person name="Lee S."/>
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                <person name="London P."/>
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                <person name="Lucier A."/>
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                <person name="Madu R.C."/>
                <person name="Mapua P."/>
                <person name="Martindale A.D."/>
                <person name="Martinez E."/>
                <person name="Massey E."/>
                <person name="Mawhiney S."/>
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                <person name="Mendez S."/>
                <person name="Mercado C."/>
                <person name="Mercado I.C."/>
                <person name="Merritt C.E."/>
                <person name="Miner Z.L."/>
                <person name="Minja E."/>
                <person name="Mitchell T."/>
                <person name="Mohabbat F."/>
                <person name="Mohabbat K."/>
                <person name="Montgomery B."/>
                <person name="Moore N."/>
                <person name="Morris S."/>
                <person name="Munidasa M."/>
                <person name="Ngo R.N."/>
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                <person name="Nickerson E."/>
                <person name="Nwaokelemeh O.O."/>
                <person name="Nwokenkwo S."/>
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                <person name="Oragunye N."/>
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                <person name="Puazo M."/>
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                <person name="Rabata D."/>
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                <person name="Sonaike T."/>
                <person name="Sorelle R.P."/>
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                <person name="Svatek A.F."/>
                <person name="Svetz L.A."/>
                <person name="Tamerisa K.S."/>
                <person name="Taylor T.R."/>
                <person name="Teague B."/>
                <person name="Thomas N."/>
                <person name="Thorn R.D."/>
                <person name="Trejos Z.Y."/>
                <person name="Trevino B.K."/>
                <person name="Ukegbu O.N."/>
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            </authorList>
            <dbReference type="PubMed" id="16541075"/>
            <dbReference type="DOI" id="10.1038/nature04569"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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                <person name="Yan X."/>
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            <dbReference type="PubMed" id="21791611"/>
            <dbReference type="DOI" id="10.1128/mcb.05448-11"/>
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        <scope>INTERACTION WITH TSC22D1</scope>
    </reference>
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            <dbReference type="PubMed" id="22799562"/>
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        <scope>STRUCTURE BY NMR OF 19-118</scope>
        <scope>FUNCTION AS BMP9 RECEPTOR</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>MUTAGENESIS OF 74-ARG--LEU-76</scope>
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            <dbReference type="PubMed" id="22718755"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 22-118 IN COMPLEX WITH BMP9 AND ACVR2B</scope>
        <scope>FUNCTION AS BMP9 AND BMP10 RECEPTOR</scope>
        <scope>DISULFIDE BONDS</scope>
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            <dbReference type="PubMed" id="8640225"/>
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        </citation>
        <scope>VARIANTS HHT2 SER-232 DEL; ARG-376 AND GLN-411</scope>
    </reference>
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            <dbReference type="PubMed" id="10694922"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(1998)12:2&lt;137::aid-humu16&gt;3.0.co;2-j"/>
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        <scope>VARIANTS HHT2 TYR-51; TRP-77 AND ASP-96</scope>
    </reference>
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            <dbReference type="PubMed" id="10767348"/>
            <dbReference type="DOI" id="10.1093/hmg/9.8.1227"/>
        </citation>
        <scope>VARIANTS HHT2 48-GLY-ALA-49 DELINS GLU-PRO; CYS-50; SER-232 DEL; ILE-333; TYR-344 AND ASP-407</scope>
    </reference>
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            <dbReference type="PubMed" id="11170071"/>
            <dbReference type="DOI" id="10.1002/1096-8628(20010201)98:4&lt;298::aid-ajmg1093&gt;3.0.co;2-k"/>
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        <scope>VARIANTS HHT2 TRP-374 AND ASN-398</scope>
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            <dbReference type="PubMed" id="11484689"/>
            <dbReference type="DOI" id="10.1056/nejm200108023450503"/>
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        <scope>VARIANTS HHT2 ASP-254 DEL; TRP-411 AND TRP-484</scope>
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                <person name="Harrison R.E."/>
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            </authorList>
            <dbReference type="PubMed" id="14684682"/>
            <dbReference type="DOI" id="10.1136/jmg.40.12.865"/>
        </citation>
        <scope>VARIANTS HHT2 ALA-179; ASP-211; TYR-344; TRP-374; GLN-374; SER-399; GLN-411 AND THR-487</scope>
        <scope>CHARACTERIZATION OF VARIANTS HHT2 CYS-50; GLN-67; TRP-77; ALA-179; ASP-211; SER-232 DEL; ASP-254 DEL; ILE-333; TYR-344; GLN-374; LEU-378; GLN-411 AND THR-487</scope>
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        <scope>ERRATUM OF PUBMED:14684682</scope>
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            <title>Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France.</title>
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                <consortium name="French Rendu-Osler network"/>
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        <scope>VARIANTS HHT2 ARG-48; LYS-215; ARG-223; ARG-229; SER-233 DEL; PHE-285; PRO-306; TYR-314; PRO-337; PRO-347; GLN-374; VAL-376; LYS-379; GLY-397; TRP-411; PRO-411; GLN-411; LEU-425; LEU-479; VAL-482 AND TRP-484</scope>
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        <scope>VARIANTS HHT2 TRP-67; TRP-374; LYS-379; ASP-407; TRP-411; VAL-425 AND PHE-425 DEL</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="16752392"/>
            <dbReference type="DOI" id="10.1002/humu.20342"/>
        </citation>
        <scope>VARIANT SER-30</scope>
        <scope>VARIANTS HHT2 TYR-34; ALA-52; ILE-197; ASP-219; LYS-237; LEU-260; PRO-289; ARG-344; CYS-426 AND ARG-433</scope>
    </reference>
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        </citation>
        <scope>VARIANTS HHT2 GLY-50; PRO-66; ARG-69; TYR-176; LEU-233; PRO-265; PRO-403 AND SER-416</scope>
    </reference>
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            <dbReference type="PubMed" id="20414677"/>
            <dbReference type="DOI" id="10.1007/s00439-010-0825-4"/>
        </citation>
        <scope>VARIANTS CYS-38; PRO-138; LYS-277; PRO-342; THR-400 AND GLU-486</scope>
        <scope>VARIANTS HHT2 SER-96; GLY-217; GLU-226; ARG-280; ARG-294; GLN-328; HIS-335; ASP-347; SER-378; ARG-424; SER-449 AND PRO-479</scope>
    </reference>
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        </citation>
        <scope>VARIANTS ASN-8; VAL-59; VAL-159; CYS-225 AND ALA-396</scope>
    </reference>
    <reference key="23">
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        </citation>
        <scope>VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; PHE-77; ASP-211; SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; ASP-379; LYS-379; GLY-404; TRP-411; MET-441 AND TYR-443</scope>
        <scope>VARIANTS ASP-111 AND PHE-417</scope>
        <scope>CHARACTERIZATION OF VARIANTS HHT2 GLY-41; TYR-41; GLY-46; PRO-47; TYR-66; PHE-77; ASP-211; SER-211; VAL-245; PRO-306; VAL-313; TYR-314; SER-378; ASP-379; LYS-379; GLY-404; TRP-411; MET-441 AND TYR-443</scope>
        <scope>CHARACTERIZATION OF VARIANTS ASP-111 AND PHE-417</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="18 19 21">Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44880"/>
            <dbReference type="Rhea" id="RHEA-COMP:11024"/>
            <dbReference type="Rhea" id="RHEA-COMP:11025"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30013"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:61977"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:18673"/>
            <dbReference type="Rhea" id="RHEA-COMP:11022"/>
            <dbReference type="Rhea" id="RHEA-COMP:11023"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:83421"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="1">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="17">Interacts with TSC22D1/TSC-22.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8043559">
            <id>P37023</id>
        </interactant>
        <interactant intactId="EBI-16227344">
            <id>PRO_0000033903</id>
            <label>GDF2</label>
            <dbReference type="UniProtKB" id="Q9UK05"/>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8043559">
            <id>P37023</id>
        </interactant>
        <interactant intactId="EBI-9083443">
            <id>P02750</id>
            <label>LRG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8043559">
            <id>P37023</id>
        </interactant>
        <interactant intactId="EBI-1048095">
            <id>Q6P474</id>
            <label>PDXDC2P</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="21">Cell membrane</location>
            <topology evidence="3">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="7 8 9 10 11 12 13 14 15 16 21 22 23">
        <disease id="DI-01717">
            <name>Telangiectasia, hereditary hemorrhagic, 2</name>
            <acronym>HHT2</acronym>
            <description>A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain.</description>
            <dbReference type="MIM" id="600376"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="24">Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.</text>
    </comment>
    <comment type="online information" name="Hereditary Hemorrhagic Telangiectasia and ENG">
        <link uri="http://arup.utah.edu/database/ACVRL1/ACVRL1_welcome.php"/>
    </comment>
    <dbReference type="EC" id="2.7.11.30"/>
    <dbReference type="EMBL" id="Z22533">
        <property type="protein sequence ID" value="CAA80255.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L17075">
        <property type="protein sequence ID" value="AAA16160.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77713">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77707">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77708">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77709">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77710">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77711">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U77712">
        <property type="protein sequence ID" value="AAB61900.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025259">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471111">
        <property type="protein sequence ID" value="EAW58213.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC042637">
        <property type="protein sequence ID" value="AAH42637.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31804.1"/>
    <dbReference type="PIR" id="A49431">
        <property type="entry name" value="A49431"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000011.2">
        <property type="nucleotide sequence ID" value="NM_000020.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001070869.1">
        <property type="nucleotide sequence ID" value="NM_001077401.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001393416.1">
        <property type="nucleotide sequence ID" value="NM_001406487.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047285857.1">
        <property type="nucleotide sequence ID" value="XM_047429901.1"/>
    </dbReference>
    <dbReference type="PDB" id="2LCR">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=22-118"/>
    </dbReference>
    <dbReference type="PDB" id="3MY0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.65 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=195-497"/>
    </dbReference>
    <dbReference type="PDB" id="4FAO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.36 A"/>
        <property type="chains" value="C/D/I/J/O/P/U/V/c/d/i/j=22-118"/>
    </dbReference>
    <dbReference type="PDB" id="6SF1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A=21-118"/>
    </dbReference>
    <dbReference type="PDB" id="6SF2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A/D=21-118"/>
    </dbReference>
    <dbReference type="PDB" id="6SF3">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A=21-118"/>
    </dbReference>
    <dbReference type="PDB" id="7PPC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="E/F/G/H=22-118"/>
    </dbReference>
    <dbReference type="PDBsum" id="2LCR"/>
    <dbReference type="PDBsum" id="3MY0"/>
    <dbReference type="PDBsum" id="4FAO"/>
    <dbReference type="PDBsum" id="6SF1"/>
    <dbReference type="PDBsum" id="6SF2"/>
    <dbReference type="PDBsum" id="6SF3"/>
    <dbReference type="PDBsum" id="7PPC"/>
    <dbReference type="AlphaFoldDB" id="P37023"/>
    <dbReference type="BMRB" id="P37023"/>
    <dbReference type="SMR" id="P37023"/>
    <dbReference type="BioGRID" id="106609">
        <property type="interactions" value="49"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-5938N"/>
    <dbReference type="FunCoup" id="P37023">
        <property type="interactions" value="335"/>
    </dbReference>
    <dbReference type="IntAct" id="P37023">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="MINT" id="P37023"/>
    <dbReference type="STRING" id="9606.ENSP00000373574"/>
    <dbReference type="BindingDB" id="P37023"/>
    <dbReference type="ChEMBL" id="CHEMBL5311"/>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P37023"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="1784"/>
    <dbReference type="GlyCosmos" id="P37023">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P37023">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P37023"/>
    <dbReference type="PhosphoSitePlus" id="P37023"/>
    <dbReference type="BioMuta" id="ACVRL1"/>
    <dbReference type="DMDM" id="3915750"/>
    <dbReference type="jPOST" id="P37023"/>
    <dbReference type="MassIVE" id="P37023"/>
    <dbReference type="PaxDb" id="9606-ENSP00000373574"/>
    <dbReference type="PeptideAtlas" id="P37023"/>
    <dbReference type="ProteomicsDB" id="55254"/>
    <dbReference type="ABCD" id="P37023">
        <property type="antibodies" value="1 sequenced antibody"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2055">
        <property type="antibodies" value="646 antibodies from 41 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="94"/>
    <dbReference type="Ensembl" id="ENST00000388922.9">
        <property type="protein sequence ID" value="ENSP00000373574.4"/>
        <property type="gene ID" value="ENSG00000139567.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000551576.6">
        <property type="protein sequence ID" value="ENSP00000455848.2"/>
        <property type="gene ID" value="ENSG00000139567.15"/>
    </dbReference>
    <dbReference type="GeneID" id="94"/>
    <dbReference type="KEGG" id="hsa:94"/>
    <dbReference type="MANE-Select" id="ENST00000388922.9">
        <property type="protein sequence ID" value="ENSP00000373574.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000020.3"/>
        <property type="RefSeq protein sequence ID" value="NP_000011.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001rzj.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:175"/>
    <dbReference type="ClinPGx" id="PA24496"/>
    <dbReference type="CTD" id="94"/>
    <dbReference type="DisGeNET" id="94"/>
    <dbReference type="GeneCards" id="ACVRL1"/>
    <dbReference type="GeneReviews" id="ACVRL1"/>
    <dbReference type="HGNC" id="HGNC:175">
        <property type="gene designation" value="ACVRL1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000139567">
        <property type="expression patterns" value="Tissue enhanced (lung)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ACVRL1"/>
    <dbReference type="MIM" id="600376">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="601284">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000139567"/>
    <dbReference type="Orphanet" id="774">
        <property type="disease" value="Hereditary hemorrhagic telangiectasia"/>
    </dbReference>
    <dbReference type="Orphanet" id="275777">
        <property type="disease" value="Heritable pulmonary arterial hypertension"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000139567"/>
    <dbReference type="eggNOG" id="KOG2052">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161446"/>
    <dbReference type="HOGENOM" id="CLU_000288_8_1_1"/>
    <dbReference type="InParanoid" id="P37023"/>
    <dbReference type="OMA" id="TIHAENQ"/>
    <dbReference type="OrthoDB" id="69842at2759"/>
    <dbReference type="PAN-GO" id="P37023">
        <property type="GO annotations" value="11 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P37023"/>
    <dbReference type="BRENDA" id="2.7.10.2">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="BRENDA" id="2.7.11.30">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="P37023"/>
    <dbReference type="Reactome" id="R-HSA-201451">
        <property type="pathway name" value="Signaling by BMP"/>
    </dbReference>
    <dbReference type="SignaLink" id="P37023"/>
    <dbReference type="SIGNOR" id="P37023"/>
    <dbReference type="Agora" id="ENSG00000139567"/>
    <dbReference type="BioGRID-ORCS" id="94">
        <property type="hits" value="32 hits in 1186 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ACVRL1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P37023"/>
    <dbReference type="GeneWiki" id="ACVRL1"/>
    <dbReference type="GenomeRNAi" id="94"/>
    <dbReference type="Pharos" id="P37023">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P37023"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="P37023">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000139567">
        <property type="expression patterns" value="Expressed in right lung and 152 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P37023">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070724">
        <property type="term" value="C:BMP receptor complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048185">
        <property type="term" value="F:activin binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016361">
        <property type="term" value="F:activin receptor activity, type I"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098821">
        <property type="term" value="F:BMP receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019901">
        <property type="term" value="F:protein kinase binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046332">
        <property type="term" value="F:SMAD binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050431">
        <property type="term" value="F:transforming growth factor beta binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005024">
        <property type="term" value="F:transforming growth factor beta receptor activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005025">
        <property type="term" value="F:transforming growth factor beta receptor activity, type I"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004675">
        <property type="term" value="F:transmembrane receptor protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001525">
        <property type="term" value="P:angiogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060840">
        <property type="term" value="P:artery development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008015">
        <property type="term" value="P:blood circulation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002043">
        <property type="term" value="P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="DFLAT"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001955">
        <property type="term" value="P:blood vessel maturation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="DFLAT"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001974">
        <property type="term" value="P:blood vessel remodeling"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030509">
        <property type="term" value="P:BMP signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071773">
        <property type="term" value="P:cellular response to BMP stimulus"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071363">
        <property type="term" value="P:cellular response to growth factor stimulus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071560">
        <property type="term" value="P:cellular response to transforming growth factor beta stimulus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035912">
        <property type="term" value="P:dorsal aorta morphogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009953">
        <property type="term" value="P:dorsal/ventral pattern formation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003203">
        <property type="term" value="P:endocardial cushion morphogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0061154">
        <property type="term" value="P:endothelial tube morphogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007507">
        <property type="term" value="P:heart development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001701">
        <property type="term" value="P:in utero embryonic development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001946">
        <property type="term" value="P:lymphangiogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060836">
        <property type="term" value="P:lymphatic endothelial cell differentiation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043537">
        <property type="term" value="P:negative regulation of blood vessel endothelial cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007162">
        <property type="term" value="P:negative regulation of cell adhesion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030308">
        <property type="term" value="P:negative regulation of cell growth"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030336">
        <property type="term" value="P:negative regulation of cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008285">
        <property type="term" value="P:negative regulation of cell population proliferation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045602">
        <property type="term" value="P:negative regulation of endothelial cell differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010596">
        <property type="term" value="P:negative regulation of endothelial cell migration"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001937">
        <property type="term" value="P:negative regulation of endothelial cell proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051895">
        <property type="term" value="P:negative regulation of focal adhesion assembly"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010629">
        <property type="term" value="P:negative regulation of gene expression"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045766">
        <property type="term" value="P:positive regulation of angiogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1903348">
        <property type="term" value="P:positive regulation of bicellular tight junction assembly"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030513">
        <property type="term" value="P:positive regulation of BMP signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032332">
        <property type="term" value="P:positive regulation of chondrocyte differentiation"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045893">
        <property type="term" value="P:positive regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000314"/>
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    <dbReference type="GO" id="GO:0008217">
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        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0043535">
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        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="DFLAT"/>
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    <dbReference type="GO" id="GO:0006275">
        <property type="term" value="P:regulation of DNA replication"/>
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        <property type="project" value="DFLAT"/>
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    <dbReference type="GO" id="GO:0006355">
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    <dbReference type="GO" id="GO:0001936">
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    <dbReference type="GO" id="GO:0061298">
        <property type="term" value="P:retina vasculature development in camera-type eye"/>
        <property type="evidence" value="ECO:0000250"/>
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    <dbReference type="GO" id="GO:0007165">
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        <property type="term" value="P:transforming growth factor beta receptor signaling pathway"/>
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    <dbReference type="GO" id="GO:0060841">
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    <dbReference type="GO" id="GO:0035313">
        <property type="term" value="P:wound healing, spreading of epidermal cells"/>
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    <dbReference type="CDD" id="cd14142">
        <property type="entry name" value="STKc_ACVR1_ALK1"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd23534">
        <property type="entry name" value="TFP_LU_ECD_ALK1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.510.10:FF:000018">
        <property type="entry name" value="Receptor protein serine/threonine kinase"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="3.30.200.20:FF:000064">
        <property type="entry name" value="Receptor protein serine/threonine kinase"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.10.60.10:FF:000014">
        <property type="entry name" value="Serine/threonine-protein kinase receptor R3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.10.60.10">
        <property type="entry name" value="CD59"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.200.20">
        <property type="entry name" value="Phosphorylase Kinase, domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.510.10">
        <property type="entry name" value="Transferase(Phosphotransferase) domain 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR003605">
        <property type="entry name" value="GS_dom"/>
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    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
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    <dbReference type="InterPro" id="IPR000719">
        <property type="entry name" value="Prot_kinase_dom"/>
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    <dbReference type="InterPro" id="IPR017441">
        <property type="entry name" value="Protein_kinase_ATP_BS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001245">
        <property type="entry name" value="Ser-Thr/Tyr_kinase_cat_dom"/>
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    <dbReference type="InterPro" id="IPR008271">
        <property type="entry name" value="Ser/Thr_kinase_AS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045860">
        <property type="entry name" value="Snake_toxin-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000333">
        <property type="entry name" value="TGFB_receptor"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23255:SF66">
        <property type="entry name" value="SERINE_THREONINE-PROTEIN KINASE RECEPTOR R3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23255">
        <property type="entry name" value="TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07714">
        <property type="entry name" value="PK_Tyr_Ser-Thr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08515">
        <property type="entry name" value="TGF_beta_GS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00653">
        <property type="entry name" value="ACTIVIN2R"/>
    </dbReference>
    <dbReference type="SMART" id="SM00467">
        <property type="entry name" value="GS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57302">
        <property type="entry name" value="Snake toxin-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51256">
        <property type="entry name" value="GS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00107">
        <property type="entry name" value="PROTEIN_KINASE_ATP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50011">
        <property type="entry name" value="PROTEIN_KINASE_DOM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00108">
        <property type="entry name" value="PROTEIN_KINASE_ST"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0037">Angiogenesis</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000024420" description="Activin receptor type-1-like">
        <location>
            <begin position="22"/>
            <end position="503"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="22"/>
            <end position="118"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="119"/>
            <end position="141"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="142"/>
            <end position="503"/>
        </location>
    </feature>
    <feature type="domain" description="GS" evidence="5">
        <location>
            <begin position="172"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase" evidence="4">
        <location>
            <begin position="202"/>
            <end position="492"/>
        </location>
    </feature>
    <feature type="region of interest" description="Mediates specificity for BMP ligand">
        <location>
            <begin position="73"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="4 6">
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="208"/>
            <end position="216"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <position position="229"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 19 25 26">
        <location>
            <begin position="34"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 19 25 26">
        <location>
            <begin position="36"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 19 25 26">
        <location>
            <begin position="46"/>
            <end position="69"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 19 25 26">
        <location>
            <begin position="77"/>
            <end position="89"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="18 19 25 26">
        <location>
            <begin position="90"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079583" evidence="20">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070308" description="In dbSNP:rs149664056." evidence="15">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="30"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070309" description="In HHT2." evidence="15">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070310" evidence="16">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="38"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075231" description="In HHT2; loss of receptor activity in response to BMP9; predominantly retained in the endoplasmic reticulum." evidence="21">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075232" description="In HHT2; loss of receptor activity in response to BMP9; predominantly retained in the endoplasmic reticulum; dbSNP:rs1184716348." evidence="21">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075233" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum." evidence="21">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075234" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs774389618." evidence="21">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026784" description="In HHT2; dbSNP:rs387906392." evidence="8">
        <original>GA</original>
        <variation>EP</variation>
        <location>
            <begin position="48"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026785" description="In HHT2." evidence="12">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006204" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs121909285." evidence="8 11 23">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070311" description="In HHT2." evidence="14">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="50"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006205" description="In HHT2; dbSNP:rs863223409." evidence="7">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070312" description="In HHT2; dbSNP:rs1131691346." evidence="15">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079584" description="Found in a patient with pulmonary arterial hypertension; uncertain significance; dbSNP:rs1466116430." evidence="20">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070313" description="In HHT2." evidence="14">
        <original>H</original>
        <variation>P</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075235" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs1480110873." evidence="21">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006206" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs863223414." evidence="11 23">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026786" description="In HHT2; dbSNP:rs1085307405." evidence="13">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070314" description="In HHT2." evidence="14">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="69"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075236" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs1330837892." evidence="21">
        <original>C</original>
        <variation>F</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006207" description="In HHT2; retained in the endoplasmic reticulum." evidence="7 11">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006208" description="In HHT2." evidence="7">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070315" description="In HHT2." evidence="16">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075237" description="No loss of receptor activity in response to BMP9; mutant protein is capable of targeting the cell surface appropriately; dbSNP:rs1481094868." evidence="21">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070316" evidence="16">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079585" description="Found in a patient with pulmonary arterial hypertension; uncertain significance." evidence="20">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070317" description="In HHT2." evidence="14">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="176"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026787" description="In HHT2; mutant protein is capable of targeting the cell surface appropriately; dbSNP:rs753792569." evidence="11">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070318" description="In HHT2." evidence="15">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="197"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026788" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs28936687." evidence="11 21">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075238" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum." evidence="21">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026789" description="In HHT2; dbSNP:rs754283265." evidence="12">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070319" description="In HHT2." evidence="16">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070320" description="In HHT2." evidence="15">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026790" description="In HHT2." evidence="12">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="223"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079586" description="Found in a patient with pulmonary arterial hypertension; uncertain significance." evidence="20">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="225"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070321" description="In HHT2; dbSNP:rs1565593639." evidence="16">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026791" description="In HHT2." evidence="12">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="229"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006209" description="In HHT2; mutant protein is capable of targeting the cell surface appropriately." evidence="8 11 22">
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070322" description="In HHT2; dbSNP:rs762773076." evidence="14">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026792" description="In HHT2." evidence="12">
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070323" description="In HHT2." evidence="15">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_011717" description="In dbSNP:rs1804508.">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075239" description="In HHT2; no loss of receptor activity in response to BMP9; mutant protein is capable of targeting the cell surface appropriately; affects splicing by inducing the creation of a new donor splice site and the loss of the 3' end of exon 6." evidence="21">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026793" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs387906393." evidence="10 11">
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070324" description="In HHT2." evidence="15">
        <original>I</original>
        <variation>L</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070325" description="In HHT2; dbSNP:rs1592223978." evidence="14">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070326" description="Found in a patient with hereditary hemorrhagic talagiectasia; uncertain significance." evidence="16">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="277"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070327" description="In HHT2." evidence="16">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026794" description="In HHT2; dbSNP:rs1085307410." evidence="12">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070328" description="In HHT2." evidence="15">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070329" description="In HHT2." evidence="16">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026795" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs1940807179." evidence="12 21">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="306"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075240" description="In HHT2; loss of receptor activity in response to BMP9; predominantly retained in the endoplasmic reticulum." evidence="21">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026796" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs1565594311." evidence="12 21">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="314"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070330" description="In HHT2; dbSNP:rs1565594410." evidence="16">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006210" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs863223413." evidence="8 11 23">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="333"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070331" description="In HHT2." evidence="16">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="335"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026797" description="In HHT2; dbSNP:rs1592224349." evidence="12">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070332" description="In dbSNP:rs762287966." evidence="16">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070333" description="In HHT2; dbSNP:rs1592224412." evidence="15">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026798" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs28936688." evidence="8 11">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070334" description="In HHT2." evidence="16">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026799" description="In HHT2." evidence="12">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026800" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs1060503248." evidence="11 12">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="374"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006211" description="In HHT2; dbSNP:rs28936401." evidence="9 11 13 23">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="374"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006212" description="In HHT2; dbSNP:rs28936399." evidence="22">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026801" description="In HHT2; dbSNP:rs1555153277." evidence="12">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026802" description="In HHT2; retained in the endoplasmic reticulum." evidence="11">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070335" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs959973779." evidence="16 21">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075241" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum." evidence="21">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026803" description="In HHT2; loss of receptor activity in response to BMP9; retained in the endoplasmic reticulum; dbSNP:rs1131691686." evidence="12 13 21">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="379"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_079587" description="Found in patients with pulmonary arterial hypertension; uncertain significance." evidence="20">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="396"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026804" description="In HHT2." evidence="12">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="397"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026805" description="In HHT2; dbSNP:rs121909286." evidence="9">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="398"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026806" description="In HHT2; dbSNP:rs121909289." evidence="11">
        <original>W</original>
        <variation>S</variation>
        <location>
            <position position="399"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070336" description="Found in a patient with hereditary hemorrhagic talagiectasia; uncertain significance." evidence="16">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070337" description="In HHT2." evidence="14">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="403"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075242" description="In HHT2; loss of receptor activity in response to BMP9; predominantly retained in the endoplasmic reticulum." evidence="21">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="404"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026807" description="In HHT2; dbSNP:rs1565595129." evidence="8 13">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026808" description="In HHT2; dbSNP:rs121909284." evidence="12">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="411"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006213" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs121909284." evidence="11 12 22">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="411"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026809" description="In HHT2; loss of receptor activity in response to BMP9; predominantly retained in the endoplasmic reticulum; dbSNP:rs121909287." evidence="10 12 13 21">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="411"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070338" description="In HHT2." evidence="14">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="416"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075243" description="No loss of receptor activity in response to BMP9; mutant protein is capable of targeting the cell surface appropriately; dbSNP:rs141653630." evidence="21">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="417"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070339" description="In HHT2; dbSNP:rs1940906429." evidence="16">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="424"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_006214" description="In HHT2; dbSNP:rs1085307419." evidence="23">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="424"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026810" description="In HHT2." evidence="12">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="425"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026811" description="In HHT2." evidence="13">
        <original>F</original>
        <variation>V</variation>
        <location>
            <position position="425"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026812" description="In HHT2." evidence="13">
        <location>
            <position position="425"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070340" description="In HHT2." evidence="15">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="426"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070341" description="In HHT2." evidence="15">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="433"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075244" description="In HHT2; retained in the endoplasmic reticulum; dbSNP:rs1565596498." evidence="21">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="441"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075245" description="In HHT2; retained in the endoplasmic reticulum." evidence="21">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="443"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070342" description="In HHT2; dbSNP:rs1940908457." evidence="16">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="449"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026813" description="In HHT2." evidence="12">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="479"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070343" description="In HHT2; dbSNP:rs1085307426." evidence="16">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="479"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026814" description="In HHT2; likely benign; dbSNP:rs139142865." evidence="12">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026815" description="In HHT2; dbSNP:rs121909288." evidence="10 12">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="484"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070344" description="Found in a patient with hereditary hemorrhagic talagiectasia; uncertain significance; dbSNP:rs113700354." evidence="16">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="486"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026816" description="In HHT2; mutant protein is capable of targeting the cell surface appropriately; dbSNP:rs1085307428." evidence="11">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="487"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Affinity for BMP9 decreased by 200-fold." evidence="19">
        <original>REL</original>
        <variation>DFQ</variation>
        <location>
            <begin position="74"/>
            <end position="76"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAA80255." evidence="24" ref="1">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="26"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="32"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="42"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="59"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="64"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="74"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="83"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="turn" evidence="30">
        <location>
            <begin position="93"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="198"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="203"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="214"/>
            <end position="221"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="224"/>
            <end position="231"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="233"/>
            <end position="235"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="236"/>
            <end position="248"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="259"/>
            <end position="265"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="267"/>
            <end position="269"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="272"/>
            <end position="278"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="285"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="296"/>
            <end position="314"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="325"/>
            <end position="327"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="335"/>
            <end position="338"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="344"/>
            <end position="346"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="353"/>
            <end position="355"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="357"/>
            <end position="359"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="373"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="378"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="390"/>
            <end position="410"/>
        </location>
    </feature>
    <feature type="turn" evidence="28">
        <location>
            <begin position="424"/>
            <end position="428"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="435"/>
            <end position="442"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="455"/>
            <end position="459"/>
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    </feature>
    <feature type="turn" evidence="28">
        <location>
            <begin position="460"/>
            <end position="462"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="463"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="476"/>
            <end position="478"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="482"/>
            <end position="491"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q61288"/>
        </source>
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    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00159"/>
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    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00585"/>
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    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10027"/>
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    <evidence type="ECO:0000269" key="7">
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            <dbReference type="PubMed" id="10694922"/>
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    <evidence type="ECO:0000269" key="8">
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            <dbReference type="PubMed" id="10767348"/>
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    <evidence type="ECO:0000269" key="9">
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    <evidence type="ECO:0000269" key="10">
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    <evidence type="ECO:0000269" key="12">
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    <evidence type="ECO:0000269" key="13">
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            <dbReference type="PubMed" id="15712270"/>
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    <evidence type="ECO:0000269" key="14">
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            <dbReference type="PubMed" id="16525724"/>
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="16752392"/>
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    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="20414677"/>
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    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="21791611"/>
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    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="22718755"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="22799562"/>
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    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="24936649"/>
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    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="26176610"/>
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    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="8640225"/>
        </source>
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    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="9245985"/>
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    <evidence type="ECO:0000305" key="24"/>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PDB" id="2LCR"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="4FAO"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="2LCR"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="3MY0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="29">
        <source>
            <dbReference type="PDB" id="6SF1"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="30">
        <source>
            <dbReference type="PDB" id="6SF3"/>
        </source>
    </evidence>
    <sequence length="503" mass="56124" checksum="074522AA802325DD" modified="1998-12-15" version="2" precursor="true">MTLGSPRKGLLMLLMALVTQGDPVKPSRGPLVTCTCESPHCKGPTCRGAWCTVVLVREEGRHPQEHRGCGNLHRELCRGRPTEFVNHYCCDSHLCNHNVSLVLEATQPPSEQPGTDGQLALILGPVLALLALVALGVLGLWHVRRRQEKQRGLHSELGESSLILKASEQGDSMLGDLLDSDCTTGSGSGLPFLVQRTVARQVALVECVGKGRYGEVWRGLWHGESVAVKIFSSRDEQSWFRETEIYNTVLLRHDNILGFIASDMTSRNSSTQLWLITHYHEHGSLYDFLQRQTLEPHLALRLAVSAACGLAHLHVEIFGTQGKPAIAHRDFKSRNVLVKSNLQCCIADLGLAVMHSQGSDYLDIGNNPRVGTKRYMAPEVLDEQIRTDCFESYKWTDIWAFGLVLWEIARRTIVNGIVEDYRPPFYDVVPNDPSFEDMKKVVCVDQQTPTIPNRLAADPVLSGLAQMMRECWYPNPSARLTALRIKKTLQKISNSPEKPKVIQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-04-01" modified="2026-01-28" version="207" xmlns="https://uniprot.org/uniprot">
    <accession>P07311</accession>
    <accession>A6NDV8</accession>
    <accession>B2R590</accession>
    <name>ACYP1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Acylphosphatase-1</fullName>
            <ecNumber evidence="5">3.6.1.7</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Acylphosphatase, erythrocyte isozyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acylphosphatase, organ-common type isozyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Acylphosphate phosphohydrolase 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ACYP1</name>
        <name type="synonym">ACYPE</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <authorList>
                <person name="Raugei G."/>
            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <tissue>Placenta</tissue>
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    </reference>
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                <person name="Tanai H."/>
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                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
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                <person name="Itakura S."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Isogai T."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
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                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
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                <person name="Trybou A."/>
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                <person name="Bluet E."/>
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                <person name="Pellouin V."/>
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                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
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                <person name="Sainte-Marthe L."/>
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            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Embryonic carcinoma</tissue>
            <tissue>Mammary gland</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1986" name="Biochemistry" volume="25" first="8089" last="8094">
            <title>A new acylphosphatase isoenzyme from human erythrocytes: purification, characterization, and primary structure.</title>
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                <person name="Liguri G."/>
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            <dbReference type="PubMed" id="3026468"/>
            <dbReference type="DOI" id="10.1021/bi00372a044"/>
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        <scope>PROTEIN SEQUENCE OF 2-99</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT ALA-2</scope>
    </reference>
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            <dbReference type="PubMed" id="7796909"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)00553-l"/>
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        <scope>PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 10-86</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="9">
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            <title>Crystallization and preliminary crystallographic analysis of human common-type acylphosphatase.</title>
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            <dbReference type="PubMed" id="16511269"/>
            <dbReference type="DOI" id="10.1107/s174430910504145x"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS)</scope>
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            <title>Rational stabilization of enzymes by computational redesign of surface charge-charge interactions.</title>
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                <person name="Gribenko A.V."/>
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            <dbReference type="PubMed" id="19196981"/>
            <dbReference type="DOI" id="10.1073/pnas.0808220106"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 2-99</scope>
    </reference>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>an acyl phosphate + H2O = a carboxylate + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:14965"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29067"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:59918"/>
            <dbReference type="EC" id="3.6.1.7"/>
        </reaction>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P07311-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P07311-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_045688"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Organ-common type isozyme is found in many different tissues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the acylphosphatase family.</text>
    </comment>
    <dbReference type="EC" id="3.6.1.7" evidence="5"/>
    <dbReference type="EMBL" id="X84194">
        <property type="protein sequence ID" value="CAA58987.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312101">
        <property type="protein sequence ID" value="BAG35037.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007055">
        <property type="protein sequence ID" value="AAD31937.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL049780">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471061">
        <property type="protein sequence ID" value="EAW81216.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035568">
        <property type="protein sequence ID" value="AAH35568.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BG614847">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9838.1">
        <molecule id="P07311-1"/>
    </dbReference>
    <dbReference type="PIR" id="S66187">
        <property type="entry name" value="QPHUE"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001098.1">
        <molecule id="P07311-1"/>
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    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="initiator methionine" description="Removed" evidence="2">
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            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000158535" description="Acylphosphatase-1">
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        <location>
            <position position="2"/>
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    <feature type="splice variant" id="VSP_045688" description="In isoform 2." evidence="3">
        <original>AEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEKVILKLDYSDFQIVK</original>
        <variation>EMTVENRIAETHSKSCVPVSFATSYAG</variation>
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    <sequence length="99" mass="11261" checksum="F9F787E490BC8296" modified="2007-01-23" version="2">MAEGNTLISVDYEIFGKVQGVFFRKHTQAEGKKLGLVGWVQNTDRGTVQGQLQGPISKVRHMQEWLETRGSPKSHIDKANFNNEKVILKLDYSDFQIVK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="223" xmlns="https://uniprot.org/uniprot">
    <accession>O43184</accession>
    <accession>O60470</accession>
    <accession>Q5JRP0</accession>
    <accession>Q5JRP1</accession>
    <accession>Q6P9E3</accession>
    <accession>Q6UWB0</accession>
    <name>ADA12_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 12</fullName>
            <shortName>ADAM 12</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Meltrin-alpha</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM12</name>
        <name type="synonym">MLTN</name>
        <name type="ORF">UNQ346/PRO545</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="157" last="166">
            <title>A novel, secreted form of human ADAM 12 (meltrin alpha) provokes myogenesis in vivo.</title>
            <authorList>
                <person name="Gilpin B.J."/>
                <person name="Loechel F."/>
                <person name="Mattei M.-G."/>
                <person name="Engvall E."/>
                <person name="Albrechtsen R."/>
                <person name="Wewer U.M."/>
            </authorList>
            <dbReference type="PubMed" id="9417060"/>
            <dbReference type="DOI" id="10.1074/jbc.273.1.157"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT ARG-48</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2001-02" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Gilpin B.J."/>
                <person name="Loechel F."/>
                <person name="Mattei M.-G."/>
                <person name="Engvall E."/>
                <person name="Albrechtsen R."/>
                <person name="Wewer U.M."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION TO 36</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Genome Res." volume="13" first="2265" last="2270">
            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
            <authorList>
                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
                <person name="Abaya E."/>
                <person name="Baker K."/>
                <person name="Baldwin D.T."/>
                <person name="Brush J."/>
                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
                <person name="Currell B."/>
                <person name="Deuel B."/>
                <person name="Dowd P."/>
                <person name="Eaton D."/>
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                <person name="Grimaldi C."/>
                <person name="Gu Q."/>
                <person name="Hass P.E."/>
                <person name="Heldens S."/>
                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>VARIANT ARG-48</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
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                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
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                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
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                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
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                <person name="Brown J.Y."/>
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                <person name="Burrill W."/>
                <person name="Burton J."/>
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                <person name="Carter N.P."/>
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                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
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                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
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                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
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                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT ARG-48</scope>
    </reference>
    <reference key="6">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <scope>VARIANT ARG-48</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="16993" last="16997">
            <title>Human ADAM 12 (meltrin alpha) is an active metalloprotease.</title>
            <authorList>
                <person name="Loechel F."/>
                <person name="Gilpin B.J."/>
                <person name="Engvall E."/>
                <person name="Albrechtsen R."/>
                <person name="Wewer U.M."/>
            </authorList>
            <dbReference type="PubMed" id="9642263"/>
            <dbReference type="DOI" id="10.1074/jbc.273.27.16993"/>
        </citation>
        <scope>CHARACTERIZATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2000" name="J. Cell Biol." volume="149" first="1143" last="1156">
            <title>The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading.</title>
            <authorList>
                <person name="Iba K."/>
                <person name="Albrechtsen R."/>
                <person name="Gilpin B.J."/>
                <person name="Froehlich C."/>
                <person name="Loechel F."/>
                <person name="Zolkiewska A."/>
                <person name="Ishiguro K."/>
                <person name="Kojima T."/>
                <person name="Liu W."/>
                <person name="Langford J.K."/>
                <person name="Sanderson R.D."/>
                <person name="Brakebusch C."/>
                <person name="Faessler R."/>
                <person name="Wewer U.M."/>
            </authorList>
            <dbReference type="PubMed" id="10831617"/>
            <dbReference type="DOI" id="10.1083/jcb.149.5.1143"/>
        </citation>
        <scope>INTERACTION WITH SYNDECANS</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="16844" last="16851">
            <title>The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells.</title>
            <authorList>
                <person name="Abram C.L."/>
                <person name="Seals D.F."/>
                <person name="Pass I."/>
                <person name="Salinsky D."/>
                <person name="Maurer L."/>
                <person name="Roth T.M."/>
                <person name="Courtneidge S.A."/>
            </authorList>
            <dbReference type="PubMed" id="12615925"/>
            <dbReference type="DOI" id="10.1074/jbc.m300267200"/>
        </citation>
        <scope>INTERACTION WITH SH3PXD2A</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2005" name="Biol. Cell" volume="97" first="577" last="588">
            <title>FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation.</title>
            <authorList>
                <person name="Bartholin L."/>
                <person name="Destaing O."/>
                <person name="Forissier S."/>
                <person name="Martel S."/>
                <person name="Maguer-Satta V."/>
                <person name="Jurdic P."/>
                <person name="Rimokh R."/>
            </authorList>
            <dbReference type="PubMed" id="15574124"/>
            <dbReference type="DOI" id="10.1042/bc20040506"/>
        </citation>
        <scope>INTERACTION WITH FST3</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="26000" last="26009">
            <title>RACK1, a new ADAM12 interacting protein. Contribution to liver fibrogenesis.</title>
            <authorList>
                <person name="Bourd-Boittin K."/>
                <person name="Le Pabic H."/>
                <person name="Bonnier D."/>
                <person name="L'Helgoualc'h A."/>
                <person name="Theret N."/>
            </authorList>
            <dbReference type="PubMed" id="18621736"/>
            <dbReference type="DOI" id="10.1074/jbc.m709829200"/>
        </citation>
        <scope>INTERACTION WITH RACK1</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] HIS-301; GLU-479 AND PHE-792</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2011" name="Hum. Mutat." volume="32" first="E2148" last="E2175">
            <title>Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Moncada-Pazos A."/>
                <person name="Cal S."/>
                <person name="Soria-Valles C."/>
                <person name="Gartner J."/>
                <person name="Rudloff U."/>
                <person name="Lin J.C."/>
                <person name="Rosenberg S.A."/>
                <person name="Lopez-Otin C."/>
                <person name="Samuels Y."/>
            </authorList>
            <dbReference type="PubMed" id="21618342"/>
            <dbReference type="DOI" id="10.1002/humu.21477"/>
        </citation>
        <scope>VARIANTS GLU-712 AND SER-893</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors (By similarity).</text>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text>Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 7 8 11 13">Interacts with alpha-actinin-2 and with syndecans (By similarity). Interacts with SH3PXD2A. Interacts with FST3. Interacts with RACK1; the interaction is required for PKC-dependent translocation of ADAM12 to the cell membrane.</text>
    </comment>
    <comment type="interaction">
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            <id>O43184</id>
        </interactant>
        <interactant intactId="EBI-1049056">
            <id>Q8N157</id>
            <label>AHI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625825">
            <id>O43184</id>
        </interactant>
        <interactant intactId="EBI-346340">
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    </comment>
    <comment type="interaction">
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            <id>O43184</id>
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        <interactant intactId="EBI-79452">
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    <comment type="interaction">
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            <id>O43184</id>
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        <interactant intactId="EBI-2563437">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
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    <comment type="interaction">
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            <id>O43184</id>
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        <interactant intactId="EBI-621482">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
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        <interactant intactId="EBI-2625790">
            <id>O95633</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-10173507">
            <id>Q6UY14-3</id>
            <label>ADAMTSL4</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        <interactant intactId="EBI-3867333">
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        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-12260294">
            <id>Q9NQ30</id>
            <label>ESM1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-750641">
            <id>Q5TD97</id>
            <label>FHL5</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-11978177">
            <id>Q96NT3-2</id>
            <label>GUCD1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>O43184-4</id>
        </interactant>
        <interactant intactId="EBI-740785">
            <id>P49639</id>
            <label>HOXA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12006944">
            <id>O43184-4</id>
        </interactant>
        <interactant intactId="EBI-10221390">
            <id>P78385</id>
            <label>KRT83</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12006944">
            <id>O43184-4</id>
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        <interactant intactId="EBI-11959885">
            <id>Q07627</id>
            <label>KRTAP1-1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-11749135">
            <id>Q8IUG1</id>
            <label>KRTAP1-3</label>
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        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
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        <experiments>5</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-10176379">
            <id>P59991</id>
            <label>KRTAP12-2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-9996449">
            <id>Q9BYR8</id>
            <label>KRTAP3-1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
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    <comment type="interaction">
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            <id>O43184-4</id>
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        <interactant intactId="EBI-751260">
            <id>Q9BYR7</id>
            <label>KRTAP3-2</label>
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        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-739863">
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            <label>KRTAP4-12</label>
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        <experiments>3</experiments>
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    <comment type="interaction">
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        <interactant intactId="EBI-10250562">
            <id>Q6L8G9</id>
            <label>KRTAP5-6</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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    <comment type="interaction">
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    <comment type="interaction">
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        <interactant intactId="EBI-947402">
            <id>O60336</id>
            <label>MAPKBP1</label>
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    <comment type="interaction">
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            <label>OTX1</label>
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    <comment type="interaction">
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            <id>O43184-4</id>
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            <id>Q6P9E2</id>
            <label>RECK</label>
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    <comment type="interaction">
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            <id>Q16348</id>
            <label>SLC15A2</label>
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            <id>O43609</id>
            <label>SPRY1</label>
        </interactant>
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        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12006944">
            <id>O43184-4</id>
        </interactant>
        <interactant intactId="EBI-354861">
            <id>Q9C004</id>
            <label>SPRY4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12006944">
            <id>O43184-4</id>
        </interactant>
        <interactant intactId="EBI-11952651">
            <id>Q7Z6R9</id>
            <label>TFAP2D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 3</molecule>
        <subcellularLocation>
            <location evidence="20">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 4</molecule>
        <subcellularLocation>
            <location evidence="20">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O43184-1</id>
            <name>1</name>
            <name>12L</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O43184-2</id>
            <name>2</name>
            <name>12S</name>
            <sequence type="described" ref="VSP_005476 VSP_005477"/>
        </isoform>
        <isoform>
            <id>O43184-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_031001 VSP_005476 VSP_005477"/>
        </isoform>
        <isoform>
            <id>O43184-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_031001 VSP_031002 VSP_031003"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Isoform 1 is expressed in placenta and skeletal, cardiac, and smooth muscle. Isoform 2 seems to be expressed only in placenta or in embryo and fetus. Both forms were expressed in some tumor cells lines. Not detected in brain, lung, liver, kidney or pancreas.</text>
    </comment>
    <comment type="domain">
        <text>The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinomas cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44084/ADAM12"/>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF023476">
        <property type="protein sequence ID" value="AAC08702.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF023477">
        <property type="protein sequence ID" value="AAC08703.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358878">
        <property type="protein sequence ID" value="AAQ89237.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC022015">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026226">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC063963">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL589787">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49206.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49209.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC060804">
        <property type="protein sequence ID" value="AAH60804.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7653.1">
        <molecule id="O43184-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7654.1">
        <molecule id="O43184-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001275903.1">
        <molecule id="O43184-4"/>
        <property type="nucleotide sequence ID" value="NM_001288974.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001275904.1">
        <molecule id="O43184-3"/>
        <property type="nucleotide sequence ID" value="NM_001288975.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003465.3">
        <molecule id="O43184-1"/>
        <property type="nucleotide sequence ID" value="NM_003474.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_067673.2">
        <molecule id="O43184-2"/>
        <property type="nucleotide sequence ID" value="NM_021641.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O43184"/>
    <dbReference type="SMR" id="O43184"/>
    <dbReference type="BioGRID" id="113731">
        <property type="interactions" value="44"/>
    </dbReference>
    <dbReference type="CORUM" id="O43184"/>
    <dbReference type="FunCoup" id="O43184">
        <property type="interactions" value="868"/>
    </dbReference>
    <dbReference type="IntAct" id="O43184">
        <property type="interactions" value="48"/>
    </dbReference>
    <dbReference type="MINT" id="O43184"/>
    <dbReference type="STRING" id="9606.ENSP00000357668"/>
    <dbReference type="BindingDB" id="O43184"/>
    <dbReference type="ChEMBL" id="CHEMBL5030"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="1660"/>
    <dbReference type="MEROPS" id="M12.212"/>
    <dbReference type="TCDB" id="8.A.77.1.5">
        <property type="family name" value="the sheddase (sheddase) family"/>
    </dbReference>
    <dbReference type="CarbonylDB" id="O43184"/>
    <dbReference type="GlyCosmos" id="O43184">
        <property type="glycosylation" value="5 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O43184">
        <property type="glycosylation" value="6 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O43184"/>
    <dbReference type="PhosphoSitePlus" id="O43184"/>
    <dbReference type="BioMuta" id="ADAM12"/>
    <dbReference type="MassIVE" id="O43184"/>
    <dbReference type="PaxDb" id="9606-ENSP00000357668"/>
    <dbReference type="PeptideAtlas" id="O43184"/>
    <dbReference type="ProteomicsDB" id="48799">
        <molecule id="O43184-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48800">
        <molecule id="O43184-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48801">
        <molecule id="O43184-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48802">
        <molecule id="O43184-4"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="19223">
        <property type="antibodies" value="459 antibodies from 40 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8038"/>
    <dbReference type="Ensembl" id="ENST00000368676.8">
        <molecule id="O43184-2"/>
        <property type="protein sequence ID" value="ENSP00000357665.4"/>
        <property type="gene ID" value="ENSG00000148848.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000368679.8">
        <molecule id="O43184-1"/>
        <property type="protein sequence ID" value="ENSP00000357668.4"/>
        <property type="gene ID" value="ENSG00000148848.15"/>
    </dbReference>
    <dbReference type="GeneID" id="8038"/>
    <dbReference type="KEGG" id="hsa:8038"/>
    <dbReference type="UCSC" id="uc001ljk.4">
        <molecule id="O43184-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:190"/>
    <dbReference type="ClinPGx" id="PA24507"/>
    <dbReference type="CTD" id="8038"/>
    <dbReference type="DisGeNET" id="8038"/>
    <dbReference type="GeneCards" id="ADAM12"/>
    <dbReference type="HGNC" id="HGNC:190">
        <property type="gene designation" value="ADAM12"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000148848">
        <property type="expression patterns" value="Tissue enriched (placenta)"/>
    </dbReference>
    <dbReference type="MIM" id="602714">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000148848"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000148848"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155495"/>
    <dbReference type="HOGENOM" id="CLU_012714_7_0_1"/>
    <dbReference type="InParanoid" id="O43184"/>
    <dbReference type="OMA" id="SYMLEPC"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="O43184">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O43184"/>
    <dbReference type="BRENDA" id="3.4.24.B10">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O43184"/>
    <dbReference type="Reactome" id="R-HSA-177929">
        <property type="pathway name" value="Signaling by EGFR"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-8941237">
        <property type="pathway name" value="Invadopodia formation"/>
    </dbReference>
    <dbReference type="SignaLink" id="O43184"/>
    <dbReference type="SIGNOR" id="O43184"/>
    <dbReference type="Agora" id="ENSG00000148848"/>
    <dbReference type="BioGRID-ORCS" id="8038">
        <property type="hits" value="11 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM12">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM12"/>
    <dbReference type="GenomeRNAi" id="8038"/>
    <dbReference type="Pharos" id="O43184">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O43184"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="O43184">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000148848">
        <property type="expression patterns" value="Expressed in placenta and 143 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O43184">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017124">
        <property type="term" value="F:SH3 domain binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007155">
        <property type="term" value="P:cell adhesion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007520">
        <property type="term" value="P:myoblast fusion"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045766">
        <property type="term" value="P:positive regulation of angiogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF112">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 12"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00142">
        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="28"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029078" evidence="1">
        <location>
            <begin position="29"/>
            <end position="207"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029079" description="Disintegrin and metalloproteinase domain-containing protein 12">
        <location>
            <begin position="208"/>
            <end position="909"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="208"/>
            <end position="708"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="709"/>
            <end position="729"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="730"/>
            <end position="909"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="214"/>
            <end position="416"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="424"/>
            <end position="510"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="656"/>
            <end position="688"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="822"/>
            <end position="862"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="177"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding; class II" evidence="1">
        <location>
            <begin position="828"/>
            <end position="834"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding; class I" evidence="1">
        <location>
            <begin position="834"/>
            <end position="841"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding; class I" evidence="1">
        <location>
            <begin position="885"/>
            <end position="891"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="851"/>
            <end position="860"/>
        </location>
    </feature>
    <feature type="active site">
        <location>
            <position position="351"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="179"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="350"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="354"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="360"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by SRC" evidence="1">
        <location>
            <position position="907"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="381"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="452"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="651"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="325"/>
            <end position="411"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="367"/>
            <end position="395"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="369"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="482"/>
            <end position="502"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="660"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="664"/>
            <end position="676"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="678"/>
            <end position="687"/>
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    </feature>
    <feature type="splice variant" id="VSP_031001" description="In isoform 3 and isoform 4." evidence="17 18">
        <location>
            <begin position="114"/>
            <end position="116"/>
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    </feature>
    <feature type="splice variant" id="VSP_031002" description="In isoform 4." evidence="18">
        <original>DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLLFT</original>
        <variation>GKEARQEAAESNRERGQGQEPVGSQEHASTASLTLI</variation>
        <location>
            <begin position="705"/>
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    </feature>
    <feature type="splice variant" id="VSP_005476" description="In isoform 2 and isoform 3." evidence="17 19">
        <original>DNQGLTIGILVTILCLLAAGFVVYLKRKTLIRLL</original>
        <variation>EARQEAAESNRERGQGQEPVGSQEHASTASLTLI</variation>
        <location>
            <begin position="705"/>
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        <location>
            <begin position="739"/>
            <end position="909"/>
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        <location>
            <begin position="741"/>
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    <feature type="sequence variant" id="VAR_038542" description="In dbSNP:rs3740199." evidence="9 10 15 16">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="48"/>
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    </feature>
    <feature type="sequence variant" id="VAR_036143" description="In a breast cancer sample; somatic mutation." evidence="12">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="301"/>
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    <feature type="sequence variant" id="VAR_036144" description="In a breast cancer sample; somatic mutation; dbSNP:rs1459457663." evidence="12">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="479"/>
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    </feature>
    <feature type="sequence variant" id="VAR_066310" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="14">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="712"/>
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    </feature>
    <feature type="sequence variant" id="VAR_036145" description="In a breast cancer sample; somatic mutation." evidence="12">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="792"/>
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    </feature>
    <feature type="sequence variant" id="VAR_066311" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs151030407." evidence="14">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="893"/>
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    <evidence type="ECO:0000250" key="1"/>
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    <evidence type="ECO:0000255" key="3">
        <source>
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        <source>
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    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
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    <evidence type="ECO:0000269" key="10">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="15574124"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="18621736"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="21618342"/>
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    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="9417060"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source ref="5"/>
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    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="12975309"/>
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    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="9417060"/>
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    </evidence>
    <evidence type="ECO:0000305" key="20"/>
    <sequence length="909" mass="99542" checksum="E28131C64C4304AB" modified="2009-05-05" version="3" precursor="true"> </sequence>
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<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>Q04771</accession>
    <name>ACVR1_HUMAN</name>
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        <recommendedName>
            <fullName>Activin receptor type-1</fullName>
            <ecNumber evidence="22">2.7.11.30</ecNumber>
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            <fullName>Activin receptor type I</fullName>
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        <alternativeName>
            <fullName>Activin receptor-like kinase 2</fullName>
            <shortName>ALK-2</shortName>
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        <alternativeName>
            <fullName>Serine/threonine-protein kinase receptor R1</fullName>
            <shortName>SKR1</shortName>
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        <alternativeName>
            <fullName>TGF-B superfamily receptor type I</fullName>
            <shortName>TSR-I</shortName>
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        <name type="primary">ACVR1</name>
        <name type="synonym">ACVRLK2</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="J. Biol. Chem." volume="268" first="12719" last="12723">
            <title>A widely expressed transmembrane serine/threonine kinase that does not bind activin, inhibin, transforming growth factor beta, or bone morphogenic factor.</title>
            <authorList>
                <person name="Matsuzaki K."/>
                <person name="McKeehan W.L."/>
            </authorList>
            <dbReference type="PubMed" id="8389764"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)31447-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
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            <title>Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity.</title>
            <authorList>
                <person name="ten Dijke P."/>
                <person name="Ichijo H."/>
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                <person name="Miyazono K."/>
            </authorList>
            <dbReference type="PubMed" id="8397373"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1996" name="Biochemistry" volume="35" first="309" last="314">
            <title>Interaction of transforming growth factor beta receptors with apolipoprotein J/clusterin.</title>
            <authorList>
                <person name="Reddy K.B."/>
                <person name="Karode M.C."/>
                <person name="Harmony A.K."/>
                <person name="Howe P.H."/>
            </authorList>
            <dbReference type="PubMed" id="8555189"/>
            <dbReference type="DOI" id="10.1021/bi951880a"/>
        </citation>
        <scope>INTERACTION WITH CLU</scope>
    </reference>
    <reference key="5">
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            <title>Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2.</title>
            <authorList>
                <person name="Macias-Silva M."/>
                <person name="Hoodless P.A."/>
                <person name="Tang S.J."/>
                <person name="Buchwald M."/>
                <person name="Wrana J.L."/>
            </authorList>
            <dbReference type="PubMed" id="9748228"/>
            <dbReference type="DOI" id="10.1074/jbc.273.40.25628"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INTERACTION WITH BMP7</scope>
        <scope>MUTAGENESIS OF GLN-207</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="J. Endocrinol." volume="195" first="95" last="103">
            <title>Activin receptor-like kinase-2 inhibits activin signaling by blocking the binding of activin to its type II receptor.</title>
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                <person name="Renlund N."/>
                <person name="O'Neill F.H."/>
                <person name="Zhang L."/>
                <person name="Sidis Y."/>
                <person name="Teixeira J."/>
            </authorList>
            <dbReference type="PubMed" id="17911401"/>
            <dbReference type="DOI" id="10.1677/joe-07-0281"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ACVR2A AND AMHR2</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="FEBS J." volume="275" first="172" last="183">
            <title>Type I receptor binding of bone morphogenetic protein 6 is dependent on N-glycosylation of the ligand.</title>
            <authorList>
                <person name="Saremba S."/>
                <person name="Nickel J."/>
                <person name="Seher A."/>
                <person name="Kotzsch A."/>
                <person name="Sebald W."/>
                <person name="Mueller T.D."/>
            </authorList>
            <dbReference type="PubMed" id="18070108"/>
            <dbReference type="DOI" id="10.1111/j.1742-4658.2007.06187.x"/>
        </citation>
        <scope>INTERACTION WITH BMP6</scope>
    </reference>
    <reference key="8">
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            <title>Large-scale proteomics analysis of the human kinome.</title>
            <authorList>
                <person name="Oppermann F.S."/>
                <person name="Gnad F."/>
                <person name="Olsen J.V."/>
                <person name="Hornberger R."/>
                <person name="Greff Z."/>
                <person name="Keri G."/>
                <person name="Mann M."/>
                <person name="Daub H."/>
            </authorList>
            <dbReference type="PubMed" id="19369195"/>
            <dbReference type="DOI" id="10.1074/mcp.m800588-mcp200"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2010" name="J. Biol. Chem." volume="285" first="29588" last="29598">
            <title>TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells.</title>
            <authorList>
                <person name="Luo J."/>
                <person name="Tang M."/>
                <person name="Huang J."/>
                <person name="He B.C."/>
                <person name="Gao J.L."/>
                <person name="Chen L."/>
                <person name="Zuo G.W."/>
                <person name="Zhang W."/>
                <person name="Luo Q."/>
                <person name="Shi Q."/>
                <person name="Zhang B.Q."/>
                <person name="Bi Y."/>
                <person name="Luo X."/>
                <person name="Jiang W."/>
                <person name="Su Y."/>
                <person name="Shen J."/>
                <person name="Kim S.H."/>
                <person name="Huang E."/>
                <person name="Gao Y."/>
                <person name="Zhou J.Z."/>
                <person name="Yang K."/>
                <person name="Luu H.H."/>
                <person name="Pan X."/>
                <person name="Haydon R.C."/>
                <person name="Deng Z.L."/>
                <person name="He T.C."/>
            </authorList>
            <dbReference type="PubMed" id="20628059"/>
            <dbReference type="DOI" id="10.1074/jbc.m110.130518"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH GDF2/BMP9</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Mol. Cell. Biol." volume="31" first="3700" last="3709">
            <title>TSC-22 promotes transforming growth factor beta-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity.</title>
            <authorList>
                <person name="Yan X."/>
                <person name="Zhang J."/>
                <person name="Pan L."/>
                <person name="Wang P."/>
                <person name="Xue H."/>
                <person name="Zhang L."/>
                <person name="Gao X."/>
                <person name="Zhao X."/>
                <person name="Ning Y."/>
                <person name="Chen Y.G."/>
            </authorList>
            <dbReference type="PubMed" id="21791611"/>
            <dbReference type="DOI" id="10.1128/mcb.05448-11"/>
        </citation>
        <scope>INTERACTION WITH TSC22D1</scope>
    </reference>
    <reference key="11">
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            <title>Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning.</title>
            <authorList>
                <person name="Umasankar P.K."/>
                <person name="Sanker S."/>
                <person name="Thieman J.R."/>
                <person name="Chakraborty S."/>
                <person name="Wendland B."/>
                <person name="Tsang M."/>
                <person name="Traub L.M."/>
            </authorList>
            <dbReference type="PubMed" id="22484487"/>
            <dbReference type="DOI" id="10.1038/ncb2473"/>
        </citation>
        <scope>INTERACTION WITH FCHO1</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2015" name="Mol. Endocrinol." volume="29" first="140" last="152">
            <title>Mutant activin-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors.</title>
            <authorList>
                <person name="Fujimoto M."/>
                <person name="Ohte S."/>
                <person name="Osawa K."/>
                <person name="Miyamoto A."/>
                <person name="Tsukamoto S."/>
                <person name="Mizuta T."/>
                <person name="Kokabu S."/>
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                <person name="Katagiri T."/>
            </authorList>
            <dbReference type="PubMed" id="25354296"/>
            <dbReference type="DOI" id="10.1210/me.2014-1301"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF THR-203 AND GLY-325</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2020" name="Blood" volume="135" first="453" last="456">
            <title>Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from binding to the BMP type I receptor ALK3.</title>
            <authorList>
                <person name="Wang C.Y."/>
                <person name="Xu Y."/>
                <person name="Traeger L."/>
                <person name="Dogan D.Y."/>
                <person name="Xiao X."/>
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            </authorList>
            <dbReference type="PubMed" id="31800957"/>
            <dbReference type="DOI" id="10.1182/blood.2019002620"/>
        </citation>
        <scope>INTERACTION WITH BMP6</scope>
    </reference>
    <reference key="14">
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            <title>Crystal structure of the kinase domain of type I activin receptor (ACVR1) in complex with FKBP12 and dorsomorphin.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 172-499 IN COMPLEX WITH FKBP1A</scope>
    </reference>
    <reference evidence="25" key="15">
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                <person name="Chaikuad A."/>
                <person name="Alfano I."/>
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            </authorList>
            <dbReference type="PubMed" id="22977237"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.365932"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 172-499</scope>
        <scope>FUNCTION</scope>
    </reference>
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                <person name="Shore E.M."/>
                <person name="Xu M."/>
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                <person name="Fenstermacher D.A."/>
                <person name="Brown M.A."/>
                <person name="Kaplan F.S."/>
            </authorList>
            <dbReference type="PubMed" id="16642017"/>
            <dbReference type="DOI" id="10.1038/ng1783"/>
        </citation>
        <scope>VARIANT FOP HIS-206</scope>
    </reference>
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                <person name="Barthorpe S."/>
                <person name="Bhamra G."/>
                <person name="Buck G."/>
                <person name="Choudhury B."/>
                <person name="Clements J."/>
                <person name="Cole J."/>
                <person name="Dicks E."/>
                <person name="Forbes S."/>
                <person name="Gray K."/>
                <person name="Halliday K."/>
                <person name="Harrison R."/>
                <person name="Hills K."/>
                <person name="Hinton J."/>
                <person name="Jenkinson A."/>
                <person name="Jones D."/>
                <person name="Menzies A."/>
                <person name="Mironenko T."/>
                <person name="Perry J."/>
                <person name="Raine K."/>
                <person name="Richardson D."/>
                <person name="Shepherd R."/>
                <person name="Small A."/>
                <person name="Tofts C."/>
                <person name="Varian J."/>
                <person name="Webb T."/>
                <person name="West S."/>
                <person name="Widaa S."/>
                <person name="Yates A."/>
                <person name="Cahill D.P."/>
                <person name="Louis D.N."/>
                <person name="Goldstraw P."/>
                <person name="Nicholson A.G."/>
                <person name="Brasseur F."/>
                <person name="Looijenga L."/>
                <person name="Weber B.L."/>
                <person name="Chiew Y.-E."/>
                <person name="DeFazio A."/>
                <person name="Greaves M.F."/>
                <person name="Green A.R."/>
                <person name="Campbell P."/>
                <person name="Birney E."/>
                <person name="Easton D.F."/>
                <person name="Chenevix-Trench G."/>
                <person name="Tan M.-H."/>
                <person name="Khoo S.K."/>
                <person name="Teh B.T."/>
                <person name="Yuen S.T."/>
                <person name="Leung S.Y."/>
                <person name="Wooster R."/>
                <person name="Futreal P.A."/>
                <person name="Stratton M.R."/>
            </authorList>
            <dbReference type="PubMed" id="17344846"/>
            <dbReference type="DOI" id="10.1038/nature05610"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] GLY-15; PHE-41; GLN-47 AND SER-115</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2009" name="Hum. Mutat." volume="30" first="379" last="390">
            <title>Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1.</title>
            <authorList>
                <person name="Kaplan F.S."/>
                <person name="Xu M."/>
                <person name="Seemann P."/>
                <person name="Connor J.M."/>
                <person name="Glaser D.L."/>
                <person name="Carroll L."/>
                <person name="Delai P."/>
                <person name="Fastnacht-Urban E."/>
                <person name="Forman S.J."/>
                <person name="Gillessen-Kaesbach G."/>
                <person name="Hoover-Fong J."/>
                <person name="Koester B."/>
                <person name="Pauli R.M."/>
                <person name="Reardon W."/>
                <person name="Zaidi S.A."/>
                <person name="Zasloff M."/>
                <person name="Morhart R."/>
                <person name="Mundlos S."/>
                <person name="Groppe J."/>
                <person name="Shore E.M."/>
            </authorList>
            <dbReference type="PubMed" id="19085907"/>
            <dbReference type="DOI" id="10.1002/humu.20868"/>
        </citation>
        <scope>VARIANTS FOP 197-PRO-PHE-198 DELINS LEU; HIS-206; GLU-207; ARG-328; TRP-328; GLU-328; ASP-356 AND PRO-375</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2009" name="PLoS ONE" volume="4" first="E5005" last="E5005">
            <title>Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients.</title>
            <authorList>
                <person name="Petrie K.A."/>
                <person name="Lee W.H."/>
                <person name="Bullock A.N."/>
                <person name="Pointon J.J."/>
                <person name="Smith R."/>
                <person name="Russell R.G."/>
                <person name="Brown M.A."/>
                <person name="Wordsworth B.P."/>
                <person name="Triffitt J.T."/>
            </authorList>
            <dbReference type="PubMed" id="19330033"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0005005"/>
        </citation>
        <scope>VARIANTS FOP ILE-202 AND GLU-328</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 10 14 17 18 22">Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:44880"/>
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            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.11.30"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="22">
            <text>L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:18673"/>
            <dbReference type="Rhea" id="RHEA-COMP:11022"/>
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        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
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        </cofactor>
        <cofactor evidence="1">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
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    </comment>
    <comment type="subunit">
        <text evidence="10 11 14 15 16 19 21 22 23">Interacts with FKBP1A (PubMed:22484487, Ref.14). Interacts with FCHO1 (PubMed:22484487). Interacts with CLU (PubMed:8555189). Interacts with type II receptors AMHR2 and ACVR2A (PubMed:17911401). Interacts with BMP7 (PubMed:9748228). Interacts with GDF2/BMP9 (PubMed:20628059). Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression (PubMed:18070108, PubMed:31800957). Interacts with TSC22D1/TSC-22 (PubMed:21791611).</text>
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    <comment type="interaction">
        <interactant intactId="EBI-1383616">
            <id>Q04771</id>
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        <interactant intactId="EBI-3950019">
            <id>Q9UF33</id>
            <label>EPHA6</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
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    <comment type="tissue specificity">
        <text evidence="20">Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells.</text>
    </comment>
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        <disease id="DI-00499">
            <name>Fibrodysplasia ossificans progressiva</name>
            <acronym>FOP</acronym>
            <description>A rare autosomal dominant connective tissue disorder resulting in skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to a debilitating ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible.</description>
            <dbReference type="MIM" id="135100"/>
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        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
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        <text evidence="24">Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.</text>
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        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0464">Manganese</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="1">
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            <begin position="1"/>
            <end position="20"/>
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    <feature type="chain" id="PRO_0000024394" description="Activin receptor type-1">
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            <begin position="21"/>
            <end position="509"/>
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            <end position="123"/>
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            <begin position="124"/>
            <end position="146"/>
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            <begin position="147"/>
            <end position="509"/>
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    <feature type="domain" description="GS" evidence="6">
        <location>
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            <end position="207"/>
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    </feature>
    <feature type="domain" description="Protein kinase" evidence="5">
        <location>
            <begin position="208"/>
            <end position="502"/>
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    </feature>
    <feature type="active site" description="Proton acceptor" evidence="5 7">
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            <position position="336"/>
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    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <begin position="214"/>
            <end position="222"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="5">
        <location>
            <position position="235"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="26">
        <location>
            <position position="501"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="102"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041392" description="In dbSNP:rs13406336." evidence="9">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041393" description="In dbSNP:rs55957214." evidence="9">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041394" description="In dbSNP:rs34056189." evidence="9">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041395" description="In a melanoma sample; somatic mutation." evidence="9">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058418" description="In FOP; variant phenotype." evidence="12">
        <original>PF</original>
        <variation>L</variation>
        <location>
            <begin position="197"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058419" description="In FOP; with some atypical features; dbSNP:rs387906591." evidence="13">
        <original>R</original>
        <variation>I</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_028444" description="In FOP; dbSNP:rs121912678." evidence="8 12">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058420" description="In FOP; with some atypical features." evidence="12">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058421" description="In FOP; variant phenotype; dbSNP:rs387906589." evidence="12 13">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058422" description="In FOP; variant phenotype; dbSNP:rs387906588." evidence="12">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058423" description="In FOP; variant phenotype; dbSNP:rs387906588." evidence="12">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="328"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058424" description="In FOP; variant phenotype; dbSNP:rs121912679." evidence="12">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="356"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_058425" description="In FOP; variant phenotype; dbSNP:rs387906590." evidence="12">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="375"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost complete loss of alcaline phosphatase induction; in association with A-325." evidence="18">
        <original>T</original>
        <variation>V</variation>
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Strong induction of SMAD1 phosphorylation." evidence="22">
        <original>Q</original>
        <variation>D</variation>
        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Almost complete loss of alcaline phosphatase induction; in association with V-203." evidence="18">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="325"/>
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    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="33"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="42"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="46"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="63"/>
            <end position="71"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="75"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="89"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="turn" evidence="30">
        <location>
            <begin position="97"/>
            <end position="102"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="180"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="strand" evidence="28">
        <location>
            <begin position="194"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="198"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="209"/>
            <end position="217"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="220"/>
            <end position="227"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="230"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="239"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="242"/>
            <end position="254"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="265"/>
            <end position="272"/>
        </location>
    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="274"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
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        <location>
            <begin position="367"/>
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        <location>
            <begin position="379"/>
            <end position="381"/>
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        <location>
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    <evidence type="ECO:0000250" key="1"/>
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            <dbReference type="UniProtKB" id="P15261"/>
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            <dbReference type="PDB" id="7YRU"/>
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    <sequence length="509" mass="57153" checksum="E2B0F051D19DD052" modified="1994-02-01" version="1" precursor="true">MVDGVMILPVLIMIALPSPSMEDEKPKVNPKLYMCVCEGLSCGNEDHCEGQQCFSSLSINDGFHVYQKGCFQVYEQGKMTCKTPPSPGQAVECCQGDWCNRNITAQLPTKGKSFPGTQNFHLEVGLIILSVVFAVCLLACLLGVALRKFKRRNQERLNPRDVEYGTIEGLITTNVGDSTLADLLDHSCTSGSGSGLPFLVQRTVARQITLLECVGKGRYGEVWRGSWQGENVAVKIFSSRDEKSWFRETELYNTVMLRHENILGFIASDMTSRHSSTQLWLITHYHEMGSLYDYLQLTTLDTVSCLRIVLSIASGLAHLHIEIFGTQGKPAIAHRDLKSKNILVKKNGQCCIADLGLAVMHSQSTNQLDVGNNPRVGTKRYMAPEVLDETIQVDCFDSYKRVDIWAFGLVLWEVARRMVSNGIVEDYKPPFYDVVPNDPSFEDMRKVVCVDQQRPNIPNRWFSDPTLTSLAKLMKECWYQNPSARLTALRIKKTLTKIDNSLDKLKTDC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
    <accession>O75077</accession>
    <accession>A2RU59</accession>
    <name>ADA23_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 23</fullName>
            <shortName>ADAM 23</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 3</fullName>
            <shortName>MDC-3</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM23</name>
        <name type="synonym">MDC3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Biochem. J." volume="334" first="93" last="98">
            <title>Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain.</title>
            <authorList>
                <person name="Sagane K."/>
                <person name="Ohya Y."/>
                <person name="Hasegawa Y."/>
                <person name="Tanaka I."/>
            </authorList>
            <dbReference type="PubMed" id="9693107"/>
            <dbReference type="DOI" id="10.1042/bj3340093"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Mol. Biol. Cell" volume="11" first="1457" last="1469">
            <title>ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alpha v beta 3 integrin through an RGD-independent mechanism.</title>
            <authorList>
                <person name="Cal S."/>
                <person name="Freije J.M.P."/>
                <person name="Lopez J.M."/>
                <person name="Takada Y."/>
                <person name="Lopez-Otin C."/>
            </authorList>
            <dbReference type="PubMed" id="10749942"/>
            <dbReference type="DOI" id="10.1091/mbc.11.4.1457"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA)</scope>
        <scope>INTERACTION WITH INTEGRIN ALPHA-V/BETA-3</scope>
        <scope>MUTAGENESIS OF GLU-566</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Gene" volume="325" first="171" last="178">
            <title>Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains.</title>
            <authorList>
                <person name="Sun Y.P."/>
                <person name="Deng K.J."/>
                <person name="Wang F."/>
                <person name="Zhang J."/>
                <person name="Huang X."/>
                <person name="Qiao S."/>
                <person name="Zhao S."/>
            </authorList>
            <dbReference type="PubMed" id="14697522"/>
            <dbReference type="DOI" id="10.1016/j.gene.2003.10.012"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Can bind to LGI1 and LGI4 (By similarity). Ligand for integrin alpha-V/beta-3.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="10">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform Gamma</molecule>
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O75077-1</id>
            <name>Alpha</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O75077-2</id>
            <name>Beta</name>
            <sequence type="described" ref="VSP_012046"/>
        </isoform>
        <isoform>
            <id>O75077-3</id>
            <name>Gamma</name>
            <sequence type="described" ref="VSP_012045"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Highly expressed in the brain and weakly expressed in the heart. In the brain, expressed prominently in the amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital pole.</text>
    </comment>
    <comment type="developmental stage">
        <text>Highly expressed in the fetal brain.</text>
    </comment>
    <comment type="domain">
        <text>A conserved motif AVN[ED]CD within the disintegrin-like domain could be involved in the binding to the integrin receptor.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44041/ADAM23"/>
    </comment>
    <dbReference type="EMBL" id="AB009672">
        <property type="protein sequence ID" value="BAA32351.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ005580">
        <property type="protein sequence ID" value="CAC20565.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471063">
        <property type="protein sequence ID" value="EAW70386.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132763">
        <property type="protein sequence ID" value="AAI32764.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132765">
        <property type="protein sequence ID" value="AAI32766.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="nucleotide sequence ID" value="NM_003812.4"/>
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        <property type="nucleotide sequence ID" value="XM_005246932.4"/>
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    <dbReference type="RefSeq" id="XP_054200314.1">
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        <property type="nucleotide sequence ID" value="XM_054344339.1"/>
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        <property type="interactions" value="8"/>
    </dbReference>
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    <dbReference type="MEROPS" id="M12.979"/>
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        <property type="glycosylation" value="8 sites, No reported glycans"/>
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    <dbReference type="ProteomicsDB" id="49742">
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    <dbReference type="Antibodypedia" id="34180">
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    <dbReference type="Ensembl" id="ENST00000264377.8">
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        <property type="gene ID" value="ENSG00000114948.14"/>
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        <property type="protein sequence ID" value="ENSP00000264377.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003812.4"/>
        <property type="RefSeq protein sequence ID" value="NP_003803.1"/>
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        <property type="organism name" value="human"/>
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    <dbReference type="ClinPGx" id="PA24519"/>
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    <dbReference type="GeneCards" id="ADAM23"/>
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        <property type="gene designation" value="ADAM23"/>
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    <dbReference type="HPA" id="ENSG00000114948">
        <property type="expression patterns" value="Tissue enhanced (brain, parathyroid gland)"/>
    </dbReference>
    <dbReference type="MIM" id="603710">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000114948"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000114948"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158781"/>
    <dbReference type="HOGENOM" id="CLU_012714_5_2_1"/>
    <dbReference type="InParanoid" id="O75077"/>
    <dbReference type="OMA" id="ECDCTES"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="O75077">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O75077"/>
    <dbReference type="PathwayCommons" id="O75077"/>
    <dbReference type="Reactome" id="R-HSA-5682910">
        <property type="pathway name" value="LGI-ADAM interactions"/>
    </dbReference>
    <dbReference type="SignaLink" id="O75077"/>
    <dbReference type="Agora" id="ENSG00000114948"/>
    <dbReference type="BioGRID-ORCS" id="8745">
        <property type="hits" value="22 hits in 1149 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM23">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM23"/>
    <dbReference type="GenomeRNAi" id="8745"/>
    <dbReference type="Pharos" id="O75077">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O75077"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="O75077">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000114948">
        <property type="expression patterns" value="Expressed in Brodmann (1909) area 10 and 161 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O75077">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="P:cellular response to leukemia inhibitory factor"/>
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        <property type="project" value="Ensembl"/>
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        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
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        <property type="entry name" value="Laminin"/>
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        <property type="entry name" value="EGF_extracell"/>
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        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
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    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
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    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
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    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
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    <dbReference type="PANTHER" id="PTHR11905:SF13">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 23"/>
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    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Disintegrin"/>
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    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="59"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029118" evidence="2">
        <location>
            <begin position="60"/>
            <end position="286"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029119" description="Disintegrin and metalloproteinase domain-containing protein 23">
        <location>
            <begin position="287"/>
            <end position="832"/>
        </location>
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    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="287"/>
            <end position="792"/>
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    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="793"/>
            <end position="813"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="814"/>
            <end position="832"/>
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    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="299"/>
            <end position="496"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="502"/>
            <end position="588"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="732"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="1"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="region of interest" description="May bind the integrin receptor">
        <location>
            <begin position="563"/>
            <end position="568"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="1"/>
            <end position="10"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="28"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="263"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="547"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="548"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="664"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="732"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="408"/>
            <end position="491"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="450"/>
            <end position="475"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="452"/>
            <end position="459"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="560"/>
            <end position="580"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="736"/>
            <end position="751"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="745"/>
            <end position="757"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="759"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012045" description="In isoform Gamma." evidence="9">
        <original>GPSATNLIIGSIAGAILVAAIVLGGTGWGFKNVKKRRFDPTQQGPI</original>
        <variation>EMSRREGSILLSKAPSESAALDGHRLALLDSGYDILAAVLLELLSL</variation>
        <location>
            <begin position="787"/>
            <end position="832"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012046" description="In isoform Beta." evidence="9">
        <original>GPSATNLIIGSIAGAILVAAIVLGGTGWGFK</original>
        <variation>VNMATSRLIGAVAGTLLALGVIFGGTGWGIE</variation>
        <location>
            <begin position="787"/>
            <end position="817"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significantly lower of adhesion-promoting activity." evidence="7">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="566"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10749942"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="14697522"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14697522"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <sequence length="832" mass="91926" checksum="7841A9670E1C24EF" modified="1998-11-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P35348</accession>
    <accession>A8K0I3</accession>
    <accession>B0ZBD1</accession>
    <accession>B0ZBD2</accession>
    <accession>B0ZBD4</accession>
    <accession>B0ZBD5</accession>
    <accession>B0ZBD6</accession>
    <accession>B0ZBD8</accession>
    <accession>B0ZBD9</accession>
    <accession>O60451</accession>
    <accession>Q13675</accession>
    <accession>Q13729</accession>
    <accession>Q4VBM7</accession>
    <accession>Q6RUJ4</accession>
    <accession>Q6RUJ5</accession>
    <accession>Q6RUJ7</accession>
    <accession>Q6RUJ8</accession>
    <accession>Q6RUJ9</accession>
    <accession>Q96RE8</accession>
    <accession>Q9UD63</accession>
    <accession>Q9UD67</accession>
    <name>ADA1A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="24">Alpha-1A adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-1A adrenoreceptor</fullName>
            <shortName evidence="4">Alpha-1A adrenoceptor</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="26">Alpha-1C adrenergic receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-adrenergic receptor 1c</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="29" type="primary">ADRA1A</name>
        <name type="synonym">ADRA1C</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="Biochem. Biophys. Res. Commun." volume="195" first="902" last="909">
            <title>Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor.</title>
            <authorList>
                <person name="Hirasawa A."/>
                <person name="Horie K."/>
                <person name="Tanaka T."/>
                <person name="Takagaki K."/>
                <person name="Murai M."/>
                <person name="Yano J."/>
                <person name="Tsujimoto G."/>
            </authorList>
            <dbReference type="PubMed" id="8396931"/>
            <dbReference type="DOI" id="10.1006/bbrc.1993.2130"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-347</scope>
        <source>
            <tissue>Prostate</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="Biochem. Biophys. Res. Commun." volume="201" first="1296" last="1304">
            <title>Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c.</title>
            <authorList>
                <person name="Weinberg D.H."/>
                <person name="Trivedi P."/>
                <person name="Tan C.P."/>
                <person name="Mitra S."/>
                <person name="Perkins-Barrow A."/>
                <person name="Borkowski D."/>
                <person name="Strader C.D."/>
                <person name="Bayne M."/>
            </authorList>
            <dbReference type="PubMed" id="8024574"/>
            <dbReference type="DOI" id="10.1006/bbrc.1994.1845"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-347</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1994" name="Mol. Pharmacol." volume="45" first="703" last="708">
            <title>The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype.</title>
            <authorList>
                <person name="Forray C."/>
                <person name="Bard J.A."/>
                <person name="Wetzel J.M."/>
                <person name="Chiu G."/>
                <person name="Shapiro E."/>
                <person name="Tang R."/>
                <person name="Lepor H."/>
                <person name="Hartig P.R."/>
                <person name="Weinshank R.L."/>
                <person name="Branchek T.A."/>
                <person name="Gluchowski C."/>
            </authorList>
            <dbReference type="PubMed" id="8183249"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Hippocampus</tissue>
            <tissue>Lymphocyte</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1995" name="Br. J. Pharmacol." volume="115" first="1475" last="1485">
            <title>The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.</title>
            <authorList>
                <person name="Tseng-Crank J."/>
                <person name="Kost T."/>
                <person name="Goetz A."/>
                <person name="Hazum S."/>
                <person name="Roberson K.M."/>
                <person name="Haizlip J."/>
                <person name="Godinot N."/>
                <person name="Robertson C.N."/>
                <person name="Saussy D."/>
            </authorList>
            <dbReference type="PubMed" id="8564208"/>
            <dbReference type="DOI" id="10.1111/j.1476-5381.1995.tb16640.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-347</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1995" name="FEBS Lett." volume="363" first="256" last="260">
            <title>Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants.</title>
            <authorList>
                <person name="Hirasawa A."/>
                <person name="Shibata K."/>
                <person name="Horie K."/>
                <person name="Takei Y."/>
                <person name="Obika K."/>
                <person name="Tanaka T."/>
                <person name="Muramoto N."/>
                <person name="Takagaki K."/>
                <person name="Yano J."/>
                <person name="Tsujimoto G."/>
            </authorList>
            <dbReference type="PubMed" id="7737411"/>
            <dbReference type="DOI" id="10.1016/0014-5793(95)00330-c"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3)</scope>
        <scope>VARIANT ARG-347</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Prostate</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1995" name="J. Pharmacol. Exp. Ther." volume="272" first="134" last="142">
            <title>Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues.</title>
            <authorList>
                <person name="Schwinn D.A."/>
                <person name="Johnston G.I."/>
                <person name="Page S.O."/>
                <person name="Mosley M.J."/>
                <person name="Wilson K.H."/>
                <person name="Worman N.P."/>
                <person name="Campbell S."/>
                <person name="Fidock M.D."/>
                <person name="Furness L.M."/>
                <person name="Parry-Smith D.J."/>
                <person name="Peter B."/>
                <person name="Bailey D.S."/>
            </authorList>
            <dbReference type="PubMed" id="7815325"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-347</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1998" name="FEBS Lett." volume="422" first="279" last="283">
            <title>Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms.</title>
            <authorList>
                <person name="Chang D.J."/>
                <person name="Chang T.K."/>
                <person name="Yamanishi S.S."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <tissue>Prostate</tissue>
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        <scope>TISSUE SPECIFICITY</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
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        <scope>INTERACTION WITH CAVIN4</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] TRP-40</scope>
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    <comment type="function">
        <text evidence="2 3 10 11 12 13 15 16 17 21">Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C (PubMed:37563160). ADRA1A binds the catecholamine ligands norepinephrine and epinephrine (PubMed:18802028, PubMed:37563160, PubMed:7815325, PubMed:8024574, PubMed:8183249, PubMed:8832064). Can also couple to G(14) protein (By similarity). Nuclear ADRA1A forms heterooligomers with ADRA1B to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes (PubMed:18802028, PubMed:22120526). At the plasma membrane, ADRA1A interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy (PubMed:24567387). Additionally, functions as a vasopressor in resistance arteries and plays a role in maintaining normal arterial blood pressure (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="11 12">Homo- and heterooligomer. Heterooligomerizes with ADRA1B homooligomers in cardiac myocytes (PubMed:22120526). Interacts with CAVIN4 (PubMed:24567387).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21288891">
            <id>P35348-1</id>
        </interactant>
        <interactant intactId="EBI-713009">
            <id>Q96HD1</id>
            <label>CRELD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10 11">Nucleus membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Membrane</location>
            <location evidence="12">Caveola</location>
        </subcellularLocation>
        <text evidence="10 11 12">Location at the nuclear membrane facilitates heterooligomerization and regulates ERK-mediated signaling in cardiac myocytes (PubMed:18802028, PubMed:22120526). Colocalizes with GNAQ, PLCB1 as well as LAP2 at the nuclear membrane of cardiac myocytes (PubMed:18802028, PubMed:22120526). Colocalizes with CAVIN4 and CAV3 at the plasma membrane and partly within the cytoplasm in cardiomyocytes (PubMed:24567387).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P35348-1</id>
            <name>1</name>
            <name>Alpha 1c-1</name>
            <name>Alpha(1A-1)</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P35348-2</id>
            <name>2</name>
            <name>Alpha 1c-2</name>
            <name>Alpha(1A-2)</name>
            <sequence type="described" ref="VSP_011055"/>
        </isoform>
        <isoform>
            <id>P35348-3</id>
            <name>3</name>
            <name>Alpha 1c-3</name>
            <name>Alpha(1A-3)</name>
            <sequence type="described" ref="VSP_011044 VSP_011045"/>
        </isoform>
        <isoform>
            <id>P35348-4</id>
            <name>4</name>
            <name>Alpha(1A-4)</name>
            <sequence type="described" ref="VSP_011050"/>
        </isoform>
        <isoform>
            <id>P35348-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_011051 VSP_011052"/>
        </isoform>
        <isoform>
            <id>P35348-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_011053 VSP_011054"/>
        </isoform>
        <isoform>
            <id>P35348-7</id>
            <name>7</name>
            <name>2b/3b</name>
            <sequence type="described" ref="VSP_011047 VSP_011048"/>
        </isoform>
        <isoform>
            <id>P35348-8</id>
            <name>8</name>
            <name>2c</name>
            <sequence type="described" ref="VSP_011046"/>
        </isoform>
        <isoform>
            <id>P35348-9</id>
            <name>9</name>
            <name>3c</name>
            <sequence type="described" ref="VSP_011049"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="14 18 22">Expressed in heart, brain, liver and prostate, but not in kidney, lung, adrenal, aorta and pituitary. Within the prostate, expressed in the apex, base, periurethral and lateral lobe. Isoform 4 is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">C-terminal Ser or Thr residues may be phosphorylated.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 7</molecule>
        <text evidence="28">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1A sub-subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="28">
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    <feature type="transmembrane region" description="Helical; Name=1" evidence="1">
        <location>
            <begin position="28"/>
            <end position="51"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="52"/>
            <end position="64"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="1">
        <location>
            <begin position="65"/>
            <end position="88"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="89"/>
            <end position="99"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="1">
        <location>
            <begin position="100"/>
            <end position="122"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="123"/>
            <end position="143"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="1">
        <location>
            <begin position="144"/>
            <end position="167"/>
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    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="168"/>
            <end position="181"/>
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    <feature type="transmembrane region" description="Helical; Name=5" evidence="1">
        <location>
            <begin position="182"/>
            <end position="205"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="206"/>
            <end position="273"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="1">
        <location>
            <begin position="274"/>
            <end position="297"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="298"/>
            <end position="305"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="1">
        <location>
            <begin position="306"/>
            <end position="329"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="330"/>
            <end position="466"/>
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    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="11">
        <location>
            <begin position="334"/>
            <end position="349"/>
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    </feature>
    <feature type="binding site" evidence="13 31">
        <location>
            <position position="106"/>
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        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    </feature>
    <feature type="binding site" evidence="13 31">
        <location>
            <position position="188"/>
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        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA" evidence="5">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="5">
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="13"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6 13 30 31">
        <location>
            <begin position="99"/>
            <end position="176"/>
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    </feature>
    <feature type="splice variant" id="VSP_011046" description="In isoform 8." evidence="23">
        <original>GSFFPDFKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTLHPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCTTARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV</original>
        <variation>DEVSLCHQAGVQWHDLGSLQPPPPGFKRFSCLSLPSSWDYRDVPPGRRHQAQLIFVFLVETGFHHVGQDDLDLLTS</variation>
        <location>
            <begin position="295"/>
            <end position="466"/>
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    <feature type="splice variant" id="VSP_011053" description="In isoform 6." evidence="23">
        <original>GSFFPDFKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLR</original>
        <variation>DEETEAQEGKNDSPSFKQPVHHAAVLGLEVMEKENLEGVSRKDTCGVW</variation>
        <location>
            <begin position="295"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011049" description="In isoform 9." evidence="23">
        <original>SFFPDFKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTLHPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCTTARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV</original>
        <variation>THTHDMKPASRPRLLSLLPKEGEHETHHWSCDPLSLESTPGAQEPCLTLGFTSLSSIHLTKAQIQHVTVTDTGKTVT</variation>
        <location>
            <begin position="296"/>
            <end position="466"/>
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    </feature>
    <feature type="splice variant" id="VSP_011047" description="In isoform 7." evidence="23">
        <original>SFFPDFKPSETVFKIVFWLGYLNSCINPI</original>
        <variation>TYILKYDVLFWRKGLSVCTRLRERKEIKN</variation>
        <location>
            <begin position="296"/>
            <end position="324"/>
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    <feature type="splice variant" id="VSP_011051" description="In isoform 5." evidence="23">
        <original>SF</original>
        <variation>KS</variation>
        <location>
            <begin position="296"/>
            <end position="297"/>
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    <feature type="splice variant" id="VSP_011052" description="In isoform 5." evidence="23">
        <location>
            <begin position="298"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011048" description="In isoform 7." evidence="23">
        <location>
            <begin position="325"/>
            <end position="466"/>
        </location>
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    <feature type="splice variant" id="VSP_011054" description="In isoform 6." evidence="23">
        <location>
            <begin position="343"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011055" description="In isoform 2." evidence="25">
        <original>VRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV</original>
        <variation>TKSRSVTRLECSGMILAHCNLRLPGSRDSPASASQAAGTTGMCHQADATRPS</variation>
        <location>
            <begin position="424"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011050" description="In isoform 4." evidence="27">
        <original>VRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV</original>
        <variation>RGMDCRYFTKNCREHIKHVNFMMPPWRKGSEC</variation>
        <location>
            <begin position="424"/>
            <end position="466"/>
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    </feature>
    <feature type="splice variant" id="VSP_011044" description="In isoform 3." evidence="25">
        <original>VRSKSF</original>
        <variation>GHTPMT</variation>
        <location>
            <begin position="424"/>
            <end position="429"/>
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    <feature type="splice variant" id="VSP_011045" description="In isoform 3." evidence="25">
        <location>
            <begin position="430"/>
            <end position="466"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035756" description="In a breast cancer sample; somatic mutation." evidence="9">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="40"/>
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    <feature type="sequence variant" id="VAR_049370" description="In dbSNP:rs2229125.">
        <original>I</original>
        <variation>S</variation>
        <location>
            <position position="200"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019509" description="In dbSNP:rs1048101." evidence="7 8 14 15 16 18 19 20 21">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_049371" description="In dbSNP:rs3730247.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="414"/>
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    </feature>
    <feature type="sequence variant" id="VAR_049372" description="In dbSNP:rs2229126.">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="465"/>
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    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with A-335; A-342; A-348 and A-349." evidence="11">
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        <variation>A</variation>
        <location>
            <position position="334"/>
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    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with A-334; A-342; A-348 and A-349." evidence="11">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="335"/>
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    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with A-334; A-335; A-348 and A-349." evidence="11">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="342"/>
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    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with A-334; A-335; A-342 and A-349." evidence="11">
        <original>R</original>
        <variation>A</variation>
        <location>
            <position position="348"/>
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    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes; when associated with A-334; A-335; A-342 and A-348." evidence="11">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="349"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA93114." evidence="28" ref="4">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA93114." evidence="28" ref="4">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAK77197." evidence="28" ref="9">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 14; AAH95512." evidence="28" ref="14">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2." evidence="28" ref="2">
        <original>Q</original>
        <variation>C</variation>
        <location>
            <position position="338"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA93114." evidence="28" ref="4">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAK77197." evidence="28" ref="9">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="384"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAK77197." evidence="28" ref="9">
        <original>R</original>
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        <location>
            <position position="387"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAK77197." evidence="28" ref="9">
        <original>K</original>
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        <location>
            <position position="390"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA04960." evidence="28" ref="1">
        <original>Q</original>
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        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAK77197." evidence="28" ref="9">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="437"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAA93114." evidence="28" ref="4">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="442"/>
        </location>
    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="34"/>
            <end position="53"/>
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    </feature>
    <feature type="turn" evidence="34">
        <location>
            <begin position="55"/>
            <end position="58"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="60"/>
            <end position="89"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="96"/>
            <end position="100"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="102"/>
            <end position="129"/>
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    </feature>
    <feature type="turn" evidence="33">
        <location>
            <begin position="131"/>
            <end position="133"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="134"/>
            <end position="137"/>
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    </feature>
    <feature type="turn" evidence="34">
        <location>
            <begin position="140"/>
            <end position="142"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="143"/>
            <end position="158"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="161"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="172"/>
            <end position="174"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="182"/>
            <end position="214"/>
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    </feature>
    <feature type="strand" evidence="33">
        <location>
            <begin position="260"/>
            <end position="264"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="269"/>
            <end position="297"/>
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    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="299"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="helix" evidence="34">
        <location>
            <begin position="305"/>
            <end position="325"/>
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    </feature>
    <feature type="helix" evidence="32">
        <location>
            <begin position="327"/>
            <end position="329"/>
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    </feature>
    <feature type="helix" evidence="33">
        <location>
            <begin position="332"/>
            <end position="342"/>
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    <feature type="sequence conflict" description="In Ref. 7; AAC06138." evidence="28" ref="7">
        <original>S</original>
        <variation>L</variation>
        <location sequence="P35348-4">
            <position position="453"/>
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    <feature type="sequence conflict" description="In Ref. 8; AAR84650." evidence="28" ref="8">
        <original>E</original>
        <variation>Q</variation>
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            <position position="302"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P18130"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P97718"/>
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    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q9WU25"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15179408"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18802028"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="22120526"/>
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    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="24567387"/>
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    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="37563160"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="7737411"/>
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    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="7815325"/>
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    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="8024574"/>
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    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="8183249"/>
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    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="8196478"/>
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    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="8396931"/>
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    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="8564208"/>
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    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="8832064"/>
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    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="9490024"/>
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    <evidence type="ECO:0000303" key="23">
        <source>
            <dbReference type="PubMed" id="10493934"/>
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    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="37563160"/>
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    <evidence type="ECO:0000303" key="25">
        <source>
            <dbReference type="PubMed" id="7737411"/>
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    <evidence type="ECO:0000303" key="26">
        <source>
            <dbReference type="PubMed" id="8396931"/>
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    </evidence>
    <evidence type="ECO:0000303" key="27">
        <source>
            <dbReference type="PubMed" id="9490024"/>
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    <evidence type="ECO:0000305" key="28"/>
    <evidence type="ECO:0000312" key="29">
        <source>
            <dbReference type="HGNC" id="HGNC:277"/>
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    </evidence>
    <evidence type="ECO:0007744" key="30">
        <source>
            <dbReference type="PDB" id="8THK"/>
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    </evidence>
    <evidence type="ECO:0007744" key="31">
        <source>
            <dbReference type="PDB" id="8THL"/>
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    <evidence type="ECO:0007829" key="32">
        <source>
            <dbReference type="PDB" id="7YM8"/>
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    <evidence type="ECO:0007829" key="33">
        <source>
            <dbReference type="PDB" id="8HN1"/>
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    <evidence type="ECO:0007829" key="34">
        <source>
            <dbReference type="PDB" id="8THK"/>
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    <sequence length="466" mass="51487" checksum="1A50487531DECDF0" modified="1995-11-01" version="2">MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSVTHYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCIISIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINEEPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKNAPAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPDFKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTLHPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCTTARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="238" xmlns="https://uniprot.org/uniprot">
    <accession>Q13444</accession>
    <accession>B3KQU5</accession>
    <accession>B4DLB5</accession>
    <accession>B4DMH8</accession>
    <accession>E9PN65</accession>
    <accession>Q13493</accession>
    <accession>Q53XQ0</accession>
    <accession>Q5SR68</accession>
    <accession>Q5SR69</accession>
    <accession>Q6R267</accession>
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    <accession>Q71S63</accession>
    <accession>Q71S64</accession>
    <accession>Q71S65</accession>
    <accession>Q71S66</accession>
    <accession>Q71S67</accession>
    <accession>Q71S68</accession>
    <accession>Q71S69</accession>
    <accession>Q96C78</accession>
    <accession>U3KQL5</accession>
    <name>ADA15_HUMAN</name>
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        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 15</fullName>
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            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Metalloprotease RGD disintegrin protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 15</fullName>
            <shortName>MDC-15</shortName>
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        <alternativeName>
            <fullName>Metargidin</fullName>
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    </protein>
    <gene>
        <name type="primary">ADAM15</name>
        <name type="synonym">MDC15</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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        <scope>VARIANTS THR-191 AND LYS-216</scope>
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            <dbReference type="PubMed" id="9516430"/>
            <dbReference type="DOI" id="10.1074/jbc.273.13.7345"/>
        </citation>
        <scope>INTERACTION WITH INTEGRIN ALPHAV-BETA3</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="31693" last="31699">
            <title>Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.</title>
            <authorList>
                <person name="Howard L."/>
                <person name="Nelson K.K."/>
                <person name="Maciewicz R.A."/>
                <person name="Blobel C.P."/>
            </authorList>
            <dbReference type="PubMed" id="10531379"/>
            <dbReference type="DOI" id="10.1074/jbc.274.44.31693"/>
        </citation>
        <scope>INTERACTION WITH SH3GL2 AND SNX9</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1999" name="J. Cell Sci." volume="112" first="579" last="587">
            <title>Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.</title>
            <authorList>
                <person name="Nath D."/>
                <person name="Slocombe P.M."/>
                <person name="Stephens P.E."/>
                <person name="Warn A."/>
                <person name="Hutchinson G.R."/>
                <person name="Yamada K.M."/>
                <person name="Docherty A.J."/>
                <person name="Murphy G."/>
            </authorList>
            <dbReference type="PubMed" id="9914169"/>
            <dbReference type="DOI" id="10.1242/jcs.112.4.579"/>
        </citation>
        <scope>INTERACTION WITH INTEGRIN ALPHAV-BETA3 AND INTEGRIN ALPHA5-BETA1</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2002" name="Exp. Cell Res." volume="279" first="239" last="247">
            <title>ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin.</title>
            <authorList>
                <person name="Ham C."/>
                <person name="Levkau B."/>
                <person name="Raines E.W."/>
                <person name="Herren B."/>
            </authorList>
            <dbReference type="PubMed" id="12243749"/>
            <dbReference type="DOI" id="10.1006/excr.2002.5606"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="4999" last="5007">
            <title>Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases.</title>
            <authorList>
                <person name="Poghosyan Z."/>
                <person name="Robbins S.M."/>
                <person name="Houslay M.D."/>
                <person name="Webster A."/>
                <person name="Murphy G."/>
                <person name="Edwards D.R."/>
            </authorList>
            <dbReference type="PubMed" id="11741929"/>
            <dbReference type="DOI" id="10.1074/jbc.m107430200"/>
        </citation>
        <scope>PHOSPHORYLATION AT TYR-715 AND TYR-735</scope>
        <scope>INTERACTION WITH GRB2; LCK AND HCK</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2002" name="J. Biol. Chem." volume="277" first="33683" last="33689">
            <title>The role of ADAM 15 in glomerular mesangial cell migration.</title>
            <authorList>
                <person name="Martin J."/>
                <person name="Eynstone L.V."/>
                <person name="Davies M."/>
                <person name="Williams J.D."/>
                <person name="Steadman R."/>
            </authorList>
            <dbReference type="PubMed" id="12091380"/>
            <dbReference type="DOI" id="10.1074/jbc.m200988200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="16844" last="16851">
            <title>The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells.</title>
            <authorList>
                <person name="Abram C.L."/>
                <person name="Seals D.F."/>
                <person name="Pass I."/>
                <person name="Salinsky D."/>
                <person name="Maurer L."/>
                <person name="Roth T.M."/>
                <person name="Courtneidge S.A."/>
            </authorList>
            <dbReference type="PubMed" id="12615925"/>
            <dbReference type="DOI" id="10.1074/jbc.m300267200"/>
        </citation>
        <scope>INTERACTION WITH SH3PXD2A</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2005" name="Arthritis Rheum." volume="52" first="1100" last="1109">
            <title>Homeostatic effects of the metalloproteinase disintegrin ADAM15 in degenerative cartilage remodeling.</title>
            <authorList>
                <person name="Bohm B.B."/>
                <person name="Aigner T."/>
                <person name="Roy B."/>
                <person name="Brodie T.A."/>
                <person name="Blobel C.P."/>
                <person name="Burkhardt H."/>
            </authorList>
            <dbReference type="PubMed" id="15818704"/>
            <dbReference type="DOI" id="10.1002/art.20974"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2007" name="Am. J. Respir. Cell Mol. Biol." volume="37" first="494" last="500">
            <title>Inhibition of airway smooth muscle adhesion and migration by the disintegrin domain of ADAM-15.</title>
            <authorList>
                <person name="Lu D."/>
                <person name="Xie S."/>
                <person name="Sukkar M.B."/>
                <person name="Lu X."/>
                <person name="Scully M.F."/>
                <person name="Chung K.F."/>
            </authorList>
            <dbReference type="PubMed" id="17575078"/>
            <dbReference type="DOI" id="10.1165/rcmb.2006-0364oc"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="16948" last="16958">
            <title>ADAM-15/metargidin mediates homotypic aggregation of human T lymphocytes and heterotypic interactions of T lymphocytes with intestinal epithelial cells.</title>
            <authorList>
                <person name="Charrier L."/>
                <person name="Yan Y."/>
                <person name="Nguyen H.T."/>
                <person name="Dalmasso G."/>
                <person name="Laboisse C.L."/>
                <person name="Gewirtz A.T."/>
                <person name="Sitaraman S.V."/>
                <person name="Merlin D."/>
            </authorList>
            <dbReference type="PubMed" id="17416588"/>
            <dbReference type="DOI" id="10.1074/jbc.m700158200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF 484-ARG-GLY-485</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2008" name="Int. J. Biochem. Cell Biol." volume="40" first="2164" last="2173">
            <title>ADAM15 suppresses cell motility by driving integrin alpha5beta1 cell surface expression via Erk inactivation.</title>
            <authorList>
                <person name="Chen Q."/>
                <person name="Meng L.H."/>
                <person name="Zhu C.H."/>
                <person name="Lin L.P."/>
                <person name="Lu H."/>
                <person name="Ding J."/>
            </authorList>
            <dbReference type="PubMed" id="18387333"/>
            <dbReference type="DOI" id="10.1016/j.biocel.2008.02.021"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="18393" last="18401">
            <title>The ectodomain shedding of E-cadherin by ADAM15 supports ErbB receptor activation.</title>
            <authorList>
                <person name="Najy A.J."/>
                <person name="Day K.C."/>
                <person name="Day M.L."/>
            </authorList>
            <dbReference type="PubMed" id="18434311"/>
            <dbReference type="DOI" id="10.1074/jbc.m801329200"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2009" name="Biochem. J." volume="420" first="105" last="113">
            <title>Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays.</title>
            <authorList>
                <person name="Maretzky T."/>
                <person name="Yang G."/>
                <person name="Ouerfelli O."/>
                <person name="Overall C.M."/>
                <person name="Worpenberg S."/>
                <person name="Hassiepen U."/>
                <person name="Eder J."/>
                <person name="Blobel C.P."/>
            </authorList>
            <dbReference type="PubMed" id="19207106"/>
            <dbReference type="DOI" id="10.1042/bj20082127"/>
        </citation>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2009" name="J. Cell. Biochem." volume="108" first="877" last="885">
            <title>Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins.</title>
            <authorList>
                <person name="Kleino I."/>
                <person name="Ortiz R.M."/>
                <person name="Yritys M."/>
                <person name="Huovila A.P."/>
                <person name="Saksela K."/>
            </authorList>
            <dbReference type="PubMed" id="19718658"/>
            <dbReference type="DOI" id="10.1002/jcb.22317"/>
        </citation>
        <scope>INTERACTION WITH HCK; ITSN1; ITSN2; LYN; NCF1; NEPHROCYSTIN; SH3PXD2A; SNX33; SNX9 AND SRC</scope>
    </reference>
    <comment type="function">
        <text evidence="10 14 16 17 18 21 22">Active metalloproteinase with gelatinolytic and collagenolytic activity. Plays a role in the wound healing process. Mediates both heterotypic intraepithelial cell/T-cell interactions and homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell adhesion and migration of airway smooth muscle cells. Suppresses cell motility on or towards fibronectin possibly by driving alpha-v/beta-1 integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation. Cleaves E-cadherin in response to growth factor deprivation. Plays a role in glomerular cell migration. Plays a role in pathological neovascularization. May play a role in cartilage remodeling. May be proteolytically processed, during sperm epididymal maturation and the acrosome reaction. May play a role in sperm-egg binding through its disintegrin domain.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="23">Inhibited by hydroxamate-type metalloproteinase inhibitors such as marimastat. Inhibited by metalloproteinase inhibitor 2 (TIMP-2) and TIMP-3 at nanomolar concentrations. Not significantly inhibited by TIMP-1 at concentrations of up to 100 nM. Not activated by PMA or ionomycin.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 8 9 12 20 24 28 29">Interacts with ITAGV-ITGB3 (vitronectin receptor). Interacts with SH3GL2 and SNX9; this interaction occurs preferentially with ADAM15 precursor, rather than the processed form, suggesting it occurs in a secretory pathway compartment prior to the medial Golgi. Interacts with ITAG9-ITGB1 (By similarity). Interacts specifically with Src family protein-tyrosine kinases (PTKs). Interacts with SH3PXD2A. Interacts with ITAGV-ITGB1. Interacts with GRB2, HCK, ITSN1, ITSN2, LYN, MAPK1, MAPK3, NCF1, NCK1, nephrocystin, PTK6, SNX33, LCK and SRC.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-744695">
            <id>Q8N9N5</id>
            <label>BANP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-624835">
            <id>Q06187</id>
            <label>BTK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-741101">
            <id>Q13643</id>
            <label>FHL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-515315">
            <id>P06241</id>
            <label>FYN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-346340">
            <id>P08631</id>
            <label>HCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-1348">
            <id>P06239</id>
            <label>LCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-79452">
            <id>P07948</id>
            <label>LYN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-953828">
            <id>O15259</id>
            <label>NPHP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-347978">
            <id>P37198</id>
            <label>NUP62</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-1051152">
            <id>Q92882</id>
            <label>OSTF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-77926">
            <id>Q9UKS6</id>
            <label>PACSIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-740322">
            <id>Q93062</id>
            <label>RBPMS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-77938">
            <id>Q99962</id>
            <label>SH3GL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-2483234">
            <id>Q5TCZ1</id>
            <label>SH3PXD2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-2481535">
            <id>Q8WV41</id>
            <label>SNX33</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-77848">
            <id>Q9Y5X1</id>
            <label>SNX9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-10198587">
            <id>Q02446</id>
            <label>SP4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77818">
            <id>Q13444</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12137265">
            <id>Q13444-2</id>
        </interactant>
        <interactant intactId="EBI-930964">
            <id>P54253</id>
            <label>ATXN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12137265">
            <id>Q13444-2</id>
        </interactant>
        <interactant intactId="EBI-5774125">
            <id>A1E959</id>
            <label>ODAM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12137265">
            <id>Q13444-2</id>
        </interactant>
        <interactant intactId="EBI-2481535">
            <id>Q8WV41</id>
            <label>SNX33</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Endomembrane system</location>
            <topology evidence="11">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11">Cell junction</location>
            <location evidence="11">Adherens junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Cilium</location>
            <location evidence="1">Flagellum</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasmic vesicle</location>
            <location evidence="1">Secretory vesicle</location>
            <location evidence="1">Acrosome</location>
        </subcellularLocation>
        <text evidence="1">The majority of the protein is localized in a perinuclear compartment which may correspond to the trans-Golgi network or the late endosome. The pro-protein is the major detectable form on the cell surface, whereas the majority of the protein in the cell is processed (By similarity).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q13444-1</id>
            <name>1</name>
            <name>6b</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13444-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_039527"/>
        </isoform>
        <isoform>
            <id>Q13444-3</id>
            <name>3</name>
            <name>6a</name>
            <sequence type="described" ref="VSP_039529"/>
        </isoform>
        <isoform>
            <id>Q13444-4</id>
            <name>4</name>
            <name>4a</name>
            <sequence type="described" ref="VSP_039531"/>
        </isoform>
        <isoform>
            <id>Q13444-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_039528"/>
        </isoform>
        <isoform>
            <id>Q13444-6</id>
            <name>6</name>
            <name>7b</name>
            <sequence type="described" ref="VSP_039533"/>
        </isoform>
        <isoform>
            <id>Q13444-7</id>
            <name>7</name>
            <name>7a</name>
            <sequence type="described" ref="VSP_039529 VSP_039533"/>
        </isoform>
        <isoform>
            <id>Q13444-8</id>
            <name>8</name>
            <sequence type="described" ref="VSP_039528 VSP_039533"/>
        </isoform>
        <isoform>
            <id>Q13444-9</id>
            <name>9</name>
            <name>3a</name>
            <sequence type="described" ref="VSP_039526 VSP_039532"/>
        </isoform>
        <isoform>
            <id>Q13444-10</id>
            <name>10</name>
            <name>1</name>
            <sequence type="described" ref="VSP_039525 VSP_039530"/>
        </isoform>
        <isoform>
            <id>Q13444-11</id>
            <name>11</name>
            <sequence type="described" ref="VSP_039524 VSP_039527"/>
        </isoform>
        <isoform>
            <id>Q13444-12</id>
            <name>12</name>
            <sequence type="described" ref="VSP_044695 VSP_039527"/>
        </isoform>
        <isoform>
            <id>Q13444-13</id>
            <name>13</name>
            <sequence type="described" ref="VSP_055143 VSP_055144 VSP_055145"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10 14 18 26">Expressed in colon and small intestine. Expressed in airway smooth muscle and glomerular mesangial cells (at protein level). Ubiquitously expressed. Overexpressed in atherosclerotic lesions. Constitutively expressed in cultured endothelium and smooth muscle. Expressed in chondrocytes. Expressed in airway smooth muscle and glomerular mesangial cells.</text>
    </comment>
    <comment type="domain">
        <text>The cytoplasmic domain is required for SH3GL2- and SNX9-binding.</text>
    </comment>
    <comment type="domain">
        <text>Disintegrin domain binds to integrin alphaV-beta3.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="PTM">
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        <property type="term" value="P:negative regulation of cell migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001953">
        <property type="term" value="P:negative regulation of cell-matrix adhesion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990910">
        <property type="term" value="P:response to hypobaric hypoxia"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042246">
        <property type="term" value="P:tissue regeneration"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000014">
        <property type="entry name" value="disintegrin and metalloproteinase domain-containing protein 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.120.260">
        <property type="entry name" value="Galactose-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF130">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 15"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01186">
        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00142">
        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0037">Angiogenesis</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0969">Cilium</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-0177">Collagen degradation</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0282">Flagellum</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="17"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029082" evidence="1">
        <location>
            <begin position="18"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029083" description="Disintegrin and metalloproteinase domain-containing protein 15">
        <location>
            <begin position="207"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="207"/>
            <end position="696"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="697"/>
            <end position="717"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="718"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="213"/>
            <end position="414"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="421"/>
            <end position="508"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="657"/>
            <end position="685"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="22"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="736"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="177"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cell attachment site" evidence="3">
        <location>
            <begin position="484"/>
            <end position="486"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding" evidence="2">
        <location>
            <begin position="815"/>
            <end position="821"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding" evidence="2">
        <location>
            <begin position="850"/>
            <end position="856"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="7">
        <location>
            <begin position="35"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="767"/>
            <end position="778"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="7">
        <location>
            <begin position="779"/>
            <end position="789"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="791"/>
            <end position="800"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="813"/>
            <end position="824"/>
        </location>
    </feature>
    <feature type="active site" evidence="5 6">
        <location>
            <position position="349"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="179"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="348"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="352"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="358"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by HCK and LCK" evidence="9">
        <location>
            <position position="715"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine; by HCK and LCK" evidence="9">
        <location>
            <position position="735"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="237"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="389"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="392"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="606"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="611"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="323"/>
            <end position="409"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="365"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="367"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="480"/>
            <end position="500"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="657"/>
            <end position="667"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="661"/>
            <end position="673"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="675"/>
            <end position="684"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044695" description="In isoform 12." evidence="32">
        <original>I</original>
        <variation>IVLSWGVLGPA</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055143" description="In isoform 13." evidence="32">
        <original>GGTEEQQAESEKAPREPLEPQVLQDDLPISLKKVLQTSLPEPLRIKLELDGDSHILELLQN</original>
        <variation>VSACNVEAPQVALRSSRQSQRRPRGSPWSPRSFRTISQLASKRCF</variation>
        <location>
            <begin position="27"/>
            <end position="87"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039524" description="In isoform 11." evidence="35">
        <location>
            <begin position="94"/>
            <end position="387"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055144" description="In isoform 13." evidence="32">
        <original>CIDHRCQRV</original>
        <variation>SSLGGQDQV</variation>
        <location>
            <begin position="641"/>
            <end position="649"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055145" description="In isoform 13." evidence="32">
        <location>
            <begin position="650"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039525" description="In isoform 10." evidence="33 36 39">
        <original>RAAQSGPSERPGPPQRALLARGTKQASALSFPAPPSR</original>
        <variation>SLRGQPSPHPQGSHCLPTPRAGAHRVTCPAQGLESRP</variation>
        <location>
            <begin position="736"/>
            <end position="772"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039526" description="In isoform 9." evidence="39">
        <original>AAQSGPSERPGPPQRALLARGTKQASALSFPAPPSRPLPPDPVSKRLQAELADRPNPPTR</original>
        <variation>LVLSASRPPLPGRCRLTLCPRDSSLRGQPSPHPQGSHCLPTPRAGAHRVTCPAQGLESRP</variation>
        <location>
            <begin position="737"/>
            <end position="796"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039527" description="In isoform 2, isoform 11 and isoform 12." evidence="32 34 35 36 37 38 39 40">
        <location>
            <begin position="760"/>
            <end position="808"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039528" description="In isoform 5 and isoform 8." evidence="39">
        <location>
            <begin position="760"/>
            <end position="784"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039529" description="In isoform 3 and isoform 7." evidence="39">
        <location>
            <position position="760"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039530" description="In isoform 10." evidence="33 36 39">
        <location>
            <begin position="773"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039531" description="In isoform 4." evidence="36 39">
        <location>
            <begin position="785"/>
            <end position="808"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039532" description="In isoform 9." evidence="39">
        <location>
            <begin position="797"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_039533" description="In isoform 6, isoform 7 and isoform 8." evidence="39">
        <original>SQGPAKPPPPRKPLPADPQGRCPSGDLPGPGAGIPPLVVPSRPAPPPPTVSSLYL</original>
        <variation>VTVGGEKGTASPPT</variation>
        <location>
            <begin position="809"/>
            <end position="863"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060315" description="In dbSNP:rs6427128." evidence="13 15 19 25 27 30 31">
        <original>K</original>
        <variation>T</variation>
        <location>
            <position position="191"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_068970" description="In dbSNP:rs115753757." evidence="13">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060316" description="In dbSNP:rs2306122.">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces ADAM15-mediated T-cell aggregation." evidence="17">
        <original>RG</original>
        <variation>SV</variation>
        <location>
            <begin position="484"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; BAG52157." evidence="41" ref="9">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="81"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; BAG59890." evidence="41" ref="8">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 8; BAG59477." evidence="41" ref="8">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="286"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; BAG52157." evidence="41" ref="9">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="649"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAC50404." evidence="41" ref="2">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="714"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC51112." evidence="41" ref="1">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="840"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="10531379"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="11741929"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12091380"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="12243749"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="12615925"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="15358598"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="15818704"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="17416588"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="17575078"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="17937806"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="18296648"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="18387333"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="18434311"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source>
            <dbReference type="PubMed" id="19207106"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="24">
        <source>
            <dbReference type="PubMed" id="19718658"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="25">
        <source>
            <dbReference type="PubMed" id="8617717"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="26">
        <source>
            <dbReference type="PubMed" id="9016778"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="27">
        <source>
            <dbReference type="PubMed" id="9039960"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="28">
        <source>
            <dbReference type="PubMed" id="9516430"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="29">
        <source>
            <dbReference type="PubMed" id="9914169"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="30">
        <source ref="6"/>
    </evidence>
    <evidence type="ECO:0000269" key="31">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000303" key="32">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="33">
        <source>
            <dbReference type="PubMed" id="15358598"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="34">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="35">
        <source>
            <dbReference type="PubMed" id="16303743"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="36">
        <source>
            <dbReference type="PubMed" id="18296648"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="37">
        <source>
            <dbReference type="PubMed" id="8617717"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="38">
        <source>
            <dbReference type="PubMed" id="9039960"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="39">
        <source ref="6"/>
    </evidence>
    <evidence type="ECO:0000303" key="40">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000305" key="41"/>
    <sequence length="863" mass="92959" checksum="004936E9182629CA" modified="2010-07-13" version="4" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="207" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKQ2</accession>
    <accession>B2RMV5</accession>
    <accession>Q9Y339</accession>
    <accession>Q9Y3S0</accession>
    <name>ADA28_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 28</fullName>
            <shortName>ADAM 28</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II</fullName>
            <shortName>eMDC II</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Metalloproteinase-like, disintegrin-like, and cysteine-rich protein L</fullName>
            <shortName>MDC-L</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM28</name>
        <name type="synonym">ADAM23</name>
        <name type="synonym">MDCL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="29251" last="29259">
            <title>MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes.</title>
            <authorList>
                <person name="Roberts C.M."/>
                <person name="Tani P.H."/>
                <person name="Bridges L.C."/>
                <person name="Laszik Z."/>
                <person name="Bowditch R.D."/>
            </authorList>
            <dbReference type="PubMed" id="10506182"/>
            <dbReference type="DOI" id="10.1074/jbc.274.41.29251"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT MET-765</scope>
        <source>
            <tissue>Lymph node</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Mol. Hum. Reprod." volume="5" first="1127" last="1134">
            <title>Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis.</title>
            <authorList>
                <person name="Jury J.A."/>
                <person name="Perry A.C."/>
                <person name="Hall L."/>
            </authorList>
            <dbReference type="PubMed" id="10587367"/>
            <dbReference type="DOI" id="10.1093/molehr/5.12.1127"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT MET-765</scope>
        <source>
            <tissue>Epididymis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="439" first="331" last="335">
            <title>DNA sequence and analysis of human chromosome 8.</title>
            <authorList>
                <person name="Nusbaum C."/>
                <person name="Mikkelsen T.S."/>
                <person name="Zody M.C."/>
                <person name="Asakawa S."/>
                <person name="Taudien S."/>
                <person name="Garber M."/>
                <person name="Kodira C.D."/>
                <person name="Schueler M.G."/>
                <person name="Shimizu A."/>
                <person name="Whittaker C.A."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Yang X."/>
                <person name="Allen N.R."/>
                <person name="Anderson S."/>
                <person name="Asakawa T."/>
                <person name="Blechschmidt K."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Butler J."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="DeArellano K."/>
                <person name="DeCaprio D."/>
                <person name="Dooley K.T."/>
                <person name="Dorris L. III"/>
                <person name="Engels R."/>
                <person name="Gloeckner G."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hall J.L."/>
                <person name="Ishikawa S.K."/>
                <person name="Jaffe D.B."/>
                <person name="Kamat A."/>
                <person name="Kudoh J."/>
                <person name="Lehmann R."/>
                <person name="Lokitsang T."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews C.D."/>
                <person name="Mauceli E."/>
                <person name="Menzel U."/>
                <person name="Mihalev A.H."/>
                <person name="Minoshima S."/>
                <person name="Murayama Y."/>
                <person name="Naylor J.W."/>
                <person name="Nicol R."/>
                <person name="Nguyen C."/>
                <person name="O'Leary S.B."/>
                <person name="O'Neill K."/>
                <person name="Parker S.C.J."/>
                <person name="Polley A."/>
                <person name="Raymond C.K."/>
                <person name="Reichwald K."/>
                <person name="Rodriguez J."/>
                <person name="Sasaki T."/>
                <person name="Schilhabel M."/>
                <person name="Siddiqui R."/>
                <person name="Smith C.L."/>
                <person name="Sneddon T.P."/>
                <person name="Talamas J.A."/>
                <person name="Tenzin P."/>
                <person name="Topham K."/>
                <person name="Venkataraman V."/>
                <person name="Wen G."/>
                <person name="Yamazaki S."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Rosenthal A."/>
                <person name="Birren B.W."/>
                <person name="Platzer M."/>
                <person name="Shimizu N."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16421571"/>
            <dbReference type="DOI" id="10.1038/nature04406"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT MET-765</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT MET-765</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="Hum. Mutat." volume="32" first="E2148" last="E2175">
            <title>Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Moncada-Pazos A."/>
                <person name="Cal S."/>
                <person name="Soria-Valles C."/>
                <person name="Gartner J."/>
                <person name="Rudloff U."/>
                <person name="Lin J.C."/>
                <person name="Rosenberg S.A."/>
                <person name="Lopez-Otin C."/>
                <person name="Samuels Y."/>
            </authorList>
            <dbReference type="PubMed" id="21618342"/>
            <dbReference type="DOI" id="10.1002/humu.21477"/>
        </citation>
        <scope>VARIANTS GLU-65; GLU-134; GLU-450; PHE-482 AND ASP-502</scope>
    </reference>
    <comment type="function">
        <text>May play a role in the adhesive and proteolytic events that occur during lymphocyte emigration or may function in ectodomain shedding of lymphocyte surface target proteins, such as FASL and CD40L. May be involved in sperm maturation.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1384181">
            <id>Q9UKQ2</id>
        </interactant>
        <interactant intactId="EBI-3905042">
            <id>P00749</id>
            <label>PLAU</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKQ2-1</id>
            <name>1</name>
            <name>MDC-LM</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKQ2-2</id>
            <name>2</name>
            <name>MDC-LS</name>
            <sequence type="described" ref="VSP_005486 VSP_005487"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed predominantly in secondary lymphoid tissues, such as lymph node, spleen, small intestine, stomach, colon, appendix and trachea. The lymphocyte population is responsible for expression of this protein in these tissues. Isoform 2 is expressed preferentially in spleen.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Pro-domain removal and maturation may be, at least in part, autocatalytic.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF137334">
        <property type="protein sequence ID" value="AAD25099.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF137335">
        <property type="protein sequence ID" value="AAD25100.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ242015">
        <property type="protein sequence ID" value="CAB42085.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC044891">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC120193">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63609.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136478">
        <property type="protein sequence ID" value="AAI36479.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34865.1">
        <molecule id="Q9UKQ2-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47830.1">
        <molecule id="Q9UKQ2-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001291280.1">
        <property type="nucleotide sequence ID" value="NM_001304351.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055080.2">
        <molecule id="Q9UKQ2-1"/>
        <property type="nucleotide sequence ID" value="NM_014265.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068547.2">
        <molecule id="Q9UKQ2-2"/>
        <property type="nucleotide sequence ID" value="NM_021777.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9UKQ2"/>
    <dbReference type="SMR" id="Q9UKQ2"/>
    <dbReference type="BioGRID" id="116072">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9UKQ2">
        <property type="interactions" value="511"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UKQ2">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000265769"/>
    <dbReference type="DrugBank" id="DB08733">
        <property type="generic name" value="(2R,3R)-N^1^-[(1S)-2,2-DIMETHYL-1-(METHYLCARBAMOYL)PROPYL]-N^4^-HYDROXY-2-(2-METHYLPROPYL)-3-{[(1,3-THIAZOL-2-YLCARBONYL)AMINO]METHYL}BUTANEDIAMIDE"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02996">
        <property type="generic name" value="2-(Thiomethylene)-4-Methylpentanoic Acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03880">
        <property type="generic name" value="Batimastat"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02215">
        <property type="generic name" value="Furoyl-Leucine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02255">
        <property type="generic name" value="Ilomastat"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02046">
        <property type="generic name" value="N-[(Furan-2-Yl)Carbonyl]-(S)-Leucyl-(R)-[1-Amino-2(1h-Indol-3-Yl)Ethyl]-Phosphonic Acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03088">
        <property type="generic name" value="Pidolic acid"/>
    </dbReference>
    <dbReference type="MEROPS" id="M12.224"/>
    <dbReference type="TCDB" id="8.A.77.1.3">
        <property type="family name" value="the sheddase (sheddase) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9UKQ2">
        <property type="glycosylation" value="5 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UKQ2">
        <property type="glycosylation" value="7 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UKQ2"/>
    <dbReference type="PhosphoSitePlus" id="Q9UKQ2"/>
    <dbReference type="BioMuta" id="ADAM28"/>
    <dbReference type="DMDM" id="317373485"/>
    <dbReference type="jPOST" id="Q9UKQ2"/>
    <dbReference type="MassIVE" id="Q9UKQ2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000265769"/>
    <dbReference type="PeptideAtlas" id="Q9UKQ2"/>
    <dbReference type="ProteomicsDB" id="84834">
        <molecule id="Q9UKQ2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84835">
        <molecule id="Q9UKQ2-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="58742">
        <property type="antibodies" value="211 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10863"/>
    <dbReference type="Ensembl" id="ENST00000265769.9">
        <molecule id="Q9UKQ2-1"/>
        <property type="protein sequence ID" value="ENSP00000265769.4"/>
        <property type="gene ID" value="ENSG00000042980.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000437154.6">
        <molecule id="Q9UKQ2-2"/>
        <property type="protein sequence ID" value="ENSP00000393699.2"/>
        <property type="gene ID" value="ENSG00000042980.15"/>
    </dbReference>
    <dbReference type="GeneID" id="10863"/>
    <dbReference type="KEGG" id="hsa:10863"/>
    <dbReference type="MANE-Select" id="ENST00000265769.9">
        <property type="protein sequence ID" value="ENSP00000265769.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014265.6"/>
        <property type="RefSeq protein sequence ID" value="NP_055080.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xdx.4">
        <molecule id="Q9UKQ2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:206"/>
    <dbReference type="ClinPGx" id="PA24523"/>
    <dbReference type="CTD" id="10863"/>
    <dbReference type="DisGeNET" id="10863"/>
    <dbReference type="GeneCards" id="ADAM28"/>
    <dbReference type="HGNC" id="HGNC:206">
        <property type="gene designation" value="ADAM28"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000042980">
        <property type="expression patterns" value="Group enriched (epididymis, stomach)"/>
    </dbReference>
    <dbReference type="MIM" id="606188">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000042980"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000042980"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156716"/>
    <dbReference type="HOGENOM" id="CLU_012714_7_1_1"/>
    <dbReference type="InParanoid" id="Q9UKQ2"/>
    <dbReference type="OMA" id="CKANDAM"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9UKQ2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UKQ2"/>
    <dbReference type="PathwayCommons" id="Q9UKQ2"/>
    <dbReference type="SignaLink" id="Q9UKQ2"/>
    <dbReference type="Agora" id="ENSG00000042980"/>
    <dbReference type="BioGRID-ORCS" id="10863">
        <property type="hits" value="12 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM28">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM28"/>
    <dbReference type="GenomeRNAi" id="10863"/>
    <dbReference type="Pharos" id="Q9UKQ2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UKQ2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9UKQ2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000042980">
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
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    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
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    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
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        <location>
            <begin position="1"/>
            <end position="18"/>
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    <feature type="propeptide" id="PRO_0000029128" evidence="1">
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            <begin position="19"/>
            <end position="198"/>
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            <begin position="199"/>
            <end position="775"/>
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            <begin position="199"/>
            <end position="665"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="666"/>
            <end position="686"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="687"/>
            <end position="775"/>
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    <feature type="domain" description="Peptidase M12B" evidence="5">
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            <begin position="204"/>
            <end position="399"/>
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            <begin position="407"/>
            <end position="493"/>
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    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="625"/>
            <end position="657"/>
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    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="690"/>
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            <begin position="167"/>
            <end position="174"/>
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="7">
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            <begin position="690"/>
            <end position="700"/>
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    <feature type="compositionally biased region" description="Basic residues" evidence="7">
        <location>
            <begin position="708"/>
            <end position="717"/>
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    <feature type="compositionally biased region" description="Polar residues" evidence="7">
        <location>
            <begin position="764"/>
            <end position="775"/>
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            <position position="340"/>
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    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="169"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="339"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="343"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="349"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="268"/>
        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="275"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="557"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="602"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="628"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="315"/>
            <end position="394"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="354"/>
            <end position="378"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="356"/>
            <end position="361"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="465"/>
            <end position="485"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="629"/>
            <end position="639"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="633"/>
            <end position="645"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="647"/>
            <end position="656"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005486" description="In isoform 2." evidence="13">
        <original>TEVADKSCYNRNEGGSK</original>
        <variation>RRTNPFPCACAKENHFR</variation>
        <location>
            <begin position="524"/>
            <end position="540"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005487" description="In isoform 2." evidence="13">
        <location>
            <begin position="541"/>
            <end position="775"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066317" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="11">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066318" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267601860." evidence="11">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057067" description="In dbSNP:rs9314282.">
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        <variation>M</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057068" description="In dbSNP:rs17736699.">
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        <variation>D</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066319" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267601862." evidence="11">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="450"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066320" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="11">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057069" description="In dbSNP:rs7001647.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="493"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066321" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267601864." evidence="11">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="502"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057070" description="In dbSNP:rs36041430.">
        <original>T</original>
        <variation>K</variation>
        <location>
            <position position="593"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057071" description="In dbSNP:rs35617826.">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="604"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057072" description="In dbSNP:rs7829965.">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="684"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_024596" description="In dbSNP:rs7814768." evidence="8 9 10 12">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="765"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD25099/AAD25100." evidence="14" ref="1">
        <original>Q</original>
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        <location>
            <position position="513"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD25099." evidence="14" ref="1">
        <original>K</original>
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        <location>
            <position position="774"/>
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    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
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    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
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    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="10506182"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="10587367"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="21618342"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source ref="4"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="10506182"/>
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    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <sequence length="775" mass="87148" checksum="895E0985840F971C" modified="2011-01-11" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-11-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P18089</accession>
    <accession>A2RUS0</accession>
    <accession>Q4TUH9</accession>
    <accession>Q53RF2</accession>
    <accession>Q9BZK0</accession>
    <name>ADA2B_HUMAN</name>
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        <recommendedName>
            <fullName evidence="17">Alpha-2B adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="16">Alpha-2 adrenergic receptor subtype C2</fullName>
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        <alternativeName>
            <fullName>Alpha-2B adrenoreceptor</fullName>
            <shortName>Alpha-2B adrenoceptor</shortName>
            <shortName>Alpha-2BAR</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="19" type="primary">ADRA2B</name>
        <name type="synonym">ADRA2L1</name>
        <name type="synonym">ADRA2RL1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1990" name="Proc. Natl. Acad. Sci. U.S.A." volume="87" first="5094" last="5098">
            <title>Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2.</title>
            <authorList>
                <person name="Lomasney J.W."/>
                <person name="Lorenz W."/>
                <person name="Allen L.F."/>
                <person name="King K."/>
                <person name="Regan J.W."/>
                <person name="Yang-Feng T.L."/>
                <person name="Caron M.G."/>
                <person name="Lefkowitz R.J."/>
            </authorList>
            <dbReference type="PubMed" id="2164221"/>
            <dbReference type="DOI" id="10.1073/pnas.87.13.5094"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1990" name="Mol. Pharmacol." volume="38" first="681" last="688">
            <title>Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor.</title>
            <authorList>
                <person name="Weinshank R.L."/>
                <person name="Zgombick J.M."/>
                <person name="Macchi M."/>
                <person name="Adham N."/>
                <person name="Lichtblau H."/>
                <person name="Branchek T.A."/>
                <person name="Hartig P.R."/>
            </authorList>
            <dbReference type="PubMed" id="2172775"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="3">
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT 301-GLU--GLU-303 DEL</scope>
        <scope>FUNCTION</scope>
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        <scope>FRAMESHIFT POLYMORPHISM</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT 301-GLU--GLU-303 DEL</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-389</scope>
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            <dbReference type="PubMed" id="23105096"/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RAB26</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH GGA1 AND GGA2</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH GGA3</scope>
        <scope>FUNCTION</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH RAB43</scope>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 9-450 IN COMPLEX WITH G PROTEINS</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <reference key="16">
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            <dbReference type="PubMed" id="24114805"/>
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        </citation>
        <scope>INVOLVEMENT IN FAME2</scope>
        <scope>VARIANT FAME2 225-HIS--LEU-229 DELINS GLN-PHE-GLY-ARG</scope>
        <scope>CHARACTERIZATION OF VARIANT FAME2 225-HIS--LEU-229 DELINS GLN-PHE-GLY-ARG</scope>
        <scope>INTERACTION WITH PPP1R9B</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="5 7 8 9 11">Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression (PubMed:11056163, PubMed:2164221, PubMed:2172775, PubMed:23105096, PubMed:26811329). Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release (PubMed:2164221). The rank order of potency for agonists of ADRA2B is clonidine &gt; norepinephrine &gt; epinephrine = oxymetazoline &gt; dopamine &gt; p-tyramine = phenylephrine &gt; serotonin &gt; p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine &gt; chlorpromazine &gt; phentolamine &gt; mianserine &gt; spiperone &gt; prazosin &gt; alprenolol &gt; propanolol &gt; pindolol (PubMed:2164221, PubMed:2172775).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10 11 12 13">Interacts with RAB26; RAB26 mediates cell surface transport from the Golgi (PubMed:23105096). Interacts with PPP1R9B (PubMed:24114805). Interacts with GGA1, GGA2 and GGA3; GGA1, GGA2 and GGA3 mediates transport from the Golgi to the cell membrane (PubMed:26811329, PubMed:27901063). Interacts with RAB43 (GTP-bound); RAB43 mediates ADRA2B ER-to-Golgi cell transport (PubMed:29069590).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-9077302">
            <id>P18089</id>
        </interactant>
        <interactant intactId="EBI-958239">
            <id>Q9ULW5</id>
            <label>RAB26</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9 11 12 13">Cell membrane</location>
            <topology evidence="9 14">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="9 11 12">Interaction with RAB26, GGA1, GGA2 and GGA3 mediates transport from the Golgi to the cell membrane.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="15">A rare polymorphic frameshift in position 451 produces a protein of 545 residues.</text>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-04469">
            <name>Epilepsy, familial adult myoclonic, 2</name>
            <acronym>FAME2</acronym>
            <description>A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME2 inheritance is autosomal dominant.</description>
            <dbReference type="MIM" id="607876"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M34041">
        <property type="protein sequence ID" value="AAA51666.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF316895">
        <property type="protein sequence ID" value="AAK01635.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AF005900">
        <property type="protein sequence ID" value="AAB62558.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY548167">
        <property type="protein sequence ID" value="AAS55646.1"/>
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        <property type="protein sequence ID" value="AAY43127.1"/>
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        <property type="protein sequence ID" value="ABY87536.1"/>
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        <property type="protein sequence ID" value="AAX93218.1"/>
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        <property type="protein sequence ID" value="EAW71390.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAI33022.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAI36538.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAA62823.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56129.1"/>
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        <property type="entry name" value="A37223"/>
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    <dbReference type="RefSeq" id="NP_000673.2">
        <property type="nucleotide sequence ID" value="NM_000682.6"/>
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    <dbReference type="PDB" id="6K41">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="R=9-450"/>
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    <dbReference type="PDB" id="6K42">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.10 A"/>
        <property type="chains" value="R=7-450"/>
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    <dbReference type="PDBsum" id="6K41"/>
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    <dbReference type="AlphaFoldDB" id="P18089"/>
    <dbReference type="EMDB" id="EMD-9911"/>
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    <dbReference type="BioGRID" id="106660">
        <property type="interactions" value="7"/>
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    <dbReference type="CORUM" id="P18089"/>
    <dbReference type="DIP" id="DIP-61453N"/>
    <dbReference type="FunCoup" id="P18089">
        <property type="interactions" value="1181"/>
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        <property type="interactions" value="5"/>
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    <dbReference type="STRING" id="9606.ENSP00000480573"/>
    <dbReference type="BindingDB" id="P18089"/>
    <dbReference type="ChEMBL" id="CHEMBL1942"/>
    <dbReference type="DrugBank" id="DB08550">
        <property type="generic name" value="7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00543">
        <property type="generic name" value="Amoxapine"/>
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    <dbReference type="DrugBank" id="DB00182">
        <property type="generic name" value="Amphetamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00714">
        <property type="generic name" value="Apomorphine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00964">
        <property type="generic name" value="Apraclonidine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09229">
        <property type="generic name" value="Aranidipine"/>
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    <dbReference type="DrugBank" id="DB01238">
        <property type="generic name" value="Aripiprazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14185">
        <property type="generic name" value="Aripiprazole lauroxil"/>
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    <feature type="transmembrane region" description="Helical; Name=7" evidence="14 20">
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<entry dataset="Swiss-Prot" created="2007-11-13" modified="2026-01-28" version="155" xmlns="https://uniprot.org/uniprot">
    <accession>Q96M93</accession>
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            <fullName>Adenosine deaminase domain-containing protein 1</fullName>
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            <fullName>Testis nuclear RNA-binding protein</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
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            <taxon>Haplorrhini</taxon>
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            <taxon>Hominidae</taxon>
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    </organism>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">Required for male fertility and normal male germ cell differentiation (By similarity). Plays a role in spermatogenesis (By similarity). Binds to RNA but not to DNA (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96M93-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96M93-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_029226"/>
        </isoform>
        <isoform>
            <id>Q96M93-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_029225"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the ADAD family.</text>
    </comment>
    <dbReference type="EMBL" id="AK057303">
        <property type="protein sequence ID" value="BAB71416.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK093297">
        <property type="protein sequence ID" value="BAC04125.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC022489">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05228.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05229.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05234.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05230.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05231.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05232.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC040229">
        <property type="protein sequence ID" value="AAH40229.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34058.1">
        <molecule id="Q96M93-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54800.1">
        <molecule id="Q96M93-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54801.1">
        <molecule id="Q96M93-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001152757.1">
        <molecule id="Q96M93-2"/>
        <property type="nucleotide sequence ID" value="NM_001159285.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001152767.1">
        <molecule id="Q96M93-3"/>
        <property type="nucleotide sequence ID" value="NM_001159295.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_640336.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="NM_139243.4"/>
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    <dbReference type="RefSeq" id="XP_005262798.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_005262741.3"/>
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    <dbReference type="RefSeq" id="XP_005262800.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_005262743.4"/>
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    <dbReference type="RefSeq" id="XP_005262801.1">
        <molecule id="Q96M93-2"/>
        <property type="nucleotide sequence ID" value="XM_005262744.4"/>
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    <dbReference type="RefSeq" id="XP_011529905.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_011531603.3"/>
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    <dbReference type="RefSeq" id="XP_024309656.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_024453888.1"/>
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    <dbReference type="RefSeq" id="XP_024309657.1">
        <molecule id="Q96M93-2"/>
        <property type="nucleotide sequence ID" value="XM_024453889.1"/>
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    <dbReference type="RefSeq" id="XP_054204874.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_054348899.1"/>
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    <dbReference type="RefSeq" id="XP_054204875.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_054348900.1"/>
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    <dbReference type="RefSeq" id="XP_054204876.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_054348901.1"/>
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    <dbReference type="RefSeq" id="XP_054204877.1">
        <molecule id="Q96M93-1"/>
        <property type="nucleotide sequence ID" value="XM_054348902.1"/>
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    <dbReference type="RefSeq" id="XP_054204878.1">
        <molecule id="Q96M93-2"/>
        <property type="nucleotide sequence ID" value="XM_054348903.1"/>
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    <dbReference type="RefSeq" id="XP_054204879.1">
        <molecule id="Q96M93-2"/>
        <property type="nucleotide sequence ID" value="XM_054348904.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96M93"/>
    <dbReference type="SMR" id="Q96M93"/>
    <dbReference type="FunCoup" id="Q96M93">
        <property type="interactions" value="33"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000296513"/>
    <dbReference type="GlyGen" id="Q96M93">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96M93"/>
    <dbReference type="PhosphoSitePlus" id="Q96M93"/>
    <dbReference type="BioMuta" id="ADAD1"/>
    <dbReference type="DMDM" id="74732329"/>
    <dbReference type="MassIVE" id="Q96M93"/>
    <dbReference type="PaxDb" id="9606-ENSP00000296513"/>
    <dbReference type="PeptideAtlas" id="Q96M93"/>
    <dbReference type="ProteomicsDB" id="77315">
        <molecule id="Q96M93-1"/>
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    <dbReference type="ProteomicsDB" id="77316">
        <molecule id="Q96M93-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77317">
        <molecule id="Q96M93-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="26838">
        <property type="antibodies" value="64 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="132612"/>
    <dbReference type="Ensembl" id="ENST00000296513.7">
        <molecule id="Q96M93-1"/>
        <property type="protein sequence ID" value="ENSP00000296513.2"/>
        <property type="gene ID" value="ENSG00000164113.11"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000388724.6">
        <molecule id="Q96M93-2"/>
        <property type="protein sequence ID" value="ENSP00000373376.2"/>
        <property type="gene ID" value="ENSG00000164113.11"/>
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    <dbReference type="Ensembl" id="ENST00000388725.2">
        <molecule id="Q96M93-3"/>
        <property type="protein sequence ID" value="ENSP00000373377.2"/>
        <property type="gene ID" value="ENSG00000164113.11"/>
    </dbReference>
    <dbReference type="GeneID" id="132612"/>
    <dbReference type="KEGG" id="hsa:132612"/>
    <dbReference type="MANE-Select" id="ENST00000296513.7">
        <property type="protein sequence ID" value="ENSP00000296513.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_139243.4"/>
        <property type="RefSeq protein sequence ID" value="NP_640336.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ieo.4">
        <molecule id="Q96M93-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30713"/>
    <dbReference type="ClinPGx" id="PA162375590"/>
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    <dbReference type="GeneCards" id="ADAD1"/>
    <dbReference type="HGNC" id="HGNC:30713">
        <property type="gene designation" value="ADAD1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164113">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="614130">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000164113"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000164113"/>
    <dbReference type="eggNOG" id="KOG2777">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156842"/>
    <dbReference type="HOGENOM" id="CLU_005382_4_1_1"/>
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    <dbReference type="OMA" id="GNCKDTR"/>
    <dbReference type="OrthoDB" id="10268011at2759"/>
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        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96M93"/>
    <dbReference type="PathwayCommons" id="Q96M93"/>
    <dbReference type="BioGRID-ORCS" id="132612">
        <property type="hits" value="15 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAD1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="132612"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96M93"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
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    <dbReference type="RNAct" id="Q96M93">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000164113">
        <property type="expression patterns" value="Expressed in sperm and 44 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96M93">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001673">
        <property type="term" value="C:male germ cell nucleus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003726">
        <property type="term" value="F:double-stranded RNA adenosine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003725">
        <property type="term" value="F:double-stranded RNA binding"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008251">
        <property type="term" value="F:tRNA-specific adenosine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006382">
        <property type="term" value="P:adenosine to inosine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006396">
        <property type="term" value="P:RNA processing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007286">
        <property type="term" value="P:spermatid development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd19905">
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.160.20:FF:000033">
        <property type="entry name" value="Adenosine deaminase domain-containing 1 (testis-specific)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.160.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002466">
        <property type="entry name" value="A_deamin"/>
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    <dbReference type="InterPro" id="IPR044455">
        <property type="entry name" value="ADAD1_DSRM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014720">
        <property type="entry name" value="dsRBD_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10910:SF103">
        <property type="entry name" value="ADENOSINE DEAMINASE DOMAIN-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10910">
        <property type="entry name" value="EUKARYOTE SPECIFIC DSRNA BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02137">
        <property type="entry name" value="A_deamin"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00035">
        <property type="entry name" value="dsrm"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00552">
        <property type="entry name" value="ADEAMc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00358">
        <property type="entry name" value="DSRM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54768">
        <property type="entry name" value="dsRNA-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50141">
        <property type="entry name" value="A_DEAMIN_EDITASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50137">
        <property type="entry name" value="DS_RBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <feature type="chain" id="PRO_0000309520" description="Adenosine deaminase domain-containing protein 1">
        <location>
            <begin position="1"/>
            <end position="576"/>
        </location>
    </feature>
    <feature type="domain" description="DRBM" evidence="3">
        <location>
            <begin position="96"/>
            <end position="164"/>
        </location>
    </feature>
    <feature type="domain" description="A to I editase" evidence="2">
        <location>
            <begin position="249"/>
            <end position="574"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029225" description="In isoform 3." evidence="4">
        <original>MASNNHWFQSSQVPSFAQM</original>
        <variation>M</variation>
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029226" description="In isoform 2." evidence="5">
        <location>
            <begin position="283"/>
            <end position="293"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC04125." evidence="6" ref="1">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAC04125." evidence="6" ref="1">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5SUE7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00240"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00266"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="576" mass="64411" checksum="379A6849ABDEEFAB" modified="2001-12-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-04-16" modified="2026-01-28" version="184" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NZK5</accession>
    <accession>A8K9H4</accession>
    <accession>Q6ICF1</accession>
    <accession>Q86UB6</accession>
    <accession>Q8NCJ2</accession>
    <accession>Q96K41</accession>
    <name>ADA2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">Adenosine deaminase 2</fullName>
            <ecNumber evidence="4 7">3.5.4.4</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Cat eye syndrome critical region protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="13" type="primary">ADA2</name>
        <name type="synonym">ADGF</name>
        <name type="synonym">CECR1</name>
        <name type="synonym">IDGFL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2000" name="Genomics" volume="64" first="277" last="285">
            <title>The human homolog of insect-derived growth factor, CECR1, is a candidate gene for features of cat eye syndrome.</title>
            <authorList>
                <person name="Riazi M.A."/>
                <person name="Brinkman-Mills P."/>
                <person name="Nguyen T."/>
                <person name="Pan H."/>
                <person name="Phan S."/>
                <person name="Ying F."/>
                <person name="Roe B.A."/>
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        <scope>DOMAINS</scope>
        <scope>GLYCOSAMINOCLYCAN BINDING</scope>
        <scope>MUTAGENESIS OF CYS-137 AND TRP-362</scope>
        <scope>GLYCOSYLATION AT ASN-127; ASN-185 AND ASN-378</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2014" name="N. Engl. J. Med." volume="370" first="911" last="920">
            <title>Early-onset stroke and vasculopathy associated with mutations in ADA2.</title>
            <authorList>
                <person name="Zhou Q."/>
                <person name="Yang D."/>
                <person name="Ombrello A.K."/>
                <person name="Zavialov A.V."/>
                <person name="Toro C."/>
                <person name="Zavialov A.V."/>
                <person name="Stone D.L."/>
                <person name="Chae J.J."/>
                <person name="Rosenzweig S.D."/>
                <person name="Bishop K."/>
                <person name="Barron K.S."/>
                <person name="Kuehn H.S."/>
                <person name="Hoffmann P."/>
                <person name="Negro A."/>
                <person name="Tsai W.L."/>
                <person name="Cowen E.W."/>
                <person name="Pei W."/>
                <person name="Milner J.D."/>
                <person name="Silvin C."/>
                <person name="Heller T."/>
                <person name="Chin D.T."/>
                <person name="Patronas N.J."/>
                <person name="Barber J.S."/>
                <person name="Lee C.C."/>
                <person name="Wood G.M."/>
                <person name="Ling A."/>
                <person name="Kelly S.J."/>
                <person name="Kleiner D.E."/>
                <person name="Mullikin J.C."/>
                <person name="Ganson N.J."/>
                <person name="Kong H.H."/>
                <person name="Hambleton S."/>
                <person name="Candotti F."/>
                <person name="Quezado M.M."/>
                <person name="Calvo K.R."/>
                <person name="Alao H."/>
                <person name="Barham B.K."/>
                <person name="Jones A."/>
                <person name="Meschia J.F."/>
                <person name="Worrall B.B."/>
                <person name="Kasner S.E."/>
                <person name="Rich S.S."/>
                <person name="Goldbach-Mansky R."/>
                <person name="Abinun M."/>
                <person name="Chalom E."/>
                <person name="Gotte A.C."/>
                <person name="Punaro M."/>
                <person name="Pascual V."/>
                <person name="Verbsky J.W."/>
                <person name="Torgerson T.R."/>
                <person name="Singer N.G."/>
                <person name="Gershon T.R."/>
                <person name="Ozen S."/>
                <person name="Karadag O."/>
                <person name="Fleisher T.A."/>
                <person name="Remmers E.F."/>
                <person name="Burgess S.M."/>
                <person name="Moir S.L."/>
                <person name="Gadina M."/>
                <person name="Sood R."/>
                <person name="Hershfield M.S."/>
                <person name="Boehm M."/>
                <person name="Kastner D.L."/>
                <person name="Aksentijevich I."/>
            </authorList>
            <dbReference type="PubMed" id="24552284"/>
            <dbReference type="DOI" id="10.1056/nejmoa1307361"/>
        </citation>
        <scope>INVOLVEMENT IN VAIHS</scope>
        <scope>VARIANTS VAIHS ARG-47; ASP-109; GLN-112; GLN-169 AND CYS-453</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2014" name="N. Engl. J. Med." volume="370" first="921" last="931">
            <title>Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy.</title>
            <authorList>
                <person name="Navon Elkan P."/>
                <person name="Pierce S.B."/>
                <person name="Segel R."/>
                <person name="Walsh T."/>
                <person name="Barash J."/>
                <person name="Padeh S."/>
                <person name="Zlotogorski A."/>
                <person name="Berkun Y."/>
                <person name="Press J.J."/>
                <person name="Mukamel M."/>
                <person name="Voth I."/>
                <person name="Hashkes P.J."/>
                <person name="Harel L."/>
                <person name="Hoffer V."/>
                <person name="Ling E."/>
                <person name="Yalcinkaya F."/>
                <person name="Kasapcopur O."/>
                <person name="Lee M.K."/>
                <person name="Klevit R.E."/>
                <person name="Renbaum P."/>
                <person name="Weinberg-Shukron A."/>
                <person name="Sener E.F."/>
                <person name="Schormair B."/>
                <person name="Zeligson S."/>
                <person name="Marek-Yagel D."/>
                <person name="Strom T.M."/>
                <person name="Shohat M."/>
                <person name="Singer A."/>
                <person name="Rubinow A."/>
                <person name="Pras E."/>
                <person name="Winkelmann J."/>
                <person name="Tekin M."/>
                <person name="Anikster Y."/>
                <person name="King M.C."/>
                <person name="Levy-Lahad E."/>
            </authorList>
            <dbReference type="PubMed" id="24552285"/>
            <dbReference type="DOI" id="10.1056/nejmoa1307362"/>
        </citation>
        <scope>VARIANTS VAIHS VAL-47; ARG-47; GLN-169; LEU-251 AND SER-264</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2014" name="N. Engl. J. Med." volume="371" first="478" last="480">
            <title>Mutant ADA2 in vasculopathies.</title>
            <authorList>
                <person name="Bras J."/>
                <person name="Guerreiro R."/>
                <person name="Santo G.C."/>
            </authorList>
            <dbReference type="PubMed" id="25075847"/>
            <dbReference type="DOI" id="10.1056/nejmc1405506"/>
        </citation>
        <scope>INVOLVEMENT IN SNDNS</scope>
        <scope>VARIANTS SNDNS ALA-119 AND SER-142</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7">Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses. Requires elevated adenosine levels for optimal enzyme activity. Binds to cell surfaces via proteoglycans and may play a role in the regulation of cell proliferation and differentiation, independently of its enzyme activity.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 7">
            <text>adenosine + H2O + H(+) = inosine + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:24408"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="EC" id="3.5.4.4"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="6">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">2.25 mM for adenosine</KM>
        </kinetics>
        <phDependence>
            <text evidence="4">Optimum pH is 6.6.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="6 7">Homodimer. Interacts with adenosine receptors. Binds heparin.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 6 7">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NZK5-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NZK5-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041509 VSP_041510"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Detected in blood plasma (at protein level). Widely expressed, with most abundant expression in human adult heart, lung, lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In embryo, expressed in the outflow tract and atrium of the developing heart, the VII/VIII cranial nerve ganglion, and the notochord.</text>
    </comment>
    <comment type="domain">
        <text evidence="6">The PRB domain is involved in receptor binding, and may be responsible for the cytokine-like growth factor activity due to its sharing of several structural properties with chemokines.</text>
    </comment>
    <comment type="domain">
        <text evidence="6">High-affinity binding to heparin/glycosaminoclycan (GAG) is mediated by a large, highly positively charged surface at the interface of dimer's subunits involving approximately residues 30-45, 389-396, and 422-428.</text>
    </comment>
    <comment type="disease" evidence="8 9">
        <disease id="DI-04055">
            <name>Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome</name>
            <acronym>VAIHS</acronym>
            <description>An autosomal recessive, systemic necrotizing vasculitis that affects medium and small arteries. The ensuing tissue ischemia can affect any organ, including the skin, musculoskeletal system, kidneys, gastrointestinal tract, and the cardiovascular and nervous systems. Organ involvement and disease severity are highly variable. Clinical features include recurrent ischemic stroke affecting the small vessels of the brain and resulting in neurologic dysfunction, recurrent fever, myalgias, livedoid rash, gastrointestinal pain and hepatosplenomegaly.</description>
            <dbReference type="MIM" id="615688"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-04206">
            <name>Sneddon syndrome</name>
            <acronym>SNDNS</acronym>
            <description>An autosomal recessive, systemic non-inflammatory thrombotic vasculopathy characterized by the association of livedo racemosa, and in some cases livedo reticularis, with cerebrovascular disease. Livedo racemosa is a persistent net-like violaceous-cyanotic, mottled discoloration of the skin affecting the legs, the arms, the buttocks and the trunk; livedo reticularis is limited to the extremities and is visible only in the cold. Cerebrovascular features include recurrent transient ischemic attacks, infarcts, and rarely spinal strokes or intracranial or subarachnoid hemorrhages. Headache and vertigo may precede the onset of livedo racemosa and cerebrovascular manifestations by several years. Rare neurologic symptoms include seizures, chorea, or myelopathies.</description>
            <dbReference type="MIM" id="182410"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Candidate gene for the Cat Eye Syndrome (CES), a developmental disorder associated with the duplication of a 2 Mb region of 22q11.2. Duplication usually takes in the form of a surpernumerary bisatellited isodicentric chromosome, resulting in four copies of the region (represents an inv dup(22)(q11)). CES is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. ADGF subfamily.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.4" evidence="4 7"/>
    <dbReference type="EMBL" id="AF190746">
        <property type="protein sequence ID" value="AAF65941.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456417">
        <property type="protein sequence ID" value="CAG30303.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027682">
        <property type="protein sequence ID" value="BAB55293.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292689">
        <property type="protein sequence ID" value="BAF85378.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK074702">
        <property type="protein sequence ID" value="BAC11148.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005300">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471193">
        <property type="protein sequence ID" value="EAW57750.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051755">
        <property type="protein sequence ID" value="AAH51755.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13742.1">
        <molecule id="Q9NZK5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13743.1">
        <molecule id="Q9NZK5-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269154.1">
        <molecule id="Q9NZK5-1"/>
        <property type="nucleotide sequence ID" value="NM_001282225.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269155.1">
        <molecule id="Q9NZK5-1"/>
        <property type="nucleotide sequence ID" value="NM_001282226.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269156.1">
        <property type="nucleotide sequence ID" value="NM_001282227.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269157.1">
        <property type="nucleotide sequence ID" value="NM_001282228.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269158.1">
        <property type="nucleotide sequence ID" value="NM_001282229.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_803124.1">
        <molecule id="Q9NZK5-2"/>
        <property type="nucleotide sequence ID" value="NM_177405.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011544435.1">
        <molecule id="Q9NZK5-1"/>
        <property type="nucleotide sequence ID" value="XM_011546133.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054181667.1">
        <molecule id="Q9NZK5-1"/>
        <property type="nucleotide sequence ID" value="XM_054325692.1"/>
    </dbReference>
    <dbReference type="PDB" id="3LGD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=29-511"/>
    </dbReference>
    <dbReference type="PDB" id="3LGG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=29-511"/>
    </dbReference>
    <dbReference type="PDBsum" id="3LGD"/>
    <dbReference type="PDBsum" id="3LGG"/>
    <dbReference type="AlphaFoldDB" id="Q9NZK5"/>
    <dbReference type="SMR" id="Q9NZK5"/>
    <dbReference type="BioGRID" id="119736">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NZK5">
        <property type="interactions" value="169"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NZK5">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000382731"/>
    <dbReference type="GlyConnect" id="1912">
        <property type="glycosylation" value="8 N-Linked glycans (4 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9NZK5">
        <property type="glycosylation" value="4 sites, 8 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9NZK5">
        <property type="glycosylation" value="5 sites, 22 N-linked glycans (4 sites), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NZK5"/>
    <dbReference type="PhosphoSitePlus" id="Q9NZK5"/>
    <dbReference type="BioMuta" id="ADA2"/>
    <dbReference type="DMDM" id="122065151"/>
    <dbReference type="MassIVE" id="Q9NZK5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000382731"/>
    <dbReference type="PeptideAtlas" id="Q9NZK5"/>
    <dbReference type="ProteomicsDB" id="83424">
        <molecule id="Q9NZK5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83425">
        <molecule id="Q9NZK5-2"/>
    </dbReference>
    <dbReference type="TopDownProteomics" id="Q9NZK5-1">
        <molecule id="Q9NZK5-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="280">
        <property type="antibodies" value="122 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="51816"/>
    <dbReference type="Ensembl" id="ENST00000262607.3">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000262607.2"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000330232.9">
        <molecule id="Q9NZK5-2"/>
        <property type="protein sequence ID" value="ENSP00000332871.4"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000399837.8">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000382731.2"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000399839.5">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000382733.1"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000543038.2">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000442482.2"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000649310.2">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000496839.2"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000649746.2">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000497913.2"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000696196.1">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000512479.1"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000696197.1">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000512480.1"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000696225.1">
        <molecule id="Q9NZK5-1"/>
        <property type="protein sequence ID" value="ENSP00000512491.1"/>
        <property type="gene ID" value="ENSG00000093072.20"/>
    </dbReference>
    <dbReference type="GeneID" id="51816"/>
    <dbReference type="KEGG" id="hsa:51816"/>
    <dbReference type="MANE-Select" id="ENST00000399837.8">
        <property type="protein sequence ID" value="ENSP00000382731.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001282225.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001269154.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002zmj.3">
        <molecule id="Q9NZK5-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:1839"/>
    <dbReference type="ClinPGx" id="PA26382"/>
    <dbReference type="CTD" id="51816"/>
    <dbReference type="DisGeNET" id="51816"/>
    <dbReference type="GeneCards" id="ADA2"/>
    <dbReference type="GeneReviews" id="ADA2"/>
    <dbReference type="HGNC" id="HGNC:1839">
        <property type="gene designation" value="ADA2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000093072">
        <property type="expression patterns" value="Tissue enhanced (lymphoid)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADA2"/>
    <dbReference type="MIM" id="182410">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="607575">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="615688">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000093072"/>
    <dbReference type="Orphanet" id="404553">
        <property type="disease" value="Deficiency of adenosine deaminase 2"/>
    </dbReference>
    <dbReference type="Orphanet" id="124">
        <property type="disease" value="Diamond-Blackfan anemia"/>
    </dbReference>
    <dbReference type="Orphanet" id="820">
        <property type="disease" value="Sneddon syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000093072"/>
    <dbReference type="eggNOG" id="KOG1097">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183113"/>
    <dbReference type="HOGENOM" id="CLU_022829_0_0_1"/>
    <dbReference type="InParanoid" id="Q9NZK5"/>
    <dbReference type="OMA" id="SMKQCIE"/>
    <dbReference type="OrthoDB" id="7202371at2759"/>
    <dbReference type="PAN-GO" id="Q9NZK5">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NZK5"/>
    <dbReference type="BRENDA" id="3.5.4.4">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NZK5"/>
    <dbReference type="Reactome" id="R-HSA-5683826">
        <property type="pathway name" value="Surfactant metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000093072"/>
    <dbReference type="BioGRID-ORCS" id="51816">
        <property type="hits" value="14 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="CECR1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NZK5"/>
    <dbReference type="GeneWiki" id="CECR1"/>
    <dbReference type="GenomeRNAi" id="51816"/>
    <dbReference type="Pharos" id="Q9NZK5">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NZK5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NZK5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000093072">
        <property type="expression patterns" value="Expressed in monocyte and 176 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NZK5">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035578">
        <property type="term" value="C:azurophil granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004000">
        <property type="term" value="F:adenosine deaminase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031685">
        <property type="term" value="F:adenosine receptor binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008083">
        <property type="term" value="F:growth factor activity"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008201">
        <property type="term" value="F:heparin binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042803">
        <property type="term" value="F:protein homodimerization activity"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043394">
        <property type="term" value="F:proteoglycan binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006154">
        <property type="term" value="P:adenosine catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046103">
        <property type="term" value="P:inosine biosynthetic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd01321">
        <property type="entry name" value="ADGF"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.20.20.140:FF:000017">
        <property type="entry name" value="Adenosine deaminase 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.20.20.140">
        <property type="entry name" value="Metal-dependent hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001365">
        <property type="entry name" value="A_deaminase_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013659">
        <property type="entry name" value="A_deaminase_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006331">
        <property type="entry name" value="ADGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006330">
        <property type="entry name" value="Ado/ade_deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032466">
        <property type="entry name" value="Metal_Hydrolase"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01431">
        <property type="entry name" value="adm_rel"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11409">
        <property type="entry name" value="ADENOSINE DEAMINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11409:SF39">
        <property type="entry name" value="ADENOSINE DEAMINASE 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00962">
        <property type="entry name" value="A_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08451">
        <property type="entry name" value="A_deaminase_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51556">
        <property type="entry name" value="Metallo-dependent hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0358">Heparin-binding</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="signal peptide" evidence="1">
        <location>
            <begin position="1"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000006725" description="Adenosine deaminase 2">
        <location>
            <begin position="30"/>
            <end position="511"/>
        </location>
    </feature>
    <feature type="region of interest" description="Dimerization">
        <location>
            <begin position="30"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="region of interest" description="PRB domain">
        <location>
            <begin position="127"/>
            <end position="185"/>
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    </feature>
    <feature type="active site" description="Proton donor" evidence="12">
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="12">
        <location>
            <position position="384"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <position position="112"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="114"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="115"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <begin position="204"/>
            <end position="211"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="293"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="326"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="356"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="441"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="442"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="127"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="174"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="6">
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5 6">
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6">
        <location>
            <begin position="137"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041509" description="In isoform 2." evidence="11">
        <location>
            <begin position="1"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041510" description="In isoform 2." evidence="11">
        <original>YMEIRARLLP</original>
        <variation>MDSLEWNWAL</variation>
        <location>
            <begin position="242"/>
            <end position="251"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071137" description="In VAIHS; there is a decreased expression of the mutant protein compared to wild-type; dbSNP:rs202134424." evidence="8 9">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071138" description="In VAIHS; dbSNP:rs200930463." evidence="9">
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        <variation>V</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071139" description="In VAIHS; dbSNP:rs587777240." evidence="8">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071140" description="In VAIHS; dbSNP:rs587777241." evidence="8">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072562" description="In SNDNS." evidence="10">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_072563" description="In SNDNS." evidence="10">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071141" description="In VAIHS; dbSNP:rs77563738." evidence="8 9">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="169"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071142" description="In VAIHS; dbSNP:rs148936893." evidence="9">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071143" description="In VAIHS; dbSNP:rs587777242." evidence="9">
        <original>W</original>
        <variation>S</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029802" description="In dbSNP:rs2231495." evidence="2 3">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="335"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_071144" description="In VAIHS; dbSNP:rs376785840." evidence="8">
        <original>Y</original>
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        <location>
            <position position="453"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes secretion." evidence="6">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="137"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces dimerization and enzyme activity." evidence="6">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAC11148." evidence="12" ref="3">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; AAH51755." evidence="12" ref="6">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="394"/>
        </location>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="30"/>
            <end position="44"/>
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    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="46"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="54"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="81"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="86"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="97"/>
            <end position="104"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="108"/>
            <end position="114"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="117"/>
            <end position="119"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="121"/>
            <end position="126"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="128"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="134"/>
            <end position="138"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="144"/>
            <end position="148"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="165"/>
            <end position="170"/>
        </location>
    </feature>
    <feature type="strand" evidence="15">
        <location>
            <begin position="171"/>
            <end position="173"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="175"/>
            <end position="185"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="193"/>
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    <feature type="helix" evidence="14">
        <location>
            <begin position="200"/>
            <end position="218"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="221"/>
            <end position="237"/>
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    <feature type="strand" evidence="14">
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            <begin position="240"/>
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            <begin position="285"/>
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            <begin position="298"/>
            <end position="314"/>
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    </feature>
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            <begin position="316"/>
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            <begin position="319"/>
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            <begin position="328"/>
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            <begin position="343"/>
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            <begin position="366"/>
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        <location>
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            <begin position="392"/>
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            <begin position="405"/>
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            <begin position="409"/>
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    <feature type="helix" evidence="14">
        <location>
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            <begin position="426"/>
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        <location>
            <begin position="436"/>
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    <evidence type="ECO:0000255" key="1"/>
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    <sequence length="511" mass="58934" checksum="A4AB0A83E8A0611E" modified="2007-01-09" version="2" precursor="true">MLVDGPSERPALCFLLLAVAMSFFGSALSIDETRAHLLLKEKMMRLGGRLVLNTKEELANERLMTLKIAEMKEAMRTLIFPPSMHFFQAKHLIERSQVFNILRMMPKGAALHLHDIGIVTMDWLVRNVTYRPHCHICFTPRGIMQFRFAHPTPRPSEKCSKWILLEDYRKRVQNVTEFDDSLLRNFTLVTQHPEVIYTNQNVVWSKFETIFFTISGLIHYAPVFRDYVFRSMQEFYEDNVLYMEIRARLLPVYELSGEHHDEEWSVKTYQEVAQKFVETHPEFIGIKIIYSDHRSKDVAVIAESIRMAMGLRIKFPTVVAGFDLVGHEDTGHSLHDYKEALMIPAKDGVKLPYFFHAGETDWQGTSIDRNILDALMLNTTRIGHGFALSKHPAVRTYSWKKDIPIEVCPISNQVLKLVSDLRNHPVATLMATGHPMVISSDDPAMFGAKGLSYDFYEVFMGIGGMKADLRTLKQLAMNSIKYSTLLESEKNTFMEIWKKRWDKFIADVATK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-02-28" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>O14672</accession>
    <accession>B4DU28</accession>
    <accession>Q10742</accession>
    <accession>Q92650</accession>
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        <recommendedName>
            <fullName evidence="43">Disintegrin and metalloproteinase domain-containing protein 10</fullName>
            <shortName>ADAM 10</shortName>
            <ecNumber evidence="9 12 13 15 16 21 34">3.4.24.81</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>CDw156</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Kuzbanian protein homolog</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Mammalian disintegrin-metalloprotease</fullName>
        </alternativeName>
        <cdAntigenName>CD156c</cdAntigenName>
    </protein>
    <gene>
        <name evidence="45" type="primary">ADAM10</name>
        <name type="synonym">KUZ</name>
        <name type="synonym">MADM</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
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            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
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            <dbReference type="PubMed" id="21288900"/>
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        <scope>FUNCTION IN CLEAVAGE OF CORIN</scope>
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        <scope>INTERACTION WITH AP2A1; AP2A2; AP2B1; AP2M1 AND DLG1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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            <dbReference type="PubMed" id="26091039"/>
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        <scope>PHOSPHORYLATION AT THR-719</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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                <person name="Jouannet S."/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH TSPAN5; TSPAN14; TSPAN15 AND TSPAN33</scope>
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        <scope>FUNCTION</scope>
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        <scope>INTERACTION WITH TSPAN14</scope>
        <scope>DOMAIN</scope>
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        <scope>FUNCTION (MICROBIAL INFECTION)</scope>
        <scope>INTERACTION WITH TSPAN33 AND AFDN</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>ACTIVE SITE</scope>
        <scope>MUTAGENESIS OF GLU-384</scope>
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                <person name="Rasila T."/>
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            <dbReference type="PubMed" id="30312582"/>
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        <scope>INTERACTION WITH FAM171A1</scope>
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                <person name="Reyat J.S."/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TSPAN5 AND TSPAN17</scope>
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                <person name="Eschenbrenner E."/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TSPAN5 AND TSPAN15</scope>
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                <person name="Lipper C.H."/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TSPAN15</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 214-654 IN COMPLEX WITH ZINC</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF GLU-384</scope>
        <scope>GLYCOSYLATION AT ASN-278</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>ACTIVE SITE</scope>
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            <dbReference type="PubMed" id="37516108"/>
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        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 214-748 IN COMPLEX WITH TSPAN15 AND ZINC</scope>
        <scope>INTERACTION WITH TSPAN15</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF 638-TYR--ARG-646 AND 653-PRO--ARG-656</scope>
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        <scope>VARIANTS AD18 HIS-170 AND GLY-181</scope>
        <scope>CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181</scope>
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        <scope>VARIANT TYR-176</scope>
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        <scope>VARIANTS RAK SER-139 AND TYR-524</scope>
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                <person name="Suh J."/>
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        <scope>CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181</scope>
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    <comment type="function">
        <text evidence="2 9 11 12 13 15 16 21 23 28 31 32 33 34 38 39 40">Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis (PubMed:11786905, PubMed:12475894, PubMed:20592283, PubMed:24990881, PubMed:26686862, PubMed:28600292, PubMed:31792032). Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity (PubMed:26686862, PubMed:28600292, PubMed:31792032, PubMed:34739841, PubMed:37516108). Cleaves the membrane-bound precursor of TNF at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:11786905, PubMed:26686862, PubMed:29224781, PubMed:34739841). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Also controls the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Required for the development of type 1 transitional B cells into marginal zone B cells, probably by cleaving Notch (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146). Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells (PubMed:28600292).</text>
    </comment>
    <comment type="function">
        <text evidence="22 37">(Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 11 12 13 15 16 21 23 31 34 35 40 44">
            <text>Endopeptidase of broad specificity.</text>
            <dbReference type="EC" id="3.4.24.81"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="34">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="34">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="4 34">Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (PubMed:29224781).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="40">22 uM for substrate (in complex with TSPAN15)</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="2 13 20 26 30 31 36 37 39 40">Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells (PubMed:16239146). Interacts with the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Forms a ternary complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens junctions (By similarity). Interacts with EPHA2 (By similarity). Interacts with NGF in a divalent cation-dependent manner (PubMed:20164177). Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression (PubMed:26668317, PubMed:26686862). Interacts with TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity, endocytosis and turnover (PubMed:26668317, PubMed:26686862, PubMed:34739841, PubMed:37516108). Interacts (via extracellular domain) with TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula adherens through a PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (PubMed:30463011). Interacts with DLG1; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (PubMed:23676497). Interacts (via extracellular domain) with BACE1 (via extracellular domain) (By similarity). Interacts with FAM171A1 (PubMed:30312582).</text>
    </comment>
    <comment type="subunit">
        <text evidence="22 37">(Microbial infection) Interacts with S.aureus hly; this interaction is necessary for toxin pore formation, disruption of focal adhesions and S.aureus hly-mediated cytotoxicity.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-375543">
            <id>P00519</id>
            <label>ABL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-77613">
            <id>P05067</id>
            <label>APP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-2433139">
            <id>P56817</id>
            <label>BACE1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-712921">
            <id>P60033</id>
            <label>CD81</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-4280101">
            <id>P21926</id>
            <label>CD9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>17</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-515315">
            <id>P06241</id>
            <label>FYN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-2847510">
            <id>Q13588</id>
            <label>GRAP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-740418">
            <id>O75791</id>
            <label>GRAP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-401755">
            <id>P62993</id>
            <label>GRB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-346340">
            <id>P08631</id>
            <label>HCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-1348">
            <id>P06239</id>
            <label>LCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-721769">
            <id>Q9BY11</id>
            <label>PACSIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-742503">
            <id>Q9UNF0</id>
            <label>PACSIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-77926">
            <id>Q9UKS6</id>
            <label>PACSIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-697911">
            <id>Q99961</id>
            <label>SH3GL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-298169">
            <id>Q96RF0</id>
            <label>SNX18</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-2466403">
            <id>O95859</id>
            <label>TSPAN12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-6308913">
            <id>Q8NG11</id>
            <label>TSPAN14</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-7361096">
            <id>O95858</id>
            <label>TSPAN15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-12045841">
            <id>Q86UF1</id>
            <label>TSPAN33</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-20977525">
            <id>P62079</id>
            <label>TSPAN5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1536151">
            <id>O14672</id>
        </interactant>
        <interactant intactId="EBI-515331">
            <id>P07947</id>
            <label>YES1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21222747">
            <id>PRO_0000029067</id>
        </interactant>
        <interactant intactId="EBI-712921">
            <id>P60033</id>
            <label>CD81</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21222747">
            <id>PRO_0000029067</id>
        </interactant>
        <interactant intactId="EBI-2466403">
            <id>O95859</id>
            <label>TSPAN12</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="22 26 28 31 35 37">Cell membrane</location>
            <topology evidence="43">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Golgi apparatus membrane</location>
            <topology evidence="43">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="12">Cytoplasmic vesicle</location>
            <location evidence="12">Clathrin-coated vesicle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Axon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Dendrite</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="37">Cell junction</location>
            <location evidence="37">Adherens junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="37">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="12 26 37">Is localized in the plasma membrane but is also expressed in the Golgi apparatus and in clathrin-coated vesicles derived likely from the Golgi (PubMed:12475894). During long term depression, it is recruited to the cell membrane by DLG1 (PubMed:23676497). The immature form is mainly located near cytoplasmic fibrillar structures, while the mature form is predominantly located at zonula adherens and the cell membrane (PubMed:30463011). The localization and clustering of mature ADAM10 to zonula adherens is regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 (PubMed:30463011).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O14672-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O14672-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056401"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10 26 41">Expressed in the brain (at protein level) (PubMed:23676497). Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver (PubMed:11511685, PubMed:9016778).</text>
    </comment>
    <comment type="induction">
        <text>In osteoarthritis affected-cartilage.</text>
    </comment>
    <comment type="domain">
        <text evidence="3">The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="domain">
        <text evidence="2 4 30">The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">The precursor is cleaved by furin and PCSK7.</text>
    </comment>
    <comment type="disease" evidence="25">
        <disease id="DI-03962">
            <name>Reticulate acropigmentation of Kitamura</name>
            <acronym>RAK</acronym>
            <description>A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia.</description>
            <dbReference type="MIM" id="615537"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="19 27">
        <disease id="DI-04003">
            <name>Alzheimer disease 18</name>
            <acronym>AD18</acronym>
            <description>A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.</description>
            <dbReference type="MIM" id="615590"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44397/ADAM10"/>
    </comment>
    <dbReference type="EC" id="3.4.24.81" evidence="9 12 13 15 16 21 34"/>
    <dbReference type="EMBL" id="AF009615">
        <property type="protein sequence ID" value="AAC51766.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300472">
        <property type="protein sequence ID" value="BAG62190.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC018904">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091046">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z48579">
        <property type="protein sequence ID" value="CAA88463.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10167.1">
        <molecule id="O14672-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001101.1">
        <molecule id="O14672-1"/>
        <property type="nucleotide sequence ID" value="NM_001110.4"/>
    </dbReference>
    <dbReference type="PDB" id="6BDZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="A=220-654"/>
    </dbReference>
    <dbReference type="PDB" id="6BE6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="A/B/C/D=214-654"/>
    </dbReference>
    <dbReference type="PDB" id="8ESV">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="A=214-748"/>
    </dbReference>
    <dbReference type="PDBsum" id="6BDZ"/>
    <dbReference type="PDBsum" id="6BE6"/>
    <dbReference type="PDBsum" id="8ESV"/>
    <dbReference type="AlphaFoldDB" id="O14672"/>
    <dbReference type="EMDB" id="EMD-28580"/>
    <dbReference type="SMR" id="O14672"/>
    <dbReference type="BioGRID" id="106616">
        <property type="interactions" value="127"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-39889N"/>
    <dbReference type="FunCoup" id="O14672">
        <property type="interactions" value="3380"/>
    </dbReference>
    <dbReference type="IntAct" id="O14672">
        <property type="interactions" value="163"/>
    </dbReference>
    <dbReference type="MINT" id="O14672"/>
    <dbReference type="STRING" id="9606.ENSP00000260408"/>
    <dbReference type="BindingDB" id="O14672"/>
    <dbReference type="ChEMBL" id="CHEMBL5028"/>
    <dbReference type="DrugBank" id="DB04991">
        <property type="generic name" value="XL784"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1658"/>
    <dbReference type="MEROPS" id="M12.210"/>
    <dbReference type="TCDB" id="8.A.77.1.4">
        <property type="family name" value="the sheddase (sheddase) family"/>
    </dbReference>
    <dbReference type="GlyConnect" id="1178">
        <property type="glycosylation" value="5 N-Linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O14672">
        <property type="glycosylation" value="5 sites, 6 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O14672">
        <property type="glycosylation" value="14 sites, 55 N-linked glycans (4 sites), 3 O-linked glycans (8 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O14672"/>
    <dbReference type="PhosphoSitePlus" id="O14672"/>
    <dbReference type="SwissPalm" id="O14672"/>
    <dbReference type="BioMuta" id="ADAM10"/>
    <dbReference type="jPOST" id="O14672"/>
    <dbReference type="MassIVE" id="O14672"/>
    <dbReference type="PaxDb" id="9606-ENSP00000260408"/>
    <dbReference type="PeptideAtlas" id="O14672"/>
    <dbReference type="ProteomicsDB" id="48162">
        <molecule id="O14672-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="5144"/>
    <dbReference type="Pumba" id="O14672"/>
    <dbReference type="ABCD" id="O14672">
        <property type="antibodies" value="29 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="3441">
        <property type="antibodies" value="598 antibodies from 44 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="102"/>
    <dbReference type="Ensembl" id="ENST00000260408.8">
        <molecule id="O14672-1"/>
        <property type="protein sequence ID" value="ENSP00000260408.3"/>
        <property type="gene ID" value="ENSG00000137845.16"/>
    </dbReference>
    <dbReference type="GeneID" id="102"/>
    <dbReference type="KEGG" id="hsa:102"/>
    <dbReference type="MANE-Select" id="ENST00000260408.8">
        <property type="protein sequence ID" value="ENSP00000260408.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001110.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001101.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002afd.3">
        <molecule id="O14672-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:188"/>
    <dbReference type="ClinPGx" id="PA24505"/>
    <dbReference type="CTD" id="102"/>
    <dbReference type="DisGeNET" id="102"/>
    <dbReference type="GeneCards" id="ADAM10"/>
    <dbReference type="HGNC" id="HGNC:188">
        <property type="gene designation" value="ADAM10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000137845">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADAM10"/>
    <dbReference type="MIM" id="602192">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="615537">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="615590">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000137845"/>
    <dbReference type="Orphanet" id="178307">
        <property type="disease" value="Reticulate acropigmentation of Kitamura"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000137845"/>
    <dbReference type="eggNOG" id="KOG3658">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160579"/>
    <dbReference type="HOGENOM" id="CLU_004602_0_0_1"/>
    <dbReference type="InParanoid" id="O14672"/>
    <dbReference type="OMA" id="MAVFIRC"/>
    <dbReference type="OrthoDB" id="2149267at2759"/>
    <dbReference type="PAN-GO" id="O14672">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O14672"/>
    <dbReference type="BioCyc" id="MetaCyc:ENSG00000137845-MONOMER"/>
    <dbReference type="BRENDA" id="3.4.24.81">
        <property type="organism ID" value="2681"/>
    </dbReference>
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    <evidence type="ECO:0007744" key="49">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="50">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="51">
        <source>
            <dbReference type="PDB" id="6BDZ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="52">
        <source>
            <dbReference type="PDB" id="6BE6"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="53">
        <source>
            <dbReference type="PDB" id="8ESV"/>
        </source>
    </evidence>
    <sequence length="748" mass="84142" checksum="0881E65B17022A71" modified="1998-01-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKF5</accession>
    <accession>Q4W5F3</accession>
    <accession>Q9UHP1</accession>
    <accession>Q9UKF3</accession>
    <accession>Q9UKF4</accession>
    <name>ADA29_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 29</fullName>
            <shortName>ADAM 29</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Cancer/testis antigen 73</fullName>
            <shortName>CT73</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM29</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA)</scope>
        <source>
            <tissue>Testis</tissue>
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            <dbReference type="PubMed" id="15815621"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>INVOLVEMENT IN CUTANEOUS MELANOMA</scope>
        <scope>VARIANTS PHE-72; MET-89; LYS-111; PHE-112; PHE-115; ASN-131; LYS-176; PHE-234; PHE-257; GLU-305; ASN-345; ASP-403; ASP-434; LYS-503 AND TYR-533</scope>
        <scope>CHARACTERIZATION OF VARIANTS LYS-111; PHE-112; PHE-115; PHE-257; ASP-434 AND LYS-503</scope>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] LEU-31 AND ILE-205</scope>
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    <comment type="function">
        <text>May be involved in spermatogenesis and fertilization. Seems to be a non catalytic metalloprotease-like protein.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKF5-1</id>
            <name>Alpha</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKF5-2</id>
            <name>Beta</name>
            <sequence type="described" ref="VSP_005491"/>
        </isoform>
        <isoform>
            <id>Q9UKF5-3</id>
            <name>Gamma</name>
            <sequence type="described" ref="VSP_005492 VSP_005493"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed specifically in testes.</text>
    </comment>
    <comment type="disease">
        <text evidence="7">Has been found to be frequently mutated in melanoma. ADAM7 mutations may play a role in melanoma progression and metastasis.</text>
    </comment>
    <dbReference type="EMBL" id="AF171929">
        <property type="protein sequence ID" value="AAF03777.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF171930">
        <property type="protein sequence ID" value="AAF03778.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF171931">
        <property type="protein sequence ID" value="AAF03779.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF134708">
        <property type="protein sequence ID" value="AAF22163.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292410">
        <property type="protein sequence ID" value="BAF85099.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC105914">
        <property type="protein sequence ID" value="AAY41055.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX04727.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX04728.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3823.1">
        <molecule id="Q9UKF5-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001124175.1">
        <molecule id="Q9UKF5-1"/>
        <property type="nucleotide sequence ID" value="NM_001130703.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001124176.1">
        <molecule id="Q9UKF5-1"/>
        <property type="nucleotide sequence ID" value="NM_001130704.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001124177.1">
        <molecule id="Q9UKF5-1"/>
        <property type="nucleotide sequence ID" value="NM_001130705.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001265054.1">
        <molecule id="Q9UKF5-1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
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        <location>
            <begin position="1"/>
            <end position="18"/>
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    <feature type="propeptide" id="PRO_0000029134" evidence="1">
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            <begin position="19"/>
            <end position="193"/>
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            <begin position="194"/>
            <end position="820"/>
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            <end position="674"/>
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            <begin position="675"/>
            <end position="695"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="696"/>
            <end position="820"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="4">
        <location>
            <begin position="198"/>
            <end position="390"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="397"/>
            <end position="483"/>
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    </feature>
    <feature type="domain" description="EGF-like">
        <location>
            <begin position="625"/>
            <end position="654"/>
        </location>
    </feature>
    <feature type="repeat" description="1">
        <location>
            <begin position="739"/>
            <end position="747"/>
        </location>
    </feature>
    <feature type="repeat" description="2">
        <location>
            <begin position="748"/>
            <end position="756"/>
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    </feature>
    <feature type="repeat" description="3">
        <location>
            <begin position="757"/>
            <end position="765"/>
        </location>
    </feature>
    <feature type="repeat" description="4">
        <location>
            <begin position="766"/>
            <end position="774"/>
        </location>
    </feature>
    <feature type="repeat" description="5">
        <location>
            <begin position="775"/>
            <end position="783"/>
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    </feature>
    <feature type="repeat" description="6">
        <location>
            <begin position="784"/>
            <end position="792"/>
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    </feature>
    <feature type="repeat" description="7">
        <location>
            <begin position="793"/>
            <end position="801"/>
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    </feature>
    <feature type="repeat" description="8">
        <location>
            <begin position="802"/>
            <end position="810"/>
        </location>
    </feature>
    <feature type="repeat" description="9">
        <location>
            <begin position="811"/>
            <end position="819"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="706"/>
            <end position="820"/>
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    </feature>
    <feature type="region of interest" description="9 X 9 AA approximate repeats">
        <location>
            <begin position="739"/>
            <end position="819"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="715"/>
            <end position="727"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="738"/>
            <end position="820"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="368"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="428"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="469"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="538"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="545"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="558"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="564"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="307"/>
            <end position="384"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="347"/>
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    <feature type="disulfide bond" evidence="1">
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            <begin position="349"/>
            <end position="354"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="455"/>
            <end position="475"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="625"/>
            <end position="636"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="630"/>
            <end position="642"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="644"/>
            <end position="653"/>
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    </feature>
    <feature type="splice variant" id="VSP_005491" description="In isoform Beta." evidence="8">
        <location>
            <begin position="750"/>
            <end position="803"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005492" description="In isoform Gamma." evidence="8">
        <original>VTPSQSQPRVMPSQSQPPVMPSQSH</original>
        <variation>QNLFLFSFSISDCVLNFRLLYLQAT</variation>
        <location>
            <begin position="763"/>
            <end position="787"/>
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    </feature>
    <feature type="splice variant" id="VSP_005493" description="In isoform Gamma." evidence="8">
        <location>
            <begin position="788"/>
            <end position="820"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036148" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs544557652." evidence="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066322" description="In a melanoma cell line." evidence="7">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="72"/>
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    </feature>
    <feature type="sequence variant" id="VAR_066323" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="7">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066324" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV; dbSNP:rs267600087." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066325" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV." evidence="7">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066326" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV." evidence="7">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066327" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="7">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066328" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs899870236." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="176"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036149" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs772388824." evidence="6">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="205"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066329" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs866380131." evidence="7">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066330" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV; dbSNP:rs140083180." evidence="7">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="257"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066331" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267600089." evidence="7">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="305"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066332" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267600090." evidence="7">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066333" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs150047888." evidence="7">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="403"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066334" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV; dbSNP:rs267600091." evidence="7">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="434"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066335" description="In a cutaneous metastatic melanoma sample; somatic mutation; increases the adhesion of melanoma cells to collagens I and IV." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="503"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066336" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267600093." evidence="7">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="533"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF22163." evidence="9" ref="2">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF22163." evidence="9" ref="2">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="744"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF22163." evidence="9" ref="2">
        <original>S</original>
        <variation>Y</variation>
        <location>
            <position position="748"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF03777." evidence="9" ref="1">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="753"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF03777." evidence="9" ref="1">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="764"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF03777." evidence="9" ref="1">
        <original>QPRVM</original>
        <variation>HPQLT</variation>
        <location>
            <begin position="769"/>
            <end position="773"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21618342"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="10512762"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <sequence length="820" mass="92759" checksum="AA2FB11342A884C9" modified="2007-04-17" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-01" modified="2026-01-28" version="149" xmlns="https://uniprot.org/uniprot">
    <accession>Q6DHV7</accession>
    <accession>A6NHZ3</accession>
    <accession>B4DQM8</accession>
    <name>ADAL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">N6-Methyl-AMP deaminase</fullName>
            <ecNumber evidence="3 4 6">3.5.4.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="9">Adenosine deaminase-like protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">N6,N6-dimethyl-AMP deaminase</fullName>
            <ecNumber evidence="6">3.5.4.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">N6-isopentenyl-AMP deaminase</fullName>
            <ecNumber evidence="6">3.5.4.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="10">N6-mAMP deaminase</fullName>
            <shortName evidence="10">HsMAPDA</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="9">N6-methyl-AMP aminohydrolase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="14" type="primary">MAPDA</name>
        <name evidence="11" type="synonym">ADAL</name>
        <name evidence="9" type="synonym">ADAL1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>COFACTOR</scope>
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    </reference>
    <comment type="function">
        <text evidence="3 4 6">Deaminase involved in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification (PubMed:40840445). Modified nucleosides are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs) and possess intrinsic cytotoxicity and must be cleared to prevent metabolic dysfunction (PubMed:40840445). Acts downstream of ADK and catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotides N(6)-methyl-AMP (m6AMP), N(6),N(6)-dimethyl-AMP (m6,6AMP) and N(6)-isopentenyl-AMP (i6AMP) to produce inositol monophosphate (IMP) (PubMed:21755941, PubMed:29884623, PubMed:40840445). Catalyzes the removal of different alkyl groups not only from N6-substituted purine or 2-aminopurine nucleoside monophosphates but also from O6-substituted compounds in vitro (PubMed:21755941).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3 4 6">
            <text>N(6)-methyl-AMP + H2O + H(+) = IMP + methylamine</text>
            <dbReference type="Rhea" id="RHEA:16001"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:59338"/>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3 4 6">
            <dbReference type="Rhea" id="RHEA:16002"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N(6),N(6)-dimethyl-AMP + H2O + H(+) = dimethylamine + IMP</text>
            <dbReference type="Rhea" id="RHEA:86223"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58040"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:235457"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:86224"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>N(6)-(dimethylallyl)adenosine 5'-phosphate + H2O + H(+) = dimethylallylamine + IMP</text>
            <dbReference type="Rhea" id="RHEA:86227"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57526"/>
            <dbReference type="ChEBI" id="CHEBI:58053"/>
            <dbReference type="ChEBI" id="CHEBI:235458"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:86228"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3 4 5">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="5 13">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">12.5 uM for N(6)-methyl-AMP (m6AMP)</KM>
            <KM evidence="6">47 uM for N(6)-methyl-AMP (m6AMP)</KM>
            <KM evidence="6">65 uM for N(6),N(6)-dimethyl-AMP (m6,6AMP)</KM>
            <KM evidence="6">35 uM for N(6)-isopentenyl-AMP (i6AMP)</KM>
            <text evidence="5">kcat is 2.4 sec(-1) with N(6)-methyl-AMP (m6AMP) as substrate. kcat is 2.6 sec(-1) with N(6),N(6)-dimethyl-AMP (m6,6AMP) as substrate. kcat is 2.9 sec(-1) with N(6)-isopentenyl-AMP (i6AMP) as substrate.</text>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="3">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-718729">
            <id>P55212</id>
            <label>CASP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-6624398">
            <id>P06307</id>
            <label>CCK</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-1054228">
            <id>P41091</id>
            <label>EIF2S3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-25852368">
            <id>O75460-2</id>
            <label>ERN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-10226858">
            <id>Q0VDC6</id>
            <label>FKBP1A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-712096">
            <id>P30519</id>
            <label>HMOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-356991">
            <id>P54652</id>
            <label>HSPA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-21591415">
            <id>P13473-2</id>
            <label>LAMP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-6165891">
            <id>Q14696</id>
            <label>MESD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-716404">
            <id>P16284</id>
            <label>PECAM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-5774511">
            <id>P05771-2</id>
            <label>PRKCB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-5280197">
            <id>O75400-2</id>
            <label>PRPF40A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-286642">
            <id>P62826</id>
            <label>RAN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-1053431">
            <id>P49591</id>
            <label>SARS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-1054052">
            <id>P31948</id>
            <label>STIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-473850">
            <id>P61086</id>
            <label>UBE2K</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18899653">
            <id>Q6DHV7-2</id>
        </interactant>
        <interactant intactId="EBI-353844">
            <id>P08670</id>
            <label>VIM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6DHV7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6DHV7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_024821"/>
        </isoform>
        <isoform>
            <id>Q6DHV7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_042782"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <text evidence="5">Involved in the activation pathway of bemnifosbuvir (AT-527) and its epimer, AT-752 (PubMed:39190717). AT-527 and AT-752 are two guanosine analogs tested in clinical trials against several RNA viruses, which are activated into their common 5'-triphosphate AT-9010 in human cells (PubMed:39190717). Mediates the third activation step by catalyzing transformation of AT-8003 into AT-8001 (PubMed:39190717).</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.-" evidence="3 4 6"/>
    <dbReference type="EMBL" id="AK126583">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298870">
        <property type="protein sequence ID" value="BAG60990.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC009852">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC018924">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC075857">
        <property type="protein sequence ID" value="AAH75857.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32214.1">
        <molecule id="Q6DHV7-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53936.1">
        <molecule id="Q6DHV7-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81868.1">
        <molecule id="Q6DHV7-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001012987.1">
        <molecule id="Q6DHV7-2"/>
        <property type="nucleotide sequence ID" value="NM_001012969.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001152752.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="NM_001159280.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311293.1">
        <molecule id="Q6DHV7-2"/>
        <property type="nucleotide sequence ID" value="NM_001324364.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311294.1">
        <molecule id="Q6DHV7-2"/>
        <property type="nucleotide sequence ID" value="NM_001324365.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311295.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="NM_001324366.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311297.1">
        <molecule id="Q6DHV7-2"/>
        <property type="nucleotide sequence ID" value="NM_001324368.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011519593.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_011521291.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016877453.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_017021964.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016877454.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_017021965.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016877455.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_017021966.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024305626.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_024449858.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288158.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_047432202.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288159.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_047432203.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288160.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_047432204.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233360.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_054377385.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233361.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_054377386.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233362.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_054377387.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233363.1">
        <molecule id="Q6DHV7-1"/>
        <property type="nucleotide sequence ID" value="XM_054377388.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233364.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_054377389.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233365.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_054377390.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233366.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_054377391.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054233367.1">
        <molecule id="Q6DHV7-3"/>
        <property type="nucleotide sequence ID" value="XM_054377392.1"/>
    </dbReference>
    <dbReference type="PDB" id="8QCH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.44 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=1-355"/>
    </dbReference>
    <dbReference type="PDBsum" id="8QCH"/>
    <dbReference type="AlphaFoldDB" id="Q6DHV7"/>
    <dbReference type="SMR" id="Q6DHV7"/>
    <dbReference type="BioGRID" id="127803">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6DHV7">
        <property type="interactions" value="977"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6DHV7">
        <property type="interactions" value="17"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000456242"/>
    <dbReference type="ChEMBL" id="CHEMBL1795150"/>
    <dbReference type="iPTMnet" id="Q6DHV7"/>
    <dbReference type="PhosphoSitePlus" id="Q6DHV7"/>
    <dbReference type="BioMuta" id="ADAL"/>
    <dbReference type="DMDM" id="146286026"/>
    <dbReference type="jPOST" id="Q6DHV7"/>
    <dbReference type="MassIVE" id="Q6DHV7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000398744"/>
    <dbReference type="PeptideAtlas" id="Q6DHV7"/>
    <dbReference type="ProteomicsDB" id="66225">
        <molecule id="Q6DHV7-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="66226">
        <molecule id="Q6DHV7-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="66227">
        <molecule id="Q6DHV7-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q6DHV7"/>
    <dbReference type="Antibodypedia" id="23863">
        <property type="antibodies" value="91 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="161823"/>
    <dbReference type="Ensembl" id="ENST00000389651.8">
        <molecule id="Q6DHV7-2"/>
        <property type="protein sequence ID" value="ENSP00000374302.4"/>
        <property type="gene ID" value="ENSG00000168803.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000422466.6">
        <molecule id="Q6DHV7-3"/>
        <property type="protein sequence ID" value="ENSP00000398744.3"/>
        <property type="gene ID" value="ENSG00000168803.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000428046.7">
        <molecule id="Q6DHV7-3"/>
        <property type="protein sequence ID" value="ENSP00000413074.3"/>
        <property type="gene ID" value="ENSG00000168803.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000562188.7">
        <molecule id="Q6DHV7-1"/>
        <property type="protein sequence ID" value="ENSP00000456242.1"/>
        <property type="gene ID" value="ENSG00000168803.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000610420.4">
        <molecule id="Q6DHV7-2"/>
        <property type="protein sequence ID" value="ENSP00000478575.1"/>
        <property type="gene ID" value="ENSG00000168803.17"/>
    </dbReference>
    <dbReference type="GeneID" id="161823"/>
    <dbReference type="KEGG" id="hsa:161823"/>
    <dbReference type="MANE-Select" id="ENST00000562188.7">
        <property type="protein sequence ID" value="ENSP00000456242.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001324366.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001311295.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001zrh.5">
        <molecule id="Q6DHV7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31853"/>
    <dbReference type="ClinPGx" id="PA142672643"/>
    <dbReference type="CTD" id="161823"/>
    <dbReference type="DisGeNET" id="161823"/>
    <dbReference type="GeneCards" id="MAPDA"/>
    <dbReference type="HGNC" id="HGNC:31853">
        <property type="gene designation" value="MAPDA"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000168803">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="619346">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000168803"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000168803"/>
    <dbReference type="eggNOG" id="KOG1097">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183113"/>
    <dbReference type="HOGENOM" id="CLU_039228_6_0_1"/>
    <dbReference type="InParanoid" id="Q6DHV7"/>
    <dbReference type="OMA" id="RPQFKPY"/>
    <dbReference type="OrthoDB" id="272271at2759"/>
    <dbReference type="PAN-GO" id="Q6DHV7">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6DHV7"/>
    <dbReference type="BioCyc" id="MetaCyc:ENSG00000168803-MONOMER"/>
    <dbReference type="PathwayCommons" id="Q6DHV7"/>
    <dbReference type="Reactome" id="R-HSA-2161541">
        <property type="pathway name" value="Abacavir metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-74217">
        <property type="pathway name" value="Purine salvage"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6DHV7"/>
    <dbReference type="Agora" id="ENSG00000168803"/>
    <dbReference type="BioGRID-ORCS" id="161823">
        <property type="hits" value="13 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAL">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="161823"/>
    <dbReference type="Pharos" id="Q6DHV7">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6DHV7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6DHV7">
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        <citation type="journal article" date="1992" name="J. Biol. Chem." volume="267" first="21936" last="21945">
            <title>Genomic organization and expression of the human alpha 1B-adrenergic receptor.</title>
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                <person name="Denker J.M."/>
                <person name="Perez D.M."/>
                <person name="Gaivin R.J."/>
                <person name="Riek R.P."/>
                <person name="Graham R.M."/>
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            <dbReference type="DOI" id="10.1016/s0021-9258(19)36703-1"/>
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        <citation type="journal article" date="1994" name="Mol. Pharmacol." volume="45" first="703" last="708">
            <title>The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype.</title>
            <authorList>
                <person name="Forray C."/>
                <person name="Bard J.A."/>
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                <person name="Branchek T.A."/>
                <person name="Gluchowski C."/>
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        <citation type="journal article" date="1995" name="J. Pharmacol. Exp. Ther." volume="272" first="134" last="142">
            <title>Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues.</title>
            <authorList>
                <person name="Schwinn D.A."/>
                <person name="Johnston G.I."/>
                <person name="Page S.O."/>
                <person name="Mosley M.J."/>
                <person name="Wilson K.H."/>
                <person name="Worman N.P."/>
                <person name="Campbell S."/>
                <person name="Fidock M.D."/>
                <person name="Furness L.M."/>
                <person name="Parry-Smith D.J."/>
                <person name="Peter B."/>
                <person name="Bailey D.S."/>
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        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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        <citation type="journal article" date="2008" name="Circ. Res." volume="103" first="992" last="1000">
            <title>Nuclear alpha1-adrenergic receptors signal activated ERK localization to caveolae in adult cardiac myocytes.</title>
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                <person name="Wright C.D."/>
                <person name="Chen Q."/>
                <person name="Baye N.L."/>
                <person name="Huang Y."/>
                <person name="Healy C.L."/>
                <person name="Kasinathan S."/>
                <person name="O'Connell T.D."/>
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    <reference key="7">
        <citation type="journal article" date="2012" name="Cell. Signal." volume="24" first="794" last="802">
            <title>Nuclear localization drives alpha1-adrenergic receptor oligomerization and signaling in cardiac myocytes.</title>
            <authorList>
                <person name="Wright C.D."/>
                <person name="Wu S.C."/>
                <person name="Dahl E.F."/>
                <person name="Sazama A.J."/>
                <person name="O'Connell T.D."/>
            </authorList>
            <dbReference type="PubMed" id="22120526"/>
            <dbReference type="DOI" id="10.1016/j.cellsig.2011.11.014"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF 368-ARG--ARG-380</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2014" name="Proc. Natl. Acad. Sci. U.S.A." volume="111" first="3811" last="3816">
            <title>MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by alpha1-adrenergic receptors.</title>
            <authorList>
                <person name="Ogata T."/>
                <person name="Naito D."/>
                <person name="Nakanishi N."/>
                <person name="Hayashi Y.K."/>
                <person name="Taniguchi T."/>
                <person name="Miyagawa K."/>
                <person name="Hamaoka T."/>
                <person name="Maruyama N."/>
                <person name="Matoba S."/>
                <person name="Ikeda K."/>
                <person name="Yamada H."/>
                <person name="Oh H."/>
                <person name="Ueyama T."/>
            </authorList>
            <dbReference type="PubMed" id="24567387"/>
            <dbReference type="DOI" id="10.1073/pnas.1315359111"/>
        </citation>
        <scope>INTERACTION WITH CAVIN4</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="2 8 9 10 11 12">Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C (By similarity). ADRA1B binds the catecholamine ligands norepinephrine and epinephrine (PubMed:7815325, PubMed:8183249). Can also couple to G(14) and G(16) proteins (By similarity). Nuclear ADRA1B forms heterooligomers with ADRA1A to regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes (PubMed:18802028, PubMed:22120526). At the plasma membrane, ADRA1B interacts with CAVIN4/MURC to regulates ERK activation in cardiomyocytes, contributing to the regulation of cardiac hypertrophy (PubMed:24567387).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10">Homo- and heterooligomer. Heterooligomerizes with ADRA1A homooligomers in cardiac myocytes (PubMed:22120526). Interacts with CAVIN4 (PubMed:24567387).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8 9">Nucleus membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Membrane</location>
            <location evidence="10">Caveola</location>
        </subcellularLocation>
        <text evidence="8 9 10">Location at the nuclear membrane facilitates heterooligomerization and regulates ERK-mediated signaling in cardiac myocytes. Colocalizes with GNAQ, PLCB1 as well as LAP2 at the nuclear membrane of cardiac myocytes (PubMed:18802028, PubMed:22120526). Colocalizes with CAVIN4 and CAV3 at the plasma membrane and partly within the cytoplasm in cardiomyocytes (PubMed:24567387).</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1B sub-subfamily.</text>
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        <property type="term" value="F:protein heterodimerization activity"/>
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        <property type="project" value="GO_Central"/>
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        <property type="entry name" value="7tmA_alpha1B_AR"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="alpha-1A adrenergic receptor"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.20.1070.10">
        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADR_fam"/>
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        <property type="entry name" value="ADRA1B_rcpt"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ALPHA-1B ADRENERGIC RECEPTOR"/>
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        <property type="entry name" value="7tm_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADRENERGICR"/>
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        <property type="entry name" value="ADRENRGCA1BR"/>
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        <property type="entry name" value="GPCRRHODOPSN"/>
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        <property type="entry name" value="7TM_GPCR_Srsx"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0297">G-protein coupled receptor</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0807">Transducer</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000069069" description="Alpha-1B adrenergic receptor">
        <location>
            <begin position="1"/>
            <end position="520"/>
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    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="1"/>
            <end position="45"/>
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        <location>
            <begin position="46"/>
            <end position="70"/>
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        <location>
            <begin position="71"/>
            <end position="83"/>
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        <location>
            <begin position="84"/>
            <end position="105"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="106"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="1">
        <location>
            <begin position="116"/>
            <end position="141"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="142"/>
            <end position="161"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="1">
        <location>
            <begin position="162"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="185"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="1">
        <location>
            <begin position="202"/>
            <end position="224"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="225"/>
            <end position="295"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="1">
        <location>
            <begin position="296"/>
            <end position="319"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="1">
        <location>
            <begin position="320"/>
            <end position="326"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="1">
        <location>
            <begin position="327"/>
            <end position="351"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="1">
        <location>
            <begin position="352"/>
            <end position="520"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="394"/>
            <end position="432"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="479"/>
            <end position="520"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal">
        <location>
            <begin position="368"/>
            <end position="380"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="125"/>
        </location>
        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
        </ligand>
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    <feature type="binding site" evidence="3">
        <location>
            <position position="207"/>
        </location>
        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    <feature type="modified residue" description="Phosphothreonine" evidence="4">
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="5">
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="6">
        <location>
            <begin position="118"/>
            <end position="195"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_019510" description="In dbSNP:rs8192448.">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="51"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes targeting to the nuclear membrane of cardiac myocytes." evidence="9">
        <original>RGRGRRRRRRRRR</original>
        <variation>AGAGAAAAAAAAA</variation>
        <location>
            <begin position="368"/>
            <end position="380"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1 and 3; AAB59485." evidence="14" ref="1 3">
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1." evidence="14" ref="1">
        <original>AAAD</original>
        <variation>PRH</variation>
        <location>
            <begin position="498"/>
            <end position="501"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P18841"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P35348"/>
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    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P97717"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="18802028"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22120526"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="24567387"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="7815325"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="8183249"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="1328250"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:278"/>
        </source>
    </evidence>
    <sequence length="520" mass="56836" checksum="F081A23D2F943F7F" modified="2006-10-17" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>P78325</accession>
    <accession>B4DVM6</accession>
    <accession>H0YL36</accession>
    <accession>H0YLR0</accession>
    <accession>H0YN39</accession>
    <name>ADAM8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 8</fullName>
            <shortName>ADAM 8</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Cell surface antigen MS2</fullName>
        </alternativeName>
        <cdAntigenName>CD156a</cdAntigenName>
    </protein>
    <gene>
        <name type="primary">ADAM8</name>
        <name type="synonym">MS2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Genomics" volume="41" first="56" last="62">
            <title>CD156 (human ADAM8): expression, primary amino acid sequence, and gene location.</title>
            <authorList>
                <person name="Yoshiyama K."/>
                <person name="Higuchi Y."/>
                <person name="Kataoka M."/>
                <person name="Matsuura K."/>
                <person name="Yamamoto S."/>
            </authorList>
            <dbReference type="PubMed" id="9126482"/>
            <dbReference type="DOI" id="10.1006/geno.1997.4607"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ARG-35</scope>
        <source>
            <tissue>Blood</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT LEU-657</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
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                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
                <person name="Swarbreck D."/>
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                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D.C."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Cahill P."/>
                <person name="Camire D."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
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                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <scope>VARIANT ARG-35</scope>
        <source>
            <tissue>Pancreatic cancer</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2005" name="Biol. Cell" volume="97" first="577" last="588">
            <title>FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation.</title>
            <authorList>
                <person name="Bartholin L."/>
                <person name="Destaing O."/>
                <person name="Forissier S."/>
                <person name="Martel S."/>
                <person name="Maguer-Satta V."/>
                <person name="Jurdic P."/>
                <person name="Rimokh R."/>
            </authorList>
            <dbReference type="PubMed" id="15574124"/>
            <dbReference type="DOI" id="10.1042/bc20040506"/>
        </citation>
        <scope>INTERACTION WITH FST3</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2012" name="Acta Crystallogr. F" volume="68" first="616" last="621">
            <title>Structure of human ADAM-8 catalytic domain complexed with batimastat.</title>
            <authorList>
                <person name="Hall T."/>
                <person name="Shieh H.S."/>
                <person name="Day J.E."/>
                <person name="Caspers N."/>
                <person name="Chrencik J.E."/>
                <person name="Williams J.M."/>
                <person name="Pegg L.E."/>
                <person name="Pauley A.M."/>
                <person name="Moon A.F."/>
                <person name="Krahn J.M."/>
                <person name="Fischer D.H."/>
                <person name="Kiefer J.R."/>
                <person name="Tomasselli A.G."/>
                <person name="Zack M.D."/>
            </authorList>
            <dbReference type="PubMed" id="22684055"/>
            <dbReference type="DOI" id="10.1107/s1744309112015618"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 196-403 IN COMPLEX WITH INHIBITOR AND ZINC IONS</scope>
        <scope>COFACTOR</scope>
    </reference>
    <comment type="function">
        <text>Possible involvement in extravasation of leukocytes.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="12">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="12">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="11">Interacts with FST3.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625954">
            <id>P78325</id>
        </interactant>
        <interactant intactId="EBI-714058">
            <id>Q5T0N5</id>
            <label>FNBP1L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625954">
            <id>P78325</id>
        </interactant>
        <interactant intactId="EBI-395044">
            <id>P14598</id>
            <label>NCF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625954">
            <id>P78325</id>
        </interactant>
        <interactant intactId="EBI-1383480">
            <id>P42680</id>
            <label>TEC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2625954">
            <id>P78325</id>
        </interactant>
        <interactant intactId="EBI-739936">
            <id>Q15642</id>
            <label>TRIP10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P78325-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P78325-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046154 VSP_046155 VSP_046156 VSP_046159"/>
        </isoform>
        <isoform>
            <id>P78325-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046157 VSP_046158"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed on neutrophils and monocytes.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="D26579">
        <property type="protein sequence ID" value="BAA05626.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301147">
        <property type="protein sequence ID" value="BAG62738.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL592071">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064500">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31319.2">
        <molecule id="P78325-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58102.1">
        <molecule id="P78325-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58103.1">
        <molecule id="P78325-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001100.3">
        <molecule id="P78325-1"/>
        <property type="nucleotide sequence ID" value="NM_001109.5"/>
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    <dbReference type="RefSeq" id="NP_001157961.1">
        <molecule id="P78325-3"/>
        <property type="nucleotide sequence ID" value="NM_001164489.2"/>
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    <dbReference type="RefSeq" id="NP_001157962.1">
        <molecule id="P78325-2"/>
        <property type="nucleotide sequence ID" value="NM_001164490.2"/>
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    <dbReference type="PDB" id="4DD8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B/C/D=196-403"/>
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    <dbReference type="PDBsum" id="4DD8"/>
    <dbReference type="AlphaFoldDB" id="P78325"/>
    <dbReference type="SMR" id="P78325"/>
    <dbReference type="BioGRID" id="106615">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="CORUM" id="P78325"/>
    <dbReference type="FunCoup" id="P78325">
        <property type="interactions" value="227"/>
    </dbReference>
    <dbReference type="IntAct" id="P78325">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000453302"/>
    <dbReference type="BindingDB" id="P78325"/>
    <dbReference type="ChEMBL" id="CHEMBL5665"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="1656"/>
    <dbReference type="MEROPS" id="M12.208"/>
    <dbReference type="GlyConnect" id="1996">
        <property type="glycosylation" value="2 N-Linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P78325">
        <property type="glycosylation" value="4 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P78325">
        <property type="glycosylation" value="5 sites, 2 N-linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P78325"/>
    <dbReference type="PhosphoSitePlus" id="P78325"/>
    <dbReference type="SwissPalm" id="P78325"/>
    <dbReference type="BioMuta" id="ADAM8"/>
    <dbReference type="DMDM" id="408359955"/>
    <dbReference type="jPOST" id="P78325"/>
    <dbReference type="MassIVE" id="P78325"/>
    <dbReference type="PaxDb" id="9606-ENSP00000453302"/>
    <dbReference type="PeptideAtlas" id="P78325"/>
    <dbReference type="ProteomicsDB" id="39834"/>
    <dbReference type="ProteomicsDB" id="40029"/>
    <dbReference type="ProteomicsDB" id="40447"/>
    <dbReference type="ProteomicsDB" id="57567">
        <molecule id="P78325-1"/>
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    <dbReference type="ABCD" id="P78325">
        <property type="antibodies" value="19 sequenced antibodies"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="19390">
        <property type="antibodies" value="399 antibodies from 39 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="101"/>
    <dbReference type="Ensembl" id="ENST00000415217.7">
        <molecule id="P78325-3"/>
        <property type="protein sequence ID" value="ENSP00000453855.1"/>
        <property type="gene ID" value="ENSG00000151651.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000445355.8">
        <molecule id="P78325-1"/>
        <property type="protein sequence ID" value="ENSP00000453302.1"/>
        <property type="gene ID" value="ENSG00000151651.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000485491.6">
        <molecule id="P78325-2"/>
        <property type="protein sequence ID" value="ENSP00000453043.1"/>
        <property type="gene ID" value="ENSG00000151651.17"/>
    </dbReference>
    <dbReference type="GeneID" id="101"/>
    <dbReference type="KEGG" id="hsa:101"/>
    <dbReference type="MANE-Select" id="ENST00000445355.8">
        <property type="protein sequence ID" value="ENSP00000453302.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001109.5"/>
        <property type="RefSeq protein sequence ID" value="NP_001100.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc009ybi.4">
        <molecule id="P78325-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:215"/>
    <dbReference type="CTD" id="101"/>
    <dbReference type="DisGeNET" id="101"/>
    <dbReference type="GeneCards" id="ADAM8"/>
    <dbReference type="HGNC" id="HGNC:215">
        <property type="gene designation" value="ADAM8"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000151651">
        <property type="expression patterns" value="Tissue enhanced (bone marrow, lymphoid tissue)"/>
    </dbReference>
    <dbReference type="MIM" id="602267">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000151651"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000151651"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158585"/>
    <dbReference type="HOGENOM" id="CLU_012714_7_1_1"/>
    <dbReference type="InParanoid" id="P78325"/>
    <dbReference type="OMA" id="HGQDHCL"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="P78325">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P78325"/>
    <dbReference type="PathwayCommons" id="P78325"/>
    <dbReference type="Reactome" id="R-HSA-1474228">
        <property type="pathway name" value="Degradation of the extracellular matrix"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-6798695">
        <property type="pathway name" value="Neutrophil degranulation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P78325"/>
    <dbReference type="Agora" id="ENSG00000151651"/>
    <dbReference type="BioGRID-ORCS" id="101">
        <property type="hits" value="8 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM8">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P78325"/>
    <dbReference type="GeneWiki" id="ADAM8"/>
    <dbReference type="GenomeRNAi" id="101"/>
    <dbReference type="Pharos" id="P78325">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P78325"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="P78325">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000151651">
        <property type="expression patterns" value="Expressed in granulocyte and 118 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P78325">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071133">
        <property type="term" value="C:alpha9-beta1 integrin-ADAM8 complex"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032127">
        <property type="term" value="C:dense core granule membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0101003">
        <property type="term" value="C:ficolin-1-rich granule membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032010">
        <property type="term" value="C:phagolysosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002102">
        <property type="term" value="C:podosome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042581">
        <property type="term" value="C:specific granule"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035579">
        <property type="term" value="C:specific granule membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070820">
        <property type="term" value="C:tertiary granule"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070821">
        <property type="term" value="C:tertiary granule membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005509">
        <property type="term" value="F:calcium ion binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050839">
        <property type="term" value="F:cell adhesion molecule binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034987">
        <property type="term" value="F:immunoglobulin receptor binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029060" description="Disintegrin and metalloproteinase domain-containing protein 8">
        <location>
            <begin position="17"/>
            <end position="824"/>
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        <location>
            <begin position="17"/>
            <end position="655"/>
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    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="656"/>
            <end position="676"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="677"/>
            <end position="824"/>
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    <feature type="domain" description="Peptidase M12B" evidence="6">
        <location>
            <begin position="200"/>
            <end position="400"/>
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    </feature>
    <feature type="domain" description="Disintegrin" evidence="4">
        <location>
            <begin position="408"/>
            <end position="494"/>
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    </feature>
    <feature type="domain" description="EGF-like" evidence="5">
        <location>
            <begin position="609"/>
            <end position="641"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="8">
        <location>
            <begin position="710"/>
            <end position="756"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="8">
        <location>
            <begin position="776"/>
            <end position="824"/>
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    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="8">
        <location>
            <begin position="747"/>
            <end position="756"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="8">
        <location>
            <begin position="788"/>
            <end position="804"/>
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    </feature>
    <feature type="active site" evidence="6 7">
        <location>
            <position position="335"/>
        </location>
    </feature>
    <feature type="binding site" evidence="12">
        <location>
            <position position="334"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="12">
        <location>
            <position position="338"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="12">
        <location>
            <position position="344"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="67"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="436"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="612"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="310"/>
            <end position="395"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="351"/>
            <end position="379"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="353"/>
            <end position="362"/>
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    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="435"/>
            <end position="457"/>
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    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="448"/>
            <end position="454"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="466"/>
            <end position="486"/>
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    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="473"/>
            <end position="503"/>
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    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="498"/>
            <end position="508"/>
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    </feature>
    <feature type="disulfide bond" evidence="2">
        <location>
            <begin position="566"/>
            <end position="613"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="613"/>
            <end position="623"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="617"/>
            <end position="629"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="631"/>
            <end position="640"/>
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    <feature type="splice variant" id="VSP_046154" description="In isoform 2." evidence="14">
        <original>AIAPSRPWALMEQYEVVLPWRLPGPRVRRALPSHLGLHPERVSYVLGATGHNFTLHLRKNRDLLGSGYTETYTAANG</original>
        <variation>GPAPREGELRPWGHRAQLHPPPAEEQGPAGLRLHRDLYGCQWLRGDGAASRAGPLLLPGPRRGVPGLSRQPQHLCRP</variation>
        <location>
            <begin position="16"/>
            <end position="92"/>
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    </feature>
    <feature type="splice variant" id="VSP_046155" description="In isoform 2." evidence="14">
        <location>
            <begin position="93"/>
            <end position="131"/>
        </location>
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    <feature type="splice variant" id="VSP_046156" description="In isoform 2." evidence="14">
        <location>
            <begin position="596"/>
            <end position="621"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046157" description="In isoform 3." evidence="15">
        <original>ASGSLPVFVVVVLVLLAVVLVTLAGIIVYRKARSRILSRNVAPKTTMGRSNPLFHQAASRVPAKGGAPAPSRGPQELVPTTHPGQPARHPASS</original>
        <variation>GCQPRAGQGRGSSPIQGPPRAGPHHPPGPARPTPGLLGGSEEAAPCSSGHCVQPTLPSSCLHPAGTKAGHQANVRTPSAPSQTRGWCGQPWSS</variation>
        <location>
            <begin position="650"/>
            <end position="742"/>
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    </feature>
    <feature type="splice variant" id="VSP_046158" description="In isoform 3." evidence="15">
        <location>
            <begin position="743"/>
            <end position="824"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046159" description="In isoform 2." evidence="14">
        <location>
            <begin position="774"/>
            <end position="799"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069144" description="In dbSNP:rs2275725." evidence="10 13">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="35"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059760" description="In dbSNP:rs11101675.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061735" description="In dbSNP:rs45451297.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="189"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061736" description="In dbSNP:rs12257830.">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="433"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069145" description="In dbSNP:rs2275720." evidence="9">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="657"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061737" description="In dbSNP:rs3008319.">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="775"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA05626." evidence="16" ref="1">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG62738." evidence="16" ref="2">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG62738." evidence="16" ref="2">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="648"/>
        </location>
    </feature>
    <feature type="strand" evidence="17">
        <location>
            <begin position="200"/>
            <end position="208"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="210"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="219"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="helix" evidence="17">
        <location>
            <begin position="238"/>
            <end position="240"/>
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    </feature>
    <feature type="strand" evidence="17">
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            <begin position="242"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="264"/>
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        </location>
    </feature>
    <feature type="turn" evidence="17">
        <location>
            <begin position="279"/>
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    <feature type="strand" evidence="17">
        <location>
            <begin position="286"/>
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    <feature type="strand" evidence="17">
        <location>
            <begin position="302"/>
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    <feature type="strand" evidence="17">
        <location>
            <begin position="315"/>
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    <feature type="helix" evidence="17">
        <location>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="345"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="378"/>
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    <feature type="helix" evidence="17">
        <location>
            <begin position="391"/>
            <end position="396"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG62738." evidence="16" ref="2">
        <original>L</original>
        <variation>F</variation>
        <location sequence="P78325-2">
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BC064500." evidence="16" ref="4">
        <original>A</original>
        <variation>S</variation>
        <location sequence="P78325-3">
            <position position="693"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q10741"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
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    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
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    </evidence>
    <evidence type="ECO:0000255" key="7">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="15574124"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="22684055"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="9126482"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="16"/>
    <evidence type="ECO:0007829" key="17">
        <source>
            <dbReference type="PDB" id="4DD8"/>
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    <sequence length="824" mass="88771" checksum="CE3D31330E153DB8" modified="2012-10-03" version="2" precursor="true"> </sequence>
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<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="252" xmlns="https://uniprot.org/uniprot">
    <accession>P78536</accession>
    <accession>O60226</accession>
    <name>ADA17_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 17</fullName>
            <shortName>ADAM 17</shortName>
            <ecNumber evidence="10 13 16 20">3.4.24.86</ecNumber>
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        <alternativeName>
            <fullName>Snake venom-like protease</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>TNF-alpha convertase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>TNF-alpha-converting enzyme</fullName>
        </alternativeName>
        <cdAntigenName>CD156b</cdAntigenName>
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    <gene>
        <name evidence="27" type="primary">ADAM17</name>
        <name type="synonym">CSVP</name>
        <name type="synonym">TACE</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Leukocyte</tissue>
            <tissue>Monocyte</tissue>
        </source>
    </reference>
    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A)</scope>
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            <dbReference type="PubMed" id="12058067"/>
            <dbReference type="DOI" id="10.1091/mbc.01-11-0561"/>
        </citation>
        <scope>PHOSPHORYLATION AT THR-735</scope>
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    <reference key="5">
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                <person name="Thathiah A."/>
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            <dbReference type="PubMed" id="12441351"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>INTERACTION WITH MUC1</scope>
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            <dbReference type="PubMed" id="12621058"/>
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        <scope>PHOSPHORYLATION AT SER-819</scope>
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            <dbReference type="PubMed" id="17081983"/>
            <dbReference type="DOI" id="10.1016/j.cell.2006.09.026"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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                <person name="Dephoure N."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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        <scope>ROLE IN PROTEOLYTICAL RELEASE OF JAM3</scope>
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    <reference key="10">
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            <dbReference type="PubMed" id="20188673"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2010.01.034"/>
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        <scope>PHOSPHORYLATION AT THR-735</scope>
        <scope>INTERACTION WITH MAPK14</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="12">
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                <person name="Blaydon D.C."/>
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            <dbReference type="PubMed" id="22010916"/>
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        <scope>INVOLVEMENT IN NISBD1</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-761 AND SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
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        <scope>FUNCTION</scope>
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        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Liver</tissue>
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        <scope>CATALYTIC ACTIVITY</scope>
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            </authorList>
            <dbReference type="PubMed" id="26876177"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2016.01.053"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2017" name="Neurosci. Lett." volume="660" first="109" last="114">
            <title>ADAM17 is the main sheddase for the generation of human triggering receptor expressed in myeloid cells (hTREM2) ectodomain and cleaves TREM2 after Histidine 157.</title>
            <authorList>
                <person name="Feuerbach D."/>
                <person name="Schindler P."/>
                <person name="Barske C."/>
                <person name="Joller S."/>
                <person name="Beng-Louka E."/>
                <person name="Worringer K.A."/>
                <person name="Kommineni S."/>
                <person name="Kaykas A."/>
                <person name="Ho D.J."/>
                <person name="Ye C."/>
                <person name="Welzenbach K."/>
                <person name="Elain G."/>
                <person name="Klein L."/>
                <person name="Brzak I."/>
                <person name="Mir A.K."/>
                <person name="Farady C.J."/>
                <person name="Aichholz R."/>
                <person name="Popp S."/>
                <person name="George N."/>
                <person name="Neumann U."/>
            </authorList>
            <dbReference type="PubMed" id="28923481"/>
            <dbReference type="DOI" id="10.1016/j.neulet.2017.09.034"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2017" name="PLoS Biol." volume="15" first="e2000080" last="e2000080">
            <title>Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation.</title>
            <authorList>
                <person name="Riethmueller S."/>
                <person name="Somasundaram P."/>
                <person name="Ehlers J.C."/>
                <person name="Hung C.W."/>
                <person name="Flynn C.M."/>
                <person name="Lokau J."/>
                <person name="Agthe M."/>
                <person name="Duesterhoeft S."/>
                <person name="Zhu Y."/>
                <person name="Groetzinger J."/>
                <person name="Lorenzen I."/>
                <person name="Koudelka T."/>
                <person name="Yamamoto K."/>
                <person name="Pickhinke U."/>
                <person name="Wichert R."/>
                <person name="Becker-Pauly C."/>
                <person name="Raedisch M."/>
                <person name="Albrecht A."/>
                <person name="Hessefort M."/>
                <person name="Stahnke D."/>
                <person name="Unverzagt C."/>
                <person name="Rose-John S."/>
                <person name="Tholey A."/>
                <person name="Garbers C."/>
            </authorList>
            <dbReference type="PubMed" id="28060820"/>
            <dbReference type="DOI" id="10.1371/journal.pbio.2000080"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2018" name="Elife" volume="7" first="0" last="0">
            <title>iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE.</title>
            <authorList>
                <person name="Oikonomidi I."/>
                <person name="Burbridge E."/>
                <person name="Cavadas M."/>
                <person name="Sullivan G."/>
                <person name="Collis B."/>
                <person name="Naegele H."/>
                <person name="Clancy D."/>
                <person name="Brezinova J."/>
                <person name="Hu T."/>
                <person name="Bileck A."/>
                <person name="Gerner C."/>
                <person name="Bolado A."/>
                <person name="von Kriegsheim A."/>
                <person name="Martin S.J."/>
                <person name="Steinberg F."/>
                <person name="Strisovsky K."/>
                <person name="Adrain C."/>
            </authorList>
            <dbReference type="PubMed" id="29897333"/>
            <dbReference type="DOI" id="10.7554/elife.35032"/>
        </citation>
        <scope>INTERACTION WITH RHBDF1 AND RHBDF2</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2018" name="Elife" volume="7" first="0" last="0">
            <title>FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex.</title>
            <authorList>
                <person name="Kuenzel U."/>
                <person name="Grieve A.G."/>
                <person name="Meng Y."/>
                <person name="Sieber B."/>
                <person name="Cowley S.A."/>
                <person name="Freeman M."/>
            </authorList>
            <dbReference type="PubMed" id="29897336"/>
            <dbReference type="DOI" id="10.7554/elife.35012"/>
        </citation>
        <scope>INTERACTION WITH FRMD8; RHBDF1 AND RHBDF2</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2022" name="Cells" volume="11" first="0" last="0">
            <title>Tetraspanin 8 Subfamily Members Regulate Substrate-Specificity of a Disintegrin and Metalloprotease 17.</title>
            <authorList>
                <person name="Mueller M."/>
                <person name="Saunders C."/>
                <person name="Senftleben A."/>
                <person name="Heidbuechel J.P.W."/>
                <person name="Halwachs B."/>
                <person name="Bolik J."/>
                <person name="Hedemann N."/>
                <person name="Roeder C."/>
                <person name="Bauerschlag D."/>
                <person name="Rose-John S."/>
                <person name="Schmidt-Arras D."/>
            </authorList>
            <dbReference type="PubMed" id="36078095"/>
            <dbReference type="DOI" id="10.3390/cells11172683"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TSPAN8</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="1998" name="Proc. Natl. Acad. Sci. U.S.A." volume="95" first="3408" last="3412">
            <title>Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.</title>
            <authorList>
                <person name="Maskos K."/>
                <person name="Fernandez-Catalan C."/>
                <person name="Huber R."/>
                <person name="Bourenkov G.P."/>
                <person name="Bartunik H."/>
                <person name="Ellestad G.A."/>
                <person name="Reddy P."/>
                <person name="Wolfson M.F."/>
                <person name="Rauch C.T."/>
                <person name="Castner B.J."/>
                <person name="Davis R."/>
                <person name="Clarke H.R.G."/>
                <person name="Petersen M."/>
                <person name="Fitzner J.N."/>
                <person name="Cerretti D.P."/>
                <person name="March C.J."/>
                <person name="Paxton R.J."/>
                <person name="Black R.A."/>
                <person name="Bode W."/>
            </authorList>
            <dbReference type="PubMed" id="9520379"/>
            <dbReference type="DOI" id="10.1073/pnas.95.7.3408"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473 IN COMPLEX WITH ZINC</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVE SITE</scope>
        <scope>DISULFIDE BONDS</scope>
    </reference>
    <comment type="function">
        <text evidence="2 10 13 15 16 17 18 19 20 22 23">Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity (PubMed:24226769, PubMed:24227843, PubMed:28060820, PubMed:28923481). Cleaves the membrane-bound precursor of TNF to its mature soluble form (PubMed:36078095, PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells. Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:28923481).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 13 16 20">
            <text>Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNFalpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.</text>
            <dbReference type="EC" id="3.4.24.86"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="24">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="24">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="10 12 21 22">Interacts with MAD2L1, MAPK14 and MUC1 (PubMed:12441351, PubMed:20188673). Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2 (PubMed:29897333). Interacts with FRMD8 via its interaction with iRhom1/RHBDF1 and iRhom2/RHBDF2 (PubMed:29897333). Interacts with TSPAN8 (PubMed:36078095).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-357481">
            <id>Q12959</id>
            <label>DLG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-80426">
            <id>Q15700</id>
            <label>DLG2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-80440">
            <id>Q92796</id>
            <label>DLG3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-80389">
            <id>P78352</id>
            <label>DLG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-8550965">
            <id>Q13585</id>
            <label>GPR50</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-703066">
            <id>P05556</id>
            <label>ITGB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-78203">
            <id>Q13257</id>
            <label>MAD2L1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-311035">
            <id>Q86UL8</id>
            <label>MAGI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-1047946">
            <id>P26045</id>
            <label>PTPN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-78188">
            <id>P78536</id>
        </interactant>
        <interactant intactId="EBI-647271">
            <id>Q80WQ6</id>
            <label>Rhbdf2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="22">Cell membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P78536-1</id>
            <name>A</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P78536-2</id>
            <name>B</name>
            <sequence type="described" ref="VSP_005478"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="17">Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney. Expressed in natural killer cells (at protein level) (PubMed:24337742).</text>
    </comment>
    <comment type="induction">
        <text>In arthritis-affected cartilage.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity).</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9 11 12">Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at Thr-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.</text>
    </comment>
    <comment type="disease" evidence="14">
        <disease id="DI-03306">
            <name>Inflammatory skin and bowel disease, neonatal, 1</name>
            <acronym>NISBD1</acronym>
            <description>A disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.</description>
            <dbReference type="MIM" id="614328"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme"/>
        <text>Tumor necrosis factor alpha-converting enzyme entry</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/572/ADAM17"/>
    </comment>
    <dbReference type="EC" id="3.4.24.86" evidence="10 13 16 20"/>
    <dbReference type="EMBL" id="U86755">
        <property type="protein sequence ID" value="AAB51586.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U69611">
        <property type="protein sequence ID" value="AAB51514.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U69612">
        <property type="protein sequence ID" value="AAB53014.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U92649">
        <property type="protein sequence ID" value="AAC39721.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1665.1">
        <molecule id="P78536-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003174.3">
        <molecule id="P78536-1"/>
        <property type="nucleotide sequence ID" value="NM_003183.5"/>
    </dbReference>
    <dbReference type="PDB" id="1BKC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/C/E/I=219-474"/>
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    <dbReference type="PDB" id="1ZXC">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.28 A"/>
        <property type="chains" value="A/B=215-477"/>
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    <dbReference type="PDB" id="2A8H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="A/B=215-477"/>
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    <dbReference type="PDB" id="2DDF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A/B=218-474"/>
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    <dbReference type="PDB" id="2FV5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A/B=216-475"/>
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    <dbReference type="PDB" id="2FV9">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.02 A"/>
        <property type="chains" value="A/B=218-475"/>
    </dbReference>
    <dbReference type="PDB" id="2I47">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B/C/D=212-492"/>
    </dbReference>
    <dbReference type="PDB" id="2M2F">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=581-642"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B=215-477"/>
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        <property type="resolution" value="2.10 A"/>
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        <property type="resolution" value="1.92 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.75 A"/>
        <property type="chains" value="A/B=215-476"/>
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        <property type="resolution" value="1.85 A"/>
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        <property type="resolution" value="2.00 A"/>
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        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A/B=215-476"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.88 A"/>
        <property type="chains" value="A/B=215-476"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="B=813-824"/>
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    <dbReference type="PDB" id="8SNL">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.78 A"/>
        <property type="chains" value="A=1-824"/>
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    <dbReference type="PDB" id="8SNN">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.32 A"/>
        <property type="chains" value="A=215-824"/>
    </dbReference>
    <dbReference type="PDB" id="8SNO">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.78 A"/>
        <property type="chains" value="A=215-824"/>
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    <dbReference type="PDB" id="9E6K">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.15 A"/>
        <property type="chains" value="C=530-644"/>
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    <dbReference type="PDBsum" id="1BKC"/>
    <dbReference type="PDBsum" id="1ZXC"/>
    <dbReference type="PDBsum" id="2A8H"/>
    <dbReference type="PDBsum" id="2DDF"/>
    <dbReference type="PDBsum" id="2FV5"/>
    <dbReference type="PDBsum" id="2FV9"/>
    <dbReference type="PDBsum" id="2I47"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
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    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
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    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
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            <begin position="741"/>
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="8">
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="8">
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    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="184"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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        <location>
            <position position="405"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
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    <feature type="binding site" evidence="24">
        <location>
            <position position="409"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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    <feature type="binding site" evidence="24">
        <location>
            <position position="415"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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            <position position="735"/>
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        <location>
            <position position="761"/>
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            <position position="767"/>
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        <location>
            <position position="791"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="11">
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            <position position="819"/>
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        <location>
            <position position="103"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="157"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="174"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="264"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="452"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="498"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="539"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="551"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="594"/>
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    <feature type="disulfide bond" evidence="24">
        <location>
            <begin position="225"/>
            <end position="333"/>
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    <feature type="disulfide bond" evidence="24">
        <location>
            <begin position="365"/>
            <end position="469"/>
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    <feature type="disulfide bond" evidence="24">
        <location>
            <begin position="423"/>
            <end position="453"/>
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    <feature type="disulfide bond" evidence="1">
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            <begin position="534"/>
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    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="573"/>
            <end position="582"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="578"/>
            <end position="591"/>
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    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="593"/>
            <end position="600"/>
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    </feature>
    <feature type="splice variant" id="VSP_005478" description="In isoform B." evidence="25">
        <location>
            <begin position="695"/>
            <end position="824"/>
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    <feature type="sequence variant" id="VAR_051586" description="In dbSNP:rs34431503.">
        <original>K</original>
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        <location>
            <position position="162"/>
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    <feature type="sequence variant" id="VAR_051587" description="In dbSNP:rs2230818.">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="202"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAC39721." evidence="26" ref="3">
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        <variation>A</variation>
        <location>
            <position position="109"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAC39721." evidence="26" ref="3">
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        <location>
            <position position="563"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAC39721." evidence="26" ref="3">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="801"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAC39721." evidence="26" ref="3">
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        <variation>N</variation>
        <location>
            <position position="818"/>
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        <location>
            <begin position="33"/>
            <end position="38"/>
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    </feature>
    <feature type="strand" evidence="41">
        <location>
            <begin position="39"/>
            <end position="43"/>
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    </feature>
    <feature type="helix" evidence="41">
        <location>
            <begin position="47"/>
            <end position="49"/>
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    </feature>
    <feature type="strand" evidence="41">
        <location>
            <begin position="50"/>
            <end position="53"/>
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    </feature>
    <feature type="strand" evidence="41">
        <location>
            <begin position="65"/>
            <end position="73"/>
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    </feature>
    <feature type="strand" evidence="41">
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            <begin position="78"/>
            <end position="85"/>
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    </feature>
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            <begin position="87"/>
            <end position="89"/>
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    <feature type="strand" evidence="41">
        <location>
            <begin position="96"/>
            <end position="99"/>
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    <feature type="strand" evidence="41">
        <location>
            <begin position="104"/>
            <end position="107"/>
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        <location>
            <begin position="111"/>
            <end position="113"/>
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    <feature type="strand" evidence="41">
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            <begin position="114"/>
            <end position="119"/>
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    <feature type="strand" evidence="41">
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            <begin position="122"/>
            <end position="130"/>
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    <feature type="strand" evidence="41">
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            <begin position="137"/>
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            <begin position="146"/>
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            <begin position="152"/>
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        <location>
            <begin position="191"/>
            <end position="193"/>
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            <begin position="220"/>
            <end position="222"/>
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        <location>
            <begin position="224"/>
            <end position="231"/>
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            <begin position="233"/>
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            <begin position="239"/>
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    <reference key="1">
        <citation type="submission" date="2001-10" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Guo J.H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
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    <reference key="2">
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                <person name="Omura Y."/>
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                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
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                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT GLU-44</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
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                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT GLU-44</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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            <authorList>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.</title>
            <authorList>
                <person name="Krausz C."/>
                <person name="Riera-Escamilla A."/>
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                <person name="Holleman K."/>
                <person name="Cioppi F."/>
                <person name="Algaba F."/>
                <person name="Pybus M."/>
                <person name="Friedrich C."/>
                <person name="Wyrwoll M.J."/>
                <person name="Casamonti E."/>
                <person name="Pietroforte S."/>
                <person name="Nagirnaja L."/>
                <person name="Lopes A.M."/>
                <person name="Kliesch S."/>
                <person name="Pilatz A."/>
                <person name="Carrell D.T."/>
                <person name="Conrad D.F."/>
                <person name="Ars E."/>
                <person name="Ruiz-Castane E."/>
                <person name="Aston K.I."/>
                <person name="Baarends W.M."/>
                <person name="Tuettelmann F."/>
            </authorList>
            <dbReference type="PubMed" id="32741963"/>
            <dbReference type="DOI" id="10.1038/s41436-020-0907-1"/>
        </citation>
        <scope>VARIANT 314-GLN--ASN-583 DEL</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Required for male fertility and normal male germ cell differentiation.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">Diffusely cytoplasmic early in pachytene spermatocytes and coalesces into several perinuclear granules by late pachynema.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NCV1-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NCV1-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_029230 VSP_029231"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the ADAD family.</text>
    </comment>
    <dbReference type="EMBL" id="AF447586">
        <property type="protein sequence ID" value="AAM22869.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK093046">
        <property type="protein sequence ID" value="BAC04032.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK315171">
        <property type="protein sequence ID" value="BAG37613.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="CH471114">
        <property type="protein sequence ID" value="EAW95491.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471114">
        <property type="protein sequence ID" value="EAW95492.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC033491">
        <property type="protein sequence ID" value="AAH33491.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS10944.1">
        <molecule id="Q8NCV1-2"/>
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        <molecule id="Q8NCV1-1"/>
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    <dbReference type="RefSeq" id="NP_001138872.1">
        <molecule id="Q8NCV1-1"/>
        <property type="nucleotide sequence ID" value="NM_001145400.2"/>
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    <dbReference type="RefSeq" id="NP_631913.3">
        <molecule id="Q8NCV1-2"/>
        <property type="nucleotide sequence ID" value="NM_139174.3"/>
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    <dbReference type="AlphaFoldDB" id="Q8NCV1"/>
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        <property type="interactions" value="10"/>
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    <dbReference type="FunCoup" id="Q8NCV1">
        <property type="interactions" value="588"/>
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    <dbReference type="IntAct" id="Q8NCV1">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000268624"/>
    <dbReference type="GlyGen" id="Q8NCV1">
        <property type="glycosylation" value="1 site"/>
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    <dbReference type="iPTMnet" id="Q8NCV1"/>
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    <dbReference type="BioMuta" id="ADAD2"/>
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        <molecule id="Q8NCV1-1"/>
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    <dbReference type="ProteomicsDB" id="72952">
        <molecule id="Q8NCV1-2"/>
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    <dbReference type="Antibodypedia" id="30571">
        <property type="antibodies" value="70 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="161931"/>
    <dbReference type="Ensembl" id="ENST00000268624.7">
        <molecule id="Q8NCV1-2"/>
        <property type="protein sequence ID" value="ENSP00000268624.3"/>
        <property type="gene ID" value="ENSG00000140955.12"/>
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    <dbReference type="Ensembl" id="ENST00000315906.10">
        <molecule id="Q8NCV1-1"/>
        <property type="protein sequence ID" value="ENSP00000325153.6"/>
        <property type="gene ID" value="ENSG00000140955.12"/>
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    <dbReference type="GeneID" id="161931"/>
    <dbReference type="KEGG" id="hsa:161931"/>
    <dbReference type="MANE-Select" id="ENST00000315906.10">
        <property type="protein sequence ID" value="ENSP00000325153.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001145400.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001138872.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002fhq.3">
        <molecule id="Q8NCV1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:30714"/>
    <dbReference type="ClinPGx" id="PA162375591"/>
    <dbReference type="CTD" id="161931"/>
    <dbReference type="DisGeNET" id="161931"/>
    <dbReference type="GeneCards" id="ADAD2"/>
    <dbReference type="HGNC" id="HGNC:30714">
        <property type="gene designation" value="ADAD2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000140955">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="619532">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000140955"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000140955"/>
    <dbReference type="eggNOG" id="KOG2777">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161900"/>
    <dbReference type="HOGENOM" id="CLU_005382_4_2_1"/>
    <dbReference type="InParanoid" id="Q8NCV1"/>
    <dbReference type="OMA" id="WCLGDED"/>
    <dbReference type="OrthoDB" id="10268011at2759"/>
    <dbReference type="PAN-GO" id="Q8NCV1">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NCV1"/>
    <dbReference type="PathwayCommons" id="Q8NCV1"/>
    <dbReference type="Agora" id="ENSG00000140955"/>
    <dbReference type="BioGRID-ORCS" id="161931">
        <property type="hits" value="17 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="161931"/>
    <dbReference type="Pharos" id="Q8NCV1">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NCV1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 16"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NCV1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000140955">
        <property type="expression patterns" value="Expressed in right testis and 133 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8NCV1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003726">
        <property type="term" value="F:double-stranded RNA adenosine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003725">
        <property type="term" value="F:double-stranded RNA binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008251">
        <property type="term" value="F:tRNA-specific adenosine deaminase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006382">
        <property type="term" value="P:adenosine to inosine editing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0006396">
        <property type="term" value="P:RNA processing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007286">
        <property type="term" value="P:spermatid development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd19906">
        <property type="entry name" value="DSRM_ADAD2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.160.20:FF:000056">
        <property type="entry name" value="Adenosine deaminase domain-containing 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.160.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002466">
        <property type="entry name" value="A_deamin"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044454">
        <property type="entry name" value="ADAD2_DSRM"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR014720">
        <property type="entry name" value="dsRBD_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10910:SF106">
        <property type="entry name" value="ADENOSINE DEAMINASE DOMAIN-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10910">
        <property type="entry name" value="EUKARYOTE SPECIFIC DSRNA BINDING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02137">
        <property type="entry name" value="A_deamin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00035">
        <property type="entry name" value="dsrm"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00552">
        <property type="entry name" value="ADEAMc"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54768">
        <property type="entry name" value="dsRNA-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50141">
        <property type="entry name" value="A_DEAMIN_EDITASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50137">
        <property type="entry name" value="DS_RBD"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0694">RNA-binding</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <feature type="chain" id="PRO_0000309524" description="Adenosine deaminase domain-containing protein 2">
        <location>
            <begin position="1"/>
            <end position="583"/>
        </location>
    </feature>
    <feature type="domain" description="DRBM" evidence="3">
        <location>
            <begin position="115"/>
            <end position="181"/>
        </location>
    </feature>
    <feature type="domain" description="A to I editase" evidence="2">
        <location>
            <begin position="261"/>
            <end position="582"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029230" description="In isoform 2." evidence="8">
        <original>P</original>
        <variation>PGKVFKYRAPGGEELKAMCLWQVEVLRAFLLRTGWRGLWRGDLDLGPDSSWANRLPFLLICEMESRIPAVEEL</variation>
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_029231" description="In isoform 2." evidence="8">
        <original>R</original>
        <variation>RGWAVSAPSCT</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036976" description="In dbSNP:rs8044695." evidence="5 7">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="44"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055650" description="In dbSNP:rs11149631.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_087421" description="Found in a patient with non-obstructive azoospermia; uncertain significance." evidence="6">
        <location>
            <begin position="314"/>
            <end position="583"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9D5P4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00240"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00266"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="32741963"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000312" key="10">
        <source>
            <dbReference type="HGNC" id="HGNC:30714"/>
        </source>
    </evidence>
    <sequence length="583" mass="61755" checksum="8F1566C88111FAD7" modified="2002-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-11-01" modified="2026-01-28" version="241" xmlns="https://uniprot.org/uniprot">
    <accession>P08913</accession>
    <accession>B0LPF6</accession>
    <accession>Q2I8G2</accession>
    <accession>Q2XN99</accession>
    <accession>Q86TH8</accession>
    <accession>Q9BZK1</accession>
    <name>ADA2A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="16">Alpha-2A adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-2 adrenergic receptor subtype C10</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-2A adrenoreceptor</fullName>
            <shortName>Alpha-2A adrenoceptor</shortName>
            <shortName>Alpha-2AAR</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="18" type="primary">ADRA2A</name>
        <name type="synonym">ADRA2R</name>
        <name type="synonym">ADRAR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="J. Biol. Chem." volume="264" first="11754" last="11761">
            <title>Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation.</title>
            <authorList>
                <person name="Fraser C.M."/>
                <person name="Arakawa S."/>
                <person name="McCombie W.R."/>
                <person name="Venter J.C."/>
            </authorList>
            <dbReference type="PubMed" id="2568356"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)80130-2"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1990" name="J. Biol. Chem." volume="265" first="17307" last="17317">
            <title>Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs.</title>
            <authorList>
                <person name="Guyer C.A."/>
                <person name="Horstman D.A."/>
                <person name="Wilson A.L."/>
                <person name="Clark J.D."/>
                <person name="Kragoe E.J. Jr."/>
                <person name="Limbird L.E."/>
            </authorList>
            <dbReference type="PubMed" id="2170371"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(17)44904-0"/>
        </citation>
        <scope>SEQUENCE REVISION TO 333-365</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Proc. Natl. Acad. Sci. U.S.A." volume="103" first="5472" last="5477">
            <title>Complex haplotypes derived from noncoding polymorphisms of the intronless alpha-2A-adrenergic gene diversify receptor expression.</title>
            <authorList>
                <person name="Small K.M."/>
                <person name="Brown K.M."/>
                <person name="Seman C.A."/>
                <person name="Theiss C.T."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="16567612"/>
            <dbReference type="DOI" id="10.1073/pnas.0601345103"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2000-07" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning and expression of human alpha-2A adrenergic receptor in SY5Y cells.</title>
            <authorList>
                <person name="Mao Z.-M."/>
                <person name="Tang K."/>
                <person name="Li B.-M."/>
                <person name="Jing N.-H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2000-08" db="EMBL/GenBank/DDBJ databases">
            <title>A search for genetic variability in the human alpha-2 adrenergic receptor on chromosome 10.</title>
            <authorList>
                <person name="Castellano M."/>
                <person name="Giacche' M."/>
                <person name="Rossi F."/>
                <person name="Rivadossi F."/>
                <person name="Perani C."/>
                <person name="Beschi M."/>
                <person name="Agabiti Rosei E."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2001-04" db="EMBL/GenBank/DDBJ databases">
            <title>Human alpha-2A adrenergic receptor gene and the genotype of -1296 nucleotide and motionsickness.</title>
            <authorList>
                <person name="Liu L."/>
                <person name="Yuan L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-11" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="SeattleSNPs variation discovery resource"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT LYS-266</scope>
    </reference>
    <reference key="8">
        <citation type="submission" date="2007-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NHLBI resequencing and genotyping service (RS&amp;G)"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
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                <person name="Johnson D."/>
                <person name="Kana A."/>
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                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
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                <person name="Lawlor S."/>
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                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
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                <person name="Loveland J."/>
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                <person name="McLaren S."/>
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                <person name="McMurray A."/>
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                <person name="Matthews L."/>
                <person name="Milne S."/>
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                <person name="Palmer S.A."/>
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                <person name="Rogosin A."/>
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                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="10">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>PNS</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="11">
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            <title>Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor.</title>
            <authorList>
                <person name="Kobilka B.K."/>
                <person name="Matsui H."/>
                <person name="Kobilka T.S."/>
                <person name="Yang-Feng T.L."/>
                <person name="Francke U."/>
                <person name="Caron M.G."/>
                <person name="Lefkowitz R.J."/>
                <person name="Regan J.W."/>
            </authorList>
            <dbReference type="PubMed" id="2823383"/>
            <dbReference type="DOI" id="10.1126/science.2823383"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 7-465</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
    <reference key="12">
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            <title>An Asn to Lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling.</title>
            <authorList>
                <person name="Small K.M."/>
                <person name="Forbes S.L."/>
                <person name="Brown K.M."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="10948191"/>
            <dbReference type="DOI" id="10.1074/jbc.m004550200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 16-465</scope>
        <scope>VARIANT LYS-266</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1991" name="FEBS Lett." volume="280" first="241" last="244">
            <title>Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR.</title>
            <authorList>
                <person name="Chhajlani V."/>
                <person name="Rangel N."/>
                <person name="Uhlen S."/>
                <person name="Wikberg J.E.S."/>
            </authorList>
            <dbReference type="PubMed" id="1849485"/>
            <dbReference type="DOI" id="10.1016/0014-5793(91)80301-i"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 92-224</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1991" name="J. Biol. Chem." volume="266" first="15488" last="15492">
            <title>A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists.</title>
            <authorList>
                <person name="Suryanarayana S."/>
                <person name="Daunt D.A."/>
                <person name="von Zastrow M."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="1678390"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)98642-4"/>
        </citation>
        <scope>MUTAGENESIS OF PHE-427</scope>
    </reference>
    <reference key="15">
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            <title>Site-directed mutagenesis of alpha 2a-adrenergic receptors: Identification of amino acids involved in ligand binding and receptor activation by agonists.</title>
            <authorList>
                <person name="Wang C.-D."/>
                <person name="Buck M.A."/>
                <person name="Fraser C.M."/>
            </authorList>
            <dbReference type="PubMed" id="1678850"/>
        </citation>
        <scope>MUTAGENESIS OF ASPARTIC ACID AND SERINE RESIDUES</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2012" name="J. Biol. Chem." volume="287" first="42784" last="42794">
            <title>Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi.</title>
            <authorList>
                <person name="Li C."/>
                <person name="Fan Y."/>
                <person name="Lan T.H."/>
                <person name="Lambert N.A."/>
                <person name="Wu G."/>
            </authorList>
            <dbReference type="PubMed" id="23105096"/>
            <dbReference type="DOI" id="10.1074/jbc.m112.410936"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="19 20 21 22" key="17">
        <citation type="journal article" date="2002" name="Biochemistry" volume="41" first="3596" last="3604">
            <title>NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix.</title>
            <authorList>
                <person name="Chung D.A."/>
                <person name="Zuiderweg E.R.P."/>
                <person name="Fowler C.B."/>
                <person name="Soyer O.S."/>
                <person name="Mosberg H.I."/>
                <person name="Neubig R.R."/>
            </authorList>
            <dbReference type="PubMed" id="11888275"/>
            <dbReference type="DOI" id="10.1021/bi015811+"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 133-164</scope>
        <scope>PROBABLE MEMBRANE TOPOLOGY</scope>
    </reference>
    <reference evidence="23 24 25 26" key="18">
        <citation type="journal article" date="2022" name="Sci. Adv." volume="8" first="eabj5347" last="eabj5347">
            <title>Structural insights into ligand recognition, activation, and signaling of the alpha2A adrenergic receptor.</title>
            <authorList>
                <person name="Xu J."/>
                <person name="Cao S."/>
                <person name="Hubner H."/>
                <person name="Weikert D."/>
                <person name="Chen G."/>
                <person name="Lu Q."/>
                <person name="Yuan D."/>
                <person name="Gmeiner P."/>
                <person name="Liu Z."/>
                <person name="Du Y."/>
            </authorList>
            <dbReference type="PubMed" id="35245122"/>
            <dbReference type="DOI" id="10.1126/sciadv.abj5347"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) IN COMPLEX WITH G PROTEINS AND NORADRENALINE</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-128; SER-215; TYR-409; PHE-427 AND TYR-431</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2016" name="JCI Insight" volume="1" first="0" last="0">
            <title>Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy.</title>
            <authorList>
                <person name="Garg A."/>
                <person name="Sankella S."/>
                <person name="Xing C."/>
                <person name="Agarwal A.K."/>
            </authorList>
            <dbReference type="PubMed" id="27376152"/>
            <dbReference type="DOI" id="10.1172/jci.insight.86870"/>
        </citation>
        <scope>VARIANT FPLD8 PHE-68</scope>
        <scope>CHARACTERIZATION OF VARIANT FPLD8 PHE-68</scope>
        <scope>INVOLVEMENT IN FPLD8</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 10 11 12 13 14">Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression (PubMed:2170371, PubMed:23105096, PubMed:2568356, PubMed:35245122, PubMed:27376152). Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release (PubMed:2568356, PubMed:27376152). ADRA2A and ADRA2C mediates the presynaptic feedback inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems. ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C modulates neurotransmission at lower levels of nerve activity (By similarity). The rank order of potency for agonists of ADRA2A is oxymetazoline &gt; clonidine &gt; epinephrine &gt; norepinephrine &gt; phenylephrine &gt; dopamine &gt; p-synephrine &gt; p-tyramine &gt; serotonin = p-octopamine. For antagonists, the rank order is yohimbine &gt; phentolamine = mianserine &gt; chlorpromazine = spiperone = prazosin &gt; propanolol &gt; alprenolol = pindolol (PubMed:2170371, PubMed:2568356).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Cell membrane</location>
            <topology evidence="14">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="13">
        <disease id="DI-06825">
            <name>Lipodystrophy, familial partial, 8</name>
            <acronym>FPLD8</acronym>
            <description>An autosomal dominant form of partial lipodystrophy, a disorder characterized by abnormal subcutaneous fat distribution. FPLD8 patients show selective loss of subcutaneous adipose tissue from the limbs, beginning around 13 to 15 years of age, and abnormal accumulation of subcutaneous adipose tissue in the dorsal neck and face, as well as in the posterior thoracic and abdominal regions. The disorder is associated with metabolic abnormalities, including diabetes mellitus and hyperlipidemia.</description>
            <dbReference type="MIM" id="620679"/>
        </disease>
        <text>The disease may be caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="17">It is uncertain whether Met-1 or Met-16 is the initiator.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA51664" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA51664" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA51665" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA51665" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAG00447" version="2"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH35047" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH50414" version="4"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAK26743" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAK51162" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAZ73101" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="ABB72683" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="ABY87535" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="M23533">
        <property type="protein sequence ID" value="AAA51665.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ149926">
        <property type="protein sequence ID" value="AAZ73101.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF284095">
        <property type="protein sequence ID" value="AAK26743.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF262016">
        <property type="protein sequence ID" value="AAG00447.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY032736">
        <property type="protein sequence ID" value="AAK51162.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ285607">
        <property type="protein sequence ID" value="ABB72683.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EU332846">
        <property type="protein sequence ID" value="ABY87535.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158163">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC035047">
        <property type="protein sequence ID" value="AAH35047.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC050414">
        <property type="protein sequence ID" value="AAH50414.4"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M18415">
        <property type="protein sequence ID" value="AAA51664.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF281308">
        <property type="protein sequence ID" value="AAF91441.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF316894">
        <property type="protein sequence ID" value="AAK01634.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7569.2"/>
    <dbReference type="PIR" id="A34169">
        <property type="entry name" value="A34169"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000672.3">
        <property type="nucleotide sequence ID" value="NM_000681.3"/>
    </dbReference>
    <dbReference type="PDB" id="1HLL">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=133-164"/>
    </dbReference>
    <dbReference type="PDB" id="1HO9">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=133-164"/>
    </dbReference>
    <dbReference type="PDB" id="1HOD">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=133-164"/>
    </dbReference>
    <dbReference type="PDB" id="1HOF">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=133-164"/>
    </dbReference>
    <dbReference type="PDB" id="6K42">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.10 A"/>
        <property type="chains" value="R=37-44"/>
    </dbReference>
    <dbReference type="PDB" id="6KUX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=35-460"/>
    </dbReference>
    <dbReference type="PDB" id="6KUY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A=35-460"/>
    </dbReference>
    <dbReference type="PDB" id="7EJ0">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="7EJ8">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="7EJA">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="7EJK">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="7W6P">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.47 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="7W7E">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="R=1-465"/>
    </dbReference>
    <dbReference type="PDB" id="9CBL">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.80 A"/>
        <property type="chains" value="R=35-460"/>
    </dbReference>
    <dbReference type="PDB" id="9CBM">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="R=35-460"/>
    </dbReference>
    <dbReference type="PDB" id="9IQR">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="B=38-456"/>
    </dbReference>
    <dbReference type="PDB" id="9PLN">
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        <property type="resolution" value="2.80 A"/>
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        <property type="project" value="Ensembl"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Rhodopsin 7-helix transmembrane proteins"/>
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        <property type="entry name" value="ADR_fam"/>
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        <property type="entry name" value="GPCR_Rhodpsn_7TM"/>
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    <dbReference type="PANTHER" id="PTHR24248">
        <property type="entry name" value="ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ALPHA-2A ADRENERGIC RECEPTOR"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00001">
        <property type="entry name" value="7tm_1"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADRENERGICR"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="Family A G protein-coupled receptor-like"/>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_1"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="G_PROTEIN_RECEP_F1_2"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0297">G-protein coupled receptor</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0449">Lipoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0564">Palmitate</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0675">Receptor</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0807">Transducer</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
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            <end position="71"/>
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            <begin position="72"/>
            <end position="85"/>
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            <end position="107"/>
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            <end position="120"/>
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            <begin position="121"/>
            <end position="144"/>
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    </feature>
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            <begin position="145"/>
            <end position="167"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="14 23">
        <location>
            <begin position="168"/>
            <end position="181"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="17">
        <location>
            <begin position="182"/>
            <end position="208"/>
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    <feature type="transmembrane region" description="Helical; Name=5" evidence="14 23">
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            <begin position="209"/>
            <end position="232"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="17">
        <location>
            <begin position="233"/>
            <end position="388"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="14 23">
        <location>
            <begin position="389"/>
            <end position="413"/>
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    </feature>
    <feature type="topological domain" description="Extracellular" evidence="17">
        <location>
            <begin position="414"/>
            <end position="421"/>
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    </feature>
    <feature type="transmembrane region" description="Helical; Name=7" evidence="14 23">
        <location>
            <begin position="422"/>
            <end position="443"/>
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    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="17">
        <location>
            <begin position="444"/>
            <end position="465"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="242"/>
            <end position="368"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="313"/>
            <end position="330"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in norepinephrine binding" evidence="9 14">
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in catechol and norepinephrine agonist binding and receptor activation" evidence="9 14">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in catechol agonist binding and receptor activation" evidence="9">
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in norepinephrine binding and receptor activation" evidence="14">
        <location>
            <position position="409"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in norepinephrine binding and receptor activation" evidence="14">
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="site" description="Implicated in norepinephrine binding and receptor activation" evidence="14">
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="346"/>
        </location>
    </feature>
    <feature type="modified residue" description="Omega-N-methylarginine" evidence="3">
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="1">
        <location>
            <position position="457"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="5 14 23">
        <location>
            <begin position="121"/>
            <end position="203"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089227" description="In FPLD8; uncertain significance; decreased function in adenylate cyclase-inhibiting adrenergic receptor signaling pathway; dbSNP:rs1224440739." evidence="13">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_014957" description="40% increase in agonist-promoted Gi coupling; dbSNP:rs1800035." evidence="7 15">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055908" description="In dbSNP:rs35658213.">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="416"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No change in binding affinity. Eliminates guanine nucleotide-sensitive agonist binding." evidence="9">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of receptor activation by norepinephrine." evidence="14">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No binding to yohimbine. Increase in adenylate cyclase activity." evidence="9">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Lower affinity for agonists. Eliminates guanine nucleotide-sensitive agonist binding." evidence="9">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="145"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Lower affinity for agonists. No change in guanine nucleotide-sensitive agonist binding. Impaired receptor activation by norepinephrine." evidence="9 14">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Lower affinity for agonists. Reduced guanine nucleotide-sensitive agonist binding." evidence="9">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired receptor activation by norepinephrine." evidence="14">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="409"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired receptor activation by norepinephrine." evidence="14">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="350-fold reduced affinity for alpha-2 antagonist yohimbine, 3000-fold increase for beta-antagonist alprenolol." evidence="8">
        <original>F</original>
        <variation>N</variation>
        <location>
            <position position="427"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired receptor activation by norepinephrine." evidence="14">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="431"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; AAA51664." evidence="17" ref="11">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 13." evidence="17" ref="13">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="139"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; AAA51664." evidence="17" ref="11">
        <original>V</original>
        <variation>C</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; AAA51664." evidence="17" ref="11">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="383"/>
        </location>
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    <feature type="strand" evidence="28">
        <location>
            <begin position="45"/>
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        <location>
            <begin position="49"/>
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    <feature type="strand" evidence="27">
        <location>
            <begin position="76"/>
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    <feature type="helix" evidence="27">
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    <feature type="helix" evidence="27">
        <location>
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    <feature type="helix" evidence="27">
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    <feature type="strand" evidence="28">
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    <feature type="helix" evidence="27">
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            <begin position="118"/>
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    <feature type="helix" evidence="27">
        <location>
            <begin position="153"/>
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    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="162"/>
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    <feature type="turn" evidence="27">
        <location>
            <begin position="209"/>
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    <feature type="helix" evidence="27">
        <location>
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    <feature type="helix" evidence="27">
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            <begin position="221"/>
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    <feature type="helix" evidence="27">
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    <feature type="helix" evidence="27">
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    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P22909"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q01338"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10948191"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="1678390"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="1678850"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="2170371"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="23105096"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="2568356"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="27376152"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="35245122"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="10948191"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0000312" key="18">
        <source>
            <dbReference type="HGNC" id="HGNC:281"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PDB" id="1HLL"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PDB" id="1HO9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PDB" id="1HOD"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PDB" id="1HOF"/>
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    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PDB" id="7EJ0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PDB" id="7EJ8"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PDB" id="7EJA"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PDB" id="7EJK"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="6KUX"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="7EJ8"/>
        </source>
    </evidence>
    <sequence length="465" mass="50647" checksum="585E576149BDB696" modified="2019-12-11" version="4">MFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGGPQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSDHAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKASRWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKKILCRGDRKRIV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-15" modified="2026-01-28" version="155" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BUB4</accession>
    <accession>Q9NVB7</accession>
    <accession>Q9UNG3</accession>
    <name>ADAT1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>tRNA-specific adenosine deaminase 1</fullName>
            <shortName>hADAT1</shortName>
            <ecNumber>3.5.4.34</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>tRNA-specific adenosine-37 deaminase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAT1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Proc. Natl. Acad. Sci. U.S.A." volume="96" first="8895" last="8900">
            <title>Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes.</title>
            <authorList>
                <person name="Maas S."/>
                <person name="Gerber A.P."/>
                <person name="Rich A."/>
            </authorList>
            <dbReference type="PubMed" id="10430867"/>
            <dbReference type="DOI" id="10.1073/pnas.96.16.8895"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT ASN-167</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>Specifically deaminates adenosine-37 to inosine in tRNA-Ala.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>adenosine(37) in tRNA(Ala) + H2O + H(+) = inosine(37) in tRNA(Ala) + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:50968"/>
            <dbReference type="Rhea" id="RHEA-COMP:12855"/>
            <dbReference type="Rhea" id="RHEA-COMP:12856"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:74411"/>
            <dbReference type="ChEBI" id="CHEBI:82852"/>
            <dbReference type="EC" id="3.5.4.34"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>1D-myo-inositol hexakisphosphate</name>
            <dbReference type="ChEBI" id="CHEBI:58130"/>
        </cofactor>
        <text evidence="1">Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BUB4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BUB4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_025579"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Ubiquitously expressed.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the ADAT1 family.</text>
    </comment>
    <dbReference type="EC" id="3.5.4.34"/>
    <dbReference type="EMBL" id="AF125188">
        <property type="protein sequence ID" value="AAD48376.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001687">
        <property type="protein sequence ID" value="BAA91837.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002758">
        <property type="protein sequence ID" value="AAH02758.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10922.1">
        <molecule id="Q9BUB4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311373.1">
        <molecule id="Q9BUB4-2"/>
        <property type="nucleotide sequence ID" value="NM_001324444.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311374.1">
        <molecule id="Q9BUB4-1"/>
        <property type="nucleotide sequence ID" value="NM_001324445.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311375.1">
        <molecule id="Q9BUB4-2"/>
        <property type="nucleotide sequence ID" value="NM_001324446.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_036223.2">
        <molecule id="Q9BUB4-1"/>
        <property type="nucleotide sequence ID" value="NM_012091.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9BUB4"/>
    <dbReference type="SMR" id="Q9BUB4"/>
    <dbReference type="BioGRID" id="117081">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BUB4">
        <property type="interactions" value="2160"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BUB4">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="MINT" id="Q9BUB4"/>
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    <sequence length="502" mass="55392" checksum="3664E4C50DA9DFE0" modified="2001-06-01" version="1">MWTADEIAQLCYEHYGIRLPKKGKPEPNHEWTLLAAVVKIQSPADKACDTPDKPVQVTKEVVSMGTGTKCIGQSKMRKNGDILNDSHAEVIARRSFQRYLLHQLQLAATLKEDSIFVPGTQKGVWKLRRDLIFVFFSSHTPCGDASIIPMLEFEDQPCCPVFRNWAHNSSVEASSNLEAPGNERKCEDPDSPVTKKMRLEPGTAAREVTNGAAHHQSFGKQKSGPISPGIHSCDLTVEGLATVTRIAPGSAKVIDVYRTGAKCVPGEAGDSGKPGAAFHQVGLLRVKPGRGDRTRSMSCSDKMARWNVLGCQGALLMHLLEEPIYLSAVVIGKCPYSQEAMQRALIGRCQNVSALPKGFGVQELKILQSDLLFEQSRSAVQAKRADSPGRLVPCGAAISWSAVPEQPLDVTANGFPQGTTKKTIGSLQARSQISKVELFRSFQKLLSRIARDKWPHSLRVQKLDTYQEYKEAASSYQEAWSTLRKQVFGSWIRNPPDYHQFK</sequence>
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    <accession>P18825</accession>
    <accession>P35369</accession>
    <accession>Q9HB49</accession>
    <name>ADA2C_HUMAN</name>
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            <fullName evidence="11">Alpha-2C adrenergic receptor</fullName>
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        <alternativeName>
            <fullName>Alpha-2C adrenoreceptor</fullName>
            <shortName>Alpha-2C adrenoceptor</shortName>
            <shortName>Alpha-2CAR</shortName>
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            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="Proc. Natl. Acad. Sci. U.S.A." volume="85" first="6301" last="6305">
            <title>Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype.</title>
            <authorList>
                <person name="Regan J.W."/>
                <person name="Kobilka T.S."/>
                <person name="Yang-Feng T.L."/>
                <person name="Caron M.G."/>
                <person name="Lefkowitz R.J."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="2842764"/>
            <dbReference type="DOI" id="10.1073/pnas.85.17.6301"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1997" name="Biochem. J." volume="328" first="431" last="438">
            <title>Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene.</title>
            <authorList>
                <person name="Schaak S."/>
                <person name="Devedjian J.C."/>
                <person name="Cayla C."/>
                <person name="Sender Y."/>
                <person name="Paris H."/>
            </authorList>
            <dbReference type="PubMed" id="9371698"/>
            <dbReference type="DOI" id="10.1042/bj3280431"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="1992-10" db="EMBL/GenBank/DDBJ databases">
            <title>Molecular cloning and expression of a novel human alpha2C-adrenerginc receptor, alpha2CII, gene.</title>
            <authorList>
                <person name="Yano K."/>
                <person name="Takeda M."/>
                <person name="Sugimoto E."/>
                <person name="Sagai H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2000" name="J. Biol. Chem." volume="275" first="23059" last="23064">
            <title>A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors.</title>
            <authorList>
                <person name="Small K.M."/>
                <person name="Forbes S.L."/>
                <person name="Rahman F.F."/>
                <person name="Bridges K.M."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="10801795"/>
            <dbReference type="DOI" id="10.1074/jbc.m000796200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT 322-GLY--PRO-325 DEL</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="13020" last="13025">
            <title>Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects.</title>
            <authorList>
                <person name="Small K.M."/>
                <person name="Mialet-Perez J."/>
                <person name="Seman C.A."/>
                <person name="Theiss C.T."/>
                <person name="Brown K.M."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="15319474"/>
            <dbReference type="DOI" id="10.1073/pnas.0405074101"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT 322-GLY--PRO-325 DEL</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2003-10" db="EMBL/GenBank/DDBJ databases">
            <title>Isolation of complete coding sequence for adrenergic receptor alpha 2C (ADRA2C).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT 322-GLY--PRO-325 DEL</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1991" name="FEBS Lett." volume="280" first="241" last="244">
            <title>Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR.</title>
            <authorList>
                <person name="Chhajlani V."/>
                <person name="Rangel N."/>
                <person name="Uhlen S."/>
                <person name="Wikberg J.E.S."/>
            </authorList>
            <dbReference type="PubMed" id="1849485"/>
            <dbReference type="DOI" id="10.1016/0014-5793(91)80301-i"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-223</scope>
    </reference>
    <reference evidence="15" key="8">
        <citation type="submission" date="2019-09" db="PDB data bank">
            <title>Crystal structure of human alpha2C adrenergic G protein-coupled receptor.</title>
            <authorList>
                <person name="Chen X.Y."/>
                <person name="Wu D."/>
                <person name="Wu L.J."/>
                <person name="Han G.W."/>
                <person name="Guo Y."/>
                <person name="Zhong G.S."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 29-241 AND 372-458 IN COMPLEX WITH G PROTEINS</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="2 8">Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression (PubMed:2842764). Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release (PubMed:2842764). ADRA2A and ADRA2C mediates the presynaptic feedback inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems. ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C modulates neurotransmission at lower levels of nerve activity (By similarity). The rank order of potency for physiological agonists of ADRA2C is epinephrine &gt; norepinephrine &gt; dopamine (PubMed:2842764).</text>
    </comment>
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        <interactant intactId="EBI-1104933">
            <id>Q8N4L8</id>
            <label>CCDC24</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
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            <id>P18825</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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            <label>CNPY2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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        <interactant intactId="EBI-12015266">
            <id>P18825</id>
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        <interactant intactId="EBI-12015266">
            <id>P18825</id>
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        <interactant intactId="EBI-6426443">
            <id>Q2WGJ6</id>
            <label>KLHL38</label>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12015266">
            <id>P18825</id>
        </interactant>
        <interactant intactId="EBI-1047093">
            <id>O76011</id>
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            <id>Q13064</id>
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    <keyword id="KW-1267">Proteomics identification</keyword>
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        <source>
            <dbReference type="PubMed" id="15319474"/>
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            <dbReference type="HGNC" id="HGNC:283"/>
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        <source>
            <dbReference type="PDB" id="6KUW"/>
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    <sequence length="462" mass="49522" checksum="E1EF9CA21E7F6EDA" modified="2002-02-11" version="2">MASPALAAALAVAAAAGPNASGAGERGSGGVANASGASWGPPRGQYSAGAVAGLAAVVGFLIVFTVVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMAYWYFGQVWCGVYLALDVLFCTSSIVHLCAISLDRYWSVTQAVEYNLKRTPRRVKATIVAVWLISAVISFPPLVSLYRQPDGAAYPQCGLNDETWYILSSCIGSFFAPCLIMGLVYARIYRVAKLRTRTLSEKRAPVGPDGASPTTENGLGAAAGAGENGHCAPPPADVEPDESSAAAERRRRRGALRRGGRRRAGAEGGAGGADGQGAGPGAAESGALTASRSPGPGGRLSRASSRSVEFFLSRRRRARSSVCRRKVAQAREKRFTFVLAVVMGVFVLCWFPFFFSYSLYGICREACQVPGPLFKFFFWIGYCNSSLNPVIYTVFNQDFRRSFKHILFRRRRRGFRQ</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="199" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKF2</accession>
    <accession>A8K8W8</accession>
    <accession>Q5T3X6</accession>
    <accession>Q9UKF1</accession>
    <name>ADA30_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 30</fullName>
            <shortName>ADAM 30</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADAM30</name>
        <name type="ORF">UNQ2509/PRO5997</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Biochem. Biophys. Res. Commun." volume="263" first="810" last="815">
            <title>Isolation of two novel metalloproteinase-disintegrin (ADAM) cDNAs that show testis-specific gene expression.</title>
            <authorList>
                <person name="Cerretti D.P."/>
                <person name="DuBose R.F."/>
                <person name="Black R.A."/>
                <person name="Nelson N."/>
            </authorList>
            <dbReference type="PubMed" id="10512762"/>
            <dbReference type="DOI" id="10.1006/bbrc.1999.1322"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA)</scope>
        <scope>VARIANT PRO-359</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Genome Res." volume="13" first="2265" last="2270">
            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
            <authorList>
                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
                <person name="Abaya E."/>
                <person name="Baker K."/>
                <person name="Baldwin D.T."/>
                <person name="Brush J."/>
                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
                <person name="Currell B."/>
                <person name="Deuel B."/>
                <person name="Dowd P."/>
                <person name="Eaton D."/>
                <person name="Foster J.S."/>
                <person name="Grimaldi C."/>
                <person name="Gu Q."/>
                <person name="Hass P.E."/>
                <person name="Heldens S."/>
                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
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                <person name="Senoh A."/>
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                <person name="Goto Y."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA)</scope>
        <scope>VARIANT PRO-359</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="16710414"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2016" name="EBioMedicine" volume="9" first="278" last="292">
            <title>ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.</title>
            <authorList>
                <person name="Letronne F."/>
                <person name="Laumet G."/>
                <person name="Ayral A.M."/>
                <person name="Chapuis J."/>
                <person name="Demiautte F."/>
                <person name="Laga M."/>
                <person name="Vandenberghe M.E."/>
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                <person name="Leroux F."/>
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            </authorList>
            <dbReference type="PubMed" id="27333034"/>
            <dbReference type="DOI" id="10.1016/j.ebiom.2016.06.002"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH CTSD</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF HIS-338; HIS-342 AND HIS-348</scope>
    </reference>
    <comment type="function">
        <text evidence="9">Plays a role in lysosomal amyloid precursor protein (APP) processing by cleaving and activating CTSD/cathepsin D which leads to APP degradation (PubMed:27333034).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">Interacts with CTSD; this leads to activation of CTSD.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Late endosome membrane</location>
            <topology evidence="2">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UKF2-1</id>
            <name>Alpha</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UKF2-2</id>
            <name>Beta</name>
            <sequence type="described" ref="VSP_005494"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 9">Expressed in brain neurons (at protein level) (PubMed:27333034). Expressed in testis (PubMed:10512762).</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF171932">
        <property type="protein sequence ID" value="AAF03780.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF171933">
        <property type="protein sequence ID" value="AAF03781.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358734">
        <property type="protein sequence ID" value="AAQ89096.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292483">
        <property type="protein sequence ID" value="BAF85172.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359752">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS907.1">
        <molecule id="Q9UKF2-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068566.2">
        <molecule id="Q9UKF2-1"/>
        <property type="nucleotide sequence ID" value="NM_021794.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9UKF2"/>
    <dbReference type="SMR" id="Q9UKF2"/>
    <dbReference type="BioGRID" id="116267">
        <property type="interactions" value="72"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9UKF2">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UKF2">
        <property type="interactions" value="58"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000358407"/>
    <dbReference type="MEROPS" id="M12.232"/>
    <dbReference type="GlyCosmos" id="Q9UKF2">
        <property type="glycosylation" value="5 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UKF2">
        <property type="glycosylation" value="5 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UKF2"/>
    <dbReference type="PhosphoSitePlus" id="Q9UKF2"/>
    <dbReference type="BioMuta" id="ADAM30"/>
    <dbReference type="DMDM" id="47117918"/>
    <dbReference type="jPOST" id="Q9UKF2"/>
    <dbReference type="MassIVE" id="Q9UKF2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000358407"/>
    <dbReference type="PeptideAtlas" id="Q9UKF2"/>
    <dbReference type="ProteomicsDB" id="84777">
        <molecule id="Q9UKF2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84778">
        <molecule id="Q9UKF2-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="20207">
        <property type="antibodies" value="85 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="11085"/>
    <dbReference type="Ensembl" id="ENST00000369400.2">
        <molecule id="Q9UKF2-1"/>
        <property type="protein sequence ID" value="ENSP00000358407.1"/>
        <property type="gene ID" value="ENSG00000134249.7"/>
    </dbReference>
    <dbReference type="GeneID" id="11085"/>
    <dbReference type="KEGG" id="hsa:11085"/>
    <dbReference type="MANE-Select" id="ENST00000369400.2">
        <property type="protein sequence ID" value="ENSP00000358407.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_021794.4"/>
        <property type="RefSeq protein sequence ID" value="NP_068566.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001eij.4">
        <molecule id="Q9UKF2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:208"/>
    <dbReference type="ClinPGx" id="PA24525"/>
    <dbReference type="CTD" id="11085"/>
    <dbReference type="DisGeNET" id="11085"/>
    <dbReference type="GeneCards" id="ADAM30"/>
    <dbReference type="HGNC" id="HGNC:208">
        <property type="gene designation" value="ADAM30"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000134249">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="604779">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000134249"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000134249"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162954"/>
    <dbReference type="HOGENOM" id="CLU_012714_4_0_1"/>
    <dbReference type="InParanoid" id="Q9UKF2"/>
    <dbReference type="OMA" id="ICGRLQC"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9UKF2">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UKF2"/>
    <dbReference type="PathwayCommons" id="Q9UKF2"/>
    <dbReference type="Reactome" id="R-HSA-2534343">
        <property type="pathway name" value="Interaction With Cumulus Cells And The Zona Pellucida"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UKF2"/>
    <dbReference type="Agora" id="ENSG00000134249"/>
    <dbReference type="BioGRID-ORCS" id="11085">
        <property type="hits" value="12 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="11085"/>
    <dbReference type="Pharos" id="Q9UKF2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UKF2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9UKF2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000134249">
        <property type="expression patterns" value="Expressed in sperm and 20 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009897">
        <property type="term" value="C:external side of plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031902">
        <property type="term" value="C:late endosome membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990913">
        <property type="term" value="C:sperm head plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008584">
        <property type="term" value="P:male gonad development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000080">
        <property type="entry name" value="A disintegrin and metallopeptidase domain 30"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
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    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
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    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
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    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
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    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
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    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
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    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
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    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
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    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF148">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 30"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
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    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
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    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01186">
        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0967">Endosome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029136" evidence="1">
        <location>
            <begin position="28"/>
            <end position="198"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029137" description="Disintegrin and metalloproteinase domain-containing protein 30">
        <location>
            <begin position="199"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="199"/>
            <end position="687"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="688"/>
            <end position="708"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="709"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="203"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="399"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="629"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="repeat" description="1">
        <location>
            <begin position="732"/>
            <end position="740"/>
        </location>
    </feature>
    <feature type="repeat" description="2">
        <location>
            <begin position="741"/>
            <end position="749"/>
        </location>
    </feature>
    <feature type="repeat" description="3">
        <location>
            <begin position="750"/>
            <end position="758"/>
        </location>
    </feature>
    <feature type="repeat" description="4">
        <location>
            <begin position="759"/>
            <end position="767"/>
        </location>
    </feature>
    <feature type="repeat" description="5">
        <location>
            <begin position="768"/>
            <end position="776"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="720"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="region of interest" description="5 X 9 AA approximate repeats">
        <location>
            <begin position="732"/>
            <end position="776"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="170"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="720"/>
            <end position="779"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="6">
        <location>
            <begin position="780"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="active site" evidence="5">
        <location>
            <position position="339"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="172"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="338"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="342"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="348"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="372"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="438"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="473"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="625"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="313"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="353"/>
            <end position="373"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="355"/>
            <end position="361"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="457"/>
            <end position="477"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="633"/>
            <end position="644"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="638"/>
            <end position="650"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="652"/>
            <end position="661"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005494" description="In isoform Beta." evidence="10">
        <location>
            <begin position="763"/>
            <end position="771"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_024597" description="In dbSNP:rs2641348." evidence="7 8">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061738" description="In dbSNP:rs35273427.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="737"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of enzymatic activity; when associated with L-342 and L-348." evidence="9">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="338"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of enzymatic activity; when associated with L-338 and L-348." evidence="9">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of enzymatic activity; when associated with L-338 and L-342." evidence="9">
        <original>H</original>
        <variation>L</variation>
        <location>
            <position position="348"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAF03781." evidence="11" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="336"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10512762"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="27333034"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="10512762"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <sequence length="790" mass="88940" checksum="42EC8A5F6B5ACDA3" modified="2004-05-10" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-05-01" modified="2026-01-28" version="198" xmlns="https://uniprot.org/uniprot">
    <accession>P25100</accession>
    <accession>Q9NPY0</accession>
    <name>ADA1D_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">Alpha-1D adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="13">Alpha-1A adrenergic receptor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-1D adrenoreceptor</fullName>
            <shortName evidence="2">Alpha-1D adrenoceptor</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-adrenergic receptor 1a</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">ADRA1D</name>
        <name type="synonym">ADRA1A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Biochem. Biophys. Res. Commun." volume="179" first="1485" last="1490">
            <title>Molecular cloning and sequencing of a cDNA encoding a human alpha 1A adrenergic receptor.</title>
            <authorList>
                <person name="Bruno J.F."/>
                <person name="Whittaker J."/>
                <person name="Song J."/>
                <person name="Berelowitz M."/>
            </authorList>
            <dbReference type="PubMed" id="1656955"/>
            <dbReference type="DOI" id="10.1016/0006-291x(91)91740-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="Mol. Pharmacol." volume="45" first="703" last="708">
            <title>The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype.</title>
            <authorList>
                <person name="Forray C."/>
                <person name="Bard J.A."/>
                <person name="Wetzel J.M."/>
                <person name="Chiu G."/>
                <person name="Shapiro E."/>
                <person name="Tang R."/>
                <person name="Lepor H."/>
                <person name="Hartig P.R."/>
                <person name="Weinshank R.L."/>
                <person name="Branchek T.A."/>
                <person name="Gluchowski C."/>
            </authorList>
            <dbReference type="PubMed" id="8183249"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Hippocampus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="J. Pharmacol. Exp. Ther." volume="272" first="134" last="142">
            <title>Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues.</title>
            <authorList>
                <person name="Schwinn D.A."/>
                <person name="Johnston G.I."/>
                <person name="Page S.O."/>
                <person name="Mosley M.J."/>
                <person name="Wilson K.H."/>
                <person name="Worman N.P."/>
                <person name="Campbell S."/>
                <person name="Fidock M.D."/>
                <person name="Furness L.M."/>
                <person name="Parry-Smith D.J."/>
                <person name="Peter B."/>
                <person name="Bailey D.S."/>
            </authorList>
            <dbReference type="PubMed" id="7815325"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1994" name="Biochem. Biophys. Res. Commun." volume="201" first="1296" last="1304">
            <title>Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c.</title>
            <authorList>
                <person name="Weinberg D.H."/>
                <person name="Trivedi P."/>
                <person name="Tan C.P."/>
                <person name="Mitra S."/>
                <person name="Perkins-Barrow A."/>
                <person name="Borkowski D."/>
                <person name="Strader C.D."/>
                <person name="Bayne M."/>
            </authorList>
            <dbReference type="PubMed" id="8024574"/>
            <dbReference type="DOI" id="10.1006/bbrc.1994.1845"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1995" name="Mol. Pharmacol." volume="47" first="977" last="985">
            <title>Cloning of the human alpha 1d-adrenergic receptor and inducible expression of three human subtypes in SK-N-MC cells.</title>
            <authorList>
                <person name="Esbenshade T.A."/>
                <person name="Hirasawa A."/>
                <person name="Tsujimoto G."/>
                <person name="Tanaka T."/>
                <person name="Yano J."/>
                <person name="Minneman K.P."/>
                <person name="Murphy T.J."/>
            </authorList>
            <dbReference type="PubMed" id="7746284"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Placenta</tissue>
            <tissue>Prostate</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Matthews L.H."/>
                <person name="Ashurst J.L."/>
                <person name="Burton J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Jones M."/>
                <person name="Stavrides G."/>
                <person name="Almeida J.P."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
                <person name="Beasley O.P."/>
                <person name="Bird C.P."/>
                <person name="Blakey S.E."/>
                <person name="Bridgeman A.M."/>
                <person name="Brown A.J."/>
                <person name="Buck D."/>
                <person name="Burrill W.D."/>
                <person name="Butler A.P."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clamp M."/>
                <person name="Clark G."/>
                <person name="Clark L.N."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Cobley V.E."/>
                <person name="Collier R.E."/>
                <person name="Connor R.E."/>
                <person name="Corby N.R."/>
                <person name="Coulson A."/>
                <person name="Coville G.J."/>
                <person name="Deadman R."/>
                <person name="Dhami P.D."/>
                <person name="Dunn M."/>
                <person name="Ellington A.G."/>
                <person name="Frankland J.A."/>
                <person name="Fraser A."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths M.N.D."/>
                <person name="Gwilliam R."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Heath P.D."/>
                <person name="Ho S."/>
                <person name="Holden J.L."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Jekosch K."/>
                <person name="Johnson C.M."/>
                <person name="Johnson D."/>
                <person name="Kay M.P."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lehvaeslaiho M.H."/>
                <person name="Leversha M.A."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J.D."/>
                <person name="Marsh V.L."/>
                <person name="Martin S.L."/>
                <person name="McConnachie L.J."/>
                <person name="McLay K."/>
                <person name="McMurray A.A."/>
                <person name="Milne S.A."/>
                <person name="Mistry D."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Nickerson T."/>
                <person name="Oliver K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce T.A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Prathalingam S.R."/>
                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Scott C.E."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
                <person name="Sulston J.E."/>
                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2015" name="Biochemistry" volume="54" first="6673" last="6683">
            <title>G Protein-Coupled Receptors Directly Bind Filamin A with High Affinity and Promote Filamin Phosphorylation.</title>
            <authorList>
                <person name="Tirupula K.C."/>
                <person name="Ithychanda S.S."/>
                <person name="Mohan M.L."/>
                <person name="Naga Prasad S.V."/>
                <person name="Qin J."/>
                <person name="Karnik S.S."/>
            </authorList>
            <dbReference type="PubMed" id="26460884"/>
            <dbReference type="DOI" id="10.1021/acs.biochem.5b00975"/>
        </citation>
        <scope>INTERACTION WITH FLNA</scope>
    </reference>
    <comment type="function">
        <text evidence="9 10 11 12">Alpha-1 adrenergic receptors are G protein-coupled receptors for catecholamines that signal through the G(q) family of G proteins, including G(q) and G(11). Upon activation, they stimulate the phosphatidylinositol-calcium second messenger pathway, leading to calcium release from intracellular stores and activation of protein kinase C (PubMed:7746284). ADRA1D binds the catecholamine ligands norepinephrine and epinephrine (PubMed:7815325, PubMed:8024574, PubMed:8183249).</text>
    </comment>
    <comment type="subunit">
        <text evidence="8">Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-489993">
            <id>P25100</id>
            <label>ADRA1D</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-357481">
            <id>Q12959</id>
            <label>DLG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>22</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-717191">
            <id>Q13424</id>
            <label>SNTA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-295843">
            <id>Q13884</id>
            <label>SNTB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>12</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-80411">
            <id>Q13425</id>
            <label>SNTB2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>16</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-310886">
            <id>Q9P202</id>
            <label>WHRN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-295952">
            <id>Q61234</id>
            <label>Snta1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-295943">
            <id>Q99L88</id>
            <label>Sntb1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-489993">
            <id>P25100</id>
        </interactant>
        <interactant intactId="EBI-8521556">
            <id>Q925E0</id>
            <label>Sntg2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="PTM">
        <text evidence="4">Palmitoylated. Palmitoylation by ZDHHC21 may increase the expression of the receptor and regulate downstream signaling.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1D sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M76446">
        <property type="protein sequence ID" value="AAA35496.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U03864">
        <property type="protein sequence ID" value="AAB60351.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB59487.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S70782">
        <property type="protein sequence ID" value="AAB31163.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D29952">
        <property type="protein sequence ID" value="BAA06222.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121675">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL357040">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="CCDS" id="CCDS13079.1"/>
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        <property type="entry name" value="I39369"/>
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    <dbReference type="PIR" id="JH0447">
        <property type="entry name" value="JH0447"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000669.1">
        <property type="nucleotide sequence ID" value="NM_000678.4"/>
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    <dbReference type="AlphaFoldDB" id="P25100"/>
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    <dbReference type="CORUM" id="P25100"/>
    <dbReference type="FunCoup" id="P25100">
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    <dbReference type="MINT" id="P25100"/>
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        <property type="generic name" value="4-Methoxyamphetamine"/>
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    <dbReference type="DrugBank" id="DB00346">
        <property type="generic name" value="Alfuzosin"/>
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    <dbReference type="DrugBank" id="DB00321">
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    <dbReference type="DrugBank" id="DB00182">
        <property type="generic name" value="Amphetamine"/>
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    <dbReference type="DrugBank" id="DB09229">
        <property type="generic name" value="Aranidipine"/>
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    <dbReference type="DrugBank" id="DB06413">
        <property type="generic name" value="Armodafinil"/>
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    <dbReference type="DrugBank" id="DB09204">
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    <dbReference type="DrugBank" id="DB00248">
        <property type="generic name" value="Cabergoline"/>
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    <dbReference type="DrugBank" id="DB00320">
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        <property type="generic name" value="Dobutamine"/>
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        <property type="generic name" value="Dronedarone"/>
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    <dbReference type="DrugBank" id="DB05492">
        <property type="generic name" value="Epicept NP-1"/>
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    <dbReference type="DrugBank" id="DB00668">
        <property type="generic name" value="Epinephrine"/>
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    <dbReference type="DrugBank" id="DB01049">
        <property type="generic name" value="Ergoloid mesylate"/>
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    <dbReference type="DrugBank" id="DB00696">
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    <dbReference type="DrugBank" id="DB00800">
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    <dbReference type="DrugBank" id="DB11577">
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    <dbReference type="DrugBank" id="DB00598">
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    <dbReference type="DrugBank" id="DB06707">
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    <dbReference type="DrugBank" id="DB09195">
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    <dbReference type="DrugBank" id="DB01403">
        <property type="generic name" value="Methotrimeprazine"/>
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    <dbReference type="DrugBank" id="DB00723">
        <property type="generic name" value="Methoxamine"/>
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    <dbReference type="DrugBank" id="DB06148">
        <property type="generic name" value="Mianserin"/>
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    <dbReference type="DrugBank" id="DB00211">
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    <dbReference type="DrugBank" id="DB00622">
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    <dbReference type="DrugBank" id="DB00368">
        <property type="generic name" value="Norepinephrine"/>
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    <dbReference type="DrugBank" id="DB00540">
        <property type="generic name" value="Nortriptyline"/>
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    <dbReference type="DrugBank" id="DB06229">
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    <dbReference type="DrugBank" id="DB11124">
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        <property type="generic name" value="Ranolazine"/>
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</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="200" xmlns="https://uniprot.org/uniprot">
    <accession>Q99965</accession>
    <accession>P78326</accession>
    <accession>Q9UQQ8</accession>
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        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 2</fullName>
            <shortName>ADAM 2</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Cancer/testis antigen 15</fullName>
            <shortName>CT15</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Fertilin subunit beta</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>PH-30</fullName>
            <shortName>PH30</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>PH30-beta</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM2</name>
        <name type="synonym">FTNB</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Mol. Reprod. Dev." volume="46" first="363" last="369">
            <title>Human fertilin beta: identification, characterization, and chromosomal mapping of an ADAM gene family member.</title>
            <authorList>
                <person name="Vidaeus C.M."/>
                <person name="von Kap-Herr C."/>
                <person name="Golden W.L."/>
                <person name="Eddy R.L."/>
                <person name="Shows T.B."/>
                <person name="Herr J.C."/>
            </authorList>
            <dbReference type="PubMed" id="9041139"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-2795(199703)46:3&lt;363::aid-mrd15&gt;3.0.co;2-#"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="Biochem. Biophys. Res. Commun." volume="224" first="318" last="326">
            <title>Molecular cloning of the human fertilin beta subunit.</title>
            <authorList>
                <person name="Gupta S.K."/>
                <person name="Alves K."/>
                <person name="Palladino L.O."/>
                <person name="Mark G.E."/>
                <person name="Hollis G.F."/>
            </authorList>
            <dbReference type="PubMed" id="8702389"/>
            <dbReference type="DOI" id="10.1006/bbrc.1996.1027"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1997" name="Genomics" volume="40" first="190" last="192">
            <title>Mapping, sequence, and expression analysis of the human fertilin beta gene (FTNB).</title>
            <authorList>
                <person name="Burkin H.R."/>
                <person name="Burkin D.J."/>
                <person name="Davey P.M."/>
                <person name="Griffin D.K."/>
                <person name="Affara N.A."/>
            </authorList>
            <dbReference type="PubMed" id="9070941"/>
            <dbReference type="DOI" id="10.1006/geno.1996.4531"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="1999-04" db="EMBL/GenBank/DDBJ databases">
            <title>Nucleotide sequence of the human fertilin beta transcript.</title>
            <authorList>
                <person name="Hall L."/>
                <person name="Frayne J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. Could have a direct role in sperm-zona binding or migration of sperm from the uterus into the oviduct. Interactions with egg membrane could be mediated via binding between its disintegrin-like domain to one or more integrins receptors on the egg. This is a non catalytic metalloprotease-like protein.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q99965-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q99965-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_005471"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed specifically in spermatogenic cells in the seminiferous cells. Not detected in fetal tissues.</text>
    </comment>
    <comment type="domain">
        <text>A tripeptide motif (FEE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.</text>
    </comment>
    <comment type="PTM">
        <text>The prodomain and the metalloprotease domain are cleaved during the epididymal maturation of the spermatozoa.</text>
    </comment>
    <comment type="miscellaneous">
        <text>In mammals, exists as a heterodimer composed of an alpha and beta subunits. In human, fertilin subunit alpha is a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="U52370">
        <property type="protein sequence ID" value="AAC51110.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U38805">
        <property type="protein sequence ID" value="AAD04206.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X99374">
        <property type="protein sequence ID" value="CAA67753.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ133005">
        <property type="protein sequence ID" value="CAB40813.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034957">
        <property type="protein sequence ID" value="AAH34957.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34884.1">
        <molecule id="Q99965-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64882.1">
        <molecule id="Q99965-2"/>
    </dbReference>
    <dbReference type="PIR" id="JC4861">
        <property type="entry name" value="JC4861"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001265042.1">
        <molecule id="Q99965-2"/>
        <property type="nucleotide sequence ID" value="NM_001278113.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001265043.1">
        <property type="nucleotide sequence ID" value="NM_001278114.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001455.3">
        <molecule id="Q99965-1"/>
        <property type="nucleotide sequence ID" value="NM_001464.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q99965"/>
    <dbReference type="SMR" id="Q99965"/>
    <dbReference type="BioGRID" id="108791">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q99965">
        <property type="interactions" value="25"/>
    </dbReference>
    <dbReference type="IntAct" id="Q99965">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000265708"/>
    <dbReference type="MEROPS" id="M12.950"/>
    <dbReference type="GlyCosmos" id="Q99965">
        <property type="glycosylation" value="5 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q99965">
        <property type="glycosylation" value="5 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q99965"/>
    <dbReference type="PhosphoSitePlus" id="Q99965"/>
    <dbReference type="BioMuta" id="ADAM2"/>
    <dbReference type="DMDM" id="28202251"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="Q99965"/>
    <dbReference type="jPOST" id="Q99965"/>
    <dbReference type="MassIVE" id="Q99965"/>
    <dbReference type="PaxDb" id="9606-ENSP00000265708"/>
    <dbReference type="PeptideAtlas" id="Q99965"/>
    <dbReference type="ProteomicsDB" id="78551">
        <molecule id="Q99965-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="78552">
        <molecule id="Q99965-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="11200">
        <property type="antibodies" value="196 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2515"/>
    <dbReference type="Ensembl" id="ENST00000265708.9">
        <molecule id="Q99965-1"/>
        <property type="protein sequence ID" value="ENSP00000265708.4"/>
        <property type="gene ID" value="ENSG00000104755.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000347580.8">
        <molecule id="Q99965-2"/>
        <property type="protein sequence ID" value="ENSP00000343854.4"/>
        <property type="gene ID" value="ENSG00000104755.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000613160.4">
        <molecule id="Q99965-2"/>
        <property type="protein sequence ID" value="ENSP00000484999.1"/>
        <property type="gene ID" value="ENSG00000276286.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000620181.4">
        <molecule id="Q99965-1"/>
        <property type="protein sequence ID" value="ENSP00000482337.1"/>
        <property type="gene ID" value="ENSG00000276286.4"/>
    </dbReference>
    <dbReference type="GeneID" id="2515"/>
    <dbReference type="KEGG" id="hsa:2515"/>
    <dbReference type="MANE-Select" id="ENST00000265708.9">
        <property type="protein sequence ID" value="ENSP00000265708.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001464.5"/>
        <property type="RefSeq protein sequence ID" value="NP_001455.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xnj.5">
        <molecule id="Q99965-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:198"/>
    <dbReference type="ClinPGx" id="PA24515"/>
    <dbReference type="CTD" id="2515"/>
    <dbReference type="DisGeNET" id="2515"/>
    <dbReference type="GeneCards" id="ADAM2"/>
    <dbReference type="HGNC" id="HGNC:198">
        <property type="gene designation" value="ADAM2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000104755">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="601533">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000104755"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000104755"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161961"/>
    <dbReference type="InParanoid" id="Q99965"/>
    <dbReference type="OMA" id="NHMGADT"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q99965">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q99965"/>
    <dbReference type="PathwayCommons" id="Q99965"/>
    <dbReference type="Reactome" id="R-HSA-2534343">
        <property type="pathway name" value="Interaction With Cumulus Cells And The Zona Pellucida"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q99965"/>
    <dbReference type="Agora" id="ENSG00000104755"/>
    <dbReference type="BioGRID-ORCS" id="2515">
        <property type="hits" value="19 hits in 1144 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM2"/>
    <dbReference type="GenomeRNAi" id="2515"/>
    <dbReference type="Pharos" id="Q99965">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q99965"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q99965">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000104755">
        <property type="expression patterns" value="Expressed in testis and 28 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q99965">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032991">
        <property type="term" value="C:protein-containing complex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005178">
        <property type="term" value="F:integrin binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030534">
        <property type="term" value="P:adult behavior"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007339">
        <property type="term" value="P:binding of sperm to zona pellucida"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007155">
        <property type="term" value="P:cell adhesion"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007342">
        <property type="term" value="P:fusion of sperm to egg plasma membrane involved in single fertilization"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010467">
        <property type="term" value="P:gene expression"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008584">
        <property type="term" value="P:male gonad development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010628">
        <property type="term" value="P:positive regulation of gene expression"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008542">
        <property type="term" value="P:visual learning"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000033">
        <property type="entry name" value="A disintegrin and metallopeptidase domain 18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF108">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029042">
        <location>
            <begin position="17"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029043" description="Disintegrin and metalloproteinase domain-containing protein 2">
        <location>
            <begin position="175"/>
            <end position="735"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="175"/>
            <end position="686"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="687"/>
            <end position="707"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="708"/>
            <end position="735"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="178"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="4">
        <location>
            <begin position="384"/>
            <end position="473"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like">
        <location>
            <begin position="612"/>
            <end position="645"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="729"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="122"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="220"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="459"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="566"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="287"/>
            <end position="370"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="329"/>
            <end position="354"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="331"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="445"/>
            <end position="465"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="616"/>
            <end position="627"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="621"/>
            <end position="633"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="635"/>
            <end position="644"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005471" description="In isoform 2." evidence="6">
        <location>
            <begin position="172"/>
            <end position="190"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035217" description="In dbSNP:rs34800519.">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="10"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAD04206." evidence="7" ref="2">
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="99"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAD04206." evidence="7" ref="2">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC51110." evidence="7" ref="1">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="288"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC51110." evidence="7" ref="1">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="388"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>EEC</original>
        <variation>DEF</variation>
        <location>
            <begin position="396"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="501"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="579"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>W</original>
        <variation>L</variation>
        <location>
            <position position="588"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="603"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>NK</original>
        <variation>KQ</variation>
        <location>
            <begin position="629"/>
            <end position="630"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAA67753." evidence="7" ref="3">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="638"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q60718"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <sequence length="735" mass="82457" checksum="92867B5340BEE01F" modified="2003-02-01" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-10-19" modified="2026-01-28" version="227" xmlns="https://uniprot.org/uniprot">
    <accession>Q13443</accession>
    <accession>B7ZLN7</accession>
    <accession>Q10718</accession>
    <accession>Q8NFM6</accession>
    <name>ADAM9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 9</fullName>
            <shortName>ADAM 9</shortName>
            <ecNumber evidence="2">3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Cellular disintegrin-related protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Meltrin-gamma</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Metalloprotease/disintegrin/cysteine-rich protein 9</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Myeloma cell metalloproteinase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM9</name>
        <name type="synonym">KIAA0021</name>
        <name type="synonym">MCMP</name>
        <name type="synonym">MDC9</name>
        <name type="synonym">MLTNG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="J. Cell Biol." volume="132" first="717" last="726">
            <title>MDC9, a widely expressed cellular disintegrin containing cytoplasmic SH3 ligand domains.</title>
            <authorList>
                <person name="Weskamp G."/>
                <person name="Kraetzschmar J."/>
                <person name="Reid M.S."/>
                <person name="Blobel C.P."/>
            </authorList>
            <dbReference type="PubMed" id="8647900"/>
            <dbReference type="DOI" id="10.1083/jcb.132.4.717"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
            <tissue>Mammary carcinoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="Biochem. J." volume="318" first="459" last="462">
            <title>Cloning of a novel membrane-linked metalloproteinase from human myeloma cells.</title>
            <authorList>
                <person name="McKie N."/>
                <person name="Dallas D.J."/>
                <person name="Edwards T."/>
                <person name="Apperley J.F."/>
                <person name="Russell R.G.G."/>
                <person name="Croucher P.I."/>
            </authorList>
            <dbReference type="PubMed" id="8809033"/>
            <dbReference type="DOI" id="10.1042/bj3180459"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2002" name="Biochem. Biophys. Res. Commun." volume="293" first="800" last="805">
            <title>A secreted form of human ADAM9 has an alpha-secretase activity for APP.</title>
            <authorList>
                <person name="Hotoda N."/>
                <person name="Koike H."/>
                <person name="Sasagawa N."/>
                <person name="Ishiura S."/>
            </authorList>
            <dbReference type="PubMed" id="12054541"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(02)00302-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="27" last="35">
            <title>Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.</title>
            <authorList>
                <person name="Nomura N."/>
                <person name="Miyajima N."/>
                <person name="Sazuka T."/>
                <person name="Tanaka A."/>
                <person name="Kawarabayasi Y."/>
                <person name="Sato S."/>
                <person name="Nagase T."/>
                <person name="Seki N."/>
                <person name="Ishikawa K."/>
                <person name="Tabata S."/>
            </authorList>
            <dbReference type="PubMed" id="7584026"/>
            <dbReference type="DOI" id="10.1093/dnares/1.1.27"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2003-03" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Nomura N."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1997" name="Biochem. Biophys. Res. Commun." volume="230" first="335" last="339">
            <title>Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes.</title>
            <authorList>
                <person name="McKie N."/>
                <person name="Edwards T."/>
                <person name="Dallas D.J."/>
                <person name="Houghton A."/>
                <person name="Stringer B."/>
                <person name="Graham R."/>
                <person name="Russell G."/>
                <person name="Croucher P.I."/>
            </authorList>
            <dbReference type="PubMed" id="9016778"/>
            <dbReference type="DOI" id="10.1006/bbrc.1996.5957"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="31693" last="31699">
            <title>Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.</title>
            <authorList>
                <person name="Howard L."/>
                <person name="Nelson K.K."/>
                <person name="Maciewicz R.A."/>
                <person name="Blobel C.P."/>
            </authorList>
            <dbReference type="PubMed" id="10531379"/>
            <dbReference type="DOI" id="10.1074/jbc.274.44.31693"/>
        </citation>
        <scope>INTERACTION WITH SH3GL2 AND SNX9</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2009" name="Am. J. Hum. Genet." volume="84" first="683" last="691">
            <title>Loss of the metalloprotease ADAM9 leads to cone-rod dystrophy in humans and retinal degeneration in mice.</title>
            <authorList>
                <person name="Parry D.A."/>
                <person name="Toomes C."/>
                <person name="Bida L."/>
                <person name="Danciger M."/>
                <person name="Towns K.V."/>
                <person name="McKibbin M."/>
                <person name="Jacobson S.G."/>
                <person name="Logan C.V."/>
                <person name="Ali M."/>
                <person name="Bond J."/>
                <person name="Chance R."/>
                <person name="Swendeman S."/>
                <person name="Daniele L.L."/>
                <person name="Springell K."/>
                <person name="Adams M."/>
                <person name="Johnson C.A."/>
                <person name="Booth A.P."/>
                <person name="Jafri H."/>
                <person name="Rashid Y."/>
                <person name="Banin E."/>
                <person name="Strom T.M."/>
                <person name="Farber D.B."/>
                <person name="Sharon D."/>
                <person name="Blobel C.P."/>
                <person name="Pugh E.N. Jr."/>
                <person name="Pierce E.A."/>
                <person name="Inglehearn C.F."/>
            </authorList>
            <dbReference type="PubMed" id="19409519"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2009.04.005"/>
        </citation>
        <scope>INVOLVEMENT IN CORD9</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-758 AND THR-761</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="2">Metalloprotease that cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="11">May act as alpha-secretase for amyloid precursor protein (APP).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="3">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Synthesized as an inactive form which is proteolytically cleaved to generate an active enzyme. Processing at the upstream site is particularly important for activation of the proenzyme, whereas processing at the boundary between the pro-domain and the catalytic domain does not appear to be essential. Inhibited by hydroxamic acid-based inhibitors.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 10">Interacts with SH3GL2 and SNX9 through its cytoplasmic tail (PubMed:10531379). Interacts with ITGA6.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77903">
            <id>Q13443</id>
        </interactant>
        <interactant intactId="EBI-77889">
            <id>Q9UI95</id>
            <label>MAD2L2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77903">
            <id>Q13443</id>
        </interactant>
        <interactant intactId="EBI-77926">
            <id>Q9UKS6</id>
            <label>PACSIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77903">
            <id>Q13443</id>
        </interactant>
        <interactant intactId="EBI-77938">
            <id>Q99962</id>
            <label>SH3GL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77903">
            <id>Q13443</id>
        </interactant>
        <interactant intactId="EBI-298169">
            <id>Q96RF0</id>
            <label>SNX18</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-77903">
            <id>Q13443</id>
        </interactant>
        <interactant intactId="EBI-77848">
            <id>Q9Y5X1</id>
            <label>SNX9</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="14">Cell membrane</location>
            <topology evidence="4">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="11">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q13443-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q13443-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011057 VSP_011058"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="11 13 14 15">Widely expressed. Expressed in chondrocytes. Isoform 2 is highly expressed in liver and heart.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Proteolytically cleaved in the trans-Golgi network before it reaches the plasma membrane to generate a mature protein. The removal of the pro-domain occurs via cleavage at two different sites. Processed most likely by a pro-protein convertase such as furin, at the boundary between the pro-domain and the catalytic domain. An additional upstream cleavage pro-protein convertase site (Arg-56/Glu-57) has an important role in the activation of ADAM9.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Phosphorylation is induced in vitro by phorbol-12-myristate-13-acetate (PMA).</text>
    </comment>
    <comment type="disease" evidence="12">
        <disease id="DI-02490">
            <name>Cone-rod dystrophy 9</name>
            <acronym>CORD9</acronym>
            <description>An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.</description>
            <dbReference type="MIM" id="612775"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="18">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="caution">
        <text evidence="18">Has sometimes been referred to as ADAM-12.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/573/ADAM9"/>
    </comment>
    <dbReference type="EC" id="3.4.24.-" evidence="2"/>
    <dbReference type="EMBL" id="U41766">
        <property type="protein sequence ID" value="AAC50403.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF495383">
        <property type="protein sequence ID" value="AAM49575.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D14665">
        <property type="protein sequence ID" value="BAA03499.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471080">
        <property type="protein sequence ID" value="EAW63284.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143923">
        <property type="protein sequence ID" value="AAI43924.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6112.1">
        <molecule id="Q13443-1"/>
    </dbReference>
    <dbReference type="PIR" id="JC7850">
        <property type="entry name" value="JC7850"/>
    </dbReference>
    <dbReference type="PIR" id="S71949">
        <property type="entry name" value="S71949"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003807.1">
        <molecule id="Q13443-1"/>
        <property type="nucleotide sequence ID" value="NM_003816.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q13443"/>
    <dbReference type="SMR" id="Q13443"/>
    <dbReference type="BioGRID" id="114290">
        <property type="interactions" value="165"/>
    </dbReference>
    <dbReference type="CORUM" id="Q13443"/>
    <dbReference type="FunCoup" id="Q13443">
        <property type="interactions" value="984"/>
    </dbReference>
    <dbReference type="IntAct" id="Q13443">
        <property type="interactions" value="107"/>
    </dbReference>
    <dbReference type="MINT" id="Q13443"/>
    <dbReference type="STRING" id="9606.ENSP00000419446"/>
    <dbReference type="BindingDB" id="Q13443"/>
    <dbReference type="ChEMBL" id="CHEMBL5982"/>
    <dbReference type="DrugBank" id="DB05033">
        <property type="generic name" value="INCB7839"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q13443"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="1657"/>
    <dbReference type="MEROPS" id="M12.209"/>
    <dbReference type="GlyConnect" id="1181">
        <property type="glycosylation" value="6 N-Linked glycans (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q13443">
        <property type="glycosylation" value="6 sites, 6 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q13443">
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
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            <begin position="414"/>
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            <begin position="644"/>
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        <location>
            <begin position="734"/>
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        <location>
            <begin position="780"/>
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        <location>
            <begin position="735"/>
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    <feature type="active site" evidence="7 8">
        <location>
            <position position="348"/>
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    <feature type="binding site" evidence="1">
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            <position position="347"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="351"/>
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        <ligand>
            <name>Zn(2+)</name>
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            <note>catalytic</note>
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    <feature type="binding site" evidence="1">
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            <position position="357"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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    <feature type="site" description="Cleavage" evidence="2">
        <location>
            <begin position="56"/>
            <end position="57"/>
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    </feature>
    <feature type="site" description="Cleavage; by furin-like protease" evidence="2">
        <location>
            <begin position="205"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="19">
        <location>
            <position position="758"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="19">
        <location>
            <position position="761"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="381"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="487"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="322"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="363"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="365"/>
            <end position="370"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="473"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="644"/>
            <end position="656"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="650"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="664"/>
            <end position="673"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011057" description="In isoform 2." evidence="16 17">
        <original>V</original>
        <variation>K</variation>
        <location>
            <position position="655"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011058" description="In isoform 2." evidence="16 17">
        <location>
            <begin position="656"/>
            <end position="819"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <location>
            <begin position="1"/>
            <end position="118"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAA03499." evidence="18" ref="4">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <original>YVEGVHNSSIALSDCFG</original>
        <variation>MWREFIIHPLLLATVLD</variation>
        <location>
            <begin position="119"/>
            <end position="135"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <original>N</original>
        <variation>M</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <original>G</original>
        <variation>GLSLKFHAPFLSTMLQEAVRQTGTYLGGSVCCMKSDCRIVTLVK</variation>
        <location>
            <position position="566"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <original>AIFIFIKRDQLWRSYFRKKRSQT</original>
        <variation>DYFYLHQEGSTVEKLLQKEEITN</variation>
        <location>
            <begin position="713"/>
            <end position="735"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; no nucleotide entry." evidence="18" ref="2">
        <location>
            <begin position="736"/>
            <end position="819"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q61072"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q9BZ11"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="7">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="8">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="9">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="10531379"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="12054541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="19409519"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="7584026"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="8647900"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="9016778"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="12054541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="18"/>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="819" mass="90556" checksum="BC186641833137FF" modified="1996-11-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="201" xmlns="https://uniprot.org/uniprot">
    <accession>O75078</accession>
    <accession>Q14808</accession>
    <accession>Q14809</accession>
    <accession>Q14810</accession>
    <name>ADA11_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 11</fullName>
            <shortName>ADAM 11</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Metalloproteinase-like, disintegrin-like, and cysteine-rich protein</fullName>
            <shortName>MDC</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM11</name>
        <name type="synonym">MDC</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Biochem. J." volume="334" first="93" last="98">
            <title>Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain.</title>
            <authorList>
                <person name="Sagane K."/>
                <person name="Ohya Y."/>
                <person name="Hasegawa Y."/>
                <person name="Tanaka I."/>
            </authorList>
            <dbReference type="PubMed" id="9693107"/>
            <dbReference type="DOI" id="10.1042/bj3340093"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="Nat. Genet." volume="5" first="151" last="157">
            <title>A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers.</title>
            <authorList>
                <person name="Emi M."/>
                <person name="Katagiri T."/>
                <person name="Harada Y."/>
                <person name="Saito H."/>
                <person name="Inazawa J."/>
                <person name="Ito I."/>
                <person name="Kasumi F."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="8252040"/>
            <dbReference type="DOI" id="10.1038/ng1093-151"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT)</scope>
        <source>
            <tissue>Cerebellum</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Cytogenet. Cell Genet." volume="68" first="39" last="44">
            <title>Human metalloprotease/disintegrin-like (MDC) gene: exon-intron organization and alternative splicing.</title>
            <authorList>
                <person name="Katagiri T."/>
                <person name="Harada Y."/>
                <person name="Emi M."/>
                <person name="Nakamura Y."/>
            </authorList>
            <dbReference type="PubMed" id="7956356"/>
            <dbReference type="DOI" id="10.1159/000133884"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 106-769 (ISOFORMS LONG AND SHORT)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Mammary gland</tissue>
            <tissue>Ovary</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R8.1" last="R8.16">
            <title>An unappreciated role for RNA surveillance.</title>
            <authorList>
                <person name="Hillman R.T."/>
                <person name="Green R.E."/>
                <person name="Brenner S.E."/>
            </authorList>
            <dbReference type="PubMed" id="14759258"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-2-r8"/>
        </citation>
        <scope>SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
                <person name="Kern S.E."/>
                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] ARG-693</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Required for localization of the potassium channel subunit proteins KCNA1/KV1.1 and KCNA2/KV1.2 at cerebellar cortex basket cell distal terminals, is thereby involved in ephaptic inhibitory synchronization of Purkinje cell firing and response to stress (By similarity). Plays a role in spatial learning and motor coordination (By similarity). Involved in the nociceptive pain response to chemical-derived stimulation (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts with LGI1 and LGI4 (By similarity). Interacts with KCNA1/KV1.1, KCNA2/KV1.2, DLG4/PSD-95 and ADAM22 (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Presynaptic cell membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Perikaryon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Axon</location>
        </subcellularLocation>
        <text evidence="2">Localizes to basket cell terminals and pinceaux.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O75078-1</id>
            <name>Long</name>
            <name>MDC-769</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O75078-2</id>
            <name>Short</name>
            <name>MDC-524</name>
            <sequence type="described" ref="VSP_005472 VSP_005473 VSP_005474 VSP_005475"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed predominantly in brain. Slightly detected or not at all in other tissues.</text>
    </comment>
    <comment type="domain">
        <text>A conserved motif [AVN[ED]CD] within the disintegrin-like domain could be involved in the binding to the integrin receptor.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform Short</molecule>
        <text evidence="10">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <dbReference type="EMBL" id="AB009675">
        <property type="protein sequence ID" value="BAA32352.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D17390">
        <property type="protein sequence ID" value="BAA04213.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D31872">
        <property type="protein sequence ID" value="BAA06670.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D31872">
        <property type="protein sequence ID" value="BAA06671.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11486.1">
        <molecule id="O75078-1"/>
    </dbReference>
    <dbReference type="PIR" id="I65967">
        <property type="entry name" value="I65967"/>
    </dbReference>
    <dbReference type="PIR" id="S38539">
        <property type="entry name" value="S38539"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002381.2">
        <molecule id="O75078-1"/>
        <property type="nucleotide sequence ID" value="NM_002390.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O75078"/>
    <dbReference type="SMR" id="O75078"/>
    <dbReference type="BioGRID" id="110351">
        <property type="interactions" value="56"/>
    </dbReference>
    <dbReference type="FunCoup" id="O75078">
        <property type="interactions" value="168"/>
    </dbReference>
    <dbReference type="IntAct" id="O75078">
        <property type="interactions" value="25"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000200557"/>
    <dbReference type="MEROPS" id="M12.976"/>
    <dbReference type="TCDB" id="8.A.77.1.1">
        <property type="family name" value="the sheddase (sheddase) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O75078">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O75078">
        <property type="glycosylation" value="5 sites, 2 N-linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O75078"/>
    <dbReference type="PhosphoSitePlus" id="O75078"/>
    <dbReference type="BioMuta" id="ADAM11"/>
    <dbReference type="MassIVE" id="O75078"/>
    <dbReference type="PaxDb" id="9606-ENSP00000200557"/>
    <dbReference type="PeptideAtlas" id="O75078"/>
    <dbReference type="ProteomicsDB" id="49743">
        <molecule id="O75078-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="49744">
        <molecule id="O75078-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="29870">
        <property type="antibodies" value="138 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="4185"/>
    <dbReference type="Ensembl" id="ENST00000200557.11">
        <molecule id="O75078-1"/>
        <property type="protein sequence ID" value="ENSP00000200557.6"/>
        <property type="gene ID" value="ENSG00000073670.15"/>
    </dbReference>
    <dbReference type="GeneID" id="4185"/>
    <dbReference type="KEGG" id="hsa:4185"/>
    <dbReference type="MANE-Select" id="ENST00000200557.11">
        <property type="protein sequence ID" value="ENSP00000200557.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_002390.6"/>
        <property type="RefSeq protein sequence ID" value="NP_002381.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ihh.4">
        <molecule id="O75078-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:189"/>
    <dbReference type="ClinPGx" id="PA24506"/>
    <dbReference type="CTD" id="4185"/>
    <dbReference type="DisGeNET" id="4185"/>
    <dbReference type="GeneCards" id="ADAM11"/>
    <dbReference type="HGNC" id="HGNC:189">
        <property type="gene designation" value="ADAM11"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000073670">
        <property type="expression patterns" value="Tissue enriched (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="155120">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000073670"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000073670"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159790"/>
    <dbReference type="InParanoid" id="O75078"/>
    <dbReference type="OMA" id="GAETHRY"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="O75078">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O75078"/>
    <dbReference type="PathwayCommons" id="O75078"/>
    <dbReference type="Reactome" id="R-HSA-5682910">
        <property type="pathway name" value="LGI-ADAM interactions"/>
    </dbReference>
    <dbReference type="SignaLink" id="O75078"/>
    <dbReference type="Agora" id="ENSG00000073670"/>
    <dbReference type="BioGRID-ORCS" id="4185">
        <property type="hits" value="38 hits in 1145 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM11">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM11"/>
    <dbReference type="GenomeRNAi" id="4185"/>
    <dbReference type="Pharos" id="O75078">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O75078"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="O75078">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000073670">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 139 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O75078">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030424">
        <property type="term" value="C:axon"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043204">
        <property type="term" value="C:perikaryon"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042734">
        <property type="term" value="C:presynaptic membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005178">
        <property type="term" value="F:integrin binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0061367">
        <property type="term" value="P:behavioral response to acetic acid induced pain"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0061368">
        <property type="term" value="P:behavioral response to formalin induced pain"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045184">
        <property type="term" value="P:establishment of protein localization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007229">
        <property type="term" value="P:integrin-mediated signaling pathway"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033555">
        <property type="term" value="P:multicellular organismal response to stress"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.10.25.10:FF:000147">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000014">
        <property type="entry name" value="disintegrin and metalloproteinase domain-containing protein 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.10.25.10">
        <property type="entry name" value="Laminin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF114">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF23106">
        <property type="entry name" value="EGF_Teneurin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00022">
        <property type="entry name" value="EGF_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0770">Synapse</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="23"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029074" evidence="1">
        <location>
            <begin position="24"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029075" description="Disintegrin and metalloproteinase domain-containing protein 11">
        <location>
            <begin position="226"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="226"/>
            <end position="734"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="735"/>
            <end position="755"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="756"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="6">
        <location>
            <begin position="239"/>
            <end position="438"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="4">
        <location>
            <begin position="444"/>
            <end position="531"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="5">
        <location>
            <begin position="677"/>
            <end position="709"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="40"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for localization to cerebellar cortex basket cell terminals. Also required for localization of KCNA1, KCNA2, DLG4 and ADAM22 to cerebellar cortex basket cell terminal perisomatic axons and pinceaux" evidence="2">
        <location>
            <begin position="332"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="7">
        <location>
            <begin position="61"/>
            <end position="73"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="605"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="673"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="349"/>
            <end position="433"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="392"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="394"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="503"/>
            <end position="523"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="677"/>
            <end position="692"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="686"/>
            <end position="698"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="700"/>
            <end position="709"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005472" description="In isoform Short." evidence="9">
        <location>
            <begin position="1"/>
            <end position="99"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005473" description="In isoform Short." evidence="9">
        <original>DLELN</original>
        <variation>MCWLS</variation>
        <location>
            <begin position="100"/>
            <end position="104"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005474" description="In isoform Short." evidence="9">
        <original>DVLCGFLLCVNISGAPRLGDLVGDISSVT</original>
        <variation>PQQGRAVWLPPLCQHLWSSSARGPGGRHQ</variation>
        <location>
            <begin position="595"/>
            <end position="623"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005475" description="In isoform Short." evidence="9">
        <location>
            <begin position="624"/>
            <end position="769"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062669" description="In a pancreatic ductal adenocarcinoma sample; somatic mutation." evidence="8">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="693"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAA06670 and 3; BAA06671." evidence="10" ref="2 3">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAA04213." evidence="10" ref="2">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="325"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9R1V4"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="18772397"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="8252040"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <sequence length="769" mass="83418" checksum="EEB091EB6730AC36" modified="2006-10-03" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="178" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TC27</accession>
    <accession>Q8TC42</accession>
    <name>ADA32_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 32</fullName>
            <shortName>ADAM 32</shortName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADAM32</name>
        <name type="ORF">UNQ5982/PRO21340</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Hong S."/>
                <person name="Jung Y.-K."/>
                <person name="Kim D.H."/>
                <person name="Cho C."/>
            </authorList>
            <dbReference type="PubMed" id="12568724"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(02)01202-7"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Cell" volume="127" first="635" last="648">
            <title>Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
                <person name="Gnad F."/>
                <person name="Macek B."/>
                <person name="Kumar C."/>
                <person name="Mortensen P."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="17081983"/>
            <dbReference type="DOI" id="10.1016/j.cell.2006.09.026"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1">May play a role in sperm development and fertilization This is a non-catalytic metalloprotease-like protein.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18273040">
            <id>Q8TC27</id>
        </interactant>
        <interactant intactId="EBI-10215641">
            <id>P56748</id>
            <label>CLDN8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Membrane</location>
            <topology evidence="11">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7">Testis specific.</text>
    </comment>
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        <property type="protein sequence ID" value="AAQ89099.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC105091">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC105185">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC026085">
        <property type="protein sequence ID" value="AAH26085.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC026169">
        <property type="protein sequence ID" value="AAH26169.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC028702">
        <property type="protein sequence ID" value="AAH28702.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC030014">
        <property type="protein sequence ID" value="AAH30014.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC030698">
        <property type="protein sequence ID" value="AAH30698.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC034975">
        <property type="protein sequence ID" value="AAH34975.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS47846.1"/>
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        <property type="nucleotide sequence ID" value="NM_001313994.1"/>
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    <dbReference type="SMR" id="Q8TC27"/>
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        <property type="interactions" value="28"/>
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    <dbReference type="FunCoup" id="Q8TC27">
        <property type="interactions" value="64"/>
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    <dbReference type="IntAct" id="Q8TC27">
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    <dbReference type="STRING" id="9606.ENSP00000369238"/>
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        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
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        <property type="glycosylation" value="4 sites"/>
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        <property type="antibodies" value="155 antibodies from 25 providers"/>
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        <property type="protein sequence ID" value="ENSP00000369238.4"/>
        <property type="gene ID" value="ENSG00000197140.16"/>
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    <dbReference type="Ensembl" id="ENST00000615420.4">
        <property type="protein sequence ID" value="ENSP00000484817.1"/>
        <property type="gene ID" value="ENSG00000275594.4"/>
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    <dbReference type="GeneID" id="203102"/>
    <dbReference type="KEGG" id="hsa:203102"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_145004.7"/>
        <property type="RefSeq protein sequence ID" value="NP_659441.4"/>
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    <dbReference type="UCSC" id="uc003xmt.5">
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:15479"/>
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        <property type="gene designation" value="ADAM32"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000197140">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="618602">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000197140"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
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    <dbReference type="OMA" id="GWQCLCP"/>
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        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
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        <property type="hits" value="18 hits in 1147 CRISPR screens"/>
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        <property type="development level" value="Tdark"/>
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    <dbReference type="PRO" id="PR:Q8TC27"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
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    <dbReference type="RNAct" id="Q8TC27">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000197140">
        <property type="expression patterns" value="Expressed in left testis and 98 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8TC27">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0009986">
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        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
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    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
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    <dbReference type="GO" id="GO:0007339">
        <property type="term" value="P:binding of sperm to zona pellucida"/>
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        <property type="term" value="P:male gonad development"/>
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    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 17"/>
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        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="2.60.120.260">
        <property type="entry name" value="Galactose-binding domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
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    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
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    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
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    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
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    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
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    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
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    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 32"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF23106">
        <property type="entry name" value="EGF_Teneurin"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00608">
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        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
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        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
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    <feature type="propeptide" id="PRO_0000029138" evidence="2">
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            <begin position="17"/>
            <end position="174"/>
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            <begin position="175"/>
            <end position="787"/>
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    <feature type="topological domain" description="Extracellular" evidence="2">
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            <begin position="175"/>
            <end position="682"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="683"/>
            <end position="703"/>
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    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="704"/>
            <end position="787"/>
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    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="186"/>
            <end position="383"/>
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    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="391"/>
            <end position="479"/>
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    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="622"/>
            <end position="654"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="715"/>
            <end position="787"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="6">
        <location>
            <begin position="728"/>
            <end position="749"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="771"/>
            <end position="787"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12 13">
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="125"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="465"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="598"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="295"/>
            <end position="378"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="337"/>
            <end position="362"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="339"/>
            <end position="344"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="450"/>
            <end position="471"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="626"/>
            <end position="636"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="630"/>
            <end position="642"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="644"/>
            <end position="653"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055241" description="In dbSNP:rs17856744." evidence="10">
        <original>Q</original>
        <variation>R</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055242" description="In dbSNP:rs17852343." evidence="10">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055243" description="In dbSNP:rs9643859.">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="327"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051591" description="In dbSNP:rs7845771." evidence="8 10">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="467"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055244" description="In dbSNP:rs13277386.">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="658"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061739" description="In dbSNP:rs28705715.">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="778"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
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    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="12568724"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12975309"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15340161"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="17081983"/>
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    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <sequence length="787" mass="87948" checksum="841EDA9EFF483A2C" modified="2010-05-18" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-07-05" modified="2026-01-28" version="194" xmlns="https://uniprot.org/uniprot">
    <accession>O75689</accession>
    <accession>A4D2Q2</accession>
    <accession>B3KRZ4</accession>
    <accession>B4DVA6</accession>
    <accession>F6XZ68</accession>
    <accession>H7C2Q4</accession>
    <name>ADAP1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with dual PH domain-containing protein 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-alpha-1</fullName>
            <shortName>Cnt-a1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Putative MAPK-activating protein PM25</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAP1</name>
        <name type="synonym">CENTA1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="12" key="1">
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            <dbReference type="PubMed" id="10448098"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF ARG-149 AND ARG-273</scope>
        <source>
            <tissue evidence="4">Blood</tissue>
        </source>
    </reference>
    <reference evidence="12 16" key="2">
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            <title>Identification of centaurin-alpha1 as a potential in vivo phosphatidylinositol 3,4,5-trisphosphate-binding protein that is functionally homologous to the yeast ADP-ribosylation factor (ARF) GTPase-activating protein, Gcs1.</title>
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                <person name="Venkateswarlu K."/>
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            <dbReference type="PubMed" id="10333475"/>
            <dbReference type="DOI" id="10.1042/bj3400359"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF CYS-21; CYS-24; ARG-149 AND ARG-273</scope>
        <scope>VARIANT SER-241</scope>
        <source>
            <tissue evidence="16">Peripheral blood</tissue>
        </source>
    </reference>
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            <title>Molecular identification of a high-affinity Ins(1,3,4,5)tetrakisphosphate/phosphatidylinositol(3,4, 5)trisphosphate binding protein from human brain, p42IP4.</title>
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                <person name="Reiser G."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-241</scope>
        <source>
            <tissue evidence="13">Brain</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="12761501"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-241</scope>
        <source>
            <tissue>Lung fibroblast</tissue>
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                <person name="Ohmori Y."/>
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                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Okumura K."/>
                <person name="Nagase T."/>
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                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Sugano S."/>
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="12690205"/>
            <dbReference type="DOI" id="10.1126/science.1083423"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-241</scope>
        <source>
            <tissue evidence="14">Brain</tissue>
        </source>
    </reference>
    <reference evidence="12" key="9">
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            <authorList>
                <person name="Zemlickova E."/>
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            <dbReference type="PubMed" id="12893243"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(03)01187-2"/>
        </citation>
        <scope>INTERACTION WITH PRKCA; PRKCI; PRKCZ AND PRKD1</scope>
        <scope>PHOSPHORYLATION AT SER-87 AND THR-276</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
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                <person name="Choudhary C."/>
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            </authorList>
            <dbReference type="PubMed" id="19608861"/>
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        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-272</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
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                <person name="Okawa Y."/>
                <person name="Akter S."/>
                <person name="Ito H."/>
                <person name="Shiba Y."/>
            </authorList>
            <dbReference type="PubMed" id="38682696"/>
            <dbReference type="DOI" id="10.1242/bio.060338"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
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            <title>Crystal structure of full length centaurin alpha-1.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 3-370</scope>
    </reference>
    <comment type="function">
        <text evidence="4 8 10 12">GTPase-activating protein for the ADP ribosylation factor family (Probable). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Regulates the incorporation of CD63 and CD9 into multivesicular bodies (PubMed:38682696).</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Interacts with PRKCA, PRKCI and PRKCZ. Interacts with the N-terminal region of PRKD1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714732">
            <id>O75689</id>
        </interactant>
        <interactant intactId="EBI-739789">
            <id>Q92997</id>
            <label>DVL3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714732">
            <id>O75689</id>
        </interactant>
        <interactant intactId="EBI-618309">
            <id>Q08379</id>
            <label>GOLGA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714732">
            <id>O75689</id>
        </interactant>
        <interactant intactId="EBI-766408">
            <id>Q9NQT8</id>
            <label>KIF13B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714732">
            <id>O75689</id>
        </interactant>
        <interactant intactId="EBI-742388">
            <id>Q9H8W4</id>
            <label>PLEKHF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-714732">
            <id>O75689</id>
        </interactant>
        <interactant intactId="EBI-742426">
            <id>Q9H190</id>
            <label>SDCBP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <text>Recruited to the plasma membrane upon epidermal growth factor-dependent activation of phosphatidylinositol 4,5-diphosphate (PtdInsP2) 3-kinase.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O75689-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O75689-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054794"/>
        </isoform>
        <isoform>
            <id>O75689-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_054793"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Expressed at highest levels in brain and at lower levels in peripheral blood leukocytes.</text>
    </comment>
    <comment type="PTM">
        <text evidence="6">Phosphorylated by PRKCA, PRKCI, PRKCZ and PRKD1 in vitro.</text>
    </comment>
    <dbReference type="EMBL" id="AJ006422">
        <property type="protein sequence ID" value="CAA07024.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF082324">
        <property type="protein sequence ID" value="AAD11414.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB097049">
        <property type="protein sequence ID" value="BAC77402.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300999">
        <property type="protein sequence ID" value="BAG62618.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073957">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092471">
        <property type="protein sequence ID" value="BAG52556.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236965">
        <property type="protein sequence ID" value="EAL23709.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471144">
        <property type="protein sequence ID" value="EAW87183.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471144">
        <property type="protein sequence ID" value="EAW87184.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033747">
        <property type="protein sequence ID" value="AAH33747.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5318.1">
        <molecule id="O75689-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64576.1">
        <molecule id="O75689-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64577.1">
        <molecule id="O75689-2"/>
    </dbReference>
    <dbReference type="PIR" id="JC7091">
        <property type="entry name" value="JC7091"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001271237.2">
        <molecule id="O75689-2"/>
        <property type="nucleotide sequence ID" value="NM_001284308.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001271238.2">
        <molecule id="O75689-3"/>
        <property type="nucleotide sequence ID" value="NM_001284309.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001271239.2">
        <molecule id="O75689-3"/>
        <property type="nucleotide sequence ID" value="NM_001284310.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001271240.2">
        <property type="nucleotide sequence ID" value="NM_001284311.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006860.2">
        <molecule id="O75689-1"/>
        <property type="nucleotide sequence ID" value="NM_006869.4"/>
    </dbReference>
    <dbReference type="PDB" id="3FEH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.90 A"/>
        <property type="chains" value="A=3-370"/>
    </dbReference>
    <dbReference type="PDB" id="3FM8">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="C/D=1-374"/>
    </dbReference>
    <dbReference type="PDB" id="3LJU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="X=3-370"/>
    </dbReference>
    <dbReference type="PDB" id="3MDB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.95 A"/>
        <property type="chains" value="C/D=1-374"/>
    </dbReference>
    <dbReference type="PDBsum" id="3FEH"/>
    <dbReference type="PDBsum" id="3FM8"/>
    <dbReference type="PDBsum" id="3LJU"/>
    <dbReference type="PDBsum" id="3MDB"/>
    <dbReference type="AlphaFoldDB" id="O75689"/>
    <dbReference type="SMR" id="O75689"/>
    <dbReference type="BioGRID" id="116222">
        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-41731N"/>
    <dbReference type="FunCoup" id="O75689">
        <property type="interactions" value="1614"/>
    </dbReference>
    <dbReference type="IntAct" id="O75689">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="MINT" id="O75689"/>
    <dbReference type="STRING" id="9606.ENSP00000442682"/>
    <dbReference type="GlyGen" id="O75689">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O75689"/>
    <dbReference type="PhosphoSitePlus" id="O75689"/>
    <dbReference type="BioMuta" id="ADAP1"/>
    <dbReference type="jPOST" id="O75689"/>
    <dbReference type="MassIVE" id="O75689"/>
    <dbReference type="PaxDb" id="9606-ENSP00000442682"/>
    <dbReference type="PeptideAtlas" id="O75689"/>
    <dbReference type="ProteomicsDB" id="28173"/>
    <dbReference type="ProteomicsDB" id="45067"/>
    <dbReference type="ProteomicsDB" id="50162">
        <molecule id="O75689-1"/>
    </dbReference>
    <dbReference type="Pumba" id="O75689"/>
    <dbReference type="Antibodypedia" id="1977">
        <property type="antibodies" value="220 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="11033"/>
    <dbReference type="Ensembl" id="ENST00000265846.10">
        <molecule id="O75689-1"/>
        <property type="protein sequence ID" value="ENSP00000265846.5"/>
        <property type="gene ID" value="ENSG00000105963.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000449296.6">
        <molecule id="O75689-3"/>
        <property type="protein sequence ID" value="ENSP00000407267.2"/>
        <property type="gene ID" value="ENSG00000105963.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000539900.5">
        <molecule id="O75689-2"/>
        <property type="protein sequence ID" value="ENSP00000442682.1"/>
        <property type="gene ID" value="ENSG00000105963.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000611167.4">
        <molecule id="O75689-3"/>
        <property type="protein sequence ID" value="ENSP00000481154.1"/>
        <property type="gene ID" value="ENSG00000105963.16"/>
    </dbReference>
    <dbReference type="GeneID" id="11033"/>
    <dbReference type="KEGG" id="hsa:11033"/>
    <dbReference type="MANE-Select" id="ENST00000265846.10">
        <property type="protein sequence ID" value="ENSP00000265846.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006869.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006860.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003sjn.5">
        <molecule id="O75689-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16486"/>
    <dbReference type="ClinPGx" id="PA26404"/>
    <dbReference type="CTD" id="11033"/>
    <dbReference type="DisGeNET" id="11033"/>
    <dbReference type="GeneCards" id="ADAP1"/>
    <dbReference type="HGNC" id="HGNC:16486">
        <property type="gene designation" value="ADAP1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000105963">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MIM" id="608114">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000105963"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000105963"/>
    <dbReference type="eggNOG" id="KOG0703">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155698"/>
    <dbReference type="HOGENOM" id="CLU_061583_0_0_1"/>
    <dbReference type="InParanoid" id="O75689"/>
    <dbReference type="OMA" id="YYNRNDA"/>
    <dbReference type="PAN-GO" id="O75689">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O75689"/>
    <dbReference type="PathwayCommons" id="O75689"/>
    <dbReference type="Reactome" id="R-HSA-1251985">
        <property type="pathway name" value="Nuclear signaling by ERBB4"/>
    </dbReference>
    <dbReference type="SignaLink" id="O75689"/>
    <dbReference type="SIGNOR" id="O75689"/>
    <dbReference type="Agora" id="ENSG00000105963"/>
    <dbReference type="BioGRID-ORCS" id="11033">
        <property type="hits" value="28 hits in 1146 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAP1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="O75689"/>
    <dbReference type="GeneWiki" id="Centaurin,_alpha_1"/>
    <dbReference type="GenomeRNAi" id="11033"/>
    <dbReference type="Pharos" id="O75689">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O75689"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="O75689">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000105963">
        <property type="expression patterns" value="Expressed in C1 segment of cervical spinal cord and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O75689">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043533">
        <property type="term" value="F:inositol 1,3,4,5 tetrakisphosphate binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902936">
        <property type="term" value="F:phosphatidylinositol bisphosphate binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005547">
        <property type="term" value="F:phosphatidylinositol-3,4,5-trisphosphate binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007166">
        <property type="term" value="P:cell surface receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043087">
        <property type="term" value="P:regulation of GTPase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd08843">
        <property type="entry name" value="ArfGap_ADAP1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13252">
        <property type="entry name" value="PH1_ADAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01251">
        <property type="entry name" value="PH2_ADAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000011">
        <property type="entry name" value="Arf-GAP with dual PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000080">
        <property type="entry name" value="Arf-GAP with dual PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000099">
        <property type="entry name" value="Arf-GAP with dual PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052589">
        <property type="entry name" value="Arf-GAP_dual-PH_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037849">
        <property type="entry name" value="PH1_ADAP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037851">
        <property type="entry name" value="PH2_ADAP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46021:SF5">
        <property type="entry name" value="ARF-GAP WITH DUAL PH DOMAIN-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46021">
        <property type="entry name" value="ARF-GAP WITH DUAL PH DOMAIN-CONTAINING PROTEIN 1-LIKE PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000074205" description="Arf-GAP with dual PH domain-containing protein 1">
        <location>
            <begin position="1"/>
            <end position="374"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="7"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="domain" description="PH 1" evidence="1">
        <location>
            <begin position="129"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="domain" description="PH 2" evidence="1">
        <location>
            <begin position="252"/>
            <end position="356"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="21"/>
            <end position="44"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by PKC" evidence="6">
        <location>
            <position position="87"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="17">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine; by PKC" evidence="6">
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054793" description="In isoform 3." evidence="11">
        <location>
            <begin position="1"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054794" description="In isoform 2." evidence="11">
        <original>MAKERRRAVLELLQRPGNARCADCGAP</original>
        <variation>MFQFVFSRVYCINPARRKWKEFEKMLGCAEEGHASLGR</variation>
        <location>
            <begin position="1"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_047470" description="In dbSNP:rs10256887." evidence="3 5 7 9">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of GTPase-activating activity." evidence="3">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of GTPase-activating activity." evidence="3">
        <original>C</original>
        <variation>A</variation>
        <location>
            <position position="24"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="40-45% reduction in PtdInsP2 3-kinase dependent membrane localization. Almost complete loss of PtdInsP2 3-kinase dependent membrane localization; when associated with C-273." evidence="3 4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="70% reduction in PtdInsP2 3-kinase dependent membrane localization. Almost complete loss of PtdInsP2 3-kinase dependent membrane localization; when associated with C-149." evidence="3 4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="273"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; BAG52556." evidence="12" ref="5">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="3"/>
            <end position="12"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="16"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="22"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="31"/>
            <end position="33"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="34"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="38"/>
            <end position="40"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="42"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="52"/>
            <end position="54"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="57"/>
            <end position="59"/>
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    <reference key="1">
        <citation type="submission" date="1999-04" db="EMBL/GenBank/DDBJ databases">
            <title>Nucleotide sequence of the human tMDC III sperm surface protein transcript.</title>
            <authorList>
                <person name="Hall L."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <tissue>Testis</tissue>
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            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
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            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <reference key="3">
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
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    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="Hum. Mutat." volume="32" first="E2148" last="E2175">
            <title>Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Moncada-Pazos A."/>
                <person name="Cal S."/>
                <person name="Soria-Valles C."/>
                <person name="Gartner J."/>
                <person name="Rudloff U."/>
                <person name="Lin J.C."/>
                <person name="Rosenberg S.A."/>
                <person name="Lopez-Otin C."/>
                <person name="Samuels Y."/>
            </authorList>
            <dbReference type="PubMed" id="21618342"/>
            <dbReference type="DOI" id="10.1002/humu.21477"/>
        </citation>
        <scope>VARIANTS SER-170; GLY-284; ILE-344; LYS-362 AND LEU-536</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Y3Q7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y3Q7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_012033"/>
        </isoform>
        <isoform>
            <id>Q9Y3Q7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043285 VSP_043286"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed specifically in testis.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">A tripeptide motif (ECD) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The prodomain and the metalloprotease-like domain are cleaved during the epididymal maturation of the spermatozoa.</text>
    </comment>
    <dbReference type="EMBL" id="AJ133004">
        <property type="protein sequence ID" value="CAB40812.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358321">
        <property type="protein sequence ID" value="AAQ88687.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313961">
        <property type="protein sequence ID" value="BAG36677.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC109633">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC136365">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC034624">
        <property type="protein sequence ID" value="AAH34624.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC070279">
        <property type="protein sequence ID" value="AAH70279.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC121045">
        <property type="protein sequence ID" value="AAI21046.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55225.1">
        <molecule id="Q9Y3Q7-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6113.1">
        <molecule id="Q9Y3Q7-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS83287.1">
        <molecule id="Q9Y3Q7-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001177885.1">
        <molecule id="Q9Y3Q7-3"/>
        <property type="nucleotide sequence ID" value="NM_001190956.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307242.1">
        <molecule id="Q9Y3Q7-2"/>
        <property type="nucleotide sequence ID" value="NM_001320313.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055052.1">
        <molecule id="Q9Y3Q7-1"/>
        <property type="nucleotide sequence ID" value="NM_014237.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9Y3Q7"/>
    <dbReference type="SMR" id="Q9Y3Q7"/>
    <dbReference type="BioGRID" id="114285">
        <property type="interactions" value="29"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y3Q7">
        <property type="interactions" value="30"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000265707"/>
    <dbReference type="MEROPS" id="M12.957"/>
    <dbReference type="GlyCosmos" id="Q9Y3Q7">
        <property type="glycosylation" value="12 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9Y3Q7">
        <property type="glycosylation" value="12 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y3Q7"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y3Q7"/>
    <dbReference type="BioMuta" id="ADAM18"/>
    <dbReference type="DMDM" id="20137582"/>
    <dbReference type="jPOST" id="Q9Y3Q7"/>
    <dbReference type="MassIVE" id="Q9Y3Q7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000265707"/>
    <dbReference type="PeptideAtlas" id="Q9Y3Q7"/>
    <dbReference type="ProteomicsDB" id="86061">
        <molecule id="Q9Y3Q7-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="86062">
        <molecule id="Q9Y3Q7-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="23870">
        <property type="antibodies" value="38 antibodies from 7 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8749"/>
    <dbReference type="Ensembl" id="ENST00000265707.10">
        <molecule id="Q9Y3Q7-1"/>
        <property type="protein sequence ID" value="ENSP00000265707.5"/>
        <property type="gene ID" value="ENSG00000168619.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000379866.5">
        <molecule id="Q9Y3Q7-2"/>
        <property type="protein sequence ID" value="ENSP00000369195.1"/>
        <property type="gene ID" value="ENSG00000168619.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000520772.5">
        <molecule id="Q9Y3Q7-3"/>
        <property type="protein sequence ID" value="ENSP00000429908.1"/>
        <property type="gene ID" value="ENSG00000168619.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000613609.4">
        <molecule id="Q9Y3Q7-1"/>
        <property type="protein sequence ID" value="ENSP00000482348.1"/>
        <property type="gene ID" value="ENSG00000278548.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000633688.1">
        <molecule id="Q9Y3Q7-3"/>
        <property type="protein sequence ID" value="ENSP00000488128.1"/>
        <property type="gene ID" value="ENSG00000278548.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000633768.1">
        <molecule id="Q9Y3Q7-2"/>
        <property type="protein sequence ID" value="ENSP00000488176.1"/>
        <property type="gene ID" value="ENSG00000278548.4"/>
    </dbReference>
    <dbReference type="GeneID" id="8749"/>
    <dbReference type="KEGG" id="hsa:8749"/>
    <dbReference type="MANE-Select" id="ENST00000265707.10">
        <property type="protein sequence ID" value="ENSP00000265707.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014237.3"/>
        <property type="RefSeq protein sequence ID" value="NP_055052.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xnh.4">
        <molecule id="Q9Y3Q7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:196"/>
    <dbReference type="ClinPGx" id="PA24513"/>
    <dbReference type="CTD" id="8749"/>
    <dbReference type="GeneCards" id="ADAM18"/>
    <dbReference type="HGNC" id="HGNC:196">
        <property type="gene designation" value="ADAM18"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000168619">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="619495">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000168619"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000168619"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162281"/>
    <dbReference type="HOGENOM" id="CLU_012714_4_3_1"/>
    <dbReference type="InParanoid" id="Q9Y3Q7"/>
    <dbReference type="OMA" id="GPQMYCV"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9Y3Q7">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y3Q7"/>
    <dbReference type="PathwayCommons" id="Q9Y3Q7"/>
    <dbReference type="Agora" id="ENSG00000168619"/>
    <dbReference type="BioGRID-ORCS" id="8749">
        <property type="hits" value="12 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM18">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM18"/>
    <dbReference type="GenomeRNAi" id="8749"/>
    <dbReference type="Pharos" id="Q9Y3Q7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y3Q7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y3Q7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000168619">
        <property type="expression patterns" value="Expressed in testis and 21 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y3Q7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007339">
        <property type="term" value="P:binding of sperm to zona pellucida"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007155">
        <property type="term" value="P:cell adhesion"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008584">
        <property type="term" value="P:male gonad development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007283">
        <property type="term" value="P:spermatogenesis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000033">
        <property type="entry name" value="A disintegrin and metallopeptidase domain 18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF158">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 18"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029096" evidence="2">
        <location>
            <begin position="17"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029097" description="Disintegrin and metalloproteinase domain-containing protein 18">
        <location>
            <begin position="185"/>
            <end position="739"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="177"/>
            <end position="687"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="688"/>
            <end position="708"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="709"/>
            <end position="739"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="4">
        <location>
            <begin position="184"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="390"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like">
        <location>
            <begin position="620"/>
            <end position="654"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="122"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="294"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="465"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="561"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="611"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="625"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="293"/>
            <end position="376"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="335"/>
            <end position="360"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="337"/>
            <end position="342"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="450"/>
            <end position="471"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="624"/>
            <end position="636"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="630"/>
            <end position="642"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="644"/>
            <end position="653"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043285" description="In isoform 3." evidence="7">
        <original>IKNLSKLL</original>
        <variation>VTVIILML</variation>
        <location>
            <begin position="175"/>
            <end position="182"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_043286" description="In isoform 3." evidence="7">
        <location>
            <begin position="183"/>
            <end position="739"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_012033" description="In isoform 2." evidence="6">
        <location>
            <begin position="197"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066312" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267601916." evidence="5">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_051588" description="In dbSNP:rs10093794.">
        <original>V</original>
        <variation>F</variation>
        <location>
            <position position="212"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066313" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="5">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066314" description="In a cutaneous metastatic melanoma sample; somatic mutation; dbSNP:rs267601918." evidence="5">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066315" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="5">
        <original>M</original>
        <variation>K</variation>
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066316" description="In a cutaneous metastatic melanoma sample; somatic mutation." evidence="5">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="536"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="21618342"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="12975309"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <sequence length="739" mass="82856" checksum="2D8BE9A975072CDD" modified="1999-11-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-27" modified="2026-01-28" version="174" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NPF8</accession>
    <accession>Q8N4Q6</accession>
    <accession>Q96SD5</accession>
    <name>ADAP2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with dual PH domain-containing protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-alpha-2</fullName>
            <shortName>Cnt-a2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAP2</name>
        <name type="synonym">CENTA2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Eur. J. Cell Biol." volume="81" first="222" last="230">
            <title>Identification of centaurin-alpha2: a phosphatidylinositide-binding protein present in fat, heart and skeletal muscle.</title>
            <authorList>
                <person name="Whitley P."/>
                <person name="Gibbard A.M."/>
                <person name="Koumanov F."/>
                <person name="Oldfield S."/>
                <person name="Kilgour E.E."/>
                <person name="Prestwich G.D."/>
                <person name="Holman G.D."/>
            </authorList>
            <dbReference type="PubMed" id="12018390"/>
            <dbReference type="DOI" id="10.1078/0171-9335-00242"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Genomics" volume="66" first="93" last="97">
            <title>A common set of at least 11 functional genes is lost in the majority of NF1 patients with gross deletions.</title>
            <authorList>
                <person name="Jenne D.E."/>
                <person name="Tinschert S."/>
                <person name="Stegmann E."/>
                <person name="Reimann H."/>
                <person name="Nuernberg P."/>
                <person name="Horn D."/>
                <person name="Naumann I."/>
                <person name="Buske A."/>
                <person name="Thiel G."/>
            </authorList>
            <dbReference type="PubMed" id="10843809"/>
            <dbReference type="DOI" id="10.1006/geno.2000.6179"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="1999-05" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Bertsch U."/>
                <person name="Illies C."/>
                <person name="Mayr G.W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Leukocyte</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="J. Neurochem." volume="88" first="326" last="336">
            <title>Identification of gene structure and subcellular localization of human centaurin alpha 2, and p42IP4, a family of two highly homologous, Ins 1,3,4,5-P4-/PtdIns 3,4,5-P3-binding, adapter proteins.</title>
            <authorList>
                <person name="Hanck T."/>
                <person name="Stricker R."/>
                <person name="Sedehizade F."/>
                <person name="Reiser G."/>
            </authorList>
            <dbReference type="PubMed" id="14690521"/>
            <dbReference type="DOI" id="10.1046/j.1471-4159.2003.02143.x"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 5">GTPase-activating protein for the ADP ribosylation factor family (Potential). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Possesses a stoichiometry of two binding sites for InsP4 with identical affinity.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-718895">
            <id>Q9NPF8</id>
        </interactant>
        <interactant intactId="EBI-81279">
            <id>Q9Y6K9</id>
            <label>IKBKG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cell membrane</location>
        </subcellularLocation>
        <text>Constitutively associated with the plasma membrane. Excluded from the nucleus.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NPF8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NPF8-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011180"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Highly expressed in placenta, spleen, kidney, skeletal muscle and adrenal gland. Weakly expressed in thyroid, liver, heart, lung, small intestine, peripheral blood leukocytes. Not detected in spinal cord, brain, stomach, trachea, colon, lymph node and bone marrow.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="5">May be due to a competing acceptor splice site.</text>
    </comment>
    <dbReference type="EMBL" id="AJ238994">
        <property type="protein sequence ID" value="CAB88383.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ272195">
        <property type="protein sequence ID" value="CAB77266.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ242782">
        <property type="protein sequence ID" value="CAC40651.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033758">
        <property type="protein sequence ID" value="AAH33758.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11261.1">
        <molecule id="Q9NPF8-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001333643.1">
        <molecule id="Q9NPF8-2"/>
        <property type="nucleotide sequence ID" value="NM_001346714.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060874.1">
        <molecule id="Q9NPF8-1"/>
        <property type="nucleotide sequence ID" value="NM_018404.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9NPF8"/>
    <dbReference type="SMR" id="Q9NPF8"/>
    <dbReference type="BioGRID" id="120915">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NPF8">
        <property type="interactions" value="892"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NPF8">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000464121"/>
    <dbReference type="iPTMnet" id="Q9NPF8"/>
    <dbReference type="PhosphoSitePlus" id="Q9NPF8"/>
    <dbReference type="BioMuta" id="ADAP2"/>
    <dbReference type="DMDM" id="27923749"/>
    <dbReference type="jPOST" id="Q9NPF8"/>
    <dbReference type="MassIVE" id="Q9NPF8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000329468"/>
    <dbReference type="PeptideAtlas" id="Q9NPF8"/>
    <dbReference type="ProteomicsDB" id="81987">
        <molecule id="Q9NPF8-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="81988">
        <molecule id="Q9NPF8-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="26908">
        <property type="antibodies" value="169 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55803"/>
    <dbReference type="Ensembl" id="ENST00000330889.8">
        <molecule id="Q9NPF8-1"/>
        <property type="protein sequence ID" value="ENSP00000329468.3"/>
        <property type="gene ID" value="ENSG00000184060.13"/>
    </dbReference>
    <dbReference type="GeneID" id="55803"/>
    <dbReference type="KEGG" id="hsa:55803"/>
    <dbReference type="MANE-Select" id="ENST00000330889.8">
        <property type="protein sequence ID" value="ENSP00000329468.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018404.3"/>
        <property type="RefSeq protein sequence ID" value="NP_060874.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002hfx.4">
        <molecule id="Q9NPF8-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16487"/>
    <dbReference type="ClinPGx" id="PA26405"/>
    <dbReference type="CTD" id="55803"/>
    <dbReference type="DisGeNET" id="55803"/>
    <dbReference type="GeneCards" id="ADAP2"/>
    <dbReference type="HGNC" id="HGNC:16487">
        <property type="gene designation" value="ADAP2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184060">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="608635">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184060"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184060"/>
    <dbReference type="eggNOG" id="KOG0703">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156498"/>
    <dbReference type="InParanoid" id="Q9NPF8"/>
    <dbReference type="OrthoDB" id="73919at2759"/>
    <dbReference type="PAN-GO" id="Q9NPF8">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NPF8"/>
    <dbReference type="PathwayCommons" id="Q9NPF8"/>
    <dbReference type="SignaLink" id="Q9NPF8"/>
    <dbReference type="Agora" id="ENSG00000184060"/>
    <dbReference type="BioGRID-ORCS" id="55803">
        <property type="hits" value="12 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAP2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="CENTA2"/>
    <dbReference type="GenomeRNAi" id="55803"/>
    <dbReference type="Pharos" id="Q9NPF8">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NPF8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NPF8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184060">
        <property type="expression patterns" value="Expressed in monocyte and 182 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9NPF8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005740">
        <property type="term" value="C:mitochondrial envelope"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043533">
        <property type="term" value="F:inositol 1,3,4,5 tetrakisphosphate binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005547">
        <property type="term" value="F:phosphatidylinositol-3,4,5-trisphosphate binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043325">
        <property type="term" value="F:phosphatidylinositol-3,4-bisphosphate binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005546">
        <property type="term" value="F:phosphatidylinositol-4,5-bisphosphate binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030674">
        <property type="term" value="F:protein-macromolecule adaptor activity"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007507">
        <property type="term" value="P:heart development"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd08844">
        <property type="entry name" value="ArfGap_ADAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13252">
        <property type="entry name" value="PH1_ADAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01251">
        <property type="entry name" value="PH2_ADAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000080">
        <property type="entry name" value="Arf-GAP with dual PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000099">
        <property type="entry name" value="Arf-GAP with dual PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000015">
        <property type="entry name" value="arf-GAP with dual PH domain-containing protein 2 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052589">
        <property type="entry name" value="Arf-GAP_dual-PH_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037849">
        <property type="entry name" value="PH1_ADAP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037851">
        <property type="entry name" value="PH2_ADAP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46021">
        <property type="entry name" value="ARF-GAP WITH DUAL PH DOMAIN-CONTAINING PROTEIN 1-LIKE PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46021:SF6">
        <property type="entry name" value="ARF-GAP WITH DUAL PH DOMAIN-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000074206" description="Arf-GAP with dual PH domain-containing protein 2">
        <location>
            <begin position="1"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="9"/>
            <end position="131"/>
        </location>
    </feature>
    <feature type="domain" description="PH 1" evidence="1">
        <location>
            <begin position="132"/>
            <end position="233"/>
        </location>
    </feature>
    <feature type="domain" description="PH 2" evidence="1">
        <location>
            <begin position="255"/>
            <end position="361"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="25"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_011180" description="In isoform 2." evidence="4">
        <location>
            <position position="269"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; CAC40651." evidence="5" ref="3">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="12"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="14690521"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="381" mass="44349" checksum="4FAE208072A92C01" modified="2000-10-01" version="1">MGDRERNKKRLLELLRAPDTGNAHCADCGAADPDWASYKLGIFICLNCCGVHRNFPDISRVKSVRLDFWDDSIVEFMIHNGNLRVKAKFEARVPAFYYIPQANDCLVLKEQWIRAKYERREFMADGETISLPGNREGFLWKRGRDNSQFLRRKFVLLAREGLLKYFTKEQGKSPKAVISIKDLNATFQTEKIGHPHGLQITYRRDGHTRNLFVYHESGKEIVDWFNALRAARLQYLKMAFPELPESELVPFLTRNYLKQGFMEKTGPKQKEPFKKRWFALDCHERRLLYYKNPLDAFEQGQVFLGNKEQGYEAYEDLPKGIRGNRWKAGLTIVTPERRFVLTCPSEKEQQEWLESLRGVLSSPLTPLNRLTASTESGRSSR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-09-02" modified="2026-01-28" version="131" xmlns="https://uniprot.org/uniprot">
    <accession>Q6NVV9</accession>
    <accession>A8MW71</accession>
    <accession>Q4G196</accession>
    <name>ADAM5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative disintegrin and metalloproteinase domain-containing protein 5</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Putative transmembrane metalloproteinase-like, disintegrin-like, and cysteine-rich protein II</fullName>
            <shortName>tMDC II</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM5</name>
        <name type="synonym">ADAM5P</name>
        <name type="synonym">TMDC2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Biochem. J." volume="341" first="771" last="775">
            <title>Transcripts encoding the sperm surface protein tMDC II are non-functional in the human.</title>
            <authorList>
                <person name="Frayne J."/>
                <person name="Dimsey E.A."/>
                <person name="Jury J.A."/>
                <person name="Hall L."/>
            </authorList>
            <dbReference type="PubMed" id="10417343"/>
            <dbReference type="DOI" id="10.1042/bj3410771"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5; 6 AND 7)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="439" first="331" last="335">
            <title>DNA sequence and analysis of human chromosome 8.</title>
            <authorList>
                <person name="Nusbaum C."/>
                <person name="Mikkelsen T.S."/>
                <person name="Zody M.C."/>
                <person name="Asakawa S."/>
                <person name="Taudien S."/>
                <person name="Garber M."/>
                <person name="Kodira C.D."/>
                <person name="Schueler M.G."/>
                <person name="Shimizu A."/>
                <person name="Whittaker C.A."/>
                <person name="Chang J.L."/>
                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Yang X."/>
                <person name="Allen N.R."/>
                <person name="Anderson S."/>
                <person name="Asakawa T."/>
                <person name="Blechschmidt K."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Butler J."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="DeArellano K."/>
                <person name="DeCaprio D."/>
                <person name="Dooley K.T."/>
                <person name="Dorris L. III"/>
                <person name="Engels R."/>
                <person name="Gloeckner G."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hall J.L."/>
                <person name="Ishikawa S.K."/>
                <person name="Jaffe D.B."/>
                <person name="Kamat A."/>
                <person name="Kudoh J."/>
                <person name="Lehmann R."/>
                <person name="Lokitsang T."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews C.D."/>
                <person name="Mauceli E."/>
                <person name="Menzel U."/>
                <person name="Mihalev A.H."/>
                <person name="Minoshima S."/>
                <person name="Murayama Y."/>
                <person name="Naylor J.W."/>
                <person name="Nicol R."/>
                <person name="Nguyen C."/>
                <person name="O'Leary S.B."/>
                <person name="O'Neill K."/>
                <person name="Parker S.C.J."/>
                <person name="Polley A."/>
                <person name="Raymond C.K."/>
                <person name="Reichwald K."/>
                <person name="Rodriguez J."/>
                <person name="Sasaki T."/>
                <person name="Schilhabel M."/>
                <person name="Siddiqui R."/>
                <person name="Smith C.L."/>
                <person name="Sneddon T.P."/>
                <person name="Talamas J.A."/>
                <person name="Tenzin P."/>
                <person name="Topham K."/>
                <person name="Venkataraman V."/>
                <person name="Wen G."/>
                <person name="Yamazaki S."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Rosenthal A."/>
                <person name="Birren B.W."/>
                <person name="Platzer M."/>
                <person name="Shimizu N."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16421571"/>
            <dbReference type="DOI" id="10.1038/nature04406"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1 4">This is a non catalytic metalloprotease-like protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts with TEX101.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6NVV9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_035340 VSP_035343 VSP_035344"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_035339 VSP_035341"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_035340"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_035340 VSP_035342"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_035345"/>
        </isoform>
        <isoform>
            <id>Q6NVV9-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_035346"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Highly expressed in testis.</text>
    </comment>
    <comment type="caution">
        <text evidence="7">Could be the product of a pseudogene. Not expected to have protease activity.</text>
    </comment>
    <dbReference type="EMBL" id="AJ132820">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132821">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132822">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132823">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132824">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132825">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132826">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ132827">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC105185">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC026083">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067864">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6NVV9"/>
    <dbReference type="SMR" id="Q6NVV9"/>
    <dbReference type="GlyGen" id="Q6NVV9">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="BioMuta" id="HGNC:212"/>
    <dbReference type="DMDM" id="121946258"/>
    <dbReference type="jPOST" id="Q6NVV9"/>
    <dbReference type="PeptideAtlas" id="Q6NVV9"/>
    <dbReference type="TopDownProteomics" id="Q6NVV9-7">
        <molecule id="Q6NVV9-7"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:212"/>
    <dbReference type="GeneCards" id="ADAM5"/>
    <dbReference type="HGNC" id="HGNC:212">
        <property type="gene designation" value="ADAM5"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q6NVV9"/>
    <dbReference type="PAN-GO" id="Q6NVV9">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6NVV9"/>
    <dbReference type="ChiTaRS" id="ADAM5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="Pharos" id="Q6NVV9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6NVV9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6NVV9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF28">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01186">
        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000349304" description="Putative disintegrin and metalloproteinase domain-containing protein 5">
        <location>
            <begin position="1"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin">
        <location>
            <begin position="111"/>
            <end position="199"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="3">
        <location>
            <begin position="351"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035339" description="In isoform 3." evidence="5">
        <location>
            <begin position="1"/>
            <end position="84"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035340" description="In isoform 2, isoform 4 and isoform 5." evidence="5 6">
        <location>
            <begin position="1"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035341" description="In isoform 3." evidence="5">
        <original>TMQLKNISYGIEPMEAVSGFIHKIYEEKYADTNILLEENDTYTWFNSEYQVRKSSEKTDFIKLFPRYIEMHIVVDKNL</original>
        <variation>MTLILGLIQSIKSEKVQKYSGGVKDFNICSLDDFKYISSHNGLTCLQTNPLEMPHRRICGNGLLEGSEECDCGTKD</variation>
        <location>
            <begin position="85"/>
            <end position="162"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035342" description="In isoform 5." evidence="5">
        <location>
            <begin position="141"/>
            <end position="162"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035343" description="In isoform 2." evidence="5 6">
        <original>FKPANMIC</original>
        <variation>VLWWCKGF</variation>
        <location>
            <begin position="163"/>
            <end position="170"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035344" description="In isoform 2." evidence="5 6">
        <location>
            <begin position="171"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035345" description="In isoform 6." evidence="5">
        <location>
            <begin position="337"/>
            <end position="365"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035346" description="In isoform 7." evidence="5">
        <original>ERSYMEEGR</original>
        <variation>APVS</variation>
        <location>
            <begin position="404"/>
            <end position="412"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3TTE0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10417343"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="10417343"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <sequence length="412" mass="47181" checksum="8F1E8FC241CFD471" modified="2005-08-30" version="2">MQTSILIKSSCRPQFQRRFHHRMQKQIQNIISILSSASVINSYDENDIRHSKPLLVQMDCNYNGYVAGIPNSLVTLSVCSGLRGTMQLKNISYGIEPMEAVSGFIHKIYEEKYADTNILLEENDTYTWFNSEYQVRKSSEKTDFIKLFPRYIEMHIVVDKNLFKPANMICRKSVGKECDFTEYCNGDLPYCLPDTYVRDGEYCDSGGAFCFQGKCRTFDKQCDDLIGRGSRGAPVFCYDEINTRGDNFGNCGTAHCLFQHILCGKLVCTWEHRDLISRPNLSVIYAHVRDQTCVSTYLPRRTPPPVNSPISITSYYSAEDRDETFVQDGSMCGPDMYCFEMHCKHVRFLMNLKLCDASNHCDRHGVCNNFNHCHCEKGYNPPYCQPKQGAFGSIDDGHLVPPTERSYMEEGR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-15" modified="2026-01-28" version="158" xmlns="https://uniprot.org/uniprot">
    <accession>Q7Z6V5</accession>
    <accession>A6NL12</accession>
    <accession>B3KWY3</accession>
    <accession>Q7Z327</accession>
    <accession>Q8IY39</accession>
    <name>ADAT2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">tRNA-specific adenosine-34 deaminase catalytic subunit ADAT2</fullName>
            <ecNumber evidence="1">3.5.4.33</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Deaminase domain-containing protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAT2</name>
        <name type="synonym">DEADC1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
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    <comment type="function">
        <text evidence="1">Catalytic subunit of the tRNA-specific adenosine-34 deaminase complex, composed of the ADAT2 catalytic subunit and the ADAT3 regulatory subunit, which deaminates adenosine-34 (the first, also called wobble position of the anticodon) to inosine in many tRNAs. Inosine-34 allows the decoding of 3 different nucleotides at the third position of mRNA codons, as inosine is able to pair with U, C, and A. Binding of the ADAT2-ADAT3 complex to tRNA is mediated by the N-terminus of ADAT3 which rotates with respect to the catalytic domain of the complex, formed by ADAT2 and the ADAT3 C-terminal domain, to position the tRNA anticodon stem-loop correctly in the ADAT2 active site. The ADAT2-ADAT3 complex is required for radial migration of projection neurons in the developing brain cortex, and the catalytic activity of the complex is necessary for this function.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>adenosine(34) in tRNA + H2O + H(+) = inosine(34) in tRNA + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:43168"/>
            <dbReference type="Rhea" id="RHEA-COMP:10373"/>
            <dbReference type="Rhea" id="RHEA-COMP:10374"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:74411"/>
            <dbReference type="ChEBI" id="CHEBI:82852"/>
            <dbReference type="EC" id="3.5.4.33"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="1">Heterodimer with regulatory subunit ADAT3 to form the tRNA-specific adenosine-34 deaminase complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
        </interactant>
        <interactant intactId="EBI-3922811">
            <id>Q96EY9</id>
            <label>ADAT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
        </interactant>
        <interactant intactId="EBI-741200">
            <id>Q8IVL1</id>
            <label>NAV2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
        </interactant>
        <interactant intactId="EBI-744081">
            <id>Q96EQ0</id>
            <label>SGTB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
        </interactant>
        <interactant intactId="EBI-358489">
            <id>Q96GM5</id>
            <label>SMARCD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
        </interactant>
        <interactant intactId="EBI-5235340">
            <id>Q7Z699</id>
            <label>SPRED1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">The ADAT2-ADAT3 complex shows a diffused expression pattern in both the cytoplasm and the nucleus.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q7Z6V5-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q7Z6V5-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_025582"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH37955" version="2"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.5.4.33" evidence="1"/>
    <dbReference type="EMBL" id="AK126201">
        <property type="protein sequence ID" value="BAG54295.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX538182">
        <property type="protein sequence ID" value="CAD98054.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL031320">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471051">
        <property type="protein sequence ID" value="EAW47868.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC037955">
        <property type="protein sequence ID" value="AAH37955.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43511.1">
        <molecule id="Q7Z6V5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS69219.1">
        <molecule id="Q7Z6V5-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273188.1">
        <molecule id="Q7Z6V5-2"/>
        <property type="nucleotide sequence ID" value="NM_001286259.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_872309.2">
        <molecule id="Q7Z6V5-1"/>
        <property type="nucleotide sequence ID" value="NM_182503.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016865749.1">
        <molecule id="Q7Z6V5-2"/>
        <property type="nucleotide sequence ID" value="XM_017010260.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024302097.1">
        <molecule id="Q7Z6V5-2"/>
        <property type="nucleotide sequence ID" value="XM_024446329.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047274145.1">
        <molecule id="Q7Z6V5-2"/>
        <property type="nucleotide sequence ID" value="XM_047418189.1"/>
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    <dbReference type="RefSeq" id="XP_054210221.1">
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0819">tRNA processing</keyword>
    <keyword id="KW-0862">Zinc</keyword>
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            <begin position="1"/>
            <end position="191"/>
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    <sequence length="191" mass="21046" checksum="7F2881A100A1782E" modified="2003-10-01" version="1">MEAKAAPKPAASGACSVSAEETEKWMEEAMHMAKEALENTEVPVGCLMVYNNEVVGKGRNEVNQTKNATRHAEMVAIDQVLDWCRQSGKSPSEVFEHTVLYVTVEPCIMCAAALRLMKIPLVVYGCQNERFGGCGSVLNIASADLPNTGRPFQCIPGYRAEEAVEMLKTFYKQENPNAPKSKVRKKECQKS</sequence>
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<entry dataset="Swiss-Prot" created="2002-03-27" modified="2026-01-28" version="208" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BZ11</accession>
    <accession>A0A1K6</accession>
    <accession>Q5JT75</accession>
    <accession>Q5JT76</accession>
    <accession>Q8N0W6</accession>
    <name>ADA33_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 33</fullName>
            <shortName>ADAM 33</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
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    <gene>
        <name type="primary">ADAM33</name>
        <name type="synonym">C20orf153</name>
        <name type="ORF">UNQ873/PRO1891</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Gene" volume="282" first="227" last="236">
            <title>Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity.</title>
            <authorList>
                <person name="Yoshinaka T."/>
                <person name="Nishii K."/>
                <person name="Yamada K."/>
                <person name="Sawada H."/>
                <person name="Nishiwaki E."/>
                <person name="Smith K."/>
                <person name="Yoshino K."/>
                <person name="Ishiguro H."/>
                <person name="Higashiyama S."/>
            </authorList>
            <dbReference type="PubMed" id="11814695"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(01)00818-6"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="Nature" volume="418" first="426" last="430">
            <title>Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.</title>
            <authorList>
                <person name="Van Eerdewegh P."/>
                <person name="Little R.D."/>
                <person name="Dupuis J."/>
                <person name="Del Mastro R.G."/>
                <person name="Falls K."/>
                <person name="Simon J."/>
                <person name="Torrey D."/>
                <person name="Pandit S."/>
                <person name="McKenny J."/>
                <person name="Braunschweiger K."/>
                <person name="Walsh A."/>
                <person name="Liu Z."/>
                <person name="Hayward B."/>
                <person name="Folz C."/>
                <person name="Manning S.P."/>
                <person name="Bawa A."/>
                <person name="Saracino L."/>
                <person name="Thackston M."/>
                <person name="Benchekroun Y."/>
                <person name="Capparell N."/>
                <person name="Wang M."/>
                <person name="Adair R."/>
                <person name="Feng Y."/>
                <person name="Dubois J."/>
                <person name="FitzGerald M.G."/>
                <person name="Huang H."/>
                <person name="Gibson R."/>
                <person name="Allen K.M."/>
                <person name="Pedan A."/>
                <person name="Danzig M.R."/>
                <person name="Umland S.P."/>
                <person name="Egan R.W."/>
                <person name="Cuss F.M."/>
                <person name="Rorke S."/>
                <person name="Clough J.B."/>
                <person name="Holloway J.W."/>
                <person name="Holgate S.T."/>
                <person name="Keith T.P."/>
            </authorList>
            <dbReference type="PubMed" id="12110844"/>
            <dbReference type="DOI" id="10.1038/nature00878"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)</scope>
        <scope>INVOLVEMENT IN ASTHMA</scope>
        <source>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Genome Res." volume="13" first="2265" last="2270">
            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
            <authorList>
                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
                <person name="Abaya E."/>
                <person name="Baker K."/>
                <person name="Baldwin D.T."/>
                <person name="Brush J."/>
                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
                <person name="Currell B."/>
                <person name="Deuel B."/>
                <person name="Dowd P."/>
                <person name="Eaton D."/>
                <person name="Foster J.S."/>
                <person name="Grimaldi C."/>
                <person name="Gu Q."/>
                <person name="Hass P.E."/>
                <person name="Heldens S."/>
                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2006-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS SER-109; ALA-178; MET-272; ILE-316; SER-336; SER-365; GLU-441; ARG-515; HIS-612; ILE-710; GLY-739; TYR-742; THR-764 AND SER-774</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Matthews L.H."/>
                <person name="Ashurst J.L."/>
                <person name="Burton J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Jones M."/>
                <person name="Stavrides G."/>
                <person name="Almeida J.P."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
                <person name="Beasley O.P."/>
                <person name="Bird C.P."/>
                <person name="Blakey S.E."/>
                <person name="Bridgeman A.M."/>
                <person name="Brown A.J."/>
                <person name="Buck D."/>
                <person name="Burrill W.D."/>
                <person name="Butler A.P."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clamp M."/>
                <person name="Clark G."/>
                <person name="Clark L.N."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Cobley V.E."/>
                <person name="Collier R.E."/>
                <person name="Connor R.E."/>
                <person name="Corby N.R."/>
                <person name="Coulson A."/>
                <person name="Coville G.J."/>
                <person name="Deadman R."/>
                <person name="Dhami P.D."/>
                <person name="Dunn M."/>
                <person name="Ellington A.G."/>
                <person name="Frankland J.A."/>
                <person name="Fraser A."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths M.N.D."/>
                <person name="Gwilliam R."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Heath P.D."/>
                <person name="Ho S."/>
                <person name="Holden J.L."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Jekosch K."/>
                <person name="Johnson C.M."/>
                <person name="Johnson D."/>
                <person name="Kay M.P."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lehvaeslaiho M.H."/>
                <person name="Leversha M.A."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J.D."/>
                <person name="Marsh V.L."/>
                <person name="Martin S.L."/>
                <person name="McConnachie L.J."/>
                <person name="McLay K."/>
                <person name="McMurray A.A."/>
                <person name="Milne S.A."/>
                <person name="Mistry D."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Nickerson T."/>
                <person name="Oliver K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce T.A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Prathalingam S.R."/>
                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Scott C.E."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
                <person name="Sulston J.E."/>
                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2006" name="Eur. J. Hum. Genet." volume="14" first="1027" last="1036">
            <title>ADAM33 haplotypes are associated with asthma in a large Australian population.</title>
            <authorList>
                <person name="Kedda M.A."/>
                <person name="Duffy D.L."/>
                <person name="Bradley B."/>
                <person name="O'Hehir R.E."/>
                <person name="Thompson P.J."/>
            </authorList>
            <dbReference type="PubMed" id="16773130"/>
            <dbReference type="DOI" id="10.1038/sj.ejhg.5201662"/>
        </citation>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Thorax" volume="64" first="381" last="387">
            <title>Positionally cloned asthma susceptibility gene polymorphisms and disease risk in the British 1958 Birth Cohort.</title>
            <authorList>
                <person name="Blakey J.D."/>
                <person name="Sayers I."/>
                <person name="Ring S.M."/>
                <person name="Strachan D.P."/>
                <person name="Hall I.P."/>
            </authorList>
            <dbReference type="PubMed" id="19237393"/>
            <dbReference type="DOI" id="10.1136/thx.2008.102053"/>
        </citation>
        <scope>INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="J. Mol. Biol." volume="335" first="129" last="137">
            <title>Crystal structure of the catalytic domain of human ADAM33.</title>
            <authorList>
                <person name="Orth P."/>
                <person name="Reichert P."/>
                <person name="Wang W."/>
                <person name="Prosise W.W."/>
                <person name="Yarosh-Tomaine T."/>
                <person name="Hammond G."/>
                <person name="Ingram R.N."/>
                <person name="Xiao L."/>
                <person name="Mirza U.A."/>
                <person name="Zou J."/>
                <person name="Strickland C."/>
                <person name="Taremi S.S."/>
                <person name="Le H.V."/>
                <person name="Madison V."/>
            </authorList>
            <dbReference type="PubMed" id="14659745"/>
            <dbReference type="DOI" id="10.1016/j.jmb.2003.10.037"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 204-410 IN COMPLEX WITH METALLOPROTEASE INHIBITOR MARIMASTAT AND ZINC</scope>
        <scope>X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 204-410</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2011" name="Hum. Mutat." volume="32" first="E2148" last="E2175">
            <title>Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Moncada-Pazos A."/>
                <person name="Cal S."/>
                <person name="Soria-Valles C."/>
                <person name="Gartner J."/>
                <person name="Rudloff U."/>
                <person name="Lin J.C."/>
                <person name="Rosenberg S.A."/>
                <person name="Lopez-Otin C."/>
                <person name="Samuels Y."/>
            </authorList>
            <dbReference type="PubMed" id="21618342"/>
            <dbReference type="DOI" id="10.1002/humu.21477"/>
        </citation>
        <scope>VARIANT VAL-305</scope>
    </reference>
    <comment type="cofactor">
        <cofactor evidence="10">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="10">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10303054">
            <id>Q9BZ11-2</id>
        </interactant>
        <interactant intactId="EBI-3939278">
            <id>Q9BXN2</id>
            <label>CLEC7A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10303054">
            <id>Q9BZ11-2</id>
        </interactant>
        <interactant intactId="EBI-8644112">
            <id>Q9BRI3</id>
            <label>SLC30A2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BZ11-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BZ11-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_005495"/>
        </isoform>
        <isoform>
            <id>Q9BZ11-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_015421 VSP_005495"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Expressed in all tissues, except liver, with high expression in placenta, lung, spleen and veins.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="disease" evidence="9 11 12">
        <disease id="DI-02482">
            <name>Asthma</name>
            <acronym>ASTHMA</acronym>
            <description>The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.</description>
            <dbReference type="MIM" id="600807"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="16">By similarity with mouse isoform.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AB055891">
        <property type="protein sequence ID" value="BAB83092.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF466287">
        <property type="protein sequence ID" value="AAM80482.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF466288">
        <property type="protein sequence ID" value="AAM80483.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY358314">
        <property type="protein sequence ID" value="AAQ88680.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ995342">
        <property type="protein sequence ID" value="ABI97387.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL109804">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL356755">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13058.1">
        <molecule id="Q9BZ11-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269376.1">
        <property type="nucleotide sequence ID" value="NM_001282447.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_079496.1">
        <molecule id="Q9BZ11-1"/>
        <property type="nucleotide sequence ID" value="NM_025220.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_694882.1">
        <molecule id="Q9BZ11-2"/>
        <property type="nucleotide sequence ID" value="NM_153202.4"/>
    </dbReference>
    <dbReference type="PDB" id="1R54">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A=204-409"/>
    </dbReference>
    <dbReference type="PDB" id="1R55">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.58 A"/>
        <property type="chains" value="A=204-409"/>
    </dbReference>
    <dbReference type="PDBsum" id="1R54"/>
    <dbReference type="PDBsum" id="1R55"/>
    <dbReference type="AlphaFoldDB" id="Q9BZ11"/>
    <dbReference type="SMR" id="Q9BZ11"/>
    <dbReference type="BioGRID" id="123243">
        <property type="interactions" value="94"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BZ11">
        <property type="interactions" value="107"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BZ11">
        <property type="interactions" value="48"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000348912"/>
    <dbReference type="BindingDB" id="Q9BZ11"/>
    <dbReference type="ChEMBL" id="CHEMBL6121"/>
    <dbReference type="DrugBank" id="DB07145">
        <property type="generic name" value="(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1673"/>
    <dbReference type="MEROPS" id="M12.244"/>
    <dbReference type="GlyCosmos" id="Q9BZ11">
        <property type="glycosylation" value="5 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9BZ11">
        <property type="glycosylation" value="5 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9BZ11"/>
    <dbReference type="PhosphoSitePlus" id="Q9BZ11"/>
    <dbReference type="BioMuta" id="ADAM33"/>
    <dbReference type="DMDM" id="20137458"/>
    <dbReference type="jPOST" id="Q9BZ11"/>
    <dbReference type="MassIVE" id="Q9BZ11"/>
    <dbReference type="PaxDb" id="9606-ENSP00000348912"/>
    <dbReference type="PeptideAtlas" id="Q9BZ11"/>
    <dbReference type="ProteomicsDB" id="79748">
        <molecule id="Q9BZ11-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="79749">
        <molecule id="Q9BZ11-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="7461">
        <property type="antibodies" value="190 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="80332"/>
    <dbReference type="Ensembl" id="ENST00000350009.6">
        <molecule id="Q9BZ11-2"/>
        <property type="protein sequence ID" value="ENSP00000322550.5"/>
        <property type="gene ID" value="ENSG00000149451.20"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000356518.7">
        <molecule id="Q9BZ11-1"/>
        <property type="protein sequence ID" value="ENSP00000348912.3"/>
        <property type="gene ID" value="ENSG00000149451.20"/>
    </dbReference>
    <dbReference type="GeneID" id="80332"/>
    <dbReference type="KEGG" id="hsa:80332"/>
    <dbReference type="MANE-Select" id="ENST00000356518.7">
        <property type="protein sequence ID" value="ENSP00000348912.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_025220.5"/>
        <property type="RefSeq protein sequence ID" value="NP_079496.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002wit.5">
        <molecule id="Q9BZ11-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15478"/>
    <dbReference type="ClinPGx" id="PA24526"/>
    <dbReference type="CTD" id="80332"/>
    <dbReference type="DisGeNET" id="80332"/>
    <dbReference type="GeneCards" id="ADAM33"/>
    <dbReference type="HGNC" id="HGNC:15478">
        <property type="gene designation" value="ADAM33"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000149451">
        <property type="expression patterns" value="Tissue enhanced (cervix)"/>
    </dbReference>
    <dbReference type="MIM" id="600807">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="607114">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000149451"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000149451"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158971"/>
    <dbReference type="HOGENOM" id="CLU_012714_7_2_1"/>
    <dbReference type="InParanoid" id="Q9BZ11"/>
    <dbReference type="OMA" id="MGAQCAH"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9BZ11">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BZ11"/>
    <dbReference type="PathwayCommons" id="Q9BZ11"/>
    <dbReference type="Reactome" id="R-HSA-9762292">
        <property type="pathway name" value="Regulation of CDH11 function"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9BZ11"/>
    <dbReference type="Agora" id="ENSG00000149451"/>
    <dbReference type="BioGRID-ORCS" id="80332">
        <property type="hits" value="20 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9BZ11"/>
    <dbReference type="GeneWiki" id="ADAM33"/>
    <dbReference type="GenomeRNAi" id="80332"/>
    <dbReference type="Pharos" id="Q9BZ11">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BZ11"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BZ11">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000149451">
        <property type="expression patterns" value="Expressed in endocervix and 174 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9BZ11">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF38">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 33"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00050">
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    <feature type="sequence variant" id="VAR_030521" description="In dbSNP:rs41434648." evidence="14">
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        <source>
            <dbReference type="PubMed" id="19237393"/>
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        <source>
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        <source ref="4"/>
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        <source>
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    <evidence type="ECO:0007829" key="17">
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            <dbReference type="PDB" id="1R55"/>
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</entry>
<entry dataset="Swiss-Prot" created="2002-01-31" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H013</accession>
    <accession>Q9BZL5</accession>
    <accession>Q9UHP2</accession>
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        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 19</fullName>
            <shortName>ADAM 19</shortName>
            <ecNumber>3.4.24.-</ecNumber>
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        <alternativeName>
            <fullName>Meltrin-beta</fullName>
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        <alternativeName>
            <fullName>Metalloprotease and disintegrin dendritic antigen marker</fullName>
            <shortName>MADDAM</shortName>
        </alternativeName>
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        <name type="primary">ADAM19</name>
        <name type="synonym">MLTNB</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2000-12" db="EMBL/GenBank/DDBJ databases">
            <title>Identification of FKSG34, a novel human gene encoding for metalloprotease-disintegrin meltrin beta.</title>
            <authorList>
                <person name="Wang Y.-G."/>
                <person name="Gong L."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2000" name="Blood" volume="96" first="732" last="739">
            <title>Molecular cloning and characterization of a human metalloprotease disintegrin a novel marker for dendritic cell differentiation.</title>
            <authorList>
                <person name="Fritsche J."/>
                <person name="Moser M."/>
                <person name="Faust S."/>
                <person name="Peuker A."/>
                <person name="Buettner R."/>
                <person name="Andreesen R."/>
                <person name="Kreutz M."/>
            </authorList>
            <dbReference type="PubMed" id="10887142"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B)</scope>
        <scope>VARIANT SER-4</scope>
        <source>
            <tissue>Lymph node</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Biochem. Biophys. Res. Commun." volume="280" first="744" last="755">
            <title>Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta.</title>
            <authorList>
                <person name="Wei P."/>
                <person name="Zhao Y.-G."/>
                <person name="Zhuang L."/>
                <person name="Ruben S."/>
                <person name="Sang Q.-X.A."/>
            </authorList>
            <dbReference type="PubMed" id="11162584"/>
            <dbReference type="DOI" id="10.1006/bbrc.2000.4200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B)</scope>
        <source>
            <tissue>Dendritic cell</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nature" volume="431" first="268" last="274">
            <title>The DNA sequence and comparative analysis of human chromosome 5.</title>
            <authorList>
                <person name="Schmutz J."/>
                <person name="Martin J."/>
                <person name="Terry A."/>
                <person name="Couronne O."/>
                <person name="Grimwood J."/>
                <person name="Lowry S."/>
                <person name="Gordon L.A."/>
                <person name="Scott D."/>
                <person name="Xie G."/>
                <person name="Huang W."/>
                <person name="Hellsten U."/>
                <person name="Tran-Gyamfi M."/>
                <person name="She X."/>
                <person name="Prabhakar S."/>
                <person name="Aerts A."/>
                <person name="Altherr M."/>
                <person name="Bajorek E."/>
                <person name="Black S."/>
                <person name="Branscomb E."/>
                <person name="Caoile C."/>
                <person name="Challacombe J.F."/>
                <person name="Chan Y.M."/>
                <person name="Denys M."/>
                <person name="Detter J.C."/>
                <person name="Escobar J."/>
                <person name="Flowers D."/>
                <person name="Fotopulos D."/>
                <person name="Glavina T."/>
                <person name="Gomez M."/>
                <person name="Gonzales E."/>
                <person name="Goodstein D."/>
                <person name="Grigoriev I."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
                <person name="Hawkins T."/>
                <person name="Haydu L."/>
                <person name="Israni S."/>
                <person name="Jett J."/>
                <person name="Kadner K."/>
                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Martinez D."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nandkeshwar R."/>
                <person name="Noonan J.P."/>
                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Priest J."/>
                <person name="Ramirez L."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="Wheeler J."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="Dickson M."/>
                <person name="Cheng J.-F."/>
                <person name="Eichler E.E."/>
                <person name="Olsen A."/>
                <person name="Pennacchio L.A."/>
                <person name="Rokhsar D.S."/>
                <person name="Richardson P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="1999-03" db="EMBL/GenBank/DDBJ databases">
            <title>Partial sequence of Homo sapiens ADAM19.</title>
            <authorList>
                <person name="Xu R."/>
                <person name="Cai J."/>
                <person name="Ying B."/>
                <person name="Wang F."/>
                <person name="Xu T."/>
                <person name="Zhao S."/>
                <person name="Li C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 99-955 (ISOFORM A)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="16844" last="16851">
            <title>The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells.</title>
            <authorList>
                <person name="Abram C.L."/>
                <person name="Seals D.F."/>
                <person name="Pass I."/>
                <person name="Salinsky D."/>
                <person name="Maurer L."/>
                <person name="Roth T.M."/>
                <person name="Courtneidge S.A."/>
            </authorList>
            <dbReference type="PubMed" id="12615925"/>
            <dbReference type="DOI" id="10.1074/jbc.m300267200"/>
        </citation>
        <scope>INTERACTION WITH SH3PXD2A</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] GLN-133 AND THR-298</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
                <person name="Kern S.E."/>
                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] GLN-609</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell. Also cleaves alpha-2 macroglobulin. May be involved in osteoblast differentiation and/or osteoblast activity in bone (By similarity).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">Interacts with SH3PXD2A.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8567699">
            <id>Q9H013</id>
        </interactant>
        <interactant intactId="EBI-743598">
            <id>Q9NYB9</id>
            <label>ABI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8567699">
            <id>Q9H013</id>
        </interactant>
        <interactant intactId="EBI-7487998">
            <id>Q8TE68</id>
            <label>EPS8L1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8567699">
            <id>Q9H013</id>
        </interactant>
        <interactant intactId="EBI-2483234">
            <id>Q5TCZ1</id>
            <label>SH3PXD2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8567699">
            <id>Q9H013</id>
        </interactant>
        <interactant intactId="EBI-5915931">
            <id>O95153</id>
            <label>TSPOAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H013-1</id>
            <name>A</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H013-2</id>
            <name>B</name>
            <sequence type="described" ref="VSP_005481"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in many normal organ tissues and several cancer cell lines.</text>
    </comment>
    <comment type="induction">
        <text>By 1,25(OH)2VD3 in monocytes.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF326918">
        <property type="protein sequence ID" value="AAG50282.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y13786">
        <property type="protein sequence ID" value="CAC20585.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF311317">
        <property type="protein sequence ID" value="AAK07852.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008676">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008694">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC106801">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF134707">
        <property type="protein sequence ID" value="AAF22162.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4338.1">
        <molecule id="Q9H013-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_150377.1">
        <molecule id="Q9H013-2"/>
        <property type="nucleotide sequence ID" value="NM_033274.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047273814.1">
        <molecule id="Q9H013-1"/>
        <property type="nucleotide sequence ID" value="XM_047417858.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054209714.1">
        <molecule id="Q9H013-1"/>
        <property type="nucleotide sequence ID" value="XM_054353739.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H013"/>
    <dbReference type="SMR" id="Q9H013"/>
    <dbReference type="BioGRID" id="114267">
        <property type="interactions" value="52"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9H013">
        <property type="interactions" value="775"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H013">
        <property type="interactions" value="44"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H013"/>
    <dbReference type="STRING" id="9606.ENSP00000257527"/>
    <dbReference type="MEROPS" id="M12.214"/>
    <dbReference type="GlyCosmos" id="Q9H013">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H013">
        <property type="glycosylation" value="8 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (4 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H013"/>
    <dbReference type="PhosphoSitePlus" id="Q9H013"/>
    <dbReference type="SwissPalm" id="Q9H013"/>
    <dbReference type="BioMuta" id="ADAM19"/>
    <dbReference type="DMDM" id="302393821"/>
    <dbReference type="jPOST" id="Q9H013"/>
    <dbReference type="MassIVE" id="Q9H013"/>
    <dbReference type="PaxDb" id="9606-ENSP00000257527"/>
    <dbReference type="PeptideAtlas" id="Q9H013"/>
    <dbReference type="ProteomicsDB" id="80195">
        <molecule id="Q9H013-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="80196">
        <molecule id="Q9H013-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="16547">
        <property type="antibodies" value="249 antibodies from 35 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8728"/>
    <dbReference type="Ensembl" id="ENST00000257527.9">
        <molecule id="Q9H013-2"/>
        <property type="protein sequence ID" value="ENSP00000257527.5"/>
        <property type="gene ID" value="ENSG00000135074.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000517905.1">
        <molecule id="Q9H013-1"/>
        <property type="protein sequence ID" value="ENSP00000428654.1"/>
        <property type="gene ID" value="ENSG00000135074.17"/>
    </dbReference>
    <dbReference type="GeneID" id="8728"/>
    <dbReference type="KEGG" id="hsa:8728"/>
    <dbReference type="MANE-Select" id="ENST00000257527.9">
        <molecule id="Q9H013-2"/>
        <property type="protein sequence ID" value="ENSP00000257527.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_033274.5"/>
        <property type="RefSeq protein sequence ID" value="NP_150377.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003lwz.5">
        <molecule id="Q9H013-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:197"/>
    <dbReference type="ClinPGx" id="PA24514"/>
    <dbReference type="CTD" id="8728"/>
    <dbReference type="DisGeNET" id="8728"/>
    <dbReference type="GeneCards" id="ADAM19"/>
    <dbReference type="HGNC" id="HGNC:197">
        <property type="gene designation" value="ADAM19"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000135074">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="603640">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000135074"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000135074"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159624"/>
    <dbReference type="HOGENOM" id="CLU_012714_7_0_1"/>
    <dbReference type="InParanoid" id="Q9H013"/>
    <dbReference type="OMA" id="HGVCCEN"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9H013">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H013"/>
    <dbReference type="PathwayCommons" id="Q9H013"/>
    <dbReference type="Reactome" id="R-HSA-8941237">
        <property type="pathway name" value="Invadopodia formation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9762292">
        <property type="pathway name" value="Regulation of CDH11 function"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q9H013"/>
    <dbReference type="SignaLink" id="Q9H013"/>
    <dbReference type="SIGNOR" id="Q9H013"/>
    <dbReference type="Agora" id="ENSG00000135074"/>
    <dbReference type="BioGRID-ORCS" id="8728">
        <property type="hits" value="9 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM19">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADAM19"/>
    <dbReference type="GenomeRNAi" id="8728"/>
    <dbReference type="Pharos" id="Q9H013">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H013"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H013">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000135074">
        <property type="expression patterns" value="Expressed in oocyte and 180 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9H013">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031012">
        <property type="term" value="C:extracellular matrix"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902945">
        <property type="term" value="F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017124">
        <property type="term" value="F:SH3 domain binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042987">
        <property type="term" value="P:amyloid precursor protein catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006509">
        <property type="term" value="P:membrane protein ectodomain proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001890">
        <property type="term" value="P:placenta development"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000049">
        <property type="term" value="P:positive regulation of cell-cell adhesion mediated by cadherin"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010628">
        <property type="term" value="P:positive regulation of gene expression"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016485">
        <property type="term" value="P:protein processing"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF19">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 19"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01186">
        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50026">
        <property type="entry name" value="EGF_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00142">
        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0729">SH3-binding</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029102" evidence="1">
        <location>
            <begin position="26"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029103" description="Disintegrin and metalloproteinase domain-containing protein 19">
        <location>
            <begin position="203"/>
            <end position="955"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="203"/>
            <end position="699"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="700"/>
            <end position="720"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="721"/>
            <end position="955"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="210"/>
            <end position="408"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="416"/>
            <end position="502"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like" evidence="4">
        <location>
            <begin position="650"/>
            <end position="682"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="753"/>
            <end position="917"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="130"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="SH3-binding" evidence="2">
        <location>
            <begin position="833"/>
            <end position="844"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="7">
        <location>
            <begin position="753"/>
            <end position="771"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="787"/>
            <end position="796"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="833"/>
            <end position="844"/>
        </location>
    </feature>
    <feature type="active site" evidence="5 6">
        <location>
            <position position="346"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="132"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="345"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="349"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="355"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="444"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="447"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="645"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="320"/>
            <end position="403"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="360"/>
            <end position="387"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="361"/>
            <end position="370"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="474"/>
            <end position="494"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="654"/>
            <end position="664"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="658"/>
            <end position="670"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="672"/>
            <end position="681"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_005481" description="In isoform B." evidence="12 13">
        <original>VSPREALKVKAGTRGLQGGRCRVEKTKQFMLLVVWTELPEQKPRAKHSCFLVPA</original>
        <variation>FPEYRSQRAGGMISSKI</variation>
        <location>
            <begin position="902"/>
            <end position="955"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_057066" description="In dbSNP:rs11465228." evidence="8">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="4"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036146" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs200894535." evidence="10">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036147" description="In a colorectal cancer sample; somatic mutation; dbSNP:rs1178207005." evidence="10">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062670" description="In a pancreatic ductal adenocarcinoma sample; somatic mutation." evidence="11">
        <original>H</original>
        <variation>Q</variation>
        <location>
            <position position="609"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG50282." evidence="14" ref="1">
        <original>R</original>
        <variation>SK</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG50282 and 5; AAF22162." evidence="14" ref="1 5">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="557"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAG50282 and 5; AAF22162." evidence="14" ref="1 5">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="622"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00076"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="10887142"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12615925"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="18772397"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="10887142"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="11162584"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <sequence length="955" mass="104997" checksum="9C9D42BED18BF7F9" modified="2010-08-10" version="3" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-12-12" modified="2026-01-28" version="140" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VUY2</accession>
    <name>ADCL4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arylacetamide deacetylase-like 4</fullName>
            <ecNumber>3.1.1.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AADACL4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2006" name="Nature" volume="441" first="315" last="321">
            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
            <authorList>
                <person name="Gregory S.G."/>
                <person name="Barlow K.F."/>
                <person name="McLay K.E."/>
                <person name="Kaul R."/>
                <person name="Swarbreck D."/>
                <person name="Dunham A."/>
                <person name="Scott C.E."/>
                <person name="Howe K.L."/>
                <person name="Woodfine K."/>
                <person name="Spencer C.C.A."/>
                <person name="Jones M.C."/>
                <person name="Gillson C."/>
                <person name="Searle S."/>
                <person name="Zhou Y."/>
                <person name="Kokocinski F."/>
                <person name="McDonald L."/>
                <person name="Evans R."/>
                <person name="Phillips K."/>
                <person name="Atkinson A."/>
                <person name="Cooper R."/>
                <person name="Jones C."/>
                <person name="Hall R.E."/>
                <person name="Andrews T.D."/>
                <person name="Lloyd C."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ambrose K.D."/>
                <person name="Anderson F."/>
                <person name="Andrew R.W."/>
                <person name="Ashwell R.I.S."/>
                <person name="Aubin K."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Beasley H."/>
                <person name="Bethel G."/>
                <person name="Bird C.P."/>
                <person name="Bray-Allen S."/>
                <person name="Brown J.Y."/>
                <person name="Brown A.J."/>
                <person name="Buckley D."/>
                <person name="Burton J."/>
                <person name="Bye J."/>
                <person name="Carder C."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C."/>
                <person name="Cobley V."/>
                <person name="Collier R.E."/>
                <person name="Corby N."/>
                <person name="Coville G.J."/>
                <person name="Davies J."/>
                <person name="Deadman R."/>
                <person name="Dunn M."/>
                <person name="Earthrowl M."/>
                <person name="Ellington A.G."/>
                <person name="Errington H."/>
                <person name="Frankish A."/>
                <person name="Frankland J."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gay L."/>
                <person name="Ghori M.R.J."/>
                <person name="Gibson R."/>
                <person name="Gilby L.M."/>
                <person name="Gillett W."/>
                <person name="Glithero R.J."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths-Jones S."/>
                <person name="Grocock R."/>
                <person name="Hammond S."/>
                <person name="Harrison E.S.I."/>
                <person name="Hart E."/>
                <person name="Haugen E."/>
                <person name="Heath P.D."/>
                <person name="Holmes S."/>
                <person name="Holt K."/>
                <person name="Howden P.J."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Hunter G."/>
                <person name="Isherwood J."/>
                <person name="James R."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Joy A."/>
                <person name="Kay M."/>
                <person name="Kershaw J.K."/>
                <person name="Kibukawa M."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A.J."/>
                <person name="Lad H."/>
                <person name="Laird G."/>
                <person name="Lawlor S."/>
                <person name="Leongamornlert D.A."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Membrane</location>
            <topology evidence="4">Single-pass type II membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the 'GDXG' lipolytic enzyme family.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.-"/>
    <dbReference type="EMBL" id="AL513016">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS30590.1"/>
    <dbReference type="RefSeq" id="NP_001013652.1">
        <property type="nucleotide sequence ID" value="NM_001013630.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VUY2"/>
    <dbReference type="SMR" id="Q5VUY2"/>
    <dbReference type="IntAct" id="Q5VUY2">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000365395"/>
    <dbReference type="ESTHER" id="human-AADACL4">
        <property type="family name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q5VUY2">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5VUY2">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VUY2"/>
    <dbReference type="PhosphoSitePlus" id="Q5VUY2"/>
    <dbReference type="BioMuta" id="AADACL4"/>
    <dbReference type="DMDM" id="74747169"/>
    <dbReference type="jPOST" id="Q5VUY2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000365395"/>
    <dbReference type="Antibodypedia" id="46608">
        <property type="antibodies" value="95 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="343066"/>
    <dbReference type="Ensembl" id="ENST00000376221.2">
        <property type="protein sequence ID" value="ENSP00000365395.1"/>
        <property type="gene ID" value="ENSG00000204518.3"/>
    </dbReference>
    <dbReference type="GeneID" id="343066"/>
    <dbReference type="KEGG" id="hsa:343066"/>
    <dbReference type="MANE-Select" id="ENST00000376221.2">
        <property type="protein sequence ID" value="ENSP00000365395.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001013630.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001013652.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001auf.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32038"/>
    <dbReference type="ClinPGx" id="PA145147537"/>
    <dbReference type="CTD" id="343066"/>
    <dbReference type="GeneCards" id="AADACL4"/>
    <dbReference type="HGNC" id="HGNC:32038">
        <property type="gene designation" value="AADACL4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000204518">
        <property type="expression patterns" value="Tissue enhanced (choroid)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000204518"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000204518"/>
    <dbReference type="eggNOG" id="KOG1515">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157630"/>
    <dbReference type="HOGENOM" id="CLU_012494_12_2_1"/>
    <dbReference type="InParanoid" id="Q5VUY2"/>
    <dbReference type="OMA" id="MIGYRKL"/>
    <dbReference type="OrthoDB" id="408631at2759"/>
    <dbReference type="PAN-GO" id="Q5VUY2">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VUY2"/>
    <dbReference type="PathwayCommons" id="Q5VUY2"/>
    <dbReference type="SignaLink" id="Q5VUY2"/>
    <dbReference type="BioGRID-ORCS" id="343066">
        <property type="hits" value="7 hits in 1138 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AADACL4_(gene)"/>
    <dbReference type="GenomeRNAi" id="343066"/>
    <dbReference type="Pharos" id="Q5VUY2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VUY2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VUY2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000204518">
        <property type="expression patterns" value="Expressed in omental fat pad and 34 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013094">
        <property type="entry name" value="AB_hydrolase_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017157">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050300">
        <property type="entry name" value="GDXG_lipolytic_enzyme"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081">
        <property type="entry name" value="AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081:SF32">
        <property type="entry name" value="ALPHA_BETA HYDROLASE FOLD-3 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07859">
        <property type="entry name" value="Abhydrolase_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037251">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0735">Signal-anchor</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000265937" description="Arylacetamide deacetylase-like 4">
        <location>
            <begin position="1"/>
            <end position="407"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="1"/>
            <end position="4"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Signal-anchor for type II membrane protein" evidence="3">
        <location>
            <begin position="5"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="topological domain" description="Lumenal" evidence="3">
        <location>
            <begin position="26"/>
            <end position="407"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole" evidence="1">
        <location>
            <begin position="119"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="377"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="168"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="269"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5NUF3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8BLF1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="407" mass="46082" checksum="CE95EEE9A2C49970" modified="2004-12-07" version="1">MAVPWLVLLLALPIFFLGVFVWAVFEHFLTTDIPATLQHPAKLRFLHCIFLYLVTLGNIFEKLGICSMPKFIRFLHDSVRIKKDPELVVTDLRFGTIPVRLFQPKAASSRPRRGIIFYHGGATVFGSLDCYHGLCNYLARETESVLLMIGYRKLPDHHSPALFQDCMNASIHFLKALETYGVDPSRVVVCGESVGGAAVAAITQALVGRSDLPRIRAQVLIYPVVQAFCLQLPSFQQNQNVPLLSRKFMVTSLCNYLAIDLSWRDAILNGTCVPPDVWRKYEKWLSPDNIPKKFKNRGYQPWSPGPFNEAAYLEAKHMLDVENSPLIADDEVIAQLPEAFLVSCENDILRDDSLLYKKRLEDQGVRVTWYHLYDGFHGSIIFFDKKALSFPCSLKIVNAVVSYIKGI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-06-10" modified="2026-01-28" version="50" xmlns="https://uniprot.org/uniprot">
    <accession>A8MUL3</accession>
    <name>ADAS1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative uncharacterized protein ADARB2-AS1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ADARB2 antisense RNA 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>ADARB2 antisense gene protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADARB2-AS1</name>
        <name type="synonym">C10orf109</name>
        <name type="synonym">NCRNA00168</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
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                <person name="Rubenfield M."/>
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                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
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                <person name="Lovell J."/>
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                <person name="McLay K.E."/>
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                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
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                <person name="Ross M.T."/>
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                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="caution">
        <text evidence="1">Product of a dubious CDS prediction. Probable non-coding RNA.</text>
    </comment>
    <dbReference type="EMBL" id="AL450386">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="A8MUL3"/>
    <dbReference type="GlyGen" id="A8MUL3">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="BioMuta" id="HGNC:23299"/>
    <dbReference type="AGR" id="HGNC:23299"/>
    <dbReference type="GeneCards" id="ADARB2-AS1"/>
    <dbReference type="HGNC" id="HGNC:23299">
        <property type="gene designation" value="ADARB2-AS1"/>
    </dbReference>
    <dbReference type="InParanoid" id="A8MUL3"/>
    <dbReference type="PAN-GO" id="A8MUL3">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="Pharos" id="A8MUL3">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A8MUL3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="A8MUL3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000340730" description="Putative uncharacterized protein ADARB2-AS1">
        <location>
            <begin position="1"/>
            <end position="147"/>
        </location>
    </feature>
    <evidence type="ECO:0000305" key="1"/>
    <sequence length="147" mass="15836" checksum="C296C718D7A4E6B7" modified="2008-06-10" version="2">MKQLFPPPPGTSLTHALGAWRGRERAQAATSLLASSASQFPTAVEDALMSVLTSHCAPSTPAATRAQQTGTRGHIHPACPCQQSCVGASRPPGRPQIFLPLTTALSLEAYAADTCSAADFLHNPSSWGKVWYLNEASFDLYSYHYFW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>O43506</accession>
    <accession>Q6GTZ1</accession>
    <accession>Q9UKJ9</accession>
    <name>ADA20_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 20</fullName>
            <shortName>ADAM 20</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADAM20</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Gene" volume="206" first="273" last="282">
            <title>ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha.</title>
            <authorList>
                <person name="Hooft van Huijsduijnen R."/>
            </authorList>
            <dbReference type="PubMed" id="9469942"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(97)00597-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT LEU-19</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Gene" volume="237" first="61" last="70">
            <title>The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries.</title>
            <authorList>
                <person name="Poindexter K."/>
                <person name="Nelson N."/>
                <person name="DuBose R.F."/>
                <person name="Black R.A."/>
                <person name="Cerretti D.P."/>
            </authorList>
            <dbReference type="PubMed" id="10524237"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(99)00302-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
                <person name="Pepin K."/>
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                <person name="Cruaud C."/>
                <person name="Bruels T."/>
                <person name="Jaillon O."/>
                <person name="Friedlander L."/>
                <person name="Samson G."/>
                <person name="Brottier P."/>
                <person name="Cure S."/>
                <person name="Segurens B."/>
                <person name="Aniere F."/>
                <person name="Samain S."/>
                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
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                <person name="Friedman C."/>
                <person name="Gouyvenoux M."/>
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                <person name="Madan A."/>
                <person name="Mairey-Estrada B."/>
                <person name="Mangenot S."/>
                <person name="Martins N."/>
                <person name="Menard M."/>
                <person name="Oztas S."/>
                <person name="Ratcliffe A."/>
                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
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                <person name="Trybou A."/>
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                <person name="Bataille E."/>
                <person name="Bluet E."/>
                <person name="Bordelais I."/>
                <person name="Dubois M."/>
                <person name="Dumont C."/>
                <person name="Guerin T."/>
                <person name="Haffray S."/>
                <person name="Hammadi R."/>
                <person name="Muanga J."/>
                <person name="Pellouin V."/>
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                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
                <person name="Roy A."/>
                <person name="Sainte-Marthe L."/>
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                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
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            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
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                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>May be involved in sperm maturation and/or fertilization.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="7">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="7">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Testis specific.</text>
    </comment>
    <comment type="domain">
        <text>A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.</text>
    </comment>
    <comment type="domain">
        <text>The cysteine-rich domain encodes putative cell-fusion peptides, which could be involved in sperm-egg fusion.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text>Has no obvious cleavage site for furin endopeptidase, suggesting that the proteolytic processing is regulated.</text>
    </comment>
    <comment type="miscellaneous">
        <text>May be the functional equivalent of ADAM 1/fertilin alpha which is a pseudogene in human.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH25378" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH25378" version="2"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="EAW81037" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF029899">
        <property type="protein sequence ID" value="AAC52041.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF158643">
        <property type="protein sequence ID" value="AAD55254.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL357153">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471061">
        <property type="protein sequence ID" value="EAW81037.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC025378">
        <property type="protein sequence ID" value="AAH25378.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32111.2"/>
    <dbReference type="RefSeq" id="XP_005268208.1">
        <property type="nucleotide sequence ID" value="XM_005268151.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O43506"/>
    <dbReference type="SMR" id="O43506"/>
    <dbReference type="BioGRID" id="114284">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="O43506">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="IntAct" id="O43506">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="MINT" id="O43506"/>
    <dbReference type="STRING" id="9606.ENSP00000498512"/>
    <dbReference type="MEROPS" id="M12.218"/>
    <dbReference type="GlyCosmos" id="O43506">
        <property type="glycosylation" value="6 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O43506">
        <property type="glycosylation" value="7 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O43506"/>
    <dbReference type="PhosphoSitePlus" id="O43506"/>
    <dbReference type="BioMuta" id="ADAM20"/>
    <dbReference type="MassIVE" id="O43506"/>
    <dbReference type="PaxDb" id="9606-ENSP00000256389"/>
    <dbReference type="PeptideAtlas" id="O43506"/>
    <dbReference type="Antibodypedia" id="25132">
        <property type="antibodies" value="167 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8748"/>
    <dbReference type="Ensembl" id="ENST00000256389.5">
        <property type="protein sequence ID" value="ENSP00000256389.3"/>
        <property type="gene ID" value="ENSG00000134007.5"/>
    </dbReference>
    <dbReference type="GeneID" id="8748"/>
    <dbReference type="KEGG" id="hsa:8748"/>
    <dbReference type="MANE-Select" id="ENST00000256389.5">
        <property type="protein sequence ID" value="ENSP00000256389.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003814.5"/>
        <property type="RefSeq protein sequence ID" value="NP_003805.4"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xme.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:199"/>
    <dbReference type="ClinPGx" id="PA24516"/>
    <dbReference type="CTD" id="8748"/>
    <dbReference type="DisGeNET" id="8748"/>
    <dbReference type="GeneCards" id="ADAM20"/>
    <dbReference type="HGNC" id="HGNC:199">
        <property type="gene designation" value="ADAM20"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000134007">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="603712">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000134007"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000134007"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161067"/>
    <dbReference type="HOGENOM" id="CLU_012714_4_0_1"/>
    <dbReference type="InParanoid" id="O43506"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="O43506">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O43506"/>
    <dbReference type="PathwayCommons" id="O43506"/>
    <dbReference type="Reactome" id="R-HSA-2534343">
        <property type="pathway name" value="Interaction With Cumulus Cells And The Zona Pellucida"/>
    </dbReference>
    <dbReference type="SignaLink" id="O43506"/>
    <dbReference type="Agora" id="ENSG00000134007"/>
    <dbReference type="BioGRID-ORCS" id="8748">
        <property type="hits" value="8 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM20">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="8748"/>
    <dbReference type="Pharos" id="O43506">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O43506"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="O43506">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000134007">
        <property type="expression patterns" value="Expressed in sperm and 37 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O43506">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009897">
        <property type="term" value="C:external side of plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990913">
        <property type="term" value="C:sperm head plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008584">
        <property type="term" value="P:male gonad development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007338">
        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF232">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 20"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00142">
        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029106" evidence="2">
        <location>
            <begin position="32"/>
            <end position="206"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029107" description="Disintegrin and metalloproteinase domain-containing protein 20">
        <location>
            <begin position="207"/>
            <end position="726"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="207"/>
            <end position="693"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="694"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="715"/>
            <end position="726"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="4">
        <location>
            <begin position="207"/>
            <end position="400"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="407"/>
            <end position="493"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like">
        <location>
            <begin position="635"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="171"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="active site" evidence="4 5">
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="173"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="342"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="346"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="352"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="191"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="438"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="479"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="587"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="317"/>
            <end position="394"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="357"/>
            <end position="379"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="359"/>
            <end position="364"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="465"/>
            <end position="485"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="635"/>
            <end position="646"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="640"/>
            <end position="652"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="654"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_047311" description="In dbSNP:rs1059166." evidence="6">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="19"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC52041." evidence="7" ref="1">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC52041." evidence="7" ref="1">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="637"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="9469942"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <sequence length="726" mass="81603" checksum="7DB864FA1796A9B0" modified="2008-11-25" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-03" modified="2026-01-28" version="160" xmlns="https://uniprot.org/uniprot">
    <accession>Q86TW2</accession>
    <accession>B3KUD5</accession>
    <accession>Q6PD65</accession>
    <accession>Q9UIE6</accession>
    <name>ADCK1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">AarF domain-containing protein kinase 1</fullName>
            <ecNumber evidence="1">2.7.-.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="6" type="primary">ADCK1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
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                <person name="Cure S."/>
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                <person name="Aniere F."/>
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                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
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            <dbReference type="PubMed" id="12508121"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Full-length cDNA libraries and normalization.</title>
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                <person name="Li W.B."/>
                <person name="Gruber C."/>
                <person name="Jessee J."/>
                <person name="Polayes D."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-93 (ISOFORM 1)</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2019" name="PLoS Genet." volume="15" first="E1008184" last="E1008184">
            <title>Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle.</title>
            <authorList>
                <person name="Yoon W."/>
                <person name="Hwang S.H."/>
                <person name="Lee S.H."/>
                <person name="Chung J."/>
            </authorList>
            <dbReference type="PubMed" id="31125351"/>
            <dbReference type="DOI" id="10.1371/journal.pgen.1008184"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ALA-164; LYS-183 AND ASP-315</scope>
    </reference>
    <reference key="7">
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            <title>A subcellular map of the human kinome.</title>
            <authorList>
                <person name="Zhang H."/>
                <person name="Cao X."/>
                <person name="Tang M."/>
                <person name="Zhong G."/>
                <person name="Si Y."/>
                <person name="Li H."/>
                <person name="Zhu F."/>
                <person name="Liao Q."/>
                <person name="Li L."/>
                <person name="Zhao J."/>
                <person name="Feng J."/>
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                <person name="Wang C."/>
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                <person name="Wang F."/>
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                <person name="Li L."/>
                <person name="Xia Z."/>
                <person name="Liang T."/>
                <person name="Lu H."/>
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                <person name="Zhao B."/>
            </authorList>
            <dbReference type="PubMed" id="33988507"/>
            <dbReference type="DOI" id="10.7554/elife.64943"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="2 7">Appears to be essential for maintaining mitochondrial cristae formation and mitochondrial function by acting via YME1L1 in a kinase-independent manner to regulate essential mitochondrial structural proteins OPA1 and IMMT (PubMed:31125351). The action of this enzyme is not yet clear (Probable). It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Mitochondrion</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q86TW2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q86TW2-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_020885"/>
        </isoform>
        <isoform>
            <id>Q86TW2-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046794"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the protein kinase superfamily. ADCK protein kinase family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAD62620" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="CAD62620" version="1"/>
        </conflict>
        <text>Aberrant splicing.</text>
    </comment>
    <dbReference type="EC" id="2.7.-.-" evidence="1"/>
    <dbReference type="EMBL" id="AK096919">
        <property type="protein sequence ID" value="BAG53397.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC008372">
        <property type="protein sequence ID" value="AAF23326.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471061">
        <property type="protein sequence ID" value="EAW81310.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC058906">
        <property type="protein sequence ID" value="AAH58906.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX248292">
        <property type="protein sequence ID" value="CAD62620.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS45144.1">
        <molecule id="Q86TW2-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9869.1">
        <molecule id="Q86TW2-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001136017.1">
        <molecule id="Q86TW2-3"/>
        <property type="nucleotide sequence ID" value="NM_001142545.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_065154.2">
        <molecule id="Q86TW2-2"/>
        <property type="nucleotide sequence ID" value="NM_020421.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q86TW2"/>
    <dbReference type="SMR" id="Q86TW2"/>
    <dbReference type="BioGRID" id="121401">
        <property type="interactions" value="80"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q86TW2">
        <property type="interactions" value="1077"/>
    </dbReference>
    <dbReference type="IntAct" id="Q86TW2">
        <property type="interactions" value="71"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000238561"/>
    <dbReference type="ChEMBL" id="CHEMBL4105885"/>
    <dbReference type="DrugCentral" id="Q86TW2"/>
    <dbReference type="GlyGen" id="Q86TW2">
        <property type="glycosylation" value="1 site, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q86TW2"/>
    <dbReference type="PhosphoSitePlus" id="Q86TW2"/>
    <dbReference type="SwissPalm" id="Q86TW2"/>
    <dbReference type="BioMuta" id="ADCK1"/>
    <dbReference type="DMDM" id="115503784"/>
    <dbReference type="CPTAC" id="non-CPTAC-6012"/>
    <dbReference type="CPTAC" id="non-CPTAC-6013"/>
    <dbReference type="jPOST" id="Q86TW2"/>
    <dbReference type="MassIVE" id="Q86TW2"/>
    <dbReference type="PaxDb" id="9606-ENSP00000238561"/>
    <dbReference type="PeptideAtlas" id="Q86TW2"/>
    <dbReference type="ProteomicsDB" id="69740">
        <molecule id="Q86TW2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="69741">
        <molecule id="Q86TW2-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="84498"/>
    <dbReference type="Pumba" id="Q86TW2"/>
    <dbReference type="Antibodypedia" id="26131">
        <property type="antibodies" value="181 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="57143"/>
    <dbReference type="Ensembl" id="ENST00000238561.10">
        <molecule id="Q86TW2-2"/>
        <property type="protein sequence ID" value="ENSP00000238561.5"/>
        <property type="gene ID" value="ENSG00000063761.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000341211.5">
        <molecule id="Q86TW2-3"/>
        <property type="protein sequence ID" value="ENSP00000339663.5"/>
        <property type="gene ID" value="ENSG00000063761.17"/>
    </dbReference>
    <dbReference type="GeneID" id="57143"/>
    <dbReference type="KEGG" id="hsa:57143"/>
    <dbReference type="MANE-Select" id="ENST00000238561.10">
        <molecule id="Q86TW2-2"/>
        <property type="protein sequence ID" value="ENSP00000238561.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_020421.4"/>
        <property type="RefSeq protein sequence ID" value="NP_065154.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xui.3">
        <molecule id="Q86TW2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:19038"/>
    <dbReference type="ClinPGx" id="PA134861355"/>
    <dbReference type="CTD" id="57143"/>
    <dbReference type="DisGeNET" id="57143"/>
    <dbReference type="GeneCards" id="ADCK1"/>
    <dbReference type="HGNC" id="HGNC:19038">
        <property type="gene designation" value="ADCK1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000063761">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="620399">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000063761"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000063761"/>
    <dbReference type="eggNOG" id="KOG1235">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158221"/>
    <dbReference type="HOGENOM" id="CLU_006533_2_0_1"/>
    <dbReference type="InParanoid" id="Q86TW2"/>
    <dbReference type="OMA" id="RCNPEDI"/>
    <dbReference type="OrthoDB" id="427480at2759"/>
    <dbReference type="PAN-GO" id="Q86TW2">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q86TW2"/>
    <dbReference type="PathwayCommons" id="Q86TW2"/>
    <dbReference type="SignaLink" id="Q86TW2"/>
    <dbReference type="Agora" id="ENSG00000063761"/>
    <dbReference type="BioGRID-ORCS" id="57143">
        <property type="hits" value="12 hits in 1189 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCK1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="57143"/>
    <dbReference type="Pharos" id="Q86TW2">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q86TW2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
    </dbReference>
    <dbReference type="RNAct" id="Q86TW2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000063761">
        <property type="expression patterns" value="Expressed in apex of heart and 179 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q86TW2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055088">
        <property type="term" value="P:lipid homeostasis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007005">
        <property type="term" value="P:mitochondrion organization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010637">
        <property type="term" value="P:negative regulation of mitochondrial fusion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1903852">
        <property type="term" value="P:positive regulation of cristae formation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd13969">
        <property type="entry name" value="ADCK1-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.510.10">
        <property type="entry name" value="Transferase(Phosphotransferase) domain 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004147">
        <property type="entry name" value="ABC1_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045307">
        <property type="entry name" value="ADCK1_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051130">
        <property type="entry name" value="Mito_struct-func_regulator"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43173:SF19">
        <property type="entry name" value="AARF DOMAIN-CONTAINING PROTEIN KINASE 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43173">
        <property type="entry name" value="ABC1 FAMILY PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03109">
        <property type="entry name" value="ABC1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="7">
        <location>
            <begin position="1"/>
            <end status="unknown"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000252249" description="AarF domain-containing protein kinase 1">
        <location>
            <begin status="unknown"/>
            <end position="530"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase" evidence="1">
        <location>
            <begin position="155"/>
            <end position="467"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="161"/>
            <end position="169"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="183"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_046794" description="In isoform 3." evidence="4">
        <location>
            <begin position="74"/>
            <end position="148"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_020885" description="In isoform 2." evidence="5">
        <location>
            <begin position="74"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on role in maintaining mitochondrial structure and function." evidence="2">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on role in maintaining mitochondrial structure and function." evidence="2">
        <original>K</original>
        <variation>I</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on role in maintaining mitochondrial structure and function." evidence="2">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAG53397." evidence="7" ref="1">
        <original>K</original>
        <variation>N</variation>
        <location>
            <position position="7"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00159"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="31125351"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="33988507"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="31125351"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <sequence length="530" mass="60577" checksum="CBB1DFA87D0F41CF" modified="2006-10-03" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-01" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UKJ8</accession>
    <accession>O43507</accession>
    <accession>Q2VPC6</accession>
    <accession>Q32MR0</accession>
    <name>ADA21_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 21</fullName>
            <shortName>ADAM 21</shortName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADAM21</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1999" name="Gene" volume="237" first="61" last="70">
            <title>The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries.</title>
            <authorList>
                <person name="Poindexter K."/>
                <person name="Nelson N."/>
                <person name="DuBose R.F."/>
                <person name="Black R.A."/>
                <person name="Cerretti D.P."/>
            </authorList>
            <dbReference type="PubMed" id="10524237"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(99)00302-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Nature" volume="421" first="601" last="607">
            <title>The DNA sequence and analysis of human chromosome 14.</title>
            <authorList>
                <person name="Heilig R."/>
                <person name="Eckenberg R."/>
                <person name="Petit J.-L."/>
                <person name="Fonknechten N."/>
                <person name="Da Silva C."/>
                <person name="Cattolico L."/>
                <person name="Levy M."/>
                <person name="Barbe V."/>
                <person name="De Berardinis V."/>
                <person name="Ureta-Vidal A."/>
                <person name="Pelletier E."/>
                <person name="Vico V."/>
                <person name="Anthouard V."/>
                <person name="Rowen L."/>
                <person name="Madan A."/>
                <person name="Qin S."/>
                <person name="Sun H."/>
                <person name="Du H."/>
                <person name="Pepin K."/>
                <person name="Artiguenave F."/>
                <person name="Robert C."/>
                <person name="Cruaud C."/>
                <person name="Bruels T."/>
                <person name="Jaillon O."/>
                <person name="Friedlander L."/>
                <person name="Samson G."/>
                <person name="Brottier P."/>
                <person name="Cure S."/>
                <person name="Segurens B."/>
                <person name="Aniere F."/>
                <person name="Samain S."/>
                <person name="Crespeau H."/>
                <person name="Abbasi N."/>
                <person name="Aiach N."/>
                <person name="Boscus D."/>
                <person name="Dickhoff R."/>
                <person name="Dors M."/>
                <person name="Dubois I."/>
                <person name="Friedman C."/>
                <person name="Gouyvenoux M."/>
                <person name="James R."/>
                <person name="Madan A."/>
                <person name="Mairey-Estrada B."/>
                <person name="Mangenot S."/>
                <person name="Martins N."/>
                <person name="Menard M."/>
                <person name="Oztas S."/>
                <person name="Ratcliffe A."/>
                <person name="Shaffer T."/>
                <person name="Trask B."/>
                <person name="Vacherie B."/>
                <person name="Bellemere C."/>
                <person name="Belser C."/>
                <person name="Besnard-Gonnet M."/>
                <person name="Bartol-Mavel D."/>
                <person name="Boutard M."/>
                <person name="Briez-Silla S."/>
                <person name="Combette S."/>
                <person name="Dufosse-Laurent V."/>
                <person name="Ferron C."/>
                <person name="Lechaplais C."/>
                <person name="Louesse C."/>
                <person name="Muselet D."/>
                <person name="Magdelenat G."/>
                <person name="Pateau E."/>
                <person name="Petit E."/>
                <person name="Sirvain-Trukniewicz P."/>
                <person name="Trybou A."/>
                <person name="Vega-Czarny N."/>
                <person name="Bataille E."/>
                <person name="Bluet E."/>
                <person name="Bordelais I."/>
                <person name="Dubois M."/>
                <person name="Dumont C."/>
                <person name="Guerin T."/>
                <person name="Haffray S."/>
                <person name="Hammadi R."/>
                <person name="Muanga J."/>
                <person name="Pellouin V."/>
                <person name="Robert D."/>
                <person name="Wunderle E."/>
                <person name="Gauguet G."/>
                <person name="Roy A."/>
                <person name="Sainte-Marthe L."/>
                <person name="Verdier J."/>
                <person name="Verdier-Discala C."/>
                <person name="Hillier L.W."/>
                <person name="Fulton L."/>
                <person name="McPherson J."/>
                <person name="Matsuda F."/>
                <person name="Wilson R."/>
                <person name="Scarpelli C."/>
                <person name="Gyapay G."/>
                <person name="Wincker P."/>
                <person name="Saurin W."/>
                <person name="Quetier F."/>
                <person name="Waterston R."/>
                <person name="Hood L."/>
                <person name="Weissenbach J."/>
            </authorList>
            <dbReference type="PubMed" id="12508121"/>
            <dbReference type="DOI" id="10.1038/nature01348"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1998" name="Gene" volume="206" first="273" last="282">
            <title>ADAM 20 and 21; two novel human testis-specific membrane metalloproteases with similarity to fertilin-alpha.</title>
            <authorList>
                <person name="Hooft van Huijsduijnen R."/>
            </authorList>
            <dbReference type="PubMed" id="9469942"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(97)00597-0"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 181-722</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <comment type="function">
        <text>May be involved in sperm maturation and/or fertilization. May also be involved in epithelia functions associated with establishing and maintaining gradients of ions or nutrients.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="6">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12046857">
            <id>Q9UKJ8</id>
        </interactant>
        <interactant intactId="EBI-2835940">
            <id>P34972</id>
            <label>CNR2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12046857">
            <id>Q9UKJ8</id>
        </interactant>
        <interactant intactId="EBI-347996">
            <id>O43765</id>
            <label>SGTA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="domain">
        <text>A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.</text>
    </comment>
    <comment type="domain">
        <text>The cysteine-rich domain encodes putative cell-fusion peptides, which could be involved in sperm-egg fusion.</text>
    </comment>
    <comment type="domain">
        <text>The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.</text>
    </comment>
    <comment type="PTM">
        <text>Has no obvious cleavage site for furin endopeptidase, suggesting that the proteolytic processing is regulated.</text>
    </comment>
    <comment type="miscellaneous">
        <text>May be the functional equivalent of ADAM 1/fertilin alpha which is a pseudogene in human.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="AF158644">
        <property type="protein sequence ID" value="AAD55255.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL357153">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL391223">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC109024">
        <property type="protein sequence ID" value="AAI09025.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC109025">
        <property type="protein sequence ID" value="AAI09026.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF029900">
        <property type="protein sequence ID" value="AAC52042.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9804.1"/>
    <dbReference type="RefSeq" id="NP_003804.2">
        <property type="nucleotide sequence ID" value="NM_003813.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9UKJ8"/>
    <dbReference type="SMR" id="Q9UKJ8"/>
    <dbReference type="BioGRID" id="114283">
        <property type="interactions" value="114"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9UKJ8">
        <property type="interactions" value="82"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9UKJ8">
        <property type="interactions" value="62"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000474385"/>
    <dbReference type="MEROPS" id="M12.234"/>
    <dbReference type="GlyCosmos" id="Q9UKJ8">
        <property type="glycosylation" value="7 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9UKJ8">
        <property type="glycosylation" value="7 sites, 4 N-linked glycans (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9UKJ8"/>
    <dbReference type="PhosphoSitePlus" id="Q9UKJ8"/>
    <dbReference type="BioMuta" id="ADAM21"/>
    <dbReference type="DMDM" id="296434388"/>
    <dbReference type="MassIVE" id="Q9UKJ8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000474385"/>
    <dbReference type="PeptideAtlas" id="Q9UKJ8"/>
    <dbReference type="ProteomicsDB" id="84810"/>
    <dbReference type="Antibodypedia" id="25130">
        <property type="antibodies" value="35 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8747"/>
    <dbReference type="Ensembl" id="ENST00000603540.2">
        <property type="protein sequence ID" value="ENSP00000474385.1"/>
        <property type="gene ID" value="ENSG00000139985.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000679631.1">
        <property type="protein sequence ID" value="ENSP00000506213.1"/>
        <property type="gene ID" value="ENSG00000139985.9"/>
    </dbReference>
    <dbReference type="GeneID" id="8747"/>
    <dbReference type="KEGG" id="hsa:8747"/>
    <dbReference type="MANE-Select" id="ENST00000603540.2">
        <property type="protein sequence ID" value="ENSP00000474385.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003813.4"/>
        <property type="RefSeq protein sequence ID" value="NP_003804.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001xmd.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:200"/>
    <dbReference type="ClinPGx" id="PA24517"/>
    <dbReference type="CTD" id="8747"/>
    <dbReference type="DisGeNET" id="8747"/>
    <dbReference type="GeneCards" id="ADAM21"/>
    <dbReference type="HGNC" id="HGNC:200">
        <property type="gene designation" value="ADAM21"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000139985">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="603713">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000139985"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000139985"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162712"/>
    <dbReference type="HOGENOM" id="CLU_012714_4_0_1"/>
    <dbReference type="InParanoid" id="Q9UKJ8"/>
    <dbReference type="OMA" id="WWTHSWF"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9UKJ8">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9UKJ8"/>
    <dbReference type="PathwayCommons" id="Q9UKJ8"/>
    <dbReference type="Reactome" id="R-HSA-2534343">
        <property type="pathway name" value="Interaction With Cumulus Cells And The Zona Pellucida"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9UKJ8"/>
    <dbReference type="Agora" id="ENSG00000139985"/>
    <dbReference type="BioGRID-ORCS" id="8747">
        <property type="hits" value="34 hits in 1114 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="8747"/>
    <dbReference type="Pharos" id="Q9UKJ8">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9UKJ8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 14"/>
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    <dbReference type="RNAct" id="Q9UKJ8">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000139985">
        <property type="expression patterns" value="Expressed in sperm and 81 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030424">
        <property type="term" value="C:axon"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0009897">
        <property type="term" value="C:external side of plasma membrane"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0043025">
        <property type="term" value="C:neuronal cell body"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="C:sperm head plasma membrane"/>
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        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
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    <dbReference type="GO" id="GO:0008237">
        <property type="term" value="F:metallopeptidase activity"/>
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        <property type="term" value="P:male gonad development"/>
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        <property type="term" value="P:proteolysis"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007338">
        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000742">
        <property type="entry name" value="EGF"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF116">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 21"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01186">
        <property type="entry name" value="EGF_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00142">
        <property type="entry name" value="ZINC_PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0245">EGF-like domain</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029108" evidence="2">
        <location>
            <begin position="32"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029109" description="Disintegrin and metalloproteinase domain-containing protein 21">
        <location>
            <begin position="197"/>
            <end position="722"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="197"/>
            <end position="681"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="682"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="703"/>
            <end position="722"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="4">
        <location>
            <begin position="208"/>
            <end position="398"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="406"/>
            <end position="492"/>
        </location>
    </feature>
    <feature type="domain" description="EGF-like">
        <location>
            <begin position="634"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Cysteine switch" evidence="1">
        <location>
            <begin position="171"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="active site" evidence="4 5">
        <location>
            <position position="342"/>
        </location>
    </feature>
    <feature type="binding site" description="in inhibited form" evidence="1">
        <location>
            <position position="173"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="341"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="345"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="351"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="227"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="377"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="437"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="478"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="546"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="600"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="316"/>
            <end position="393"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="356"/>
            <end position="378"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="358"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="464"/>
            <end position="484"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="634"/>
            <end position="645"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="639"/>
            <end position="651"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="653"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD55255 and 3; AAI09025/AAI09026." evidence="6" ref="1 3">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD55255 and 3; AAI09025/AAI09026." evidence="6" ref="1 3">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD55255 and 3; AAI09025/AAI09026." evidence="6" ref="1 3">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="161"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAC52042." evidence="6" ref="3">
        <original>A</original>
        <variation>G</variation>
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD55255 and 3; AAI09025/AAI09026." evidence="6" ref="1 3">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAC52042." evidence="6" ref="3">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="345"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="722" mass="80834" checksum="4D18503812A6C02F" modified="2010-05-18" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-01-31" modified="2026-01-28" version="175" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H2U9</accession>
    <accession>A8K8X7</accession>
    <accession>O75959</accession>
    <accession>Q6PEJ6</accession>
    <name>ADAM7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="9">Disintegrin and metalloproteinase domain-containing protein 7</fullName>
            <shortName>ADAM 7</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Sperm maturation-related glycoprotein GP-83</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="9" type="primary">ADAM7</name>
        <name evidence="9" type="synonym">GP83</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1999-12" db="EMBL/GenBank/DDBJ databases">
            <title>Expression of human ADAM7 (GP-83).</title>
            <authorList>
                <person name="Lin Y.C."/>
                <person name="Lee Y.M."/>
                <person name="Sun G.H."/>
                <person name="Liu H.W."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Epididymis</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="439" first="331" last="335">
            <title>DNA sequence and analysis of human chromosome 8.</title>
            <authorList>
                <person name="Nusbaum C."/>
                <person name="Mikkelsen T.S."/>
                <person name="Zody M.C."/>
                <person name="Asakawa S."/>
                <person name="Taudien S."/>
                <person name="Garber M."/>
                <person name="Kodira C.D."/>
                <person name="Schueler M.G."/>
                <person name="Shimizu A."/>
                <person name="Whittaker C.A."/>
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                <person name="Cuomo C.A."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M.G."/>
                <person name="Yang X."/>
                <person name="Allen N.R."/>
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                <person name="Blechschmidt K."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Butler J."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="DeArellano K."/>
                <person name="DeCaprio D."/>
                <person name="Dooley K.T."/>
                <person name="Dorris L. III"/>
                <person name="Engels R."/>
                <person name="Gloeckner G."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hall J.L."/>
                <person name="Ishikawa S.K."/>
                <person name="Jaffe D.B."/>
                <person name="Kamat A."/>
                <person name="Kudoh J."/>
                <person name="Lehmann R."/>
                <person name="Lokitsang T."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews C.D."/>
                <person name="Mauceli E."/>
                <person name="Menzel U."/>
                <person name="Mihalev A.H."/>
                <person name="Minoshima S."/>
                <person name="Murayama Y."/>
                <person name="Naylor J.W."/>
                <person name="Nicol R."/>
                <person name="Nguyen C."/>
                <person name="O'Leary S.B."/>
                <person name="O'Neill K."/>
                <person name="Parker S.C.J."/>
                <person name="Polley A."/>
                <person name="Raymond C.K."/>
                <person name="Reichwald K."/>
                <person name="Rodriguez J."/>
                <person name="Sasaki T."/>
                <person name="Schilhabel M."/>
                <person name="Siddiqui R."/>
                <person name="Smith C.L."/>
                <person name="Sneddon T.P."/>
                <person name="Talamas J.A."/>
                <person name="Tenzin P."/>
                <person name="Topham K."/>
                <person name="Venkataraman V."/>
                <person name="Wen G."/>
                <person name="Yamazaki S."/>
                <person name="Young S.K."/>
                <person name="Zeng Q."/>
                <person name="Zimmer A.R."/>
                <person name="Rosenthal A."/>
                <person name="Birren B.W."/>
                <person name="Platzer M."/>
                <person name="Shimizu N."/>
                <person name="Lander E.S."/>
            </authorList>
            <dbReference type="PubMed" id="16421571"/>
            <dbReference type="DOI" id="10.1038/nature04406"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="1998-09" db="EMBL/GenBank/DDBJ databases">
            <title>A ADAM-like cDNA sequence identified in cDNA library of human epididymis.</title>
            <authorList>
                <person name="Liu H.W."/>
                <person name="Lin Y.C."/>
                <person name="Sun G.H."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 167-754 (ISOFORM 1)</scope>
        <source>
            <tissue>Epididymis</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="Hum. Mutat." volume="32" first="E2148" last="E2175">
            <title>Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Moncada-Pazos A."/>
                <person name="Cal S."/>
                <person name="Soria-Valles C."/>
                <person name="Gartner J."/>
                <person name="Rudloff U."/>
                <person name="Lin J.C."/>
                <person name="Rosenberg S.A."/>
                <person name="Lopez-Otin C."/>
                <person name="Samuels Y."/>
            </authorList>
            <dbReference type="PubMed" id="21618342"/>
            <dbReference type="DOI" id="10.1002/humu.21477"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INVOLVEMENT IN CUTANEOUS MELANOMA</scope>
        <scope>VARIANTS SER-14; CYS-31; SER-36; TYR-106; PRO-173; ALA-180; TYR-243; GLU-302; ILE-359; GLU-533; LEU-593; LYS-639 AND ASN-703</scope>
        <scope>CHARACTERIZATION OF VARIANTS TYR-243; ILE-359; LYS-639 AND ASN-703</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development (By similarity). Plays a role in sperm motility, flagella morphology and tyrosine phosphorylation during sperm capacitance (By similarity). Plays a role in normal expression levels of HSPA5, ITM2B and ADAM2 in sperm both prior to and post-capacitation (By similarity). This is a non catalytic metalloprotease-like protein (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts with ITM2B in sperm; the interaction increases following capacitation (By similarity). Interacts with HSPA5 and CANX (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Membrane</location>
            <topology evidence="3">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9H2U9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9H2U9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_056602 VSP_056603"/>
        </isoform>
    </comment>
    <comment type="disease">
        <text evidence="6">Has been found to be frequently mutated in melanoma (PubMed:21618342). ADAM7 mutations may play a role in melanoma progression and metastasis (PubMed:21618342). Expressed in melanoma cells but not in healthy melanocytes (PubMed:21618342).</text>
    </comment>
    <dbReference type="EMBL" id="AF215824">
        <property type="protein sequence ID" value="AAG43987.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292492">
        <property type="protein sequence ID" value="BAF85181.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC024958">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC120193">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC058037">
        <property type="protein sequence ID" value="AAH58037.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF090327">
        <property type="protein sequence ID" value="AAC36742.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6045.1">
        <molecule id="Q9H2U9-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_003808.2">
        <molecule id="Q9H2U9-1"/>
        <property type="nucleotide sequence ID" value="NM_003817.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H2U9"/>
    <dbReference type="SMR" id="Q9H2U9"/>
    <dbReference type="BioGRID" id="114292">
        <property type="interactions" value="52"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9H2U9">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H2U9">
        <property type="interactions" value="33"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000175238"/>
    <dbReference type="MEROPS" id="M12.956"/>
    <dbReference type="GlyCosmos" id="Q9H2U9">
        <property type="glycosylation" value="6 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H2U9">
        <property type="glycosylation" value="6 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H2U9"/>
    <dbReference type="PhosphoSitePlus" id="Q9H2U9"/>
    <dbReference type="SwissPalm" id="Q9H2U9"/>
    <dbReference type="BioMuta" id="ADAM7"/>
    <dbReference type="DMDM" id="296439449"/>
    <dbReference type="jPOST" id="Q9H2U9"/>
    <dbReference type="MassIVE" id="Q9H2U9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000175238"/>
    <dbReference type="PeptideAtlas" id="Q9H2U9"/>
    <dbReference type="ProteomicsDB" id="67078"/>
    <dbReference type="ProteomicsDB" id="80599">
        <molecule id="Q9H2U9-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="22842">
        <property type="antibodies" value="81 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8756"/>
    <dbReference type="Ensembl" id="ENST00000175238.10">
        <molecule id="Q9H2U9-1"/>
        <property type="protein sequence ID" value="ENSP00000175238.5"/>
        <property type="gene ID" value="ENSG00000069206.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000441335.6">
        <molecule id="Q9H2U9-2"/>
        <property type="protein sequence ID" value="ENSP00000393073.2"/>
        <property type="gene ID" value="ENSG00000069206.15"/>
    </dbReference>
    <dbReference type="GeneID" id="8756"/>
    <dbReference type="KEGG" id="hsa:8756"/>
    <dbReference type="MANE-Select" id="ENST00000175238.10">
        <property type="protein sequence ID" value="ENSP00000175238.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003817.4"/>
        <property type="RefSeq protein sequence ID" value="NP_003808.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xea.2">
        <molecule id="Q9H2U9-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:214"/>
    <dbReference type="ClinPGx" id="PA24532"/>
    <dbReference type="CTD" id="8756"/>
    <dbReference type="DisGeNET" id="8756"/>
    <dbReference type="GeneCards" id="ADAM7"/>
    <dbReference type="HGNC" id="HGNC:214">
        <property type="gene designation" value="ADAM7"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000069206">
        <property type="expression patterns" value="Tissue enriched (epididymis)"/>
    </dbReference>
    <dbReference type="MIM" id="607310">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000069206"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000069206"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161406"/>
    <dbReference type="HOGENOM" id="CLU_1309742_0_0_1"/>
    <dbReference type="InParanoid" id="Q9H2U9"/>
    <dbReference type="OMA" id="RFSTWQE"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9H2U9">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H2U9"/>
    <dbReference type="PathwayCommons" id="Q9H2U9"/>
    <dbReference type="Agora" id="ENSG00000069206"/>
    <dbReference type="BioGRID-ORCS" id="8756">
        <property type="hits" value="12 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="8756"/>
    <dbReference type="Pharos" id="Q9H2U9">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H2U9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H2U9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000069206">
        <property type="expression patterns" value="Expressed in corpus epididymis and 16 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9H2U9">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1905867">
        <property type="term" value="P:epididymis development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003382">
        <property type="term" value="P:epithelial cell morphogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902093">
        <property type="term" value="P:positive regulation of flagellated sperm motility"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1902492">
        <property type="term" value="P:positive regulation of sperm capacitation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd04269">
        <property type="entry name" value="ZnMc_adamalysin_II_like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.390.10:FF:000002">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="4.10.70.10:FF:000001">
        <property type="entry name" value="Disintegrin and metalloproteinase domain-containing protein 22"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.390.10">
        <property type="entry name" value="Collagenase (Catalytic Domain)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.70.10">
        <property type="entry name" value="Disintegrin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006586">
        <property type="entry name" value="ADAM_Cys-rich"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018358">
        <property type="entry name" value="Disintegrin_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001762">
        <property type="entry name" value="Disintegrin_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036436">
        <property type="entry name" value="Disintegrin_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR024079">
        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001590">
        <property type="entry name" value="Peptidase_M12B"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002870">
        <property type="entry name" value="Peptidase_M12B_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034027">
        <property type="entry name" value="Reprolysin_adamalysin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11905:SF21">
        <property type="entry name" value="DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08516">
        <property type="entry name" value="ADAM_CR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00200">
        <property type="entry name" value="Disintegrin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00289">
        <property type="entry name" value="DISINTEGRIN"/>
    </dbReference>
    <dbReference type="SMART" id="SM00608">
        <property type="entry name" value="ACR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00050">
        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57552">
        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55486">
        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50215">
        <property type="entry name" value="ADAM_MEPRO"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00427">
        <property type="entry name" value="DISINTEGRIN_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50214">
        <property type="entry name" value="DISINTEGRIN_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029052" evidence="1">
        <location>
            <begin position="19"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029053" description="Disintegrin and metalloproteinase domain-containing protein 7">
        <location>
            <begin position="177"/>
            <end position="754"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="3">
        <location>
            <begin position="19"/>
            <end position="668"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="669"/>
            <end position="689"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="3">
        <location>
            <begin position="690"/>
            <end position="754"/>
        </location>
    </feature>
    <feature type="domain" description="Peptidase M12B" evidence="5">
        <location>
            <begin position="199"/>
            <end position="394"/>
        </location>
    </feature>
    <feature type="domain" description="Disintegrin" evidence="4">
        <location>
            <begin position="402"/>
            <end position="488"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="167"/>
        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="668"/>
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    <feature type="disulfide bond" evidence="1">
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    <feature type="disulfide bond" evidence="1">
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    <feature type="disulfide bond" evidence="1">
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    <feature type="splice variant" id="VSP_056602" description="In isoform 2." evidence="7">
        <original>GIHDEKYVELFIVADDT</original>
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        <variation>S</variation>
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    <feature type="sequence variant" id="VAR_066308" description="In a cutaneous metastatic melanoma sample; somatic mutation; does not affect cell growth but conferes reduced cell adhesion to collagen IV and laminin-1; increases cell migration capabilities compared to wild-type." evidence="6">
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        <variation>N</variation>
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            <position position="703"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAG43987." evidence="8" ref="1">
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        <variation>DL</variation>
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                <person name="Alsagheir A."/>
                <person name="Alowain M."/>
                <person name="Tamim A."/>
                <person name="Alfayez K."/>
                <person name="Alhashem A."/>
                <person name="Alnuzha A."/>
                <person name="Kamel M."/>
                <person name="Al-Awam B.S."/>
                <person name="Elnaggar W."/>
                <person name="Almenabawy N."/>
                <person name="O'Donnell-Luria A."/>
                <person name="Neil J.E."/>
                <person name="Gleeson J.G."/>
                <person name="Walsh C.A."/>
                <person name="Alkuraya F.S."/>
                <person name="AlAbdi L."/>
                <person name="Elkhateeb N."/>
                <person name="Selim L."/>
                <person name="Srivastava S."/>
                <person name="Nedialkova D.D."/>
                <person name="Drouard L."/>
                <person name="Romier C."/>
                <person name="Bayam E."/>
                <person name="Godin J.D."/>
            </authorList>
            <dbReference type="PubMed" id="40120092"/>
            <dbReference type="DOI" id="10.1093/brain/awaf109"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT NEDBGF MET-144</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Non-catalytic subunit of the tRNA-specific adenosine-34 deaminase complex, composed of the ADAT2 catalytic subunit and the ADAT3 regulatory subunit, which deaminates adenosine-34 (the first, also called wobble position of the anticodon) to inosine in many tRNAs. Inosine-34 allows the decoding of 3 different nucleotides at the third position of mRNA codons, as inosine is able to pair with U, C, and A. Required for binding of the ADAT2-ADAT3 complex to tRNA through its N-terminus, which rotates with respect to the catalytic domain of the complex, formed by ADAT2 and the ADAT3 C-terminal domain, to position the tRNA anticodon stem-loop correctly in the ADAT2 active site. The ADAT2-ADAT3 complex is required for radial migration of projection neurons in the developing brain cortex, and the catalytic activity of the complex is necessary for this function.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Heterodimer with catalytic subunit ADAT2 to form the tRNA-specific adenosine-34 deaminase complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3922811">
            <id>Q96EY9</id>
        </interactant>
        <interactant intactId="EBI-2809203">
            <id>Q7Z6V5</id>
            <label>ADAT2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3922811">
            <id>Q96EY9</id>
        </interactant>
        <interactant intactId="EBI-9250559">
            <id>P32320</id>
            <label>CDA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3922811">
            <id>Q96EY9</id>
        </interactant>
        <interactant intactId="EBI-3864120">
            <id>Q8WUP2</id>
            <label>FBLIM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3922811">
            <id>Q96EY9</id>
        </interactant>
        <interactant intactId="EBI-741237">
            <id>O60504</id>
            <label>SORBS3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="1">The ADAT2-ADAT3 complex shows a diffuse expression pattern in both the cytoplasm and the nucleus.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative initiation"/>
        <isoform>
            <id>Q96EY9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96EY9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_062626"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="1">The N-terminal domain adopts a fold that shares similarity with the ferredoxin-like domains of other tRNA-modifying enzymes and is required for tRNA-binding and deamination activity of the ADAT2-ADAT3 heterodimer. The domain can rotate with respect to the catalytic domain formed by ADAT2 and the ADAT3 C-terminal domain without affecting the structure of the catalytic domain. Rotation positions the tRNA anticodon stem-loop correctly in the ADAT2 active site.</text>
    </comment>
    <comment type="disease" evidence="5 7">
        <disease id="DI-03799">
            <name>Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies</name>
            <acronym>NEDBGF</acronym>
            <description>An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, and speech delay apparent from infancy or early childhood. Most patients have dysmorphic facial features, and white matter abnormalities on brain imaging. More variable features may include teeth anomalies, distal joint contractures, spasticity, peripheral neuropathy, and behavioral problems.</description>
            <dbReference type="MIM" id="615286"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the cytidine and deoxycytidylate deaminase family. ADAT3 subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="1">Val-241 is present instead of the conserved active site Glu normally found in the cytidine and deoxycytidylate deaminase family of enzymes. ADAT3 is inactivated due to the replacement by Val of the active site Glu usually involved in proton shuttling during catalysis, and also by the capping of its zinc binding pocket by the C-terminus and loss of binding pockets for the anticodon loop nucleosides.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH11824" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AC012615">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471139">
        <property type="protein sequence ID" value="EAW69434.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC011824">
        <property type="protein sequence ID" value="AAH11824.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001316462.1">
        <property type="nucleotide sequence ID" value="NM_001329533.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_612431.2">
        <property type="nucleotide sequence ID" value="NM_138422.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96EY9"/>
    <dbReference type="SMR" id="Q96EY9"/>
    <dbReference type="BioGRID" id="125231">
        <property type="interactions" value="26"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96EY9">
        <property type="interactions" value="1988"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96EY9">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000332448"/>
    <dbReference type="iPTMnet" id="Q96EY9"/>
    <dbReference type="PhosphoSitePlus" id="Q96EY9"/>
    <dbReference type="BioMuta" id="ADAT3"/>
    <dbReference type="DMDM" id="74731634"/>
    <dbReference type="jPOST" id="Q96EY9"/>
    <dbReference type="MassIVE" id="Q96EY9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000332448"/>
    <dbReference type="ProteomicsDB" id="76475"/>
    <dbReference type="Pumba" id="Q96EY9"/>
    <dbReference type="Antibodypedia" id="22864">
        <property type="antibodies" value="86 antibodies from 11 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="113179"/>
    <dbReference type="GeneID" id="113179"/>
    <dbReference type="KEGG" id="hsa:113179"/>
    <dbReference type="MANE-Select" id="ENST00000329478.4">
        <property type="protein sequence ID" value="ENSP00000332448.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_138422.4"/>
        <property type="RefSeq protein sequence ID" value="NP_612431.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002luh.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25151"/>
    <dbReference type="ClinPGx" id="PA162375609"/>
    <dbReference type="CTD" id="113179"/>
    <dbReference type="DisGeNET" id="113179"/>
    <dbReference type="GeneCards" id="ADAT3"/>
    <dbReference type="HGNC" id="HGNC:25151">
        <property type="gene designation" value="ADAT3"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADAT3"/>
    <dbReference type="MIM" id="615286">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="615302">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000213638"/>
    <dbReference type="Orphanet" id="363528">
        <property type="disease" value="Intellectual disability-strabismus syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000213638"/>
    <dbReference type="eggNOG" id="KOG2771">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000010706"/>
    <dbReference type="HOGENOM" id="CLU_013817_2_1_1"/>
    <dbReference type="InParanoid" id="Q96EY9"/>
    <dbReference type="OMA" id="QHWPTSF"/>
    <dbReference type="OrthoDB" id="3180714at2759"/>
    <dbReference type="PAN-GO" id="Q96EY9">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96EY9"/>
    <dbReference type="PathwayCommons" id="Q96EY9"/>
    <dbReference type="Reactome" id="R-HSA-6782315">
        <property type="pathway name" value="tRNA modification in the nucleus and cytosol"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q96EY9"/>
    <dbReference type="BioGRID-ORCS" id="113179">
        <property type="hits" value="336 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="113179"/>
    <dbReference type="Pharos" id="Q96EY9">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96EY9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96EY9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000213638">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 92 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96EY9">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003824">
        <property type="term" value="F:catalytic activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008033">
        <property type="term" value="P:tRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd01285">
        <property type="entry name" value="nucleoside_deaminase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.140.10">
        <property type="entry name" value="Cytidine Deaminase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002125">
        <property type="entry name" value="CMP_dCMP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016193">
        <property type="entry name" value="Cytidine_deaminase-like"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11079">
        <property type="entry name" value="CYTOSINE DEAMINASE FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11079:SF156">
        <property type="entry name" value="INACTIVE TRNA-SPECIFIC ADENOSINE DEAMINASE-LIKE PROTEIN 3-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00383">
        <property type="entry name" value="dCMP_cyt_deam_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53927">
        <property type="entry name" value="Cytidine deaminase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51747">
        <property type="entry name" value="CYT_DCMP_DEAMINASES_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0024">Alternative initiation</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0819">tRNA processing</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000287658" description="tRNA-specific adenosine-34 deaminase regulatory subunit ADAT3">
        <location>
            <begin position="1"/>
            <end position="367"/>
        </location>
    </feature>
    <feature type="domain" description="CMP/dCMP-type deaminase" evidence="2">
        <location>
            <begin position="187"/>
            <end position="352"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="239"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="307"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="310"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="366"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_062626" description="In isoform 2." evidence="8">
        <location>
            <begin position="1"/>
            <end position="16"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_069778" description="In NEDBGF; severe depletion of ADAT3 protein levels; defective deamination activity." evidence="5">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035804" description="In a breast cancer sample; somatic mutation." evidence="4">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="348"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="9">
        <location sequence="Q96EY9-2">
            <position position="1"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q6PAT0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01083"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16959974"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="23620220"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="25916855"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="40120092"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <sequence length="367" mass="39844" checksum="26D2E357D5C29C3D" modified="2026-01-28" version="2">MILCSRLCLPQSASLRMEPAPGLVEQPKCLEAGSPEPEPAPWQALPVLSEKQSGDVELVLAYAAPVLDKRQTSRLLKEVSALHPLPAQPHLKRVRPSRDAGSPHALEMLLCLAGPASGPRSLAELLPRPAVDPRGLGQPFLVPVPARPPLTRGQFEEARAHWPTSFHEDKQVTSALAGRLFSTQERAAMQSHMERAVWAARRAAARGLRAVGAVVVDPASDRVLATGHDCSCADNPLLHAVMVCVDLVARGQGRGTYDFRPFPACSFAPAAAPQAVRAGAVRKLDADEDGLPYLCTGYDLYVTREPCAMCAMALVHARILRVFYGAPSPDGALGTRFRIHARPDLNHRFQVFRGVLEEQCRWLDPDT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-08" modified="2026-01-28" version="189" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NFM4</accession>
    <accession>B3KV74</accession>
    <accession>D3DS75</accession>
    <accession>Q17R40</accession>
    <accession>Q6ZTM6</accession>
    <accession>Q96ML7</accession>
    <name>ADCY4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenylate cyclase type 4</fullName>
            <ecNumber evidence="2">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase type IV</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylyl cyclase 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="J. Recept. Signal Transduct." volume="22" first="79" last="110">
            <title>Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms.</title>
            <authorList>
                <person name="Ludwig M.G."/>
                <person name="Seuwen K."/>
            </authorList>
            <dbReference type="PubMed" id="12503609"/>
            <dbReference type="DOI" id="10.1081/rrs-120014589"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
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                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
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                <person name="Ono Y."/>
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                <person name="Yosida M."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Placenta</tissue>
            <tissue>Tongue</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="12508121"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="6">
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            <title>Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland.</title>
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                <person name="Gallo-Payet N."/>
            </authorList>
            <dbReference type="PubMed" id="11549699"/>
            <dbReference type="DOI" id="10.1210/jcem.86.9.7837"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="7">
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            <title>Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains.</title>
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                <person name="Bogard A.S."/>
                <person name="Xu C."/>
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            </authorList>
            <dbReference type="PubMed" id="21228062"/>
            <dbReference type="DOI" id="10.1124/jpet.110.177923"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="3">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="2">Activated by forskolin. Insensitive to calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and gamma subunit complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838710">
            <id>Q8NFM4</id>
        </interactant>
        <interactant intactId="EBI-2874661">
            <id>Q9BV19</id>
            <label>C1orf50</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838710">
            <id>Q8NFM4</id>
        </interactant>
        <interactant intactId="EBI-12001340">
            <id>P62508-3</id>
            <label>ESRRG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838710">
            <id>Q8NFM4</id>
        </interactant>
        <interactant intactId="EBI-781384">
            <id>P37231</id>
            <label>PPARG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838710">
            <id>Q8NFM4</id>
        </interactant>
        <interactant intactId="EBI-2130429">
            <id>Q9BYV2</id>
            <label>TRIM54</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838710">
            <id>Q8NFM4</id>
        </interactant>
        <interactant intactId="EBI-9090990">
            <id>Q5W5X9-3</id>
            <label>TTC23</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cell membrane</location>
            <topology evidence="9">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NFM4-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NFM4-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055816 VSP_055817 VSP_055818 VSP_055819"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Detected in the zona glomerulosa and the zona fasciculata in the adrenal gland (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="3">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB71270" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="2"/>
    <dbReference type="EMBL" id="AF497516">
        <property type="protein sequence ID" value="AAM94373.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK056745">
        <property type="protein sequence ID" value="BAB71270.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK122714">
        <property type="protein sequence ID" value="BAG53686.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK126468">
        <property type="protein sequence ID" value="BAC86560.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL096870">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66023.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66026.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66027.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471078">
        <property type="protein sequence ID" value="EAW66028.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117473">
        <property type="protein sequence ID" value="AAI17474.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117475">
        <property type="protein sequence ID" value="AAI17476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS9627.1">
        <molecule id="Q8NFM4-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185497.1">
        <molecule id="Q8NFM4-1"/>
        <property type="nucleotide sequence ID" value="NM_001198568.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001185521.1">
        <molecule id="Q8NFM4-1"/>
        <property type="nucleotide sequence ID" value="NM_001198592.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_640340.2">
        <molecule id="Q8NFM4-1"/>
        <property type="nucleotide sequence ID" value="NM_139247.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8NFM4"/>
    <dbReference type="SMR" id="Q8NFM4"/>
    <dbReference type="BioGRID" id="128229">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8NFM4">
        <property type="interactions" value="1605"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8NFM4">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000312126"/>
    <dbReference type="BindingDB" id="Q8NFM4"/>
    <dbReference type="ChEMBL" id="CHEMBL2097167"/>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q8NFM4">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8NFM4">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8NFM4"/>
    <dbReference type="PhosphoSitePlus" id="Q8NFM4"/>
    <dbReference type="BioMuta" id="ADCY4"/>
    <dbReference type="DMDM" id="25008336"/>
    <dbReference type="jPOST" id="Q8NFM4"/>
    <dbReference type="MassIVE" id="Q8NFM4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000312126"/>
    <dbReference type="PeptideAtlas" id="Q8NFM4"/>
    <dbReference type="ProteomicsDB" id="73323">
        <molecule id="Q8NFM4-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="3908">
        <property type="antibodies" value="234 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="196883"/>
    <dbReference type="Ensembl" id="ENST00000310677.8">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000312126.4"/>
        <property type="gene ID" value="ENSG00000129467.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000418030.7">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000393177.2"/>
        <property type="gene ID" value="ENSG00000129467.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000554068.6">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000452250.2"/>
        <property type="gene ID" value="ENSG00000129467.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000642645.1">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000495316.1"/>
        <property type="gene ID" value="ENSG00000284814.1"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000644961.1">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000494454.1"/>
        <property type="gene ID" value="ENSG00000284814.1"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000646612.1">
        <molecule id="Q8NFM4-1"/>
        <property type="protein sequence ID" value="ENSP00000494977.1"/>
        <property type="gene ID" value="ENSG00000284814.1"/>
    </dbReference>
    <dbReference type="GeneID" id="196883"/>
    <dbReference type="KEGG" id="hsa:196883"/>
    <dbReference type="MANE-Select" id="ENST00000418030.7">
        <property type="protein sequence ID" value="ENSP00000393177.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001198568.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001185497.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001wow.4">
        <molecule id="Q8NFM4-1"/>
        <property type="organism name" value="human"/>
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            <fullName>Uncharacterized aarF domain-containing protein kinase 2</fullName>
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    <reference key="1">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Huang C.Q."/>
                <person name="Shan Y.X."/>
                <person name="Cheng Z."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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    <reference key="2">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
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                <person name="Torrents D."/>
                <person name="Chinwalla A.T."/>
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            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-388</scope>
        <source>
            <tissue>Muscle</tissue>
        </source>
    </reference>
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            <title>ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.</title>
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            <dbReference type="PubMed" id="31480808"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>VARIANT 333-ARG--PRO-626 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANT 333-ARG--PRO-626 DEL</scope>
    </reference>
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            <title>A subcellular map of the human kinome.</title>
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                <person name="Zhang H."/>
                <person name="Cao X."/>
                <person name="Tang M."/>
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                <person name="Si Y."/>
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                <person name="Zhu F."/>
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            <dbReference type="PubMed" id="33988507"/>
            <dbReference type="DOI" id="10.7554/elife.64943"/>
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        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="6">
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            <title>Patterns of somatic mutation in human cancer genomes.</title>
            <authorList>
                <person name="Greenman C."/>
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                <person name="Hunter C."/>
                <person name="Bignell G."/>
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            </authorList>
            <dbReference type="PubMed" id="17344846"/>
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        </citation>
        <scope>VARIANTS [LARGE SCALE ANALYSIS] PRO-307; LEU-418; LEU-622 AND LEU-626</scope>
    </reference>
    <comment type="function">
        <text evidence="4 6">The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable). Involved in the mitochondrial import of CoQ precursors, plays a role in muscle mitochondrial function and fatty acid beta-oxidation (PubMed:31480808).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21505425">
            <id>Q7Z695</id>
        </interactant>
        <interactant intactId="EBI-355133">
            <id>P05141</id>
            <label>SLC25A5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Membrane</location>
            <topology evidence="2">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the protein kinase superfamily. ADCK protein kinase family.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="AAH14107" version="1"/>
        </conflict>
        <text>Aberrant splicing.</text>
    </comment>
    <dbReference type="EC" id="2.7.11.-"/>
    <dbReference type="EMBL" id="AY302592">
        <property type="protein sequence ID" value="AAP60021.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006344">
        <property type="protein sequence ID" value="AAD43192.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006452">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014107">
        <property type="protein sequence ID" value="AAH14107.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5861.1"/>
    <dbReference type="RefSeq" id="NP_443085.2">
        <property type="nucleotide sequence ID" value="NM_052853.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q7Z695"/>
    <dbReference type="BioGRID" id="124782">
        <property type="interactions" value="91"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q7Z695">
        <property type="interactions" value="501"/>
    </dbReference>
    <dbReference type="IntAct" id="Q7Z695">
        <property type="interactions" value="79"/>
    </dbReference>
    <dbReference type="MINT" id="Q7Z695"/>
    <dbReference type="STRING" id="9606.ENSP00000072869"/>
    <dbReference type="iPTMnet" id="Q7Z695"/>
    <dbReference type="PhosphoSitePlus" id="Q7Z695"/>
    <dbReference type="SwissPalm" id="Q7Z695"/>
    <dbReference type="BioMuta" id="ADCK2"/>
    <dbReference type="DMDM" id="74723374"/>
    <dbReference type="jPOST" id="Q7Z695"/>
    <dbReference type="MassIVE" id="Q7Z695"/>
    <dbReference type="PaxDb" id="9606-ENSP00000072869"/>
    <dbReference type="PeptideAtlas" id="Q7Z695"/>
    <dbReference type="ProteomicsDB" id="69383"/>
    <dbReference type="Antibodypedia" id="32457">
        <property type="antibodies" value="167 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="90956"/>
    <dbReference type="Ensembl" id="ENST00000072869.9">
        <property type="protein sequence ID" value="ENSP00000072869.4"/>
        <property type="gene ID" value="ENSG00000133597.12"/>
    </dbReference>
    <dbReference type="GeneID" id="90956"/>
    <dbReference type="KEGG" id="hsa:90956"/>
    <dbReference type="MANE-Select" id="ENST00000072869.9">
        <property type="protein sequence ID" value="ENSP00000072869.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_052853.4"/>
        <property type="RefSeq protein sequence ID" value="NP_443085.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003vvy.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:19039"/>
    <dbReference type="ClinPGx" id="PA134902329"/>
    <dbReference type="CTD" id="90956"/>
    <dbReference type="DisGeNET" id="90956"/>
    <dbReference type="GeneCards" id="ADCK2"/>
    <dbReference type="HGNC" id="HGNC:19039">
        <property type="gene designation" value="ADCK2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000133597">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621162">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000133597"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000133597"/>
    <dbReference type="eggNOG" id="KOG1236">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000001536"/>
    <dbReference type="HOGENOM" id="CLU_006533_6_1_1"/>
    <dbReference type="InParanoid" id="Q7Z695"/>
    <dbReference type="OMA" id="SMVRTHH"/>
    <dbReference type="OrthoDB" id="427480at2759"/>
    <dbReference type="PAN-GO" id="Q7Z695">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7Z695"/>
    <dbReference type="PathwayCommons" id="Q7Z695"/>
    <dbReference type="SignaLink" id="Q7Z695"/>
    <dbReference type="Agora" id="ENSG00000133597"/>
    <dbReference type="BioGRID-ORCS" id="90956">
        <property type="hits" value="31 hits in 1189 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCK2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="90956"/>
    <dbReference type="Pharos" id="Q7Z695">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7Z695"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7Z695">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000133597">
        <property type="expression patterns" value="Expressed in buccal mucosa cell and 207 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q7Z695">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010795">
        <property type="term" value="P:regulation of ubiquinone biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd13971">
        <property type="entry name" value="ADCK2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004147">
        <property type="entry name" value="ABC1_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR044095">
        <property type="entry name" value="ADCK2_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052402">
        <property type="entry name" value="ADCK_kinase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45890:SF1">
        <property type="entry name" value="AARF DOMAIN CONTAINING KINASE 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45890">
        <property type="entry name" value="AARF DOMAIN CONTAINING KINASE 2 (PREDICTED)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03109">
        <property type="entry name" value="ABC1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000271792" description="Uncharacterized aarF domain-containing protein kinase 2">
        <location>
            <begin position="1"/>
            <end position="626"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="103"/>
            <end position="123"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase">
        <location>
            <begin position="200"/>
            <end position="618"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="1">
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="206"/>
            <end position="214"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="311"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_060990" description="In dbSNP:rs2968558.">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029992" description="In dbSNP:rs1140034." evidence="3">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_088468" description="Found in a patient with slow and progressive proximal muscle weakness with permanent myalgia both at rest and during muscular exertion which results in permanent disability; uncertain significance; decreased levels of coenzyme Q10." evidence="4">
        <location>
            <begin position="333"/>
            <end position="626"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041418" description="In dbSNP:rs3748092." evidence="3">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029993" description="In dbSNP:rs3748092.">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="418"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029994" description="In dbSNP:rs1046515." evidence="3">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="622"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_041419" description="In dbSNP:rs55922126." evidence="3">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="626"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="17344846"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="31480808"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="33988507"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="626" mass="68982" checksum="F8E25DB672017AF4" modified="2003-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1999-07-15" modified="2026-01-28" version="204" xmlns="https://uniprot.org/uniprot">
    <accession>O60503</accession>
    <accession>A7E2V5</accession>
    <accession>A7E2X2</accession>
    <accession>D3DUD1</accession>
    <accession>O60273</accession>
    <accession>Q4ZHT9</accession>
    <accession>Q4ZIR5</accession>
    <accession>Q9BWT4</accession>
    <accession>Q9UGP2</accession>
    <name>ADCY9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">Adenylate cyclase type 9</fullName>
            <ecNumber evidence="7 8 10 12">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 9</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">Adenylate cyclase type IX</fullName>
            <shortName evidence="13">ACIX</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylyl cyclase 9</fullName>
            <shortName evidence="14">AC9</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY9</name>
        <name type="synonym">KIAA0520</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9).</title>
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                <person name="Hacker B.M."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <tissue>Heart</tissue>
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    </reference>
    <reference key="2">
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                <person name="Small K.M."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT MET-772</scope>
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    <reference key="3">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANT MET-772</scope>
    </reference>
    <reference key="4">
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                <person name="Paterson J.M."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT SER-1154</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2001-03" db="EMBL/GenBank/DDBJ databases">
            <title>Mutation screening, case control study and transmission disequilibrium analysis of adenylate cyclase type 9 (ADCY9) gene in functional psychoses.</title>
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                <person name="Toyota T."/>
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                <person name="Saito K."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="31" last="39">
            <title>Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
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            </authorList>
            <dbReference type="PubMed" id="9628581"/>
            <dbReference type="DOI" id="10.1093/dnares/5.1.31"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-1154</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2002" name="DNA Res." volume="9" first="99" last="106">
            <title>Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.</title>
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                <person name="Nakajima D."/>
                <person name="Okazaki N."/>
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                <person name="Kikuno R."/>
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            </authorList>
            <dbReference type="PubMed" id="12168954"/>
            <dbReference type="DOI" id="10.1093/dnares/9.3.99"/>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="8">
        <citation type="submission" date="2005-08" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
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        </citation>
        <scope>SEQUENCE REVISION</scope>
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    <reference key="9">
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            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT SER-1154</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
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            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1259</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
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                <person name="Kumar C."/>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1307</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
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            <authorList>
                <person name="Zhou H."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1257 AND SER-1259</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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    <reference key="14">
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            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="7 8 10 12">Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:10987815, PubMed:12972952, PubMed:15879435, PubMed:9628827). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7 8 10 12">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="2">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="7 12">Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation (PubMed:9628827). Activity is down-regulated by calcium/calcineurin (PubMed:10987815).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6871081">
            <id>O60503</id>
        </interactant>
        <interactant intactId="EBI-53949969">
            <id>Q8TE99</id>
            <label>PXYLP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7 12">Cell membrane</location>
            <topology evidence="16">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 8 12">Detected in skeletal muscle, pancreas, lung, heart, kidney, liver, brain and placenta (PubMed:10987815, PubMed:9628827). Expressed in multiple cells of the lung, with expression highest in airway smooth muscle (PubMed:12972952).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAC24201" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="16">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA25446" version="3"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="7 8 10 12"/>
    <dbReference type="EMBL" id="AF036927">
        <property type="protein sequence ID" value="AAC24201.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ008441">
        <property type="protein sequence ID" value="AAY27880.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ005545">
        <property type="protein sequence ID" value="AAY21237.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ133123">
        <property type="protein sequence ID" value="CAB65084.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028959">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028949">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028950">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028951">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028952">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028953">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028954">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028955">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028956">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY028957">
        <property type="protein sequence ID" value="AAK29464.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB011092">
        <property type="protein sequence ID" value="BAA25446.3"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471112">
        <property type="protein sequence ID" value="EAW85331.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471112">
        <property type="protein sequence ID" value="EAW85332.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136657">
        <property type="protein sequence ID" value="AAI36658.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136658">
        <property type="protein sequence ID" value="AAI36659.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC151207">
        <property type="protein sequence ID" value="AAI51208.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC151229">
        <property type="protein sequence ID" value="AAI51230.1"/>
        <property type="molecule type" value="mRNA"/>
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            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
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    <feature type="binding site" evidence="5">
        <location>
            <position position="400"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="441"/>
            <end position="443"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="443"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="5">
        <location>
            <position position="443"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="487"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="1108"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="1185"/>
            <end position="1187"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="1">
        <location>
            <begin position="1192"/>
            <end position="1196"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="binding site" evidence="1">
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            <position position="1232"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
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            <position position="610"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
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            <position position="688"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
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            <position position="691"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="20">
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            <position position="706"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="19">
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            <position position="1257"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="17 19">
        <location>
            <position position="1259"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="1295"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="18">
        <location>
            <position position="1307"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="206"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="955"/>
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    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="964"/>
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    </feature>
    <feature type="sequence variant" id="VAR_023750" description="Found in 37.5% of the Asian population, in 30% of the Caucasian population and in 16.3% of the African-American population; reduced adenylyl cyclase activity in response to stimulation of the beta-adregnergic receptor by Mn(2+) agonists isoproteronol and NaF; increased albuterol-stimulated adenylyl cyclase activity in the presence of corticosteroid; dbSNP:rs2230739." evidence="8 10">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="772"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_070887" description="In dbSNP:rs61731445." evidence="7 9 11">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="1154"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAB65084." evidence="16" ref="4">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="493"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAB65084." evidence="16" ref="4">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="884"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAB65084." evidence="16" ref="4">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="1308"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P26769"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P30803"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P51830"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00099"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10987815"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12972952"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="15879435"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="9628581"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="9628827"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="10987815"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="15879435"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="9628827"/>
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    </evidence>
    <evidence type="ECO:0000305" key="16"/>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="1353" mass="150701" checksum="4CBF051EA49B5B7B" modified="2002-12-13" version="4"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-01-09" modified="2026-01-28" version="148" xmlns="https://uniprot.org/uniprot">
    <accession>Q3MIX3</accession>
    <accession>B3KS46</accession>
    <accession>Q5U4P1</accession>
    <accession>Q6P2S4</accession>
    <accession>Q8N5V3</accession>
    <name>ADCK5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Uncharacterized aarF domain-containing protein kinase 5</fullName>
            <ecNumber>2.7.11.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADCK5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <dbReference type="DOI" id="10.1038/nature05610"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] ARG-17</scope>
    </reference>
    <comment type="function">
        <text>The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3923548">
            <id>Q3MIX3</id>
        </interactant>
        <interactant intactId="EBI-945833">
            <id>Q7Z3S9</id>
            <label>NOTCH2NLA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <topology evidence="3">Single-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the protein kinase superfamily. ADCK protein kinase family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH31570" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="2.7.11.-"/>
    <dbReference type="EMBL" id="AK092773">
        <property type="protein sequence ID" value="BAG52608.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC233992">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031570">
        <property type="protein sequence ID" value="AAH31570.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064345">
        <property type="protein sequence ID" value="AAH64345.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC085013">
        <property type="protein sequence ID" value="AAH85013.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC101659">
        <property type="protein sequence ID" value="AAI01660.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34965.2"/>
    <dbReference type="RefSeq" id="NP_777582.4">
        <property type="nucleotide sequence ID" value="NM_174922.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q3MIX3"/>
    <dbReference type="SMR" id="Q3MIX3"/>
    <dbReference type="BioGRID" id="128442">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q3MIX3">
        <property type="interactions" value="97"/>
    </dbReference>
    <dbReference type="IntAct" id="Q3MIX3">
        <property type="interactions" value="36"/>
    </dbReference>
    <dbReference type="MINT" id="Q3MIX3"/>
    <dbReference type="STRING" id="9606.ENSP00000310547"/>
    <dbReference type="ChEMBL" id="CHEMBL4105886"/>
    <dbReference type="DrugCentral" id="Q3MIX3"/>
    <dbReference type="iPTMnet" id="Q3MIX3"/>
    <dbReference type="PhosphoSitePlus" id="Q3MIX3"/>
    <dbReference type="BioMuta" id="ADCK5"/>
    <dbReference type="DMDM" id="121958055"/>
    <dbReference type="CPTAC" id="non-CPTAC-5660"/>
    <dbReference type="jPOST" id="Q3MIX3"/>
    <dbReference type="MassIVE" id="Q3MIX3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000310547"/>
    <dbReference type="PeptideAtlas" id="Q3MIX3"/>
    <dbReference type="ProteomicsDB" id="61799"/>
    <dbReference type="Pumba" id="Q3MIX3"/>
    <dbReference type="Antibodypedia" id="28478">
        <property type="antibodies" value="180 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="203054"/>
    <dbReference type="Ensembl" id="ENST00000308860.11">
        <property type="protein sequence ID" value="ENSP00000310547.6"/>
        <property type="gene ID" value="ENSG00000173137.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000645968.2">
        <property type="protein sequence ID" value="ENSP00000494807.1"/>
        <property type="gene ID" value="ENSG00000285451.2"/>
    </dbReference>
    <dbReference type="GeneID" id="203054"/>
    <dbReference type="KEGG" id="hsa:203054"/>
    <dbReference type="MANE-Select" id="ENST00000308860.11">
        <property type="protein sequence ID" value="ENSP00000310547.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_174922.5"/>
        <property type="RefSeq protein sequence ID" value="NP_777582.4"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003zch.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21738"/>
    <dbReference type="ClinPGx" id="PA134963849"/>
    <dbReference type="CTD" id="203054"/>
    <dbReference type="DisGeNET" id="203054"/>
    <dbReference type="GeneCards" id="ADCK5"/>
    <dbReference type="HGNC" id="HGNC:21738">
        <property type="gene designation" value="ADCK5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000173137">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCK5"/>
    <dbReference type="MIM" id="621165">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000173137"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000173137"/>
    <dbReference type="eggNOG" id="KOG1235">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159821"/>
    <dbReference type="HOGENOM" id="CLU_006533_2_6_1"/>
    <dbReference type="InParanoid" id="Q3MIX3"/>
    <dbReference type="OMA" id="DVMTTMV"/>
    <dbReference type="OrthoDB" id="427480at2759"/>
    <dbReference type="PAN-GO" id="Q3MIX3">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q3MIX3"/>
    <dbReference type="PathwayCommons" id="Q3MIX3"/>
    <dbReference type="SignaLink" id="Q3MIX3"/>
    <dbReference type="SIGNOR" id="Q3MIX3"/>
    <dbReference type="Agora" id="ENSG00000173137"/>
    <dbReference type="BioGRID-ORCS" id="203054">
        <property type="hits" value="14 hits in 1191 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCK5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="203054"/>
    <dbReference type="Pharos" id="Q3MIX3">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q3MIX3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 8"/>
    </dbReference>
    <dbReference type="RNAct" id="Q3MIX3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000173137">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 96 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q3MIX3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004674">
        <property type="term" value="F:protein serine/threonine kinase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd13969">
        <property type="entry name" value="ADCK1-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004147">
        <property type="entry name" value="ABC1_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045307">
        <property type="entry name" value="ADCK1_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011009">
        <property type="entry name" value="Kinase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051130">
        <property type="entry name" value="Mito_struct-func_regulator"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43173:SF28">
        <property type="entry name" value="AARF DOMAIN CONTAINING KINASE 5"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43173">
        <property type="entry name" value="ABC1 FAMILY PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03109">
        <property type="entry name" value="ABC1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56112">
        <property type="entry name" value="Protein kinase-like (PK-like)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0723">Serine/threonine-protein kinase</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000271800" description="Uncharacterized aarF domain-containing protein kinase 5">
        <location>
            <begin position="1"/>
            <end position="580"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="50"/>
            <end position="67"/>
        </location>
    </feature>
    <feature type="domain" description="Protein kinase">
        <location>
            <begin position="179"/>
            <end position="419"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029996" description="In dbSNP:rs6599528." evidence="2">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="17"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAG52608." evidence="3" ref="1">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="275"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH85013." evidence="3" ref="3">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="283"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAH64345." evidence="3" ref="3">
        <original>NDVEAIRSQGLAVHD</original>
        <variation>GGLVLCPLQCLSSPQ</variation>
        <location>
            <begin position="324"/>
            <end position="338"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="580" mass="65828" checksum="ACA0DB28B7B16F0C" modified="2018-09-12" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-06-20" modified="2026-01-28" version="215" xmlns="https://uniprot.org/uniprot">
    <accession>Q9P0K1</accession>
    <accession>O75075</accession>
    <accession>O75076</accession>
    <accession>Q9P0K2</accession>
    <accession>Q9UIA1</accession>
    <accession>Q9UKK2</accession>
    <name>ADA22_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Disintegrin and metalloproteinase domain-containing protein 22</fullName>
            <shortName>ADAM 22</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Metalloproteinase-disintegrin ADAM22-3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAM22</name>
        <name type="synonym">MDC2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="Biochem. J." volume="334" first="93" last="98">
            <title>Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain.</title>
            <authorList>
                <person name="Sagane K."/>
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            </authorList>
            <dbReference type="PubMed" id="9693107"/>
            <dbReference type="DOI" id="10.1042/bj3340093"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
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            <authorList>
                <person name="Harada T."/>
                <person name="Nishie A."/>
                <person name="Torigoe K."/>
                <person name="Ikezaki K."/>
                <person name="Shono T."/>
                <person name="Maehara Y."/>
                <person name="Kuwano M."/>
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            </authorList>
            <dbReference type="PubMed" id="11050470"/>
            <dbReference type="DOI" id="10.1111/j.1349-7006.2000.tb00877.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2000-01" db="EMBL/GenBank/DDBJ databases">
            <title>Isolation and tissue specific expression of novel ADAM family from 7q21.1 region.</title>
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                <person name="Wada M."/>
                <person name="Torigoe K."/>
                <person name="Harada T."/>
                <person name="Kuwano M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5)</scope>
        <scope>VARIANT ARG-81</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2003" name="Nature" volume="424" first="157" last="164">
            <title>The DNA sequence of human chromosome 7.</title>
            <authorList>
                <person name="Hillier L.W."/>
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                <person name="Layman D."/>
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                <person name="Bork P."/>
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                <person name="McPherson J.D."/>
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                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="Gene" volume="237" first="61" last="70">
            <title>The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries.</title>
            <authorList>
                <person name="Poindexter K."/>
                <person name="Nelson N."/>
                <person name="DuBose R.F."/>
                <person name="Black R.A."/>
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            <dbReference type="PubMed" id="10524237"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(99)00302-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 40-906 (ISOFORM 1)</scope>
        <scope>VARIANT ARG-81</scope>
        <source>
            <tissue>Cerebellum</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="Biochem. Biophys. Res. Commun." volume="301" first="991" last="999">
            <title>The interaction between ADAM 22 and 14-3-3zeta: regulation of cell adhesion and spreading.</title>
            <authorList>
                <person name="Zhu P."/>
                <person name="Sun Y."/>
                <person name="Xu R."/>
                <person name="Sang Y."/>
                <person name="Zhao J."/>
                <person name="Liu G."/>
                <person name="Cai L."/>
                <person name="Li C."/>
                <person name="Zhao S."/>
            </authorList>
            <dbReference type="PubMed" id="12589811"/>
            <dbReference type="DOI" id="10.1016/s0006-291x(03)00056-1"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH YWHAZ</scope>
        <scope>MUTAGENESIS OF SER-834 AND SER-857</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Biol." volume="5" first="R8.1" last="R8.16">
            <title>An unappreciated role for RNA surveillance.</title>
            <authorList>
                <person name="Hillman R.T."/>
                <person name="Green R.E."/>
                <person name="Brenner S.E."/>
            </authorList>
            <dbReference type="PubMed" id="14759258"/>
            <dbReference type="DOI" id="10.1186/gb-2004-5-2-r8"/>
        </citation>
        <scope>SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S)</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2005" name="Biochem. Biophys. Res. Commun." volume="331" first="938" last="946">
            <title>ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3.</title>
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                <person name="Zhu P."/>
                <person name="Sang Y."/>
                <person name="Xu H."/>
                <person name="Zhao J."/>
                <person name="Xu R."/>
                <person name="Sun Y."/>
                <person name="Xu T."/>
                <person name="Wang X."/>
                <person name="Chen L."/>
                <person name="Feng H."/>
                <person name="Li C."/>
                <person name="Zhao S."/>
            </authorList>
            <dbReference type="PubMed" id="15882968"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2005.03.229"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH YWHAB</scope>
        <scope>MUTAGENESIS OF SER-834 AND SER-857</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="Neurosurgery" volume="58" first="179" last="186">
            <title>ADAM22, expressed in normal brain but not in high-grade gliomas, inhibits cellular proliferation via the disintegrin domain.</title>
            <authorList>
                <person name="D'Abaco G.M."/>
                <person name="Ng K."/>
                <person name="Paradiso L."/>
                <person name="Godde N.J."/>
                <person name="Kaye A."/>
                <person name="Novak U."/>
            </authorList>
            <dbReference type="PubMed" id="16385342"/>
            <dbReference type="DOI" id="10.1227/01.neu.0000192363.84287.8b"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-834</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2016" name="Neurol. Genet." volume="2" first="E46" last="E46">
            <title>Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy.</title>
            <authorList>
                <person name="Muona M."/>
                <person name="Fukata Y."/>
                <person name="Anttonen A.K."/>
                <person name="Laari A."/>
                <person name="Palotie A."/>
                <person name="Pihko H."/>
                <person name="Loennqvist T."/>
                <person name="Valanne L."/>
                <person name="Somer M."/>
                <person name="Fukata M."/>
                <person name="Lehesjoki A.E."/>
            </authorList>
            <dbReference type="PubMed" id="27066583"/>
            <dbReference type="DOI" id="10.1212/nxg.0000000000000046"/>
        </citation>
        <scope>INVOLVEMENT IN DEE61</scope>
        <scope>VARIANT DEE61 TYR-401</scope>
        <scope>INTERACTION WITH LGI1 AND DLG4</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANT DEE61 TYR-401</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2009" name="J. Biol. Chem." volume="284" first="29077" last="29086">
            <title>Structural characterization of the ectodomain of a disintegrin and metalloproteinase-22 (ADAM22), a neural adhesion receptor instead of metalloproteinase: insights on ADAM function.</title>
            <authorList>
                <person name="Liu H."/>
                <person name="Shim A.H."/>
                <person name="He X."/>
            </authorList>
            <dbReference type="PubMed" id="19692335"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.014258"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS) OF 233-736</scope>
        <scope>GLYCOSYLATION AT ASN-519; ASN-634 AND ASN-675</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="8 9 10 11">Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein (PubMed:19692335). Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation. Neuronal receptor for LGI1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 8 9 12">Interacts with LGI1 (PubMed:27066583). Interacts with DLG4/PSD95 (PubMed:27066583). Also binds LGI4 (By similarity). Interacts with KCNA2 and DLG2 (By similarity). Interacts with ADAM11 (By similarity). Interacts (via C-terminus) with YWHAB/14-3-3 beta (PubMed:15882968). Interacts (via C-terminus) with YWHAZ/14-3-3 zeta (PubMed:12589811).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-357481">
            <id>Q12959</id>
            <label>DLG1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-80440">
            <id>Q92796</id>
            <label>DLG3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-80389">
            <id>P78352</id>
            <label>DLG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-724390">
            <id>Q8NI35</id>
            <label>PATJ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-310886">
            <id>Q9P202</id>
            <label>WHRN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567236">
            <id>Q9P0K1</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
        </interactant>
        <interactant intactId="EBI-359815">
            <id>P31946</id>
            <label>YWHAB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
        </interactant>
        <interactant intactId="EBI-359854">
            <id>P27348</id>
            <label>YWHAQ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1567267">
            <id>Q9P0K1-3</id>
        </interactant>
        <interactant intactId="EBI-347088">
            <id>P63104</id>
            <label>YWHAZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12">Cell membrane</location>
            <topology evidence="17">Single-pass type I membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cell projection</location>
            <location evidence="2">Axon</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9P0K1-1</id>
            <name>1</name>
            <name>Epsilon</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9P0K1-2</id>
            <name>2</name>
            <name>Delta</name>
            <sequence type="described" ref="VSP_005482 VSP_005484"/>
        </isoform>
        <isoform>
            <id>Q9P0K1-3</id>
            <name>3</name>
            <name>Alpha</name>
            <sequence type="described" ref="VSP_005483"/>
        </isoform>
        <isoform>
            <id>Q9P0K1-4</id>
            <name>4</name>
            <name>Beta</name>
            <sequence type="described" ref="VSP_005482 VSP_005483"/>
        </isoform>
        <isoform>
            <id>Q9P0K1-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_005482"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Highly expressed in the brain and in some high-grade but not low-grade gliomas. Detected slightly or not at all in other tissues.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">The precursor is cleaved by a furin endopeptidase.</text>
    </comment>
    <comment type="disease" evidence="12">
        <disease id="DI-05227">
            <name>Developmental and epileptic encephalopathy 61</name>
            <acronym>DEE61</acronym>
            <description>A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE61 is an autosomal recessive condition characterized by onset of seizures in infancy.</description>
            <dbReference type="MIM" id="617933"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="17">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <dbReference type="EMBL" id="AB009671">
        <property type="protein sequence ID" value="BAA32349.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB009671">
        <property type="protein sequence ID" value="BAA32350.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF155381">
        <property type="protein sequence ID" value="AAF73288.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF155382">
        <property type="protein sequence ID" value="AAF73289.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF073291">
        <property type="protein sequence ID" value="AAF22476.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005075">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF158637">
        <property type="protein sequence ID" value="AAD55251.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43608.1">
        <molecule id="Q9P0K1-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43609.1">
        <molecule id="Q9P0K1-5"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43610.1">
        <molecule id="Q9P0K1-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47637.1">
        <molecule id="Q9P0K1-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS94138.1">
        <molecule id="Q9P0K1-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004185.1">
        <molecule id="Q9P0K1-3"/>
        <property type="nucleotide sequence ID" value="NM_004194.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068367.1">
        <molecule id="Q9P0K1-4"/>
        <property type="nucleotide sequence ID" value="NM_021721.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068368.2">
        <molecule id="Q9P0K1-2"/>
        <property type="nucleotide sequence ID" value="NM_021722.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_068369.1">
        <molecule id="Q9P0K1-1"/>
        <property type="nucleotide sequence ID" value="NM_021723.5"/>
    </dbReference>
    <dbReference type="PDB" id="3G5C">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.36 A"/>
        <property type="chains" value="A/B=233-736"/>
    </dbReference>
    <dbReference type="PDB" id="5Y2Z">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.67 A"/>
        <property type="chains" value="A/C/E/G/I/K=233-729"/>
    </dbReference>
    <dbReference type="PDB" id="5Y31">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="7.12 A"/>
        <property type="chains" value="A/C=233-729"/>
    </dbReference>
    <dbReference type="PDB" id="7CQF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=892-906"/>
    </dbReference>
    <dbReference type="PDB" id="8HPY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="5.87 A"/>
        <property type="chains" value="A/B=233-718"/>
    </dbReference>
    <dbReference type="PDB" id="8HQ1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="4.17 A"/>
        <property type="chains" value="A/B/C=233-718"/>
    </dbReference>
    <dbReference type="PDB" id="8HQ2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.93 A"/>
        <property type="chains" value="A/B=233-718"/>
    </dbReference>
    <dbReference type="PDB" id="8Y6B">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.49 A"/>
        <property type="chains" value="A/B/C=233-718"/>
    </dbReference>
    <dbReference type="PDB" id="9KZC">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.78 A"/>
        <property type="chains" value="A=233-718"/>
    </dbReference>
    <dbReference type="PDB" id="9KZT">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.79 A"/>
        <property type="chains" value="A/C/E=233-729"/>
    </dbReference>
    <dbReference type="PDBsum" id="3G5C"/>
    <dbReference type="PDBsum" id="5Y2Z"/>
    <dbReference type="PDBsum" id="5Y31"/>
    <dbReference type="PDBsum" id="7CQF"/>
    <dbReference type="PDBsum" id="8HPY"/>
    <dbReference type="PDBsum" id="8HQ1"/>
    <dbReference type="PDBsum" id="8HQ2"/>
    <dbReference type="PDBsum" id="8Y6B"/>
    <dbReference type="PDBsum" id="9KZC"/>
    <dbReference type="PDBsum" id="9KZT"/>
    <dbReference type="AlphaFoldDB" id="Q9P0K1"/>
    <dbReference type="EMDB" id="EMD-62659"/>
    <dbReference type="EMDB" id="EMD-62668"/>
    <dbReference type="SMR" id="Q9P0K1"/>
    <dbReference type="BioGRID" id="119789">
        <property type="interactions" value="32"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9P0K1"/>
    <dbReference type="ELM" id="Q9P0K1"/>
    <dbReference type="FunCoup" id="Q9P0K1">
        <property type="interactions" value="773"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9P0K1">
        <property type="interactions" value="60"/>
    </dbReference>
    <dbReference type="MINT" id="Q9P0K1"/>
    <dbReference type="STRING" id="9606.ENSP00000265727"/>
    <dbReference type="MEROPS" id="M12.978"/>
    <dbReference type="GlyCosmos" id="Q9P0K1">
        <property type="glycosylation" value="4 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9P0K1">
        <property type="glycosylation" value="5 sites, 9 N-linked glycans (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9P0K1"/>
    <dbReference type="PhosphoSitePlus" id="Q9P0K1"/>
    <dbReference type="BioMuta" id="ADAM22"/>
    <dbReference type="DMDM" id="14423634"/>
    <dbReference type="jPOST" id="Q9P0K1"/>
    <dbReference type="MassIVE" id="Q9P0K1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000265727"/>
    <dbReference type="PeptideAtlas" id="Q9P0K1"/>
    <dbReference type="ProteomicsDB" id="83556">
        <molecule id="Q9P0K1-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83557">
        <molecule id="Q9P0K1-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83558">
        <molecule id="Q9P0K1-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83559">
        <molecule id="Q9P0K1-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="83560">
        <molecule id="Q9P0K1-5"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9P0K1"/>
    <dbReference type="Antibodypedia" id="29782">
        <property type="antibodies" value="313 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="53616"/>
    <dbReference type="Ensembl" id="ENST00000265727.11">
        <molecule id="Q9P0K1-1"/>
        <property type="protein sequence ID" value="ENSP00000265727.7"/>
        <property type="gene ID" value="ENSG00000008277.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000398201.8">
        <molecule id="Q9P0K1-3"/>
        <property type="protein sequence ID" value="ENSP00000381260.4"/>
        <property type="gene ID" value="ENSG00000008277.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000398204.8">
        <molecule id="Q9P0K1-5"/>
        <property type="protein sequence ID" value="ENSP00000381262.4"/>
        <property type="gene ID" value="ENSG00000008277.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000398209.7">
        <molecule id="Q9P0K1-2"/>
        <property type="protein sequence ID" value="ENSP00000381267.3"/>
        <property type="gene ID" value="ENSG00000008277.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000684002.1">
        <molecule id="Q9P0K1-4"/>
        <property type="protein sequence ID" value="ENSP00000508320.1"/>
        <property type="gene ID" value="ENSG00000008277.16"/>
    </dbReference>
    <dbReference type="GeneID" id="53616"/>
    <dbReference type="KEGG" id="hsa:53616"/>
    <dbReference type="UCSC" id="uc003ujk.3">
        <molecule id="Q9P0K1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:201"/>
    <dbReference type="ClinPGx" id="PA24518"/>
    <dbReference type="CTD" id="53616"/>
    <dbReference type="DisGeNET" id="53616"/>
    <dbReference type="GeneCards" id="ADAM22"/>
    <dbReference type="HGNC" id="HGNC:201">
        <property type="gene designation" value="ADAM22"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000008277">
        <property type="expression patterns" value="Tissue enriched (brain)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADAM22"/>
    <dbReference type="MIM" id="603709">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="617933">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000008277"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000008277"/>
    <dbReference type="eggNOG" id="KOG3607">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156889"/>
    <dbReference type="InParanoid" id="Q9P0K1"/>
    <dbReference type="OMA" id="TAWGYNM"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
    <dbReference type="PAN-GO" id="Q9P0K1">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9P0K1"/>
    <dbReference type="PathwayCommons" id="Q9P0K1"/>
    <dbReference type="Reactome" id="R-HSA-5682910">
        <property type="pathway name" value="LGI-ADAM interactions"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9P0K1"/>
    <dbReference type="Agora" id="ENSG00000008277"/>
    <dbReference type="BioGRID-ORCS" id="53616">
        <property type="hits" value="8 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADAM22">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9P0K1"/>
    <dbReference type="GeneWiki" id="ADAM22"/>
    <dbReference type="GenomeRNAi" id="53616"/>
    <dbReference type="Pharos" id="Q9P0K1">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9P0K1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9P0K1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000008277">
        <property type="expression patterns" value="Expressed in lateral nuclear group of thalamus and 157 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9P0K1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030424">
        <property type="term" value="C:axon"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
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    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
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    <keyword id="KW-0887">Epilepsy</keyword>
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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            <begin position="569"/>
            <end position="635"/>
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    <feature type="disulfide bond" evidence="11">
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            <end position="593"/>
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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    <feature type="disulfide bond" evidence="11">
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            <end position="803"/>
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            <position position="81"/>
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        <original>C</original>
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            <begin position="235"/>
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        </location>
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    <feature type="strand" evidence="19">
        <location>
            <begin position="656"/>
            <end position="658"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="661"/>
            <end position="666"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="668"/>
            <end position="670"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="671"/>
            <end position="674"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="688"/>
            <end position="690"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="692"/>
            <end position="695"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="700"/>
            <end position="702"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="706"/>
            <end position="708"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAF73288." evidence="17" ref="2">
        <original>G</original>
        <variation>E</variation>
        <location sequence="Q9P0K1-2">
            <position position="848"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9R1V6"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
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    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10524237"/>
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    <evidence type="ECO:0000269" key="8">
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            <dbReference type="PubMed" id="12589811"/>
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    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15882968"/>
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    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="16385342"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="19692335"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="27066583"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="11050470"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="9693107"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="3G5C"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="5Y2Z"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="8HQ2"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="8Y6B"/>
        </source>
    </evidence>
    <sequence length="906" mass="100433" checksum="265ECCD0FA6C088B" modified="2000-10-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>O00116</accession>
    <accession>A5D8U9</accession>
    <accession>Q2TU35</accession>
    <name>ADAS_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alkyldihydroxyacetonephosphate synthase, peroxisomal</fullName>
            <shortName>Alkyl-DHAP synthase</shortName>
            <ecNumber evidence="8 9">2.5.1.26</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Aging-associated gene 5 protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alkylglycerone-phosphate synthase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGPS</name>
        <name type="ORF">AAG5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Biochim. Biophys. Acta" volume="1346" first="25" last="29">
            <title>Nucleotide sequence of human alkyl-dihydroxyacetonephosphate synthase cDNA reveals the presence of a peroxisomal targeting signal 2.</title>
            <authorList>
                <person name="de Vet E.C.J.M."/>
                <person name="van den Broek B.T.E."/>
                <person name="van den Bosch H."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
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            <title>Identification of a human aging-associated gene.</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Makita H."/>
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                <person name="Moriya S."/>
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                <person name="Terashima Y."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Tongue</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1993" name="Biochim. Biophys. Acta" volume="1170" first="189" last="196">
            <title>Ether lipid synthesis: purification and identification of alkyl dihydroxyacetone phosphate synthase from guinea-pig liver.</title>
            <authorList>
                <person name="Zomer A.W."/>
                <person name="de Weerd W.F."/>
                <person name="Langeveld J."/>
                <person name="van den Bosch H."/>
            </authorList>
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            <dbReference type="DOI" id="10.1016/0005-2760(93)90070-p"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
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            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
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                <person name="Choudhary C."/>
                <person name="Kumar C."/>
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            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-102 AND LYS-347</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
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                <person name="Burkard T.R."/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND THR-74</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
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    </reference>
    <reference key="10">
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND THR-74</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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                <person name="Rabilloud T."/>
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                <person name="Rompais M."/>
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                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="10296" last="10301">
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            </authorList>
            <dbReference type="PubMed" id="9553082"/>
            <dbReference type="DOI" id="10.1074/jbc.273.17.10296"/>
        </citation>
        <scope>VARIANT RCDP3 HIS-419</scope>
        <scope>CHARACTERIZATION OF VARIANT RCDP3</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
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                <person name="Rodemer C."/>
                <person name="Jauch A."/>
                <person name="Hunziker A."/>
                <person name="Moser A."/>
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                <person name="Just W.W."/>
            </authorList>
            <dbReference type="PubMed" id="11152660"/>
            <dbReference type="DOI" id="10.1093/hmg/10.2.127"/>
        </citation>
        <scope>VARIANTS RCDP3 ILE-309 AND PRO-469</scope>
    </reference>
    <reference key="14">
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            <title>Functional characterization of novel mutations in GNPAT and AGPS, causing rhizomelic chondrodysplasia punctata (RCDP) types 2 and 3.</title>
            <authorList>
                <person name="Itzkovitz B."/>
                <person name="Jiralerspong S."/>
                <person name="Nimmo G."/>
                <person name="Loscalzo M."/>
                <person name="Horovitz D.D."/>
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            <dbReference type="PubMed" id="21990100"/>
            <dbReference type="DOI" id="10.1002/humu.21623"/>
        </citation>
        <scope>VARIANTS RCDP3 GLN-182; LYS-471 AND MET-568</scope>
        <scope>CHARACTERIZATION OF VARIANTS RCDP3 GLN-182; LYS-471 AND MET-568</scope>
    </reference>
    <comment type="function">
        <text evidence="8 9">Catalyzes the exchange of the acyl chain in acyl-dihydroxyacetonephosphate (acyl-DHAP) for a long chain fatty alcohol, yielding the first ether linked intermediate, i.e. alkyl-dihydroxyacetonephosphate (alkyl-DHAP), in the pathway of ether lipid biosynthesis.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="8 9">
            <text>a long chain fatty alcohol + a 1-acylglycerone 3-phosphate = a 1-O-alkylglycerone 3-phosphate + a long-chain fatty acid + H(+)</text>
            <dbReference type="Rhea" id="RHEA:36171"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17135"/>
            <dbReference type="ChEBI" id="CHEBI:57534"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:73315"/>
            <dbReference type="EC" id="2.5.1.26"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11 12">
            <dbReference type="Rhea" id="RHEA:36172"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>hexadecan-1-ol + 1-hexadecanoylglycerone 3-phosphate = 1-O-hexadecylglycerone 3-phosphate + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40659"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16125"/>
            <dbReference type="ChEBI" id="CHEBI:58303"/>
            <dbReference type="ChEBI" id="CHEBI:77429"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:40660"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>1-hexadecanoylglycerone 3-phosphate + a long-chain fatty acid = a 1-acylglycerone 3-phosphate + hexadecanoate</text>
            <dbReference type="Rhea" id="RHEA:40727"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:57534"/>
            <dbReference type="ChEBI" id="CHEBI:57560"/>
            <dbReference type="ChEBI" id="CHEBI:58303"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:40728"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="pathway">
        <text>Glycerolipid metabolism; ether lipid biosynthesis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838732">
            <id>O00116</id>
        </interactant>
        <interactant intactId="EBI-2561458">
            <id>Q9BQQ3</id>
            <label>GORASP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Peroxisome membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Peroxisome</location>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="6 7 9">
        <disease id="DI-01003">
            <name>Rhizomelic chondrodysplasia punctata 3</name>
            <acronym>RCDP3</acronym>
            <description>A form of rhizomelic chondrodysplasia punctata, a disease characterized by severely disturbed endochondral bone formation, rhizomelic shortening of femur and humerus, vertebral disorders, dwarfism, cataract, cutaneous lesions, facial dysmorphism, and severe intellectual disability with spasticity.</description>
            <dbReference type="MIM" id="600121"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the FAD-binding oxidoreductase/transferase type 4 family.</text>
    </comment>
    <dbReference type="EC" id="2.5.1.26" evidence="8 9"/>
    <dbReference type="EMBL" id="Y09443">
        <property type="protein sequence ID" value="CAA70591.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY544121">
        <property type="protein sequence ID" value="AAT11152.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK314259">
        <property type="protein sequence ID" value="BAG36924.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC141820">
        <property type="protein sequence ID" value="AAI41821.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2275.1"/>
    <dbReference type="RefSeq" id="NP_003650.1">
        <property type="nucleotide sequence ID" value="NM_003659.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O00116"/>
    <dbReference type="SMR" id="O00116"/>
    <dbReference type="BioGRID" id="114110">
        <property type="interactions" value="208"/>
    </dbReference>
    <dbReference type="CORUM" id="O00116"/>
    <dbReference type="FunCoup" id="O00116">
        <property type="interactions" value="2667"/>
    </dbReference>
    <dbReference type="IntAct" id="O00116">
        <property type="interactions" value="38"/>
    </dbReference>
    <dbReference type="MINT" id="O00116"/>
    <dbReference type="STRING" id="9606.ENSP00000264167"/>
    <dbReference type="ChEMBL" id="CHEMBL4295643"/>
    <dbReference type="SwissLipids" id="SLP:000000611"/>
    <dbReference type="GlyGen" id="O00116">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O00116"/>
    <dbReference type="MetOSite" id="O00116"/>
    <dbReference type="PhosphoSitePlus" id="O00116"/>
    <dbReference type="SwissPalm" id="O00116"/>
    <dbReference type="BioMuta" id="AGPS"/>
    <dbReference type="jPOST" id="O00116"/>
    <dbReference type="MassIVE" id="O00116"/>
    <dbReference type="PaxDb" id="9606-ENSP00000264167"/>
    <dbReference type="PeptideAtlas" id="O00116"/>
    <dbReference type="ProteomicsDB" id="47718"/>
    <dbReference type="Pumba" id="O00116"/>
    <dbReference type="Antibodypedia" id="33922">
        <property type="antibodies" value="190 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8540"/>
    <dbReference type="Ensembl" id="ENST00000264167.11">
        <property type="protein sequence ID" value="ENSP00000264167.4"/>
        <property type="gene ID" value="ENSG00000018510.19"/>
    </dbReference>
    <dbReference type="GeneID" id="8540"/>
    <dbReference type="KEGG" id="hsa:8540"/>
    <dbReference type="MANE-Select" id="ENST00000264167.11">
        <property type="protein sequence ID" value="ENSP00000264167.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_003659.4"/>
        <property type="RefSeq protein sequence ID" value="NP_003650.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002ull.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:327"/>
    <dbReference type="ClinPGx" id="PA24624"/>
    <dbReference type="CTD" id="8540"/>
    <dbReference type="DisGeNET" id="8540"/>
    <dbReference type="GeneCards" id="AGPS"/>
    <dbReference type="HGNC" id="HGNC:327">
        <property type="gene designation" value="AGPS"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000018510">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AGPS"/>
    <dbReference type="MIM" id="600121">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="603051">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000018510"/>
    <dbReference type="Orphanet" id="309803">
        <property type="disease" value="Rhizomelic chondrodysplasia punctata type 3"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000018510"/>
    <dbReference type="eggNOG" id="KOG1233">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156112"/>
    <dbReference type="HOGENOM" id="CLU_017779_2_2_1"/>
    <dbReference type="InParanoid" id="O00116"/>
    <dbReference type="OMA" id="GTISHQH"/>
    <dbReference type="OrthoDB" id="7786253at2759"/>
    <dbReference type="PAN-GO" id="O00116">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O00116"/>
    <dbReference type="BioCyc" id="MetaCyc:HS00389-MONOMER"/>
    <dbReference type="BRENDA" id="2.5.1.26">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O00116"/>
    <dbReference type="Reactome" id="R-HSA-75896">
        <property type="pathway name" value="Plasmalogen biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9033241">
        <property type="pathway name" value="Peroxisomal protein import"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9033500">
        <property type="pathway name" value="TYSND1 cleaves peroxisomal proteins"/>
    </dbReference>
    <dbReference type="SignaLink" id="O00116"/>
    <dbReference type="UniPathway" id="UPA00781"/>
    <dbReference type="Agora" id="ENSG00000018510"/>
    <dbReference type="BioGRID-ORCS" id="8540">
        <property type="hits" value="38 hits in 1178 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGPS">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="8540"/>
    <dbReference type="Pharos" id="O00116">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O00116"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="O00116">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000018510">
        <property type="expression patterns" value="Expressed in sperm and 193 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O00116">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005782">
        <property type="term" value="C:peroxisomal matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005778">
        <property type="term" value="C:peroxisomal membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005777">
        <property type="term" value="C:peroxisome"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008609">
        <property type="term" value="F:alkylglycerone-phosphate synthase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071949">
        <property type="term" value="F:FAD binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008611">
        <property type="term" value="P:ether lipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008610">
        <property type="term" value="P:lipid biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.45.10:FF:000002">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.160.650:FF:000001">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.300.330:FF:000001">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.43.10:FF:000003">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.465.10:FF:000011">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.3450:FF:000001">
        <property type="entry name" value="Alkylglycerone-phosphate synthase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.160.650">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.300.330">
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.30.465.10">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.3450">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.43.10">
        <property type="entry name" value="Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase, domain 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.45.10">
        <property type="entry name" value="Vanillyl-alcohol Oxidase, Chain A, domain 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR025650">
        <property type="entry name" value="Alkyl-DHAP_Synthase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR004113">
        <property type="entry name" value="FAD-bd_oxidored_4_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016166">
        <property type="entry name" value="FAD-bd_PCMH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036318">
        <property type="entry name" value="FAD-bd_PCMH-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016167">
        <property type="entry name" value="FAD-bd_PCMH_sub1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016169">
        <property type="entry name" value="FAD-bd_PCMH_sub2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016164">
        <property type="entry name" value="FAD-linked_Oxase-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006094">
        <property type="entry name" value="Oxid_FAD_bind_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016171">
        <property type="entry name" value="Vanillyl_alc_oxidase_C-sub2"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46568">
        <property type="entry name" value="ALKYLDIHYDROXYACETONEPHOSPHATE SYNTHASE, PEROXISOMAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46568:SF1">
        <property type="entry name" value="ALKYLDIHYDROXYACETONEPHOSPHATE SYNTHASE, PEROXISOMAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF02913">
        <property type="entry name" value="FAD-oxidase_C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01565">
        <property type="entry name" value="FAD_binding_4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF56176">
        <property type="entry name" value="FAD-binding/transporter-associated domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF55103">
        <property type="entry name" value="FAD-linked oxidases, C-terminal domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51387">
        <property type="entry name" value="FAD_PCMH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0898">Cataract</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0242">Dwarfism</keyword>
    <keyword id="KW-0274">FAD</keyword>
    <keyword id="KW-0285">Flavoprotein</keyword>
    <keyword id="KW-0444">Lipid biosynthesis</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0576">Peroxisome</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0685">Rhizomelic chondrodysplasia punctata</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <feature type="transit peptide" description="Peroxisome" evidence="1">
        <location>
            <begin position="1"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000020431" description="Alkyldihydroxyacetonephosphate synthase, peroxisomal">
        <location>
            <begin position="59"/>
            <end position="658"/>
        </location>
    </feature>
    <feature type="domain" description="FAD-binding PCMH-type" evidence="4">
        <location>
            <begin position="202"/>
            <end position="384"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="1"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="63"/>
            <end position="86"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for enzyme activity" evidence="2">
        <location>
            <begin position="615"/>
            <end position="617"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for enzyme activity" evidence="2">
        <location>
            <begin position="654"/>
            <end position="658"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="23"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="63"/>
            <end position="77"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor/acceptor" evidence="2">
        <location>
            <position position="578"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="234"/>
            <end position="240"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="303"/>
            <end position="309"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="316"/>
            <end position="319"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <begin position="368"/>
            <end position="374"/>
        </location>
        <ligand>
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="515"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="site" description="Important for enzyme activity" evidence="9">
        <location>
            <position position="419"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="14 15">
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="14 15">
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="13">
        <location>
            <position position="102"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="13">
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066929" description="In RCDP3; severely reduced protein levels." evidence="7">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025895" description="In RCDP3; dbSNP:rs121434412." evidence="6">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_005002" description="In RCDP3; loss of enzyme activity; dbSNP:rs121434411." evidence="9">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="419"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025896" description="In RCDP3; dbSNP:rs121434413." evidence="6">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="469"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066930" description="In RCDP3; severely reduced protein levels." evidence="7">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_066931" description="In RCDP3; does not affect protein levels; dbSNP:rs387907214." evidence="7">
        <original>T</original>
        <variation>M</variation>
        <location>
            <position position="568"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P97275"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8C0I1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00718"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="11152660"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21990100"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="8399344"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="9553082"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="8399344"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="9553082"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="658" mass="72912" checksum="0E97AE86B513DF32" modified="1997-07-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-10-01" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>Q08828</accession>
    <accession>A4D2L8</accession>
    <accession>Q75MI1</accession>
    <name>ADCY1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenylate cyclase type 1</fullName>
            <ecNumber evidence="3">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase type I</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylyl cyclase 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Ca(2+)/calmodulin-activated adenylyl cyclase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>The DNA sequence of human chromosome 7.</title>
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                <person name="Hillier L.W."/>
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                <person name="Furey T.S."/>
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                <person name="Olson M.V."/>
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                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2003" name="Science" volume="300" first="767" last="772">
            <title>Human chromosome 7: DNA sequence and biology.</title>
            <authorList>
                <person name="Scherer S.W."/>
                <person name="Cheung J."/>
                <person name="MacDonald J.R."/>
                <person name="Osborne L.R."/>
                <person name="Nakabayashi K."/>
                <person name="Herbrick J.-A."/>
                <person name="Carson A.R."/>
                <person name="Parker-Katiraee L."/>
                <person name="Skaug J."/>
                <person name="Khaja R."/>
                <person name="Zhang J."/>
                <person name="Hudek A.K."/>
                <person name="Li M."/>
                <person name="Haddad M."/>
                <person name="Duggan G.E."/>
                <person name="Fernandez B.A."/>
                <person name="Kanematsu E."/>
                <person name="Gentles S."/>
                <person name="Christopoulos C.C."/>
                <person name="Choufani S."/>
                <person name="Kwasnicka D."/>
                <person name="Zheng X.H."/>
                <person name="Lai Z."/>
                <person name="Nusskern D.R."/>
                <person name="Zhang Q."/>
                <person name="Gu Z."/>
                <person name="Lu F."/>
                <person name="Zeesman S."/>
                <person name="Nowaczyk M.J."/>
                <person name="Teshima I."/>
                <person name="Chitayat D."/>
                <person name="Shuman C."/>
                <person name="Weksberg R."/>
                <person name="Zackai E.H."/>
                <person name="Grebe T.A."/>
                <person name="Cox S.R."/>
                <person name="Kirkpatrick S.J."/>
                <person name="Rahman N."/>
                <person name="Friedman J.M."/>
                <person name="Heng H.H.Q."/>
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                <person name="Lo-Coco F."/>
                <person name="Belloni E."/>
                <person name="Shaffer L.G."/>
                <person name="Pober B."/>
                <person name="Morton C.C."/>
                <person name="Gusella J.F."/>
                <person name="Bruns G.A.P."/>
                <person name="Korf B.R."/>
                <person name="Quade B.J."/>
                <person name="Ligon A.H."/>
                <person name="Ferguson H."/>
                <person name="Higgins A.W."/>
                <person name="Leach N.T."/>
                <person name="Herrick S.R."/>
                <person name="Lemyre E."/>
                <person name="Farra C.G."/>
                <person name="Kim H.-G."/>
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                <person name="Gripp K.W."/>
                <person name="Roberts W."/>
                <person name="Szatmari P."/>
                <person name="Winsor E.J.T."/>
                <person name="Grzeschik K.-H."/>
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                <person name="Minassian B.A."/>
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                <person name="Estivill X."/>
                <person name="Wilson M.D."/>
                <person name="Koop B.F."/>
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                <person name="Rommens J.M."/>
                <person name="Vincent J.B."/>
                <person name="Venter J.C."/>
                <person name="Li P.W."/>
                <person name="Mural R.J."/>
                <person name="Adams M.D."/>
                <person name="Tsui L.-C."/>
            </authorList>
            <dbReference type="PubMed" id="12690205"/>
            <dbReference type="DOI" id="10.1126/science.1083423"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1993" name="Genomics" volume="16" first="473" last="478">
            <title>Cloning, chromosomal mapping, and expression of human fetal brain type I adenylyl cyclase.</title>
            <authorList>
                <person name="Villacres E.C."/>
                <person name="Xia Z."/>
                <person name="Bookbinder L.H."/>
                <person name="Edelhoff S."/>
                <person name="Disteche C.M."/>
                <person name="Storm D.R."/>
            </authorList>
            <dbReference type="PubMed" id="8314585"/>
            <dbReference type="DOI" id="10.1006/geno.1993.1213"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 281-1119</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="J. Clin. Endocrinol. Metab." volume="86" first="4495" last="4503">
            <title>Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland.</title>
            <authorList>
                <person name="Cote M."/>
                <person name="Guillon G."/>
                <person name="Payet M.D."/>
                <person name="Gallo-Payet N."/>
            </authorList>
            <dbReference type="PubMed" id="11549699"/>
            <dbReference type="DOI" id="10.1210/jcem.86.9.7837"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2014" name="Hum. Mol. Genet." volume="23" first="3289" last="3298">
            <title>Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish.</title>
            <authorList>
                <person name="Santos-Cortez R.L."/>
                <person name="Lee K."/>
                <person name="Giese A.P."/>
                <person name="Ansar M."/>
                <person name="Amin-Ud-Din M."/>
                <person name="Rehn K."/>
                <person name="Wang X."/>
                <person name="Aziz A."/>
                <person name="Chiu I."/>
                <person name="Hussain Ali R."/>
                <person name="Smith J.D."/>
                <person name="Shendure J."/>
                <person name="Bamshad M."/>
                <person name="Nickerson D.A."/>
                <person name="Ahmed Z.M."/>
                <person name="Ahmad W."/>
                <person name="Riazuddin S."/>
                <person name="Leal S.M."/>
            </authorList>
            <dbReference type="PubMed" id="24482543"/>
            <dbReference type="DOI" id="10.1093/hmg/ddu042"/>
        </citation>
        <scope>INVOLVEMENT IN DFNB44</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3">Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (By similarity). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="3">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="5">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Activated by G(s) G alpha protein GNAS. Inhibited by G(i) G alpha protein GNAI1. Is further activated by the complex formed by GNB1 and GNG2. Activated by calcium/calmodulin. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Interacts with CALM.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <topology evidence="3">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="9">Cell membrane</location>
            <topology evidence="12">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Membrane raft</location>
        </subcellularLocation>
        <text evidence="2">Expressed in the cytoplasm of supporting cells and hair cells of the cochlea vestibule, as well as to the cochlear hair cell nuclei and stereocilia.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 11">Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Brain, retina and adrenal medulla.</text>
    </comment>
    <comment type="domain">
        <text evidence="5">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">N-glycosylated.</text>
    </comment>
    <comment type="disease" evidence="10">
        <disease id="DI-04170">
            <name>Deafness, autosomal recessive, 44</name>
            <acronym>DFNB44</acronym>
            <description>A form of non-syndromic deafness characterized by prelingual profound hearing loss affecting all frequencies.</description>
            <dbReference type="MIM" id="610154"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="3"/>
    <dbReference type="EMBL" id="AC069008">
        <property type="protein sequence ID" value="AAS07467.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC091439">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH236960">
        <property type="protein sequence ID" value="EAL23741.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L05500">
        <property type="protein sequence ID" value="AAA02907.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34631.1"/>
    <dbReference type="PIR" id="A47007">
        <property type="entry name" value="A47007"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_066939.1">
        <property type="nucleotide sequence ID" value="NM_021116.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q08828"/>
    <dbReference type="SMR" id="Q08828"/>
    <dbReference type="BioGRID" id="106621">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q08828">
        <property type="interactions" value="1608"/>
    </dbReference>
    <dbReference type="IntAct" id="Q08828">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="MINT" id="Q08828"/>
    <dbReference type="STRING" id="9606.ENSP00000297323"/>
    <dbReference type="BindingDB" id="Q08828"/>
    <dbReference type="ChEMBL" id="CHEMBL2899"/>
    <dbReference type="DrugBank" id="DB00131">
        <property type="generic name" value="Adenosine phosphate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09121">
        <property type="generic name" value="Aurothioglucose"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00424">
        <property type="generic name" value="Hyoscyamine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13749">
        <property type="generic name" value="Magnesium gluconate"/>
    </dbReference>
    <dbReference type="DrugCentral" id="Q08828"/>
    <dbReference type="GuidetoPHARMACOLOGY" id="1278"/>
    <dbReference type="GlyCosmos" id="Q08828">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q08828">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q08828"/>
    <dbReference type="PhosphoSitePlus" id="Q08828"/>
    <dbReference type="BioMuta" id="ADCY1"/>
    <dbReference type="DMDM" id="62512172"/>
    <dbReference type="MassIVE" id="Q08828"/>
    <dbReference type="PaxDb" id="9606-ENSP00000297323"/>
    <dbReference type="PeptideAtlas" id="Q08828"/>
    <dbReference type="ProteomicsDB" id="58648"/>
    <dbReference type="Antibodypedia" id="4335">
        <property type="antibodies" value="242 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="107"/>
    <dbReference type="Ensembl" id="ENST00000297323.12">
        <property type="protein sequence ID" value="ENSP00000297323.7"/>
        <property type="gene ID" value="ENSG00000164742.17"/>
    </dbReference>
    <dbReference type="GeneID" id="107"/>
    <dbReference type="KEGG" id="hsa:107"/>
    <dbReference type="MANE-Select" id="ENST00000297323.12">
        <property type="protein sequence ID" value="ENSP00000297323.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_021116.4"/>
        <property type="RefSeq protein sequence ID" value="NP_066939.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003tne.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:232"/>
    <dbReference type="ClinPGx" id="PA24560"/>
    <dbReference type="CTD" id="107"/>
    <dbReference type="DisGeNET" id="107"/>
    <dbReference type="GeneCards" id="ADCY1"/>
    <dbReference type="HGNC" id="HGNC:232">
        <property type="gene designation" value="ADCY1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164742">
        <property type="expression patterns" value="Group enriched (brain, liver, retina)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCY1"/>
    <dbReference type="MIM" id="103072">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="610154">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000164742"/>
    <dbReference type="Orphanet" id="90636">
        <property type="disease" value="Rare autosomal recessive non-syndromic sensorineural deafness type DFNB"/>
    </dbReference>
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        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6"/>
    <evidence type="ECO:0000255" key="7">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00099"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="11549699"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="24482543"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="8314585"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <sequence length="1119" mass="123440" checksum="E8DDC8FCB58743D7" modified="2005-04-12" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-01-15" modified="2026-01-28" version="143" xmlns="https://uniprot.org/uniprot">
    <accession>Q6P093</accession>
    <accession>Q5HYJ4</accession>
    <name>ADCL2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arylacetamide deacetylase-like 2</fullName>
            <ecNumber>3.1.1.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AADACL2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
                <person name="Schmidt C.P."/>
                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
                <person name="Bloecker H."/>
                <person name="Heubner D."/>
                <person name="Hoerlein A."/>
                <person name="Michel G."/>
                <person name="Wedler H."/>
                <person name="Koehrer K."/>
                <person name="Ottenwaelder B."/>
                <person name="Poustka A."/>
                <person name="Wiemann S."/>
                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Adipose tissue</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1194" last="1198">
            <title>The DNA sequence, annotation and analysis of human chromosome 3.</title>
            <authorList>
                <person name="Muzny D.M."/>
                <person name="Scherer S.E."/>
                <person name="Kaul R."/>
                <person name="Wang J."/>
                <person name="Yu J."/>
                <person name="Sudbrak R."/>
                <person name="Buhay C.J."/>
                <person name="Chen R."/>
                <person name="Cree A."/>
                <person name="Ding Y."/>
                <person name="Dugan-Rocha S."/>
                <person name="Gill R."/>
                <person name="Gunaratne P."/>
                <person name="Harris R.A."/>
                <person name="Hawes A.C."/>
                <person name="Hernandez J."/>
                <person name="Hodgson A.V."/>
                <person name="Hume J."/>
                <person name="Jackson A."/>
                <person name="Khan Z.M."/>
                <person name="Kovar-Smith C."/>
                <person name="Lewis L.R."/>
                <person name="Lozado R.J."/>
                <person name="Metzker M.L."/>
                <person name="Milosavljevic A."/>
                <person name="Miner G.R."/>
                <person name="Morgan M.B."/>
                <person name="Nazareth L.V."/>
                <person name="Scott G."/>
                <person name="Sodergren E."/>
                <person name="Song X.-Z."/>
                <person name="Steffen D."/>
                <person name="Wei S."/>
                <person name="Wheeler D.A."/>
                <person name="Wright M.W."/>
                <person name="Worley K.C."/>
                <person name="Yuan Y."/>
                <person name="Zhang Z."/>
                <person name="Adams C.Q."/>
                <person name="Ansari-Lari M.A."/>
                <person name="Ayele M."/>
                <person name="Brown M.J."/>
                <person name="Chen G."/>
                <person name="Chen Z."/>
                <person name="Clendenning J."/>
                <person name="Clerc-Blankenburg K.P."/>
                <person name="Chen R."/>
                <person name="Chen Z."/>
                <person name="Davis C."/>
                <person name="Delgado O."/>
                <person name="Dinh H.H."/>
                <person name="Dong W."/>
                <person name="Draper H."/>
                <person name="Ernst S."/>
                <person name="Fu G."/>
                <person name="Gonzalez-Garay M.L."/>
                <person name="Garcia D.K."/>
                <person name="Gillett W."/>
                <person name="Gu J."/>
                <person name="Hao B."/>
                <person name="Haugen E."/>
                <person name="Havlak P."/>
                <person name="He X."/>
                <person name="Hennig S."/>
                <person name="Hu S."/>
                <person name="Huang W."/>
                <person name="Jackson L.R."/>
                <person name="Jacob L.S."/>
                <person name="Kelly S.H."/>
                <person name="Kube M."/>
                <person name="Levy R."/>
                <person name="Li Z."/>
                <person name="Liu B."/>
                <person name="Liu J."/>
                <person name="Liu W."/>
                <person name="Lu J."/>
                <person name="Maheshwari M."/>
                <person name="Nguyen B.-V."/>
                <person name="Okwuonu G.O."/>
                <person name="Palmeiri A."/>
                <person name="Pasternak S."/>
                <person name="Perez L.M."/>
                <person name="Phelps K.A."/>
                <person name="Plopper F.J."/>
                <person name="Qiang B."/>
                <person name="Raymond C."/>
                <person name="Rodriguez R."/>
                <person name="Saenphimmachak C."/>
                <person name="Santibanez J."/>
                <person name="Shen H."/>
                <person name="Shen Y."/>
                <person name="Subramanian S."/>
                <person name="Tabor P.E."/>
                <person name="Verduzco D."/>
                <person name="Waldron L."/>
                <person name="Wang J."/>
                <person name="Wang J."/>
                <person name="Wang Q."/>
                <person name="Williams G.A."/>
                <person name="Wong G.K.-S."/>
                <person name="Yao Z."/>
                <person name="Zhang J."/>
                <person name="Zhang X."/>
                <person name="Zhao G."/>
                <person name="Zhou J."/>
                <person name="Zhou Y."/>
                <person name="Nelson D."/>
                <person name="Lehrach H."/>
                <person name="Reinhardt R."/>
                <person name="Naylor S.L."/>
                <person name="Yang H."/>
                <person name="Olson M."/>
                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT SER-186</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6P093-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6P093-3</id>
            <name>2</name>
            <sequence type="described" ref="VSP_038389 VSP_038390"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="8">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the 'GDXG' lipolytic enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH65724" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="CAI46075" version="1"/>
        </conflict>
        <text>Wrong choice of CDS.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.-"/>
    <dbReference type="EMBL" id="BX647585">
        <property type="protein sequence ID" value="CAI46075.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC069067">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC065724">
        <property type="protein sequence ID" value="AAH65724.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3161.2">
        <molecule id="Q6P093-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_997248.2">
        <molecule id="Q6P093-1"/>
        <property type="nucleotide sequence ID" value="NM_207365.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6P093"/>
    <dbReference type="SMR" id="Q6P093"/>
    <dbReference type="BioGRID" id="131319">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000348911"/>
    <dbReference type="DrugBank" id="DB07814">
        <property type="generic name" value="Gibberellic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB07815">
        <property type="generic name" value="Gibberellin A4"/>
    </dbReference>
    <dbReference type="ESTHER" id="human-AADACL2">
        <property type="family name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6P093"/>
    <dbReference type="PhosphoSitePlus" id="Q6P093"/>
    <dbReference type="BioMuta" id="AADACL2"/>
    <dbReference type="DMDM" id="269849709"/>
    <dbReference type="jPOST" id="Q6P093"/>
    <dbReference type="MassIVE" id="Q6P093"/>
    <dbReference type="PaxDb" id="9606-ENSP00000348911"/>
    <dbReference type="PeptideAtlas" id="Q6P093"/>
    <dbReference type="ProteomicsDB" id="66809">
        <molecule id="Q6P093-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="33616">
        <property type="antibodies" value="118 antibodies from 15 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="344752"/>
    <dbReference type="Ensembl" id="ENST00000356517.4">
        <molecule id="Q6P093-1"/>
        <property type="protein sequence ID" value="ENSP00000348911.3"/>
        <property type="gene ID" value="ENSG00000197953.6"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000570799.1">
        <molecule id="Q6P093-1"/>
        <property type="protein sequence ID" value="ENSP00000461239.1"/>
        <property type="gene ID" value="ENSG00000261846.2"/>
    </dbReference>
    <dbReference type="GeneID" id="344752"/>
    <dbReference type="KEGG" id="hsa:344752"/>
    <dbReference type="MANE-Select" id="ENST00000356517.4">
        <property type="protein sequence ID" value="ENSP00000348911.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_207365.4"/>
        <property type="RefSeq protein sequence ID" value="NP_997248.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ezc.4">
        <molecule id="Q6P093-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24427"/>
    <dbReference type="ClinPGx" id="PA142670463"/>
    <dbReference type="CTD" id="344752"/>
    <dbReference type="DisGeNET" id="344752"/>
    <dbReference type="GeneCards" id="AADACL2"/>
    <dbReference type="HGNC" id="HGNC:24427">
        <property type="gene designation" value="AADACL2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000197953">
        <property type="expression patterns" value="Tissue enriched (skin)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000197953"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000197953"/>
    <dbReference type="eggNOG" id="KOG1515">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161405"/>
    <dbReference type="HOGENOM" id="CLU_012494_12_0_1"/>
    <dbReference type="InParanoid" id="Q6P093"/>
    <dbReference type="OMA" id="DHVYTEP"/>
    <dbReference type="OrthoDB" id="408631at2759"/>
    <dbReference type="PAN-GO" id="Q6P093">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6P093"/>
    <dbReference type="PathwayCommons" id="Q6P093"/>
    <dbReference type="SABIO-RK" id="Q6P093"/>
    <dbReference type="Agora" id="ENSG00000197953"/>
    <dbReference type="BioGRID-ORCS" id="344752">
        <property type="hits" value="13 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AADACL2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="344752"/>
    <dbReference type="Pharos" id="Q6P093">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6P093"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6P093">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000197953">
        <property type="expression patterns" value="Expressed in skin of abdomen and 40 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6P093">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013094">
        <property type="entry name" value="AB_hydrolase_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017157">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050300">
        <property type="entry name" value="GDXG_lipolytic_enzyme"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033140">
        <property type="entry name" value="Lipase_GDXG_put_SER_AS"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081">
        <property type="entry name" value="AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081:SF28">
        <property type="entry name" value="ALPHA_BETA HYDROLASE FOLD-3 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07859">
        <property type="entry name" value="Abhydrolase_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037251">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01174">
        <property type="entry name" value="LIPASE_GDXG_SER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="4">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000314960" description="Arylacetamide deacetylase-like 2">
        <location>
            <begin position="19"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole" evidence="2">
        <location>
            <begin position="111"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="active site" evidence="3 5">
        <location>
            <position position="189"/>
        </location>
    </feature>
    <feature type="active site" evidence="3">
        <location>
            <position position="341"/>
        </location>
    </feature>
    <feature type="active site" evidence="3">
        <location>
            <position position="371"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="116"/>
            <end position="338"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_038389" description="In isoform 2." evidence="7">
        <original>AMCFENM</original>
        <variation>NRGPLTS</variation>
        <location>
            <begin position="47"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_038390" description="In isoform 2." evidence="7">
        <location>
            <begin position="54"/>
            <end position="401"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038140" description="In dbSNP:rs1972977." evidence="6">
        <original>A</original>
        <variation>S</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038141" description="In dbSNP:rs1052562.">
        <original>L</original>
        <variation>I</variation>
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAI46075." evidence="8" ref="1">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q5NUF3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8BLF1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10038"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <sequence length="401" mass="46099" checksum="801AF004D9E6A3DA" modified="2009-11-24" version="3" precursor="true">MGLKALCLGLLCVLFVSHFYTPMPDNIEESWKIMALDAIAKTCTFTAMCFENMRIMRYEEFISMIFRLDYTQPLSDEYITVTDTTFVDIPVRLYLPKRKSETRRRAVIYFHGGGFCFGSSKQRAFDFLNRWTANTLDAVVVGVDYRLAPQHHFPAQFEDGLAAVKFFLLEKILTKYGVDPTRICIAGDSSGGNLATAVTQQVQNDAEIKHKIKMQVLLYPGLQITDSYLPSHRENEHGIVLTRDVAIKLVSLYFTKDEALPWAMRRNQHMPLESRHLFKFVNWSILLPEKYRKDYVYTEPILGGLSYSLPGLTDSRALPLLANDSQLQNLPLTYILTCQHDLLRDDGLMYVTRLRNVGVQVVHEHIEDGIHGALSFMTSPFYLRLGLRIRDMYVSWLDKNL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-12-12" modified="2026-01-28" version="145" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VUY0</accession>
    <accession>B3KXR9</accession>
    <accession>Q5VUY1</accession>
    <name>ADCL3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arylacetamide deacetylase-like 3</fullName>
            <ecNumber>3.1.1.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AADACL3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
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            <title>The DNA sequence and biological annotation of human chromosome 1.</title>
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                <person name="White S."/>
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                <person name="Willey D.L."/>
                <person name="Williams H."/>
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                <person name="Wu Z."/>
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            </authorList>
            <dbReference type="PubMed" id="16710414"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="similarity">
        <text evidence="3">Belongs to the 'GDXG' lipolytic enzyme family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="BAG54581" version="1"/>
        </conflict>
        <text>Aberrant splicing.</text>
    </comment>
    <dbReference type="EC" id="3.1.1.-"/>
    <dbReference type="EMBL" id="AK127828">
        <property type="protein sequence ID" value="BAG54581.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC244670">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS41253.2"/>
    <dbReference type="RefSeq" id="NP_001096640.2">
        <property type="nucleotide sequence ID" value="NM_001103170.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VUY0"/>
    <dbReference type="SMR" id="Q5VUY0"/>
    <dbReference type="BioGRID" id="126013">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000352268"/>
    <dbReference type="ESTHER" id="human-AADACL3">
        <property type="family name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VUY0"/>
    <dbReference type="PhosphoSitePlus" id="Q5VUY0"/>
    <dbReference type="BioMuta" id="AADACL3"/>
    <dbReference type="DMDM" id="317373552"/>
    <dbReference type="PaxDb" id="9606-ENSP00000352268"/>
    <dbReference type="Antibodypedia" id="57582">
        <property type="antibodies" value="41 antibodies from 10 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="126767"/>
    <dbReference type="Ensembl" id="ENST00000359318.8">
        <property type="protein sequence ID" value="ENSP00000352268.6"/>
        <property type="gene ID" value="ENSG00000188984.12"/>
    </dbReference>
    <dbReference type="GeneID" id="126767"/>
    <dbReference type="KEGG" id="hsa:126767"/>
    <dbReference type="MANE-Select" id="ENST00000359318.8">
        <property type="protein sequence ID" value="ENSP00000352268.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001103170.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001096640.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc057ckc.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32037"/>
    <dbReference type="ClinPGx" id="PA145147526"/>
    <dbReference type="CTD" id="126767"/>
    <dbReference type="DisGeNET" id="126767"/>
    <dbReference type="GeneCards" id="AADACL3"/>
    <dbReference type="HGNC" id="HGNC:32037">
        <property type="gene designation" value="AADACL3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000188984">
        <property type="expression patterns" value="Tissue enhanced (placenta, skin)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000188984"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000188984"/>
    <dbReference type="eggNOG" id="KOG1515">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162160"/>
    <dbReference type="HOGENOM" id="CLU_012494_12_2_1"/>
    <dbReference type="InParanoid" id="Q5VUY0"/>
    <dbReference type="OMA" id="TLWVICS"/>
    <dbReference type="OrthoDB" id="408631at2759"/>
    <dbReference type="PAN-GO" id="Q5VUY0">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VUY0"/>
    <dbReference type="PathwayCommons" id="Q5VUY0"/>
    <dbReference type="SABIO-RK" id="Q5VUY0"/>
    <dbReference type="BioGRID-ORCS" id="126767">
        <property type="hits" value="13 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AADACL3_(gene)"/>
    <dbReference type="GenomeRNAi" id="126767"/>
    <dbReference type="Pharos" id="Q5VUY0">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VUY0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VUY0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000188984">
        <property type="expression patterns" value="Expressed in placenta and 8 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0052689">
        <property type="term" value="F:carboxylic ester hydrolase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.1820">
        <property type="entry name" value="alpha/beta hydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013094">
        <property type="entry name" value="AB_hydrolase_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029058">
        <property type="entry name" value="AB_hydrolase_fold"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR017157">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050300">
        <property type="entry name" value="GDXG_lipolytic_enzyme"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081">
        <property type="entry name" value="AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR48081:SF32">
        <property type="entry name" value="ALPHA_BETA HYDROLASE FOLD-3 DOMAIN-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF07859">
        <property type="entry name" value="Abhydrolase_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF037251">
        <property type="entry name" value="Arylacetamide_deacetylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53474">
        <property type="entry name" value="alpha/beta-Hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000265936" description="Arylacetamide deacetylase-like 3">
        <location>
            <begin position="1"/>
            <end position="407"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole" evidence="1">
        <location>
            <begin position="119"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="347"/>
        </location>
    </feature>
    <feature type="active site" evidence="2">
        <location>
            <position position="377"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060666" description="In dbSNP:rs3010877.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060667" description="In dbSNP:rs3000859.">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060668" description="In dbSNP:rs17038445.">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060665" description="In dbSNP:rs7513079.">
        <original>F</original>
        <variation>C</variation>
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060670" description="In dbSNP:rs3000931.">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="307"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060671" description="In dbSNP:rs11121969.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5NUF3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8BLF1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="407" mass="46155" checksum="0BAB3056EEED2B19" modified="2018-03-28" version="5">MWDLALIFLAAACVFSLGVTLWVICSHFFTVHIPAAVGHPVKLRVLHCIFQLLLTWGMIFEKLRICSMPQFFCFMQDLPPLKYDPDVVVTDFRFGTIPVKLYQPKASTCTLKPGIVYYHGGGGVMGSLKTHHGICSRLCKESDSVVLAVGYRKLPKHKFPVPVRDCLVATIHFLKSLDAYGVDPARVVVCGDSFGGAIAAVVCQQLVDRPDLPRIRAQILIYAILQALDLQTPSFQQRKNIPLLTWSFICYFFFQNLDFSSSWQEVIMKGAHLPAEVWEKYRKWLGPENIPERFKERGYQLKPHEPMNEAAYLEVSVVLDVMCSPLIAEDDIVSQLPETCIVSCEYDALRDNSLLYKKRLEDLGVPVTWHHMEDGFHGVLRTIDMSFLHFPCSMRILSALVQFVKGL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="255" xmlns="https://uniprot.org/uniprot">
    <accession>P00813</accession>
    <accession>Q53F92</accession>
    <accession>Q6LA59</accession>
    <name>ADA_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenosine deaminase</fullName>
            <ecNumber evidence="11 17 19 31 34">3.5.4.4</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Adenosine aminohydrolase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADA</name>
        <name type="synonym">ADA1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <dbReference type="PubMed" id="3839456"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Placenta</tissue>
        </source>
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        <scope>PROTEIN SEQUENCE OF 2-11</scope>
        <scope>ACETYLATION AT ALA-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>B-cell lymphoma</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 141-363</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>INTERACTION WITH DPP4</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>INTERACTION WITH DPP4</scope>
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        <scope>INTERACTION WITH DPP4</scope>
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        <scope>INTERACTION WITH DPP4 AND PLG</scope>
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        <scope>INTERACTION WITH DPP4</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-54 AND LYS-232</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>FUNCTION</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2013" name="FASEB J." volume="27" first="1048" last="1061">
            <title>The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors.</title>
            <authorList>
                <person name="Gracia E."/>
                <person name="Farre D."/>
                <person name="Cortes A."/>
                <person name="Ferrer-Costa C."/>
                <person name="Orozco M."/>
                <person name="Mallol J."/>
                <person name="Lluis C."/>
                <person name="Canela E.I."/>
                <person name="McCormick P.J."/>
                <person name="Franco R."/>
                <person name="Fanelli F."/>
                <person name="Casado V."/>
            </authorList>
            <dbReference type="PubMed" id="23193172"/>
            <dbReference type="DOI" id="10.1096/fj.12-212621"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>MUTAGENESIS OF LEU-58; ASP-60; PHE-61; LEU-62; LYS-64; PHE-65; ASP-66; MET-69; ILE-115; ASN-118; MET-155; HIS-157; GLY-184; ASP-185 AND LEU-194</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2015" name="Pharmacol. Res. Perspect." volume="3" first="e00121" last="e00121">
            <title>Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances.</title>
            <authorList>
                <person name="Li G."/>
                <person name="Nakagome I."/>
                <person name="Hirono S."/>
                <person name="Itoh T."/>
                <person name="Fujiwara R."/>
            </authorList>
            <dbReference type="PubMed" id="26038697"/>
            <dbReference type="DOI" id="10.1002/prp2.121"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="25">
        <citation type="submission" date="2009-08" db="PDB data bank">
            <title>The crystal structure of human adenosine deaminase.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.52 ANGSTROMS) OF 5-363 IN COMPLEX WITH NICKEL IONS AND 2-DEAOXYADENOSINE</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="1990" name="Proc. Natl. Acad. Sci. U.S.A." volume="87" first="6171" last="6175">
            <title>Hot spot mutations in adenosine deaminase deficiency.</title>
            <authorList>
                <person name="Hirschhorn R."/>
                <person name="Tzall S."/>
                <person name="Ellenbogen A."/>
            </authorList>
            <dbReference type="PubMed" id="2166947"/>
            <dbReference type="DOI" id="10.1073/pnas.87.16.6171"/>
        </citation>
        <scope>VARIANTS ADASCID TRP-76; PRO-107; GLN-149; CYS-211; THR-215 AND LEU-274</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="1994" name="Ann. Hum. Genet." volume="58" first="1" last="9">
            <title>An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover.</title>
            <authorList>
                <person name="Hirschhorn R."/>
                <person name="Yang D.R."/>
                <person name="Israni A."/>
            </authorList>
            <dbReference type="PubMed" id="8031011"/>
            <dbReference type="DOI" id="10.1111/j.1469-1809.1994.tb00720.x"/>
        </citation>
        <scope>VARIANT ADA*2 ASN-8</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="1984" name="Mol. Cell. Biol." volume="4" first="1712" last="1717">
            <title>Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines.</title>
            <authorList>
                <person name="Adrian G.S."/>
                <person name="Wiginton D.A."/>
                <person name="Hutton J."/>
            </authorList>
            <dbReference type="PubMed" id="6208479"/>
            <dbReference type="DOI" id="10.1128/mcb.4.9.1712-1717.1984"/>
        </citation>
        <scope>VARIANTS ADASCID</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="1985" name="J. Clin. Invest." volume="76" first="894" last="897">
            <title>Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency.</title>
            <authorList>
                <person name="Bonthron D.T."/>
                <person name="Markham A.F."/>
                <person name="Ginsburg D."/>
                <person name="Orkin S.H."/>
            </authorList>
            <dbReference type="PubMed" id="3839802"/>
            <dbReference type="DOI" id="10.1172/jci112050"/>
        </citation>
        <scope>VARIANT ADASCID GLN-101</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="1986" name="EMBO J." volume="5" first="113" last="119">
            <title>One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity.</title>
            <authorList>
                <person name="Valerio D."/>
                <person name="Dekker B.M."/>
                <person name="Duyvesteyn M.G."/>
                <person name="van der Voorn L."/>
                <person name="Berkvens T.M."/>
                <person name="van Ormondt H."/>
                <person name="van der Eb A.J."/>
            </authorList>
            <dbReference type="PubMed" id="3007108"/>
            <dbReference type="DOI" id="10.1002/j.1460-2075.1986.tb04184.x"/>
        </citation>
        <scope>VARIANT ADASCID ARG-304</scope>
    </reference>
    <reference key="31">
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            <title>Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts.</title>
            <authorList>
                <person name="Akeson A.L."/>
                <person name="Wiginton D.A."/>
                <person name="Dusing M.R."/>
                <person name="States J.C."/>
                <person name="Hutton J.J."/>
            </authorList>
            <dbReference type="PubMed" id="3182793"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)37591-4"/>
        </citation>
        <scope>VARIANTS ADASCID TRP-101; HIS-211 AND VAL-329</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="1989" name="J. Clin. Invest." volume="83" first="497" last="501">
            <title>Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency.</title>
            <authorList>
                <person name="Hirschhorn R."/>
                <person name="Tzall S."/>
                <person name="Ellenbogen A."/>
                <person name="Orkin S.H."/>
            </authorList>
            <dbReference type="PubMed" id="2783588"/>
            <dbReference type="DOI" id="10.1172/jci113909"/>
        </citation>
        <scope>VARIANT ADASCID GLN-297</scope>
    </reference>
    <reference key="33">
        <citation type="journal article" date="1992" name="Hum. Mutat." volume="1" first="166" last="168">
            <title>Identification of two new missense mutations (R156C and S291L) in two ADA-SCID patients unusual for response to therapy with partial exchange transfusions.</title>
            <authorList>
                <person name="Hirschhorn R."/>
            </authorList>
            <dbReference type="PubMed" id="1284479"/>
            <dbReference type="DOI" id="10.1002/humu.1380010214"/>
        </citation>
        <scope>VARIANTS ADASCID CYS-156 AND LEU-291</scope>
    </reference>
    <reference key="34">
        <citation type="journal article" date="1993" name="J. Clin. Invest." volume="92" first="2291" last="2302">
            <title>Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.</title>
            <authorList>
                <person name="Santisteban I."/>
                <person name="Arredondo-Vega F.X."/>
                <person name="Kelly S."/>
                <person name="Mary A."/>
                <person name="Fischer A."/>
                <person name="Hummell D.S."/>
                <person name="Lawton A."/>
                <person name="Sorensen R.U."/>
                <person name="Stiehm E.R."/>
                <person name="Uribe L."/>
                <person name="Weinberg K."/>
                <person name="Hershfield M.S."/>
            </authorList>
            <dbReference type="PubMed" id="8227344"/>
            <dbReference type="DOI" id="10.1172/jci116833"/>
        </citation>
        <scope>VARIANTS ADASCID LEU-101; HIS-156; MET-177; ARG-216 AND LEU-291</scope>
    </reference>
    <reference key="35">
        <citation type="journal article" date="1994" name="Clin. Immunol. Immunopathol." volume="70" first="171" last="175">
            <title>Homozygosity for a missense mutation (G20R) associated with neonatal onset adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID).</title>
            <authorList>
                <person name="Yang D.R."/>
                <person name="Huie M.L."/>
                <person name="Hirschhorn R."/>
            </authorList>
            <dbReference type="PubMed" id="8299233"/>
            <dbReference type="DOI" id="10.1006/clin.1994.1026"/>
        </citation>
        <scope>VARIANT ADASCID ARG-20</scope>
    </reference>
    <reference key="36">
        <citation type="journal article" date="1995" name="Hum. Mol. Genet." volume="4" first="2081" last="2087">
            <title>Three new adenosine deaminase mutations that define a splicing enhancer and cause severe and partial phenotypes: implications for evolution of a CpG hotspot and expression of a transduced ADA cDNA.</title>
            <authorList>
                <person name="Santisteban I."/>
                <person name="Arredondo-Vega F.X."/>
                <person name="Kelly S."/>
                <person name="Loubser M."/>
                <person name="Meydan N."/>
                <person name="Roifman C."/>
                <person name="Howell P.L."/>
                <person name="Bowen T."/>
                <person name="Weinberg K.I."/>
                <person name="Schroeder M.L."/>
                <person name="Hershfield M.S."/>
            </authorList>
            <dbReference type="PubMed" id="8589684"/>
            <dbReference type="DOI" id="10.1093/hmg/4.11.2081"/>
        </citation>
        <scope>VARIANTS ARG-80 AND GLN-142</scope>
    </reference>
    <reference key="37">
        <citation type="journal article" date="1995" name="Hum. Mutat." volume="5" first="243" last="250">
            <title>Four new adenosine deaminase mutations, altering a zinc-binding histidine, two conserved alanines, and a 5' splice site.</title>
            <authorList>
                <person name="Santisteban I."/>
                <person name="Arredondo-Vega F.X."/>
                <person name="Kelly S."/>
                <person name="Debre M."/>
                <person name="Fisher A."/>
                <person name="Perignon J.L."/>
                <person name="Hilman B."/>
                <person name="Eldahr J."/>
                <person name="Dreyfus D.H."/>
                <person name="Gelfand E.W."/>
                <person name="Howell P.L."/>
                <person name="Hershfield M.S."/>
            </authorList>
            <dbReference type="PubMed" id="7599635"/>
            <dbReference type="DOI" id="10.1002/humu.1380050309"/>
        </citation>
        <scope>VARIANTS ADASCID ASP-15; ASP-83 AND ASP-179</scope>
    </reference>
    <reference key="38">
        <citation type="journal article" date="1997" name="Hum. Genet." volume="100" first="22" last="29">
            <title>Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA-) individuals that result in differing biochemical and metabolic phenotypes.</title>
            <authorList>
                <person name="Hirschhorn R."/>
                <person name="Borkowsky W."/>
                <person name="Jiang C.-K."/>
                <person name="Yang D.R."/>
                <person name="Jenkins T."/>
            </authorList>
            <dbReference type="PubMed" id="9225964"/>
            <dbReference type="DOI" id="10.1007/s004390050460"/>
        </citation>
        <scope>VARIANTS MET-152 AND ILE-233</scope>
    </reference>
    <reference key="39">
        <citation type="journal article" date="1997" name="Hum. Mol. Genet." volume="6" first="2271" last="2278">
            <title>An adenosine deaminase (ADA) allele contains two newly identified deleterious mutations (Y97C and L106V) that interact to abolish enzyme activity.</title>
            <authorList>
                <person name="Jiang C."/>
                <person name="Hong R."/>
                <person name="Horowitz S.D."/>
                <person name="Kong X."/>
                <person name="Hirschhorn R."/>
            </authorList>
            <dbReference type="PubMed" id="9361033"/>
            <dbReference type="DOI" id="10.1093/hmg/6.13.2271"/>
        </citation>
        <scope>VARIANTS ADASCID CYS-97 AND VAL-106</scope>
        <scope>CHARACTERIZATION OF VARIANTS ADASCID CYS-97; VAL-106; CYS-211 AND THR-215</scope>
        <scope>CHARACTERIZATION OF VARIANT ILE-233</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="40">
        <citation type="journal article" date="1998" name="Hum. Mutat." volume="11" first="482" last="482">
            <title>Seven novel mutations in the adenosine deaminase (ADA) gene in patients with severe and delayed onset combined immunodeficiency: G74C, V129M, G140E, R149W, Q199P, 462delG, and E337del.</title>
            <authorList>
                <person name="Arrendondo-Vega F.X."/>
                <person name="Santisteban I."/>
                <person name="Notarangelo L.D."/>
                <person name="El Dahr J."/>
                <person name="Buckley R."/>
                <person name="Roifman C."/>
                <person name="Conley M.E."/>
                <person name="Hershfield M.S."/>
            </authorList>
            <dbReference type="PubMed" id="10200056"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(1998)11:6&lt;482::aid-humu15&gt;3.0.co;2-e"/>
        </citation>
        <scope>VARIANTS ADASCID CYS-74; MET-129; GLU-140; TRP-149 AND PRO-199</scope>
    </reference>
    <reference key="41">
        <citation type="journal article" date="2005" name="Proc. Natl. Acad. Sci. U.S.A." volume="102" first="15676" last="15681">
            <title>A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans.</title>
            <authorList>
                <person name="Retey J.V."/>
                <person name="Adam M."/>
                <person name="Honegger E."/>
                <person name="Khatami R."/>
                <person name="Luhmann U.F.O."/>
                <person name="Jung H.H."/>
                <person name="Berger W."/>
                <person name="Landolt H.-P."/>
            </authorList>
            <dbReference type="PubMed" id="16221767"/>
            <dbReference type="DOI" id="10.1073/pnas.0505414102"/>
        </citation>
        <scope>EFFECT OF VARIANT ADA*2 ASN-8 ON SLEEP</scope>
    </reference>
    <reference key="42">
        <citation type="journal article" date="2008" name="Science" volume="321" first="1801" last="1806">
            <title>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</title>
            <authorList>
                <person name="Jones S."/>
                <person name="Zhang X."/>
                <person name="Parsons D.W."/>
                <person name="Lin J.C."/>
                <person name="Leary R.J."/>
                <person name="Angenendt P."/>
                <person name="Mankoo P."/>
                <person name="Carter H."/>
                <person name="Kamiyama H."/>
                <person name="Jimeno A."/>
                <person name="Hong S.M."/>
                <person name="Fu B."/>
                <person name="Lin M.T."/>
                <person name="Calhoun E.S."/>
                <person name="Kamiyama M."/>
                <person name="Walter K."/>
                <person name="Nikolskaya T."/>
                <person name="Nikolsky Y."/>
                <person name="Hartigan J."/>
                <person name="Smith D.R."/>
                <person name="Hidalgo M."/>
                <person name="Leach S.D."/>
                <person name="Klein A.P."/>
                <person name="Jaffee E.M."/>
                <person name="Goggins M."/>
                <person name="Maitra A."/>
                <person name="Iacobuzio-Donahue C."/>
                <person name="Eshleman J.R."/>
                <person name="Kern S.E."/>
                <person name="Hruban R.H."/>
                <person name="Karchin R."/>
                <person name="Papadopoulos N."/>
                <person name="Parmigiani G."/>
                <person name="Vogelstein B."/>
                <person name="Velculescu V.E."/>
                <person name="Kinzler K.W."/>
            </authorList>
            <dbReference type="PubMed" id="18772397"/>
            <dbReference type="DOI" id="10.1126/science.1164368"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] GLN-142</scope>
    </reference>
    <reference key="43">
        <citation type="journal article" date="2012" name="Cereb. Cortex" volume="22" first="962" last="970">
            <title>Functional ADA polymorphism increases sleep depth and reduces vigilant attention in humans.</title>
            <authorList>
                <person name="Bachmann V."/>
                <person name="Klaus F."/>
                <person name="Bodenmann S."/>
                <person name="Schaefer N."/>
                <person name="Brugger P."/>
                <person name="Huber S."/>
                <person name="Berger W."/>
                <person name="Landolt H.P."/>
            </authorList>
            <dbReference type="PubMed" id="21734253"/>
            <dbReference type="DOI" id="10.1093/cercor/bhr173"/>
        </citation>
        <scope>VARIANT ADA*2 ASN-8</scope>
        <scope>CHARACTERIZATION OF VARIANT ASN-8</scope>
    </reference>
    <reference key="44">
        <citation type="journal article" date="2015" name="Urology" volume="86" first="730" last="734">
            <title>The Role of G22 A Adenosine Deaminase 1 Gene Polymorphism and the Activities of ADA Isoenzymes in Fertile and Infertile Men.</title>
            <authorList>
                <person name="Fattahi A."/>
                <person name="Khodadadi I."/>
                <person name="Amiri I."/>
                <person name="Latifi Z."/>
                <person name="Ghorbani M."/>
                <person name="Tavilani H."/>
            </authorList>
            <dbReference type="PubMed" id="26166670"/>
            <dbReference type="DOI" id="10.1016/j.urology.2015.06.034"/>
        </citation>
        <scope>VARIANT ADA*2 ASN-8</scope>
        <scope>CHARACTERIZATION OF VARIANT ASN-8</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 6 9 11 13 16 17 18 19 31 34">Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:16670267, PubMed:23193172, PubMed:26166670, PubMed:8452534, PubMed:9361033). Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (PubMed:20959412). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (PubMed:23193172). Stimulates plasminogen activation (PubMed:15016824). Plays a role in male fertility (PubMed:21919946, PubMed:26166670). Plays a protective role in early postimplantation embryonic development (By similarity). Also responsible for the deamination of cordycepin (3'-deoxyadenosine), a fungal natural product that shows antitumor, antibacterial, antifungal, antivirus, and immune regulation properties (PubMed:26038697).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11 17 19 31 34">
            <text>adenosine + H2O + H(+) = inosine + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:24408"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:17596"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="EC" id="3.5.4.4"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="38">
            <dbReference type="Rhea" id="RHEA:24409"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="34">
            <text>2'-deoxyadenosine + H2O + H(+) = 2'-deoxyinosine + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:28190"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17256"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:28997"/>
            <dbReference type="EC" id="3.5.4.4"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="38">
            <dbReference type="Rhea" id="RHEA:28191"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="18">
            <text>cordycepin + H2O + H(+) = 3'-deoxyinosine + NH4(+)</text>
            <dbReference type="Rhea" id="RHEA:79047"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28938"/>
            <dbReference type="ChEBI" id="CHEBI:29014"/>
            <dbReference type="ChEBI" id="CHEBI:229694"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:79048"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="39">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="39">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="11 18 31">Inhibited by Cu(2+) and Hg(2+), coformycin, deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, 2-3-iso-propylidene-adenosine, pentostatin, naringin and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="31">37 uM for adenosine (at 25 degrees Celsius and pH 5.5)</KM>
            <KM evidence="18">54.9 uM for cordycepin</KM>
            <Vmax evidence="17">41.0 umol/min/mg enzyme</Vmax>
            <Vmax evidence="18">45.8 nmol/min/mg enzyme towards cordycepin</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="5 8 9 26 28">Interacts with DPP4 (via extracellular domain) (PubMed:10951221, PubMed:14691230, PubMed:15016824, PubMed:7907293, PubMed:8101391). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4 (PubMed:15016824).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3904496">
            <id>P00813</id>
        </interactant>
        <interactant intactId="EBI-6150673">
            <id>A5A3E0</id>
            <label>POTEF</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 28">Cell membrane</location>
            <topology>Peripheral membrane protein</topology>
            <orientation>Extracellular side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cell junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasmic vesicle lumen</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="31">Lysosome</location>
        </subcellularLocation>
        <text evidence="6">Colocalized with DPP4 at the cell surface.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="13">Found in all tissues, occurs in large amounts in T-lymphocytes (PubMed:20959412). Expressed at the time of weaning in gastrointestinal tissues.</text>
    </comment>
    <comment type="induction">
        <text evidence="11">Up-regulated by hypoxia.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="10">There is a common allele, ADA*2, also known as the ADA 2 allozyme. It is associated with the reduced metabolism of adenosine to inosine. It specifically enhances deep sleep and slow-wave activity (SWA) during sleep.</text>
    </comment>
    <comment type="disease" evidence="4 7 14 20 21 22 23 24 25 29 30 34">
        <disease id="DI-01016">
            <name>Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-negative due to adenosine deaminase deficiency</name>
            <acronym>ADASCID</acronym>
            <description>An autosomal recessive disorder accounting for about 50% of non-X-linked SCIDs. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.</description>
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        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="37">Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.</text>
    </comment>
    <comment type="sequence caution" evidence="37">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA26130" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Mendelian genes adenosine deaminase (ADA)">
        <link uri="https://databases.lovd.nl/shared/genes/ADA"/>
        <text>Leiden Open Variation Database (LOVD)</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Adenosine_deaminase"/>
        <text>Adenosine deaminase entry</text>
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    </dbReference>
    <dbReference type="InterPro" id="IPR006330">
        <property type="entry name" value="Ado/ade_deaminase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032466">
        <property type="entry name" value="Metal_Hydrolase"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01430">
        <property type="entry name" value="aden_deam"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11409">
        <property type="entry name" value="ADENOSINE DEAMINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR11409:SF43">
        <property type="entry name" value="ADENOSINE DEAMINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00962">
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        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51556">
        <property type="entry name" value="Metallo-dependent hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00485">
        <property type="entry name" value="A_DEAMINASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0360">Hereditary hemolytic anemia</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0458">Lysosome</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0546">Nucleotide metabolism</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0705">SCID</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="initiator methionine" description="Removed" evidence="36">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000194352" description="Adenosine deaminase">
        <location>
            <begin position="2"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for binding to DDP4" evidence="9">
        <location>
            <begin position="126"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="active site" description="Proton donor" evidence="2">
        <location>
            <position position="217"/>
        </location>
    </feature>
    <feature type="binding site" evidence="39">
        <location>
            <position position="15"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 40">
        <location>
            <position position="17"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="39">
        <location>
            <position position="17"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 40">
        <location>
            <position position="19"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 40">
        <location>
            <position position="184"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="39">
        <location>
            <position position="214"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="39">
        <location>
            <position position="295"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 40">
        <location>
            <position position="296"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="site" description="Important for interaction with adenosine receptors and increasing their affinity for agonists" evidence="17">
        <location>
            <position position="58"/>
        </location>
    </feature>
    <feature type="site" description="Important for interaction with adenosine receptors and increasing their affinity for agonists" evidence="17">
        <location>
            <position position="62"/>
        </location>
    </feature>
    <feature type="site" description="Important for catalytic activity" evidence="2">
        <location>
            <position position="238"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="36">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="41">
        <location>
            <position position="54"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="41">
        <location>
            <position position="232"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002209" description="Allele ADA*2; found in about 10% of the population; affects duration and intensity of deep sleep; enhances negative effects of sleep loss during sleep deprivation; may have a protective role against male infertility; 20% to 30% decrease in activity; dbSNP:rs73598374." evidence="10 15 19 27">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002210" description="In ADASCID; loss of activity; dbSNP:rs121908725." evidence="25">
        <original>H</original>
        <variation>D</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002211" description="In ADASCID; loss of activity; dbSNP:rs121908724." evidence="30">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002212" description="In ADASCID; delayed-onset; dbSNP:rs121908730." evidence="4">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002213" description="In ADASCID; dbSNP:rs121908736." evidence="14">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002214" description="In dbSNP:rs11555566." evidence="32">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002215" description="In ADASCID; loss of activity; dbSNP:rs121908726." evidence="25">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="83"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076954" description="In ADASCID; uncertain significance; loss of activity on its own; total loss of activity; when associated with V-106; dbSNP:rs267606634." evidence="34">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002216" description="In ADASCID; dbSNP:rs121908714." evidence="29">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002218" description="In ADASCID; loss of activity; dbSNP:rs121908714." evidence="23">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002217" description="In ADASCID; dbSNP:rs121908717." evidence="22">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076955" description="In ADASCID; uncertain significance; 30% of activity; total loss of activity; when associated with C-97; dbSNP:rs267606635." evidence="34">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002219" description="In ADASCID; dbSNP:rs121908739." evidence="14">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002220" description="In ADASCID; delayed-onset; dbSNP:rs121908731." evidence="4">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="129"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002221" description="In ADASCID; dbSNP:rs121908732." evidence="4">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002222" description="In dbSNP:rs61732239." evidence="12 32">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002223" description="In ADASCID; uncertain significance; dbSNP:rs121908737." evidence="14">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002224" description="In ADASCID; dbSNP:rs121908733." evidence="4">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002225" description="Found in an individual with partial ADA deficiency but no immunodeficiency; uncertain significance; 1,5% of activity; dbSNP:rs121908728." evidence="33">
        <original>L</original>
        <variation>M</variation>
        <location>
            <position position="152"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002226" description="In ADASCID; dbSNP:rs121908735." evidence="7">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002227" description="In ADASCID; loss of activity; dbSNP:rs121908722." evidence="29">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002228" description="In ADASCID; loss of activity; dbSNP:rs121908719." evidence="29">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002229" description="In ADASCID; loss of activity; dbSNP:rs121908727." evidence="25">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="179"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002230" description="In ADASCID; delayed-onset; dbSNP:rs121908734." evidence="4">
        <original>Q</original>
        <variation>P</variation>
        <location>
            <position position="199"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002231" description="In ADASCID; late onset; 4% of activity; dbSNP:rs121908740." evidence="14 34">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002232" description="In ADASCID; dbSNP:rs121908716." evidence="22">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002233" description="In ADASCID; 8% of activity; dbSNP:rs114025668." evidence="14 34">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002234" description="In ADASCID; severe; dbSNP:rs121908723." evidence="29">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002235" description="In an individual with partial ADA deficiency but no immunodeficiency; 20% of activity; dbSNP:rs121908729." evidence="33 34">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002236" description="In ADASCID; dbSNP:rs121908738." evidence="14">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_002237" description="In ADASCID; dbSNP:rs121908721." evidence="7 29">
        <original>S</original>
        <variation>L</variation>
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            <position position="291"/>
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    <feature type="sequence variant" id="VAR_002238" description="In ADASCID; dbSNP:rs121908718." evidence="20">
        <original>P</original>
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            <position position="297"/>
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    <feature type="sequence variant" id="VAR_002239" description="In ADASCID; loss of activity; dbSNP:rs199422327." evidence="21">
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        <location>
            <position position="304"/>
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    <feature type="sequence variant" id="VAR_002240" description="In ADASCID; dbSNP:rs121908715." evidence="22">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="329"/>
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            <position position="337"/>
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    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing substrate affinity and maximum velocity; abolishes ADORA1 and ADORA2A modulator function." evidence="17">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="58"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity; reduces ADORA1 and ADORA2A modulation." evidence="17">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="60"/>
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    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing maximum velocity; reduces ADORA1 modulation." evidence="17">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="61"/>
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    </feature>
    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing substrate affinity and maximum velocity; abolishes ADORA1 and ADORA2A modulator function." evidence="17">
        <original>L</original>
        <variation>A</variation>
        <location>
            <position position="62"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity; no change in ADORA1 and ADORA2A modulation." evidence="17">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="64"/>
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    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing substrate affinity and maximum velocity; reduces ADORA1 and ADORA2A modulation." evidence="17">
        <original>F</original>
        <variation>A</variation>
        <location>
            <position position="65"/>
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    <feature type="mutagenesis site" description="No change in enzyme activity; no change in ADORA1 and ADORA2A modulation." evidence="17">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="66"/>
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    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing maximum velocity; reduces ADORA2A modulation." evidence="17">
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            <position position="69"/>
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    <feature type="mutagenesis site" description="No change in enzyme activity; no change in ADORA1 and ADORA2A modulation." evidence="17">
        <original>I</original>
        <variation>A</variation>
        <location>
            <position position="115"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity; no change in ADORA1 and ADORA2A modulation." evidence="17">
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            <position position="118"/>
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    <feature type="mutagenesis site" description="Decreases enzyme activity by reducing substrate affinity and maximum velocity." evidence="17">
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            <position position="155"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity; no change in ADORA1 and ADORA2A modulation." evidence="17">
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        <location>
            <position position="157"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity." evidence="17">
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            <position position="184"/>
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    <feature type="mutagenesis site" description="Moderately reduces enzyme activity." evidence="17">
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            <position position="185"/>
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    <feature type="mutagenesis site" description="No change in enzyme activity." evidence="17">
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        <location>
            <position position="194"/>
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    <feature type="sequence conflict" description="In Ref. 5; BAD97117." evidence="37" ref="5">
        <original>K</original>
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        <location>
            <position position="340"/>
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    <feature type="strand" evidence="42">
        <location>
            <begin position="11"/>
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    <feature type="helix" evidence="42">
        <location>
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    <feature type="helix" evidence="42">
        <location>
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    <feature type="helix" evidence="42">
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    <feature type="helix" evidence="42">
        <location>
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    <feature type="turn" evidence="42">
        <location>
            <begin position="92"/>
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    <feature type="strand" evidence="42">
        <location>
            <begin position="95"/>
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        <location>
            <begin position="104"/>
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    <feature type="strand" evidence="42">
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            <begin position="109"/>
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<entry dataset="Swiss-Prot" created="2008-02-05" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="31698" last="31708">
            <title>Identification and functional analysis of splice variants of the germ cell soluble adenylyl cyclase.</title>
            <authorList>
                <person name="Jaiswal B.S."/>
                <person name="Conti M."/>
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            <dbReference type="PubMed" id="11423534"/>
            <dbReference type="DOI" id="10.1074/jbc.m011698200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT VAL-697</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2002" name="J. Clin. Endocrinol. Metab." volume="87" first="1476" last="1485">
            <title>Identification and characterization of a gene with base substitutions associated with the absorptive hypercalciuria phenotype and low spinal bone density.</title>
            <authorList>
                <person name="Reed B.Y."/>
                <person name="Gitomer W.L."/>
                <person name="Heller H.J."/>
                <person name="Hsu M.C."/>
                <person name="Lemke M."/>
                <person name="Padalino P."/>
                <person name="Pak C.Y.C."/>
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            <dbReference type="PubMed" id="11932268"/>
            <dbReference type="DOI" id="10.1210/jcem.87.4.8300"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>INVOLVEMENT IN HCA2</scope>
        <scope>VARIANT VAL-697</scope>
        <source>
            <tissue>Intestine</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="15922" last="15926">
            <title>Kinetic properties of 'soluble' adenylyl cyclase. Synergism between calcium and bicarbonate.</title>
            <authorList>
                <person name="Litvin T.N."/>
                <person name="Kamenetsky M."/>
                <person name="Zarifyan A."/>
                <person name="Buck J."/>
                <person name="Levin L.R."/>
            </authorList>
            <dbReference type="PubMed" id="12609998"/>
            <dbReference type="DOI" id="10.1074/jbc.m212475200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>VARIANT VAL-697</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2000-08" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of a human testicular soluble adenylyl cyclase.</title>
            <authorList>
                <person name="Khole V.V."/>
                <person name="Westbrook V.A."/>
                <person name="Mandal A."/>
                <person name="Herr J.C."/>
                <person name="Visconti P.E."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="1999-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Rhodes S."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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            <dbReference type="PubMed" id="24616449"/>
            <dbReference type="DOI" id="10.1002/cmdc.201300480"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-469 IN COMPLEX WITH HYDROGENCARBONATE; CALCIUM AND ATP ANALOG</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>DOMAIN</scope>
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        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>DOMAIN</scope>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-469 IN COMPLEX WITH CALCIUM; HYDROGENCARBONATE AND ATP ANALOGS</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF LYS-95 AND ARG-176</scope>
        <scope>DOMAIN</scope>
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    <comment type="function">
        <text evidence="1 7 8 9 10 11">Catalyzes the formation of the signaling molecule cAMP (PubMed:12609998, PubMed:15659711, PubMed:24567411, PubMed:24616449, PubMed:25040695). May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels (PubMed:15659711, PubMed:17591988). Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization (By similarity). Involved in ciliary beat regulation (PubMed:17591988).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7 9 10 11">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6 7 9 11 20">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="6 7 10">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="6 7 10 21">Binds 2 magnesium ions per subunit (PubMed:25040695). Is also active with manganese (in vitro) (PubMed:12609998, PubMed:15659711, PubMed:24616449).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="6 7 9 10 11">Activated by manganese or magnesium ions (PubMed:12609998, PubMed:24616449). In the presence of magnesium ions, the enzyme is activated by bicarbonate (PubMed:12609998, PubMed:15659711, PubMed:24567411). In the presence of manganese ions, the enzyme is inhibited by bicarbonate (PubMed:15659711). In the absence of magnesium and bicarbonate, the enzyme is weakly activated by calcium (PubMed:15659711). Calcium mildly increases the enzyme activity, also in the presence of magnesium ions (PubMed:15659711, PubMed:25040695).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">0.8 mM for ATP-Mn(2+)</KM>
            <KM evidence="6">2.41 mM for Mg(2+)</KM>
        </kinetics>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cell membrane</location>
            <topology evidence="7">Peripheral membrane protein</topology>
            <orientation evidence="7">Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 7">Cytoplasm</location>
            <location evidence="5 7">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 7">Cytoplasm</location>
            <location evidence="5 7">Perinuclear region</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 7">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cell projection</location>
            <location evidence="8">Cilium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Mitochondrion</location>
        </subcellularLocation>
        <text evidence="5 7">Distributed to subcellular compartments containing cAMP targets. Found as a plasma membrane-associated protein, protein concentrated in the perinuclear region and protein colocalized with actin or tubulin.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96PN6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96PN6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_030867"/>
        </isoform>
        <isoform>
            <id>Q96PN6-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_030866 VSP_030868 VSP_030869 VSP_030870"/>
        </isoform>
        <isoform>
            <id>Q96PN6-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046329"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 7 8">Detected in airway epithelial cells and testis (at protein level) (PubMed:17591988). Weakly expressed in multiple tissues. Expressed in brain, heart, kidney, liver, lung, pancreas, peripheral blood leukocytes, placenta, skeletal muscle, stomach, thymus, airway epithelial cells, duodenum, jejunum and ileum. Very low level of expression in bone.</text>
    </comment>
    <comment type="domain">
        <text evidence="9 10 11">The N-terminal guanylate cyclase domains are required for enzyme activity. Fragments or isoforms containing the first 470 amino acid residues are fully active.</text>
    </comment>
    <comment type="PTM">
        <text evidence="18">Cleavage may occur to generate the active 48 kDa form.</text>
    </comment>
    <comment type="disease" evidence="4">
        <disease id="DI-02646">
            <name>Hypercalciuria absorptive 2</name>
            <acronym>HCA2</acronym>
            <description>A common type of hypercalciuria, a condition characterized by excessive urinary calcium excretion. Absorptive hypercalciuria is due to gastrointestinal hyperabsorption of calcium and is a frequent cause of calcium oxalate nephrolithiasis.</description>
            <dbReference type="MIM" id="143870"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="2">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="6 7 9 10 11"/>
    <dbReference type="EMBL" id="AF271058">
        <property type="protein sequence ID" value="AAF74296.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF331033">
        <property type="protein sequence ID" value="AAL57036.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF176813">
        <property type="protein sequence ID" value="AAF65931.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF299350">
        <property type="protein sequence ID" value="AAK96045.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL035122">
        <property type="protein sequence ID" value="CAA22684.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK302884">
        <property type="protein sequence ID" value="BAG64062.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z97876">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z99943">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471067">
        <property type="protein sequence ID" value="EAW90804.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471067">
        <property type="protein sequence ID" value="EAW90807.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117366">
        <property type="protein sequence ID" value="AAI17367.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117372">
        <property type="protein sequence ID" value="AAI17373.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1265.1">
        <molecule id="Q96PN6-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53426.1">
        <molecule id="Q96PN6-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS72977.1">
        <molecule id="Q96PN6-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001161221.1">
        <molecule id="Q96PN6-4"/>
        <property type="nucleotide sequence ID" value="NM_001167749.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001284701.1">
        <molecule id="Q96PN6-2"/>
        <property type="nucleotide sequence ID" value="NM_001297772.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060887.2">
        <molecule id="Q96PN6-1"/>
        <property type="nucleotide sequence ID" value="NM_018417.6"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011508062.1">
        <molecule id="Q96PN6-1"/>
        <property type="nucleotide sequence ID" value="XM_011509760.4"/>
    </dbReference>
    <dbReference type="PDB" id="4CLF">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A=1-469"/>
    </dbReference>
    <dbReference type="PDB" id="4CLK">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A=1-469"/>
    </dbReference>
    <dbReference type="PDB" id="4CLL">
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    </dbReference>
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        <property type="resolution" value="1.90 A"/>
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    </dbReference>
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        <property type="resolution" value="1.85 A"/>
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    </dbReference>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.95 A"/>
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    </dbReference>
    <dbReference type="PDB" id="4CLU">
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        <property type="resolution" value="2.15 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A=1-469"/>
    </dbReference>
    <dbReference type="PDB" id="4CM2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=1-469"/>
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    <dbReference type="PDB" id="4OYA">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.03 A"/>
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        <property type="resolution" value="1.75 A"/>
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        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.28 A"/>
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        <property type="resolution" value="1.89 A"/>
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        <property type="resolution" value="1.74 A"/>
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        <property type="resolution" value="1.95 A"/>
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    <dbReference type="PDBsum" id="4CLF"/>
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    <dbReference type="PDBsum" id="4OYA"/>
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    <dbReference type="PDBsum" id="8IL7"/>
    <dbReference type="AlphaFoldDB" id="Q96PN6"/>
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    <dbReference type="BioGRID" id="120921">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96PN6">
        <property type="interactions" value="500"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96PN6">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="MINT" id="Q96PN6"/>
    <dbReference type="STRING" id="9606.ENSP00000356825"/>
    <dbReference type="BindingDB" id="Q96PN6"/>
    <dbReference type="ChEMBL" id="CHEMBL5854"/>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="3068"/>
    <dbReference type="GlyGen" id="Q96PN6">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (3 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96PN6"/>
    <dbReference type="PhosphoSitePlus" id="Q96PN6"/>
    <dbReference type="SwissPalm" id="Q96PN6"/>
    <dbReference type="BioMuta" id="ADCY10"/>
    <dbReference type="DMDM" id="308153637"/>
    <dbReference type="MassIVE" id="Q96PN6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000356825"/>
    <dbReference type="PeptideAtlas" id="Q96PN6"/>
    <dbReference type="ProteomicsDB" id="24204"/>
    <dbReference type="ProteomicsDB" id="77715">
        <molecule id="Q96PN6-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77716">
        <molecule id="Q96PN6-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77717">
        <molecule id="Q96PN6-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="3017">
        <property type="antibodies" value="154 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55811"/>
    <dbReference type="Ensembl" id="ENST00000367848.1">
        <molecule id="Q96PN6-2"/>
        <property type="protein sequence ID" value="ENSP00000356822.1"/>
        <property type="gene ID" value="ENSG00000143199.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000367851.9">
        <molecule id="Q96PN6-1"/>
        <property type="protein sequence ID" value="ENSP00000356825.4"/>
        <property type="gene ID" value="ENSG00000143199.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000545172.5">
        <molecule id="Q96PN6-4"/>
        <property type="protein sequence ID" value="ENSP00000441992.1"/>
        <property type="gene ID" value="ENSG00000143199.18"/>
    </dbReference>
    <dbReference type="GeneID" id="55811"/>
    <dbReference type="KEGG" id="hsa:55811"/>
    <dbReference type="MANE-Select" id="ENST00000367851.9">
        <property type="protein sequence ID" value="ENSP00000356825.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018417.6"/>
        <property type="RefSeq protein sequence ID" value="NP_060887.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001ger.4">
        <molecule id="Q96PN6-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21285"/>
    <dbReference type="ClinPGx" id="PA162375618"/>
    <dbReference type="CTD" id="55811"/>
    <dbReference type="DisGeNET" id="55811"/>
    <dbReference type="GeneCards" id="ADCY10"/>
    <dbReference type="HGNC" id="HGNC:21285">
        <property type="gene designation" value="ADCY10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000143199">
        <property type="expression patterns" value="Group enriched (liver, testis)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCY10"/>
    <dbReference type="MIM" id="143870">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="605205">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000143199"/>
    <dbReference type="Orphanet" id="2197">
        <property type="disease" value="Idiopathic hypercalciuria"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000143199"/>
    <dbReference type="eggNOG" id="ENOG502QPPT">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000001322"/>
    <dbReference type="HOGENOM" id="CLU_004055_1_0_1"/>
    <dbReference type="InParanoid" id="Q96PN6"/>
    <dbReference type="OMA" id="HIIRFCK"/>
    <dbReference type="OrthoDB" id="194468at2759"/>
    <dbReference type="PAN-GO" id="Q96PN6">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96PN6"/>
    <dbReference type="BRENDA" id="4.6.1.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q96PN6"/>
    <dbReference type="Reactome" id="R-HSA-5610787">
        <property type="pathway name" value="Hedgehog 'off' state"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="Q96PN6"/>
    <dbReference type="SignaLink" id="Q96PN6"/>
    <dbReference type="SIGNOR" id="Q96PN6"/>
    <dbReference type="Agora" id="ENSG00000143199"/>
    <dbReference type="BioGRID-ORCS" id="55811">
        <property type="hits" value="8 hits in 1145 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCY10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q96PN6"/>
    <dbReference type="GeneWiki" id="ADCY10"/>
    <dbReference type="GenomeRNAi" id="55811"/>
    <dbReference type="Pharos" id="Q96PN6">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96PN6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96PN6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000143199">
        <property type="expression patterns" value="Expressed in sperm and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96PN6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045177">
        <property type="term" value="C:apical part of cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097450">
        <property type="term" value="C:astrocyte end-foot"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045178">
        <property type="term" value="C:basal part of cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090724">
        <property type="term" value="C:central region of growth cone"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005856">
        <property type="term" value="C:cytoskeleton"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="205" xmlns="https://uniprot.org/uniprot">
    <accession>O95622</accession>
    <accession>B7Z8A6</accession>
    <accession>Q7RTV7</accession>
    <accession>Q8NFM3</accession>
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            <fullName>Adenylate cyclase type 5</fullName>
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            <fullName>ATP pyrophosphate-lyase 5</fullName>
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            <fullName>Adenylate cyclase type V</fullName>
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        <alternativeName>
            <fullName>Adenylyl cyclase 5</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Metazoa</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
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            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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                <person name="Ono T."/>
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            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Testis</tissue>
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            <dbReference type="PubMed" id="16641997"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <dbReference type="DOI" id="10.1081/rrs-120014589"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 368-1261 (ISOFORM 1)</scope>
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            <tissue>Heart</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 560-664 (ISOFORM 1)</scope>
        <source>
            <tissue>Heart muscle</tissue>
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            <dbReference type="PubMed" id="15385642"/>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PHOSPHORYLATION BY RAF1</scope>
        <scope>INTERACTION WITH RAF1</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <authorList>
                <person name="Hodson D.J."/>
                <person name="Mitchell R.K."/>
                <person name="Marselli L."/>
                <person name="Pullen T.J."/>
                <person name="Gimeno Brias S."/>
                <person name="Semplici F."/>
                <person name="Everett K.L."/>
                <person name="Cooper D.M."/>
                <person name="Bugliani M."/>
                <person name="Marchetti P."/>
                <person name="Lavallard V."/>
                <person name="Bosco D."/>
                <person name="Piemonti L."/>
                <person name="Johnson P.R."/>
                <person name="Hughes S.J."/>
                <person name="Li D."/>
                <person name="Li W.H."/>
                <person name="Shapiro A.M."/>
                <person name="Rutter G.A."/>
            </authorList>
            <dbReference type="PubMed" id="24740569"/>
            <dbReference type="DOI" id="10.2337/db13-1607"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2015" name="Mol. Pharmacol." volume="88" first="758" last="767">
            <title>Adenylyl cyclase 5 regulation by Gbetagamma involves isoform specific use of multiple interaction sites.</title>
            <authorList>
                <person name="Brand C.S."/>
                <person name="Sadana R."/>
                <person name="Malik S."/>
                <person name="Smrcka A.V."/>
                <person name="Dessauer C.W."/>
            </authorList>
            <dbReference type="PubMed" id="26206488"/>
            <dbReference type="DOI" id="10.1124/mol.115.099556"/>
        </citation>
        <scope>INTERACTION WITH GNAS; GNB1 AND GNG2</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2012" name="Arch. Neurol." volume="69" first="630" last="635">
            <title>Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.</title>
            <authorList>
                <person name="Chen Y.Z."/>
                <person name="Matsushita M.M."/>
                <person name="Robertson P."/>
                <person name="Rieder M."/>
                <person name="Girirajan S."/>
                <person name="Antonacci F."/>
                <person name="Lipe H."/>
                <person name="Eichler E.E."/>
                <person name="Nickerson D.A."/>
                <person name="Bird T.D."/>
                <person name="Raskind W.H."/>
            </authorList>
            <dbReference type="PubMed" id="22782511"/>
            <dbReference type="DOI" id="10.1001/archneurol.2012.54"/>
        </citation>
        <scope>VARIANT DSKOD THR-726</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2014" name="Ann. Neurol." volume="75" first="542" last="549">
            <title>Gain-of-function ADCY5 mutations in familial dyskinesia with facial myokymia.</title>
            <authorList>
                <person name="Chen Y.Z."/>
                <person name="Friedman J.R."/>
                <person name="Chen D.H."/>
                <person name="Chan G.C."/>
                <person name="Bloss C.S."/>
                <person name="Hisama F.M."/>
                <person name="Topol S.E."/>
                <person name="Carson A.R."/>
                <person name="Pham P.H."/>
                <person name="Bonkowski E.S."/>
                <person name="Scott E.R."/>
                <person name="Lee J.K."/>
                <person name="Zhang G."/>
                <person name="Oliveira G."/>
                <person name="Xu J."/>
                <person name="Scott-Van Zeeland A.A."/>
                <person name="Chen Q."/>
                <person name="Levy S."/>
                <person name="Topol E.J."/>
                <person name="Storm D."/>
                <person name="Swanson P.D."/>
                <person name="Bird T.D."/>
                <person name="Schork N.J."/>
                <person name="Raskind W.H."/>
                <person name="Torkamani A."/>
            </authorList>
            <dbReference type="PubMed" id="24700542"/>
            <dbReference type="DOI" id="10.1002/ana.24119"/>
        </citation>
        <scope>VARIANT DSKOD TRP-418</scope>
        <scope>CHARACTERIZATION OF VARIANTS DSKOD TRP-418 AND THR-726</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2015" name="Neurology" volume="85" first="80" last="88">
            <title>ADCY5 mutations are another cause of benign hereditary chorea.</title>
            <authorList>
                <person name="Mencacci N.E."/>
                <person name="Erro R."/>
                <person name="Wiethoff S."/>
                <person name="Hersheson J."/>
                <person name="Ryten M."/>
                <person name="Balint B."/>
                <person name="Ganos C."/>
                <person name="Stamelou M."/>
                <person name="Quinn N."/>
                <person name="Houlden H."/>
                <person name="Wood N.W."/>
                <person name="Bhatia K.P."/>
            </authorList>
            <dbReference type="PubMed" id="26085604"/>
            <dbReference type="DOI" id="10.1212/wnl.0000000000001720"/>
        </citation>
        <scope>VARIANTS LEU-10 AND VAL-706</scope>
        <scope>VARIANT DSKOD TRP-418</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2017" name="Neurol. Genet." volume="3" first="193" last="193">
            <title>Autosomal recessive inheritance of ADCY5-related generalized dystonia and myoclonus.</title>
            <authorList>
                <person name="Barrett M.J."/>
                <person name="Williams E.S."/>
                <person name="Chambers C."/>
                <person name="Dhamija R."/>
            </authorList>
            <dbReference type="PubMed" id="28971144"/>
            <dbReference type="DOI" id="10.1212/nxg.0000000000000193"/>
        </citation>
        <scope>VARIANT DSKOR CYS-1013</scope>
        <scope>INVOLVEMENT IN DSKOR</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2019" name="Parkinsonism Relat. Disord." volume="64" first="145" last="149">
            <title>Autosomal recessive ADCY5-Related dystonia and myoclonus: Expanding the genetic spectrum of ADCY5-Related movement disorders.</title>
            <authorList>
                <person name="Bohlega S.A."/>
                <person name="Abou-Al-Shaar H."/>
                <person name="Al-Dakheel A."/>
                <person name="Alajlan H."/>
                <person name="Bohlega B.S."/>
                <person name="Meyer B.F."/>
                <person name="Monies D."/>
                <person name="Cupler E.J."/>
                <person name="Al-Saif A.M."/>
            </authorList>
            <dbReference type="PubMed" id="30975617"/>
            <dbReference type="DOI" id="10.1016/j.parkreldis.2019.02.039"/>
        </citation>
        <scope>VARIANT DSKOR ASN-588</scope>
        <scope>INVOLVEMENT IN DSKOR</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2021" name="Neurol. Sci." volume="42" first="2975" last="2978">
            <title>Homozygous ADCY5 mutation causes early-onset movement disorder with severe intellectual disability.</title>
            <authorList>
                <person name="Okamoto N."/>
                <person name="Miya F."/>
                <person name="Kitai Y."/>
                <person name="Tsunoda T."/>
                <person name="Kato M."/>
                <person name="Saitoh S."/>
                <person name="Kanemura Y."/>
                <person name="Kosaki K."/>
            </authorList>
            <dbReference type="PubMed" id="33704598"/>
            <dbReference type="DOI" id="10.1007/s10072-021-05152-y"/>
        </citation>
        <scope>VARIANT DSKOR TRP-1238</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2021" name="Mov. Disord. Clin. Pract." volume="8" first="1140" last="1143">
            <title>A Novel Homozygous ADCY5 Variant is Associated with a Neurodevelopmental Disorder and Movement Abnormalities.</title>
            <authorList>
                <person name="Kaiyrzhanov R."/>
                <person name="Zaki M.S."/>
                <person name="Maroofian R."/>
                <person name="Dominik N."/>
                <person name="Rad A."/>
                <person name="Vona B."/>
                <person name="Houlden H."/>
            </authorList>
            <dbReference type="PubMed" id="34631954"/>
            <dbReference type="DOI" id="10.1002/mdc3.13310"/>
        </citation>
        <scope>INVOLVEMENT IN NEDHYD</scope>
    </reference>
    <comment type="function">
        <text evidence="9 11 12 14">Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642, PubMed:24700542, PubMed:26206488). Mediates signaling downstream of ADRB1 (PubMed:24700542). Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion (PubMed:24740569).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9 11 14">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="9">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="3">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3 9 11 14">Activated by G(s) G alpha protein GNAS (PubMed:26206488). Inhibited by G(i) G alpha protein GNAI1 (By similarity). Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2 (PubMed:26206488). Activated by forskolin (PubMed:24700542). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs (PubMed:26206488). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 9 14">Interacts with GNAS, GNB1 and GNG2 (PubMed:26206488). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="21 22">Cell membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Cilium</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O95622-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O95622-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_042914 VSP_042915"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="12 13">Detected in pancreas islets (at protein level). Expressed in the brain, with high expression in the corpus striatum (PubMed:26085604).</text>
    </comment>
    <comment type="domain">
        <text evidence="3">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="9">Phosphorylated by RAF1.</text>
    </comment>
    <comment type="disease" evidence="15 16 17">
        <disease id="DI-06289">
            <name>Dyskinesia with orofacial involvement, autosomal recessive</name>
            <acronym>DSKOR</acronym>
            <description>An autosomal recessive disorder characterized by abnormal involuntary movements mainly affecting the limbs and causing walking difficulties, oro-facial dyskinesia, and speech delay. Some patients develop neuropsychiatric features. Cardiomyopathy has rarely been described and may be a manifestation of the disorder.</description>
            <dbReference type="MIM" id="619647"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="10 11 13">
        <disease id="DI-03514">
            <name>Dyskinesia with orofacial involvement, autosomal dominant</name>
            <acronym>DSKOD</acronym>
            <description>A disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages.</description>
            <dbReference type="MIM" id="606703"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="18">
        <disease id="DI-06286">
            <name>Neurodevelopmental disorder with hyperkinetic movements and dyskinesia</name>
            <acronym>NEDHYD</acronym>
            <description>An autosomal recessive disorder characterized by severe global developmental delay, axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements.</description>
            <dbReference type="MIM" id="619651"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="9 11 14"/>
    <dbReference type="EMBL" id="AK303070">
        <property type="protein sequence ID" value="BAH13892.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025571">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC112503">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF497517">
        <property type="protein sequence ID" value="AAM94374.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U65473">
        <property type="protein sequence ID" value="AAD00121.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BK000371">
        <property type="protein sequence ID" value="DAA00057.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3022.1">
        <molecule id="O95622-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS56274.1">
        <molecule id="O95622-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001186571.1">
        <molecule id="O95622-2"/>
        <property type="nucleotide sequence ID" value="NM_001199642.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_899200.1">
        <molecule id="O95622-1"/>
        <property type="nucleotide sequence ID" value="NM_183357.3"/>
    </dbReference>
    <dbReference type="PDB" id="8SL3">
        <property type="method" value="EM"/>
        <property type="resolution" value="7.00 A"/>
        <property type="chains" value="A=1-1261"/>
    </dbReference>
    <dbReference type="PDB" id="8SL4">
        <property type="method" value="EM"/>
        <property type="resolution" value="7.00 A"/>
        <property type="chains" value="A/B=1-1261"/>
    </dbReference>
    <dbReference type="PDBsum" id="8SL3"/>
    <dbReference type="PDBsum" id="8SL4"/>
    <dbReference type="AlphaFoldDB" id="O95622"/>
    <dbReference type="EMDB" id="EMD-40572"/>
    <dbReference type="EMDB" id="EMD-40573"/>
    <dbReference type="SMR" id="O95622"/>
    <dbReference type="BioGRID" id="106624">
        <property type="interactions" value="19"/>
    </dbReference>
    <dbReference type="FunCoup" id="O95622">
        <property type="interactions" value="1519"/>
    </dbReference>
    <dbReference type="IntAct" id="O95622">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000419361"/>
    <dbReference type="BindingDB" id="O95622"/>
    <dbReference type="ChEMBL" id="CHEMBL3189"/>
    <dbReference type="DrugBank" id="DB06843">
        <property type="generic name" value="2',5'-DIDEOXY-ADENOSINE 3'-MONOPHOSPHATE"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09121">
        <property type="generic name" value="Aurothioglucose"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1282"/>
    <dbReference type="GlyCosmos" id="O95622">
        <property type="glycosylation" value="2 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O95622">
        <property type="glycosylation" value="3 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O95622"/>
    <dbReference type="PhosphoSitePlus" id="O95622"/>
    <dbReference type="SwissPalm" id="O95622"/>
    <dbReference type="BioMuta" id="ADCY5"/>
    <dbReference type="jPOST" id="O95622"/>
    <dbReference type="MassIVE" id="O95622"/>
    <dbReference type="PaxDb" id="9606-ENSP00000419361"/>
    <dbReference type="PeptideAtlas" id="O95622"/>
    <dbReference type="ProteomicsDB" id="50954">
        <molecule id="O95622-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="50955">
        <molecule id="O95622-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2807">
        <property type="antibodies" value="163 antibodies from 28 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="111"/>
    <dbReference type="Ensembl" id="ENST00000309879.9">
        <molecule id="O95622-2"/>
        <property type="protein sequence ID" value="ENSP00000308685.5"/>
        <property type="gene ID" value="ENSG00000173175.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000462833.6">
        <molecule id="O95622-1"/>
        <property type="protein sequence ID" value="ENSP00000419361.1"/>
        <property type="gene ID" value="ENSG00000173175.17"/>
    </dbReference>
    <dbReference type="GeneID" id="111"/>
    <dbReference type="KEGG" id="hsa:111"/>
    <dbReference type="MANE-Select" id="ENST00000462833.6">
        <property type="protein sequence ID" value="ENSP00000419361.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_183357.3"/>
        <property type="RefSeq protein sequence ID" value="NP_899200.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003egh.3">
        <molecule id="O95622-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:236"/>
    <dbReference type="ClinPGx" id="PA24563"/>
    <dbReference type="CTD" id="111"/>
    <dbReference type="DisGeNET" id="111"/>
    <dbReference type="GeneCards" id="ADCY5"/>
    <dbReference type="GeneReviews" id="ADCY5"/>
    <dbReference type="HGNC" id="HGNC:236">
        <property type="gene designation" value="ADCY5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000173175">
        <property type="expression patterns" value="Tissue enhanced (brain, heart muscle)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCY5"/>
    <dbReference type="MIM" id="600293">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="606703">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="619647">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="619651">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000173175"/>
    <dbReference type="Orphanet" id="1429">
        <property type="disease" value="Benign hereditary chorea"/>
    </dbReference>
    <dbReference type="Orphanet" id="324588">
        <property type="disease" value="Familial dyskinesia and facial myokymia"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000173175"/>
    <dbReference type="eggNOG" id="KOG3619">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158054"/>
    <dbReference type="HOGENOM" id="CLU_001072_2_0_1"/>
    <dbReference type="InParanoid" id="O95622"/>
    <dbReference type="OMA" id="HNSSHWT"/>
    <dbReference type="OrthoDB" id="10261550at2759"/>
    <dbReference type="PAN-GO" id="O95622">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O95622"/>
    <dbReference type="BRENDA" id="4.6.1.1">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="O95622"/>
    <dbReference type="Reactome" id="R-HSA-163359">
        <property type="pathway name" value="Glucagon signaling in metabolic regulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163615">
        <property type="pathway name" value="PKA activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-164378">
        <property type="pathway name" value="PKA activation in glucagon signalling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170660">
        <property type="pathway name" value="Adenylate cyclase activating pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170670">
        <property type="pathway name" value="Adenylate cyclase inhibitory pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-381676">
        <property type="pathway name" value="Glucagon-like Peptide-1 (GLP1) regulates insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-400042">
        <property type="pathway name" value="Adrenaline,noradrenaline inhibits insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418555">
        <property type="pathway name" value="G alpha (s) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418594">
        <property type="pathway name" value="G alpha (i) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418597">
        <property type="pathway name" value="G alpha (z) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-432040">
        <property type="pathway name" value="Vasopressin regulates renal water homeostasis via Aquaporins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5610787">
        <property type="pathway name" value="Hedgehog 'off' state"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9634597">
        <property type="pathway name" value="GPER1 signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9660821">
        <property type="pathway name" value="ADORA2B mediated anti-inflammatory cytokines production"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9664323">
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        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="26085604"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="26206488"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="28971144"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="30975617"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="33704598"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="34631954"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="26206488"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="21">
        <source>
            <dbReference type="PubMed" id="15385642"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="22">
        <source>
            <dbReference type="PubMed" id="26206488"/>
        </source>
    </evidence>
    <sequence length="1261" mass="138908" checksum="C50492A0B053694F" modified="2006-11-28" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-10-01" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>Q08462</accession>
    <accession>B7Z2C1</accession>
    <accession>Q2NKL8</accession>
    <accession>Q9UDB2</accession>
    <accession>Q9UPU2</accession>
    <name>ADCY2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenylate cyclase type 2</fullName>
            <ecNumber evidence="6">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase type II</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylyl cyclase 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY2</name>
        <name type="synonym">KIAA1060</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2001-08" db="EMBL/GenBank/DDBJ databases">
            <title>Molecular cloning of human adenylyl cyclase gene.</title>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Sugawara M."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
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                <person name="Momiyama H."/>
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                <person name="Takami S."/>
                <person name="Terashima Y."/>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Amygdala</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="431" first="268" last="274">
            <title>The DNA sequence and comparative analysis of human chromosome 5.</title>
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                <person name="Pitluck S."/>
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                <person name="Predki P."/>
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                <person name="Ramirez L."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
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                <person name="Ustaszewska A."/>
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            </authorList>
            <dbReference type="PubMed" id="15372022"/>
            <dbReference type="DOI" id="10.1038/nature02919"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT LEU-147</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1999" name="DNA Res." volume="6" first="197" last="205">
            <title>Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Kikuno R."/>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
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                <person name="Miyajima N."/>
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                <person name="Kotani H."/>
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            </authorList>
            <dbReference type="PubMed" id="10470851"/>
            <dbReference type="DOI" id="10.1093/dnares/6.3.197"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-1091 (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1992" name="Hum. Genet." volume="90" first="126" last="130">
            <title>Different chromosomal localization of two adenylyl cyclase genes expressed in human brain.</title>
            <authorList>
                <person name="Stengel D."/>
                <person name="Parma J."/>
                <person name="Gannage M.-H."/>
                <person name="Roeckel N."/>
                <person name="Mattei M.-G."/>
                <person name="Barouki R."/>
                <person name="Hanoune J."/>
            </authorList>
            <dbReference type="PubMed" id="1427768"/>
            <dbReference type="DOI" id="10.1007/bf00210755"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 616-1091 (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1993" name="Biochem. Biophys. Res. Commun." volume="192" first="311" last="318">
            <title>A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line.</title>
            <authorList>
                <person name="Hellevuo K."/>
                <person name="Yoshimura M."/>
                <person name="Kao M."/>
                <person name="Hoffman P.L."/>
                <person name="Cooper D.M.F."/>
                <person name="Tabakoff B."/>
            </authorList>
            <dbReference type="PubMed" id="8476432"/>
            <dbReference type="DOI" id="10.1006/bbrc.1993.1415"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 948-1017 (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2001" name="J. Clin. Endocrinol. Metab." volume="86" first="4495" last="4503">
            <title>Expression and regulation of adenylyl cyclase isoforms in the human adrenal gland.</title>
            <authorList>
                <person name="Cote M."/>
                <person name="Guillon G."/>
                <person name="Payet M.D."/>
                <person name="Gallo-Payet N."/>
            </authorList>
            <dbReference type="PubMed" id="11549699"/>
            <dbReference type="DOI" id="10.1210/jcem.86.9.7837"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="Mol. Pharmacol." volume="66" first="921" last="928">
            <title>Raf kinase activation of adenylyl cyclases: isoform-selective regulation.</title>
            <authorList>
                <person name="Ding Q."/>
                <person name="Gros R."/>
                <person name="Gray I.D."/>
                <person name="Taussig R."/>
                <person name="Ferguson S.S."/>
                <person name="Feldman R.D."/>
            </authorList>
            <dbReference type="PubMed" id="15385642"/>
            <dbReference type="DOI" id="10.1124/mol.66.4.921"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>PHOSPHORYLATION BY RAF1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH RAF1</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2011" name="J. Pharmacol. Exp. Ther." volume="337" first="209" last="217">
            <title>Human bronchial smooth muscle cells express adenylyl cyclase isoforms 2, 4, and 6 in distinct membrane microdomains.</title>
            <authorList>
                <person name="Bogard A.S."/>
                <person name="Xu C."/>
                <person name="Ostrom R.S."/>
            </authorList>
            <dbReference type="PubMed" id="21228062"/>
            <dbReference type="DOI" id="10.1124/jpet.110.177923"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 6">Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:15385642). Down-stream signaling cascades mediate changes in gene expression patterns and lead to increased IL6 production. Functions in signaling cascades downstream of the muscarinic acetylcholine receptors (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="6">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="1">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 6">Activated by forskolin (PubMed:15385642). Is not activated by calmodulin. Inhibited by calcium ions, already at micromolar concentration. Activated by the G protein alpha subunit GNAS. Activated by the G protein beta and gamma subunit complex (By similarity). Phosphorylation by RAF1 results in its activation (PubMed:15385642). Phosphorylation by PKC activates the enzyme (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 6">Interacts with RAF1 (PubMed:15385642). Interacts with GNAS. Interacts with the G protein beta and gamma subunit complex (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5 8">Cell membrane</location>
            <topology evidence="11">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q08462-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q08462-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055811 VSP_055812"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5 9">Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Expressed in brain, especially in caudate nucleus, cerebellum and hippocampus.</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="6">Phosphorylated by RAF1.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="6"/>
    <dbReference type="EMBL" id="AF410885">
        <property type="protein sequence ID" value="AAP97285.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK294555">
        <property type="protein sequence ID" value="BAH11807.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010346">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010437">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC024577">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093305">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC113366">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC111743">
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    <feature type="modified residue" description="Phosphoserine; by PKC" evidence="1">
        <location>
            <position position="491"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine; by PKC" evidence="1">
        <location>
            <position position="544"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="713"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="3">
        <location>
            <position position="716"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055811" description="In isoform 2." evidence="10">
        <original>MWQEAMRRRRYLRDRSEEAAGGGDGLPRSRDWLYESYYCMSQQHPLIVFLLLIVMGSCL</original>
        <variation>MDLRWARDLHLREASRSVAFTTLRLGAVTTGLLTFREPGDKEKSGKGLGKRWRIQREES</variation>
        <location>
            <begin position="1"/>
            <end position="59"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_055812" description="In isoform 2." evidence="10">
        <location>
            <begin position="60"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_029012" description="In dbSNP:rs13166360." evidence="7">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048247" description="In dbSNP:rs34043481.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAP97285." evidence="11" ref="1">
        <original>VWQILANVIIFICGNLAGAY</original>
        <variation>GLADPGQCDHFHLWEPGXTN</variation>
        <location>
            <begin position="188"/>
            <end position="207"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 6; CAA52282/AAA64923." evidence="11" ref="6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="675"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P26769"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P30803"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00099"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="11549699"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15385642"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="21228062"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="8476432"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <sequence length="1091" mass="123603" checksum="41FD8BC607C075D1" modified="2006-11-28" version="5"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2001-04-27" modified="2026-01-28" version="221" xmlns="https://uniprot.org/uniprot">
    <accession>O60266</accession>
    <accession>B3KT86</accession>
    <accession>Q53T54</accession>
    <accession>Q9UDB1</accession>
    <name>ADCY3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adenylate cyclase type 3</fullName>
            <ecNumber evidence="4">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase type III</fullName>
            <shortName>AC-III</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase, olfactive type</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="16">Adenylyl cyclase 3</fullName>
            <shortName evidence="15">AC3</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY3</name>
        <name type="synonym">KIAA0511</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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                <person name="Dahl-Petersen I.K."/>
                <person name="Gilly A."/>
                <person name="Suveges D."/>
                <person name="Dedoussis G."/>
                <person name="Zeggini E."/>
                <person name="Pedersen O."/>
                <person name="Andersson R."/>
                <person name="Bjerregaard P."/>
                <person name="Joergensen M.E."/>
                <person name="Albrechtsen A."/>
                <person name="Hansen T."/>
            </authorList>
            <dbReference type="PubMed" id="29311636"/>
            <dbReference type="DOI" id="10.1038/s41588-017-0022-7"/>
        </citation>
        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN BMIQ19</scope>
        <scope>INVOLVEMENT IN OBESITY</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2018" name="Nat. Genet." volume="50" first="175" last="179">
            <title>Loss-of-function mutations in ADCY3 cause monogenic severe obesity.</title>
            <authorList>
                <person name="Saeed S."/>
                <person name="Bonnefond A."/>
                <person name="Tamanini F."/>
                <person name="Mirza M.U."/>
                <person name="Manzoor J."/>
                <person name="Janjua Q.M."/>
                <person name="Din S.M."/>
                <person name="Gaitan J."/>
                <person name="Milochau A."/>
                <person name="Durand E."/>
                <person name="Vaillant E."/>
                <person name="Haseeb A."/>
                <person name="De Graeve F."/>
                <person name="Rabearivelo I."/>
                <person name="Sand O."/>
                <person name="Queniat G."/>
                <person name="Boutry R."/>
                <person name="Schott D.A."/>
                <person name="Ayesha H."/>
                <person name="Ali M."/>
                <person name="Khan W.I."/>
                <person name="Butt T.A."/>
                <person name="Rinne T."/>
                <person name="Stumpel C."/>
                <person name="Abderrahmani A."/>
                <person name="Lang J."/>
                <person name="Arslan M."/>
                <person name="Froguel P."/>
            </authorList>
            <dbReference type="PubMed" id="29311637"/>
            <dbReference type="DOI" id="10.1038/s41588-017-0023-6"/>
        </citation>
        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN BMIQ19</scope>
        <scope>INVOLVEMENT IN OBESITY</scope>
        <scope>VARIANT OBESITY PHE-1118 DEL</scope>
        <scope>VARIANT ILE-64</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2023" name="J. Clin. Res. Pediatr. Endocrinol." volume="0" first="0" last="0">
            <title>A Rare Case of Monogenic Obesity due to a Novel Variant in the ADCY3 Gene: Challenges in Follow-up and Treatment.</title>
            <authorList>
                <person name="Oezcabi B."/>
                <person name="Durmaz A."/>
                <person name="Aykut A."/>
                <person name="Oenal H."/>
                <person name="Oezen S."/>
            </authorList>
            <dbReference type="PubMed" id="37855273"/>
            <dbReference type="DOI" id="10.4274/jcrpe.galenos.2023.2023-7-2"/>
        </citation>
        <scope>POLYMORPHISM</scope>
        <scope>INVOLVEMENT IN BMIQ19</scope>
        <scope>VARIANT OBESITY ASN-368</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis: specifically activated by G alpha protein GNAL/G(olf) in olfactory epithelium. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="3">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="3">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="1">Specifically activated by the G alpha protein GNAL/G(olf) in signaling cascades triggered by odorant receptors. Activated by forskolin. After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Cell membrane</location>
            <topology evidence="16">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Cilium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Golgi apparatus</location>
        </subcellularLocation>
        <text evidence="8">Also detected in the cytoplasm, close to lipid droplets.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O60266-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O60266-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055813 VSP_055814 VSP_055815"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8 9 13">Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Expressed in brain, heart, kidney, liver, lung, pancreas islets, placenta, and skeletal muscle (PubMed:9920776). Detected in testis (PubMed:15705663).</text>
    </comment>
    <comment type="domain">
        <text evidence="3">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Sumoylated. Sumoylation is required for targeting ot olfactory cilia.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">N-glycosylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="4">Rapidly phosphorylated after stimulation by odorants or forskolin. Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="10 11 12">Genetic variations at the ADCY3 locus define the body mass index quantitative trait locus 19 (BMIQ19) [MIM:617885]. Variance in body mass index is a susceptibility factor for obesity.</text>
    </comment>
    <comment type="disease" evidence="10 11 12">
        <disease id="DI-01221">
            <name>Obesity</name>
            <acronym>OBESITY</acronym>
            <description>A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.</description>
            <dbReference type="MIM" id="601665"/>
        </disease>
        <text>Disease susceptibility is associated with variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="4"/>
    <dbReference type="EMBL" id="AF033861">
        <property type="protein sequence ID" value="AAD13403.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK095173">
        <property type="protein sequence ID" value="BAG52998.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012073">
        <property type="protein sequence ID" value="AAY14787.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126235">
        <property type="protein sequence ID" value="AAI26236.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB011083">
        <property type="protein sequence ID" value="BAA25437.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1715.1">
        <molecule id="O60266-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307542.1">
        <property type="nucleotide sequence ID" value="NM_001320613.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001364061.1">
        <molecule id="O60266-1"/>
        <property type="nucleotide sequence ID" value="NM_001377132.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004027.2">
        <molecule id="O60266-1"/>
        <property type="nucleotide sequence ID" value="NM_004036.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O60266"/>
    <dbReference type="SMR" id="O60266"/>
    <dbReference type="BioGRID" id="106623">
        <property type="interactions" value="104"/>
    </dbReference>
    <dbReference type="FunCoup" id="O60266">
        <property type="interactions" value="2776"/>
    </dbReference>
    <dbReference type="IntAct" id="O60266">
        <property type="interactions" value="65"/>
    </dbReference>
    <dbReference type="MINT" id="O60266"/>
    <dbReference type="STRING" id="9606.ENSP00000384484"/>
    <dbReference type="BindingDB" id="O60266"/>
    <dbReference type="ChEMBL" id="CHEMBL3164"/>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O60266">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O60266">
        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O60266"/>
    <dbReference type="PhosphoSitePlus" id="O60266"/>
    <dbReference type="SwissPalm" id="O60266"/>
    <dbReference type="BioMuta" id="ADCY3"/>
    <dbReference type="jPOST" id="O60266"/>
    <dbReference type="MassIVE" id="O60266"/>
    <dbReference type="PaxDb" id="9606-ENSP00000260600"/>
    <dbReference type="PeptideAtlas" id="O60266"/>
    <dbReference type="ProteomicsDB" id="3671"/>
    <dbReference type="ProteomicsDB" id="49298">
        <molecule id="O60266-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="4130">
        <property type="antibodies" value="152 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="109"/>
    <dbReference type="Ensembl" id="ENST00000260600.9">
        <molecule id="O60266-1"/>
        <property type="protein sequence ID" value="ENSP00000260600.5"/>
        <property type="gene ID" value="ENSG00000138031.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000679454.1">
        <molecule id="O60266-1"/>
        <property type="protein sequence ID" value="ENSP00000505261.1"/>
        <property type="gene ID" value="ENSG00000138031.16"/>
    </dbReference>
    <dbReference type="GeneID" id="109"/>
    <dbReference type="KEGG" id="hsa:109"/>
    <dbReference type="MANE-Select" id="ENST00000679454.1">
        <property type="protein sequence ID" value="ENSP00000505261.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004036.5"/>
        <property type="RefSeq protein sequence ID" value="NP_004027.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002rfs.5">
        <molecule id="O60266-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:234"/>
    <dbReference type="ClinPGx" id="PA164741137"/>
    <dbReference type="CTD" id="109"/>
    <dbReference type="DisGeNET" id="109"/>
    <dbReference type="GeneCards" id="ADCY3"/>
    <dbReference type="HGNC" id="HGNC:234">
        <property type="gene designation" value="ADCY3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000138031">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCY3"/>
    <dbReference type="MIM" id="600291">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="601665">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="617885">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000138031"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000138031"/>
    <dbReference type="eggNOG" id="KOG3619">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156549"/>
    <dbReference type="HOGENOM" id="CLU_001072_2_4_1"/>
    <dbReference type="InParanoid" id="O60266"/>
    <dbReference type="OrthoDB" id="10261550at2759"/>
    <dbReference type="PAN-GO" id="O60266">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O60266"/>
    <dbReference type="PathwayCommons" id="O60266"/>
    <dbReference type="Reactome" id="R-HSA-163359">
        <property type="pathway name" value="Glucagon signaling in metabolic regulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163615">
        <property type="pathway name" value="PKA activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-164378">
        <property type="pathway name" value="PKA activation in glucagon signalling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170660">
        <property type="pathway name" value="Adenylate cyclase activating pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170670">
        <property type="pathway name" value="Adenylate cyclase inhibitory pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-381753">
        <property type="pathway name" value="Olfactory Signaling Pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418555">
        <property type="pathway name" value="G alpha (s) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418594">
        <property type="pathway name" value="G alpha (i) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418597">
        <property type="pathway name" value="G alpha (z) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-432040">
        <property type="pathway name" value="Vasopressin regulates renal water homeostasis via Aquaporins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5610787">
        <property type="pathway name" value="Hedgehog 'off' state"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9634597">
        <property type="pathway name" value="GPER1 signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9660821">
        <property type="pathway name" value="ADORA2B mediated anti-inflammatory cytokines production"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9664323">
        <property type="pathway name" value="FCGR3A-mediated IL10 synthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9856530">
        <property type="pathway name" value="High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells"/>
    </dbReference>
    <dbReference type="SignaLink" id="O60266"/>
    <dbReference type="SIGNOR" id="O60266"/>
    <dbReference type="Agora" id="ENSG00000138031"/>
    <dbReference type="BioGRID-ORCS" id="109">
        <property type="hits" value="20 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCY3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADCY3"/>
    <dbReference type="GenomeRNAi" id="109"/>
    <dbReference type="Pharos" id="O60266">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O60266"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="O60266">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000138031">
        <property type="expression patterns" value="Expressed in tibial nerve and 200 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O60266">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060170">
        <property type="term" value="C:ciliary membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="ARUK-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004016">
        <property type="term" value="F:adenylate cyclase activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005516">
        <property type="term" value="F:calmodulin binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007340">
        <property type="term" value="P:acrosome reaction"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007189">
        <property type="term" value="P:adenylate cyclase-activating G protein-coupled receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006171">
        <property type="term" value="P:cAMP biosynthetic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904322">
        <property type="term" value="P:cellular response to forskolin"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071377">
        <property type="term" value="P:cellular response to glucagon stimulus"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030317">
        <property type="term" value="P:flagellated sperm motility"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035556">
        <property type="term" value="P:intracellular signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008355">
        <property type="term" value="P:olfactory learning"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003091">
        <property type="term" value="P:renal water homeostasis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007608">
        <property type="term" value="P:sensory perception of smell"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007165">
        <property type="term" value="P:signal transduction"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007338">
        <property type="term" value="P:single fertilization"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097700">
        <property type="term" value="P:vascular endothelial cell response to laminar fluid shear stress"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="CDD" id="cd07302">
        <property type="entry name" value="CHD"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.1230:FF:000006">
        <property type="entry name" value="Adenylate cyclase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.70.1230:FF:000009">
        <property type="entry name" value="Adenylate cyclase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.70.1230">
        <property type="entry name" value="Nucleotide cyclase"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001054">
        <property type="entry name" value="A/G_cyclase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018297">
        <property type="entry name" value="A/G_cyclase_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR032628">
        <property type="entry name" value="AC_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR030672">
        <property type="entry name" value="Adcy"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR029787">
        <property type="entry name" value="Nucleotide_cyclase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45627">
        <property type="entry name" value="ADENYLATE CYCLASE TYPE 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45627:SF30">
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            <taxon>Mammalia</taxon>
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    <reference key="1">
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            <title>Cloning and expression of human adenylyl cyclase type VI in normal thyroid tissues.</title>
            <authorList>
                <person name="Wicker R."/>
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            </authorList>
            <dbReference type="PubMed" id="10978539"/>
            <dbReference type="DOI" id="10.1016/s0167-4781(00)00187-1"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Thyroid</tissue>
        </source>
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    <reference key="2">
        <citation type="journal article" date="1997" name="DNA Res." volume="4" first="307" last="313">
            <title>Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Ishikawa K."/>
                <person name="Nagase T."/>
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                <person name="Seki N."/>
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                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="9455477"/>
            <dbReference type="DOI" id="10.1093/dnares/4.5.307"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2002" name="DNA Res." volume="9" first="99" last="106">
            <title>Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.</title>
            <authorList>
                <person name="Nakajima D."/>
                <person name="Okazaki N."/>
                <person name="Yamakawa H."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
                <person name="Nagase T."/>
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            <dbReference type="PubMed" id="12168954"/>
            <dbReference type="DOI" id="10.1093/dnares/9.3.99"/>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Retina</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1993" name="Biochem. Biophys. Res. Commun." volume="192" first="311" last="318">
            <title>A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line.</title>
            <authorList>
                <person name="Hellevuo K."/>
                <person name="Yoshimura M."/>
                <person name="Kao M."/>
                <person name="Hoffman P.L."/>
                <person name="Cooper D.M.F."/>
                <person name="Tabakoff B."/>
            </authorList>
            <dbReference type="PubMed" id="8476432"/>
            <dbReference type="DOI" id="10.1006/bbrc.1993.1415"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1040-1103</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Mol. Pharmacol." volume="66" first="921" last="928">
            <title>Raf kinase activation of adenylyl cyclases: isoform-selective regulation.</title>
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                <person name="Ding Q."/>
                <person name="Gros R."/>
                <person name="Gray I.D."/>
                <person name="Taussig R."/>
                <person name="Ferguson S.S."/>
                <person name="Feldman R.D."/>
            </authorList>
            <dbReference type="PubMed" id="15385642"/>
            <dbReference type="DOI" id="10.1124/mol.66.4.921"/>
        </citation>
        <scope>INTERACTION WITH RAF1</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="J. Proteome Res." volume="7" first="526" last="534">
            <title>Phosphoproteome of resting human platelets.</title>
            <authorList>
                <person name="Zahedi R.P."/>
                <person name="Lewandrowski U."/>
                <person name="Wiesner J."/>
                <person name="Wortelkamp S."/>
                <person name="Moebius J."/>
                <person name="Schuetz C."/>
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            </authorList>
            <dbReference type="PubMed" id="18088087"/>
            <dbReference type="DOI" id="10.1021/pr0704130"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Platelet</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
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            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
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    <reference key="9">
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                <person name="Di Palma S."/>
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            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-576</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2007" name="Arterioscler. Thromb. Vasc. Biol." volume="27" first="2657" last="2663">
            <title>Increased enzyme activity and beta-adrenergic mediated vasodilation in subjects expressing a single-nucleotide variant of human adenylyl cyclase 6.</title>
            <authorList>
                <person name="Gros R."/>
                <person name="Van Uum S."/>
                <person name="Hutchinson-Jaffe A."/>
                <person name="Ding Q."/>
                <person name="Pickering J.G."/>
                <person name="Hegele R.A."/>
                <person name="Feldman R.D."/>
            </authorList>
            <dbReference type="PubMed" id="17916776"/>
            <dbReference type="DOI" id="10.1161/atvbaha.107.145557"/>
        </citation>
        <scope>VARIANT SER-674</scope>
        <scope>CHARACTERIZATION OF VARIANT SER-674</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="294" last="302">
            <title>Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits.</title>
            <authorList>
                <person name="Gao X."/>
                <person name="Sadana R."/>
                <person name="Dessauer C.W."/>
                <person name="Patel T.B."/>
            </authorList>
            <dbReference type="PubMed" id="17110384"/>
            <dbReference type="DOI" id="10.1074/jbc.m607522200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH GNAS; GNB1 AND GNG2</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2014" name="Hum. Mol. Genet." volume="23" first="2279" last="2289">
            <title>Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects.</title>
            <authorList>
                <person name="Laquerriere A."/>
                <person name="Maluenda J."/>
                <person name="Camus A."/>
                <person name="Fontenas L."/>
                <person name="Dieterich K."/>
                <person name="Nolent F."/>
                <person name="Zhou J."/>
                <person name="Monnier N."/>
                <person name="Latour P."/>
                <person name="Gentil D."/>
                <person name="Heron D."/>
                <person name="Desguerres I."/>
                <person name="Landrieu P."/>
                <person name="Beneteau C."/>
                <person name="Delaporte B."/>
                <person name="Bellesme C."/>
                <person name="Baumann C."/>
                <person name="Capri Y."/>
                <person name="Goldenberg A."/>
                <person name="Lyonnet S."/>
                <person name="Bonneau D."/>
                <person name="Estournet B."/>
                <person name="Quijano-Roy S."/>
                <person name="Francannet C."/>
                <person name="Odent S."/>
                <person name="Saint-Frison M.H."/>
                <person name="Sigaudy S."/>
                <person name="Figarella-Branger D."/>
                <person name="Gelot A."/>
                <person name="Mussini J.M."/>
                <person name="Lacroix C."/>
                <person name="Drouin-Garraud V."/>
                <person name="Malinge M.C."/>
                <person name="Attie-Bitach T."/>
                <person name="Bessieres B."/>
                <person name="Bonniere M."/>
                <person name="Encha-Razavi F."/>
                <person name="Beaufrere A.M."/>
                <person name="Khung-Savatovsky S."/>
                <person name="Perez M.J."/>
                <person name="Vasiljevic A."/>
                <person name="Mercier S."/>
                <person name="Roume J."/>
                <person name="Trestard L."/>
                <person name="Saugier-Veber P."/>
                <person name="Cordier M.P."/>
                <person name="Layet V."/>
                <person name="Legendre M."/>
                <person name="Vigouroux-Castera A."/>
                <person name="Lunardi J."/>
                <person name="Bayes M."/>
                <person name="Jouk P.S."/>
                <person name="Rigonnot L."/>
                <person name="Granier M."/>
                <person name="Sternberg D."/>
                <person name="Warszawski J."/>
                <person name="Gut I."/>
                <person name="Gonzales M."/>
                <person name="Tawk M."/>
                <person name="Melki J."/>
            </authorList>
            <dbReference type="PubMed" id="24319099"/>
            <dbReference type="DOI" id="10.1093/hmg/ddt618"/>
        </citation>
        <scope>INVOLVEMENT IN LCCS8</scope>
        <scope>VARIANT LCCS8 CYS-1116</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 10 11">Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17110384, PubMed:17916776). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). Contributes to bone cell responses to mechanical stimuli (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 11">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="9">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="9">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="2">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3 4 5 10 11">Activated by G(s) G alpha protein GNAS (By similarity). Inhibited by G(i) G alpha protein GNAI1 (By similarity). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Activated by forskolin (PubMed:17110384, PubMed:17916776). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Phosphorylation by RAF1 results in its activation (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 9 10">Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (PubMed:17110384).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Cell membrane</location>
            <topology evidence="15">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Cilium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Stereocilium</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O43306-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O43306-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_000244"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Detected in peripheral blood mononuclear leukocytes (at protein level) (PubMed:17916776). Detected in thyroid (PubMed:10978539).</text>
    </comment>
    <comment type="domain">
        <text evidence="1">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5">Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA at Ser-662 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919 inhibits catalytic activity.</text>
    </comment>
    <comment type="disease" evidence="12">
        <disease id="DI-04380">
            <name>Lethal congenital contracture syndrome 8</name>
            <acronym>LCCS8</acronym>
            <description>A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS8 is an axoglial form of arthrogryposis multiplex congenita, characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period.</description>
            <dbReference type="MIM" id="616287"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <comment type="sequence caution" evidence="15">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA24852" version="2"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="10 11"/>
    <dbReference type="EMBL" id="AF250226">
        <property type="protein sequence ID" value="AAF82478.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB007882">
        <property type="protein sequence ID" value="BAA24852.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064923">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8767.1">
        <molecule id="O43306-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8768.1">
        <molecule id="O43306-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001377759.1">
        <molecule id="O43306-2"/>
        <property type="nucleotide sequence ID" value="NM_001390830.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001377760.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_001390831.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399748.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_001412819.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399749.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_001412820.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399750.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_001412821.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001399751.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_001412822.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056085.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="NM_015270.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_006719273.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="XM_006719210.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047284129.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="XM_047428173.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054226875.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="XM_054370900.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054226876.1">
        <molecule id="O43306-1"/>
        <property type="nucleotide sequence ID" value="XM_054370901.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O43306"/>
    <dbReference type="SMR" id="O43306"/>
    <dbReference type="BioGRID" id="106625">
        <property type="interactions" value="70"/>
    </dbReference>
    <dbReference type="FunCoup" id="O43306">
        <property type="interactions" value="2471"/>
    </dbReference>
    <dbReference type="IntAct" id="O43306">
        <property type="interactions" value="52"/>
    </dbReference>
    <dbReference type="MINT" id="O43306"/>
    <dbReference type="STRING" id="9606.ENSP00000311405"/>
    <dbReference type="BindingDB" id="O43306"/>
    <dbReference type="ChEMBL" id="CHEMBL2097167"/>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="GuidetoPHARMACOLOGY" id="1283"/>
    <dbReference type="GlyCosmos" id="O43306">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O43306">
        <property type="glycosylation" value="3 sites, 1 N-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O43306"/>
    <dbReference type="PhosphoSitePlus" id="O43306"/>
    <dbReference type="SwissPalm" id="O43306"/>
    <dbReference type="BioMuta" id="ADCY6"/>
    <dbReference type="jPOST" id="O43306"/>
    <dbReference type="MassIVE" id="O43306"/>
    <dbReference type="PaxDb" id="9606-ENSP00000311405"/>
    <dbReference type="PeptideAtlas" id="O43306"/>
    <dbReference type="ProteomicsDB" id="48880">
        <molecule id="O43306-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48881">
        <molecule id="O43306-2"/>
    </dbReference>
    <dbReference type="Pumba" id="O43306"/>
    <dbReference type="Antibodypedia" id="4336">
        <property type="antibodies" value="189 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="112"/>
    <dbReference type="Ensembl" id="ENST00000307885.4">
        <molecule id="O43306-1"/>
        <property type="protein sequence ID" value="ENSP00000311405.4"/>
        <property type="gene ID" value="ENSG00000174233.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000357869.8">
        <molecule id="O43306-1"/>
        <property type="protein sequence ID" value="ENSP00000350536.4"/>
        <property type="gene ID" value="ENSG00000174233.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000550422.5">
        <molecule id="O43306-2"/>
        <property type="protein sequence ID" value="ENSP00000446730.1"/>
        <property type="gene ID" value="ENSG00000174233.13"/>
    </dbReference>
    <dbReference type="GeneID" id="112"/>
    <dbReference type="KEGG" id="hsa:112"/>
    <dbReference type="MANE-Select" id="ENST00000357869.8">
        <property type="protein sequence ID" value="ENSP00000350536.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_015270.5"/>
        <property type="RefSeq protein sequence ID" value="NP_056085.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001rsh.5">
        <molecule id="O43306-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:237"/>
    <dbReference type="ClinPGx" id="PA27"/>
    <dbReference type="CTD" id="112"/>
    <dbReference type="DisGeNET" id="112"/>
    <dbReference type="GeneCards" id="ADCY6"/>
    <dbReference type="HGNC" id="HGNC:237">
        <property type="gene designation" value="ADCY6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000174233">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADCY6"/>
    <dbReference type="MIM" id="600294">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="616287">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000174233"/>
    <dbReference type="Orphanet" id="2680">
        <property type="disease" value="Hypomyelination neuropathy-arthrogryposis syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000174233"/>
    <dbReference type="eggNOG" id="KOG3619">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155687"/>
    <dbReference type="HOGENOM" id="CLU_001072_2_0_1"/>
    <dbReference type="InParanoid" id="O43306"/>
    <dbReference type="OMA" id="CEGTMPT"/>
    <dbReference type="OrthoDB" id="2107370at2759"/>
    <dbReference type="PAN-GO" id="O43306">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O43306"/>
    <dbReference type="PathwayCommons" id="O43306"/>
    <dbReference type="Reactome" id="R-HSA-163359">
        <property type="pathway name" value="Glucagon signaling in metabolic regulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163615">
        <property type="pathway name" value="PKA activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-164378">
        <property type="pathway name" value="PKA activation in glucagon signalling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170660">
        <property type="pathway name" value="Adenylate cyclase activating pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170670">
        <property type="pathway name" value="Adenylate cyclase inhibitory pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-381676">
        <property type="pathway name" value="Glucagon-like Peptide-1 (GLP1) regulates insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-400042">
        <property type="pathway name" value="Adrenaline,noradrenaline inhibits insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418555">
        <property type="pathway name" value="G alpha (s) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418594">
        <property type="pathway name" value="G alpha (i) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418597">
        <property type="pathway name" value="G alpha (z) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-432040">
        <property type="pathway name" value="Vasopressin regulates renal water homeostasis via Aquaporins"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5610787">
        <property type="pathway name" value="Hedgehog 'off' state"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9634597">
        <property type="pathway name" value="GPER1 signaling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9660821">
        <property type="pathway name" value="ADORA2B mediated anti-inflammatory cytokines production"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9664323">
        <property type="pathway name" value="FCGR3A-mediated IL10 synthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9856530">
        <property type="pathway name" value="High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells"/>
    </dbReference>
    <dbReference type="SignaLink" id="O43306"/>
    <dbReference type="SIGNOR" id="O43306"/>
    <dbReference type="Agora" id="ENSG00000174233"/>
    <dbReference type="BioGRID-ORCS" id="112">
        <property type="hits" value="20 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="232F8A39">
        <property type="entry name" value="P-body"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADCY6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADCY6"/>
    <dbReference type="GenomeRNAi" id="112"/>
    <dbReference type="Pharos" id="O43306">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:O43306"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="O43306">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000174233">
        <property type="expression patterns" value="Expressed in apex of heart and 129 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O43306">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032420">
        <property type="term" value="C:stereocilium"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004016">
        <property type="term" value="F:adenylate cyclase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019901">
        <property type="term" value="F:protein kinase binding"/>
        <property type="evidence" value="ECO:0000250"/>
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<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="227" xmlns="https://uniprot.org/uniprot">
    <accession>P35611</accession>
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    <accession>D3DVR4</accession>
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    <accession>Q13734</accession>
    <accession>Q14729</accession>
    <accession>Q16156</accession>
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    <accession>Q9UJB6</accession>
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        <recommendedName>
            <fullName>Alpha-adducin</fullName>
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        <alternativeName>
            <fullName>Erythrocyte adducin subunit alpha</fullName>
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        <name type="primary">ADD1</name>
        <name type="synonym">ADDA</name>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="J. Cell Biol." volume="115" first="665" last="675">
            <title>Primary structure and domain organization of human alpha and beta adducin.</title>
            <authorList>
                <person name="Joshi R.L."/>
                <person name="Gilligan D.M."/>
                <person name="Otto E."/>
                <person name="McLaughlin T."/>
                <person name="Bennett V.D."/>
            </authorList>
            <dbReference type="PubMed" id="1840603"/>
            <dbReference type="DOI" id="10.1083/jcb.115.3.665"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PROTEIN SEQUENCE OF 24-36; 41-47; 516-569 AND 722-729</scope>
        <scope>VARIANT CYS-586</scope>
        <source>
            <tissue>Reticulocyte</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1992" name="Hum. Mol. Genet." volume="1" first="669" last="675">
            <title>Cloning and mapping of the alpha-adducin gene close to D4S95 and assessment of its relationship to Huntington disease.</title>
            <authorList>
                <person name="Goldberg Y.P."/>
                <person name="Lin B.Y."/>
                <person name="Andrew S.E."/>
                <person name="Nasir J."/>
                <person name="Graham R."/>
                <person name="Glaves M.L."/>
                <person name="Hutchinson G."/>
                <person name="Theilmann J."/>
                <person name="Ginzinger D.G."/>
                <person name="Schappert K."/>
            </authorList>
            <dbReference type="PubMed" id="1284592"/>
            <dbReference type="DOI" id="10.1093/hmg/1.9.669"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="Genomics" volume="25" first="93" last="99">
            <title>Genomic organization of the human alpha-adducin gene and its alternately spliced isoforms.</title>
            <authorList>
                <person name="Lin B."/>
                <person name="Nasir J."/>
                <person name="McDonald H."/>
                <person name="Graham R."/>
                <person name="Rommens J.M."/>
                <person name="Goldberg Y.P."/>
                <person name="Hayden M.R."/>
            </authorList>
            <dbReference type="PubMed" id="7774961"/>
            <dbReference type="DOI" id="10.1016/0888-7543(95)80113-z"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-358; SER-465; SER-707; SER-710 AND SER-714</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-353; SER-355; SER-358; SER-366; SER-431 AND SER-465</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-59; SER-64; SER-358; SER-678; SER-707 AND SER-716</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="1998" name="Hypertension" volume="32" first="138" last="143">
            <title>Human alpha-adducin gene, blood pressure, and sodium metabolism.</title>
            <authorList>
                <person name="Kamitani A."/>
                <person name="Wong Z.Y."/>
                <person name="Fraser R."/>
                <person name="Davies D.L."/>
                <person name="Connor J.M."/>
                <person name="Foy C.J."/>
                <person name="Watt G.C."/>
                <person name="Harrap S.B."/>
            </authorList>
            <dbReference type="PubMed" id="9674650"/>
            <dbReference type="DOI" id="10.1161/01.hyp.32.1.138"/>
        </citation>
        <scope>VARIANT TRP-460</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="22" first="239" last="247">
            <title>Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.</title>
            <authorList>
                <person name="Halushka M.K."/>
                <person name="Fan J.-B."/>
                <person name="Bentley K."/>
                <person name="Hsie L."/>
                <person name="Shen N."/>
                <person name="Weder A."/>
                <person name="Cooper R."/>
                <person name="Lipshutz R."/>
                <person name="Chakravarti A."/>
            </authorList>
            <dbReference type="PubMed" id="10391210"/>
            <dbReference type="DOI" id="10.1038/10297"/>
        </citation>
        <scope>VARIANTS TRP-460 AND CYS-586</scope>
    </reference>
    <comment type="function">
        <text>Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.</text>
    </comment>
    <comment type="subunit">
        <text>Heterodimer of an alpha and a beta subunit or an alpha and a gamma subunit.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809187">
            <id>P35611</id>
        </interactant>
        <interactant intactId="EBI-16777913">
            <id>P35612</id>
            <label>ADD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809187">
            <id>P35611</id>
        </interactant>
        <interactant intactId="EBI-6875961">
            <id>P02489</id>
            <label>CRYAA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809187">
            <id>P35611</id>
        </interactant>
        <interactant intactId="EBI-1307">
            <id>Q13153</id>
            <label>PAK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2809187">
            <id>P35611</id>
        </interactant>
        <interactant intactId="EBI-716037">
            <id>P22670</id>
            <label>RFX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10206868">
            <id>P35611-5</id>
        </interactant>
        <interactant intactId="EBI-740641">
            <id>Q9NP66</id>
            <label>HMG20A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Peripheral membrane protein</topology>
            <orientation>Cytoplasmic side</orientation>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P35611-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P35611-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_000175 VSP_000176"/>
        </isoform>
        <isoform>
            <id>P35611-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_000174"/>
        </isoform>
        <isoform>
            <id>P35611-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_054420 VSP_000175 VSP_000176"/>
        </isoform>
        <isoform>
            <id>P35611-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_055402 VSP_055403"/>
        </isoform>
        <isoform>
            <id>P35611-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_000174 VSP_000175 VSP_000176"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed in all tissues. Found in much higher levels in reticulocytes than the beta subunit.</text>
    </comment>
    <comment type="domain">
        <text>Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the aldolase class II family. Adducin subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="12">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAA98970" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X58141">
        <property type="protein sequence ID" value="CAA41149.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L07261">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29296">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29286">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29287">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29289">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29290">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29291">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29292">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29293">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29294">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29295">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29297">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L29298">
        <property type="protein sequence ID" value="AAB05645.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK295457">
        <property type="protein sequence ID" value="BAG58391.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z74617">
        <property type="protein sequence ID" value="CAA98970.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Z68280">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390065">
        <property type="protein sequence ID" value="CAM21299.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121750">
        <property type="protein sequence ID" value="CAM21299.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX465861">
        <property type="protein sequence ID" value="CAM21299.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX465861">
        <property type="protein sequence ID" value="CAM25274.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121750">
        <property type="protein sequence ID" value="CAM25274.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390065">
        <property type="protein sequence ID" value="CAM25274.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121750">
        <property type="protein sequence ID" value="CAM28230.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390065">
        <property type="protein sequence ID" value="CAM28230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX465861">
        <property type="protein sequence ID" value="CAM28230.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121750">
        <property type="protein sequence ID" value="CAM28231.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390065">
        <property type="protein sequence ID" value="CAM28231.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX465861">
        <property type="protein sequence ID" value="CAM28231.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL121750">
        <property type="protein sequence ID" value="CAM28232.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL390065">
        <property type="protein sequence ID" value="CAM28232.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX465861">
        <property type="protein sequence ID" value="CAM28232.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82498.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82499.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82501.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82502.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82503.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82504.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471131">
        <property type="protein sequence ID" value="EAW82505.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC042998">
        <property type="protein sequence ID" value="AAH42998.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AH004561">
        <property type="protein sequence ID" value="AAB30914.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3363.1">
        <molecule id="P35611-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3364.1">
        <molecule id="P35611-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43205.1">
        <molecule id="P35611-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS75094.1">
        <molecule id="P35611-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS93468.1">
        <molecule id="P35611-2"/>
    </dbReference>
    <dbReference type="PIR" id="S18207">
        <property type="entry name" value="S18207"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001110.2">
        <molecule id="P35611-1"/>
        <property type="nucleotide sequence ID" value="NM_001119.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273574.1">
        <molecule id="P35611-4"/>
        <property type="nucleotide sequence ID" value="NM_001286645.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001341683.1">
        <molecule id="P35611-1"/>
        <property type="nucleotide sequence ID" value="NM_001354754.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001341684.1">
        <molecule id="P35611-1"/>
        <property type="nucleotide sequence ID" value="NM_001354755.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001341686.1">
        <molecule id="P35611-2"/>
        <property type="nucleotide sequence ID" value="NM_001354757.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001341687.1">
        <molecule id="P35611-2"/>
        <property type="nucleotide sequence ID" value="NM_001354758.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001341688.1">
        <molecule id="P35611-4"/>
        <property type="nucleotide sequence ID" value="NM_001354759.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_054908.2">
        <molecule id="P35611-3"/>
        <property type="nucleotide sequence ID" value="NM_014189.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_054909.2">
        <molecule id="P35611-2"/>
        <property type="nucleotide sequence ID" value="NM_014190.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_789771.1">
        <molecule id="P35611-6"/>
        <property type="nucleotide sequence ID" value="NM_176801.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016863193.1">
        <molecule id="P35611-3"/>
        <property type="nucleotide sequence ID" value="XM_017007704.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016863195.1">
        <molecule id="P35611-1"/>
        <property type="nucleotide sequence ID" value="XM_017007706.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016863198.1">
        <molecule id="P35611-2"/>
        <property type="nucleotide sequence ID" value="XM_017007709.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024309655.1">
        <molecule id="P35611-6"/>
        <property type="nucleotide sequence ID" value="XM_024453887.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204844.1">
        <molecule id="P35611-3"/>
        <property type="nucleotide sequence ID" value="XM_054348869.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204847.1">
        <molecule id="P35611-1"/>
        <property type="nucleotide sequence ID" value="XM_054348872.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204848.1">
        <molecule id="P35611-6"/>
        <property type="nucleotide sequence ID" value="XM_054348873.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054204849.1">
        <molecule id="P35611-2"/>
        <property type="nucleotide sequence ID" value="XM_054348874.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P35611"/>
    <dbReference type="SMR" id="P35611"/>
    <dbReference type="BioGRID" id="106631">
        <property type="interactions" value="176"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2638">
        <property type="entry name" value="Adducin complex, alpha-beta variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2643">
        <property type="entry name" value="Adducin complex, alpha-gamma variant"/>
    </dbReference>
    <dbReference type="FunCoup" id="P35611">
        <property type="interactions" value="2715"/>
    </dbReference>
    <dbReference type="IntAct" id="P35611">
        <property type="interactions" value="85"/>
    </dbReference>
    <dbReference type="MINT" id="P35611"/>
    <dbReference type="STRING" id="9606.ENSP00000264758"/>
    <dbReference type="GlyCosmos" id="P35611">
        <property type="glycosylation" value="7 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P35611">
        <property type="glycosylation" value="10 sites, 2 O-linked glycans (8 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P35611"/>
    <dbReference type="MetOSite" id="P35611"/>
    <dbReference type="PhosphoSitePlus" id="P35611"/>
    <dbReference type="SwissPalm" id="P35611"/>
    <dbReference type="BioMuta" id="ADD1"/>
    <dbReference type="DMDM" id="12644231"/>
    <dbReference type="jPOST" id="P35611"/>
    <dbReference type="MassIVE" id="P35611"/>
    <dbReference type="PaxDb" id="9606-ENSP00000264758"/>
    <dbReference type="PeptideAtlas" id="P35611"/>
    <dbReference type="ProteomicsDB" id="289"/>
    <dbReference type="ProteomicsDB" id="55102">
        <molecule id="P35611-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55103">
        <molecule id="P35611-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55104">
        <molecule id="P35611-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="70300"/>
    <dbReference type="Pumba" id="P35611"/>
    <dbReference type="Antibodypedia" id="4065">
        <property type="antibodies" value="747 antibodies from 41 providers"/>
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    <dbReference type="DNASU" id="118"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="1">
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            <position position="714"/>
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            <position position="716"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA and PKC" evidence="7">
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            <position position="535"/>
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            <position position="445"/>
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            <position position="480"/>
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    <feature type="sequence conflict" description="In Ref. 3; AAB05645." evidence="12" ref="3">
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    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10209029"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="10391210"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="1840603"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="8810272"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="9674650"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="1284592"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="18088087"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="737" mass="80955" checksum="DF13AB30B12F20B6" modified="2000-12-01" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>P51828</accession>
    <accession>A0AVA6</accession>
    <name>ADCY7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">Adenylate cyclase type 7</fullName>
            <ecNumber evidence="16 17">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 7</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylate cyclase type VII</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adenylyl cyclase 7</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="14">Cyclic di-AMP synthase ADCY7</fullName>
            <ecNumber evidence="3">2.7.7.85</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="18" type="primary">ADCY7</name>
        <name evidence="13" type="synonym">KIAA0037</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="DNA Res." volume="1" first="27" last="35">
            <title>Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.</title>
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                <person name="Nomura N."/>
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                <person name="Sazuka T."/>
                <person name="Tanaka A."/>
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            <dbReference type="PubMed" id="7584026"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nature" volume="432" first="988" last="994">
            <title>The sequence and analysis of duplication-rich human chromosome 16.</title>
            <authorList>
                <person name="Martin J."/>
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                <person name="She X."/>
                <person name="Xie G."/>
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                <person name="Black S."/>
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                <person name="Campbell C.S."/>
                <person name="Campbell M.L."/>
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                <person name="Caoile C."/>
                <person name="Challacombe J.F."/>
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                <person name="Chertkov O."/>
                <person name="Chi H.C."/>
                <person name="Christensen M."/>
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                <person name="Detter J.C."/>
                <person name="Dickson M."/>
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                <person name="Flowers D."/>
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                <person name="Grigoriev I."/>
                <person name="Groza M."/>
                <person name="Hammon N."/>
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                <person name="Haydu L."/>
                <person name="Hildebrand C.E."/>
                <person name="Huang W."/>
                <person name="Israni S."/>
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                <person name="Jewett P.B."/>
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                <person name="Kobayashi A."/>
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                <person name="Ludeman T."/>
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                <person name="Pitluck S."/>
                <person name="Pollard M."/>
                <person name="Predki P."/>
                <person name="Parson-Quintana B."/>
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                <person name="Ricke D.O."/>
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                <person name="Shough T."/>
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                <person name="Stalvey M."/>
                <person name="Sutherland R.D."/>
                <person name="Tapia R."/>
                <person name="Tesmer J.G."/>
                <person name="Thayer N."/>
                <person name="Thompson L.S."/>
                <person name="Tice H."/>
                <person name="Torney D.C."/>
                <person name="Tran-Gyamfi M."/>
                <person name="Tsai M."/>
                <person name="Ulanovsky L.E."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="White P.S."/>
                <person name="Williams A.L."/>
                <person name="Wills P.L."/>
                <person name="Wu J.-R."/>
                <person name="Wu K."/>
                <person name="Yang J."/>
                <person name="DeJong P."/>
                <person name="Bruce D."/>
                <person name="Doggett N.A."/>
                <person name="Deaven L."/>
                <person name="Schmutz J."/>
                <person name="Grimwood J."/>
                <person name="Richardson P."/>
                <person name="Rokhsar D.S."/>
                <person name="Eichler E.E."/>
                <person name="Gilna P."/>
                <person name="Lucas S.M."/>
                <person name="Myers R.M."/>
                <person name="Rubin E.M."/>
                <person name="Pennacchio L.A."/>
            </authorList>
            <dbReference type="PubMed" id="15616553"/>
            <dbReference type="DOI" id="10.1038/nature03187"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2001" name="J. Biol. Chem." volume="276" first="8500" last="8506">
            <title>The regulation of type 7 adenylyl cyclase by its C1b region and Escherichia coli peptidylprolyl isomerase, SlyD.</title>
            <authorList>
                <person name="Yan S.Z."/>
                <person name="Beeler J.A."/>
                <person name="Chen Y."/>
                <person name="Shelton R.K."/>
                <person name="Tang W.J."/>
            </authorList>
            <dbReference type="PubMed" id="11113152"/>
            <dbReference type="DOI" id="10.1074/jbc.m010361200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="4552" last="4560">
            <title>Ethanol-induced phosphorylation and potentiation of the activity of type 7 adenylyl cyclase. Involvement of protein kinase C delta.</title>
            <authorList>
                <person name="Nelson E.J."/>
                <person name="Hellevuo K."/>
                <person name="Yoshimura M."/>
                <person name="Tabakoff B."/>
            </authorList>
            <dbReference type="PubMed" id="12454008"/>
            <dbReference type="DOI" id="10.1074/jbc.m210386200"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="15463" last="15471">
            <title>A soluble C1b protein and its regulation of soluble type 7 adenylyl cyclase.</title>
            <authorList>
                <person name="Beeler J.A."/>
                <person name="Yan S.Z."/>
                <person name="Bykov S."/>
                <person name="Murza A."/>
                <person name="Asher S."/>
                <person name="Tang W.J."/>
            </authorList>
            <dbReference type="PubMed" id="15581358"/>
            <dbReference type="DOI" id="10.1021/bi049088+"/>
        </citation>
        <scope>REGION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="23429" last="23439">
            <title>Regulation of cAMP responses by the G12/13 pathway converges on adenylyl cyclase VII.</title>
            <authorList>
                <person name="Jiang L.I."/>
                <person name="Collins J."/>
                <person name="Davis R."/>
                <person name="Fraser I.D."/>
                <person name="Sternweis P.C."/>
            </authorList>
            <dbReference type="PubMed" id="18541530"/>
            <dbReference type="DOI" id="10.1074/jbc.m803281200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2013" name="Mol. Pharmacol." volume="83" first="587" last="593">
            <title>Regions on adenylyl cyclase VII required for selective regulation by the G13 pathway.</title>
            <authorList>
                <person name="Jiang L.I."/>
                <person name="Wang J.E."/>
                <person name="Sternweis P.C."/>
            </authorList>
            <dbReference type="PubMed" id="23229509"/>
            <dbReference type="DOI" id="10.1124/mol.112.082446"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>REGION</scope>
        <scope>MUTAGENESIS OF 477-LYS--VAL-482; 485-THR--SER-490; 491-TRP--PRO-496; 494-ALA--HIS-499 AND 564-SER--PHE-569</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2013" name="Mol. Pharmacol." volume="84" first="476" last="486">
            <title>Prostaglandin E receptor EP1 forms a complex with dopamine D1 receptor and directs D1-induced cAMP production to adenylyl cyclase 7 through mobilizing G(betagamma) subunits in human embryonic kidney 293T cells.</title>
            <authorList>
                <person name="Ehrlich A.T."/>
                <person name="Furuyashiki T."/>
                <person name="Kitaoka S."/>
                <person name="Kakizuka A."/>
                <person name="Narumiya S."/>
            </authorList>
            <dbReference type="PubMed" id="23842570"/>
            <dbReference type="DOI" id="10.1124/mol.113.087288"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="3 7 10 11 12">Adenylate cyclase that mediates formation of both cyclic AMP (cAMP) and cyclic di-AMP (c-di-AMP) (PubMed:11113152, PubMed:18541530, PubMed:23229509). Acts as a key mediator of G protein-coupled receptor signaling by catalyzing the formation of cAMP downstream of G protein-coupled receptors (PubMed:18541530, PubMed:23229509). Functions in G protein-coupled receptor signaling cascades activated by thrombin, sphingosine 1-phosphate, dopamine and anaphylatoxin C5a (PubMed:18541530, PubMed:23229509, PubMed:23842570). Mediates regulation of cAMP synthesis through synergistic action of the G alpha protein G(s) (GNAS) with G(13) (GNA13) (PubMed:18541530, PubMed:23229509). Also involved in inflammation by acting as a diadenylate cyclase that catalyzes the condensation of 2 ATP molecules into c-di-AMP (By similarity). Following activation by TLR9, mediates formation of c-di-AMP, which directly activates NLRP3, thereby promoting assembly and maturation of the NLRP3 inflammasome (By similarity). It is also required for the optimal functions of B- and T cells during adaptive immune responses by regulating cAMP synthesis in both B- and T-cells (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="15 16 17">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>2 ATP = 3',3'-c-di-AMP + 2 diphosphate</text>
            <dbReference type="Rhea" id="RHEA:35655"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:71500"/>
            <dbReference type="EC" id="2.7.7.85"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="3">
            <dbReference type="Rhea" id="RHEA:35656"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="2">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="2">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3 8 10 11 14">Activated by G(s) G alpha protein (GNAS) (PubMed:18541530). Inhibited by G(i) G alpha protein GNAI1 (Probable). Activated by GNA13 and GNA12 (PubMed:18541530, PubMed:23229509). Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E1(1-) in a PKC-dependent manner (PubMed:12454008). Inhibited by lithium (By similarity). Activated by TLR9, promoting synthesis of cyclic di-AMP (c-di-AMP) (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Interacts with TLR9; leading to ADCY7 activation and synthesis of cyclic di-AMP (c-di-AMP).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Membrane</location>
            <topology>Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="domain">
        <text evidence="1">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="8">Phosphorylated by PRKCD.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <comment type="sequence caution" evidence="14">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA05021" version="2"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="16 17"/>
    <dbReference type="EC" id="2.7.7.85" evidence="3"/>
    <dbReference type="EMBL" id="D25538">
        <property type="protein sequence ID" value="BAA05021.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007597">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126271">
        <property type="protein sequence ID" value="AAI26272.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10741.1"/>
    <dbReference type="PIR" id="PN0453">
        <property type="entry name" value="PN0453"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001105.1">
        <property type="nucleotide sequence ID" value="NM_001114.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289510.1">
        <property type="nucleotide sequence ID" value="XM_047433554.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289511.1">
        <property type="nucleotide sequence ID" value="XM_047433555.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289512.1">
        <property type="nucleotide sequence ID" value="XM_047433556.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289513.1">
        <property type="nucleotide sequence ID" value="XM_047433557.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289514.1">
        <property type="nucleotide sequence ID" value="XM_047433558.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289515.1">
        <property type="nucleotide sequence ID" value="XM_047433559.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289516.1">
        <property type="nucleotide sequence ID" value="XM_047433560.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289517.1">
        <property type="nucleotide sequence ID" value="XM_047433561.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289518.1">
        <property type="nucleotide sequence ID" value="XM_047433562.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047289519.1">
        <property type="nucleotide sequence ID" value="XM_047433563.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235463.1">
        <property type="nucleotide sequence ID" value="XM_054379488.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235464.1">
        <property type="nucleotide sequence ID" value="XM_054379489.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235465.1">
        <property type="nucleotide sequence ID" value="XM_054379490.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235466.1">
        <property type="nucleotide sequence ID" value="XM_054379491.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235467.1">
        <property type="nucleotide sequence ID" value="XM_054379492.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235468.1">
        <property type="nucleotide sequence ID" value="XM_054379493.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235469.1">
        <property type="nucleotide sequence ID" value="XM_054379494.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054235470.1">
        <property type="nucleotide sequence ID" value="XM_054379495.1"/>
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        <location>
            <position position="781"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation. Reduces by 40% cAMP biosynthetic process in response to C5 alpha chain stimulation." evidence="11">
        <original>KMRASV</original>
        <variation>NAAIRS</variation>
        <location>
            <begin position="477"/>
            <end position="482"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces cAMP biosynthetic process in response to C5 alpha chain stimulation and more severely in response to sphingosine 1-phosphate stimulation." evidence="11">
        <original>TRYLE</original>
        <variation>NAAIR</variation>
        <location>
            <begin position="485"/>
            <end position="489"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect cAMP biosynthetic process in response to C5 alpha chain stimulation. Reduces by 40?60% cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation." evidence="11">
        <original>WGAARP</original>
        <variation>NAAIRS</variation>
        <location>
            <begin position="491"/>
            <end position="496"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect cAMP biosynthetic process in response to C5 alpha chain stimulation. Reduces by 40?60% cAMP biosynthetic process in response to sphingosine 1-phosphate stimulation." evidence="11">
        <original>ARPFAH</original>
        <variation>NAAIRS</variation>
        <location>
            <begin position="494"/>
            <end position="499"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces cAMP biosynthetic process in response to C5 alpha chain stimulation and more severely in response to sphingosine 1-phosphate stimulation." evidence="11">
        <original>SKSDDF</original>
        <variation>NAAIRS</variation>
        <location>
            <begin position="564"/>
            <end position="569"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P26769"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P30803"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P51829"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00099"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11113152"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12454008"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15581358"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="18541530"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="23229509"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="23842570"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="7584026"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="11113152"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="18541530"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="17">
        <source>
            <dbReference type="PubMed" id="23229509"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="18">
        <source>
            <dbReference type="HGNC" id="HGNC:238"/>
        </source>
    </evidence>
    <sequence length="1080" mass="120308" checksum="E33951621E281242" modified="1996-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-02-01" modified="2026-01-28" version="206" xmlns="https://uniprot.org/uniprot">
    <accession>P40145</accession>
    <name>ADCY8_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="13">Adenylate cyclase type 8</fullName>
            <ecNumber evidence="3">4.6.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ATP pyrophosphate-lyase 8</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="12">Adenylate cyclase type VIII</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="11">Adenylyl cyclase 8</fullName>
            <shortName>AC8</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Ca(2+)/calmodulin-activated adenylyl cyclase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADCY8</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="FEBS Lett." volume="351" first="109" last="113">
            <title>Molecular cloning of the human type VIII adenylyl cyclase.</title>
            <authorList>
                <person name="Defer N."/>
                <person name="Marinx O."/>
                <person name="Stengel D."/>
                <person name="Danisova A."/>
                <person name="Iourgenko V."/>
                <person name="Matsuoka I."/>
                <person name="Caput D."/>
                <person name="Hanoune J."/>
            </authorList>
            <dbReference type="PubMed" id="8076676"/>
            <dbReference type="DOI" id="10.1016/0014-5793(94)00836-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Brain stem</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1991" name="Biochem. Biophys. Res. Commun." volume="179" first="455" last="462">
            <title>Sequence of a human brain adenylyl cyclase partial cDNA: evidence for a consensus cyclase specific domain.</title>
            <authorList>
                <person name="Parma J."/>
                <person name="Stengel D."/>
                <person name="Gannage M.H."/>
                <person name="Poyard M."/>
                <person name="Barouki R."/>
                <person name="Hanoune J."/>
            </authorList>
            <dbReference type="PubMed" id="1715695"/>
            <dbReference type="DOI" id="10.1016/0006-291x(91)91392-p"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 577-1251</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2015" name="Diabetologia" volume="58" first="749" last="757">
            <title>Multilevel control of glucose homeostasis by adenylyl cyclase 8.</title>
            <authorList>
                <person name="Raoux M."/>
                <person name="Vacher P."/>
                <person name="Papin J."/>
                <person name="Picard A."/>
                <person name="Kostrzewa E."/>
                <person name="Devin A."/>
                <person name="Gaitan J."/>
                <person name="Limon I."/>
                <person name="Kas M.J."/>
                <person name="Magnan C."/>
                <person name="Lang J."/>
            </authorList>
            <dbReference type="PubMed" id="25403481"/>
            <dbReference type="DOI" id="10.1007/s00125-014-3445-z"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2006" name="Science" volume="314" first="268" last="274">
            <title>The consensus coding sequences of human breast and colorectal cancers.</title>
            <authorList>
                <person name="Sjoeblom T."/>
                <person name="Jones S."/>
                <person name="Wood L.D."/>
                <person name="Parsons D.W."/>
                <person name="Lin J."/>
                <person name="Barber T.D."/>
                <person name="Mandelker D."/>
                <person name="Leary R.J."/>
                <person name="Ptak J."/>
                <person name="Silliman N."/>
                <person name="Szabo S."/>
                <person name="Buckhaults P."/>
                <person name="Farrell C."/>
                <person name="Meeh P."/>
                <person name="Markowitz S.D."/>
                <person name="Willis J."/>
                <person name="Dawson D."/>
                <person name="Willson J.K.V."/>
                <person name="Gazdar A.F."/>
                <person name="Hartigan J."/>
                <person name="Wu L."/>
                <person name="Liu C."/>
                <person name="Parmigiani G."/>
                <person name="Park B.H."/>
                <person name="Bachman K.E."/>
                <person name="Papadopoulos N."/>
                <person name="Vogelstein B."/>
                <person name="Kinzler K.W."/>
                <person name="Velculescu V.E."/>
            </authorList>
            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
        </citation>
        <scope>VARIANT [LARGE SCALE ANALYSIS] LEU-881</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Catalyzes the formation of cAMP in response to calcium entry leadings to cAMP signaling activation that affect processes suche as synaptic plasticity and insulin secretion. Plays a role in many brain functions, such as learning, memory, drug addiction, and anxiety modulation through regulation of synaptic plasticity by modulating long-term memory and long-term potentiation (LTP) through CREB transcription factor activity modulation. Plays a central role in insulin secretion by controlling glucose homeostasis through glucagon-like peptide 1 and glucose signaling pathway and maintains insulin secretion through calcium-dependent PKA activation leading to vesicle pool replenishment. Also, allows PTGER3 to induce potentiation of PTGER4-mediated PLA2 secretion by switching from a negative to a positive regulation, during the IL1B induced-dedifferentiation of smooth muscle cells.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>ATP = 3',5'-cyclic AMP + diphosphate</text>
            <dbReference type="Rhea" id="RHEA:15389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:33019"/>
            <dbReference type="ChEBI" id="CHEBI:58165"/>
            <dbReference type="EC" id="4.6.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <cofactor evidence="3">
            <name>Mn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29035"/>
        </cofactor>
        <text evidence="2">Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex. In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable. CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1. In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient. Activated via stimulation of the GLP1R. Synergistically activated by calcium/calmodulin and GNAS. Stimulated by forskolin. Inhibited by PKA directly bound to AKAP5 at membrane raft. Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Homodimer; via transmembrane domain. Monomer. Heterodimer. Oligemer; via transmembrane domain. Interacts with PRKAR2A and AKAP5; inhibits adenylate cyclase activity through PKA phosphorylation. Interacts with PPP2CA and PPP2R1A; does not mediate the inhibitory effects of PKA on adenylate cyclase activity; interaction is dependent of catalytically active PPP2CA; antagonizes interaction with calmodulin. Interacts with AKAP5 (palmitoylated form); promotes the phosphorylation of ADCY8 after store-operated calcium entry (SOCE) stimulation at membrane raft. Interacts with ORAI1; interaction is calcium store depletion independent; interaction occurs in membrane raft; interaction increases markedly after store depletion; positively regulates SOCE-induced adenylate cyclase activity; contributes to the targeting of ADCY8 to discrete regions of the plasma membrane that are shielded from other calcium events. Interacts with STIM1. Interacts with actin; interaction is calcium independent; interaction is affected by calcium-calmodulin; interaction controls the distribution and regulation of ADCY8. Interacts with calmodulin; at rest, interacts via N-terminal domain; upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain forming an autoinhibitory complex; fully calcium-saturated calmodulin leaves the N-terminal domain, binding solely to the C-terminal domain leading to dissociation of autoinhibitory complex and resulting in activation of adenylate cyclase; antagonizes interaction with PPP2CA; interaction is calcium dependent. Interacts with PPP2R5D.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cell membrane</location>
            <topology evidence="4">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Basolateral cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Apical cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Synapse</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Dendrite</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cell projection</location>
            <location evidence="4">Axon</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Presynaptic cell membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Postsynaptic density</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Membrane raft</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <location evidence="3">Coated pit</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Cytoplasmic vesicle</location>
            <location evidence="3">Clathrin-coated vesicle membrane</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <location evidence="3">Caveola</location>
        </subcellularLocation>
        <text evidence="3 4">Localized to dendritic arbors (By similarity). Monomeric N-glycosylated species localizes in membrane raft. In contrast, monomeric unglycosylated forms are enriched in clathrin-coated pits and vesicles. Dimers are also localized outside of membrane rafts. Membrane raft localization and integrity is indispensable for CCE-stimulated adenylate cyclase activity (By similarity).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 10">Detected in brain cortex (PubMed:1715695). Expressed in islet (PubMed:25403481).</text>
    </comment>
    <comment type="domain">
        <text evidence="1 3">The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly. The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Phosphorylated by PKA; mediates inhibition of adenylate cyclase activity at membrane raft; does not influence either CALM1 or PPP2CA interaction with ADCY8.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">N-glycosylated; N-glycosylation is responsible for raft-targeting; is not necessary for CCE-stimulated adenylate cyclase activity.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.</text>
    </comment>
    <dbReference type="EC" id="4.6.1.1" evidence="3"/>
    <dbReference type="EMBL" id="Z35309">
        <property type="protein sequence ID" value="CAA84552.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M83533">
        <property type="protein sequence ID" value="AAA35523.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6363.1"/>
    <dbReference type="PIR" id="PQ0227">
        <property type="entry name" value="PQ0227"/>
    </dbReference>
    <dbReference type="PIR" id="S48687">
        <property type="entry name" value="S48687"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001106.1">
        <property type="nucleotide sequence ID" value="NM_001115.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P40145"/>
    <dbReference type="SMR" id="P40145"/>
    <dbReference type="BioGRID" id="106627">
        <property type="interactions" value="30"/>
    </dbReference>
    <dbReference type="FunCoup" id="P40145">
        <property type="interactions" value="1416"/>
    </dbReference>
    <dbReference type="IntAct" id="P40145">
        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000286355"/>
    <dbReference type="BindingDB" id="P40145"/>
    <dbReference type="ChEMBL" id="CHEMBL2960"/>
    <dbReference type="DrugBank" id="DB02587">
        <property type="generic name" value="Colforsin"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P40145"/>
    <dbReference type="TCDB" id="8.A.85.1.9">
        <property type="family name" value="the guanylate cyclase (gc) family"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="P40145">
        <property type="glycosylation" value="3 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P40145">
        <property type="glycosylation" value="4 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P40145"/>
    <dbReference type="PhosphoSitePlus" id="P40145"/>
    <dbReference type="BioMuta" id="ADCY8"/>
    <dbReference type="DMDM" id="729242"/>
    <dbReference type="jPOST" id="P40145"/>
    <dbReference type="MassIVE" id="P40145"/>
    <dbReference type="PaxDb" id="9606-ENSP00000286355"/>
    <dbReference type="PeptideAtlas" id="P40145"/>
    <dbReference type="ProteomicsDB" id="55337"/>
    <dbReference type="Antibodypedia" id="4355">
        <property type="antibodies" value="251 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="114"/>
    <dbReference type="Ensembl" id="ENST00000286355.10">
        <property type="protein sequence ID" value="ENSP00000286355.5"/>
        <property type="gene ID" value="ENSG00000155897.11"/>
    </dbReference>
    <dbReference type="GeneID" id="114"/>
    <dbReference type="KEGG" id="hsa:114"/>
    <dbReference type="MANE-Select" id="ENST00000286355.10">
        <property type="protein sequence ID" value="ENSP00000286355.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001115.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001106.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ytd.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:239"/>
    <dbReference type="ClinPGx" id="PA29"/>
    <dbReference type="CTD" id="114"/>
    <dbReference type="DisGeNET" id="114"/>
    <dbReference type="GeneCards" id="ADCY8"/>
    <dbReference type="HGNC" id="HGNC:239">
        <property type="gene designation" value="ADCY8"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000155897">
        <property type="expression patterns" value="Group enriched (brain, epididymis)"/>
    </dbReference>
    <dbReference type="MIM" id="103070">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000155897"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000155897"/>
    <dbReference type="eggNOG" id="KOG3619">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158742"/>
    <dbReference type="HOGENOM" id="CLU_001072_3_0_1"/>
    <dbReference type="InParanoid" id="P40145"/>
    <dbReference type="OMA" id="HRTIFIC"/>
    <dbReference type="OrthoDB" id="10006362at2759"/>
    <dbReference type="PAN-GO" id="P40145">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P40145"/>
    <dbReference type="PathwayCommons" id="P40145"/>
    <dbReference type="Reactome" id="R-HSA-163359">
        <property type="pathway name" value="Glucagon signaling in metabolic regulation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-163615">
        <property type="pathway name" value="PKA activation"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-164378">
        <property type="pathway name" value="PKA activation in glucagon signalling"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170660">
        <property type="pathway name" value="Adenylate cyclase activating pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-170670">
        <property type="pathway name" value="Adenylate cyclase inhibitory pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-381676">
        <property type="pathway name" value="Glucagon-like Peptide-1 (GLP1) regulates insulin secretion"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-418555">
        <property type="pathway name" value="G alpha (s) signalling events"/>
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    <feature type="region of interest" description="Required for both calcium stimulation and maintenance of autoinhibition" evidence="3">
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    <feature type="region of interest" description="Disordered" evidence="7">
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            <begin position="1223"/>
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    <feature type="short sequence motif" description="Essential for CALM1 interaction" evidence="3">
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            <begin position="38"/>
            <end position="40"/>
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    </feature>
    <feature type="short sequence motif" description="Essential for CALM1 interaction" evidence="3">
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            <begin position="49"/>
            <end position="51"/>
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    <feature type="compositionally biased region" description="Gly residues" evidence="7">
        <location>
            <begin position="56"/>
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    <feature type="binding site" evidence="2">
        <location>
            <begin position="419"/>
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        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
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    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="419"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="6">
        <location>
            <position position="419"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
            <note>catalytic</note>
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    <feature type="binding site" evidence="6">
        <location>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
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        <ligand>
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    <feature type="site" description="Essential for autoinhibition maintenance" evidence="3">
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    <feature type="site" description="Essential for autoinhibition maintenance by promoting interaction of the N and C termini" evidence="3">
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    <feature type="site" description="Essential for CALM1 interaction" evidence="3">
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    <feature type="site" description="Essential for CALM1 interaction" evidence="3">
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            <position position="1207"/>
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    <feature type="modified residue" description="Omega-N-methylarginine" evidence="4">
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            <position position="55"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="4">
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            <position position="614"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="4">
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            <position position="624"/>
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            <position position="817"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
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            <position position="821"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="5">
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            <position position="888"/>
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        <variation>T</variation>
        <location>
            <position position="80"/>
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    </feature>
    <feature type="sequence variant" id="VAR_036328" description="In a colorectal cancer sample; somatic mutation." evidence="8">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="881"/>
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    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P26769"/>
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    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P30803"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P40146"/>
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    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P97490"/>
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    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00099"/>
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    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="1715695"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="25403481"/>
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    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="25403481"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="8076676"/>
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    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <sequence length="1251" mass="140122" checksum="ABF25C40493E07C3" modified="1995-02-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-06-01" modified="2026-01-28" version="210" xmlns="https://uniprot.org/uniprot">
    <accession>P35612</accession>
    <accession>A8K4P2</accession>
    <accession>B4DM17</accession>
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    <accession>D6W5G8</accession>
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    <accession>Q16412</accession>
    <accession>Q59G82</accession>
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    <accession>Q7Z689</accession>
    <accession>Q7Z690</accession>
    <accession>Q7Z691</accession>
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        <recommendedName>
            <fullName>Beta-adducin</fullName>
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        <alternativeName>
            <fullName>Erythrocyte adducin subunit beta</fullName>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <source>
            <tissue>Reticulocyte</tissue>
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    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6 AND 7)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 8 AND 9)</scope>
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            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <scope>VARIANT ALA-439</scope>
        <source>
            <tissue>Eye</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1995" name="Mol. Biol. Cell" volume="6" first="269" last="269">
            <title>A novel isoform of beta adducin utilizes an alternatively spliced exon near the C-terminus.</title>
            <authorList>
                <person name="Sinard J.H."/>
                <person name="Stewart G.W."/>
                <person name="Argent A.C."/>
                <person name="Gilligan D.M."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 332-726 (ISOFORM 3)</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1995" name="Gene" volume="167" first="313" last="316">
            <title>Genomic organisation and chromosomal localisation of the gene encoding human beta adducin.</title>
            <authorList>
                <person name="Tisminetzky S."/>
                <person name="Devescovi G."/>
                <person name="Tripodi G."/>
                <person name="Muro A."/>
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            <dbReference type="PubMed" id="8566798"/>
            <dbReference type="DOI" id="10.1016/0378-1119(95)00591-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 462-559 (ISOFORM 2)</scope>
        <scope>ALTERNATIVE SPLICING</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1996" name="J. Biol. Chem." volume="271" first="25157" last="25166">
            <title>Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C.</title>
            <authorList>
                <person name="Matsuoka Y."/>
                <person name="Hughes C.A."/>
                <person name="Bennett V."/>
            </authorList>
            <dbReference type="PubMed" id="8810272"/>
            <dbReference type="DOI" id="10.1074/jbc.271.41.25157"/>
        </citation>
        <scope>PHOSPHORYLATION AT THR-55; SER-703 AND SER-713</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2008" name="J. Biol. Chem." volume="283" first="14600" last="14609">
            <title>Dematin and adducin provide a novel link between the spectrin cytoskeleton and human erythrocyte membrane by directly interacting with glucose transporter-1.</title>
            <authorList>
                <person name="Khan A.A."/>
                <person name="Hanada T."/>
                <person name="Mohseni M."/>
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                <person name="Zeng L."/>
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                <person name="Li D."/>
                <person name="Reed B.C."/>
                <person name="Speicher D.W."/>
                <person name="Chishti A.H."/>
            </authorList>
            <dbReference type="PubMed" id="18347014"/>
            <dbReference type="DOI" id="10.1074/jbc.m707818200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN A COMPLEX WITH DMTN AND SLC2A1</scope>
        <scope>INTERACTION WITH SLC2A1</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
            <authorList>
                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
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                <person name="Kassem M."/>
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                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-530; SER-592; SER-596; SER-600; SER-604; THR-611; SER-613; SER-617; SER-693 AND SER-697</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
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                <person name="Polat A.N."/>
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            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-530; SER-532; SER-592; SER-596; SER-600; SER-613; SER-617; SER-621; THR-675; SER-693 AND SER-697</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-596</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="7">Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Heterodimer of an alpha and a beta subunit. Found in a complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-16777913">
            <id>P35612</id>
        </interactant>
        <interactant intactId="EBI-2809187">
            <id>P35611</id>
            <label>ADD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
            <location>Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology>Peripheral membrane protein</topology>
            <orientation>Cytoplasmic side</orientation>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P35612-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P35612-2</id>
            <name>2</name>
            <name>Adducin 63</name>
            <sequence type="described" ref="VSP_000181 VSP_000182"/>
        </isoform>
        <isoform>
            <id>P35612-3</id>
            <name>3</name>
            <name>Beta-4</name>
            <name>E</name>
            <sequence type="described" ref="VSP_000183"/>
        </isoform>
        <isoform>
            <id>P35612-4</id>
            <name>4</name>
            <name>Beta-4a</name>
            <sequence type="described" ref="VSP_017244 VSP_017246"/>
        </isoform>
        <isoform>
            <id>P35612-5</id>
            <name>5</name>
            <name>Beta-4b</name>
            <sequence type="described" ref="VSP_017242 VSP_017243 VSP_017245"/>
        </isoform>
        <isoform>
            <id>P35612-6</id>
            <name>6</name>
            <name>Beta-4c</name>
            <sequence type="described" ref="VSP_017242 VSP_017244 VSP_017246"/>
        </isoform>
        <isoform>
            <id>P35612-7</id>
            <name>7</name>
            <name>Beta-4d</name>
            <sequence type="described" ref="VSP_017241 VSP_017244 VSP_017246"/>
        </isoform>
        <isoform>
            <id>P35612-8</id>
            <name>8</name>
            <sequence type="described" ref="VSP_043625 VSP_000181 VSP_000182"/>
        </isoform>
        <isoform>
            <id>P35612-9</id>
            <name>9</name>
            <sequence type="described" ref="VSP_055309 VSP_000181 VSP_000182"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Expressed mainly in brain, spleen, kidney cortex and medulla, and heart. Also expressed in human umbilical vein endothelial cells, human vascular smooth muscle cells, kidney tubular cells and K-562 cell line.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="5">Fetal kidney expresses isoforms 3, 4, 5, 6 and 7, and fetal liver expresses isoforms 3 and 4.</text>
    </comment>
    <comment type="domain">
        <text>Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.</text>
    </comment>
    <comment type="PTM">
        <text>The N-terminus is blocked.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the aldolase class II family. Adducin subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="14">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD92464" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="X58199">
        <property type="protein sequence ID" value="CAA41176.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF486420">
        <property type="protein sequence ID" value="AAP71863.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF486421">
        <property type="protein sequence ID" value="AAP71864.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF486422">
        <property type="protein sequence ID" value="AAP71865.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF486423">
        <property type="protein sequence ID" value="AAP71866.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291007">
        <property type="protein sequence ID" value="BAF83696.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK297250">
        <property type="protein sequence ID" value="BAG59729.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK309773">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB209227">
        <property type="protein sequence ID" value="BAD92464.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB593080">
        <property type="protein sequence ID" value="BAJ84020.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005234">
        <property type="protein sequence ID" value="AAD12715.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC007395">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAW99801.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAW99806.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAW99807.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471053">
        <property type="protein sequence ID" value="EAW99808.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC041666">
        <property type="protein sequence ID" value="AAH41666.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC051882">
        <property type="protein sequence ID" value="AAH51882.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC056881">
        <property type="protein sequence ID" value="AAH56881.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC065525">
        <property type="protein sequence ID" value="AAH65525.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U43959">
        <property type="protein sequence ID" value="AAA86421.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S81079">
        <property type="protein sequence ID" value="AAD14349.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S81077">
        <property type="protein sequence ID" value="AAD14349.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1906.1">
        <molecule id="P35612-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS1909.1">
        <molecule id="P35612-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46318.1">
        <molecule id="P35612-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54365.1">
        <molecule id="P35612-9"/>
    </dbReference>
    <dbReference type="PIR" id="S18208">
        <property type="entry name" value="S18208"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001171983.1">
        <molecule id="P35612-1"/>
        <property type="nucleotide sequence ID" value="NM_001185054.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001171984.1">
        <molecule id="P35612-9"/>
        <property type="nucleotide sequence ID" value="NM_001185055.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001608.1">
        <molecule id="P35612-1"/>
        <property type="nucleotide sequence ID" value="NM_001617.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_059516.2">
        <molecule id="P35612-2"/>
        <property type="nucleotide sequence ID" value="NM_017482.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_059522.1">
        <molecule id="P35612-3"/>
        <property type="nucleotide sequence ID" value="NM_017488.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011530804.1">
        <molecule id="P35612-1"/>
        <property type="nucleotide sequence ID" value="XM_011532502.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054196402.1">
        <molecule id="P35612-1"/>
        <property type="nucleotide sequence ID" value="XM_054340427.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P35612"/>
    <dbReference type="SMR" id="P35612"/>
    <dbReference type="BioGRID" id="106632">
        <property type="interactions" value="84"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2638">
        <property type="entry name" value="Adducin complex, alpha-beta variant"/>
    </dbReference>
    <dbReference type="CORUM" id="P35612"/>
    <dbReference type="FunCoup" id="P35612">
        <property type="interactions" value="995"/>
    </dbReference>
    <dbReference type="IntAct" id="P35612">
        <property type="interactions" value="39"/>
    </dbReference>
    <dbReference type="MINT" id="P35612"/>
    <dbReference type="STRING" id="9606.ENSP00000264436"/>
    <dbReference type="GlyGen" id="P35612">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P35612"/>
    <dbReference type="PhosphoSitePlus" id="P35612"/>
    <dbReference type="SwissPalm" id="P35612"/>
    <dbReference type="BioMuta" id="ADD2"/>
    <dbReference type="DMDM" id="543774"/>
    <dbReference type="jPOST" id="P35612"/>
    <dbReference type="MassIVE" id="P35612"/>
    <dbReference type="PaxDb" id="9606-ENSP00000264436"/>
    <dbReference type="PeptideAtlas" id="P35612"/>
    <dbReference type="ProteomicsDB" id="55105">
        <molecule id="P35612-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55106">
        <molecule id="P35612-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55107">
        <molecule id="P35612-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55108">
        <molecule id="P35612-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55109">
        <molecule id="P35612-5"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55110">
        <molecule id="P35612-6"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55111">
        <molecule id="P35612-7"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55112">
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        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="12951058"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="18347014"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="8810272"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="12951058"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source ref="9"/>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="726" mass="80854" checksum="B07F7303D929DBA4" modified="2007-01-23" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-12-01" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UEY8</accession>
    <accession>D3DRA8</accession>
    <accession>O43243</accession>
    <accession>Q5VU09</accession>
    <accession>Q92773</accession>
    <accession>Q9UEY7</accession>
    <name>ADDG_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Gamma-adducin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adducin-like protein 70</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADD3</name>
        <name type="synonym">ADDL</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Russman B.S."/>
                <person name="Blasco P.A."/>
                <person name="Fan G."/>
                <person name="Pollock J."/>
                <person name="Green S."/>
                <person name="Woltjer R.L."/>
                <person name="Mooney C."/>
                <person name="Kretzschmar D."/>
                <person name="Paisan-Ruiz C."/>
                <person name="Houlden H."/>
            </authorList>
            <dbReference type="PubMed" id="23836506"/>
            <dbReference type="DOI" id="10.1002/ana.23971"/>
        </citation>
        <scope>INVOLVEMENT IN CPSQ3</scope>
        <scope>VARIANT CPSQ3 ASP-367</scope>
        <scope>CHARACTERIZATION OF VARIANT CPSQ3 ASP-367</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42; SER-64; SER-442; SER-461; SER-673; SER-677; SER-681 AND SER-683</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-484</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2021" name="Prog. Neurobiol." volume="203" first="102074" last="102074">
            <title>A gamma-adducin cleavage fragment induces neurite deficits and synaptic dysfunction in Alzheimer's disease.</title>
            <authorList>
                <person name="Xiong M."/>
                <person name="Zou L."/>
                <person name="Meng L."/>
                <person name="Zhang X."/>
                <person name="Tian Y."/>
                <person name="Zhang G."/>
                <person name="Yang J."/>
                <person name="Chen G."/>
                <person name="Xiong J."/>
                <person name="Ye K."/>
                <person name="Zhang Z."/>
            </authorList>
            <dbReference type="PubMed" id="33992672"/>
            <dbReference type="DOI" id="10.1016/j.pneurobio.2021.102074"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2 6 12">Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin (Probable). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA (By similarity). Promotes the growth of neurites (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text>Heterodimer of an alpha and a gamma subunit.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cytoplasm</location>
            <location evidence="1">Cytoskeleton</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Cell membrane</location>
            <topology>Peripheral membrane protein</topology>
            <orientation>Cytoplasmic side</orientation>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
        </subcellularLocation>
        <text evidence="2">Full-length protein and the cleavage fragment 358-706 localize mainly to the cytoplasm, while cleavage fragment 1-357 translocates from the cytoplasm to the nucleus.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UEY8-1</id>
            <name>2</name>
            <name>Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UEY8-2</id>
            <name>1</name>
            <name>Short</name>
            <sequence type="described" ref="VSP_000188"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <molecule>Isoform 1</molecule>
        <text evidence="8">ubiquitously expressed.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7">Cleavage fragment 1-357 is abundantly expressed in the brain of patients with Alzheimer disease (AD), but hardly detectable in age-matched control individuals (at protein level).</text>
    </comment>
    <comment type="domain">
        <text>Comprised of three regions: a N-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5">Sumoylated.</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Proteolytically cleaved by asparagine endopeptidase (AEP) into 2 fragments. Overexpression of the 1-357 fragment induces neuronal apoptosis, and overexpression of either 1-357 or 358-706 fragment increases the degeneration of dendritic spines. Overexpression of the 1-357 fragment impairs neurite outgrowth by downregulating the expression of Rac2, and induces synaptic dysfunction and cognitive impairments in tau P301S transgenic mice, a mouse model for Alzheimer disease (AD).</text>
    </comment>
    <comment type="disease" evidence="6">
        <disease id="DI-04750">
            <name>Cerebral palsy, spastic quadriplegic 3</name>
            <acronym>CPSQ3</acronym>
            <description>A form of cerebral palsy, a group of non-progressive disorders of movement and/or posture resulting from defects in the developing central nervous system. CPSQ3 is an autosomal recessive neurodevelopmental disorder characterized by variable spasticity and cognitive impairment.</description>
            <dbReference type="MIM" id="617008"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="12">Belongs to the aldolase class II family. Adducin subfamily.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/520/ADD3"/>
    </comment>
    <dbReference type="EMBL" id="D67031">
        <property type="protein sequence ID" value="BAA23783.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U37122">
        <property type="protein sequence ID" value="AAB17126.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14372">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14373">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14374">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14375">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14376">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14377">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14378">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14379">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14380">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14381">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14382">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14383">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14384">
        <property type="protein sequence ID" value="CAB51805.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14372">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14373">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14374">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14375">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14376">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14377">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14378">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14379">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14380">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14381">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14382">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="Y14384">
        <property type="protein sequence ID" value="CAB51806.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BX647403">
        <property type="protein sequence ID" value="CAI46048.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL590628">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49573.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471066">
        <property type="protein sequence ID" value="EAW49574.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC062559">
        <property type="protein sequence ID" value="AAH62559.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7561.1">
        <molecule id="Q9UEY8-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7562.1">
        <molecule id="Q9UEY8-2"/>
    </dbReference>
    <dbReference type="PIR" id="JC7164">
        <property type="entry name" value="JC7164"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001112.2">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="NM_001121.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307520.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="NM_001320591.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307521.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="NM_001320592.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307522.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="NM_001320593.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001307523.1">
        <property type="nucleotide sequence ID" value="NM_001320594.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_058432.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="NM_016824.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_063968.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="NM_019903.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303562.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447794.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303563.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447795.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303564.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447796.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303565.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447797.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303566.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447798.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303567.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447799.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303568.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447800.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303569.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447801.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303570.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_024447802.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303571.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_024447803.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303572.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_024447804.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303573.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_024447805.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303574.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_024447806.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_024303575.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_024447807.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280543.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_047424587.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280544.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_047424588.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280545.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_047424589.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280546.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_047424590.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280547.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_047424591.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280548.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_047424592.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280549.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_047424593.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280550.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_047424594.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047280551.1">
        <molecule id="Q9UEY8-2"/>
        <property type="nucleotide sequence ID" value="XM_047424595.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220742.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364767.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220743.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364768.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220744.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364769.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220745.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364770.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220746.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364771.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220747.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364772.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220748.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364773.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220749.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364774.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220750.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364775.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220751.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364776.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054220752.1">
        <molecule id="Q9UEY8-1"/>
        <property type="nucleotide sequence ID" value="XM_054364777.1"/>
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        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="18088087"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <sequence length="706" mass="79155" checksum="EB8EAF602A4D7B41" modified="2000-05-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-12-07" modified="2026-01-28" version="178" xmlns="https://uniprot.org/uniprot">
    <accession>O15204</accession>
    <accession>B7ZAK5</accession>
    <name>ADEC1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ADAM DEC1</fullName>
            <ecNumber>3.4.24.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>A disintegrin and metalloproteinase domain-like protein decysin-1</fullName>
            <shortName>ADAM-like protein decysin-1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADAMDEC1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="14702039"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="4">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="5">
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            <title>Inverse regulation of the ADAM-family members, decysin and MADDAM/ADAM19 during monocyte differentiation.</title>
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                <person name="Fritsche J."/>
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            <dbReference type="PubMed" id="14632642"/>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="6">
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-237</scope>
        <source>
            <tissue>Plasma</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Mol. Cell. Proteomics" volume="8" first="913" last="923">
            <title>A strategy for precise and large scale identification of core fucosylated glycoproteins.</title>
            <authorList>
                <person name="Jia W."/>
                <person name="Lu Z."/>
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                <person name="Wang L.H."/>
                <person name="Chi H."/>
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                <person name="Han H.H."/>
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            <dbReference type="DOI" id="10.1074/mcp.m800504-mcp200"/>
        </citation>
        <scope>GLYCOSYLATION AT ASN-184</scope>
    </reference>
    <comment type="function">
        <text evidence="1">May play an important role in the control of the immune response and during pregnancy.</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O15204-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O15204-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043124"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 10">Expressed highly in the small intestine and appendix, moderately in lymph node, mucosal lining of the colon, thymus, spleen and very weakly in the bone marrow. Predominantly expressed in dendritic cells (DC) of the germinal center. Weakly expressed in monocyte and highly expressed in macrophage. Absent in immature DC.</text>
    </comment>
    <comment type="induction">
        <text evidence="7 10">Induced during DC maturation and up-regulated in response to T-cell signals. In macrophage up-regulated by bacterial lipopolysaccharides (LPS). Up-regulated by 1-alpha,25-dihydroxyvitamin D3 during differentiation of primary monocyte into macrophage.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-"/>
    <dbReference type="EMBL" id="Y13323">
        <property type="protein sequence ID" value="CAA73764.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK316320">
        <property type="protein sequence ID" value="BAH14691.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK316322">
        <property type="protein sequence ID" value="BAH14693.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC120193">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC069582">
        <property type="protein sequence ID" value="AAH69582.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074877">
        <property type="protein sequence ID" value="AAH74877.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074878">
        <property type="protein sequence ID" value="AAH74878.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55212.1">
        <molecule id="O15204-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6044.1">
        <molecule id="O15204-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138743.1">
        <molecule id="O15204-2"/>
        <property type="nucleotide sequence ID" value="NM_001145271.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001138744.1">
        <molecule id="O15204-2"/>
        <property type="nucleotide sequence ID" value="NM_001145272.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055294.1">
        <molecule id="O15204-1"/>
        <property type="nucleotide sequence ID" value="NM_014479.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O15204"/>
    <dbReference type="SMR" id="O15204"/>
    <dbReference type="BioGRID" id="118122">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="IntAct" id="O15204">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000256412"/>
    <dbReference type="MEROPS" id="M12.219"/>
    <dbReference type="GlyConnect" id="1910">
        <property type="glycosylation" value="19 N-Linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="O15204">
        <property type="glycosylation" value="4 sites, 25 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O15204">
        <property type="glycosylation" value="4 sites, 31 N-linked glycans (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O15204"/>
    <dbReference type="PhosphoSitePlus" id="O15204"/>
    <dbReference type="BioMuta" id="ADAMDEC1"/>
    <dbReference type="jPOST" id="O15204"/>
    <dbReference type="MassIVE" id="O15204"/>
    <dbReference type="PaxDb" id="9606-ENSP00000256412"/>
    <dbReference type="PeptideAtlas" id="O15204"/>
    <dbReference type="ProteomicsDB" id="48507">
        <molecule id="O15204-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="48508">
        <molecule id="O15204-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="22827">
        <property type="antibodies" value="166 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="27299"/>
    <dbReference type="Ensembl" id="ENST00000256412.8">
        <molecule id="O15204-1"/>
        <property type="protein sequence ID" value="ENSP00000256412.4"/>
        <property type="gene ID" value="ENSG00000134028.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000522298.1">
        <molecule id="O15204-2"/>
        <property type="protein sequence ID" value="ENSP00000428993.1"/>
        <property type="gene ID" value="ENSG00000134028.15"/>
    </dbReference>
    <dbReference type="GeneID" id="27299"/>
    <dbReference type="KEGG" id="hsa:27299"/>
    <dbReference type="MANE-Select" id="ENST00000256412.8">
        <property type="protein sequence ID" value="ENSP00000256412.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014479.3"/>
        <property type="RefSeq protein sequence ID" value="NP_055294.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003xdz.2">
        <molecule id="O15204-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16299"/>
    <dbReference type="ClinPGx" id="PA24535"/>
    <dbReference type="CTD" id="27299"/>
    <dbReference type="DisGeNET" id="27299"/>
    <dbReference type="GeneCards" id="ADAMDEC1"/>
    <dbReference type="HGNC" id="HGNC:16299">
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    <dbReference type="MIM" id="606393">
        <property type="type" value="gene"/>
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    <dbReference type="OpenTargets" id="ENSG00000134028"/>
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    <dbReference type="eggNOG" id="KOG3607">
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    <dbReference type="GeneTree" id="ENSGT00900000141143"/>
    <dbReference type="HOGENOM" id="CLU_012714_8_0_1"/>
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    <dbReference type="OMA" id="KMKIHDH"/>
    <dbReference type="OrthoDB" id="5951731at2759"/>
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        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
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    <dbReference type="PhylomeDB" id="O15204"/>
    <dbReference type="PathwayCommons" id="O15204"/>
    <dbReference type="SignaLink" id="O15204"/>
    <dbReference type="Agora" id="ENSG00000134028"/>
    <dbReference type="BioGRID-ORCS" id="27299">
        <property type="hits" value="8 hits in 1149 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ADAMDEC1">
        <property type="organism name" value="human"/>
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    <dbReference type="GenomeRNAi" id="27299"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 8"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000134028">
        <property type="expression patterns" value="Expressed in jejunal mucosa and 111 other cell types or tissues"/>
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    <dbReference type="ExpressionAtlas" id="O15204">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0031012">
        <property type="term" value="C:extracellular matrix"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="term" value="C:extracellular region"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000318"/>
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        <property type="term" value="F:zinc ion binding"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:immune response"/>
        <property type="evidence" value="ECO:0000303"/>
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        <property type="term" value="P:negative regulation of cell adhesion"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000318"/>
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        <property type="entry name" value="ADAM like decysin 1"/>
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        <property type="entry name" value="Disintegrin_dom_sf"/>
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        <property type="entry name" value="MetalloPept_cat_dom_sf"/>
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        <property type="entry name" value="Peptidase_M12B"/>
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        <property type="entry name" value="Peptidase_M12B_N"/>
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        <property type="entry name" value="Reprolysin_adamalysin"/>
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    <dbReference type="PANTHER" id="PTHR11905">
        <property type="entry name" value="ADAM A DISINTEGRIN AND METALLOPROTEASE DOMAIN"/>
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        <property type="entry name" value="ADAM DEC1"/>
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    <dbReference type="Pfam" id="PF01562">
        <property type="entry name" value="Pep_M12B_propep"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF01421">
        <property type="entry name" value="Reprolysin"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="DISIN"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Blood coagulation inhibitor (disintegrin)"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Metalloproteases ('zincins'), catalytic domain"/>
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        <property type="entry name" value="ZINC_PROTEASE"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0865">Zymogen</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="30"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000029146" evidence="2">
        <location>
            <begin position="31"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000029147" description="ADAM DEC1">
        <location>
            <begin position="206"/>
            <end position="470"/>
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    <feature type="domain" description="Peptidase M12B" evidence="4">
        <location>
            <begin position="218"/>
            <end position="412"/>
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    <feature type="domain" description="Disintegrin" evidence="3">
        <location>
            <begin position="420"/>
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    <feature type="region of interest" description="Disordered" evidence="6">
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            <begin position="173"/>
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    <feature type="active site" evidence="4 5">
        <location>
            <position position="353"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="352"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
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    <feature type="binding site" evidence="1">
        <location>
            <position position="356"/>
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        <ligand>
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    <feature type="binding site" evidence="2">
        <location>
            <position position="362"/>
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        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="61"/>
        </location>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) (complex) asparagine" evidence="9">
        <location>
            <position position="184"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="8">
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            <position position="237"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
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            <position position="466"/>
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            <begin position="328"/>
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    <feature type="disulfide bond" evidence="1">
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            <begin position="369"/>
            <end position="374"/>
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    <feature type="splice variant" id="VSP_043124" description="In isoform 2." evidence="11">
        <location>
            <begin position="1"/>
            <end position="79"/>
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        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_021848" description="In dbSNP:rs3765124.">
        <original>N</original>
        <variation>S</variation>
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            <position position="444"/>
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            <dbReference type="PROSITE-ProRule" id="PRU00068"/>
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    </evidence>
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        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00276"/>
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    </evidence>
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        <source>
            <dbReference type="PROSITE-ProRule" id="PRU10095"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="14632642"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16335952"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="19139490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="9271581"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <sequence length="470" mass="52775" checksum="35A454DD8A6A7E53" modified="1999-11-01" version="2" precursor="true">MLRGISQLPAVATMSWVLLPVLWLIVQTQAIAIKQTPELTLHEIVCPKKLHILHKREIKNNQTEKHGKEERYEPEVQYQMILNGEEIILSLQKTKHLLGPDYTETLYSPRGEEITTKPENMEHCYYKGNILNEKNSVASISTCDGLRGYFTHHHQRYQIKPLKSTDEKEHAVFTSNQEEQDPANHTCGVKSTDGKQGPIRISRSLKSPEKEDFLRAQKYIDLYLVLDNAFYKNYNENLTLIRSFVFDVMNLLNVIYNTIDVQVALVGMEIWSDGDKIKVVPSASTTFDNFLRWHSSNLGKKIHDHAQLLSGISFNNRRVGLAASNSLCSPSSVAVIEAKKKNNVALVGVMSHELGHVLGMPDVPFNTKCPSGSCVMNQYLSSKFPKDFSTSCRAHFERYLLSQKPKCLLQAPIPTNIMTTPVCGNHLLEVGEDCDCGSPKECTNLCCEALTCKLKPGTDCGGDAPNHTTE</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1986-07-21" modified="2026-01-28" version="221" xmlns="https://uniprot.org/uniprot">
    <accession>P00326</accession>
    <accession>Q4PJ18</accession>
    <accession>Q5WRV0</accession>
    <accession>Q6LBW4</accession>
    <accession>Q6NWV0</accession>
    <accession>Q6NZA7</accession>
    <name>ADH1G_HUMAN</name>
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        <recommendedName>
            <fullName>Alcohol dehydrogenase 1C</fullName>
            <ecNumber evidence="7">1.1.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase subunit gamma</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADH1C</name>
        <name type="synonym">ADH3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1986" name="Eur. J. Biochem." volume="159" first="215" last="218">
            <title>The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties.</title>
            <authorList>
                <person name="Hoeoeg J.-O."/>
                <person name="Heden L.-O."/>
                <person name="Larsson K."/>
                <person name="Joernvall H."/>
            </authorList>
            <dbReference type="PubMed" id="3758060"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1986.tb09855.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANTS GAMMA-2 GLN-272 AND VAL-350</scope>
        <scope>POLYMORPHISM</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1986" name="Proc. Natl. Acad. Sci. U.S.A." volume="83" first="634" last="638">
            <title>Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence.</title>
            <authorList>
                <person name="Ikuta T."/>
                <person name="Szeto S."/>
                <person name="Yoshida A."/>
            </authorList>
            <dbReference type="PubMed" id="2935875"/>
            <dbReference type="DOI" id="10.1073/pnas.83.3.634"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1992" name="Jpn. J. Genet." volume="67" first="167" last="171">
            <title>Molecular structure of the human alcohol dehydrogenase 3 gene.</title>
            <authorList>
                <person name="Yokoyama S."/>
                <person name="Matsuo Y."/>
                <person name="Rajasekharan S."/>
                <person name="Yokoyama R."/>
            </authorList>
            <dbReference type="PubMed" id="1524834"/>
            <dbReference type="DOI" id="10.1266/jjg.67.167"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-06" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS HIS-48; SER-166; GLN-272; VAL-350 AND THR-352</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
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                <person name="Hillier L.W."/>
                <person name="Graves T.A."/>
                <person name="Fulton R.S."/>
                <person name="Fulton L.A."/>
                <person name="Pepin K.H."/>
                <person name="Minx P."/>
                <person name="Wagner-McPherson C."/>
                <person name="Layman D."/>
                <person name="Wylie K."/>
                <person name="Sekhon M."/>
                <person name="Becker M.C."/>
                <person name="Fewell G.A."/>
                <person name="Delehaunty K.D."/>
                <person name="Miner T.L."/>
                <person name="Nash W.E."/>
                <person name="Kremitzki C."/>
                <person name="Oddy L."/>
                <person name="Du H."/>
                <person name="Sun H."/>
                <person name="Bradshaw-Cordum H."/>
                <person name="Ali J."/>
                <person name="Carter J."/>
                <person name="Cordes M."/>
                <person name="Harris A."/>
                <person name="Isak A."/>
                <person name="van Brunt A."/>
                <person name="Nguyen C."/>
                <person name="Du F."/>
                <person name="Courtney L."/>
                <person name="Kalicki J."/>
                <person name="Ozersky P."/>
                <person name="Abbott S."/>
                <person name="Armstrong J."/>
                <person name="Belter E.A."/>
                <person name="Caruso L."/>
                <person name="Cedroni M."/>
                <person name="Cotton M."/>
                <person name="Davidson T."/>
                <person name="Desai A."/>
                <person name="Elliott G."/>
                <person name="Erb T."/>
                <person name="Fronick C."/>
                <person name="Gaige T."/>
                <person name="Haakenson W."/>
                <person name="Haglund K."/>
                <person name="Holmes A."/>
                <person name="Harkins R."/>
                <person name="Kim K."/>
                <person name="Kruchowski S.S."/>
                <person name="Strong C.M."/>
                <person name="Grewal N."/>
                <person name="Goyea E."/>
                <person name="Hou S."/>
                <person name="Levy A."/>
                <person name="Martinka S."/>
                <person name="Mead K."/>
                <person name="McLellan M.D."/>
                <person name="Meyer R."/>
                <person name="Randall-Maher J."/>
                <person name="Tomlinson C."/>
                <person name="Dauphin-Kohlberg S."/>
                <person name="Kozlowicz-Reilly A."/>
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                <person name="Swearengen-Shahid S."/>
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                <person name="Radionenko M."/>
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                <person name="Wang C."/>
                <person name="Rock S.M."/>
                <person name="Tin-Wollam A.-M."/>
                <person name="Maupin R."/>
                <person name="Latreille P."/>
                <person name="Wendl M.C."/>
                <person name="Yang S.-P."/>
                <person name="Pohl C."/>
                <person name="Wallis J.W."/>
                <person name="Spieth J."/>
                <person name="Bieri T.A."/>
                <person name="Berkowicz N."/>
                <person name="Nelson J.O."/>
                <person name="Osborne J."/>
                <person name="Ding L."/>
                <person name="Meyer R."/>
                <person name="Sabo A."/>
                <person name="Shotland Y."/>
                <person name="Sinha P."/>
                <person name="Wohldmann P.E."/>
                <person name="Cook L.L."/>
                <person name="Hickenbotham M.T."/>
                <person name="Eldred J."/>
                <person name="Williams D."/>
                <person name="Jones T.A."/>
                <person name="She X."/>
                <person name="Ciccarelli F.D."/>
                <person name="Izaurralde E."/>
                <person name="Taylor J."/>
                <person name="Schmutz J."/>
                <person name="Myers R.M."/>
                <person name="Cox D.R."/>
                <person name="Huang X."/>
                <person name="McPherson J.D."/>
                <person name="Mardis E.R."/>
                <person name="Clifton S.W."/>
                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
                <person name="Marra M.A."/>
                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
                <person name="Miller W."/>
                <person name="Eichler E.E."/>
                <person name="Bork P."/>
                <person name="Suyama M."/>
                <person name="Torrents D."/>
                <person name="Waterston R.H."/>
                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS GAMMA-2 GLN-272 AND VAL-350</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Femoral artery</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1984" name="Eur. J. Biochem." volume="145" first="447" last="453">
            <title>Human liver alcohol dehydrogenase. 2. The primary structure of the gamma 1 protein chain.</title>
            <authorList>
                <person name="Buhler R."/>
                <person name="Hempel J."/>
                <person name="Kaiser R."/>
                <person name="de Zalenski C."/>
                <person name="von Wartburg J.-P."/>
                <person name="Joernvall H."/>
            </authorList>
            <dbReference type="PubMed" id="6391921"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1984.tb08575.x"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-375</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT SER-2</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1984" name="FEBS Lett." volume="178" first="249" last="252">
            <title>Differential susceptibility of human alcohol dehydrogenase isoenzymes to anions.</title>
            <authorList>
                <person name="Buehler R."/>
                <person name="Von Wartburg J.P."/>
            </authorList>
            <dbReference type="PubMed" id="6391957"/>
            <dbReference type="DOI" id="10.1016/0014-5793(84)80610-9"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2001" name="Protein Sci." volume="10" first="697" last="706">
            <title>Three-dimensional structures of the three human class I alcohol dehydrogenases.</title>
            <authorList>
                <person name="Niederhut M.S."/>
                <person name="Gibbons B.J."/>
                <person name="Perez-Miller S."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="11274460"/>
            <dbReference type="DOI" id="10.1110/ps.45001"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="12555" last="12562">
            <title>Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors.</title>
            <authorList>
                <person name="Gibbons B.J."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="15449945"/>
            <dbReference type="DOI" id="10.1021/bi0489107"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Alcohol dehydrogenase. Exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>a primary alcohol + NAD(+) = an aldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10736"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15734"/>
            <dbReference type="ChEBI" id="CHEBI:17478"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>ethanol + NAD(+) = acetaldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:25290"/>
            <dbReference type="ChEBI" id="CHEBI:15343"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16236"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:25291"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2 3">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="2 3">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3">Dimer of identical or non-identical chains of class I alcohol dehydrogenase: ADH1A, ADH1B, and ADH1C.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-21822364">
            <id>P00326</id>
        </interactant>
        <interactant intactId="EBI-2838677">
            <id>P00325</id>
            <label>ADH1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="polymorphism">
        <text evidence="5">Two main alleles are known, ADH3*1 or gamma-1 has Arg-272/Ile-350 while ADH3*2 or gamma-2 has Gln-272/Val-350. ADH3*1 is associated with a fast rate of ethanol oxidation and ADH3*2 with a slow rate.</text>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: ADH1A, ADH1B, and ADH1C, one to class-II: ADH4, one to class-III: ADH5, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the zinc-containing alcohol dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.1.1.1" evidence="7"/>
    <dbReference type="EMBL" id="X04299">
        <property type="protein sequence ID" value="CAA27842.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X04350">
        <property type="protein sequence ID" value="CAA27876.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M12272">
        <property type="protein sequence ID" value="AAC41757.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D11067">
        <property type="protein sequence ID" value="BAC06856.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ088981">
        <property type="protein sequence ID" value="AAY68222.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC133528">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC062476">
        <property type="protein sequence ID" value="AAH62476.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC066227">
        <property type="protein sequence ID" value="AAH66227.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC066228">
        <property type="protein sequence ID" value="AAH66228.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067419">
        <property type="protein sequence ID" value="AAH67419.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067420">
        <property type="protein sequence ID" value="AAH67420.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067421">
        <property type="protein sequence ID" value="AAH67421.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC067422">
        <property type="protein sequence ID" value="AAH67422.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074771">
        <property type="protein sequence ID" value="AAH74771.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074786">
        <property type="protein sequence ID" value="AAH74786.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54780.1"/>
    <dbReference type="PIR" id="C25428">
        <property type="entry name" value="DEHUAG"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000660.1">
        <property type="nucleotide sequence ID" value="NM_000669.5"/>
    </dbReference>
    <dbReference type="PDB" id="1HT0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1U3W">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.45 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDBsum" id="1HT0"/>
    <dbReference type="PDBsum" id="1U3W"/>
    <dbReference type="AlphaFoldDB" id="P00326"/>
    <dbReference type="SMR" id="P00326"/>
    <dbReference type="BioGRID" id="106638">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="CORUM" id="P00326"/>
    <dbReference type="FunCoup" id="P00326">
        <property type="interactions" value="304"/>
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    <dbReference type="IntAct" id="P00326">
        <property type="interactions" value="17"/>
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    <dbReference type="STRING" id="9606.ENSP00000426083"/>
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    <dbReference type="ChEMBL" id="CHEMBL3285"/>
    <dbReference type="DrugBank" id="DB03061">
        <property type="generic name" value="(R)-N-(1-Methyl-Hexyl)-Formamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01711">
        <property type="generic name" value="2,3,4,5,6-Pentafluorobenzyl Alcohol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04312">
        <property type="generic name" value="2,3-Difluorobenzyl Alcohol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04448">
        <property type="generic name" value="2,4-Difluorobenzyl Alcohol 2,4-Difluoro-1-(Hydroxymethyl)Benzene"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02249">
        <property type="generic name" value="2-Ethoxyethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02871">
        <property type="generic name" value="3-Butylthiolane 1-Oxide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02721">
        <property type="generic name" value="4-Iodopyrazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03020">
        <property type="generic name" value="5-beta-D-ribofuranosylnicotinamide adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02659">
        <property type="generic name" value="Cholic Acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04071">
        <property type="generic name" value="Cpad"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03559">
        <property type="generic name" value="Cyclohexylformamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01213">
        <property type="generic name" value="Fomepizole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02131">
        <property type="generic name" value="N-1-methylheptylformamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04113">
        <property type="generic name" value="N-Formylpiperidine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02822">
        <property type="generic name" value="Para-Bromobenzyl Alcohol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02757">
        <property type="generic name" value="Pyrazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03226">
        <property type="generic name" value="Trifluoroethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14487">
        <property type="generic name" value="Zinc acetate"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14533">
        <property type="generic name" value="Zinc chloride"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB14548">
        <property type="generic name" value="Zinc sulfate, unspecified form"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P00326"/>
    <dbReference type="GlyGen" id="P00326">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P00326"/>
    <dbReference type="PhosphoSitePlus" id="P00326"/>
    <dbReference type="BioMuta" id="ADH1C"/>
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    <dbReference type="jPOST" id="P00326"/>
    <dbReference type="MassIVE" id="P00326"/>
    <dbReference type="PaxDb" id="9606-ENSP00000426083"/>
    <dbReference type="PeptideAtlas" id="P00326"/>
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    <dbReference type="TopDownProteomics" id="P00326"/>
    <dbReference type="Antibodypedia" id="73653">
        <property type="antibodies" value="144 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="126"/>
    <dbReference type="Ensembl" id="ENST00000515683.6">
        <property type="protein sequence ID" value="ENSP00000426083.1"/>
        <property type="gene ID" value="ENSG00000248144.7"/>
    </dbReference>
    <dbReference type="GeneID" id="126"/>
    <dbReference type="KEGG" id="hsa:126"/>
    <dbReference type="MANE-Select" id="ENST00000515683.6">
        <property type="protein sequence ID" value="ENSP00000426083.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000669.5"/>
        <property type="RefSeq protein sequence ID" value="NP_000660.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc032trd.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:251"/>
    <dbReference type="ClinPGx" id="PA24572"/>
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    <dbReference type="GeneCards" id="ADH1C"/>
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        <property type="gene designation" value="ADH1C"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000248144">
        <property type="expression patterns" value="Group enriched (intestine, liver, stomach)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADH1C"/>
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        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000248144"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000248144"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155234"/>
    <dbReference type="HOGENOM" id="CLU_026673_14_0_1"/>
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    <dbReference type="OMA" id="YIFAVEP"/>
    <dbReference type="OrthoDB" id="417550at2759"/>
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        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
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        <property type="organism ID" value="2681"/>
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        <property type="pathway name" value="RA biosynthesis pathway"/>
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        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P00326"/>
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    <dbReference type="Agora" id="ENSG00000248144"/>
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        <property type="hits" value="5 hits in 237 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADH1C">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P00326"/>
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        <property type="development level" value="Tclin"/>
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        <property type="component" value="Chromosome 4"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 130 other cell types or tissues"/>
    </dbReference>
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        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0036064">
        <property type="term" value="C:ciliary basal body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
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        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0004022">
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        <property type="project" value="UniProtKB"/>
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0042572">
        <property type="term" value="P:retinol metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="entry name" value="alcohol_DH_class_I_II_IV"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="Medium-chain alcohol dehydrogenases, catalytic domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADH-like_C"/>
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    <dbReference type="InterPro" id="IPR013154">
        <property type="entry name" value="ADH-like_N"/>
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    <dbReference type="InterPro" id="IPR002328">
        <property type="entry name" value="ADH_Zn_CS"/>
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    <dbReference type="InterPro" id="IPR020843">
        <property type="entry name" value="ER"/>
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    <dbReference type="InterPro" id="IPR011032">
        <property type="entry name" value="GroES-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880">
        <property type="entry name" value="ALCOHOL DEHYDROGENASE"/>
        <property type="match status" value="1"/>
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    <sequence length="375" mass="39868" checksum="414D73CC4C104C84" modified="2007-01-23" version="2">MSTAGKVIKCKAAVLWELKKPFSIEEVEVAPPKAHEVRIKMVAAGICRSDEHVVSGNLVTPLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLFTPQCGKCRICKNPESNYCLKNDLGNPRGTLQDGTRRFTCSGKPIHHFVGVSTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTGYGSAVKVAKVTPGSTCAVFGLGGVGLSVVMGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPDSQNLSINPMLLLTGRTWKGAIFGGFKSKESVPKLVADFMAKKFSLDALITNILPFEKINEGFDLLRSGKSIRTVLTF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-04-18" modified="2026-01-28" version="156" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N7X0</accession>
    <accession>Q5T402</accession>
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        <name evidence="12 15" type="primary">ADGB</name>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
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            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
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        <citation type="journal article" date="2003" name="Nature" volume="425" first="805" last="811">
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            <authorList>
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                <person name="Lloyd D.M."/>
                <person name="Loveland J.E."/>
                <person name="Lovell J."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Maslen G.L."/>
                <person name="Matthews L."/>
                <person name="McCann O.T."/>
                <person name="McLaren S.J."/>
                <person name="McLay K."/>
                <person name="McMurray A."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Niblett D."/>
                <person name="Nickerson T."/>
                <person name="Novik K.L."/>
                <person name="Oliver K."/>
                <person name="Overton-Larty E.K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Phillips S."/>
                <person name="Plumb R.W."/>
                <person name="Porter K.M."/>
                <person name="Ramsey Y."/>
                <person name="Ranby S.A."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Searle S.M."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Skuce C.D."/>
                <person name="Smith S."/>
                <person name="Smith M."/>
                <person name="Spraggon L."/>
                <person name="Squares S.L."/>
                <person name="Steward C.A."/>
                <person name="Sycamore N."/>
                <person name="Tamlyn-Hall G."/>
                <person name="Tester J."/>
                <person name="Theaker A.J."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tubby B."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="West A.P."/>
                <person name="White S.S."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker H."/>
                <person name="Wild A."/>
                <person name="Willey D.J."/>
                <person name="Wilmer T.E."/>
                <person name="Wood J.M."/>
                <person name="Wray P.W."/>
                <person name="Wyatt J.C."/>
                <person name="Young L."/>
                <person name="Younger R.M."/>
                <person name="Bentley D.R."/>
                <person name="Coulson A."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Sulston J.E."/>
                <person name="Dunham I."/>
                <person name="Rogers J."/>
                <person name="Beck S."/>
            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT ALA-1637</scope>
    </reference>
    <reference key="3">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
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                <person name="Nishikawa T."/>
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                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
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                <person name="Nagahari K."/>
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                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
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                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
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                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
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                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
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                <person name="Senoh A."/>
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                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-754 (ISOFORM 1)</scope>
        <scope>VARIANT THR-310</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
            <title>Exhaustive RT-PCR and sequencing of all novel TWINSCAN predictions in human.</title>
            <authorList>
                <person name="Stevens M."/>
                <person name="Wei C."/>
                <person name="Gross S.S."/>
                <person name="McPherson J."/>
                <person name="Brent M.R."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 697-964</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2012" name="Mol. Biol. Evol." volume="29" first="1105" last="1114">
            <title>Androglobin: a chimeric globin in metazoans that is preferentially expressed in mammalian testes.</title>
            <authorList>
                <person name="Hoogewijs D."/>
                <person name="Ebner B."/>
                <person name="Germani F."/>
                <person name="Hoffmann F.G."/>
                <person name="Fabrizius A."/>
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                <person name="Hankeln T."/>
            </authorList>
            <dbReference type="PubMed" id="22115833"/>
            <dbReference type="DOI" id="10.1093/molbev/msr246"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>CAUTION</scope>
        <scope>HEME-BINDING</scope>
        <scope>REGION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2023" name="Hum. Genet." volume="142" first="735" last="748">
            <title>ADGB variants cause asthenozoospermia and male infertility.</title>
            <authorList>
                <person name="Qu R."/>
                <person name="Zhang Z."/>
                <person name="Wu L."/>
                <person name="Li Q."/>
                <person name="Mu J."/>
                <person name="Zhao L."/>
                <person name="Yan Z."/>
                <person name="Wang W."/>
                <person name="Zeng Y."/>
                <person name="Liu R."/>
                <person name="Dong J."/>
                <person name="Li Q."/>
                <person name="Sun X."/>
                <person name="Wang L."/>
                <person name="Sang Q."/>
                <person name="Chen B."/>
                <person name="Kuang Y."/>
            </authorList>
            <dbReference type="PubMed" id="36995441"/>
            <dbReference type="DOI" id="10.1007/s00439-023-02546-0"/>
        </citation>
        <scope>INVOLVEMENT IN ASTHENOZOOSPERMIA</scope>
        <scope>VARIANT 1107-GLU--LYS-1667 DEL</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH CALMODULIN</scope>
    </reference>
    <comment type="function">
        <text evidence="9 10">Probable chimeric globin with a bis-histidyl six-coordinate heme-iron atom through which it could bind dioxygen, carbon monoxide and nitric oxide (PubMed:22115833). Required for sperm flagellum formation and maturation of elongating spermatids, thus playing an essential role in male fertility (PubMed:36995441).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 10">Interacts with septin SEPT10; contributes to in vitro proteolytic cleavage of SEPT10 in a calmodulin-dependent manner. Interacts with CFAP69. Interacts with SPEF2 (By similarity). May interact with calmodulin (PubMed:36995441).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell projection</location>
            <location evidence="1">Cilium</location>
            <location evidence="1">Flagellum</location>
        </subcellularLocation>
        <text evidence="1">Expressed within the midpiece and along the whole sperm flagellum. Detected in the annulus of the sperm flagellum in S12 and S15 spermatids and mature sperm.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N7X0-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N7X0-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_039243 VSP_039244"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="5 9">The globin domain is circularly permuted. The globin domain, which normally consists of eight consecutive alpha-helices from A (N-terminal) to H (C-terminal), is circularly permutated and split into two parts. The part containing helices A and B is shifted C-terminally and is separated from the main globin sequence (helices C-H) by a potential calmodulin-binding IQ domain.</text>
    </comment>
    <comment type="disease">
        <text evidence="10">Defects in ADGB may be the cause of asthenozoospermia, a condition in which the percentage of progressively motile sperm is abnormally low.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">In the central section; belongs to the globin family.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">In the N-terminal section; belongs to the peptidase C2 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="14">The calpain domain lacks the conserved active site residues. Probably catalytically inactive as a calcium-dependent cysteine-type endopeptidase.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="AL832192"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL" id="AL832192"/>
        </conflict>
        <text>Intron retention.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAI16490" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="CAI20488" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="DN831198"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AL832192">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138916">
        <property type="protein sequence ID" value="CAI14697.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI14697.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138916">
        <property type="protein sequence ID" value="CAI14698.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI14698.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI20488.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359547">
        <property type="protein sequence ID" value="CAI20488.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI20489.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138916">
        <property type="protein sequence ID" value="CAI20489.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI20490.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138916">
        <property type="protein sequence ID" value="CAI20490.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359547">
        <property type="protein sequence ID" value="CAI16490.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL158199">
        <property type="protein sequence ID" value="CAI16490.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK097570">
        <property type="protein sequence ID" value="BAC05106.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DN831198">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_078970.3">
        <molecule id="Q8N7X0-1"/>
        <property type="nucleotide sequence ID" value="NM_024694.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8N7X0"/>
    <dbReference type="SMR" id="Q8N7X0"/>
    <dbReference type="BioGRID" id="122859">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8N7X0">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N7X0">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000381036"/>
    <dbReference type="MEROPS" id="C02.972"/>
    <dbReference type="iPTMnet" id="Q8N7X0"/>
    <dbReference type="PhosphoSitePlus" id="Q8N7X0"/>
    <dbReference type="BioMuta" id="ADGB"/>
    <dbReference type="DMDM" id="298286920"/>
    <dbReference type="jPOST" id="Q8N7X0"/>
    <dbReference type="MassIVE" id="Q8N7X0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000381036"/>
    <dbReference type="PeptideAtlas" id="Q8N7X0"/>
    <dbReference type="ProteomicsDB" id="72338">
        <molecule id="Q8N7X0-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="72339">
        <molecule id="Q8N7X0-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="50988">
        <property type="antibodies" value="16 antibodies from 8 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="79747"/>
    <dbReference type="Ensembl" id="ENST00000397944.8">
        <molecule id="Q8N7X0-1"/>
        <property type="protein sequence ID" value="ENSP00000381036.3"/>
        <property type="gene ID" value="ENSG00000118492.19"/>
    </dbReference>
    <dbReference type="GeneID" id="79747"/>
    <dbReference type="KEGG" id="hsa:79747"/>
    <dbReference type="MANE-Select" id="ENST00000397944.8">
        <property type="protein sequence ID" value="ENSP00000381036.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_024694.4"/>
        <property type="RefSeq protein sequence ID" value="NP_078970.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc010khx.4">
        <molecule id="Q8N7X0-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21212"/>
    <dbReference type="ClinPGx" id="PA134944476"/>
    <dbReference type="CTD" id="79747"/>
    <dbReference type="DisGeNET" id="79747"/>
    <dbReference type="GeneCards" id="ADGB"/>
    <dbReference type="HGNC" id="HGNC:21212">
        <property type="gene designation" value="ADGB"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000118492">
        <property type="expression patterns" value="Tissue enhanced (choroid plexus, fallopian tube, testis)"/>
    </dbReference>
    <dbReference type="MIM" id="614630">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000118492"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000118492"/>
    <dbReference type="eggNOG" id="KOG0045">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000014904"/>
    <dbReference type="HOGENOM" id="CLU_003228_0_0_1"/>
    <dbReference type="InParanoid" id="Q8N7X0"/>
    <dbReference type="OMA" id="DMYKEMR"/>
    <dbReference type="OrthoDB" id="9374162at2759"/>
    <dbReference type="PAN-GO" id="Q8N7X0">
        <property type="GO annotations" value="0 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N7X0"/>
    <dbReference type="PathwayCommons" id="Q8N7X0"/>
    <dbReference type="SignaLink" id="Q8N7X0"/>
    <dbReference type="Agora" id="ENSG00000118492"/>
    <dbReference type="BioGRID-ORCS" id="79747">
        <property type="hits" value="3 hits in 306 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADGB">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="79747"/>
    <dbReference type="Pharos" id="Q8N7X0">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8N7X0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8N7X0">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000118492">
        <property type="expression patterns" value="Expressed in right uterine tube and 94 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8N7X0">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097227">
        <property type="term" value="C:sperm annulus"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
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        <ligandPart>
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        <variation>T</variation>
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            <position position="310"/>
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    <feature type="sequence variant" id="VAR_063158" description="In dbSNP:rs1052445." evidence="7">
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        <variation>A</variation>
        <location>
            <position position="1637"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AL832192." evidence="13" ref="1">
        <location>
            <begin position="205"/>
            <end position="280"/>
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    <feature type="sequence conflict" description="In Ref. 1; AL832192." evidence="13" ref="1">
        <location>
            <begin position="570"/>
            <end position="580"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 4; DN831198." evidence="13" ref="4">
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        <variation>R</variation>
        <location>
            <position position="716"/>
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    <feature type="sequence conflict" description="In Ref. 3; BAC05106." evidence="13" ref="3">
        <original>RHMLLFNA</original>
        <variation>YEVASFFP</variation>
        <location>
            <begin position="747"/>
            <end position="754"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AL832192." evidence="13" ref="1">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="810"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; DN831198." evidence="13" ref="4">
        <original>P</original>
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        <location>
            <position position="931"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 4; DN831198." evidence="13" ref="4">
        <original>Q</original>
        <variation>L</variation>
        <location>
            <position position="944"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAI14697/CAI20489." evidence="13" ref="2">
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            <position position="1639"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="G3UZ78"/>
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    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00116"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00239"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01386"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="14574404"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22115833"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="36995441"/>
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    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="22115833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="22115833"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:21212"/>
        </source>
    </evidence>
    <sequence length="1667" mass="189713" checksum="46732C56A6C63B3F" modified="2010-06-15" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-04-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P07327</accession>
    <accession>A8K3E3</accession>
    <accession>Q17R68</accession>
    <name>ADH1A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Alcohol dehydrogenase 1A</fullName>
            <ecNumber evidence="4">1.1.1.1</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase subunit alpha</fullName>
        </alternativeName>
    </protein>
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        <name type="primary">ADH1A</name>
        <name type="synonym">ADH1</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1986" name="Biochemistry" volume="25" first="2465" last="2470">
            <title>cDNA and protein structure for the alpha subunit of human liver alcohol dehydrogenase.</title>
            <authorList>
                <person name="von Bahr-Lindstroem H."/>
                <person name="Hoeoeg J.-O."/>
                <person name="Heden L.-O."/>
                <person name="Kaiser R."/>
                <person name="Fleetwood L."/>
                <person name="Larsson K."/>
                <person name="Lake M."/>
                <person name="Holmquist B."/>
                <person name="Holmgren A."/>
                <person name="Hempel J."/>
                <person name="Vallee B.L."/>
                <person name="Joernvall H."/>
            </authorList>
            <dbReference type="PubMed" id="3013304"/>
            <dbReference type="DOI" id="10.1021/bi00357a026"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>PROTEIN SEQUENCE OF 2-375</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT SER-2</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1986" name="Proc. Natl. Acad. Sci. U.S.A." volume="83" first="634" last="638">
            <title>Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence.</title>
            <authorList>
                <person name="Ikuta T."/>
                <person name="Szeto S."/>
                <person name="Yoshida A."/>
            </authorList>
            <dbReference type="PubMed" id="2935875"/>
            <dbReference type="DOI" id="10.1073/pnas.83.3.634"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1989" name="FEBS Lett." volume="243" first="57" last="60">
            <title>Molecular structure of the human alcohol dehydrogenase 1 gene.</title>
            <authorList>
                <person name="Matsuo Y."/>
                <person name="Yokoyama S."/>
            </authorList>
            <dbReference type="PubMed" id="2920825"/>
            <dbReference type="DOI" id="10.1016/0014-5793(89)81217-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-10" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-02" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
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                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1990" name="Genomics" volume="7" first="152" last="158">
            <title>The human class I alcohol dehydrogenase gene cluster: three genes are tandemly organized in an 80-kb-long segment of the genome.</title>
            <authorList>
                <person name="Yasunami M."/>
                <person name="Kikuchi I."/>
                <person name="Sarapata D."/>
                <person name="Yoshida A."/>
            </authorList>
            <dbReference type="PubMed" id="2347582"/>
            <dbReference type="DOI" id="10.1016/0888-7543(90)90535-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1989" name="J. Biol. Chem." volume="264" first="11112" last="11116">
            <title>Stereospecific oxidation of secondary alcohols by human alcohol dehydrogenases.</title>
            <authorList>
                <person name="Stone C.L."/>
                <person name="Li T.K."/>
                <person name="Bosron W.F."/>
            </authorList>
            <dbReference type="PubMed" id="2738060"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)60436-3"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2004" name="Biochemistry" volume="43" first="12555" last="12562">
            <title>Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors.</title>
            <authorList>
                <person name="Gibbons B.J."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="15449945"/>
            <dbReference type="DOI" id="10.1021/bi0489107"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 2-375 IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2001" name="Protein Sci." volume="10" first="697" last="706">
            <title>Three-dimensional structures of the three human class I alcohol dehydrogenases.</title>
            <authorList>
                <person name="Niederhut M.S."/>
                <person name="Gibbons B.J."/>
                <person name="Perez-Miller S."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="11274460"/>
            <dbReference type="DOI" id="10.1110/ps.45001"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-375 IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Alcohol dehydrogenase (PubMed:2738060). Oxidizes primary as well as secondary alcohols. Ethanol is a very poor substrate (PubMed:2738060).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a primary alcohol + NAD(+) = an aldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10736"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15734"/>
            <dbReference type="ChEBI" id="CHEBI:17478"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a secondary alcohol + NAD(+) = a ketone + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10740"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17087"/>
            <dbReference type="ChEBI" id="CHEBI:35681"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>butan-1-ol + NAD(+) = butanal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:33199"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15743"/>
            <dbReference type="ChEBI" id="CHEBI:28885"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-propanol + NAD(+) = propanal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:50704"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17153"/>
            <dbReference type="ChEBI" id="CHEBI:28831"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2 3">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="2 3">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="4">32 uM for butan-1-ol</KM>
            <KM evidence="4">14 uM for 1-propanol</KM>
            <KM evidence="4">6100 uM for ethanol</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="2 3">Dimer of identical or heterodimer of closely related subunits alpha, beta, or gamma that are encoded by genes ADH1A, ADH1B, and ADH1C, respectively.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: ADH1A, ADH1B, and ADH1C, one to class-II: ADH4, one to class-III: ADH5, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the zinc-containing alcohol dehydrogenase family.</text>
    </comment>
    <dbReference type="EC" id="1.1.1.1" evidence="4"/>
    <dbReference type="EMBL" id="M12963">
        <property type="protein sequence ID" value="AAA51590.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M12271">
        <property type="protein sequence ID" value="AAA68131.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT019812">
        <property type="protein sequence ID" value="AAV38615.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY948115">
        <property type="protein sequence ID" value="AAX20115.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290558">
        <property type="protein sequence ID" value="BAF83247.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471057">
        <property type="protein sequence ID" value="EAX06094.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074738">
        <property type="protein sequence ID" value="AAH74738.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC117442">
        <property type="protein sequence ID" value="AAI17443.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC126306">
        <property type="protein sequence ID" value="AAI26307.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M37066">
        <property type="protein sequence ID" value="AAA51591.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3648.1"/>
    <dbReference type="PIR" id="S02265">
        <property type="entry name" value="DEHUAA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000658.1">
        <property type="nucleotide sequence ID" value="NM_000667.4"/>
    </dbReference>
    <dbReference type="PDB" id="1HSO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=2-375"/>
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    <dbReference type="PDB" id="1U3T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.49 A"/>
        <property type="chains" value="A/B=2-375"/>
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    <dbReference type="PDBsum" id="1HSO"/>
    <dbReference type="PDBsum" id="1U3T"/>
    <dbReference type="AlphaFoldDB" id="P07327"/>
    <dbReference type="SMR" id="P07327"/>
    <dbReference type="BioGRID" id="106636">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="CORUM" id="P07327"/>
    <dbReference type="FunCoup" id="P07327">
        <property type="interactions" value="247"/>
    </dbReference>
    <dbReference type="IntAct" id="P07327">
        <property type="interactions" value="4"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000209668"/>
    <dbReference type="BindingDB" id="P07327"/>
    <dbReference type="ChEMBL" id="CHEMBL1970"/>
    <dbReference type="DrugBank" id="DB02721">
        <property type="generic name" value="4-Iodopyrazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01213">
        <property type="generic name" value="Fomepizole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04065">
        <property type="generic name" value="N-Cyclopentyl-N-Cyclobutylformamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P07327"/>
    <dbReference type="GlyGen" id="P07327">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P07327"/>
    <dbReference type="PhosphoSitePlus" id="P07327"/>
    <dbReference type="BioMuta" id="ADH1A"/>
    <dbReference type="DMDM" id="113390"/>
    <dbReference type="jPOST" id="P07327"/>
    <dbReference type="MassIVE" id="P07327"/>
    <dbReference type="PaxDb" id="9606-ENSP00000209668"/>
    <dbReference type="PeptideAtlas" id="P07327"/>
    <dbReference type="ProteomicsDB" id="51988"/>
    <dbReference type="Antibodypedia" id="4031">
        <property type="antibodies" value="263 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="124"/>
    <dbReference type="Ensembl" id="ENST00000209668.3">
        <property type="protein sequence ID" value="ENSP00000209668.2"/>
        <property type="gene ID" value="ENSG00000187758.9"/>
    </dbReference>
    <dbReference type="GeneID" id="124"/>
    <dbReference type="KEGG" id="hsa:124"/>
    <dbReference type="MANE-Select" id="ENST00000209668.3">
        <property type="protein sequence ID" value="ENSP00000209668.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000667.4"/>
        <property type="RefSeq protein sequence ID" value="NP_000658.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003hur.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:249"/>
    <dbReference type="ClinPGx" id="PA24570"/>
    <dbReference type="CTD" id="124"/>
    <dbReference type="DisGeNET" id="124"/>
    <dbReference type="GeneCards" id="ADH1A"/>
    <dbReference type="HGNC" id="HGNC:249">
        <property type="gene designation" value="ADH1A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000187758">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="103700">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000187758"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000187758"/>
    <dbReference type="eggNOG" id="KOG0022">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155234"/>
    <dbReference type="HOGENOM" id="CLU_026673_14_0_1"/>
    <dbReference type="InParanoid" id="P07327"/>
    <dbReference type="OMA" id="EPWYCFA"/>
    <dbReference type="OrthoDB" id="417550at2759"/>
    <dbReference type="PAN-GO" id="P07327">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P07327"/>
    <dbReference type="PathwayCommons" id="P07327"/>
    <dbReference type="Reactome" id="R-HSA-2161541">
        <property type="pathway name" value="Abacavir metabolism"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5365859">
        <property type="pathway name" value="RA biosynthesis pathway"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-71384">
        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P07327"/>
    <dbReference type="SignaLink" id="P07327"/>
    <dbReference type="Agora" id="ENSG00000187758"/>
    <dbReference type="BioGRID-ORCS" id="124">
        <property type="hits" value="13 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADH1A">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P07327"/>
    <dbReference type="GeneWiki" id="ADH1A"/>
    <dbReference type="GenomeRNAi" id="124"/>
    <dbReference type="Pharos" id="P07327">
        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P07327"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="P07327">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000187758">
        <property type="expression patterns" value="Expressed in right lobe of liver and 112 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036064">
        <property type="term" value="C:ciliary basal body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0004022">
        <property type="term" value="F:alcohol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0004745">
        <property type="term" value="F:all-trans-retinol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:1990362">
        <property type="term" value="F:butanol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="RHEA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0006066">
        <property type="term" value="P:alcohol metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042573">
        <property type="term" value="P:retinoic acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <sequence length="375" mass="39859" checksum="B6DF4D57080D9BC1" modified="2007-01-23" version="2">MSTAGKVIKCKAAVLWELKKPFSIEEVEVAPPKAHEVRIKMVAVGICGTDDHVVSGTMVTPLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLAIPQCGKCRICKNPESNYCLKNDVSNPQGTLQDGTSRFTCRRKPIHHFLGISTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTGYGSAVNVAKVTPGSTCAVFGLGGVGLSAIMGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPDSQNLSMNPMLLLTGRTWKGAILGGFKSKECVPKLVADFMAKKFSLDALITHVLPFEKINEGFDLLHSGKSIRTILMF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1992-12-01" modified="2026-01-28" version="197" xmlns="https://uniprot.org/uniprot">
    <accession>P28332</accession>
    <accession>A0A0A0MS56</accession>
    <accession>B3KS45</accession>
    <accession>Q58F53</accession>
    <name>ADH6_HUMAN</name>
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        <recommendedName>
            <fullName>Alcohol dehydrogenase 6</fullName>
            <ecNumber evidence="3">1.1.1.1</ecNumber>
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        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1991" name="Proc. Natl. Acad. Sci. U.S.A." volume="88" first="7610" last="7614">
            <title>A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme.</title>
            <authorList>
                <person name="Yasunami M."/>
                <person name="Chen C.-S."/>
                <person name="Yoshida A."/>
            </authorList>
            <dbReference type="PubMed" id="1881901"/>
            <dbReference type="DOI" id="10.1073/pnas.88.17.7610"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
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                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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                <person name="Itoh T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
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                <person name="Sasaki M."/>
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                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
    <reference key="3">
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            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS GLY-102 AND VAL-114</scope>
    </reference>
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                <person name="Warren W.C."/>
                <person name="Chinwalla A.T."/>
                <person name="Eddy S.R."/>
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                <person name="Suyama M."/>
                <person name="Torrents D."/>
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                <person name="Wilson R.K."/>
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            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <title>Enzymatic properties of the protein encoded by newly cloned human alcohol dehydrogenase ADH6 gene.</title>
            <authorList>
                <person name="Chen C.S."/>
                <person name="Yoshida A."/>
            </authorList>
            <dbReference type="PubMed" id="1755855"/>
            <dbReference type="DOI" id="10.1016/0006-291x(91)91253-9"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
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                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
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            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1 3">Alcohol dehydrogenase (PubMed:1755855). Catalyzes the NAD-dependent oxidation of primary alcohols to the corresponding aldehydes (PubMed:1755855). Oxidizes secondary alcohols to the corresponding ketones (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>a primary alcohol + NAD(+) = an aldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10736"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15734"/>
            <dbReference type="ChEBI" id="CHEBI:17478"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>a secondary alcohol + NAD(+) = a ketone + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10740"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17087"/>
            <dbReference type="ChEBI" id="CHEBI:35681"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Inhibited partially by pyrazole (10 mM) in the reaction mixture containing 100 mM ethanol at pH 10.0.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">28 mM for ethanol (at pH 10.0 and 25 degrees Celsius)</KM>
            <KM evidence="3">3.2 mM for 1-propanol (at pH 10.0 and 25 degrees Celsius)</KM>
            <KM evidence="3">0.12 mM for benzyl alcohol (at pH 10.0 and 25 degrees Celsius)</KM>
        </kinetics>
        <phDependence>
            <text evidence="3">Optimum pH is 10.0.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="2">Dimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P28332-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P28332-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_037702"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4">Stomach and liver.</text>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="3">Isoelectric point (pH(I)) is 8.6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the zinc-containing alcohol dehydrogenase family. Class-V subfamily.</text>
    </comment>
    <dbReference type="EC" id="1.1.1.1" evidence="3"/>
    <dbReference type="EMBL" id="M84402">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84403">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84404">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84405">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84406">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84407">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84408">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M84409">
        <property type="protein sequence ID" value="AAA35509.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK092768">
        <property type="protein sequence ID" value="BAG52607.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY962311">
        <property type="protein sequence ID" value="AAX44051.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP002026">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="KF457794">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3647.1">
        <molecule id="P28332-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43255.1">
        <molecule id="P28332-2"/>
    </dbReference>
    <dbReference type="PIR" id="A41274">
        <property type="entry name" value="DEHUA6"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000663.1">
        <molecule id="P28332-1"/>
        <property type="nucleotide sequence ID" value="NM_000672.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001095940.1">
        <molecule id="P28332-2"/>
        <property type="nucleotide sequence ID" value="NM_001102470.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P28332"/>
    <dbReference type="SMR" id="P28332"/>
    <dbReference type="BioGRID" id="106642">
        <property type="interactions" value="11"/>
    </dbReference>
    <dbReference type="FunCoup" id="P28332">
        <property type="interactions" value="247"/>
    </dbReference>
    <dbReference type="IntAct" id="P28332">
        <property type="interactions" value="9"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000378359"/>
    <dbReference type="ChEMBL" id="CHEMBL2096668"/>
    <dbReference type="DrugBank" id="DB01048">
        <property type="generic name" value="Abacavir"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="GlyGen" id="P28332">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P28332"/>
    <dbReference type="PhosphoSitePlus" id="P28332"/>
    <dbReference type="BioMuta" id="ADH6"/>
    <dbReference type="DMDM" id="254763246"/>
    <dbReference type="jPOST" id="P28332"/>
    <dbReference type="MassIVE" id="P28332"/>
    <dbReference type="PaxDb" id="9606-ENSP00000378359"/>
    <dbReference type="PeptideAtlas" id="P28332"/>
    <dbReference type="ProteomicsDB" id="54474">
        <molecule id="P28332-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="54475">
        <molecule id="P28332-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="14841">
        <property type="antibodies" value="164 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="130"/>
    <dbReference type="Ensembl" id="ENST00000237653.11">
        <molecule id="P28332-1"/>
        <property type="protein sequence ID" value="ENSP00000237653.7"/>
        <property type="gene ID" value="ENSG00000172955.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000394899.6">
        <molecule id="P28332-2"/>
        <property type="protein sequence ID" value="ENSP00000378359.2"/>
        <property type="gene ID" value="ENSG00000172955.18"/>
    </dbReference>
    <dbReference type="GeneID" id="130"/>
    <dbReference type="KEGG" id="hsa:130"/>
    <dbReference type="MANE-Select" id="ENST00000394899.6">
        <molecule id="P28332-2"/>
        <property type="protein sequence ID" value="ENSP00000378359.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001102470.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001095940.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003hup.5">
        <molecule id="P28332-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:255"/>
    <dbReference type="ClinPGx" id="PA24576"/>
    <dbReference type="CTD" id="130"/>
    <dbReference type="DisGeNET" id="130"/>
    <dbReference type="GeneCards" id="ADH6"/>
    <dbReference type="HGNC" id="HGNC:255">
        <property type="gene designation" value="ADH6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000172955">
        <property type="expression patterns" value="Tissue enriched (liver)"/>
    </dbReference>
    <dbReference type="MIM" id="103735">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000172955"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000172955"/>
    <dbReference type="eggNOG" id="KOG0022">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163645"/>
    <dbReference type="HOGENOM" id="CLU_026673_14_0_1"/>
    <dbReference type="InParanoid" id="P28332"/>
    <dbReference type="OMA" id="QVNEGYQ"/>
    <dbReference type="OrthoDB" id="417550at2759"/>
    <dbReference type="PAN-GO" id="P28332">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P28332"/>
    <dbReference type="PathwayCommons" id="P28332"/>
    <dbReference type="Reactome" id="R-HSA-71384">
        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P28332"/>
    <dbReference type="Agora" id="ENSG00000172955"/>
    <dbReference type="BioGRID-ORCS" id="130">
        <property type="hits" value="14 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADH6"/>
    <dbReference type="GenomeRNAi" id="130"/>
    <dbReference type="Pharos" id="P28332">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P28332"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="P28332">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000172955">
        <property type="expression patterns" value="Expressed in right lobe of liver and 113 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P28332">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070062">
        <property type="term" value="C:extracellular exosome"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004022">
        <property type="term" value="F:alcohol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004745">
        <property type="term" value="F:all-trans-retinol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042573">
        <property type="term" value="P:retinoic acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042572">
        <property type="term" value="P:retinol metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd08299">
        <property type="entry name" value="alcohol_DH_class_I_II_IV"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.180.10:FF:000007">
        <property type="entry name" value="Alcohol dehydrogenase 6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.720:FF:000003">
        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.180.10">
        <property type="entry name" value="Medium-chain alcohol dehydrogenases, catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.720">
        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013149">
        <property type="entry name" value="ADH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013154">
        <property type="entry name" value="ADH-like_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002328">
        <property type="entry name" value="ADH_Zn_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020843">
        <property type="entry name" value="ER"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011032">
        <property type="entry name" value="GroES-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880">
        <property type="entry name" value="ALCOHOL DEHYDROGENASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880:SF20">
        <property type="entry name" value="ALCOHOL DEHYDROGENASE 6"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08240">
        <property type="entry name" value="ADH_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00107">
        <property type="entry name" value="ADH_zinc_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00829">
        <property type="entry name" value="PKS_ER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50129">
        <property type="entry name" value="GroES-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51735">
        <property type="entry name" value="NAD(P)-binding Rossmann-fold domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00059">
        <property type="entry name" value="ADH_ZINC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0520">NAD</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000160687" description="Alcohol dehydrogenase 6">
        <location>
            <begin position="1"/>
            <end position="368"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="47"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="69"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="99"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="102"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="105"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="113"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="175"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="200"/>
            <end position="205"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="224"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <position position="229"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="293"/>
            <end position="295"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="8">
        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_037702" description="In isoform 2." evidence="6">
        <original>W</original>
        <variation>CIRCILLL</variation>
        <location>
            <position position="368"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022655" description="In dbSNP:rs28720152." evidence="5">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="102"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022656" description="In dbSNP:rs28720153." evidence="5">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048198" description="In dbSNP:rs34582580.">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAG52607." evidence="7" ref="2">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P07327"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P41681"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="1755855"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="1881901"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="368" mass="39073" checksum="EC8E81E9571E6241" modified="2018-09-12" version="3">MSTTGQVIRCKAAILWKPGAPFSIEEVEVAPPKAKEVRIKVVATGLCGTEMKVLGSKHLDLLYPTILGHEGAGIVESIGEGVSTVKPGDKVITLFLPQCGECTSCLNSEGNFCIQFKQSKTQLMSDGTSRFTCKGKSIYHFGNTSTFCEYTVIKEISVAKIDAVAPLEKVCLISCGFSTGFGAAINTAKVTPGSTCAVFGLGGVGLSVVMGCKAAGAARIIGVDVNKEKFKKAQELGATECLNPQDLKKPIQEVLFDMTDAGIDFCFEAIGNLDVLAAALASCNESYGVCVVVGVLPASVQLKISGQLFFSGRSLKGSVFGGWKSRQHIPKLVADYMAEKLNLDPLITHTLNLDKINEAVELMKTGKW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-02-01" modified="2026-01-28" version="211" xmlns="https://uniprot.org/uniprot">
    <accession>P40394</accession>
    <accession>A2RRB6</accession>
    <accession>A8MVN9</accession>
    <accession>B2R760</accession>
    <accession>B4DWV6</accession>
    <accession>Q13713</accession>
    <name>ADH7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">All-trans-retinol dehydrogenase [NAD(+)] ADH7</fullName>
            <ecNumber evidence="2 3">1.1.1.105</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase class 4 mu/sigma chain</fullName>
            <ecNumber evidence="4">1.1.1.1</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase class IV mu/sigma chain</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Gastric alcohol dehydrogenase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="6">Omega-hydroxydecanoate dehydrogenase ADH7</fullName>
            <ecNumber evidence="4">1.1.1.66</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Retinol dehydrogenase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="10" type="primary">ADH7</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Alcohol dehydrogenase of class IV (sigma sigma-ADH) from human stomach. cDNA sequence and structure/function relationships.</title>
            <authorList>
                <person name="Farres J."/>
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            </authorList>
            <dbReference type="PubMed" id="7925371"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1994.00549.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="J. Biol. Chem." volume="269" first="15606" last="15612">
            <title>The complete structure of human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene.</title>
            <authorList>
                <person name="Satre M.A."/>
                <person name="Zgombic-Knight M."/>
                <person name="Duester G."/>
            </authorList>
            <dbReference type="PubMed" id="8195208"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(17)40724-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1995" name="J. Biol. Chem." volume="270" first="4305" last="4311">
            <title>Genomic structure and expression of the ADH7 gene encoding human class IV alcohol dehydrogenase, the form most efficient for retinol metabolism in vitro.</title>
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                <person name="Zgombic-Knight M."/>
                <person name="Foglio M.H."/>
                <person name="Duester G."/>
            </authorList>
            <dbReference type="PubMed" id="7876191"/>
            <dbReference type="DOI" id="10.1074/jbc.270.9.4305"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
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                <person name="Murakawa K."/>
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                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Esophagus</tissue>
            <tissue>Trachea</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="15815621"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
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            <dbReference type="PubMed" id="8082805"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 13-386 (ISOFORM 1)</scope>
        <scope>ZINC-BINDING SITES</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
    </reference>
    <reference key="9">
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            <dbReference type="PubMed" id="7876099"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 13-386 (ISOFORM 1)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
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                <person name="Yokoyama H."/>
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            </authorList>
            <dbReference type="PubMed" id="8824810"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-386</scope>
        <source>
            <tissue>Foreskin</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="1592118"/>
            <dbReference type="DOI" id="10.1016/0014-5793(92)80479-z"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 24-33; 53-58; 74-92; 97-123; 147-154 AND 181-186</scope>
    </reference>
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            <dbReference type="PubMed" id="7771649"/>
            <dbReference type="DOI" id="10.1111/j.1530-0277.1995.tb01490.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 239-311 (ISOFORM 1)</scope>
        <source>
            <tissue>Stomach</tissue>
        </source>
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                <person name="Allali-Hassani A."/>
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            </authorList>
            <dbReference type="PubMed" id="9600267"/>
            <dbReference type="DOI" id="10.1016/s0014-5793(98)00374-3"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>ACTIVITY REGULATION</scope>
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            <title>Kinetics of human alcohol dehydrogenase with ring-oxidized retinoids: effect of Tween 80.</title>
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                <person name="Martras S."/>
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                <person name="de Lera A.R."/>
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            </authorList>
            <dbReference type="PubMed" id="15369820"/>
            <dbReference type="DOI" id="10.1016/j.abb.2004.07.002"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
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                <person name="Gallego O."/>
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                <person name="Porte S."/>
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                <person name="Pares X."/>
                <person name="Kedishvili N.Y."/>
            </authorList>
            <dbReference type="PubMed" id="16787387"/>
            <dbReference type="DOI" id="10.1042/bj20051988"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1997" name="J. Biol. Chem." volume="272" first="18558" last="18563">
            <title>X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity.</title>
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                <person name="Xie P."/>
                <person name="Parsons S.H."/>
                <person name="Speckhard D.C."/>
                <person name="Bosron W.F."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="9228021"/>
            <dbReference type="DOI" id="10.1074/jbc.272.30.18558"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 14-386</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="1999" name="Protein Sci." volume="8" first="2639" last="2644">
            <title>Methionine-141 directly influences the binding of 4-methylpyrazole in human sigma sigma alcohol dehydrogenase.</title>
            <authorList>
                <person name="Xie P.T."/>
                <person name="Hurley T.D."/>
            </authorList>
            <dbReference type="PubMed" id="10631979"/>
            <dbReference type="DOI" id="10.1110/ps.8.12.2639"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 14-386 IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 4">Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, and omega-hydroxy fatty acids and their derivatives (PubMed:15369820, PubMed:16787387, PubMed:9600267). Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol, 9-cis-retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such as juniperic acid (PubMed:15369820, PubMed:16787387, PubMed:9600267). In vitro can also catalyze the NADH-dependent reduction of all-trans-retinal and aldehydes and their derivatives (PubMed:15369820, PubMed:16787387, PubMed:9600267). Reduces preferentially all trans-retinal, all-trans-4-oxoretinal and hexanal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:15369820, PubMed:16787387). Therefore may participate in retinoid metabolism, fatty acid omega-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation (PubMed:15369820, PubMed:16787387, PubMed:9600267).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a primary alcohol + NAD(+) = an aldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10736"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15734"/>
            <dbReference type="ChEBI" id="CHEBI:17478"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:10737"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="9">
            <dbReference type="Rhea" id="RHEA:10738"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>10-hydroxydecanoate + NAD(+) = 10-oxodecanoate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20880"/>
            <dbReference type="ChEBI" id="CHEBI:11305"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:58022"/>
            <dbReference type="EC" id="1.1.1.66"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:20881"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3 4">
            <text>all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:21284"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17336"/>
            <dbReference type="ChEBI" id="CHEBI:17898"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.105"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:21285"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>9-cis-retinol + NAD(+) = 9-cis-retinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:42052"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:78272"/>
            <dbReference type="ChEBI" id="CHEBI:78273"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:42053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>all-trans-3,4-didehydroretinol + NAD(+) = all-trans-3,4-didehydroretinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55940"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28537"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:132246"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:55941"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-hydroxyretinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55936"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:132259"/>
            <dbReference type="ChEBI" id="CHEBI:139346"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:55937"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60632"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:44597"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:139347"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="7">
            <dbReference type="Rhea" id="RHEA:60634"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>12-hydroxydodecanoate + NAD(+) = 12-oxododecanoate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60980"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:36204"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:144067"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:60981"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>16-hydroxyhexadecanoate + NAD(+) = 16-oxohexadecanoate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60984"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:55329"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:144068"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:60985"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>hexan-1-ol + NAD(+) = hexanal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60972"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:87393"/>
            <dbReference type="ChEBI" id="CHEBI:88528"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:60973"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="9">
            <dbReference type="Rhea" id="RHEA:60974"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>(E)-hex-2-en-1-ol + NAD(+) = (E)-hex-2-enal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60988"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28913"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:141205"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:60989"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="9">
            <dbReference type="Rhea" id="RHEA:60990"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>(E)-4-hydroxynon-2-en-1-ol + NAD(+) = (E)-4-hydroxynon-2-enal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60976"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:58968"/>
            <dbReference type="ChEBI" id="CHEBI:142617"/>
        </reaction>
        <physiologicalReaction direction="right-to-left" evidence="9">
            <dbReference type="Rhea" id="RHEA:60978"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="1">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="2 4">Retinol oxidation is inhibited by the detergent Tween 80 (PubMed:15369820). Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation (PubMed:9600267). 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation (PubMed:9600267). All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation (PubMed:9600267). Cimetidine competitively inhibited ethanol oxidation (PubMed:9600267).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="2">23 uM for all-trans-retinol</KM>
            <KM evidence="2">15 uM for all-trans-4-hydroxyretinol</KM>
            <KM evidence="2">28 uM for all-trans-3,4-didehydroretinol</KM>
            <KM evidence="2 4">34 uM for all-trans-retinal</KM>
            <KM evidence="2">17 uM for all-trans-4-oxoretinal</KM>
            <KM evidence="2">26 uM for all-trans-3,4-didehydroretinal</KM>
            <KM evidence="3">0.3 uM for all-trans-retinol</KM>
            <KM evidence="3">0.8 uM for all-trans-retinal</KM>
            <KM evidence="4">0.1 mM for 10-OH-decanoic acid (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.17 mM for 12-OH-dodecanoic acid (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.07 mM for 12-OH-dodecanoic acid (with 0.1 M glycine/NaOH at pH 10)</KM>
            <KM evidence="4">0.035 mM for 16-OH-hexadecanoic acid (with 0.1 M glycine/NaOH at pH 10)</KM>
            <KM evidence="4">0.14 mM for hexanol (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.02 mM for hexanal (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.017 mM for 2-hexenol (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.025 mM for 2-hexenal (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">0.038 mM for 4-hydroxynonenal (with 0.1 M sodium phosphate at pH 7.5)</KM>
            <KM evidence="4">15 uM for all-trans-retinol</KM>
            <KM evidence="4">36 uM for 9-cis-retinol</KM>
            <KM evidence="4">21 uM for 9-cis-retinal</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homodimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P40394-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P40394-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043093"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Preferentially expressed in stomach.</text>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the zinc-containing alcohol dehydrogenase family. Class-IV subfamily.</text>
    </comment>
    <comment type="caution">
        <text evidence="6">It is uncertain whether Met-1 or Met-13 is the initiator.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAA19002" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAC51351" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAG35707" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA53960" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="CAA53961" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="1.1.1.105" evidence="2 3"/>
    <dbReference type="EC" id="1.1.1.1" evidence="4"/>
    <dbReference type="EC" id="1.1.1.66" evidence="4"/>
    <dbReference type="EMBL" id="X76342">
        <property type="protein sequence ID" value="CAA53961.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X76342">
        <property type="protein sequence ID" value="CAA53960.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U07821">
        <property type="protein sequence ID" value="AAA19002.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16293">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16286">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16287">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16288">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16289">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16290">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16291">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U16292">
        <property type="protein sequence ID" value="AAC51351.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301696">
        <property type="protein sequence ID" value="BAG63168.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312854">
        <property type="protein sequence ID" value="BAG35707.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP001960">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471057">
        <property type="protein sequence ID" value="EAX06101.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC131512">
        <property type="protein sequence ID" value="AAI31513.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L33179">
        <property type="protein sequence ID" value="AAA59211.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U09623">
        <property type="protein sequence ID" value="AAA82165.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L47166">
        <property type="protein sequence ID" value="AAB38424.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="S77168">
        <property type="protein sequence ID" value="AAB34478.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54781.1">
        <molecule id="P40394-2"/>
    </dbReference>
    <dbReference type="PIR" id="A55878">
        <property type="entry name" value="DEHUAS"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000664.3">
        <property type="nucleotide sequence ID" value="NM_000673.7"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159976.1">
        <molecule id="P40394-2"/>
        <property type="nucleotide sequence ID" value="NM_001166504.2"/>
    </dbReference>
    <dbReference type="PDB" id="1AGN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D=14-386"/>
    </dbReference>
    <dbReference type="PDB" id="1D1S">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B/C/D=14-386"/>
    </dbReference>
    <dbReference type="PDB" id="1D1T">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B/C/D=14-386"/>
    </dbReference>
    <dbReference type="PDBsum" id="1AGN"/>
    <dbReference type="PDBsum" id="1D1S"/>
    <dbReference type="PDBsum" id="1D1T"/>
    <dbReference type="AlphaFoldDB" id="P40394"/>
    <dbReference type="SMR" id="P40394"/>
    <dbReference type="BioGRID" id="106643">
        <property type="interactions" value="14"/>
    </dbReference>
    <dbReference type="FunCoup" id="P40394">
        <property type="interactions" value="273"/>
    </dbReference>
    <dbReference type="IntAct" id="P40394">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000420269"/>
    <dbReference type="BindingDB" id="P40394"/>
    <dbReference type="ChEMBL" id="CHEMBL3867"/>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="SwissLipids" id="SLP:000001879"/>
    <dbReference type="iPTMnet" id="P40394"/>
    <dbReference type="PhosphoSitePlus" id="P40394"/>
    <dbReference type="BioMuta" id="ADH7"/>
    <dbReference type="DMDM" id="292495000"/>
    <dbReference type="jPOST" id="P40394"/>
    <dbReference type="MassIVE" id="P40394"/>
    <dbReference type="PaxDb" id="9606-ENSP00000420269"/>
    <dbReference type="PeptideAtlas" id="P40394"/>
    <dbReference type="PRIDE" id="P40394"/>
    <dbReference type="ProteomicsDB" id="55365">
        <molecule id="P40394-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="55366">
        <molecule id="P40394-2"/>
    </dbReference>
    <dbReference type="Pumba" id="P40394"/>
    <dbReference type="Antibodypedia" id="25891">
        <property type="antibodies" value="364 antibodies from 32 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="131"/>
    <dbReference type="Ensembl" id="ENST00000209665.8">
        <molecule id="P40394-1"/>
        <property type="protein sequence ID" value="ENSP00000209665.4"/>
        <property type="gene ID" value="ENSG00000196344.12"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000476959.5">
        <molecule id="P40394-2"/>
        <property type="protein sequence ID" value="ENSP00000420269.1"/>
        <property type="gene ID" value="ENSG00000196344.12"/>
    </dbReference>
    <dbReference type="GeneID" id="131"/>
    <dbReference type="KEGG" id="hsa:131"/>
    <dbReference type="UCSC" id="uc003huv.2">
        <molecule id="P40394-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:256"/>
    <dbReference type="ClinPGx" id="PA24577"/>
    <dbReference type="CTD" id="131"/>
    <dbReference type="DisGeNET" id="131"/>
    <dbReference type="GeneCards" id="ADH7"/>
    <dbReference type="HGNC" id="HGNC:256">
        <property type="gene designation" value="ADH7"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000196344">
        <property type="expression patterns" value="Tissue enriched (esophagus)"/>
    </dbReference>
    <dbReference type="MIM" id="600086">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000196344"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000196344"/>
    <dbReference type="eggNOG" id="KOG0022">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162708"/>
    <dbReference type="InParanoid" id="P40394"/>
    <dbReference type="OrthoDB" id="417550at2759"/>
    <dbReference type="PAN-GO" id="P40394">
        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P40394"/>
    <dbReference type="PathwayCommons" id="P40394"/>
    <dbReference type="Reactome" id="R-HSA-71384">
        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P40394"/>
    <dbReference type="Agora" id="ENSG00000196344"/>
    <dbReference type="BioGRID-ORCS" id="131">
        <property type="hits" value="8 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P40394"/>
    <dbReference type="GeneWiki" id="ADH7"/>
    <dbReference type="GenomeRNAi" id="131"/>
    <dbReference type="Pharos" id="P40394">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P40394"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="P40394">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000196344">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 111 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P40394">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004022">
        <property type="term" value="F:alcohol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004031">
        <property type="term" value="F:aldehyde oxidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004745">
        <property type="term" value="F:all-trans-retinol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035276">
        <property type="term" value="F:ethanol binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050153">
        <property type="term" value="F:omega-hydroxydecanoate dehydrogenase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-EC"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048019">
        <property type="term" value="F:receptor antagonist activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0019841">
        <property type="term" value="F:retinol binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010430">
        <property type="term" value="P:fatty acid omega-oxidation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009617">
        <property type="term" value="P:response to bacterium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045471">
        <property type="term" value="P:response to ethanol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042573">
        <property type="term" value="P:retinoic acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001523">
        <property type="term" value="P:retinoid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042572">
        <property type="term" value="P:retinol metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd08299">
        <property type="entry name" value="alcohol_DH_class_I_II_IV"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.720:FF:001857">
        <property type="entry name" value="Alcohol dehydrogenase class 4 mu/sigma chain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.180.10:FF:000001">
        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.180.10">
        <property type="entry name" value="Medium-chain alcohol dehydrogenases, catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.720">
        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013149">
        <property type="entry name" value="ADH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013154">
        <property type="entry name" value="ADH-like_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002328">
        <property type="entry name" value="ADH_Zn_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011032">
        <property type="entry name" value="GroES-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880">
        <property type="entry name" value="ALCOHOL DEHYDROGENASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880:SF2">
        <property type="entry name" value="ALL-TRANS-RETINOL DEHYDROGENASE [NAD(+)] ADH7"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08240">
        <property type="entry name" value="ADH_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00107">
        <property type="entry name" value="ADH_zinc_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50129">
        <property type="entry name" value="GroES-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF51735">
        <property type="entry name" value="NAD(P)-binding Rossmann-fold domains"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00059">
        <property type="entry name" value="ADH_ZINC"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0520">NAD</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="chain" id="PRO_0000160691" description="All-trans-retinol dehydrogenase [NAD(+)] ADH7">
        <location>
            <begin position="1"/>
            <end position="386"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="59"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <begin position="60"/>
            <end position="64"/>
        </location>
        <ligand>
            <name>NAD(+)</name>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="80"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>1</label>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="110"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="113"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="116"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="124"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 11 12 13">
        <location>
            <position position="186"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
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        <citation type="journal article" date="1985" name="Proc. Natl. Acad. Sci. U.S.A." volume="82" first="2703" last="2707">
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                <person name="Fujiyoshi T."/>
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                <person name="Yoshida A."/>
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                <person name="Fujiyoshi T."/>
                <person name="Kurachi K."/>
                <person name="Yoshida A."/>
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        <citation type="journal article" date="1986" name="FEBS Lett." volume="194" first="327" last="332">
            <title>cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions.</title>
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                <person name="Hoeoeg J.-O."/>
                <person name="Larsson K."/>
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                <person name="Lagerholm E."/>
                <person name="Holmgren A."/>
                <person name="Vallee B.L."/>
                <person name="Joernvall H."/>
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            <title>Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit.</title>
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                <person name="Bilanchone V."/>
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            <dbReference type="DOI" id="10.1016/s0021-9258(17)35892-1"/>
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            <title>Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence.</title>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <citation type="journal article" date="1987" name="Jpn. J. Genet." volume="62" first="241" last="256">
            <title>Molecular characterization of cDNA clones encoding the human alcohol dehydrogenase beta 1 and the evolutionary relationship to the other class I subunits alpha and gamma.</title>
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                <person name="Rotwein P."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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    <reference key="7">
        <citation type="journal article" date="1989" name="Alcohol. Clin. Exp. Res." volume="13" first="594" last="596">
            <title>Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit.</title>
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        <citation type="journal article" date="1989" name="Eur. J. Biochem." volume="183" first="317" last="320">
            <title>The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide.</title>
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                <person name="Matsuo Y."/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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            <authorList>
                <person name="Polin L."/>
                <person name="Hey-Chi H."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <tissue>Liver</tissue>
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        <citation type="submission" date="2005-04" db="EMBL/GenBank/DDBJ databases">
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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    <reference key="11">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
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    <comment type="function">
        <text evidence="3 5">Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitro can also catalyze the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387). Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal (PubMed:15369820).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:21284"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17336"/>
            <dbReference type="ChEBI" id="CHEBI:17898"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.105"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:21285"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>all-trans-4-hydroxyretinol + NAD(+) = all-trans-4-hydroxyretinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:55936"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:132259"/>
            <dbReference type="ChEBI" id="CHEBI:139346"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="20">
            <dbReference type="Rhea" id="RHEA:55937"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>all-trans-4-oxoretinol + NAD(+) = all-trans-4-oxoretinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:60632"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:44597"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:139347"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text>Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">4 uM for all-trans-4-hydroxyretinol (in allele ADH1B*1)</KM>
            <KM evidence="3">25 uM for all-trans-4-oxoretinal (in allele ADH1B*1)</KM>
            <KM evidence="3">11 uM for all-trans-4-hydroxyretinol (in allele ADH1B*2)</KM>
            <KM evidence="3">27 uM for all-trans-4-oxoretinal (in allele ADH1B*2)</KM>
            <KM evidence="3">24 uM for all-trans-3,4-didehydroretinol(in allele ADH1B*2)</KM>
            <KM evidence="3">25 uM for all-trans-3,4-didehydroretinal(in allele ADH1B*2)</KM>
            <KM evidence="5">0.4 uM for all-trans-retinaldehyde (in allele ADH1B*2)</KM>
            <KM evidence="5">0.3 uM for all-trans-retinol (in allele ADH1B*2)</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text>Dimer of identical or non-identical chains of three types; alpha, beta and gamma.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838677">
            <id>P00325</id>
        </interactant>
        <interactant intactId="EBI-21822364">
            <id>P00326</id>
            <label>ADH1C</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P00325-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P00325-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054847"/>
        </isoform>
    </comment>
    <comment type="polymorphism">
        <text evidence="1 6 7 12 13">Three alleles are known: ADH1B*1 (ADH2*1) corresponding to variant beta-1, ADH1B*2 (ADH2*2) corresponding to variant beta-2, ADH1B*3 (ADH2*3) corresponding to variant beta-3. The sequence shown is that of allele ADH1B*2. The ADH1B*2 allele frequency in orientals is approximately 75%, whereas it is less than 5% in most Caucasian populations. The ADH1B*2 allele is associated with a lower risk of alcoholism. ADH1B variations have been associated with protection against alcohol dependence and alcohol-related aerodigestive tract cancer [MIM:103720].</text>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the zinc-containing alcohol dehydrogenase family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA51884.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X03350">
        <property type="protein sequence ID" value="CAA27056.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M24316">
        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M24312">
        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M24313">
        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M24314">
        <property type="protein sequence ID" value="AAB59496.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D00137">
        <property type="protein sequence ID" value="BAA00084.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L38290">
        <property type="protein sequence ID" value="AAB48003.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB48003.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L38284">
        <property type="protein sequence ID" value="AAB48003.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <property type="protein sequence ID" value="AAB48003.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAB48003.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAB48003.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAB48003.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAB48003.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X15447">
        <property type="protein sequence ID" value="CAA33487.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA33487.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA33487.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA33487.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="CAA33487.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X15454">
        <property type="protein sequence ID" value="CAA33487.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X15455">
        <property type="protein sequence ID" value="CAA33487.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF153821">
        <property type="protein sequence ID" value="AAD37446.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ017646">
        <property type="protein sequence ID" value="AAY22180.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301018">
        <property type="protein sequence ID" value="BAG62635.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC097530">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033009">
        <property type="protein sequence ID" value="AAH33009.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M21692">
        <property type="protein sequence ID" value="AAA51592.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF040967">
        <property type="protein sequence ID" value="AAB96912.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34033.1">
        <molecule id="P00325-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS68761.1">
        <molecule id="P00325-2"/>
    </dbReference>
    <dbReference type="PIR" id="A23607">
        <property type="entry name" value="DEHUAB"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000659.2">
        <molecule id="P00325-1"/>
        <property type="nucleotide sequence ID" value="NM_000668.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273579.1">
        <molecule id="P00325-2"/>
        <property type="nucleotide sequence ID" value="NM_001286650.2"/>
    </dbReference>
    <dbReference type="PDB" id="1DEH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1HDX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1HDY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1HDZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1HSZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.20 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1HTB">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.40 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1U3U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="1U3V">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.65 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDB" id="3HUD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.20 A"/>
        <property type="chains" value="A/B=2-375"/>
    </dbReference>
    <dbReference type="PDBsum" id="1DEH"/>
    <dbReference type="PDBsum" id="1HDX"/>
    <dbReference type="PDBsum" id="1HDY"/>
    <dbReference type="PDBsum" id="1HDZ"/>
    <dbReference type="PDBsum" id="1HSZ"/>
    <dbReference type="PDBsum" id="1HTB"/>
    <dbReference type="PDBsum" id="1U3U"/>
    <dbReference type="PDBsum" id="1U3V"/>
    <dbReference type="PDBsum" id="3HUD"/>
    <dbReference type="AlphaFoldDB" id="P00325"/>
    <dbReference type="SMR" id="P00325"/>
    <dbReference type="BioGRID" id="106637">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="CORUM" id="P00325"/>
    <dbReference type="FunCoup" id="P00325">
        <property type="interactions" value="299"/>
    </dbReference>
    <dbReference type="IntAct" id="P00325">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="MINT" id="P00325"/>
    <dbReference type="STRING" id="9606.ENSP00000306606"/>
    <dbReference type="BindingDB" id="P00325"/>
    <dbReference type="ChEMBL" id="CHEMBL3284"/>
    <dbReference type="DrugBank" id="DB02721">
        <property type="generic name" value="4-Iodopyrazole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03703">
        <property type="generic name" value="Cyclohexanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00898">
        <property type="generic name" value="Ethanol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01213">
        <property type="generic name" value="Fomepizole"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB09462">
        <property type="generic name" value="Glycerin"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB02481">
        <property type="generic name" value="N-Benzylformamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB04105">
        <property type="generic name" value="N-Heptylformamide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB00157">
        <property type="generic name" value="NADH"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03461">
        <property type="generic name" value="Nicotinamide adenine dinucleotide phosphate"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P00325"/>
    <dbReference type="SwissLipids" id="SLP:000001880"/>
    <dbReference type="GlyGen" id="P00325">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P00325"/>
    <dbReference type="PhosphoSitePlus" id="P00325"/>
    <dbReference type="SwissPalm" id="P00325"/>
    <dbReference type="BioMuta" id="ADH1B"/>
    <dbReference type="DMDM" id="113394"/>
    <dbReference type="jPOST" id="P00325"/>
    <dbReference type="MassIVE" id="P00325"/>
    <dbReference type="PaxDb" id="9606-ENSP00000306606"/>
    <dbReference type="PeptideAtlas" id="P00325"/>
    <dbReference type="ProteomicsDB" id="2413"/>
    <dbReference type="ProteomicsDB" id="51228">
        <molecule id="P00325-1"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="14861">
        <property type="antibodies" value="302 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="125"/>
    <dbReference type="Ensembl" id="ENST00000305046.13">
        <molecule id="P00325-1"/>
        <property type="protein sequence ID" value="ENSP00000306606.8"/>
        <property type="gene ID" value="ENSG00000196616.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000506651.5">
        <molecule id="P00325-2"/>
        <property type="protein sequence ID" value="ENSP00000425998.2"/>
        <property type="gene ID" value="ENSG00000196616.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000625860.2">
        <molecule id="P00325-2"/>
        <property type="protein sequence ID" value="ENSP00000486614.1"/>
        <property type="gene ID" value="ENSG00000196616.16"/>
    </dbReference>
    <dbReference type="GeneID" id="125"/>
    <dbReference type="KEGG" id="hsa:125"/>
    <dbReference type="MANE-Select" id="ENST00000305046.13">
        <property type="protein sequence ID" value="ENSP00000306606.8"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_000668.6"/>
        <property type="RefSeq protein sequence ID" value="NP_000659.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc011cei.3">
        <molecule id="P00325-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:250"/>
    <dbReference type="ClinPGx" id="PA24571"/>
    <dbReference type="CTD" id="125"/>
    <dbReference type="DisGeNET" id="125"/>
    <dbReference type="GeneCards" id="ADH1B"/>
    <dbReference type="HGNC" id="HGNC:250">
        <property type="gene designation" value="ADH1B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000196616">
        <property type="expression patterns" value="Tissue enhanced (adipose tissue, liver)"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADH1B"/>
    <dbReference type="MIM" id="103720">
        <property type="type" value="gene+phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000196616"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000155234"/>
    <dbReference type="HOGENOM" id="CLU_026673_14_0_1"/>
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    <dbReference type="OrthoDB" id="417550at2759"/>
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        <property type="GO annotations" value="7 GO annotations based on evolutionary models"/>
    </dbReference>
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    <dbReference type="Reactome" id="R-HSA-71384">
        <property type="pathway name" value="Ethanol oxidation"/>
    </dbReference>
    <dbReference type="SABIO-RK" id="P00325"/>
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    <dbReference type="Agora" id="ENSG00000196616"/>
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        <property type="hits" value="6 hits in 1119 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADH1B">
        <property type="organism name" value="human"/>
    </dbReference>
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        <property type="development level" value="Tclin"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P00325"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="P00325">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000196616">
        <property type="expression patterns" value="Expressed in right lobe of liver and 172 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P00325">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036064">
        <property type="term" value="C:ciliary basal body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035869">
        <property type="term" value="C:ciliary transition zone"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005929">
        <property type="term" value="C:cilium"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004022">
        <property type="term" value="F:alcohol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004745">
        <property type="term" value="F:all-trans-retinol dehydrogenase (NAD+) activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042573">
        <property type="term" value="P:retinoic acid metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001523">
        <property type="term" value="P:retinoid metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042572">
        <property type="term" value="P:retinol metabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd08299">
        <property type="entry name" value="alcohol_DH_class_I_II_IV"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.720:FF:000003">
        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.90.180.10:FF:000001">
        <property type="entry name" value="S-(hydroxymethyl)glutathione dehydrogenase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.90.180.10">
        <property type="entry name" value="Medium-chain alcohol dehydrogenases, catalytic domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.720">
        <property type="entry name" value="NAD(P)-binding Rossmann-like Domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013149">
        <property type="entry name" value="ADH-like_C"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013154">
        <property type="entry name" value="ADH-like_N"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002328">
        <property type="entry name" value="ADH_Zn_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR020843">
        <property type="entry name" value="ER"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011032">
        <property type="entry name" value="GroES-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036291">
        <property type="entry name" value="NAD(P)-bd_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880">
        <property type="entry name" value="ALCOHOL DEHYDROGENASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43880:SF11">
        <property type="entry name" value="ALL-TRANS-RETINOL DEHYDROGENASE [NAD(+)] ADH1B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF08240">
        <property type="entry name" value="ADH_N"/>
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    <dbReference type="Pfam" id="PF00107">
        <property type="entry name" value="ADH_zinc_N"/>
        <property type="match status" value="1"/>
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    <dbReference type="SMART" id="SM00829">
        <property type="entry name" value="PKS_ER"/>
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        <property type="entry name" value="ADH_ZINC"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
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    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
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    <keyword id="KW-0560">Oxidoreductase</keyword>
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    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
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            <position position="1"/>
        </location>
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            <begin position="2"/>
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            <position position="47"/>
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            <dbReference type="ChEBI" id="CHEBI:29105"/>
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            <note>catalytic</note>
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    <feature type="binding site">
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        <ligand>
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    <feature type="binding site">
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            <position position="101"/>
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        <ligand>
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            <label>2</label>
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        <ligand>
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            <label>2</label>
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    <feature type="binding site">
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        <ligand>
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    <feature type="binding site">
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            <position position="175"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:29105"/>
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    <feature type="binding site">
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            <begin position="200"/>
            <end position="205"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57540"/>
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    <feature type="binding site">
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            <position position="224"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57540"/>
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    <feature type="binding site">
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            <position position="229"/>
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    <feature type="binding site">
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    <feature type="binding site">
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            <position position="370"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:57540"/>
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            <position position="2"/>
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    </feature>
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        <location>
            <position position="23"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="23">
        <location>
            <position position="35"/>
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            <begin position="1"/>
            <end position="40"/>
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        <location>
            <position position="48"/>
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        <location>
            <position position="57"/>
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    <feature type="sequence variant" id="VAR_019323" description="In dbSNP:rs6413413." evidence="15">
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        <variation>S</variation>
        <location>
            <position position="60"/>
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    </feature>
    <feature type="sequence variant" id="VAR_000427" description="In beta-3/Indianapolis; allele ADH1B*3; decreased NAD(H) binding; dbSNP:rs2066702." evidence="7 12 15">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="370"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 15; AAA51592." evidence="19" ref="15">
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            <position position="8"/>
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    <feature type="sequence conflict" description="In Ref. 14; AA sequence." evidence="19" ref="14">
        <location>
            <position position="130"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 15; AAA51592." evidence="19" ref="15">
        <original>P</original>
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        <location>
            <position position="166"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 8; CAA33487." evidence="19" ref="8">
        <original>V</original>
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        <location>
            <position position="190"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 11; BAG62635." evidence="19" ref="11">
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            <position position="220"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAA51884." evidence="19" ref="1">
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        <location>
            <position position="230"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 15; AAA51592." evidence="19" ref="15">
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            <position position="235"/>
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    <feature type="sequence conflict" description="In Ref. 11; BAG62635." evidence="19" ref="11">
        <location>
            <begin position="338"/>
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            <begin position="23"/>
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            <dbReference type="PubMed" id="3397059"/>
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        <source>
            <dbReference type="PubMed" id="3619918"/>
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        <source>
            <dbReference type="PubMed" id="6374651"/>
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        <source>
            <dbReference type="PubMed" id="6391920"/>
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    <evidence type="ECO:0000305" key="19"/>
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            <dbReference type="PubMed" id="16787387"/>
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    <evidence type="ECO:0000312" key="22">
        <source>
            <dbReference type="HGNC" id="HGNC:250"/>
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        <source>
            <dbReference type="PubMed" id="24275569"/>
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    </evidence>
    <evidence type="ECO:0007829" key="24">
        <source>
            <dbReference type="PDB" id="1HDY"/>
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    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="1U3U"/>
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    <sequence length="375" mass="39835" checksum="2C5104F834950B1A" modified="2022-02-23" version="3">MSTAGKVIKCKAAVLWEVKKPFSIEDVEVAPPKAYEVRIKMVAVGICHTDDHVVSGNLVTPLPVILGHEAAGIVESVGEGVTTVKPGDKVIPLFTPQCGKCRVCKNPESNYCLKNDLGNPRGTLQDGTRRFTCRGKPIHHFLGTSTFSQYTVVDENAVAKIDAASPLEKVCLIGCGFSTGYGSAVNVAKVTPGSTCAVFGLGGVGLSAVMGCKAAGAARIIAVDINKDKFAKAKELGATECINPQDYKKPIQEVLKEMTDGGVDFSFEVIGRLDTMMASLLCCHEACGTSVIVGVPPASQNLSINPMLLLTGRTWKGAVYGGFKSKEGIPKLVADFMAKKFSLDALITHVLPFEKINEGFDLLHSGKSIRTVLTF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-08-01" modified="2026-01-28" version="228" xmlns="https://uniprot.org/uniprot">
    <accession>P08319</accession>
    <accession>A8K470</accession>
    <accession>B4DIE7</accession>
    <accession>C9J4A9</accession>
    <accession>Q8TCD7</accession>
    <name>ADH4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">All-trans-retinol dehydrogenase [NAD(+)] ADH4</fullName>
            <ecNumber evidence="6">1.1.1.105</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="10">Alcohol dehydrogenase 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alcohol dehydrogenase class II pi chain</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15" type="primary">ADH4</name>
        <name evidence="10" type="synonym">ADH2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="Biochemistry" volume="26" first="1926" last="1932">
            <title>Structure of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the pi subunit.</title>
            <authorList>
                <person name="Hoeoeg J.-O."/>
                <person name="von Bahr-Lindstroem H."/>
                <person name="Heden L.-O."/>
                <person name="Holmquist B."/>
                <person name="Larsson K."/>
                <person name="Hempel J."/>
                <person name="Vallee B.L."/>
                <person name="Joernvall H."/>
            </authorList>
            <dbReference type="PubMed" id="3036213"/>
            <dbReference type="DOI" id="10.1021/bi00381a021"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1991" name="Gene" volume="103" first="269" last="274">
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>FUNCTION</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC IONS</scope>
    </reference>
    <comment type="function">
        <text evidence="2 5 6">Catalyzes the NAD-dependent oxidation of either all-trans-retinol or 9-cis-retinol (PubMed:17279314). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Also catalyzes the reduction of benzoquinones (PubMed:10514444).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:21284"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17336"/>
            <dbReference type="ChEBI" id="CHEBI:17898"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.105"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:21285"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>9-cis-retinol + NAD(+) = 9-cis-retinal + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:42052"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:78272"/>
            <dbReference type="ChEBI" id="CHEBI:78273"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:42053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenedioate + NADH + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:39803"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:76645"/>
            <dbReference type="ChEBI" id="CHEBI:76647"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:39804"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) = 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39799"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:76624"/>
            <dbReference type="ChEBI" id="CHEBI:76645"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="13">
            <dbReference type="Rhea" id="RHEA:39800"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>1,4-benzoquinone + NADH + H(+) = hydroquinone + NAD(+)</text>
            <dbReference type="Rhea" id="RHEA:60660"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16509"/>
            <dbReference type="ChEBI" id="CHEBI:17594"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="12">
            <dbReference type="Rhea" id="RHEA:60661"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text>Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 5">Oxydation of 20-HETE is inhibited by low concentrations of N-heptylformamide (PubMed:16081420). Oxydation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid. Strongly inhibited by omega-hydroxy fatty acids (By similarity).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="6">0.14 uM for all-trans-retinol</KM>
            <KM evidence="6">0.29 uM for all-trans-retinal</KM>
            <KM evidence="6">0.054 uM for 9-cis-retinol</KM>
            <KM evidence="6">0.21 uM for 9-cis-retinal</KM>
            <KM evidence="5">9.5 uM for 20-HETE</KM>
            <KM evidence="2">0.088 mM for 1,4-benzoquinone</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="7">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3927856">
            <id>P08319</id>
        </interactant>
        <interactant intactId="EBI-11525489">
            <id>Q86WT6-2</id>
            <label>TRIM69</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P08319-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P08319-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_036788"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the zinc-containing alcohol dehydrogenase family. Class-II subfamily.</text>
    </comment>
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        <property type="antibodies" value="279 antibodies from 30 providers"/>
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        <property type="gene designation" value="ADH4"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
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            <begin position="1"/>
            <end position="380"/>
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    <sequence length="380" mass="40222" checksum="45721A08197629F1" modified="2010-10-05" version="5">MGTKGKVIKCKAAIAWEAGKPLCIEEVEVAPPKAHEVRIQIIATSLCHTDATVIDSKFEGLAFPVIVGHEAAGIVESIGPGVTNVKPGDKVIPLYAPLCRKCKFCLSPLTNLCGKISNLKSPASDQQLMEDKTSRFTCKGKPVYHFFGTSTFSQYTVVSDINLAKIDDDANLERVCLLGCGFSTGYGAAINNAKVTPGSTCAVFGLGGVGLSAVMGCKAAGASRIIGIDINSEKFVKAKALGATDCLNPRDLHKPIQEVIIELTKGGVDFALDCAGGSETMKAALDCTTAGWGSCTFIGVAAGSKGLTIFPEELIIGRTINGTFFGGWKSVDSIPKLVTDYKNKKFNLDALVTHTLPFDKISEAFDLMNQGKSVRTILIF</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1994-02-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
    <accession>P35318</accession>
    <accession>B2R793</accession>
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            <taxon>Mammalia</taxon>
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            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
        <citation type="journal article" date="1993" name="Biochem. Biophys. Res. Commun." volume="194" first="720" last="725">
            <title>Cloning and characterization of cDNA encoding a precursor for human adrenomedullin.</title>
            <authorList>
                <person name="Kitamura K."/>
                <person name="Sakata J."/>
                <person name="Kangawa K."/>
                <person name="Kojima M."/>
                <person name="Matsuo H."/>
                <person name="Eto T."/>
            </authorList>
            <dbReference type="PubMed" id="7688224"/>
            <dbReference type="DOI" id="10.1006/bbrc.1993.1881"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Pheochromocytoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1994" name="Biochem. Biophys. Res. Commun." volume="203" first="631" last="639">
            <title>Genomic structure of human adrenomedullin gene.</title>
            <authorList>
                <person name="Ishimitsu T."/>
                <person name="Kojima M."/>
                <person name="Kangawa K."/>
                <person name="Hino J."/>
                <person name="Matsuoka H."/>
                <person name="Kitamura K."/>
                <person name="Eto T."/>
                <person name="Matsuo H."/>
            </authorList>
            <dbReference type="PubMed" id="8074714"/>
            <dbReference type="DOI" id="10.1006/bbrc.1994.2229"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Halleck A."/>
                <person name="Ebert L."/>
                <person name="Mkoundinya M."/>
                <person name="Schick M."/>
                <person name="Eisenstein S."/>
                <person name="Neubert P."/>
                <person name="Kstrang K."/>
                <person name="Schatten R."/>
                <person name="Shen B."/>
                <person name="Henze S."/>
                <person name="Mar W."/>
                <person name="Korn B."/>
                <person name="Zuo D."/>
                <person name="Hu Y."/>
                <person name="LaBaer J."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain cortex</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NIEHS SNPs program"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ARG-50</scope>
    </reference>
    <reference key="7">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1993" name="Biochem. Biophys. Res. Commun." volume="192" first="553" last="560">
            <title>Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma.</title>
            <authorList>
                <person name="Kitamura K."/>
                <person name="Kangawa K."/>
                <person name="Kawamoto M."/>
                <person name="Ichiki Y."/>
                <person name="Nakamura S."/>
                <person name="Matsuo H."/>
                <person name="Eto T."/>
            </authorList>
            <dbReference type="PubMed" id="8387282"/>
            <dbReference type="DOI" id="10.1006/bbrc.1993.1451"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 95-146</scope>
        <scope>AMIDATION AT TYR-146</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Pheochromocytoma</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1998" name="Nature" volume="393" first="333" last="339">
            <title>RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.</title>
            <authorList>
                <person name="McLatchie L.M."/>
                <person name="Fraser N.J."/>
                <person name="Main M.J."/>
                <person name="Wise A."/>
                <person name="Brown J."/>
                <person name="Thompson N."/>
                <person name="Solari R."/>
                <person name="Lee M.G."/>
                <person name="Foord S.M."/>
            </authorList>
            <dbReference type="PubMed" id="9620797"/>
            <dbReference type="DOI" id="10.1038/30666"/>
        </citation>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="1998" name="Front. Neuroendocrinol." volume="19" first="100" last="127">
            <title>Proadrenomedullin-derived peptides.</title>
            <authorList>
                <person name="Samson W.K."/>
            </authorList>
            <dbReference type="PubMed" id="9578982"/>
            <dbReference type="DOI" id="10.1006/frne.1998.0164"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1999" name="Regul. Pept." volume="85" first="1" last="8">
            <title>Structure-activity relationships of adrenomedullin in the circulation and adrenal gland.</title>
            <authorList>
                <person name="Champion H.C."/>
                <person name="Nussdorfer G.G."/>
                <person name="Kadowitz P.J."/>
            </authorList>
            <dbReference type="PubMed" id="10588445"/>
            <dbReference type="DOI" id="10.1016/s0167-0115(99)00025-7"/>
        </citation>
        <scope>REVIEW</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2005" name="Biochem. Biophys. Res. Commun." volume="330" first="1146" last="1152">
            <title>Identification of MrgX2 as a human G-protein-coupled receptor for proadrenomedullin N-terminal peptides.</title>
            <authorList>
                <person name="Kamohara M."/>
                <person name="Matsuo A."/>
                <person name="Takasaki J."/>
                <person name="Kohda M."/>
                <person name="Matsumoto M."/>
                <person name="Matsumoto S."/>
                <person name="Soga T."/>
                <person name="Hiyama H."/>
                <person name="Kobori M."/>
                <person name="Katou M."/>
            </authorList>
            <dbReference type="PubMed" id="15823563"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2005.03.088"/>
        </citation>
        <scope>FUNCTION (PROADRENOMEDULLIN 9-20 TERMINAL PEPTIDE)</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2006" name="Biopolymers" volume="81" first="295" last="308">
            <title>NMR conformational analysis of proadrenomedullin N-terminal 20 peptide, a proangiogenic factor involved in tumor growth.</title>
            <authorList>
                <person name="Lucyk S."/>
                <person name="Taha H."/>
                <person name="Yamamoto H."/>
                <person name="Miskolzie M."/>
                <person name="Kotovych G."/>
            </authorList>
            <dbReference type="PubMed" id="16315141"/>
            <dbReference type="DOI" id="10.1002/bip.20418"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 22-41</scope>
        <scope>AMIDATION AT ARG-41</scope>
    </reference>
    <reference evidence="18 19" key="15">
        <citation type="journal article" date="2020" name="ACS Pharmacol. Transl. Sci." volume="3" first="263" last="284">
            <title>Structure and Dynamics of Adrenomedullin Receptors AM1 and AM2 Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins.</title>
            <authorList>
                <person name="Liang Y.L."/>
                <person name="Belousoff M.J."/>
                <person name="Fletcher M.M."/>
                <person name="Zhang X."/>
                <person name="Khoshouei M."/>
                <person name="Deganutti G."/>
                <person name="Koole C."/>
                <person name="Furness S.G.B."/>
                <person name="Miller L.J."/>
                <person name="Hay D.L."/>
                <person name="Christopoulos A."/>
                <person name="Reynolds C.A."/>
                <person name="Danev R."/>
                <person name="Wootten D."/>
                <person name="Sexton P.M."/>
            </authorList>
            <dbReference type="PubMed" id="32296767"/>
            <dbReference type="DOI" id="10.1021/acsptsci.9b00080"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.40 ANGSTROMS) OF 95-146 IN COMPLEX WITH CALCRL; RAMP2; RAMP3 AND G PROTEINS</scope>
    </reference>
    <reference evidence="20" key="16">
        <citation type="journal article" date="2021" name="Nature" volume="600" first="164" last="169">
            <title>Structure, function and pharmacology of human itch receptor complexes.</title>
            <authorList>
                <person name="Yang F."/>
                <person name="Guo L."/>
                <person name="Li Y."/>
                <person name="Wang G."/>
                <person name="Wang J."/>
                <person name="Zhang C."/>
                <person name="Fang G.X."/>
                <person name="Chen X."/>
                <person name="Liu L."/>
                <person name="Yan X."/>
                <person name="Liu Q."/>
                <person name="Qu C."/>
                <person name="Xu Y."/>
                <person name="Xiao P."/>
                <person name="Zhu Z."/>
                <person name="Li Z."/>
                <person name="Zhou J."/>
                <person name="Yu X."/>
                <person name="Gao N."/>
                <person name="Sun J.P."/>
            </authorList>
            <dbReference type="PubMed" id="34789875"/>
            <dbReference type="DOI" id="10.1038/s41586-021-04077-y"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 30-41 IN COMPLEX WITH MRGPRX2</scope>
        <scope>FUNCTION (PROADRENOMEDULLIN 9-20 TERMINAL PEPTIDE)</scope>
    </reference>
    <comment type="function">
        <text evidence="8 9">Adrenomedullin/ADM and proadrenomedullin N-20 terminal peptide/PAMP are peptide hormones that act as potent hypotensive and vasodilatator agents (PubMed:8387282, PubMed:9620797). Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, ADM is diuretic and natriuretic, and both ADM and PAMP inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels.</text>
    </comment>
    <comment type="function">
        <molecule>Adrenomedullin</molecule>
        <text evidence="6 8 9">Peptide hormone that act as potent hypotensive and vasodilatator agents (PubMed:8387282). ADM function is mediated by the CALCRL-RAMP2 and CALCRL-RAMP3 receptor complexes with ADM showing the highest potency for the CALCRL-RAMP2 complex (PubMed:32296767, PubMed:9620797).</text>
    </comment>
    <comment type="function">
        <molecule>Proadrenomedullin N-20 terminal peptide</molecule>
        <text evidence="4 11 15">Peptide hormone that act as potent hypotensive and vasodilatator agents by inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells (PubMed:10588445, PubMed:9578982). Acts as a ligand for MRGPRX2 receptor in mast cells (PubMed:15823563).</text>
    </comment>
    <comment type="function">
        <molecule>Proadrenomedullin 9-20 terminal peptide</molecule>
        <text evidence="4 7 11 15">Peptide hormone that act as potent hypotensive and vasodilatator agents by inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells (PubMed:10588445, PubMed:9578982). Acts as a ligand for MRGPRX2 receptor in mast cells (PubMed:15823563, PubMed:34789875).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Highest levels found in pheochromocytoma and adrenal medulla. Also found in lung, ventricle and kidney tissues.</text>
    </comment>
    <comment type="similarity">
        <text evidence="16">Belongs to the adrenomedullin family.</text>
    </comment>
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        <property type="protein sequence ID" value="BAA03589.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="S73906">
        <property type="protein sequence ID" value="AAC60642.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="D43639">
        <property type="protein sequence ID" value="BAA07756.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CR541995">
        <property type="protein sequence ID" value="CAG46792.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAP35548.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAG35740.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAZ38717.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW68571.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471064">
        <property type="protein sequence ID" value="EAW68572.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH15961.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="entry name" value="JN0684"/>
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    <dbReference type="RefSeq" id="NP_001115.1">
        <property type="nucleotide sequence ID" value="NM_001124.3"/>
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    <dbReference type="PDB" id="2FLY">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=22-41"/>
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        <property type="chains" value="A=95-146"/>
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        <property type="resolution" value="1.76 A"/>
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        <property type="resolution" value="2.80 A"/>
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    <dbReference type="PDB" id="6UUN">
        <property type="method" value="EM"/>
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        <property type="resolution" value="1.83 A"/>
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        <property type="method" value="EM"/>
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    <dbReference type="PDBsum" id="2FLY"/>
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    <dbReference type="AlphaFoldDB" id="P35318"/>
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        <property type="interactions" value="8"/>
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    <dbReference type="FunCoup" id="P35318">
        <property type="interactions" value="631"/>
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        <property type="interactions" value="2"/>
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        <property type="antibodies" value="631 antibodies from 36 providers"/>
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        <property type="protein sequence ID" value="ENSP00000278175.5"/>
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        <property type="gene ID" value="ENSG00000148926.11"/>
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        <property type="RefSeq nucleotide sequence ID" value="NM_001124.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001115.1"/>
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        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:259"/>
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    <dbReference type="GeneCards" id="ADM"/>
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        <property type="gene designation" value="ADM"/>
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    <dbReference type="HPA" id="ENSG00000148926">
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
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        <property type="pathway name" value="G alpha (s) signalling events"/>
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        <property type="pathway name" value="Calcitonin-like ligand receptors"/>
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        <property type="pathway name" value="High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells"/>
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        <property type="hits" value="16 hits in 1152 CRISPR screens"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 11"/>
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        <property type="molecule type" value="protein"/>
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    <dbReference type="ExpressionAtlas" id="P35318">
        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
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    <dbReference type="GO" id="GO:0034774">
        <property type="term" value="C:secretory granule lumen"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
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    <dbReference type="GO" id="GO:0031700">
        <property type="term" value="F:adrenomedullin receptor binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005179">
        <property type="term" value="F:hormone activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
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    <dbReference type="GO" id="GO:0005102">
        <property type="term" value="F:signaling receptor binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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    <dbReference type="GO" id="GO:0007189">
        <property type="term" value="P:adenylate cyclase-activating G protein-coupled receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:1990410">
        <property type="term" value="P:adrenomedullin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0060670">
        <property type="term" value="P:branching involved in labyrinthine layer morphogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0008283">
        <property type="term" value="P:cell population proliferation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0048589">
        <property type="term" value="P:developmental growth"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <keyword id="KW-0903">Direct protein sequencing</keyword>
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            <position position="41"/>
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        <variation>R</variation>
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            <dbReference type="HGNC" id="HGNC:259"/>
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            <dbReference type="PDB" id="6UUN"/>
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            <dbReference type="PDB" id="2L7S"/>
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    <sequence length="185" mass="20420" checksum="64C7D2A0B4654DFE" modified="1994-02-01" version="1" precursor="true">MKLVSVALMYLGSLAFLGADTARLDVASEFRKKWNKWALSRGKRELRMSSSYPTGLADVKAGPAQTLIRPQDMKGASRSPEDSSPDAARIRVKRYRQSMNNFQGLRSFGCRFGTCTVQKLAHQIYQFTDKDKDNVAPRSKISPQGYGRRRRRSLPEAGPGRTLVSSKPQAHGAPAPPSGSAPHFL</sequence>
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<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="231" xmlns="https://uniprot.org/uniprot">
    <accession>Q15848</accession>
    <accession>Q58EX9</accession>
    <name>ADIPO_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adiponectin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>30 kDa adipocyte complement-related protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adipocyte complement-related 30 kDa protein</fullName>
            <shortName>ACRP30</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Adipocyte, C1q and collagen domain-containing protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="18">Adipose most abundant gene transcript 1 protein</fullName>
            <shortName evidence="17">apM-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Gelatin-binding protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADIPOQ</name>
        <name type="synonym">ACDC</name>
        <name type="synonym">ACRP30</name>
        <name type="synonym">APM1</name>
        <name evidence="16 19" type="synonym">GBP28</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="Biochem. Biophys. Res. Commun." volume="221" first="286" last="289">
            <title>cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1).</title>
            <authorList>
                <person name="Maeda K."/>
                <person name="Okubo K."/>
                <person name="Shimomura I."/>
                <person name="Funahashi T."/>
                <person name="Matsuzawa Y."/>
                <person name="Matsubara K."/>
            </authorList>
            <dbReference type="PubMed" id="8619847"/>
            <dbReference type="DOI" id="10.1006/bbrc.1996.0587"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Adipose tissue</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Gene" volume="229" first="67" last="73">
            <title>Organization of the gene for gelatin-binding protein (GBP28).</title>
            <authorList>
                <person name="Saito K."/>
                <person name="Tobe T."/>
                <person name="Minoshima S."/>
                <person name="Asakawa S."/>
                <person name="Sumiya J."/>
                <person name="Yoda M."/>
                <person name="Nakano Y."/>
                <person name="Shimizu N."/>
                <person name="Tomita M."/>
            </authorList>
            <dbReference type="PubMed" id="10095105"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(99)00041-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1999" name="Biochem. Biophys. Res. Commun." volume="260" first="416" last="425">
            <title>The human apM-1, an adipocyte-specific gene linked to the family of TNF's and to genes expressed in activated T cells, is mapped to chromosome 1q21.3-q23, a susceptibility locus identified for familial combined hyperlipidemia (FCH).</title>
            <authorList>
                <person name="Schaeffler A."/>
                <person name="Orso E."/>
                <person name="Palitzsch K.D."/>
                <person name="Buechler C."/>
                <person name="Drobnik W."/>
                <person name="Fuerst A."/>
                <person name="Schoelmerich J."/>
                <person name="Schmitz G."/>
            </authorList>
            <dbReference type="PubMed" id="10403784"/>
            <dbReference type="DOI" id="10.1006/bbrc.1999.0865"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Protein Sci." volume="13" first="2819" last="2824">
            <title>Signal peptide prediction based on analysis of experimentally verified cleavage sites.</title>
            <authorList>
                <person name="Zhang Z."/>
                <person name="Henzel W.J."/>
            </authorList>
            <dbReference type="PubMed" id="15340161"/>
            <dbReference type="DOI" id="10.1110/ps.04682504"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 19-33</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="1996" name="J. Biochem." volume="120" first="803" last="812">
            <title>Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma.</title>
            <authorList>
                <person name="Nakano Y."/>
                <person name="Tobe T."/>
                <person name="Choi-Miura N.H."/>
                <person name="Mazda T."/>
                <person name="Tomita M."/>
            </authorList>
            <dbReference type="PubMed" id="8947845"/>
            <dbReference type="DOI" id="10.1093/oxfordjournals.jbchem.a021483"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF N-TERMINUS</scope>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2000" name="Blood" volume="96" first="1723" last="1732">
            <title>Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.</title>
            <authorList>
                <person name="Yokota T."/>
                <person name="Oritani K."/>
                <person name="Takahashi I."/>
                <person name="Ishikawa J."/>
                <person name="Matsuyama A."/>
                <person name="Ouchi N."/>
                <person name="Kihara S."/>
                <person name="Funahashi T."/>
                <person name="Tenner A.J."/>
                <person name="Tomiyama Y."/>
                <person name="Matsuzawa Y."/>
            </authorList>
            <dbReference type="PubMed" id="10961870"/>
        </citation>
        <scope>CHARACTERIZATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2000" name="Circulation" volume="102" first="1296" last="1301">
            <title>Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway.</title>
            <authorList>
                <person name="Ouchi N."/>
                <person name="Kihara S."/>
                <person name="Arita Y."/>
                <person name="Okamoto Y."/>
                <person name="Maeda K."/>
                <person name="Kuriyama H."/>
                <person name="Hotta K."/>
                <person name="Nishida M."/>
                <person name="Takahashi M."/>
                <person name="Muraguchi M."/>
                <person name="Ohmoto Y."/>
                <person name="Nakamura T."/>
                <person name="Yamashita S."/>
                <person name="Funahashi T."/>
                <person name="Matsuzawa Y."/>
            </authorList>
            <dbReference type="PubMed" id="10982546"/>
            <dbReference type="DOI" id="10.1161/01.cir.102.11.1296"/>
        </citation>
        <scope>CHARACTERIZATION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2001" name="Nat. Med." volume="7" first="941" last="946">
            <title>The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.</title>
            <authorList>
                <person name="Yamauchi T."/>
                <person name="Kamon J."/>
                <person name="Waki H."/>
                <person name="Terauchi Y."/>
                <person name="Kubota N."/>
                <person name="Hara K."/>
                <person name="Mori Y."/>
                <person name="Ide T."/>
                <person name="Murakami K."/>
                <person name="Tsuboyama-Kasaoka N."/>
                <person name="Ezaki O."/>
                <person name="Akanuma Y."/>
                <person name="Gavrilova O."/>
                <person name="Vinson C."/>
                <person name="Reitman M.L."/>
                <person name="Kagechika H."/>
                <person name="Shudo K."/>
                <person name="Yoda M."/>
                <person name="Nakano Y."/>
                <person name="Tobe K."/>
                <person name="Nagai R."/>
                <person name="Kimura S."/>
                <person name="Tomita M."/>
                <person name="Froguel P."/>
                <person name="Kadowaki T."/>
            </authorList>
            <dbReference type="PubMed" id="11479627"/>
            <dbReference type="DOI" id="10.1038/90984"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2003" name="J. Biol. Chem." volume="278" first="40352" last="40363">
            <title>Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin.</title>
            <authorList>
                <person name="Waki H."/>
                <person name="Yamauchi T."/>
                <person name="Kamon J."/>
                <person name="Ito Y."/>
                <person name="Uchida S."/>
                <person name="Kita S."/>
                <person name="Hara K."/>
                <person name="Hada Y."/>
                <person name="Vasseur F."/>
                <person name="Froguel P."/>
                <person name="Kimura S."/>
                <person name="Nagai R."/>
                <person name="Kadowaki T."/>
            </authorList>
            <dbReference type="PubMed" id="12878598"/>
            <dbReference type="DOI" id="10.1074/jbc.m300365200"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>MUTAGENESIS OF CYS-36</scope>
        <scope>CHARACTERIZATION OF VARIANTS ARG-84; SER-90; CYS-112 AND THR-164</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2006" name="Mol. Endocrinol." volume="20" first="1673" last="1687">
            <title>Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications.</title>
            <authorList>
                <person name="Richards A.A."/>
                <person name="Stephens T."/>
                <person name="Charlton H.K."/>
                <person name="Jones A."/>
                <person name="Macdonald G.A."/>
                <person name="Prins J.B."/>
                <person name="Whitehead J.P."/>
            </authorList>
            <dbReference type="PubMed" id="16497731"/>
            <dbReference type="DOI" id="10.1210/me.2005-0390"/>
        </citation>
        <scope>SUBUNIT</scope>
        <scope>HYDROXYLATION AT PRO-44; PRO-47; PRO-53; LYS-65; LYS-68; PRO-71; PRO-76; LYS-77; PRO-91; PRO-95 AND LYS-101</scope>
        <scope>GLYCOSYLATION AT LYS-65; LYS-68; LYS-77 AND LYS-101</scope>
        <scope>DISULFIDE BOND</scope>
        <scope>LACK OF HYDROXYLATION AT PRO-62; PRO-86 AND PRO-104</scope>
        <scope>LACK OF GLYCOSYLATION AT ASN-230</scope>
        <scope>MUTAGENESIS OF LYS-33; CYS-36; LYS-65; LYS-68; LYS-77 AND LYS-101</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2010" name="Mol. Endocrinol." volume="24" first="229" last="239">
            <title>Sialic acid modification of adiponectin is not required for multimerization or secretion but determines half-life in circulation.</title>
            <authorList>
                <person name="Richards A.A."/>
                <person name="Colgrave M.L."/>
                <person name="Zhang J."/>
                <person name="Webster J."/>
                <person name="Simpson F."/>
                <person name="Preston E."/>
                <person name="Wilks D."/>
                <person name="Hoehn K.L."/>
                <person name="Stephenson M."/>
                <person name="Macdonald G.A."/>
                <person name="Prins J.B."/>
                <person name="Cooney G.J."/>
                <person name="Xu A."/>
                <person name="Whitehead J.P."/>
            </authorList>
            <dbReference type="PubMed" id="19855092"/>
            <dbReference type="DOI" id="10.1210/me.2009-0133"/>
        </citation>
        <scope>GLYCOSYLATION AT THR-21 AND THR-22</scope>
        <scope>SUBUNIT</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>MUTAGENESIS OF THR-20; THR-21 AND THR-22</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2012" name="J. Proteome Res." volume="11" first="4733" last="4743">
            <title>Resveratrol-induced changes of the human adipocyte secretion profile.</title>
            <authorList>
                <person name="Rosenow A."/>
                <person name="Noben J.P."/>
                <person name="Jocken J."/>
                <person name="Kallendrusch S."/>
                <person name="Fischer-Posovszky P."/>
                <person name="Mariman E.C."/>
                <person name="Renes J."/>
            </authorList>
            <dbReference type="PubMed" id="22905912"/>
            <dbReference type="DOI" id="10.1021/pr300539b"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2012" name="FEBS Lett." volume="586" first="912" last="917">
            <title>Crystal structure of a single-chain trimer of human adiponectin globular domain.</title>
            <authorList>
                <person name="Min X."/>
                <person name="Lemon B."/>
                <person name="Tang J."/>
                <person name="Liu Q."/>
                <person name="Zhang R."/>
                <person name="Walker N."/>
                <person name="Li Y."/>
                <person name="Wang Z."/>
            </authorList>
            <dbReference type="PubMed" id="22449980"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2012.02.024"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 104-244</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2000" name="Int. J. Obes. Relat. Metab. Disord." volume="24" first="861" last="868">
            <title>Genomic structure and mutations in adipose-specific gene, adiponectin.</title>
            <authorList>
                <person name="Takahashi M."/>
                <person name="Arita Y."/>
                <person name="Yamagata K."/>
                <person name="Matsukawa Y."/>
                <person name="Okutomi K."/>
                <person name="Horie M."/>
                <person name="Shimomura I."/>
                <person name="Hotta K."/>
                <person name="Kuriyama H."/>
                <person name="Kihara S."/>
                <person name="Nakamura T."/>
                <person name="Yamashita S."/>
                <person name="Funahashi T."/>
                <person name="Matsuzawa Y."/>
            </authorList>
            <dbReference type="PubMed" id="10918532"/>
            <dbReference type="DOI" id="10.1038/sj.ijo.0801244"/>
        </citation>
        <scope>VARIANT ADPOD CYS-112</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2002" name="Diabetes" volume="51" first="536" last="540">
            <title>Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.</title>
            <authorList>
                <person name="Hara K."/>
                <person name="Boutin P."/>
                <person name="Mori Y."/>
                <person name="Tobe K."/>
                <person name="Dina C."/>
                <person name="Yasuda K."/>
                <person name="Yamauchi T."/>
                <person name="Otabe S."/>
                <person name="Okada T."/>
                <person name="Eto K."/>
                <person name="Kadowaki H."/>
                <person name="Hagura R."/>
                <person name="Akanuma Y."/>
                <person name="Yazaki Y."/>
                <person name="Nagai R."/>
                <person name="Taniyama M."/>
                <person name="Matsubara K."/>
                <person name="Yoda M."/>
                <person name="Nakano Y."/>
                <person name="Kimura S."/>
                <person name="Tomita M."/>
                <person name="Kimura S."/>
                <person name="Ito C."/>
                <person name="Froguel P."/>
                <person name="Kadowaki T."/>
            </authorList>
            <dbReference type="PubMed" id="11812766"/>
            <dbReference type="DOI" id="10.2337/diabetes.51.2.536"/>
        </citation>
        <scope>VARIANTS ARG-84; MET-117; THR-164; SER-221 AND PRO-241</scope>
        <scope>INVOLVEMENT IN ADPOD</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2002" name="Diabetes" volume="51" first="1294" last="1294">
            <authorList>
                <person name="Hara K."/>
                <person name="Boutin P."/>
                <person name="Mori Y."/>
                <person name="Tobe K."/>
                <person name="Dina C."/>
                <person name="Yasuda K."/>
                <person name="Yamauchi T."/>
                <person name="Otabe S."/>
                <person name="Okada T."/>
                <person name="Eto K."/>
                <person name="Kadowaki H."/>
                <person name="Hagura R."/>
                <person name="Akanuma Y."/>
                <person name="Yazaki Y."/>
                <person name="Nagai R."/>
                <person name="Taniyama M."/>
                <person name="Matsubara K."/>
                <person name="Yoda M."/>
                <person name="Nakano Y."/>
                <person name="Kimura S."/>
                <person name="Tomita M."/>
                <person name="Kimura S."/>
                <person name="Ito C."/>
                <person name="Froguel P."/>
                <person name="Kadowaki T."/>
            </authorList>
        </citation>
        <scope>ERRATUM OF PUBMED:11812766</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2002" name="Diabetes" volume="51" first="2325" last="2328">
            <title>Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.</title>
            <authorList>
                <person name="Kondo H."/>
                <person name="Shimomura I."/>
                <person name="Matsukawa Y."/>
                <person name="Kumada M."/>
                <person name="Takahashi M."/>
                <person name="Matsuda M."/>
                <person name="Ouchi N."/>
                <person name="Kihara S."/>
                <person name="Kawamoto T."/>
                <person name="Sumitsuji S."/>
                <person name="Funahashi T."/>
                <person name="Matsuzawa Y."/>
            </authorList>
            <dbReference type="PubMed" id="12086969"/>
            <dbReference type="DOI" id="10.2337/diabetes.51.7.2325"/>
        </citation>
        <scope>VARIANTS SER-221 AND PRO-241</scope>
        <scope>POLYMORPHISM</scope>
        <scope>VARIANTS ADPOD CYS-112 AND THR-164</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2002" name="Hum. Mol. Genet." volume="11" first="2607" last="2614">
            <title>Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians.</title>
            <authorList>
                <person name="Vasseur F."/>
                <person name="Helbecque N."/>
                <person name="Dina C."/>
                <person name="Lobbens S."/>
                <person name="Delannoy V."/>
                <person name="Gaget S."/>
                <person name="Boutin P."/>
                <person name="Vaxillaire M."/>
                <person name="Lepretre F."/>
                <person name="Dupont S."/>
                <person name="Hara K."/>
                <person name="Clement K."/>
                <person name="Bihain B."/>
                <person name="Kadowaki T."/>
                <person name="Froguel P."/>
            </authorList>
            <dbReference type="PubMed" id="12354786"/>
            <dbReference type="DOI" id="10.1093/hmg/11.21.2607"/>
        </citation>
        <scope>VARIANTS ARG-84; SER-90 AND HIS-111</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2022" name="NPJ Genom. Med." volume="7" first="43" last="43">
            <title>A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia.</title>
            <authorList>
                <person name="Simeone C.A."/>
                <person name="Wilkerson J.L."/>
                <person name="Poss A.M."/>
                <person name="Banks J.A."/>
                <person name="Varre J.V."/>
                <person name="Guevara J.L."/>
                <person name="Hernandez E.J."/>
                <person name="Gorsi B."/>
                <person name="Atkinson D.L."/>
                <person name="Turapov T."/>
                <person name="Frodsham S.G."/>
                <person name="Morales J.C.F."/>
                <person name="O'Neil K."/>
                <person name="Moore B."/>
                <person name="Yandell M."/>
                <person name="Summers S.A."/>
                <person name="Krolewski A.S."/>
                <person name="Holland W.L."/>
                <person name="Pezzolesi M.G."/>
            </authorList>
            <dbReference type="PubMed" id="35869090"/>
            <dbReference type="DOI" id="10.1038/s41525-022-00314-z"/>
        </citation>
        <scope>INVOLVEMENT IN ADPOD</scope>
    </reference>
    <comment type="function">
        <text evidence="7">Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Polymerization and secretion of adiponectin is inhibited by succination of cysteine residues by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues.</text>
    </comment>
    <comment type="subunit">
        <text evidence="3">Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly is also modulated by the degree of lysine hydroxylation and glycosylation. LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9 via the C1q domain (heterotrimeric complex).</text>
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        <interactant intactId="EBI-19125216">
            <id>Q86WK6</id>
            <label>AMIGO1</label>
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    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="15">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="15">Synthesized exclusively by adipocytes and secreted into plasma.</text>
    </comment>
    <comment type="domain">
        <text>The C1q domain is commonly called the globular domain.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagen-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13 14">O-glycosylated. Not N-glycosylated. O-linked glycans on hydroxylysines consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups. Sialylated to varying degrees depending on tissue. Thr-22 appears to be the major site of sialylation. Higher sialylation found in SGBS adipocytes than in HEK fibroblasts. Sialylation is not required neither for heterodimerization nor for secretion. Not sialylated on the glycosylated hydroxylysines. Desialylated forms are rapidly cleared from the circulation.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Succination of Cys-36 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits polymerization and secretion of adiponectin. Adiponectin is a major target for succination in both adipocytes and adipose tissue of diabetic mammals. It was proposed that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="6 9">Genetic variations in ADIPOQ influence the variance in adiponectin serum levels and define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556].</text>
    </comment>
    <comment type="disease" evidence="6 8 9">
        <disease id="DI-00041">
            <name>Adiponectin deficiency</name>
            <acronym>ADPOD</acronym>
            <description>An autosomal dominant condition characterized by very low concentrations of plasma adiponectin. Levels of adiponectin are decreased in obesity and may contribute to a chronic state of inflammation that leads to insulin resistance, type 2 diabetes, coronary artery disease, myocardial infarction, non-alcoholic steatohepatitis, and kidney disease.</description>
            <dbReference type="MIM" id="612556"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="pharmaceutical">
        <text>Adiponectin might be used in the treatment of diabetes type 2 and insulin resistance.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Variants Arg-84 and Ser-90 show impaired formation of HMW complexes whereas variants Cys-112 and Thr-164 show impaired secretion of adiponectin in any form.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="1">HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion (By similarity). In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation are significantly decreased as compared with healthy controls.</text>
    </comment>
    <comment type="caution">
        <text evidence="13">The expected hydroxylation of Lys-33 was not identified, probably due to poor representation of the N-terminal peptide in mass fingerprinting.</text>
    </comment>
    <comment type="online information" name="Wikipedia">
        <link uri="https://en.wikipedia.org/wiki/Adiponectin"/>
        <text>Adiponectin entry</text>
    </comment>
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        <property type="protein sequence ID" value="BAA08227.1"/>
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        <property type="protein sequence ID" value="BAA86716.1"/>
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        <property type="protein sequence ID" value="CAB52413.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH96310.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH96311.1"/>
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        <property type="resolution" value="2.15 A"/>
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    <feature type="glycosylation site" description="O-linked (GalNAc...) threonine" evidence="14">
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (Gal...) hydroxylysine; partial" evidence="13">
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (Gal...) hydroxylysine; partial" evidence="13">
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (Gal...) hydroxylysine; partial" evidence="13">
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (Gal...) hydroxylysine; partial" evidence="13">
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="disulfide bond" description="Interchain; in form MMW and form HMW" evidence="11 13">
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013273" description="Does not form high molecular weight multimers; dbSNP:rs199646033." evidence="8 10 11">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027395" description="Does not form high molecular weight multimers; dbSNP:rs62625753." evidence="10 11">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_027396" description="In dbSNP:rs17366743." evidence="10">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="111"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013274" description="In ADPOD; does not assemble into trimers resulting in impaired secretion from the cell; dbSNP:rs121917815." evidence="6 9 11">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013275" description="In dbSNP:rs747223144." evidence="8">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013276" description="In ADPOD; does not assemble into trimers resulting in impaired secretion from the cell; dbSNP:rs185847354." evidence="8 9 11">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013277" description="In dbSNP:rs138773406." evidence="8 9">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="221"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_013278" description="In dbSNP:rs141205818." evidence="8 9">
        <original>H</original>
        <variation>P</variation>
        <location>
            <position position="241"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No change in sialylated isoforms." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Some loss of sialylated isoforms." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes sialylated isoforms." evidence="14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="22"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on formation of HMW multimers." evidence="13">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired formation of MMW and HMW multimers." evidence="11 13">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired formation of HMW multimers; when associated with R-68." evidence="13">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired formation of HMW multimers; when associated with R-65." evidence="13">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="68"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired formation of HMW multimers; when associated with R-101." evidence="13">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Impaired formation of HMW multimers; when associated with R-77." evidence="13">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="101"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="114"/>
            <end position="118"/>
        </location>
    </feature>
    <feature type="strand" evidence="22">
        <location>
            <begin position="126"/>
            <end position="129"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="134"/>
            <end position="137"/>
        </location>
    </feature>
    <feature type="turn" evidence="21">
        <location>
            <begin position="145"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="156"/>
            <end position="177"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="180"/>
            <end position="187"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="195"/>
            <end position="205"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="210"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="strand" evidence="20">
        <location>
            <begin position="218"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="222"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="strand" evidence="21">
        <location>
            <begin position="233"/>
            <end position="241"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3Y5Z3"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q60994"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00368"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10918532"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11479627"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="11812766"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12086969"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="12354786"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="12878598"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="15340161"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="16497731"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="19855092"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="8947845"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="10095105"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="10403784"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="8619847"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="8947845"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="4DOU"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="21">
        <source>
            <dbReference type="PDB" id="6U66"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="22">
        <source>
            <dbReference type="PDB" id="6U6N"/>
        </source>
    </evidence>
    <sequence length="244" mass="26414" checksum="64D8C6C1204B1018" modified="1996-11-01" version="1" precursor="true">MLLLGAVLLLLALPGHDQETTTQGPGVLLPLPKGACTGWMAGIPGHPGHNGAPGRDGRDGTPGEKGEKGDPGLIGPKGDIGETGVPGAEGPRGFPGIQGRKGEPGEGAYVYRSAFSVGLETYVTIPNMPIRFTKIFYNQQNHYDGSTGKFHCNIPGLYYFAYHITVYMKDVKVSLFKKDKAMLFTYDQYQENNVDQASGSVLLHLEVGDQVWLQVYGEGERNGLYADNDNDSTFTGFLLYHDTN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-07-24" modified="2026-01-28" version="102" xmlns="https://uniprot.org/uniprot">
    <accession>Q0VDE8</accession>
    <name>ADIG_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adipogenin</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="5" type="primary">ADIG</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="Nature" volume="414" first="865" last="871">
            <title>The DNA sequence and comparative analysis of human chromosome 20.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Matthews L.H."/>
                <person name="Ashurst J.L."/>
                <person name="Burton J."/>
                <person name="Gilbert J.G.R."/>
                <person name="Jones M."/>
                <person name="Stavrides G."/>
                <person name="Almeida J.P."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Barlow K.F."/>
                <person name="Bates K.N."/>
                <person name="Beard L.M."/>
                <person name="Beare D.M."/>
                <person name="Beasley O.P."/>
                <person name="Bird C.P."/>
                <person name="Blakey S.E."/>
                <person name="Bridgeman A.M."/>
                <person name="Brown A.J."/>
                <person name="Buck D."/>
                <person name="Burrill W.D."/>
                <person name="Butler A.P."/>
                <person name="Carder C."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clamp M."/>
                <person name="Clark G."/>
                <person name="Clark L.N."/>
                <person name="Clark S.Y."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Cobley V.E."/>
                <person name="Collier R.E."/>
                <person name="Connor R.E."/>
                <person name="Corby N.R."/>
                <person name="Coulson A."/>
                <person name="Coville G.J."/>
                <person name="Deadman R."/>
                <person name="Dhami P.D."/>
                <person name="Dunn M."/>
                <person name="Ellington A.G."/>
                <person name="Frankland J.A."/>
                <person name="Fraser A."/>
                <person name="French L."/>
                <person name="Garner P."/>
                <person name="Grafham D.V."/>
                <person name="Griffiths C."/>
                <person name="Griffiths M.N.D."/>
                <person name="Gwilliam R."/>
                <person name="Hall R.E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Heath P.D."/>
                <person name="Ho S."/>
                <person name="Holden J.L."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hunt A.R."/>
                <person name="Hunt S.E."/>
                <person name="Jekosch K."/>
                <person name="Johnson C.M."/>
                <person name="Johnson D."/>
                <person name="Kay M.P."/>
                <person name="Kimberley A.M."/>
                <person name="King A."/>
                <person name="Knights A."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lehvaeslaiho M.H."/>
                <person name="Leversha M.A."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Lovell J.D."/>
                <person name="Marsh V.L."/>
                <person name="Martin S.L."/>
                <person name="McConnachie L.J."/>
                <person name="McLay K."/>
                <person name="McMurray A.A."/>
                <person name="Milne S.A."/>
                <person name="Mistry D."/>
                <person name="Moore M.J.F."/>
                <person name="Mullikin J.C."/>
                <person name="Nickerson T."/>
                <person name="Oliver K."/>
                <person name="Parker A."/>
                <person name="Patel R."/>
                <person name="Pearce T.A.V."/>
                <person name="Peck A.I."/>
                <person name="Phillimore B.J.C.T."/>
                <person name="Prathalingam S.R."/>
                <person name="Plumb R.W."/>
                <person name="Ramsay H."/>
                <person name="Rice C.M."/>
                <person name="Ross M.T."/>
                <person name="Scott C.E."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M.L."/>
                <person name="Soderlund C."/>
                <person name="Steward C.A."/>
                <person name="Sulston J.E."/>
                <person name="Swann R.M."/>
                <person name="Sycamore N."/>
                <person name="Taylor R."/>
                <person name="Tee L."/>
                <person name="Thomas D.W."/>
                <person name="Thorpe A."/>
                <person name="Tracey A."/>
                <person name="Tromans A.C."/>
                <person name="Vaudin M."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="Whitehead S.L."/>
                <person name="Whittaker P."/>
                <person name="Willey D.L."/>
                <person name="Williams L."/>
                <person name="Williams S.A."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Hubbard T."/>
                <person name="Durbin R.M."/>
                <person name="Bentley D.R."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="11780052"/>
            <dbReference type="DOI" id="10.1038/414865a"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="5" key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="2">Plays a role in stimulating adipocyte differentiation and development.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="3">Membrane</location>
            <topology evidence="3">Single-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the adipogenin family.</text>
    </comment>
    <dbReference type="EMBL" id="AL035419">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC119704">
        <property type="protein sequence ID" value="AAI19705.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC119705">
        <property type="protein sequence ID" value="AAI19706.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54461.1"/>
    <dbReference type="RefSeq" id="NP_001380745.1">
        <property type="nucleotide sequence ID" value="NM_001393816.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q0VDE8"/>
    <dbReference type="SMR" id="Q0VDE8"/>
    <dbReference type="FunCoup" id="Q0VDE8">
        <property type="interactions" value="34"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000440331"/>
    <dbReference type="TCDB" id="9.B.434.1.1">
        <property type="family name" value="the adipogenin (adig) family"/>
    </dbReference>
    <dbReference type="PhosphoSitePlus" id="Q0VDE8"/>
    <dbReference type="BioMuta" id="ADIG"/>
    <dbReference type="DMDM" id="156630981"/>
    <dbReference type="MassIVE" id="Q0VDE8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000440331"/>
    <dbReference type="PeptideAtlas" id="Q0VDE8"/>
    <dbReference type="ProteomicsDB" id="58824"/>
    <dbReference type="Antibodypedia" id="51583">
        <property type="antibodies" value="12 antibodies from 8 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="149685"/>
    <dbReference type="Ensembl" id="ENST00000470147.5">
        <property type="protein sequence ID" value="ENSP00000434385.1"/>
        <property type="gene ID" value="ENSG00000182035.13"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000537425.3">
        <property type="protein sequence ID" value="ENSP00000440331.2"/>
        <property type="gene ID" value="ENSG00000182035.13"/>
    </dbReference>
    <dbReference type="GeneID" id="149685"/>
    <dbReference type="KEGG" id="hsa:149685"/>
    <dbReference type="MANE-Select" id="ENST00000537425.3">
        <property type="protein sequence ID" value="ENSP00000440331.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001393816.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001380745.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002xjb.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28606"/>
    <dbReference type="ClinPGx" id="PA162375689"/>
    <dbReference type="CTD" id="149685"/>
    <dbReference type="DisGeNET" id="149685"/>
    <dbReference type="GeneCards" id="ADIG"/>
    <dbReference type="HGNC" id="HGNC:28606">
        <property type="gene designation" value="ADIG"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000182035">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="611396">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000182035"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000182035"/>
    <dbReference type="eggNOG" id="ENOG502SXJP">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000018723"/>
    <dbReference type="HOGENOM" id="CLU_2605436_0_0_1"/>
    <dbReference type="InParanoid" id="Q0VDE8"/>
    <dbReference type="OMA" id="QGPAEFC"/>
    <dbReference type="OrthoDB" id="9426851at2759"/>
    <dbReference type="PAN-GO" id="Q0VDE8">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q0VDE8"/>
    <dbReference type="PathwayCommons" id="Q0VDE8"/>
    <dbReference type="SignaLink" id="Q0VDE8"/>
    <dbReference type="Agora" id="ENSG00000182035"/>
    <dbReference type="BioGRID-ORCS" id="149685">
        <property type="hits" value="12 hits in 1141 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="149685"/>
    <dbReference type="Pharos" id="Q0VDE8">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q0VDE8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q0VDE8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000182035">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 68 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q0VDE8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005811">
        <property type="term" value="C:lipid droplet"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050873">
        <property type="term" value="P:brown fat cell differentiation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045600">
        <property type="term" value="P:positive regulation of fat cell differentiation"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007283">
        <property type="term" value="P:spermatogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050872">
        <property type="term" value="P:white fat cell differentiation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027938">
        <property type="entry name" value="Adipogenin"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR38499">
        <property type="entry name" value="ADIPOGENIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR38499:SF1">
        <property type="entry name" value="ADIPOGENIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF15202">
        <property type="entry name" value="Adipogenin"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000296375" description="Adipogenin">
        <location>
            <begin position="1"/>
            <end position="80"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="3">
        <location>
            <begin position="14"/>
            <end position="34"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8R400"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="EMBL" id="AAI19706.1"/>
        </source>
    </evidence>
    <sequence length="80" mass="9465" checksum="7DC102D170BBF86F" modified="2007-02-20" version="1">MKYPLMPLVNDLTFSFLVFWFCLPVGLLLLLIIWLRFLLSQDSEENDSSVCLDWEPWSKGPAEFCWKGTLHGQEKERPCW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-10-11" modified="2026-01-28" version="194" xmlns="https://uniprot.org/uniprot">
    <accession>Q9Y2D8</accession>
    <accession>A8K8W0</accession>
    <accession>B4DFE3</accession>
    <accession>D3DT13</accession>
    <accession>J3KR02</accession>
    <accession>Q6P2P8</accession>
    <accession>Q6ULS1</accession>
    <accession>Q7L168</accession>
    <accession>Q9UIX0</accession>
    <name>ADIP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Afadin- and alpha-actinin-binding protein</fullName>
            <shortName>ADIP</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Afadin DIL domain-interacting protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>SSX2-interacting protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">SSX2IP</name>
        <name type="synonym">KIAA0923</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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            <tissue>Testis</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Eye</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2007" name="Br. J. Haematol." volume="138" first="668" last="669">
            <title>The leukaemia-associated antigen, SSX2IP, is expressed during mitosis on the surface of myeloid leukaemia cells.</title>
            <authorList>
                <person name="Denniss F.A."/>
                <person name="Breslin A."/>
                <person name="Ingram W."/>
                <person name="Hardwick N.R."/>
                <person name="Mufti G.J."/>
                <person name="Guinn B.A."/>
            </authorList>
            <dbReference type="PubMed" id="17686061"/>
            <dbReference type="DOI" id="10.1111/j.1365-2141.2007.06706.x"/>
        </citation>
        <scope>MYELOID LEUKEMIA-ASSOCIATED ANTIGEN</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312 AND SER-536</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2009" name="Blood" volume="113" first="1203" last="1204">
            <title>Elevated expression of the leukemia-associated antigen SSX2IP predicts survival in acute myeloid leukemia patients who lack detectable cytogenetic rearrangements.</title>
            <authorList>
                <person name="Guinn B."/>
                <person name="Greiner J."/>
                <person name="Schmitt M."/>
                <person name="Mills K.I."/>
            </authorList>
            <dbReference type="PubMed" id="19179477"/>
            <dbReference type="DOI" id="10.1182/blood-2008-09-178848"/>
        </citation>
        <scope>MYELOID LEUKEMIA-ASSOCIATED ANTIGEN</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-290; SER-293 AND SER-312</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2013" name="J. Cell Biol." volume="202" first="81" last="95">
            <title>The centriolar satellite protein SSX2IP promotes centrosome maturation.</title>
            <authorList>
                <person name="Barenz F."/>
                <person name="Inoue D."/>
                <person name="Yokoyama H."/>
                <person name="Tegha-Dunghu J."/>
                <person name="Freiss S."/>
                <person name="Draeger S."/>
                <person name="Mayilo D."/>
                <person name="Cado I."/>
                <person name="Merker S."/>
                <person name="Klinger M."/>
                <person name="Hoeckendorf B."/>
                <person name="Pilz S."/>
                <person name="Hupfeld K."/>
                <person name="Steinbeisser H."/>
                <person name="Lorenz H."/>
                <person name="Ruppert T."/>
                <person name="Wittbrodt J."/>
                <person name="Gruss O.J."/>
            </authorList>
            <dbReference type="PubMed" id="23816619"/>
            <dbReference type="DOI" id="10.1083/jcb.201302122"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293; SER-312; SER-536; SER-540 AND SER-542</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2013" name="PLoS ONE" volume="8" first="E66782" last="E66782">
            <title>Epigenetic silencing of miR-338-3p contributes to tumorigenicity in gastric cancer by targeting SSX2IP.</title>
            <authorList>
                <person name="Li P."/>
                <person name="Chen X."/>
                <person name="Su L."/>
                <person name="Li C."/>
                <person name="Zhi Q."/>
                <person name="Yu B."/>
                <person name="Sheng H."/>
                <person name="Wang J."/>
                <person name="Feng R."/>
                <person name="Cai Q."/>
                <person name="Li J."/>
                <person name="Yu Y."/>
                <person name="Yan M."/>
                <person name="Liu B."/>
                <person name="Zhu Z."/>
            </authorList>
            <dbReference type="PubMed" id="23826132"/>
            <dbReference type="DOI" id="10.1371/journal.pone.0066782"/>
        </citation>
        <scope>DEVELOPMENTAL STAGE</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2014" name="Mol. Biol. Cell" volume="25" first="495" last="507">
            <title>The novel centriolar satellite protein SSX2IP targets Cep290 to the ciliary transition zone.</title>
            <authorList>
                <person name="Klinger M."/>
                <person name="Wang W."/>
                <person name="Kuhns S."/>
                <person name="Baerenz F."/>
                <person name="Draeger-Meurer S."/>
                <person name="Pereira G."/>
                <person name="Gruss O.J."/>
            </authorList>
            <dbReference type="PubMed" id="24356449"/>
            <dbReference type="DOI" id="10.1091/mbc.e13-09-0526"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2015" name="Biochem. Biophys. Res. Commun." volume="468" first="39" last="45">
            <title>The conserved Wdr8-hMsd1/SSX2IP complex localises to the centrosome and ensures proper spindle length and orientation.</title>
            <authorList>
                <person name="Hori A."/>
                <person name="Morand A."/>
                <person name="Ikebe C."/>
                <person name="Frith D."/>
                <person name="Snijders A.P."/>
                <person name="Toda T."/>
            </authorList>
            <dbReference type="PubMed" id="26545777"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2015.10.169"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH WRAP73</scope>
    </reference>
    <comment type="function">
        <text evidence="2 8 10 17">Belongs to an adhesion system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). May connect the nectin-afadin and E-cadherin-catenin system through alpha-actinin and may be involved in organization of the actin cytoskeleton at AJs through afadin and alpha-actinin (By similarity). Involved in cell movement: localizes at the leading edge of moving cells in response to PDGF and is required for the formation of the leading edge and the promotion of cell movement, possibly via activation of Rac signaling (By similarity). Acts as a centrosome maturation factor, probably by maintaining the integrity of the pericentriolar material and proper microtubule nucleation at mitotic spindle poles. The function seems to implicate at least in part WRAP73; the SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome (PubMed:23816619, PubMed:26545777). Involved in ciliogenesis (PubMed:24356449). It is required for targeted recruitment of the BBSome, CEP290, RAB8, and SSTR3 to the cilia (PubMed:24356449).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 5 11">Interacts with afadin and alpha-actinin (By similarity). Interacts with VAV2 (By similarity). Interacts with SSX2 and SSX3. Does not interact with SSX1 and SSX4 (PubMed:12007189). Interacts with PCM1 (By similarity). Interacts with WRAP73 (PubMed:26545777).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Cell junction</location>
            <location evidence="1">Adherens junction</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8 10">Cytoplasm</location>
            <location evidence="8 10">Cytoskeleton</location>
            <location evidence="8 10">Microtubule organizing center</location>
            <location evidence="8 10">Centrosome</location>
            <location evidence="8 10">Centriolar satellite</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Cytoplasm</location>
            <location evidence="10">Cytoskeleton</location>
            <location evidence="10">Cilium basal body</location>
        </subcellularLocation>
        <text evidence="1">Not found at cell-matrix AJs.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9Y2D8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9Y2D8-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_011724 VSP_011725"/>
        </isoform>
        <isoform>
            <id>Q9Y2D8-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046368"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed, with the highest expression in brain, intermediate expression in kidney, testis, spinal cord, liver, heart, lung, skeletal muscle, ovary, fetal liver and fetal brain, and little to no expression in pancreas and spleen. All specific brain regions showed intermediate to high expression, with highest expression in amygdala. Also expressed in fetal tissues, mainly in liver and brain.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="8 9">Expressed in interphase and M phase cells. Down-regulated by the miRNA miR338-3p.</text>
    </comment>
    <comment type="domain">
        <text>Both the N-terminal (up to position 79) and the C-terminal (from position 304) sequences are required for interaction with SSX2.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="15 16">Acts as an acute myeloid leukemia-associated antigen and may be used as a potential immunotherapy target for leukemia (PubMed:17686061, PubMed:19179477).</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the ADIP family.</text>
    </comment>
    <comment type="sequence caution" evidence="14">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA76767" version="2"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/42407/SSX2IP"/>
    </comment>
    <dbReference type="EMBL" id="AY367055">
        <property type="protein sequence ID" value="AAQ72373.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB023140">
        <property type="protein sequence ID" value="BAA76767.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292475">
        <property type="protein sequence ID" value="BAF85164.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK294057">
        <property type="protein sequence ID" value="BAG57404.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133046">
        <property type="protein sequence ID" value="CAB61373.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC114482">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471097">
        <property type="protein sequence ID" value="EAW73224.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471097">
        <property type="protein sequence ID" value="EAW73226.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471097">
        <property type="protein sequence ID" value="EAW73227.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471097">
        <property type="protein sequence ID" value="EAW73228.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033637">
        <property type="protein sequence ID" value="AAH33637.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC064389">
        <property type="protein sequence ID" value="AAH64389.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS53337.1">
        <molecule id="Q9Y2D8-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS699.1">
        <molecule id="Q9Y2D8-1"/>
    </dbReference>
    <dbReference type="PIR" id="T42649">
        <property type="entry name" value="T42649"/>
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    <dbReference type="RefSeq" id="NP_001159765.1">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="NM_001166293.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001159766.1">
        <molecule id="Q9Y2D8-3"/>
        <property type="nucleotide sequence ID" value="NM_001166294.2"/>
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    <dbReference type="RefSeq" id="NP_001159767.1">
        <molecule id="Q9Y2D8-3"/>
        <property type="nucleotide sequence ID" value="NM_001166295.2"/>
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    <dbReference type="RefSeq" id="NP_001159889.1">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="NM_001166417.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_054740.3">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="NM_014021.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005270484.1">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="XM_005270427.3"/>
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    <dbReference type="RefSeq" id="XP_005270485.1">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="XM_005270428.3"/>
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    <dbReference type="RefSeq" id="XP_006710394.1">
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        <property type="nucleotide sequence ID" value="XM_006710331.3"/>
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    <dbReference type="RefSeq" id="XP_016855723.1">
        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="XM_017000234.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047300153.1">
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        <property type="nucleotide sequence ID" value="XM_047444197.1"/>
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    <dbReference type="RefSeq" id="XP_047300158.1">
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        <property type="nucleotide sequence ID" value="XM_047444202.1"/>
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        <property type="nucleotide sequence ID" value="XM_047444208.1"/>
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        <property type="nucleotide sequence ID" value="XM_047444216.1"/>
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    <dbReference type="RefSeq" id="XP_047300204.1">
        <molecule id="Q9Y2D8-3"/>
        <property type="nucleotide sequence ID" value="XM_047444248.1"/>
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    <dbReference type="RefSeq" id="XP_054190155.1">
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        <property type="nucleotide sequence ID" value="XM_054334180.1"/>
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        <property type="nucleotide sequence ID" value="XM_054334181.1"/>
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        <property type="nucleotide sequence ID" value="XM_054334183.1"/>
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        <property type="nucleotide sequence ID" value="XM_054334184.1"/>
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    <dbReference type="RefSeq" id="XP_054190160.1">
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        <property type="nucleotide sequence ID" value="XM_054334185.1"/>
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        <molecule id="Q9Y2D8-1"/>
        <property type="nucleotide sequence ID" value="XM_054334186.1"/>
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        <molecule id="Q9Y2D8-3"/>
        <property type="nucleotide sequence ID" value="XM_054334194.1"/>
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        <molecule id="Q9Y2D8-3"/>
        <property type="nucleotide sequence ID" value="XM_054334195.1"/>
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    <dbReference type="AlphaFoldDB" id="Q9Y2D8"/>
    <dbReference type="SMR" id="Q9Y2D8"/>
    <dbReference type="BioGRID" id="125567">
        <property type="interactions" value="320"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9Y2D8">
        <property type="interactions" value="1085"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y2D8"/>
    <dbReference type="STRING" id="9606.ENSP00000340279"/>
    <dbReference type="MoonDB" id="Q9Y2D8">
        <property type="type" value="Predicted"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9Y2D8">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y2D8"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y2D8"/>
    <dbReference type="BioMuta" id="SSX2IP"/>
    <dbReference type="DMDM" id="54035738"/>
    <dbReference type="jPOST" id="Q9Y2D8"/>
    <dbReference type="MassIVE" id="Q9Y2D8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000340279"/>
    <dbReference type="PeptideAtlas" id="Q9Y2D8"/>
    <dbReference type="ProteomicsDB" id="85743">
        <molecule id="Q9Y2D8-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="85744">
        <molecule id="Q9Y2D8-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9Y2D8"/>
    <dbReference type="Antibodypedia" id="19778">
        <property type="antibodies" value="239 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="117178"/>
    <dbReference type="Ensembl" id="ENST00000342203.8">
        <molecule id="Q9Y2D8-1"/>
        <property type="protein sequence ID" value="ENSP00000340279.3"/>
        <property type="gene ID" value="ENSG00000117155.18"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0130">Cell adhesion</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0970">Cilium biogenesis/degradation</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
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            <begin position="1"/>
            <end position="614"/>
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    <feature type="region of interest" description="Disordered" evidence="4">
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            <begin position="292"/>
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    <feature type="coiled-coil region" evidence="3">
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            <begin position="131"/>
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    <feature type="coiled-coil region" evidence="3">
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    <feature type="coiled-coil region" evidence="3">
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            <begin position="374"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="20">
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            <position position="290"/>
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            <begin position="1"/>
            <end position="27"/>
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    <feature type="splice variant" id="VSP_011724" description="In isoform 2." evidence="13">
        <original>SSIN</original>
        <variation>RAKN</variation>
        <location>
            <begin position="557"/>
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    </feature>
    <feature type="splice variant" id="VSP_011725" description="In isoform 2." evidence="13">
        <location>
            <begin position="561"/>
            <end position="614"/>
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    <feature type="sequence variant" id="VAR_056726" description="In dbSNP:rs1057746." evidence="6 7">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="578"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAQ72373." evidence="14" ref="2">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="232"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 8; AAH64389." evidence="14" ref="8">
        <location>
            <position position="405"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAQ72373." evidence="14" ref="2">
        <original>G</original>
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        <location>
            <position position="576"/>
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    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q8VC66"/>
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            <dbReference type="SAM" id="MobiDB-lite"/>
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            <dbReference type="PubMed" id="12007189"/>
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            <dbReference type="PubMed" id="23826132"/>
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        <source>
            <dbReference type="PubMed" id="24356449"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="26545777"/>
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        <source>
            <dbReference type="PubMed" id="14702039"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="17686061"/>
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    <evidence type="ECO:0000305" key="16">
        <source>
            <dbReference type="PubMed" id="19179477"/>
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        <source>
            <dbReference type="PubMed" id="26545777"/>
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    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="18669648"/>
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        <source>
            <dbReference type="PubMed" id="19690332"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="20068231"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <sequence length="614" mass="71236" checksum="427903EF86A6FE31" modified="2004-10-11" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
    <accession>P54922</accession>
    <accession>B2R8H1</accession>
    <accession>D3DN83</accession>
    <name>ADPRH_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="6">ADP-ribosylhydrolase ARH1</fullName>
            <ecNumber evidence="2">3.2.2.19</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ADP-ribose-L-arginine cleaving enzyme</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>[Protein ADP-ribosylarginine] hydrolase</fullName>
            <shortName>ADP-ribosylarginine hydrolase</shortName>
            <shortName evidence="5">hARH1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADPRH</name>
        <name type="synonym">ARH1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1993" name="J. Biol. Chem." volume="268" first="17837" last="17843">
            <title>Cloning and site-directed mutagenesis of human ADP-ribosylarginine hydrolase.</title>
            <authorList>
                <person name="Takada T."/>
                <person name="Iida K."/>
                <person name="Moss J."/>
            </authorList>
            <dbReference type="PubMed" id="8349667"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(17)46780-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Thymus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2019" name="ACS Chem. Biol." volume="14" first="2576" last="2584">
            <title>The ARH and Macrodomain Families of alpha-ADP-ribose-acceptor Hydrolases Catalyze alpha-NAD+ Hydrolysis.</title>
            <authorList>
                <person name="Stevens L.A."/>
                <person name="Kato J."/>
                <person name="Kasamatsu A."/>
                <person name="Oda H."/>
                <person name="Lee D.Y."/>
                <person name="Moss J."/>
            </authorList>
            <dbReference type="PubMed" id="31599159"/>
            <dbReference type="DOI" id="10.1021/acschembio.9b00429"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF ASP-55 AND ASP-56</scope>
    </reference>
    <reference evidence="8" key="6">
        <citation type="journal article" date="2009" name="Acta Crystallogr. F" volume="65" first="529" last="532">
            <title>Cloning, expression, purification and crystallization as well as X-ray fluorescence and preliminary X-ray diffraction analyses of human ADP-ribosylhydrolase 1.</title>
            <authorList>
                <person name="Kernstock S."/>
                <person name="Koch-Nolte F."/>
                <person name="Mueller-Dieckmann J."/>
                <person name="Weiss M.S."/>
                <person name="Mueller-Dieckmann C."/>
            </authorList>
            <dbReference type="PubMed" id="19407395"/>
            <dbReference type="DOI" id="10.1107/s1744309109014067"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) IN COMPLEX WITH ADP AND MAGNESIUM</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2018" name="Cell Chem. Biol." volume="0" first="0" last="0">
            <title>(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition.</title>
            <authorList>
                <person name="Rack J.G.M."/>
                <person name="Ariza A."/>
                <person name="Drown B.S."/>
                <person name="Henfrey C."/>
                <person name="Bartlett E."/>
                <person name="Shirai T."/>
                <person name="Hergenrother P.J."/>
                <person name="Ahel I."/>
            </authorList>
            <dbReference type="PubMed" id="30472116"/>
            <dbReference type="DOI" id="10.1016/j.chembiol.2018.11.001"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.23 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND ADP-RIBOSE</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF SER-54; ASP-55; ASP-56; ASP-302 AND SER-305</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">Specifically acts as an arginine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to arginine residues on proteins.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>N(omega)-(ADP-D-ribosyl)-L-arginyl-[protein] + H2O = ADP-D-ribose + L-arginyl-[protein]</text>
            <dbReference type="Rhea" id="RHEA:14885"/>
            <dbReference type="Rhea" id="RHEA-COMP:10532"/>
            <dbReference type="Rhea" id="RHEA-COMP:15087"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:29965"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:142554"/>
            <dbReference type="EC" id="3.2.2.19"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="2">
            <dbReference type="Rhea" id="RHEA:14886"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>alpha-NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+)</text>
            <dbReference type="Rhea" id="RHEA:68792"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17154"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:77017"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="2">Binds 2 magnesium ions per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6657604">
            <id>P54922</id>
        </interactant>
        <interactant intactId="EBI-2659201">
            <id>Q96BD6</id>
            <label>SPSB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6657604">
            <id>P54922</id>
        </interactant>
        <interactant intactId="EBI-717422">
            <id>Q12800</id>
            <label>TFCP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the ADP-ribosylglycohydrolase family.</text>
    </comment>
    <dbReference type="EC" id="3.2.2.19" evidence="2"/>
    <dbReference type="EMBL" id="L13291">
        <property type="protein sequence ID" value="AAA35555.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK313369">
        <property type="protein sequence ID" value="BAG36168.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79562.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471052">
        <property type="protein sequence ID" value="EAW79563.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC063883">
        <property type="protein sequence ID" value="AAH63883.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC074769">
        <property type="protein sequence ID" value="AAH74769.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS2990.1"/>
    <dbReference type="PIR" id="B47411">
        <property type="entry name" value="B47411"/>
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    <dbReference type="RefSeq" id="NP_001116.1">
        <property type="nucleotide sequence ID" value="NM_001125.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001278878.1">
        <property type="nucleotide sequence ID" value="NM_001291949.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001278879.1">
        <property type="nucleotide sequence ID" value="NM_001291950.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001358021.1">
        <property type="nucleotide sequence ID" value="NM_001371092.1"/>
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    <dbReference type="RefSeq" id="NP_001378921.1">
        <property type="nucleotide sequence ID" value="NM_001391992.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047303432.1">
        <property type="nucleotide sequence ID" value="XM_047447476.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054201282.1">
        <property type="nucleotide sequence ID" value="XM_054345307.1"/>
    </dbReference>
    <dbReference type="PDB" id="3HFW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="A=1-357"/>
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    <dbReference type="PDB" id="6G28">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.23 A"/>
        <property type="chains" value="A=1-357"/>
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    <dbReference type="PDB" id="6G2A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A=1-357"/>
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    <dbReference type="PDB" id="6IUX">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.20 A"/>
        <property type="chains" value="A=2-357"/>
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    <dbReference type="PDBsum" id="3HFW"/>
    <dbReference type="PDBsum" id="6G28"/>
    <dbReference type="PDBsum" id="6G2A"/>
    <dbReference type="PDBsum" id="6IUX"/>
    <dbReference type="AlphaFoldDB" id="P54922"/>
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        <property type="interactions" value="11"/>
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    <dbReference type="FunCoup" id="P54922">
        <property type="interactions" value="32"/>
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    <dbReference type="IntAct" id="P54922">
        <property type="interactions" value="11"/>
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    <dbReference type="MINT" id="P54922"/>
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    <dbReference type="MassIVE" id="P54922"/>
    <dbReference type="PaxDb" id="9606-ENSP00000420200"/>
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    <dbReference type="Antibodypedia" id="32747">
        <property type="antibodies" value="136 antibodies from 22 providers"/>
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    <dbReference type="DNASU" id="141"/>
    <dbReference type="Ensembl" id="ENST00000357003.8">
        <property type="protein sequence ID" value="ENSP00000349496.3"/>
        <property type="gene ID" value="ENSG00000144843.13"/>
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    <dbReference type="Ensembl" id="ENST00000465513.1">
        <property type="protein sequence ID" value="ENSP00000417430.1"/>
        <property type="gene ID" value="ENSG00000144843.13"/>
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    <dbReference type="Ensembl" id="ENST00000478399.5">
        <property type="protein sequence ID" value="ENSP00000420200.1"/>
        <property type="gene ID" value="ENSG00000144843.13"/>
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    <dbReference type="Ensembl" id="ENST00000478927.5">
        <property type="protein sequence ID" value="ENSP00000417528.1"/>
        <property type="gene ID" value="ENSG00000144843.13"/>
    </dbReference>
    <dbReference type="GeneID" id="141"/>
    <dbReference type="KEGG" id="hsa:141"/>
    <dbReference type="MANE-Select" id="ENST00000357003.8">
        <property type="protein sequence ID" value="ENSP00000349496.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001125.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001116.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ecs.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:269"/>
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    <dbReference type="GeneCards" id="ADPRH"/>
    <dbReference type="HGNC" id="HGNC:269">
        <property type="gene designation" value="ADPRH"/>
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    <dbReference type="HPA" id="ENSG00000144843">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="603081">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000144843"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00530000063627"/>
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        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P54922"/>
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        <property type="organism ID" value="2681"/>
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    <dbReference type="Agora" id="ENSG00000144843"/>
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        <property type="hits" value="10 hits in 1145 CRISPR screens"/>
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    <dbReference type="EvolutionaryTrace" id="P54922"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P54922"/>
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        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="P54922">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000144843">
        <property type="expression patterns" value="Expressed in monocyte and 133 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P54922">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003875">
        <property type="term" value="F:ADP-ribosylarginine hydrolase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000287">
        <property type="term" value="F:magnesium ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030955">
        <property type="term" value="F:potassium ion binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051725">
        <property type="term" value="P:protein de-ADP-ribosylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036211">
        <property type="term" value="P:protein modification process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="FunFam" id="1.10.4080.10:FF:000002">
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        <property type="entry name" value="ADP-ribosylation/Crystallin J1"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR012108">
        <property type="entry name" value="ADP-ribosylarg_hydro"/>
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    <dbReference type="InterPro" id="IPR050792">
        <property type="entry name" value="ADP-ribosylglycohydrolase"/>
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    <dbReference type="InterPro" id="IPR005502">
        <property type="entry name" value="Ribosyl_crysJ1"/>
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    <dbReference type="InterPro" id="IPR036705">
        <property type="entry name" value="Ribosyl_crysJ1_sf"/>
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    <dbReference type="PANTHER" id="PTHR16222">
        <property type="entry name" value="ADP-RIBOSYLGLYCOHYDROLASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR16222:SF26">
        <property type="entry name" value="ADP-RIBOSYLHYDROLASE ARH1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03747">
        <property type="entry name" value="ADP_ribosyl_GH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF016939">
        <property type="entry name" value="ADP_ribslarg_hdr"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF101478">
        <property type="entry name" value="ADP-ribosylglycohydrolase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000157283" description="ADP-ribosylhydrolase ARH1">
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            <begin position="1"/>
            <end position="357"/>
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    <feature type="binding site" evidence="1 2 8">
        <location>
            <position position="54"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 2 8">
        <location>
            <position position="55"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
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    <feature type="binding site" evidence="1 2 8">
        <location>
            <position position="56"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
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    <feature type="binding site" evidence="7 8">
        <location>
            <position position="85"/>
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        <ligand>
            <name>substrate</name>
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    <feature type="binding site" evidence="7 8">
        <location>
            <begin position="101"/>
            <end position="103"/>
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        <ligand>
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    <feature type="binding site" evidence="2 7 8">
        <location>
            <position position="124"/>
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        <ligand>
            <name>substrate</name>
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    <feature type="binding site" evidence="2 7 8">
        <location>
            <position position="130"/>
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        <ligand>
            <name>substrate</name>
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    <feature type="binding site" evidence="2 7 8">
        <location>
            <begin position="163"/>
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        <ligand>
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    <feature type="binding site" evidence="2 7 8">
        <location>
            <begin position="263"/>
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        <ligand>
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    <feature type="binding site" evidence="2 7 8">
        <location>
            <begin position="269"/>
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        <ligand>
            <name>substrate</name>
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    <feature type="binding site" evidence="2">
        <location>
            <position position="302"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1 2 8">
        <location>
            <position position="304"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
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    <feature type="binding site" evidence="2">
        <location>
            <position position="304"/>
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<entry dataset="Swiss-Prot" created="2005-11-08" modified="2026-01-28" version="179" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NRN7</accession>
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    <accession>Q9P0Q3</accession>
    <accession>Q9UG80</accession>
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            <fullName>Alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase</fullName>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
    <reference key="1">
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            <title>Identification of the alpha-aminoadipic semialdehyde dehydrogenase-phosphopantetheinyl transferase gene, the human ortholog of the yeast LYS5 gene.</title>
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                <person name="Praphanphoj V."/>
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            <dbReference type="PubMed" id="11286508"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="2">
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            </authorList>
            <dbReference type="PubMed" id="10810093"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2000" name="Genome Res." volume="10" first="1546" last="1560">
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            </authorList>
            <dbReference type="PubMed" id="11042152"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Umbilical cord blood</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.</title>
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            <dbReference type="PubMed" id="10931946"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Adrenal gland</tissue>
        </source>
    </reference>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Dendritic cell</tissue>
        </source>
    </reference>
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                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
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                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Tongue</tissue>
            <tissue>Urinary bladder</tissue>
        </source>
    </reference>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="8">
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            <authorList>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Urinary bladder</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
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            <dbReference type="PubMed" id="17974005"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-309 (ISOFORM 1)</scope>
        <source>
            <tissue>Kidney</tissue>
        </source>
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        <scope>PROTEIN SEQUENCE OF 235-246</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Cajal-Retzius cell</tissue>
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                <person name="Joshi A.K."/>
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            </authorList>
            <dbReference type="PubMed" id="12815048"/>
            <dbReference type="DOI" id="10.1074/jbc.m305459200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBUNIT</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>COFACTOR</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="13">
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            <title>ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.</title>
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                <person name="Matsuoka S."/>
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            <dbReference type="PubMed" id="17525332"/>
            <dbReference type="DOI" id="10.1126/science.1140321"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Embryonic kidney</tissue>
        </source>
    </reference>
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            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
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                <person name="Bakalarski C.E."/>
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                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <title>Acyl carrier protein-specific 4'-phosphopantetheinyl transferase activates 10-formyltetrahydrofolate dehydrogenase.</title>
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                <person name="Strickland K.C."/>
                <person name="Hoeferlin L.A."/>
                <person name="Oleinik N.V."/>
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            </authorList>
            <dbReference type="PubMed" id="19933275"/>
            <dbReference type="DOI" id="10.1074/jbc.m109.080556"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="16">
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            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
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                <person name="Olsen J.V."/>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2011" name="Chem. Biol. Interact." volume="191" first="129" last="136">
            <title>Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase.</title>
            <authorList>
                <person name="Strickland K.C."/>
                <person name="Krupenko N.I."/>
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                <person name="Hu C.J."/>
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            </authorList>
            <dbReference type="PubMed" id="21238436"/>
            <dbReference type="DOI" id="10.1016/j.cbi.2011.01.008"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="19">
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            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
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                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="20">
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
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                <person name="Wang L."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2007" name="Chem. Biol." volume="14" first="1243" last="1253">
            <title>Mechanism and substrate recognition of human holo ACP synthase.</title>
            <authorList>
                <person name="Bunkoczi G."/>
                <person name="Pasta S."/>
                <person name="Joshi A."/>
                <person name="Wu X."/>
                <person name="Kavanagh K.L."/>
                <person name="Smith S."/>
                <person name="Oppermann U."/>
            </authorList>
            <dbReference type="PubMed" id="18022563"/>
            <dbReference type="DOI" id="10.1016/j.chembiol.2007.10.013"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 14-309 IN COMPLEXES WITH COENZYME A; MAGNESIUM IONS AND FASN</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF ARG-47; ARG-86; HIS-111; GLN-112; ASP-129; GLU-181 AND LYS-185</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2 3 4 5">Catalyzes the post-translational modification of target proteins by phosphopantetheine. Can transfer the 4'-phosphopantetheine moiety from coenzyme A, regardless of whether the CoA is presented in the free thiol form or as an acetyl thioester, to a serine residue of a broad range of acceptors including the acyl carrier domain of FASN.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3 4 5">
            <text>apo-[ACP] + CoA = holo-[ACP] + adenosine 3',5'-bisphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:12068"/>
            <dbReference type="Rhea" id="RHEA-COMP:9685"/>
            <dbReference type="Rhea" id="RHEA-COMP:9690"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:57287"/>
            <dbReference type="ChEBI" id="CHEBI:58343"/>
            <dbReference type="ChEBI" id="CHEBI:64479"/>
            <dbReference type="EC" id="2.7.8.7"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4 5">
            <dbReference type="Rhea" id="RHEA:12069"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2 3">
            <text>apo-[ACP] + acetyl-CoA = acetyl-[ACP] + adenosine 3',5'-bisphosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:46564"/>
            <dbReference type="Rhea" id="RHEA-COMP:9621"/>
            <dbReference type="Rhea" id="RHEA-COMP:9690"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:57288"/>
            <dbReference type="ChEBI" id="CHEBI:58343"/>
            <dbReference type="ChEBI" id="CHEBI:78446"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="8">
            <dbReference type="Rhea" id="RHEA:46565"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="2 3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="2 3">Binds 1 Mg(2+) ion.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="3">0.44 mM for magnesium</KM>
            <KM evidence="3">0.025 mM for coenzyme A</KM>
        </kinetics>
        <phDependence>
            <text evidence="2">Optimum pH is 6-10.</text>
        </phDependence>
    </comment>
    <comment type="subunit">
        <text evidence="2">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-748171">
            <id>O43186</id>
            <label>CRX</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-2349927">
            <id>Q5JST6</id>
            <label>EFHC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-747107">
            <id>Q8IUQ4</id>
            <label>SIAH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-355744">
            <id>Q12933</id>
            <label>TRAF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-723510">
            <id>Q9UPT9</id>
            <label>USP22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740884">
            <id>Q9NRN7</id>
        </interactant>
        <interactant intactId="EBI-12074414">
            <id>Q9UPT9-2</id>
            <label>USP22</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9NRN7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9NRN7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_055783 VSP_055784"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="1 2">Detected in heart, skeletal muscle, placenta, testis, brain, pancreas, liver and kidney.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the P-Pant transferase superfamily. AcpS family.</text>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAD34075" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="7">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAF86879" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="2.7.8.7" evidence="2 3 4 5"/>
    <dbReference type="EMBL" id="AF302110">
        <property type="protein sequence ID" value="AAG30872.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF151838">
        <property type="protein sequence ID" value="AAD34075.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF151057">
        <property type="protein sequence ID" value="AAF36143.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF136978">
        <property type="protein sequence ID" value="AAG49439.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF201943">
        <property type="protein sequence ID" value="AAF86879.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312529">
        <property type="protein sequence ID" value="BAG35428.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293362">
        <property type="protein sequence ID" value="BAG56878.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AP001001">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471065">
        <property type="protein sequence ID" value="EAW67078.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015470">
        <property type="protein sequence ID" value="AAH15470.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC016728">
        <property type="protein sequence ID" value="AAH16728.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL050073">
        <property type="protein sequence ID" value="CAB43257.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31664.1">
        <molecule id="Q9NRN7-1"/>
    </dbReference>
    <dbReference type="PIR" id="T08733">
        <property type="entry name" value="T08733"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056238.2">
        <molecule id="Q9NRN7-1"/>
        <property type="nucleotide sequence ID" value="NM_015423.2"/>
    </dbReference>
    <dbReference type="PDB" id="2BYD">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A=14-309"/>
    </dbReference>
    <dbReference type="PDB" id="2C43">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.93 A"/>
        <property type="chains" value="A=14-309"/>
    </dbReference>
    <dbReference type="PDB" id="2CG5">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=14-309"/>
    </dbReference>
    <dbReference type="PDBsum" id="2BYD"/>
    <dbReference type="PDBsum" id="2C43"/>
    <dbReference type="PDBsum" id="2CG5"/>
    <dbReference type="AlphaFoldDB" id="Q9NRN7"/>
    <dbReference type="SMR" id="Q9NRN7"/>
    <dbReference type="BioGRID" id="121927">
        <property type="interactions" value="88"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NRN7">
        <property type="interactions" value="1009"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NRN7">
        <property type="interactions" value="44"/>
    </dbReference>
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<entry dataset="Swiss-Prot" created="1989-10-01" modified="2026-01-28" version="241" xmlns="https://uniprot.org/uniprot">
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        <alternativeName>
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            <ecNumber evidence="5">1.1.1.284</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">ADH5</name>
        <name type="synonym">ADHX</name>
        <name type="synonym">FDH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <dbReference type="PubMed" id="2818582"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
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            <dbReference type="PubMed" id="1446828"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
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                <person name="Halleck A."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <authorList>
                <consortium name="NIEHS SNPs program"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS SER-163 AND ILE-309</scope>
    </reference>
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                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>B-cell</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1988" name="Biochemistry" volume="27" first="1132" last="1140">
            <title>Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes.</title>
            <authorList>
                <person name="Kaiser R."/>
                <person name="Holmquist B."/>
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                <person name="Vallee B.L."/>
                <person name="Joernvall H."/>
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            <dbReference type="PubMed" id="3365377"/>
            <dbReference type="DOI" id="10.1021/bi00404a009"/>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-374</scope>
        <scope>COFACTOR</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="9">
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            <title>Role of arginine 115 in fatty acid activation and formaldehyde dehydrogenase activity of human class III alcohol dehydrogenase.</title>
            <authorList>
                <person name="Holmquist B."/>
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                <person name="Vallee B.L."/>
            </authorList>
            <dbReference type="PubMed" id="8494891"/>
            <dbReference type="DOI" id="10.1021/bi00070a024"/>
        </citation>
        <scope>PARTIAL PROTEIN SEQUENCE</scope>
        <scope>MUTAGENESIS OF ARG-115</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1993" name="Proc. Natl. Acad. Sci. U.S.A." volume="90" first="2491" last="2494">
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                <person name="Engeland K."/>
                <person name="Hoeoeg J.-O."/>
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                <person name="Estonius M."/>
                <person name="Joernvall H."/>
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            </authorList>
            <dbReference type="PubMed" id="8460164"/>
            <dbReference type="DOI" id="10.1073/pnas.90.6.2491"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF ARG-115</scope>
    </reference>
    <reference key="11">
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                <person name="Collins X.H."/>
                <person name="Harmon S.D."/>
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            </authorList>
            <dbReference type="PubMed" id="16081420"/>
            <dbReference type="DOI" id="10.1074/jbc.m504055200"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2009" name="Anal. Chem." volume="81" first="4493" last="4501">
            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
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                <person name="Heck A.J."/>
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            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <dbReference type="DOI" id="10.1021/pr300630k"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324 AND SER-351</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Erythroleukemia</tissue>
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    </reference>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-247</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
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            <title>Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase.</title>
            <authorList>
                <person name="Yang Z.-N."/>
                <person name="Bosron W.F."/>
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            </authorList>
            <dbReference type="PubMed" id="9018047"/>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS)</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2020" name="Sci. Adv." volume="6" first="0" last="0">
            <title>Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome.</title>
            <authorList>
                <person name="Oka Y."/>
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            </authorList>
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        </citation>
        <scope>VARIANT AMEDS PRO-278</scope>
        <scope>INVOLVEMENT IN AMEDS</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2 3 5">Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione (PubMed:8460164). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Class-III ADH is remarkably ineffective in oxidizing ethanol (PubMed:8460164). Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage (PubMed:33355142). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADH-dependent reduction of S-nitrosoglutathione, thereby regulating protein S-nitrosylation (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a primary alcohol + NAD(+) = an aldehyde + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10736"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15734"/>
            <dbReference type="ChEBI" id="CHEBI:17478"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>a secondary alcohol + NAD(+) = a ketone + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10740"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17087"/>
            <dbReference type="ChEBI" id="CHEBI:35681"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="EC" id="1.1.1.1"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + NADPH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19981"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57688"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="ChEBI" id="CHEBI:58758"/>
            <dbReference type="EC" id="1.1.1.284"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>S-(hydroxymethyl)glutathione + NAD(+) = S-formylglutathione + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19985"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57688"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:58758"/>
            <dbReference type="EC" id="1.1.1.284"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenedioate + NADH + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:39803"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:76645"/>
            <dbReference type="ChEBI" id="CHEBI:76647"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:39804"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="2">
            <text>20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NAD(+) = 20-oxo-(5Z,8Z,11Z,14Z)-eicosatetraenoate + NADH + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39799"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:76624"/>
            <dbReference type="ChEBI" id="CHEBI:76645"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:39800"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>S-nitrosoglutathione + NADH + H(+) = S-(hydroxysulfenamide)glutathione + NAD(+)</text>
            <dbReference type="Rhea" id="RHEA:78371"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57540"/>
            <dbReference type="ChEBI" id="CHEBI:57945"/>
            <dbReference type="ChEBI" id="CHEBI:145544"/>
            <dbReference type="ChEBI" id="CHEBI:229723"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:78372"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="4">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="4">Binds 2 Zn(2+) ions per subunit.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="2">21 uM for 20-HETE</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="7">Homodimer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="9">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="disease" evidence="3">
        <disease id="DI-06008">
            <name>AMED syndrome, digenic</name>
            <acronym>AMEDS</acronym>
            <description>A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature.</description>
            <dbReference type="MIM" id="619151"/>
        </disease>
        <text evidence="3">The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. AMEDS patients carry ADH5 biallelic variants and homozygous or heterozygous ALDH2 variant p.Glu504Lys, affecting protein activity. Cellular and animal studies demonstrate that the simultaneous loss of ALDH2 and ADH5 activities leads to an increase of cellular formaldehyde sensitivity and multisystem abnormalities including hematopoietic failure.</text>
    </comment>
    <comment type="miscellaneous">
        <text>There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.</text>
    </comment>
    <dbReference type="EC" id="1.1.1.1" evidence="5"/>
    <dbReference type="EC" id="1.1.1.-"/>
    <dbReference type="EC" id="1.1.1.284" evidence="5"/>
    <dbReference type="EMBL" id="M30471">
        <property type="protein sequence ID" value="AAA79018.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M29872">
        <property type="protein sequence ID" value="AAA51597.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M81118">
        <property type="protein sequence ID" value="AAA51596.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M81112">
        <property type="protein sequence ID" value="AAA51596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M81113">
        <property type="protein sequence ID" value="AAA51596.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
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        <ligand>
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        <ligand>
            <name>Zn(2+)</name>
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            <position position="115"/>
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            <position position="2"/>
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            <position position="233"/>
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        <location>
            <position position="247"/>
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            <position position="315"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="13">
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            <position position="351"/>
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        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="163"/>
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        <original>A</original>
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<entry dataset="Swiss-Prot" created="2004-05-10" modified="2026-01-28" version="149" xmlns="https://uniprot.org/uniprot">
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    <reference key="1">
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            <title>Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes.</title>
            <authorList>
                <person name="Roh J."/>
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            </authorList>
            <dbReference type="PubMed" id="14615490"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="2">
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            <authorList>
                <person name="Takei Y."/>
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            </authorList>
            <dbReference type="PubMed" id="14706825"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Peptides" volume="27" first="1383" last="1389">
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            <authorList>
                <person name="Takahashi K."/>
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            </authorList>
            <dbReference type="PubMed" id="16359754"/>
            <dbReference type="DOI" id="10.1016/j.peptides.2005.11.004"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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            <dbReference type="DOI" id="10.1038/990031"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference evidence="14" key="5">
        <citation type="journal article" date="2020" name="ACS Pharmacol. Transl. Sci." volume="3" first="263" last="284">
            <title>Structure and Dynamics of Adrenomedullin Receptors AM1 and AM2 Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins.</title>
            <authorList>
                <person name="Liang Y.L."/>
                <person name="Belousoff M.J."/>
                <person name="Fletcher M.M."/>
                <person name="Zhang X."/>
                <person name="Khoshouei M."/>
                <person name="Deganutti G."/>
                <person name="Koole C."/>
                <person name="Furness S.G.B."/>
                <person name="Miller L.J."/>
                <person name="Hay D.L."/>
                <person name="Christopoulos A."/>
                <person name="Reynolds C.A."/>
                <person name="Danev R."/>
                <person name="Wootten D."/>
                <person name="Sexton P.M."/>
            </authorList>
            <dbReference type="PubMed" id="32296767"/>
            <dbReference type="DOI" id="10.1021/acsptsci.9b00080"/>
        </citation>
        <scope>STRUCTURE BY ELECTRON MICROSCOPY (2.30 ANGSTROMS) OF 101-147 IN COMPLEX WITH CALCRL; RAMP3 AND G PROTEINS</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Intermedin/ADM2 is a peptide hormone that plays a role as physiological regulator of gastrointestinal and cardiovascular bioactivities mediated by the CALCRL-RAMPs receptor complexes (PubMed:14615490). Activates the cAMP-dependent pathway through interaction with CALCRL-RAMP3 receptor complex (PubMed:14615490).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="12">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 7">Expressed in the esophagus, stomach, jejunum, ileum, ileocecum, ascending colon, transverse colon, descending colon and rectum. Expressed in myocardial cells of the heart, renal tubular cells, hypothalamus, and pituitary.</text>
    </comment>
    <comment type="similarity">
        <text evidence="11">Belongs to the adrenomedullin family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAQ09100.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB121034">
        <property type="protein sequence ID" value="BAD07411.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB236970">
        <property type="protein sequence ID" value="BAE46395.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL096767">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS33682.1"/>
    <dbReference type="RefSeq" id="NP_001240774.1">
        <property type="nucleotide sequence ID" value="NM_001253845.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001356811.1">
        <property type="nucleotide sequence ID" value="NM_001369882.1"/>
    </dbReference>
    <dbReference type="PDB" id="6D1U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="D/E/F=129-147"/>
    </dbReference>
    <dbReference type="PDB" id="6UVA">
        <property type="method" value="EM"/>
        <property type="resolution" value="2.30 A"/>
        <property type="chains" value="P=101-147"/>
    </dbReference>
    <dbReference type="PDBsum" id="6D1U"/>
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    <dbReference type="AlphaFoldDB" id="Q7Z4H4"/>
    <dbReference type="EMDB" id="EMD-20906"/>
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        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q7Z4H4">
        <property type="interactions" value="627"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000379087"/>
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    <dbReference type="ChEMBL" id="CHEMBL5267"/>
    <dbReference type="PhosphoSitePlus" id="Q7Z4H4"/>
    <dbReference type="BioMuta" id="ADM2"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000379087"/>
    <dbReference type="PeptideAtlas" id="Q7Z4H4"/>
    <dbReference type="ProteomicsDB" id="69182"/>
    <dbReference type="Antibodypedia" id="52597">
        <property type="antibodies" value="163 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="79924"/>
    <dbReference type="Ensembl" id="ENST00000395737.2">
        <property type="protein sequence ID" value="ENSP00000379086.1"/>
        <property type="gene ID" value="ENSG00000128165.9"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000395738.2">
        <property type="protein sequence ID" value="ENSP00000379087.2"/>
        <property type="gene ID" value="ENSG00000128165.9"/>
    </dbReference>
    <dbReference type="GeneID" id="79924"/>
    <dbReference type="KEGG" id="hsa:79924"/>
    <dbReference type="MANE-Select" id="ENST00000395737.2">
        <property type="protein sequence ID" value="ENSP00000379086.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001253845.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001240774.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003blj.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28898"/>
    <dbReference type="ClinPGx" id="PA134898869"/>
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    <dbReference type="DisGeNET" id="79924"/>
    <dbReference type="GeneCards" id="ADM2"/>
    <dbReference type="HGNC" id="HGNC:28898">
        <property type="gene designation" value="ADM2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000128165">
        <property type="expression patterns" value="Tissue enhanced (kidney, pancreas, thyroid gland)"/>
    </dbReference>
    <dbReference type="MIM" id="608682">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000128165"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000128165"/>
    <dbReference type="eggNOG" id="ENOG502S7F2">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000154380"/>
    <dbReference type="HOGENOM" id="CLU_134508_0_0_1"/>
    <dbReference type="InParanoid" id="Q7Z4H4"/>
    <dbReference type="OMA" id="VTFGCIS"/>
    <dbReference type="OrthoDB" id="9907777at2759"/>
    <dbReference type="PAN-GO" id="Q7Z4H4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q7Z4H4"/>
    <dbReference type="PathwayCommons" id="Q7Z4H4"/>
    <dbReference type="Reactome" id="R-HSA-418555">
        <property type="pathway name" value="G alpha (s) signalling events"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-419812">
        <property type="pathway name" value="Calcitonin-like ligand receptors"/>
    </dbReference>
    <dbReference type="Agora" id="ENSG00000128165"/>
    <dbReference type="BioGRID-ORCS" id="79924">
        <property type="hits" value="16 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADM2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="ADM2"/>
    <dbReference type="GenomeRNAi" id="79924"/>
    <dbReference type="Pharos" id="Q7Z4H4">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q7Z4H4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 22"/>
    </dbReference>
    <dbReference type="RNAct" id="Q7Z4H4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000128165">
        <property type="expression patterns" value="Expressed in body of pancreas and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005179">
        <property type="term" value="F:hormone activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0044877">
        <property type="term" value="F:protein-containing complex binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007189">
        <property type="term" value="P:adenylate cyclase-activating G protein-coupled receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990410">
        <property type="term" value="P:adrenomedullin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001525">
        <property type="term" value="P:angiogenesis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007631">
        <property type="term" value="P:feeding behavior"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045776">
        <property type="term" value="P:negative regulation of blood pressure"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045766">
        <property type="term" value="P:positive regulation of angiogenesis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010628">
        <property type="term" value="P:positive regulation of gene expression"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010460">
        <property type="term" value="P:positive regulation of heart rate"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006468">
        <property type="term" value="P:protein phosphorylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003073">
        <property type="term" value="P:regulation of systemic arterial blood pressure"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051665">
        <property type="entry name" value="Adrenomedullin-reg_peptide"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23414">
        <property type="entry name" value="ADRENOMEDULLIN, ADM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23414:SF2">
        <property type="entry name" value="PROTEIN ADM2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0027">Amidation</keyword>
    <keyword id="KW-0165">Cleavage on pair of basic residues</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0372">Hormone</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000000977" evidence="1">
        <location>
            <begin position="25"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000000978" description="Adrenomedullin-2" evidence="1">
        <location>
            <begin position="101"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="peptide" id="PRO_0000000979" description="Intermedin-short" evidence="4">
        <location>
            <begin position="108"/>
            <end position="147"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="26"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="70"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="site" description="Required for CALCRL receptor interaction" evidence="8">
        <location>
            <position position="107"/>
        </location>
    </feature>
    <feature type="site" description="Required for CALCRL receptor interaction" evidence="8">
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="site" description="Required for CALCRL receptor interaction" evidence="8">
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="modified residue" description="Tyrosine amide" evidence="2">
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="8">
        <location>
            <begin position="110"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="helix" evidence="15">
        <location>
            <begin position="116"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="strand" evidence="15">
        <location>
            <begin position="130"/>
            <end position="132"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P35318"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P61312"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="14615490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16359754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="32296767"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="14615490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="16359754"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0000305" key="12">
        <source>
            <dbReference type="PubMed" id="14615490"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="13">
        <source>
            <dbReference type="HGNC" id="HGNC:28898"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PDB" id="6UVA"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="15">
        <source>
            <dbReference type="PDB" id="6UVA"/>
        </source>
    </evidence>
    <sequence length="148" mass="15865" checksum="6E0E3098CFCE5BF2" modified="2003-10-01" version="1" precursor="true">MARIPTAALGCISLLCLQLPGSLSRSLGGDPRPVKPREPPARSPSSSLQPRHPAPRPVVWKLHRALQAQRGAGLAPVMGQPLRDGGRQHSGPRRHSGPRRTQAQLLRVGCVLGTCQVQNLSHRLWQLMGPAGRQDSAPVDPSSPHSYG</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="127" xmlns="https://uniprot.org/uniprot">
    <accession>Q5T7M4</accession>
    <accession>Q5EBL5</accession>
    <name>ADIPL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adipolin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adipose-derived insulin-sensitizing factor</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="7">C1q and TNF related protein 12</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Complement C1q tumor necrosis factor-related protein 12</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>Adipolin fC1QTNF12</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>Adipolin fCTRP12</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Adipolin full-length form</fullName>
            </alternativeName>
        </component>
        <component>
            <recommendedName>
                <fullName>Adipolin gC1QTNF12</fullName>
            </recommendedName>
            <alternativeName>
                <fullName>Adipolin cleaved form</fullName>
            </alternativeName>
            <alternativeName>
                <fullName>Adipolin gCTRP12</fullName>
            </alternativeName>
        </component>
    </protein>
    <gene>
        <name evidence="9" type="primary">C1QTNF12</name>
        <name type="synonym">C1QDC2</name>
        <name type="synonym">CTRP12</name>
        <name evidence="9" type="synonym">FAM132A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="Lush M.J."/>
                <person name="Lyne R."/>
                <person name="Martin S."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Matthews N.S.W."/>
                <person name="McLaren S."/>
                <person name="Milne S."/>
                <person name="Mistry S."/>
                <person name="Moore M.J.F."/>
                <person name="Nickerson T."/>
                <person name="O'Dell C.N."/>
                <person name="Oliver K."/>
                <person name="Palmeiri A."/>
                <person name="Palmer S.A."/>
                <person name="Parker A."/>
                <person name="Patel D."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phelps K."/>
                <person name="Phillimore B.J."/>
                <person name="Plumb R."/>
                <person name="Rajan J."/>
                <person name="Raymond C."/>
                <person name="Rouse G."/>
                <person name="Saenphimmachak C."/>
                <person name="Sehra H.K."/>
                <person name="Sheridan E."/>
                <person name="Shownkeen R."/>
                <person name="Sims S."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Steward C."/>
                <person name="Subramanian S."/>
                <person name="Sycamore N."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Van Helmond Z."/>
                <person name="Wall M."/>
                <person name="Wallis J.M."/>
                <person name="White S."/>
                <person name="Whitehead S.L."/>
                <person name="Wilkinson J.E."/>
                <person name="Willey D.L."/>
                <person name="Williams H."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Wu Z."/>
                <person name="Coulson A."/>
                <person name="Vaudin M."/>
                <person name="Sulston J.E."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Wooster R."/>
                <person name="Dunham I."/>
                <person name="Carter N.P."/>
                <person name="McVean G."/>
                <person name="Ross M.T."/>
                <person name="Harrow J."/>
                <person name="Olson M.V."/>
                <person name="Beck S."/>
                <person name="Rogers J."/>
                <person name="Bentley D.R."/>
            </authorList>
            <dbReference type="PubMed" id="16710414"/>
            <dbReference type="DOI" id="10.1038/nature04727"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2012" name="J. Biol. Chem." volume="287" first="10301" last="10315">
            <title>C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes.</title>
            <authorList>
                <person name="Wei Z."/>
                <person name="Peterson J.M."/>
                <person name="Lei X."/>
                <person name="Cebotaru L."/>
                <person name="Wolfgang M.J."/>
                <person name="Baldeviano G.C."/>
                <person name="Wong G.W."/>
            </authorList>
            <dbReference type="PubMed" id="22275362"/>
            <dbReference type="DOI" id="10.1074/jbc.m111.303651"/>
        </citation>
        <scope>PROTEOLYTIC PROCESSING</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2014" name="J. Endocrinol." volume="221" first="111" last="119">
            <title>Insulin regulates the novel adipokine adipolin/CTRP12: in vivo and ex vivo effects.</title>
            <authorList>
                <person name="Tan B.K."/>
                <person name="Lewandowski K.C."/>
                <person name="O'Hare J.P."/>
                <person name="Randeva H.S."/>
            </authorList>
            <dbReference type="PubMed" id="24492466"/>
            <dbReference type="DOI" id="10.1530/joe-13-0537"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Insulin-sensitizing adipocyte-secreted protein (adipokine) that regulates glucose metabolism in liver and adipose tissue. Promotes glucose uptake in adipocytes and suppresses de novo glucose production in hepatocytes via the PI3K-Akt signaling pathway. Administration lead to reduction of blood glucose. Able to attenuate inflammation in fat tissue.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Homomultimer; disulfide-linked. May interact with ERFE (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Adipolin fC1QTNF12</molecule>
        <subcellularLocation>
            <location evidence="5">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Adipolin gC1QTNF12</molecule>
        <subcellularLocation>
            <location evidence="5">Secreted</location>
        </subcellularLocation>
        <text evidence="5">In sera is the predominant form.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Predominantly expressed by adipose tissues.</text>
    </comment>
    <comment type="induction">
        <text evidence="6">By insulin in subcutaneous adipose tissue.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Processed into Adipolin fC1QTNF12 and Adipolin gC1QTNF12 by FURIN. Insulin enhances endogenous C1QTNF12 cleavage.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the adipolin/erythroferrone family.</text>
    </comment>
    <dbReference type="EMBL" id="AL162741">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC089443">
        <property type="protein sequence ID" value="AAH89443.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS30554.1"/>
    <dbReference type="RefSeq" id="NP_001014980.1">
        <property type="nucleotide sequence ID" value="NM_001014980.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5T7M4"/>
    <dbReference type="BioGRID" id="132758">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5T7M4">
        <property type="interactions" value="279"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000329137"/>
    <dbReference type="GlyCosmos" id="Q5T7M4">
        <property type="glycosylation" value="1 site, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5T7M4">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="PhosphoSitePlus" id="Q5T7M4"/>
    <dbReference type="BioMuta" id="C1QTNF12"/>
    <dbReference type="DMDM" id="145558864"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000329137"/>
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    <dbReference type="ProteomicsDB" id="64664"/>
    <dbReference type="Antibodypedia" id="12127">
        <property type="antibodies" value="39 antibodies from 13 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="388581"/>
    <dbReference type="Ensembl" id="ENST00000330388.2">
        <property type="protein sequence ID" value="ENSP00000329137.2"/>
        <property type="gene ID" value="ENSG00000184163.3"/>
    </dbReference>
    <dbReference type="GeneID" id="388581"/>
    <dbReference type="KEGG" id="hsa:388581"/>
    <dbReference type="MANE-Select" id="ENST00000330388.2">
        <property type="protein sequence ID" value="ENSP00000329137.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001014980.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001014980.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001adl.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:32308"/>
    <dbReference type="ClinPGx" id="PA162386101"/>
    <dbReference type="CTD" id="388581"/>
    <dbReference type="DisGeNET" id="388581"/>
    <dbReference type="GeneCards" id="C1QTNF12"/>
    <dbReference type="HGNC" id="HGNC:32308">
        <property type="gene designation" value="C1QTNF12"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000184163">
        <property type="expression patterns" value="Tissue enhanced (intestine, skin)"/>
    </dbReference>
    <dbReference type="MIM" id="616593">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000184163"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000184163"/>
    <dbReference type="eggNOG" id="ENOG502QQVR">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160300"/>
    <dbReference type="HOGENOM" id="CLU_057344_1_0_1"/>
    <dbReference type="InParanoid" id="Q5T7M4"/>
    <dbReference type="OMA" id="RCRGRDK"/>
    <dbReference type="OrthoDB" id="6431870at2759"/>
    <dbReference type="PAN-GO" id="Q5T7M4">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5T7M4"/>
    <dbReference type="PathwayCommons" id="Q5T7M4"/>
    <dbReference type="Agora" id="ENSG00000184163"/>
    <dbReference type="BioGRID-ORCS" id="388581">
        <property type="hits" value="15 hits in 1145 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="388581"/>
    <dbReference type="Pharos" id="Q5T7M4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5T7M4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5T7M4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000184163">
        <property type="expression patterns" value="Expressed in mucosa of transverse colon and 103 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005179">
        <property type="term" value="F:hormone activity"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046323">
        <property type="term" value="P:D-glucose import"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051649">
        <property type="term" value="P:establishment of localization in cell"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0006094">
        <property type="term" value="P:gluconeogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045721">
        <property type="term" value="P:negative regulation of gluconeogenesis"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050728">
        <property type="term" value="P:negative regulation of inflammatory response"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043491">
        <property type="term" value="P:phosphatidylinositol 3-kinase/protein kinase B signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046326">
        <property type="term" value="P:positive regulation of D-glucose import"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046628">
        <property type="term" value="P:positive regulation of insulin receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035774">
        <property type="term" value="P:positive regulation of insulin secretion involved in cellular response to glucose stimulus"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051897">
        <property type="term" value="P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046324">
        <property type="term" value="P:regulation of D-glucose import"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.120.40:FF:000012">
        <property type="entry name" value="Adipolin isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.120.40">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052136">
        <property type="entry name" value="Adipolin/Erythroferrone-rel"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001073">
        <property type="entry name" value="C1q_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008983">
        <property type="entry name" value="Tumour_necrosis_fac-like_dom"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24019">
        <property type="entry name" value="ADIPOLIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR24019:SF12">
        <property type="entry name" value="ADIPOLIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF49842">
        <property type="entry name" value="TNF-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50871">
        <property type="entry name" value="C1Q"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0372">Hormone</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="20"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000284354" description="Adipolin fC1QTNF12" evidence="1">
        <location>
            <begin position="21"/>
            <end position="302"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000430248" description="Adipolin gC1QTNF12" evidence="1">
        <location>
            <begin position="98"/>
            <end position="302"/>
        </location>
    </feature>
    <feature type="domain" description="C1q" evidence="3">
        <location>
            <begin position="147"/>
            <end position="302"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="28"/>
            <end position="68"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="86"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="86"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="site" description="Cleavage; by FURIN" evidence="1">
        <location>
            <begin position="97"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="2">
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054065" description="In dbSNP:rs7539412.">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="14"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8R2Z0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00368"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="22275362"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="24492466"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="22275362"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0000312" key="9">
        <source>
            <dbReference type="HGNC" id="HGNC:32308"/>
        </source>
    </evidence>
    <sequence length="302" mass="32416" checksum="7A3AA620CD94B31A" modified="2007-02-20" version="2" precursor="true">MRRWAWAAVVVLLGPQLVLLGGVGARREAQRTQQPGQRADPPNATASASSREGLPEAPKPSQASGPEFSDAHMTWLNFVRRPDDGALRKRCGSRDKKPRDLFGPPGPPGAEVTAETLLHEFQELLKEATERRFSGLLDPLLPQGAGLRLVGEAFHCRLQGPRRVDKRTLVELHGFQAPAAQGAFLRGSGLSLASGRFTAPVSGIFQFSASLHVDHSELQGKARLRARDVVCVLICIESLCQRHTCLEAVSGLESNSRVFTLQVQGLLQLQAGQYASVFVDNGSGAVLTIQAGSSFSGLLLGT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-20" modified="2026-01-28" version="182" xmlns="https://uniprot.org/uniprot">
    <accession>Q6IQ32</accession>
    <accession>A8K951</accession>
    <accession>O94943</accession>
    <accession>Q9H9P3</accession>
    <name>ADNP2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Activity-dependent neuroprotector homeobox protein 2</fullName>
            <shortName>ADNP homeobox protein 2</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Zinc finger protein 508</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADNP2</name>
        <name type="synonym">KIAA0863</name>
        <name type="synonym">ZNF508</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="DNA Res." volume="5" first="355" last="364">
            <title>Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
                <person name="Suyama M."/>
                <person name="Kikuno R."/>
                <person name="Hirosawa M."/>
                <person name="Miyajima N."/>
                <person name="Tanaka A."/>
                <person name="Kotani H."/>
                <person name="Nomura N."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="10048485"/>
            <dbReference type="DOI" id="10.1093/dnares/5.6.355"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-01" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Ohara O."/>
                <person name="Suyama M."/>
                <person name="Kikuno R."/>
                <person name="Nagase T."/>
                <person name="Ishikawa K."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
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                <person name="Yamazaki M."/>
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                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
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                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
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                <person name="Yuuki H."/>
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                <person name="Moriya S."/>
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                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
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                <person name="Kumagai A."/>
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                <person name="Fukuzumi Y."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
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                <person name="Kawakami T."/>
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                <person name="Senba T."/>
                <person name="Matsumura K."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
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                <person name="Oyama M."/>
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                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1024</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2014" name="Proc. Natl. Acad. Sci. U.S.A." volume="111" first="12432" last="12437">
            <title>Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli.</title>
            <authorList>
                <person name="Impens F."/>
                <person name="Radoshevich L."/>
                <person name="Cossart P."/>
                <person name="Ribet D."/>
            </authorList>
            <dbReference type="PubMed" id="25114211"/>
            <dbReference type="DOI" id="10.1073/pnas.1413825111"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1032</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-118; LYS-146; LYS-979; LYS-1018 AND LYS-1032</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">May be involved in transcriptional regulation. May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress. May be involved in erythroid differentiation (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">May interact with SMARCA4/BRG1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838654">
            <id>Q6IQ32</id>
        </interactant>
        <interactant intactId="EBI-78129">
            <id>P83916</id>
            <label>CBX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2838654">
            <id>Q6IQ32</id>
        </interactant>
        <interactant intactId="EBI-78176">
            <id>Q13185</id>
            <label>CBX3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the krueppel C2H2-type zinc-finger protein family.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA74886" version="2"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="BAB14180" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AB020670">
        <property type="protein sequence ID" value="BAA74886.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK022688">
        <property type="protein sequence ID" value="BAB14180.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292566">
        <property type="protein sequence ID" value="BAF85255.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471117">
        <property type="protein sequence ID" value="EAW66646.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC071589">
        <property type="protein sequence ID" value="AAH71589.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS32853.1"/>
    <dbReference type="RefSeq" id="NP_055728.1">
        <property type="nucleotide sequence ID" value="NM_014913.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6IQ32"/>
    <dbReference type="BioGRID" id="116522">
        <property type="interactions" value="61"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6IQ32">
        <property type="interactions" value="1033"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6IQ32">
        <property type="interactions" value="30"/>
    </dbReference>
    <dbReference type="MINT" id="Q6IQ32"/>
    <dbReference type="STRING" id="9606.ENSP00000262198"/>
    <dbReference type="GlyGen" id="Q6IQ32">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6IQ32"/>
    <dbReference type="PhosphoSitePlus" id="Q6IQ32"/>
    <dbReference type="BioMuta" id="ADNP2"/>
    <dbReference type="DMDM" id="74757998"/>
    <dbReference type="jPOST" id="Q6IQ32"/>
    <dbReference type="MassIVE" id="Q6IQ32"/>
    <dbReference type="PaxDb" id="9606-ENSP00000262198"/>
    <dbReference type="PeptideAtlas" id="Q6IQ32"/>
    <dbReference type="ProteomicsDB" id="66483"/>
    <dbReference type="Pumba" id="Q6IQ32"/>
    <dbReference type="Antibodypedia" id="1760">
        <property type="antibodies" value="63 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="22850"/>
    <dbReference type="Ensembl" id="ENST00000262198.9">
        <property type="protein sequence ID" value="ENSP00000262198.3"/>
        <property type="gene ID" value="ENSG00000101544.10"/>
    </dbReference>
    <dbReference type="GeneID" id="22850"/>
    <dbReference type="KEGG" id="hsa:22850"/>
    <dbReference type="MANE-Select" id="ENST00000262198.9">
        <property type="protein sequence ID" value="ENSP00000262198.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_014913.4"/>
        <property type="RefSeq protein sequence ID" value="NP_055728.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc032hie.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23803"/>
    <dbReference type="ClinPGx" id="PA162375700"/>
    <dbReference type="CTD" id="22850"/>
    <dbReference type="DisGeNET" id="22850"/>
    <dbReference type="GeneCards" id="ADNP2"/>
    <dbReference type="HGNC" id="HGNC:23803">
        <property type="gene designation" value="ADNP2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000101544">
        <property type="expression patterns" value="Tissue enhanced (bone)"/>
    </dbReference>
    <dbReference type="MIM" id="617422">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000101544"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000101544"/>
    <dbReference type="eggNOG" id="ENOG502QU0M">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00530000063631"/>
    <dbReference type="HOGENOM" id="CLU_009119_1_0_1"/>
    <dbReference type="InParanoid" id="Q6IQ32"/>
    <dbReference type="OMA" id="MEVAHKQ"/>
    <dbReference type="OrthoDB" id="10053955at2759"/>
    <dbReference type="PAN-GO" id="Q6IQ32">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6IQ32"/>
    <dbReference type="PathwayCommons" id="Q6IQ32"/>
    <dbReference type="SignaLink" id="Q6IQ32"/>
    <dbReference type="Agora" id="ENSG00000101544"/>
    <dbReference type="BioGRID-ORCS" id="22850">
        <property type="hits" value="14 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADNP2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="22850"/>
    <dbReference type="Pharos" id="Q6IQ32">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6IQ32"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 18"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6IQ32">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000101544">
        <property type="expression patterns" value="Expressed in secondary oocyte and 209 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6IQ32">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000785">
        <property type="term" value="C:chromatin"/>
        <property type="evidence" value="ECO:0000247"/>
        <property type="project" value="NTNU_SB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000981">
        <property type="term" value="F:DNA-binding transcription factor activity, RNA polymerase II-specific"/>
        <property type="evidence" value="ECO:0000247"/>
        <property type="project" value="NTNU_SB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007399">
        <property type="term" value="P:nervous system development"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010468">
        <property type="term" value="P:regulation of gene expression"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd00086">
        <property type="entry name" value="homeodomain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038861">
        <property type="entry name" value="ADNP/ADNP2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR045762">
        <property type="entry name" value="ADNP_Znf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001356">
        <property type="entry name" value="HD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009057">
        <property type="entry name" value="Homeodomain-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013087">
        <property type="entry name" value="Znf_C2H2_type"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15740:SF2">
        <property type="entry name" value="ACTIVITY-DEPENDENT NEUROPROTECTOR HOMEOBOX PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15740">
        <property type="entry name" value="NEUROPROTECTIVE PEPTIDE-CONTAINING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF19627">
        <property type="entry name" value="ADNP_N"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00389">
        <property type="entry name" value="HOX"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00355">
        <property type="entry name" value="ZnF_C2H2"/>
        <property type="match status" value="8"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF46689">
        <property type="entry name" value="Homeodomain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00028">
        <property type="entry name" value="ZINC_FINGER_C2H2_1"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50157">
        <property type="entry name" value="ZINC_FINGER_C2H2_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0371">Homeobox</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000280416" description="Activity-dependent neuroprotector homeobox protein 2">
        <location>
            <begin position="1"/>
            <end position="1131"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 1" evidence="2">
        <location>
            <begin position="73"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 2; degenerate" evidence="2">
        <location>
            <begin position="106"/>
            <end position="128"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 3; degenerate" evidence="2">
        <location>
            <begin position="155"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 4" evidence="2">
        <location>
            <begin position="215"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 5; degenerate" evidence="2">
        <location>
            <begin position="694"/>
            <end position="716"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 6; degenerate" evidence="2">
        <location>
            <begin position="747"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 7" evidence="2">
        <location>
            <begin position="770"/>
            <end position="793"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 8" evidence="2">
        <location>
            <begin position="875"/>
            <end position="898"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 9; degenerate" evidence="2">
        <location>
            <begin position="913"/>
            <end position="937"/>
        </location>
    </feature>
    <feature type="DNA-binding region" description="Homeobox" evidence="3">
        <location>
            <begin position="1043"/>
            <end position="1102"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="274"/>
            <end position="329"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="4">
        <location>
            <begin position="274"/>
            <end position="285"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="6">
        <location>
            <position position="1024"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="8">
        <location>
            <position position="118"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="8">
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="8">
        <location>
            <position position="979"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="8">
        <location>
            <position position="1018"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate" evidence="7">
        <location>
            <position position="1032"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate" evidence="8">
        <location>
            <position position="1032"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAB14180." evidence="5" ref="3">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="757"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q8CHC8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00042"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00108"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="25114211"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="8">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <sequence length="1131" mass="122833" checksum="73BCB3F755E6906D" modified="2004-07-05" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-15" modified="2026-01-28" version="143" xmlns="https://uniprot.org/uniprot">
    <accession>Q3LIE5</accession>
    <accession>A8K9B4</accession>
    <accession>D3DTS4</accession>
    <accession>Q9BVD4</accession>
    <accession>Q9NRU8</accession>
    <name>ADPRM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Manganese-dependent ADP-ribose/CDP-alcohol diphosphatase</fullName>
            <ecNumber>3.6.1.13</ecNumber>
            <ecNumber>3.6.1.16</ecNumber>
            <ecNumber>3.6.1.53</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>ADPRibase-Mn</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>CDP-choline phosphohydrolase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADPRM</name>
        <name type="synonym">C17orf48</name>
        <name type="ORF">MDS006</name>
        <name type="ORF">Nbla03831</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="Cancer Lett." volume="197" first="63" last="68">
            <title>Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma.</title>
            <authorList>
                <person name="Ohira M."/>
                <person name="Morohashi A."/>
                <person name="Nakamura Y."/>
                <person name="Isogai E."/>
                <person name="Furuya K."/>
                <person name="Hamano S."/>
                <person name="Machida T."/>
                <person name="Aoyama M."/>
                <person name="Fukumura M."/>
                <person name="Miyazaki K."/>
                <person name="Suzuki Y."/>
                <person name="Sugano S."/>
                <person name="Hirato J."/>
                <person name="Nakagawara A."/>
            </authorList>
            <dbReference type="PubMed" id="12880961"/>
            <dbReference type="DOI" id="10.1016/s0304-3835(03)00085-5"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Neuroblastoma</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Thymus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Placenta</tissue>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="1999-07" db="EMBL/GenBank/DDBJ databases">
            <title>Novel genes expressed in hematopoietic stem/progenitor cells from myelodysplastic syndrome patients.</title>
            <authorList>
                <person name="Huang C."/>
                <person name="Zhang C."/>
                <person name="Tu Y."/>
                <person name="Gu W."/>
                <person name="Wang Y."/>
                <person name="Han Z."/>
                <person name="Chen Z."/>
                <person name="Zhou J."/>
                <person name="Gu J."/>
                <person name="Huang Q."/>
                <person name="Yu Y."/>
                <person name="Xu S."/>
                <person name="Ren S."/>
                <person name="Fu G."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-217 (ISOFORM 1)</scope>
        <source>
            <tissue>Hematopoietic stem cell</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>CDP-choline + H2O = phosphocholine + CMP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:32487"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:58779"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
            <dbReference type="ChEBI" id="CHEBI:295975"/>
            <dbReference type="EC" id="3.6.1.53"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>ADP-D-ribose + H2O = D-ribose 5-phosphate + AMP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:10412"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:78346"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="3.6.1.13"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>ADP-D-ribose + H2O = D-ribose 5-phosphate + AMP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:10412"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:78346"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="EC" id="3.6.1.53"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>CDP-glycerol + H2O = sn-glycerol 3-phosphate + CMP + 2 H(+)</text>
            <dbReference type="Rhea" id="RHEA:21692"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57597"/>
            <dbReference type="ChEBI" id="CHEBI:58311"/>
            <dbReference type="ChEBI" id="CHEBI:60377"/>
            <dbReference type="EC" id="3.6.1.16"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q3LIE5-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q3LIE5-3</id>
            <name>2</name>
            <sequence type="described" ref="VSP_025092 VSP_025093"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
        <text evidence="4">May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the ADPRibase-Mn family.</text>
    </comment>
    <comment type="sequence caution" evidence="4">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAF87317" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.6.1.13"/>
    <dbReference type="EC" id="3.6.1.16"/>
    <dbReference type="EC" id="3.6.1.53"/>
    <dbReference type="EMBL" id="AB073393">
        <property type="protein sequence ID" value="BAE45723.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292629">
        <property type="protein sequence ID" value="BAF85318.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW89995.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471108">
        <property type="protein sequence ID" value="EAW89996.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC001294">
        <property type="protein sequence ID" value="AAH01294.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC070155">
        <property type="protein sequence ID" value="AAH70155.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF168715">
        <property type="protein sequence ID" value="AAF87317.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11159.2">
        <molecule id="Q3LIE5-1"/>
    </dbReference>
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            <begin position="202"/>
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            <position position="113"/>
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            <position position="202"/>
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            <dbReference type="PubMed" id="15489334"/>
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            <dbReference type="PubMed" id="22814378"/>
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    <sequence length="342" mass="39529" checksum="2DBD4499D9DA2AC2" modified="2005-11-08" version="1">MDDKPNPEALSDSSERLFSFGVIADVQFADLEDGFNFQGTRRRYYRHSLLHLQGAIEDWNNESSMPCCVLQLGDIIDGYNAQYNASKKSLELVMDMFKRLKVPVHHTWGNHEFYNFSREYLTHSKLNTKFLEDQIVHHPETMPSEDYYAYHFVPFPKFRFILLDAYDLSVLGVDQSSPKYEQCMKILREHNPNTELNSPQGLSEPQFVQFNGGFSQEQLNWLNEVLTFSDTNQEKVVIVSHLPIYPDASDNVCLAWNYRDALAVIWSHECVVCFFAGHTHDGGYSEDPFGVYHVNLEGVIETAPDSQAFGTVHVYPDKMMLKGRGRVPDRIMNYKKERAFHC</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-12-01" modified="2026-01-28" version="168" xmlns="https://uniprot.org/uniprot">
    <accession>Q15847</accession>
    <name>ADIRF_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adipogenesis regulatory factor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adipogenesis factor rich in obesity</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adipose most abundant gene transcript 2 protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Adipose-specific protein 2</fullName>
            <shortName>apM-2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADIRF</name>
        <name type="synonym">AFRO</name>
        <name type="synonym">APM2</name>
        <name type="synonym">C10orf116</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <authorList>
                <person name="Maeda K."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Adipose tissue</tissue>
        </source>
    </reference>
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                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
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                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
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                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
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                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
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            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
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        <citation type="submission" date="2004-09" db="UniProtKB">
            <authorList>
                <person name="Richardson M."/>
            </authorList>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <dbReference type="PubMed" id="19444912"/>
            <dbReference type="DOI" id="10.1002/ijc.24465"/>
        </citation>
        <scope>FUNCTION IN RESISTANCE TO CISPLATIN</scope>
        <scope>INDUCTION</scope>
    </reference>
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                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="7">
        <citation type="journal article" date="2013" name="J. Bioenerg. Biomembr." volume="45" first="219" last="228">
            <title>A Novel pro-adipogenesis factor abundant in adipose tissues and over-expressed in obesity acts upstream of PPARgamma and C/EBPalpha.</title>
            <authorList>
                <person name="Ni Y."/>
                <person name="Ji C."/>
                <person name="Wang B."/>
                <person name="Qiu J."/>
                <person name="Wang J."/>
                <person name="Guo X."/>
            </authorList>
            <dbReference type="PubMed" id="23239344"/>
            <dbReference type="DOI" id="10.1007/s10863-012-9492-6"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="1 2">Plays a role in fat cell development; promotes adipogenic differentiation and stimulates transcription initiation of master adipogenesis factors like PPARG and CEBPA at early stages of preadipocyte differentiation. Its overexpression confers resistance to the anticancer chemotherapeutic drug cisplatin.</text>
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    <comment type="interaction">
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            <id>Q15847</id>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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        <subcellularLocation>
            <location evidence="2">Nucleus</location>
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    <comment type="tissue specificity">
        <text evidence="2 3">Expressed in adipose tissue (at protein level). Highly expressed in omental and subcutaneous adipose tissues. Expressed in heart, cornea, liver, kidney and spleen.</text>
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    <comment type="induction">
        <text evidence="1 2">Up-regulated during pre-adipocyte differentiation. Up-regulated following DNA damage induced by UV irradiation.</text>
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        <property type="expression patterns" value="Expressed in popliteal artery and 200 other cell types or tissues"/>
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<entry dataset="Swiss-Prot" created="2010-03-23" modified="2026-01-28" version="83" xmlns="https://uniprot.org/uniprot">
    <accession>C9JUS6</accession>
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        <recommendedName>
            <fullName>Putative adrenomedullin-5-like protein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ADM5</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="428" first="529" last="535">
            <title>The DNA sequence and biology of human chromosome 19.</title>
            <authorList>
                <person name="Grimwood J."/>
                <person name="Gordon L.A."/>
                <person name="Olsen A.S."/>
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                <person name="Schmutz J."/>
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                <person name="Hellsten U."/>
                <person name="Goodstein D."/>
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                <person name="Aerts A."/>
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                <person name="Flowers D."/>
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                <person name="Gomez M."/>
                <person name="Gonzales E."/>
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                <person name="Ho I."/>
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                <person name="Kimball H."/>
                <person name="Kobayashi A."/>
                <person name="Larionov V."/>
                <person name="Leem S.-H."/>
                <person name="Lopez F."/>
                <person name="Lou Y."/>
                <person name="Lowry S."/>
                <person name="Malfatti S."/>
                <person name="Martinez D."/>
                <person name="McCready P.M."/>
                <person name="Medina C."/>
                <person name="Morgan J."/>
                <person name="Nelson K."/>
                <person name="Nolan M."/>
                <person name="Ovcharenko I."/>
                <person name="Pitluck S."/>
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                <person name="Predki P."/>
                <person name="Quan G."/>
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                <person name="Rash S."/>
                <person name="Retterer J."/>
                <person name="Rodriguez A."/>
                <person name="Rogers S."/>
                <person name="Salamov A."/>
                <person name="Salazar A."/>
                <person name="She X."/>
                <person name="Smith D."/>
                <person name="Slezak T."/>
                <person name="Solovyev V."/>
                <person name="Thayer N."/>
                <person name="Tice H."/>
                <person name="Tsai M."/>
                <person name="Ustaszewska A."/>
                <person name="Vo N."/>
                <person name="Wagner M."/>
                <person name="Wheeler J."/>
                <person name="Wu K."/>
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                <person name="DeJong P."/>
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                <person name="Eichler E.E."/>
                <person name="Pennacchio L.A."/>
                <person name="Richardson P."/>
                <person name="Stubbs L."/>
                <person name="Rokhsar D.S."/>
                <person name="Myers R.M."/>
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                <person name="Lucas S.M."/>
            </authorList>
            <dbReference type="PubMed" id="15057824"/>
            <dbReference type="DOI" id="10.1038/nature02399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
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                <person name="Flanigan M.J."/>
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                <person name="Fasulo D."/>
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                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2008" name="J. Endocrinol." volume="197" first="391" last="400">
            <title>Central and peripheral cardiovascular actions of adrenomedullin 5, a novel member of the calcitonin gene-related peptide family, in mammals.</title>
            <authorList>
                <person name="Takei Y."/>
                <person name="Hashimoto H."/>
                <person name="Inoue K."/>
                <person name="Osaki T."/>
                <person name="Yoshizawa-Kumagaye K."/>
                <person name="Tsunemi M."/>
                <person name="Watanabe T.X."/>
                <person name="Ogoshi M."/>
                <person name="Minamino N."/>
                <person name="Ueta Y."/>
            </authorList>
            <dbReference type="PubMed" id="18434369"/>
            <dbReference type="DOI" id="10.1677/joe-07-0541"/>
        </citation>
        <scope>IDENTIFICATION</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Probable non-functional remnant of adrenomedullin-5.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the adrenomedullin family.</text>
    </comment>
    <dbReference type="EMBL" id="AC011495">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471177">
        <property type="protein sequence ID" value="EAW52522.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC032764">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS46146.1"/>
    <dbReference type="RefSeq" id="NP_001094810.1">
        <property type="nucleotide sequence ID" value="NM_001101340.2"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="C9JUS6"/>
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        <property type="interactions" value="24"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000393631"/>
    <dbReference type="BioMuta" id="ADM5"/>
    <dbReference type="MassIVE" id="C9JUS6"/>
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    <dbReference type="PeptideAtlas" id="C9JUS6"/>
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        <property type="antibodies" value="3 antibodies from 3 providers"/>
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    <dbReference type="DNASU" id="199800"/>
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        <property type="protein sequence ID" value="ENSP00000393631.2"/>
        <property type="gene ID" value="ENSG00000224420.5"/>
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    <dbReference type="GeneID" id="199800"/>
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        <property type="protein sequence ID" value="ENSP00000393631.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001101340.2"/>
        <property type="RefSeq protein sequence ID" value="NP_001094810.1"/>
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    <dbReference type="UCSC" id="uc002pph.3">
        <property type="organism name" value="human"/>
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    <dbReference type="HGNC" id="HGNC:27293">
        <property type="gene designation" value="ADM5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000224420">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621171">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000224420"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000224420"/>
    <dbReference type="eggNOG" id="ENOG502RJSC">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00730000112484"/>
    <dbReference type="HOGENOM" id="CLU_147097_0_0_1"/>
    <dbReference type="InParanoid" id="C9JUS6"/>
    <dbReference type="OMA" id="YLGVCRT"/>
    <dbReference type="OrthoDB" id="9530181at2759"/>
    <dbReference type="PAN-GO" id="C9JUS6">
        <property type="GO annotations" value="6 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="C9JUS6"/>
    <dbReference type="PathwayCommons" id="C9JUS6"/>
    <dbReference type="Agora" id="ENSG00000224420"/>
    <dbReference type="BioGRID-ORCS" id="199800">
        <property type="hits" value="31 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="199800"/>
    <dbReference type="Pharos" id="C9JUS6">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:C9JUS6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 19"/>
    </dbReference>
    <dbReference type="RNAct" id="C9JUS6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000224420">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 104 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007189">
        <property type="term" value="P:adenylate cyclase-activating G protein-coupled receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010460">
        <property type="term" value="P:positive regulation of heart rate"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003073">
        <property type="term" value="P:regulation of systemic arterial blood pressure"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051665">
        <property type="entry name" value="Adrenomedullin-reg_peptide"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23414">
        <property type="entry name" value="ADRENOMEDULLIN, ADM"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23414:SF6">
        <property type="entry name" value="ADRENOMEDULLIN-5-LIKE PROTEIN-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000392551" description="Putative adrenomedullin-5-like protein">
        <location>
            <begin position="19"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="1">
        <location>
            <begin position="39"/>
            <end position="44"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="18434369"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="153" mass="16532" checksum="2AC1CFBEB867B30D" modified="2009-11-03" version="1" precursor="true">MTIHILILLLLLAFSAQGDLDTAARRGQHQVPQHRGHVCYLGVCRTHRLAEIIYWIRCLHQGALGEGQPRAPGPLQLWAPPVARGGSPARFPGFRPAARGLAQCPARWVTSGTARPLLGFSLPICMLELLLHISSPLTPAPETVFPSPSPGCD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2002-11-01" modified="2026-01-28" version="203" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H2P0</accession>
    <accession>E1P5Y2</accession>
    <accession>O94881</accession>
    <accession>Q5BKU2</accession>
    <accession>Q9UG34</accession>
    <name>ADNP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Activity-dependent neuroprotector homeobox protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Activity-dependent neuroprotective protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADNP</name>
        <name type="synonym">ADNP1</name>
        <name type="synonym">KIAA0784</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
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            <dbReference type="PubMed" id="11780052"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Lymph</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-1102</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-953 AND SER-955</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="19091000"/>
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        <scope>CHARACTERIZATION OF NAP PEPTIDE</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-736 AND SER-953</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1035 AND LYS-1042</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="14">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
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            </authorList>
            <dbReference type="PubMed" id="20068231"/>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-709; SER-805; SER-953 AND SER-955</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="15">
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="16">
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                <person name="Rigbolt K.T."/>
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            <dbReference type="PubMed" id="21406692"/>
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        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-409; SER-921 AND SER-953</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
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            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98; SER-409; SER-608; SER-709; SER-736; SER-921; SER-953 AND SER-955</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
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    </reference>
    <reference key="18">
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            <authorList>
                <person name="Bian Y."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-953</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2014" name="Nat. Genet." volume="46" first="380" last="384">
            <title>A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP.</title>
            <authorList>
                <person name="Helsmoortel C."/>
                <person name="Vulto-van Silfhout A.T."/>
                <person name="Coe B.P."/>
                <person name="Vandeweyer G."/>
                <person name="Rooms L."/>
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            </authorList>
            <dbReference type="PubMed" id="24531329"/>
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        </citation>
        <scope>INVOLVEMENT IN HVDAS</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2014" name="Nat. Struct. Mol. Biol." volume="21" first="927" last="936">
            <title>Uncovering global SUMOylation signaling networks in a site-specific manner.</title>
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            <dbReference type="DOI" id="10.1038/nsmb.2890"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-144; LYS-279; LYS-408; LYS-716; LYS-731; LYS-930 AND LYS-1035</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>SUMO-2 orchestrates chromatin modifiers in response to DNA damage.</title>
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            </authorList>
            <dbReference type="PubMed" id="25772364"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2015.02.033"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-144; LYS-266; LYS-367; LYS-408; LYS-427; LYS-621; LYS-716; LYS-731 AND LYS-1035</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability.</title>
            <authorList>
                <person name="Xiao Z."/>
                <person name="Chang J.G."/>
                <person name="Hendriks I.A."/>
                <person name="Sigurdsson J.O."/>
                <person name="Olsen J.V."/>
                <person name="Vertegaal A.C."/>
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            <dbReference type="PubMed" id="25755297"/>
            <dbReference type="DOI" id="10.1074/mcp.o114.044792"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-144; LYS-600; LYS-606; LYS-930 AND LYS-1035</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
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                <person name="Hendriks I.A."/>
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            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-39; LYS-72; LYS-144; LYS-155; LYS-203; LYS-231; LYS-266; LYS-274; LYS-278; LYS-311; LYS-335; LYS-367; LYS-408; LYS-427; LYS-600; LYS-606; LYS-616; LYS-621; LYS-632; LYS-658; LYS-699; LYS-716; LYS-728; LYS-731; LYS-745; LYS-807; LYS-829; LYS-835; LYS-914; LYS-930; LYS-935; LYS-1016; LYS-1035 AND LYS-1042</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2015" name="Neuron" volume="88" first="910" last="917">
            <title>Targeted DNA Sequencing from Autism Spectrum Disorder Brains Implicates Multiple Genetic Mechanisms.</title>
            <authorList>
                <person name="D'Gama A.M."/>
                <person name="Pochareddy S."/>
                <person name="Li M."/>
                <person name="Jamuar S.S."/>
                <person name="Reiff R.E."/>
                <person name="Lam A.T."/>
                <person name="Sestan N."/>
                <person name="Walsh C.A."/>
            </authorList>
            <dbReference type="PubMed" id="26637798"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2015.11.009"/>
        </citation>
        <scope>VARIANT VAL-1094</scope>
    </reference>
    <comment type="function">
        <text evidence="2">May be involved in transcriptional regulation. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1. May be required for neural induction and neuronal differentiation. May be involved in erythroid differentiation (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2">Interacts (via N-terminal region) with beta-catenin/CTNNB1 (via the central armadillo domains); interaction is direct and stabilizes CTNNB1 by modulating its phosphorylation by glycogen synthase kinase-3 beta GSK3B.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1764854">
            <id>Q9H2P0</id>
        </interactant>
        <interactant intactId="EBI-78129">
            <id>P83916</id>
            <label>CBX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1764854">
            <id>Q9H2P0</id>
        </interactant>
        <interactant intactId="EBI-78176">
            <id>Q13185</id>
            <label>CBX3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1764854">
            <id>Q9H2P0</id>
        </interactant>
        <interactant intactId="EBI-78219">
            <id>P45973</id>
            <label>CBX5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Chromosome</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Widely expressed. Strong expression in heart, skeletal muscle, kidney and placenta. In brain, expression is stronger in the cerebellum and cortex regions. No expression detected in the colon. Strong increase of expression in colon and breast cancer tissues.</text>
    </comment>
    <comment type="disease" evidence="7">
        <disease id="DI-04149">
            <name>Helsmoortel-van der Aa syndrome</name>
            <acronym>HVDAS</acronym>
            <description>A disorder characterized by intellectual disability, autism spectrum disorder, and dysmorphic facial features including prominent forehead, high hairline, downslanting palpebral fissures, notched eyelids, broad nasal bridge, thin upper lip, and smooth philtrum.</description>
            <dbReference type="MIM" id="615873"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <text>When isolated from the sequence, neuroprotective peptide (NAP) provides neuroprotection against the amyloid-beta peptide.</text>
    </comment>
    <dbReference type="EMBL" id="AF250860">
        <property type="protein sequence ID" value="AAG47651.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL034553">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW75611.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471077">
        <property type="protein sequence ID" value="EAW75612.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC090933">
        <property type="protein sequence ID" value="AAH90933.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB018327">
        <property type="protein sequence ID" value="BAA34504.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL080163">
        <property type="protein sequence ID" value="CAB45752.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS13433.1"/>
    <dbReference type="PIR" id="T12546">
        <property type="entry name" value="T12546"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269460.1">
        <property type="nucleotide sequence ID" value="NM_001282531.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001269461.1">
        <property type="nucleotide sequence ID" value="NM_001282532.2"/>
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    <dbReference type="RefSeq" id="NP_001334440.1">
        <property type="nucleotide sequence ID" value="NM_001347511.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_056154.1">
        <property type="nucleotide sequence ID" value="NM_015339.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_852107.1">
        <property type="nucleotide sequence ID" value="NM_181442.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011527049.2">
        <property type="nucleotide sequence ID" value="XM_011528747.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047296031.1">
        <property type="nucleotide sequence ID" value="XM_047440075.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047296032.1">
        <property type="nucleotide sequence ID" value="XM_047440076.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047296033.1">
        <property type="nucleotide sequence ID" value="XM_047440077.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179270.1">
        <property type="nucleotide sequence ID" value="XM_054323295.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179271.1">
        <property type="nucleotide sequence ID" value="XM_054323296.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054179272.1">
        <property type="nucleotide sequence ID" value="XM_054323297.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H2P0"/>
    <dbReference type="BioGRID" id="116967">
        <property type="interactions" value="222"/>
    </dbReference>
    <dbReference type="DIP" id="DIP-47288N"/>
    <dbReference type="FunCoup" id="Q9H2P0">
        <property type="interactions" value="3848"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9H2P0">
        <property type="interactions" value="115"/>
    </dbReference>
    <dbReference type="MINT" id="Q9H2P0"/>
    <dbReference type="STRING" id="9606.ENSP00000360662"/>
    <dbReference type="GlyConnect" id="2014">
        <property type="glycosylation" value="1 N-Linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q9H2P0">
        <property type="glycosylation" value="4 sites, 4 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q9H2P0">
        <property type="glycosylation" value="7 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (6 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9H2P0"/>
    <dbReference type="MetOSite" id="Q9H2P0"/>
    <dbReference type="PhosphoSitePlus" id="Q9H2P0"/>
    <dbReference type="SwissPalm" id="Q9H2P0"/>
    <dbReference type="BioMuta" id="ADNP"/>
    <dbReference type="DMDM" id="24636245"/>
    <dbReference type="jPOST" id="Q9H2P0"/>
    <dbReference type="MassIVE" id="Q9H2P0"/>
    <dbReference type="PaxDb" id="9606-ENSP00000379346"/>
    <dbReference type="PeptideAtlas" id="Q9H2P0"/>
    <dbReference type="ProteomicsDB" id="80571"/>
    <dbReference type="Pumba" id="Q9H2P0"/>
    <dbReference type="Antibodypedia" id="1423">
        <property type="antibodies" value="352 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="23394"/>
    <dbReference type="YCharOS" id="Q9H2P0">
        <property type="antibodies" value="Tested 7 antibodies from 5 manufacturers"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000349014.8">
        <property type="protein sequence ID" value="ENSP00000342905.3"/>
        <property type="gene ID" value="ENSG00000101126.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000371602.9">
        <property type="protein sequence ID" value="ENSP00000360662.2"/>
        <property type="gene ID" value="ENSG00000101126.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000396029.8">
        <property type="protein sequence ID" value="ENSP00000379346.3"/>
        <property type="gene ID" value="ENSG00000101126.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000396032.8">
        <property type="protein sequence ID" value="ENSP00000379349.2"/>
        <property type="gene ID" value="ENSG00000101126.19"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000621696.5">
        <property type="protein sequence ID" value="ENSP00000483881.1"/>
        <property type="gene ID" value="ENSG00000101126.19"/>
    </dbReference>
    <dbReference type="GeneID" id="23394"/>
    <dbReference type="KEGG" id="hsa:23394"/>
    <dbReference type="MANE-Select" id="ENST00000621696.5">
        <property type="protein sequence ID" value="ENSP00000483881.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001282531.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001269460.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002xvt.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:15766"/>
    <dbReference type="ClinPGx" id="PA24582"/>
    <dbReference type="CTD" id="23394"/>
    <dbReference type="DisGeNET" id="23394"/>
    <dbReference type="GeneCards" id="ADNP"/>
    <dbReference type="GeneReviews" id="ADNP"/>
    <dbReference type="HGNC" id="HGNC:15766">
        <property type="gene designation" value="ADNP"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000101126">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADNP"/>
    <dbReference type="MIM" id="611386">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="615873">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000101126"/>
    <dbReference type="Orphanet" id="404448">
        <property type="disease" value="ADNP syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000101126"/>
    <dbReference type="eggNOG" id="ENOG502QSYX">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00530000063631"/>
    <dbReference type="HOGENOM" id="CLU_009119_0_0_1"/>
    <dbReference type="InParanoid" id="Q9H2P0"/>
    <dbReference type="OMA" id="PYCTFNG"/>
    <dbReference type="OrthoDB" id="8891572at2759"/>
    <dbReference type="PAN-GO" id="Q9H2P0">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H2P0"/>
    <dbReference type="PathwayCommons" id="Q9H2P0"/>
    <dbReference type="SignaLink" id="Q9H2P0"/>
    <dbReference type="SIGNOR" id="Q9H2P0"/>
    <dbReference type="Agora" id="ENSG00000101126"/>
    <dbReference type="BioGRID-ORCS" id="23394">
        <property type="hits" value="129 hits in 1188 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADNP">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="23394"/>
    <dbReference type="Pharos" id="Q9H2P0">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H2P0"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 20"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H2P0">
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        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="21">
        <location>
            <position position="835"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="21">
        <location>
            <position position="914"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="18 19 21">
        <location>
            <position position="930"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="21">
        <location>
            <position position="935"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="21">
        <location>
            <position position="1016"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate" evidence="18 19 20 21">
        <location>
            <position position="1035"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate" evidence="21">
        <location>
            <position position="1042"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078696" description="Found in a patient with autism; uncertain significance; dbSNP:rs780706686." evidence="8">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1094"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9JKL8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q9Z103"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00042"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00108"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="19091000"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="24531329"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="26637798"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="17525332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="25218447"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="25755297"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="25772364"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <sequence length="1102" mass="123563" checksum="4132E3EF814AF43B" modified="2001-03-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-04-26" modified="2026-01-28" version="179" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BRR6</accession>
    <accession>Q49AU7</accession>
    <accession>Q8NBI1</accession>
    <accession>Q8WZ90</accession>
    <accession>Q96NF8</accession>
    <accession>Q9H0A7</accession>
    <name>ADPGK_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>ADP-dependent glucokinase</fullName>
            <shortName>ADP-GK</shortName>
            <shortName>ADPGK</shortName>
            <ecNumber>2.7.1.147</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>RbBP-35</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADPGK</name>
        <name type="ORF">PSEC0260</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="1999-11" db="EMBL/GenBank/DDBJ databases">
            <title>RbBP-35 interacted with pRb.</title>
            <authorList>
                <person name="Fan Z.S."/>
                <person name="Ao S.Z."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5)</scope>
        <source>
            <tissue>Lymph node</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
                <person name="Wellenreuther R."/>
                <person name="Gassenhuber J."/>
                <person name="Glassl S."/>
                <person name="Ansorge W."/>
                <person name="Boecher M."/>
                <person name="Bloecker H."/>
                <person name="Bauersachs S."/>
                <person name="Blum H."/>
                <person name="Lauber J."/>
                <person name="Duesterhoeft A."/>
                <person name="Beyer A."/>
                <person name="Koehrer K."/>
                <person name="Strack N."/>
                <person name="Mewes H.-W."/>
                <person name="Ottenwaelder B."/>
                <person name="Obermaier B."/>
                <person name="Tampe J."/>
                <person name="Heubner D."/>
                <person name="Wambutt R."/>
                <person name="Korn B."/>
                <person name="Klein M."/>
                <person name="Poustka A."/>
            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Heart</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="submission" date="2004-06" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).</title>
            <authorList>
                <person name="Ebert L."/>
                <person name="Schick M."/>
                <person name="Neubert P."/>
                <person name="Schatten R."/>
                <person name="Henze S."/>
                <person name="Korn B."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2005" name="DNA Res." volume="12" first="117" last="126">
            <title>Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.</title>
            <authorList>
                <person name="Otsuki T."/>
                <person name="Ota T."/>
                <person name="Nishikawa T."/>
                <person name="Hayashi K."/>
                <person name="Suzuki Y."/>
                <person name="Yamamoto J."/>
                <person name="Wakamatsu A."/>
                <person name="Kimura K."/>
                <person name="Sakamoto K."/>
                <person name="Hatano N."/>
                <person name="Kawai Y."/>
                <person name="Ishii S."/>
                <person name="Saito K."/>
                <person name="Kojima S."/>
                <person name="Sugiyama T."/>
                <person name="Ono T."/>
                <person name="Okano K."/>
                <person name="Yoshikawa Y."/>
                <person name="Aotsuka S."/>
                <person name="Sasaki N."/>
                <person name="Hattori A."/>
                <person name="Okumura K."/>
                <person name="Nagai K."/>
                <person name="Sugano S."/>
                <person name="Isogai T."/>
            </authorList>
            <dbReference type="PubMed" id="16303743"/>
            <dbReference type="DOI" id="10.1093/dnares/12.2.117"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 6)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Kidney</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
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                <person name="Carapito C."/>
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            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor. GDP and CDP can replace ADP, but with reduced efficiency (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction>
            <text>D-glucose + ADP = D-glucose 6-phosphate + AMP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:11460"/>
            <dbReference type="ChEBI" id="CHEBI:4167"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:61548"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.1.147"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="3">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="3">Binds 1 Mg(2+) ion per subunit.</text>
    </comment>
    <comment type="pathway">
        <text evidence="3">Carbohydrate degradation; glycolysis.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="10">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BRR6-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BRR6-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_013552"/>
        </isoform>
        <isoform>
            <id>Q9BRR6-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_013549"/>
        </isoform>
        <isoform>
            <id>Q9BRR6-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_013550 VSP_013551 VSP_013552"/>
        </isoform>
        <isoform>
            <id>Q9BRR6-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_013548 VSP_013553 VSP_013554"/>
        </isoform>
        <isoform>
            <id>Q9BRR6-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_035014"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the ADP-dependent glucokinase family.</text>
    </comment>
    <dbReference type="EC" id="2.7.1.147"/>
    <dbReference type="EMBL" id="AF204270">
        <property type="protein sequence ID" value="AAL31473.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136873">
        <property type="protein sequence ID" value="CAB66807.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK055526">
        <property type="protein sequence ID" value="BAB70941.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR533447">
        <property type="protein sequence ID" value="CAG38478.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK075560">
        <property type="protein sequence ID" value="BAC11699.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006112">
        <property type="protein sequence ID" value="AAH06112.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC018074">
        <property type="protein sequence ID" value="AAH18074.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS42057.1">
        <molecule id="Q9BRR6-2"/>
    </dbReference>
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        <property type="nucleotide sequence ID" value="NM_031284.4"/>
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        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
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    <dbReference type="iPTMnet" id="Q9BRR6"/>
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        <property type="gene designation" value="ADPGK"/>
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
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        <property type="organism ID" value="2681"/>
    </dbReference>
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        <property type="pathway name" value="Glycolysis"/>
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    <dbReference type="Agora" id="ENSG00000159322"/>
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        <property type="hits" value="16 hits in 1153 CRISPR screens"/>
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    <dbReference type="ChiTaRS" id="ADPGK">
        <property type="organism name" value="human"/>
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    <dbReference type="GeneWiki" id="ADP-specific_glucokinase"/>
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        <property type="development level" value="Tbio"/>
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        <property type="component" value="Chromosome 15"/>
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        <property type="molecule type" value="protein"/>
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        <property type="expression patterns" value="Expressed in oocyte and 177 other cell types or tissues"/>
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        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="CACAO"/>
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        <property type="term" value="C:endoplasmic reticulum membrane"/>
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        <property type="term" value="C:extracellular region"/>
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        <property type="project" value="UniProtKB-SubCell"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="F:ADP-specific glucokinase activity"/>
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    <dbReference type="GO" id="GO:0046872">
        <property type="term" value="F:metal ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="P:glucose metabolic process"/>
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        <property type="term" value="P:glycolytic process through glucose-6-phosphate"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="ADP_PFK/GK"/>
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        <property type="entry name" value="Ribokinase-like"/>
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    <dbReference type="PANTHER" id="PTHR21208">
        <property type="entry name" value="ADP-DEPENDENT GLUCOKINASE"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="ADP-DEPENDENT GLUCOKINASE"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF04587">
        <property type="entry name" value="ADP_PFK_GK"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53613">
        <property type="entry name" value="Ribokinase-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51255">
        <property type="entry name" value="ADPK"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0324">Glycolysis</keyword>
    <keyword id="KW-0418">Kinase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="signal peptide" evidence="2">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000184776" description="ADP-dependent glucokinase">
        <location>
            <begin position="23"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="domain" description="ADPK" evidence="3">
        <location>
            <begin position="52"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="active site" description="Proton acceptor" evidence="3">
        <location>
            <position position="481"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="297"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <position position="328"/>
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        <ligand>
            <name>Mg(2+)</name>
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    <feature type="binding site" evidence="3">
        <location>
            <position position="481"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </ligand>
    </feature>
    <feature type="splice variant" id="VSP_013550" description="In isoform 4." evidence="4 9">
        <location>
            <begin position="1"/>
            <end position="274"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013549" description="In isoform 3." evidence="5">
        <location>
            <begin position="1"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013548" description="In isoform 5." evidence="8">
        <location>
            <begin position="1"/>
            <end position="122"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_035014" description="In isoform 6." evidence="6">
        <location>
            <begin position="79"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013551" description="In isoform 4." evidence="4 9">
        <original>RKRLLE</original>
        <variation>MAASCR</variation>
        <location>
            <begin position="275"/>
            <end position="280"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013552" description="In isoform 2 and isoform 4." evidence="4 7 9">
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013553" description="In isoform 5." evidence="8">
        <original>AAGARVAGTQACATETIDTSRVSLRAPQEFMTSHSEAGSRIVLNPNKPVVEWHREGISFHFTPVLV</original>
        <variation>LGSSCGWDTGLRHRNHRHQPSVSEGTPRVHDFPFGGRLQDCIKPKQASSRMAQRGNILPLHTSIGV</variation>
        <location>
            <begin position="404"/>
            <end position="469"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_013554" description="In isoform 5." evidence="8">
        <location>
            <begin position="470"/>
            <end position="497"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_060085" description="In dbSNP:rs8024644.">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00584"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="11230166"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="16303743"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <sequence length="497" mass="54089" checksum="B758E977CDA88F8F" modified="2001-06-01" version="1" precursor="true">MALWRGSAYAGFLALAVGCVFLLEPELPGSALRSLWSSLCLGPAPAPPGPVSPEGRLAAAWDALIVRPVRRWRRVAVGVNACVDVVLSGVKLLQALGLSPGNGKDHSILHSRNDLEEAFIHFMGKGAAAERFFSDKETFHDIAQVASEFPGAQHYVGGNAALIGQKFAANSDLKVLLCGPVGPKLHELLDDNVFVPPESLQEVDEFHLILEYQAGEEWGQLKAPHANRFIFSHDLSNGAMNMLEVFVSSLEEFQPDLVVLSGLHMMEGQSKELQRKRLLEVVTSISDIPTGIPVHLELASMTNRELMSSIVHQQVFPAVTSLGLNEQELLFLTQSASGPHSSLSSWNGVPDVGMVSDILFWILKEHGRSKSRASDLTRIHFHTLVYHILATVDGHWANQLAAVAAGARVAGTQACATETIDTSRVSLRAPQEFMTSHSEAGSRIVLNPNKPVVEWHREGISFHFTPVLVCKDPIRTVGLGDAISAEGLFYSEVHPHY</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-08-01" modified="2026-01-28" version="232" xmlns="https://uniprot.org/uniprot">
    <accession>P08588</accession>
    <accession>B0LPE2</accession>
    <accession>Q5T5Y4</accession>
    <accession>Q9UKG7</accession>
    <accession>Q9UKG8</accession>
    <name>ADRB1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="17">Beta-1 adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Beta-1 adrenoreceptor</fullName>
            <shortName>Beta-1 adrenoceptor</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="20" type="primary">ADRB1</name>
        <name type="synonym">ADRB1R</name>
        <name type="synonym">B1AR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="7920" last="7924">
            <title>Cloning of the cDNA for the human beta 1-adrenergic receptor.</title>
            <authorList>
                <person name="Frielle T."/>
                <person name="Collins S."/>
                <person name="Daniel K.W."/>
                <person name="Caron M.G."/>
                <person name="Lefkowitz R.J."/>
                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="2825170"/>
            <dbReference type="DOI" id="10.1073/pnas.84.22.7920"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1999" name="Hum. Mutat." volume="14" first="271" last="271">
            <title>Racial differences in the frequencies of cardiac beta(1)-adrenergic receptor polymorphisms: analysis of c145A&gt;G and c1165G&gt;C.</title>
            <authorList>
                <person name="Moore J.D."/>
                <person name="Mason D.A."/>
                <person name="Green S.A."/>
                <person name="Hsu J."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="10477438"/>
            <dbReference type="DOI" id="10.1002/(sici)1098-1004(1999)14:3&lt;271::aid-humu14&gt;3.0.co;2-q"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT GLY-49</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2004-03" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="SeattleSNPs variation discovery resource"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT GLY-49</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2007-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NHLBI resequencing and genotyping service (RS&amp;G)"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
                <person name="Swarbreck D."/>
                <person name="Ashurst J.L."/>
                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D.C."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Cahill P."/>
                <person name="Camire D."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2002" name="Mol. Cell. Biol." volume="22" first="7942" last="7952">
            <title>Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation.</title>
            <authorList>
                <person name="Pak Y."/>
                <person name="Pham N."/>
                <person name="Rotin D."/>
            </authorList>
            <dbReference type="PubMed" id="12391161"/>
            <dbReference type="DOI" id="10.1128/mcb.22.22.7942-7952.2002"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH RAPGEF2</scope>
        <scope>MUTAGENESIS OF SER-475 AND VAL-477</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="50190" last="50196">
            <title>Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic receptor surface expression.</title>
            <authorList>
                <person name="He J."/>
                <person name="Bellini M."/>
                <person name="Xu J."/>
                <person name="Castleberry A.M."/>
                <person name="Hall R.A."/>
            </authorList>
            <dbReference type="PubMed" id="15358775"/>
            <dbReference type="DOI" id="10.1074/jbc.m404876200"/>
        </citation>
        <scope>INTERACTION WITH GOPC AND DLG4</scope>
        <scope>MUTAGENESIS OF GLU-474; SER-475; LYS-476 AND VAL-477</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="J. Biol. Chem." volume="286" first="22441" last="22455">
            <title>Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway.</title>
            <authorList>
                <person name="Cheng S.B."/>
                <person name="Quinn J.A."/>
                <person name="Graeber C.T."/>
                <person name="Filardo E.J."/>
            </authorList>
            <dbReference type="PubMed" id="21540189"/>
            <dbReference type="DOI" id="10.1074/jbc.m111.224071"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference evidence="21 22 23 24" key="9">
        <citation type="journal article" date="2021" name="Cell Res." volume="31" first="569" last="579">
            <title>Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR.</title>
            <authorList>
                <person name="Xu X."/>
                <person name="Kaindl J."/>
                <person name="Clark M.J."/>
                <person name="Hubner H."/>
                <person name="Hirata K."/>
                <person name="Sunahara R.K."/>
                <person name="Gmeiner P."/>
                <person name="Kobilka B.K."/>
                <person name="Liu X."/>
            </authorList>
            <dbReference type="PubMed" id="33093660"/>
            <dbReference type="DOI" id="10.1038/s41422-020-00424-2"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 54-399 IN COMPLEX WITH G PROTEINS; (R)-ADRENALINE AND NORADRENALINE</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF TRP-199; LYS-347 AND PHE-359</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="12670" last="12674">
            <title>A gain-of-function polymorphism in a G-protein coupling domain of the human beta1-adrenergic receptor.</title>
            <authorList>
                <person name="Mason D.A."/>
                <person name="Moore J.D."/>
                <person name="Green S.A."/>
                <person name="Liggett S.B."/>
            </authorList>
            <dbReference type="PubMed" id="10212248"/>
            <dbReference type="DOI" id="10.1074/jbc.274.18.12670"/>
        </citation>
        <scope>VARIANT ARG-389</scope>
        <scope>CHARACTERIZATION OF VARIANT ARG-389</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2000" name="Eur. Heart J." volume="21" first="1853" last="1858">
            <title>A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure.</title>
            <authorList>
                <person name="Borjesson M."/>
                <person name="Magnusson Y."/>
                <person name="Hjalmarson A."/>
                <person name="Andersson B."/>
            </authorList>
            <dbReference type="PubMed" id="11052857"/>
            <dbReference type="DOI" id="10.1053/euhj.1999.1994"/>
        </citation>
        <scope>VARIANT GLY-49</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2002" name="Am. J. Hum. Genet." volume="70" first="935" last="942">
            <title>A polymorphism in the beta1 adrenergic receptor is associated with resting heart rate.</title>
            <authorList>
                <person name="Ranade K."/>
                <person name="Jorgenson E."/>
                <person name="Sheu W.H.-H."/>
                <person name="Pei D."/>
                <person name="Hsiung C.A."/>
                <person name="Chiang F.-T."/>
                <person name="Chen Y.-D.I."/>
                <person name="Pratt R."/>
                <person name="Olshen R.A."/>
                <person name="Curb D."/>
                <person name="Cox D.R."/>
                <person name="Botstein D."/>
                <person name="Risch N."/>
            </authorList>
            <dbReference type="PubMed" id="11854867"/>
            <dbReference type="DOI" id="10.1086/339621"/>
        </citation>
        <scope>VARIANT GLY-49</scope>
        <scope>POLYMORPHISM</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2019" name="Neuron" volume="0" first="0" last="0">
            <title>A rare mutation of beta1-adrenergic receptor affects sleep/wake behaviors.</title>
            <authorList>
                <person name="Shi G."/>
                <person name="Xing L."/>
                <person name="Wu D."/>
                <person name="Bhattacharyya B.J."/>
                <person name="Jones C.R."/>
                <person name="McMahon T."/>
                <person name="Chong S.Y.C."/>
                <person name="Chen J.A."/>
                <person name="Coppola G."/>
                <person name="Geschwind D."/>
                <person name="Krystal A."/>
                <person name="Ptacek L.J."/>
                <person name="Fu Y.H."/>
            </authorList>
            <dbReference type="PubMed" id="31473062"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2019.07.026"/>
        </citation>
        <scope>VARIANT VAL-187</scope>
        <scope>CHARACTERIZATION OF VARIANT VAL-187</scope>
        <scope>FUNCTION</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <comment type="function">
        <text evidence="3 7 9 10 11 12 14 15">G protein-coupled receptor for catecholamines that couples to G(s) proteins to activate adenylate cyclase and cAMP-dependent pathway (PubMed:10212248, PubMed:12391161, PubMed:15358775). Binds epinephrine and norepinephrine with approximately equal affinity (PubMed:33093660). Mediates the activation of Ras via binding with cAMP-dependent RAPGEF2 (PubMed:12391161). As part of the sympathetic nervous system, plays a role in the physiologic regulation of cardiac functions such as stimulation of cardiomyocyte contraction (PubMed:11052857). Also delivers proapoptotic signals in cardiomyocytes (By similarity). Involved in the regulation of sleep/wake behaviors (PubMed:11854867, PubMed:31473062).</text>
    </comment>
    <comment type="subunit">
        <text evidence="11 12">Interacts (via PDZ-binding motif) with RAPGEF2 (via PDZ domain); the interaction is direct and is required for Ras activation upon ligand stimulation (PubMed:12391161). Interacts (via PDZ-binding motif) with GOPC, MAGI3 and DLG4; interaction mediates ADRB1 trafficking and signaling in a cell-specific manner (PubMed:15358775).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-2903663">
            <id>P30542</id>
            <label>ADORA1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-80389">
            <id>P78352</id>
            <label>DLG4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-311035">
            <id>Q86UL8</id>
            <label>MAGI2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>9</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-310506">
            <id>Q5TCQ9</id>
            <label>MAGI3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-357345">
            <id>Q14160</id>
            <label>SCRIB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-375655">
            <id>P31016</id>
            <label>Dlg4</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-991009">
            <id>P08588</id>
        </interactant>
        <interactant intactId="EBI-8333209">
            <id>P14270</id>
            <label>Pde4d</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Cell membrane</location>
            <topology evidence="15">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="2 12 13">Colocalizes with RAPGEF2 at the plasma membrane (By similarity). Localized at the plasma membrane (By similarity). Found in the Golgi upon GOPC overexpression (PubMed:15358775). Localized to early endosomes during endocytic trafficking (PubMed:21540189).</text>
    </comment>
    <comment type="domain">
        <text evidence="12">The PDZ domain-binding motif mediates competitive interactions with GOPC, MAGI3 and DLG4 and plays a role in subcellular location of the receptor.</text>
    </comment>
    <comment type="PTM">
        <text>Homologous desensitization of the receptor is mediated by its phosphorylation by beta-adrenergic receptor kinase.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="10">Genetic variations in ADRB1 are associated with inter-individual variability in the resting heart rate. This quantitative trait has been significantly correlated with cardiovascular morbidity and mortality [MIM:607276].</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="14">Genetic variations in ADRB1 are associated with the familial natural short sleep 2 (FNSS2) phenotype, an autosomal dominant trait [MIM:618591]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB1 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="J03019">
        <property type="protein sequence ID" value="AAA51667.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF169006">
        <property type="protein sequence ID" value="AAD53696.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF169007">
        <property type="protein sequence ID" value="AAD53697.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AY567837">
        <property type="protein sequence ID" value="AAS66983.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="EU332832">
        <property type="protein sequence ID" value="ABY87521.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AL355543">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="CCDS" id="CCDS7586.1"/>
    <dbReference type="PIR" id="A39911">
        <property type="entry name" value="QRHUB1"/>
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    <dbReference type="RefSeq" id="NP_000675.1">
        <property type="nucleotide sequence ID" value="NM_000684.3"/>
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    <dbReference type="PDB" id="2LSQ">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=197-221"/>
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    <dbReference type="PDB" id="7BTS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.13 A"/>
        <property type="chains" value="A=54-399"/>
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    <dbReference type="PDB" id="7BU6">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.70 A"/>
        <property type="chains" value="A=54-399"/>
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    <dbReference type="PDB" id="7BU7">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.60 A"/>
        <property type="chains" value="A=54-399"/>
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    <dbReference type="PDB" id="7BVQ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="A/B=54-399"/>
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    <dbReference type="PDB" id="8S2T">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.30 A"/>
        <property type="chains" value="R=1-477"/>
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    <dbReference type="PDBsum" id="2LSQ"/>
    <dbReference type="PDBsum" id="7BTS"/>
    <dbReference type="PDBsum" id="7BU6"/>
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    <dbReference type="PDBsum" id="7BVQ"/>
    <dbReference type="PDBsum" id="8S2T"/>
    <dbReference type="AlphaFoldDB" id="P08588"/>
    <dbReference type="EMDB" id="EMD-19683"/>
    <dbReference type="EMDB" id="EMD-40120"/>
    <dbReference type="EMDB" id="EMD-40151"/>
    <dbReference type="SMR" id="P08588"/>
    <dbReference type="BioGRID" id="106662">
        <property type="interactions" value="10"/>
    </dbReference>
    <dbReference type="CORUM" id="P08588"/>
    <dbReference type="DIP" id="DIP-36294N"/>
    <dbReference type="FunCoup" id="P08588">
        <property type="interactions" value="1433"/>
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    <dbReference type="IntAct" id="P08588">
        <property type="interactions" value="35"/>
    </dbReference>
    <dbReference type="MINT" id="P08588"/>
    <dbReference type="STRING" id="9606.ENSP00000358301"/>
    <dbReference type="BindingDB" id="P08588"/>
    <dbReference type="ChEMBL" id="CHEMBL213"/>
    <dbReference type="DrugBank" id="DB08558">
        <property type="generic name" value="2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB08347">
        <property type="generic name" value="4-{[(2S)-3-(tert-butylamino)-2-hydroxypropyl]oxy}-3H-indole-2-carbonitrile"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01193">
        <property type="generic name" value="Acebutolol"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01001">
        <property type="generic name" value="Albuterol"/>
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    <dbReference type="DrugBank" id="DB00866">
        <property type="generic name" value="Alprenolol"/>
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    <dbReference type="DrugBank" id="DB01118">
        <property type="generic name" value="Amiodarone"/>
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    <dbReference type="DrugBank" id="DB00182">
        <property type="generic name" value="Amphetamine"/>
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    <dbReference type="DrugBank" id="DB11785">
        <property type="generic name" value="Anisodamine"/>
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    <dbReference type="DrugBank" id="DB01102">
        <property type="generic name" value="Arbutamine"/>
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    <dbReference type="DrugBank" id="DB01238">
        <property type="generic name" value="Aripiprazole"/>
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    <dbReference type="DrugBank" id="DB09204">
        <property type="generic name" value="Arotinolol"/>
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    <dbReference type="DrugBank" id="DB06216">
        <property type="generic name" value="Asenapine"/>
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    <dbReference type="DrugBank" id="DB00335">
        <property type="generic name" value="Atenolol"/>
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    <dbReference type="DrugBank" id="DB09013">
        <property type="generic name" value="Befunolol"/>
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    <dbReference type="DrugBank" id="DB00195">
        <property type="generic name" value="Betaxolol"/>
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    <dbReference type="DrugBank" id="DB00217">
        <property type="generic name" value="Bethanidine"/>
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    <dbReference type="DrugBank" id="DB01295">
        <property type="generic name" value="Bevantolol"/>
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    <dbReference type="DrugBank" id="DB00612">
        <property type="generic name" value="Bisoprolol"/>
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    <dbReference type="DrugBank" id="DB08807">
        <property type="generic name" value="Bopindolol"/>
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    <dbReference type="DrugBank" id="DB01158">
        <property type="generic name" value="Bretylium"/>
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    <dbReference type="DrugBank" id="DB12752">
        <property type="generic name" value="Bucindolol"/>
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    <dbReference type="DrugBank" id="DB06726">
        <property type="generic name" value="Bufuralol"/>
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    <dbReference type="DrugBank" id="DB08808">
        <property type="generic name" value="Bupranolol"/>
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    <dbReference type="DrugBank" id="DB00248">
        <property type="generic name" value="Cabergoline"/>
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    <dbReference type="DrugBank" id="DB00521">
        <property type="generic name" value="Carteolol"/>
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    <dbReference type="DrugBank" id="DB01136">
        <property type="generic name" value="Carvedilol"/>
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    <dbReference type="DrugBank" id="DB04846">
        <property type="generic name" value="Celiprolol"/>
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    <dbReference type="DrugBank" id="DB01407">
        <property type="generic name" value="Clenbuterol"/>
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    <dbReference type="DrugBank" id="DB00785">
        <property type="generic name" value="Cryptenamine"/>
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    <dbReference type="DrugBank" id="DB01151">
        <property type="generic name" value="Desipramine"/>
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    <dbReference type="DrugBank" id="DB12803">
        <property type="generic name" value="Dichloroisoproterenol"/>
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    <dbReference type="DrugBank" id="DB11273">
        <property type="generic name" value="Dihydroergocornine"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB13345">
        <property type="generic name" value="Dihydroergocristine"/>
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    <dbReference type="DrugBank" id="DB00449">
        <property type="generic name" value="Dipivefrin"/>
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    <dbReference type="DrugBank" id="DB11278">
        <property type="generic name" value="DL-Methylephedrine"/>
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    <dbReference type="DrugBank" id="DB00841">
        <property type="generic name" value="Dobutamine"/>
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            <end position="477"/>
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    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="270"/>
            <end position="292"/>
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    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="293"/>
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    <feature type="binding site" evidence="15 21">
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            <position position="138"/>
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        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    <feature type="binding site" evidence="19 22">
        <location>
            <position position="138"/>
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        <ligand>
            <name>(R)-noradrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:72587"/>
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    <feature type="binding site" evidence="15 21">
        <location>
            <position position="344"/>
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        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    </feature>
    <feature type="binding site" evidence="19 22">
        <location>
            <position position="344"/>
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        <ligand>
            <name>(R)-noradrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:72587"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="15 21">
        <location>
            <position position="363"/>
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        <ligand>
            <name>(R)-adrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:71406"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="19 22">
        <location>
            <position position="363"/>
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        <ligand>
            <name>(R)-noradrenaline</name>
            <dbReference type="ChEBI" id="CHEBI:72587"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA" evidence="4">
        <location>
            <position position="312"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA" evidence="4">
        <location>
            <position position="412"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="428"/>
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    <feature type="lipid moiety-binding region" description="S-palmitoyl cysteine" evidence="1">
        <location>
            <position position="392"/>
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    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="18">
        <location>
            <position position="15"/>
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    <feature type="disulfide bond" evidence="5">
        <location>
            <begin position="131"/>
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    <feature type="disulfide bond" evidence="5">
        <location>
            <begin position="209"/>
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    <feature type="sequence variant" id="VAR_055909" description="In dbSNP:rs34844626.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="26"/>
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    <feature type="sequence variant" id="VAR_055910" description="In dbSNP:rs35720093.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="29"/>
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    <feature type="sequence variant" id="VAR_055911" description="In dbSNP:rs35230616.">
        <original>R</original>
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        <location>
            <position position="31"/>
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    <feature type="sequence variant" id="VAR_009879" description="Correlated with low mean resting heart rate and decreased mortality risk in patients with congestive heart failure; dbSNP:rs1801252." evidence="8 9 10 16">
        <original>S</original>
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        <location>
            <position position="49"/>
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    <feature type="sequence variant" id="VAR_082587" description="Found in individuals with short sleep; results in decreased adenylate cyclase-activating adrenergic receptor signaling; decreased protein stability; dbSNP:rs776439595." evidence="14">
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            <position position="187"/>
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        <original>G</original>
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        <location>
            <position position="389"/>
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        <original>R</original>
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        <location>
            <position position="399"/>
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    <feature type="sequence variant" id="VAR_055913" description="In dbSNP:rs35705839.">
        <original>H</original>
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        <location>
            <position position="405"/>
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    <feature type="mutagenesis site" description="Decreased noradrenaline affinity." evidence="15">
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        <location>
            <position position="199"/>
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    <feature type="mutagenesis site" description="Decreased noradrenaline affinity." evidence="15">
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        <location>
            <position position="347"/>
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    <feature type="mutagenesis site" description="Decreased noradrenaline affinity." evidence="15">
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        <variation>Y</variation>
        <location>
            <position position="359"/>
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        <original>E</original>
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        <location>
            <position position="474"/>
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    <feature type="mutagenesis site" description="Loss of interaction with GOPC; when associated with A-477." evidence="12">
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        <location>
            <position position="474"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with GOPC. Loss of interaction with RAPGEF2. Abolishes agonist-induced Ras activation." evidence="11 12">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="475"/>
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    <feature type="mutagenesis site" description="Loss of interaction with RAPGEF2." evidence="11 12">
        <original>S</original>
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        <location>
            <position position="475"/>
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    <feature type="mutagenesis site" description="Partial loss of interaction with GOPC." evidence="11 12">
        <original>S</original>
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        <location>
            <position position="475"/>
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    <feature type="mutagenesis site" description="Partial loss of interaction with GOPC." evidence="12">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="476"/>
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    <feature type="mutagenesis site" description="Loss of interaction with GOPC." evidence="11 12">
        <original>V</original>
        <variation>A</variation>
        <variation>F</variation>
        <variation>L</variation>
        <variation>I</variation>
        <variation>M</variation>
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            <position position="477"/>
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    </feature>
    <feature type="mutagenesis site" description="Loss of interaction with RAPGEF2. Abolishes agonist-induced Ras activation." evidence="11 12">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="477"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="54"/>
            <end position="85"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="87"/>
            <end position="89"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="92"/>
            <end position="110"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="112"/>
            <end position="121"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="127"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="163"/>
            <end position="169"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="172"/>
            <end position="195"/>
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    <feature type="turn" evidence="26">
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            <begin position="196"/>
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            <begin position="204"/>
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    <feature type="helix" evidence="25">
        <location>
            <begin position="213"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="222"/>
            <end position="232"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="234"/>
            <end position="253"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="316"/>
            <end position="349"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="351"/>
            <end position="353"/>
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    <feature type="helix" evidence="26">
        <location>
            <begin position="356"/>
            <end position="377"/>
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    <feature type="helix" evidence="26">
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            <begin position="381"/>
            <end position="391"/>
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    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P18090"/>
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    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P34971"/>
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    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
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            <dbReference type="PROSITE-ProRule" id="PRU00521"/>
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    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="10212248"/>
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    <evidence type="ECO:0000269" key="8">
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            <dbReference type="PubMed" id="10477438"/>
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        <source>
            <dbReference type="PubMed" id="11854867"/>
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        <source>
            <dbReference type="PubMed" id="12391161"/>
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        <source>
            <dbReference type="PubMed" id="15358775"/>
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            <dbReference type="PubMed" id="21540189"/>
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    <evidence type="ECO:0000305" key="19">
        <source>
            <dbReference type="PubMed" id="33093660"/>
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    <evidence type="ECO:0000312" key="20">
        <source>
            <dbReference type="HGNC" id="HGNC:285"/>
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    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PDB" id="7BTS"/>
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    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PDB" id="7BU6"/>
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        <source>
            <dbReference type="PDB" id="7BU7"/>
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            <dbReference type="PDB" id="7BVQ"/>
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    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="7BVQ"/>
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    <sequence length="477" mass="51224" checksum="1D15E6390B5364B8" modified="2023-09-13" version="3">MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAGMGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVVWGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVCTVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIMAFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAPLANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFVFFNWLGYANSAFNPIIYCRSPDFRKAFQGLLCCARRAARRRHATHGDRPRASGCLARPGPPPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-02-06" modified="2026-01-28" version="189" xmlns="https://uniprot.org/uniprot">
    <accession>Q9NX46</accession>
    <accession>Q53G94</accession>
    <accession>Q6IAB8</accession>
    <accession>Q9BY47</accession>
    <name>ADPRS_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="29">ADP-ribosylhydrolase ARH3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="29">ADP-ribose glycohydrolase ARH3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="28">ADP-ribosylhydrolase 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="29">O-acetyl-ADP-ribose deacetylase ARH3</fullName>
            <ecNumber evidence="4 7">3.5.1.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="29">Poly(ADP-ribose) glycohydrolase ARH3</fullName>
            <ecNumber evidence="1 4 9">3.2.1.143</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="29">[Protein ADP-ribosylarginine] hydrolase-like protein 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="29">[Protein ADP-ribosylserine] hydrolase</fullName>
            <ecNumber evidence="10 11 25">3.2.2.-</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="31" type="primary">ADPRS</name>
        <name type="synonym">ADPRHL2</name>
        <name evidence="28" type="synonym">ARH3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Protein Sci." volume="11" first="1657" last="1670">
            <title>The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse.</title>
            <authorList>
                <person name="Glowacki G."/>
                <person name="Braren R."/>
                <person name="Firner K."/>
                <person name="Nissen M."/>
                <person name="Kuehl M."/>
                <person name="Reche P."/>
                <person name="Bazan J.F."/>
                <person name="Cetkovic-Cvrlje M."/>
                <person name="Leiter E."/>
                <person name="Haag F."/>
                <person name="Koch-Nolte F."/>
            </authorList>
            <dbReference type="PubMed" id="12070318"/>
            <dbReference type="DOI" id="10.1110/ps.0200602"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="1999-12" db="EMBL/GenBank/DDBJ databases">
            <title>A novel gene expressed in human liver cancer tissue.</title>
            <authorList>
                <person name="Li Y."/>
                <person name="Wu T."/>
                <person name="Xu S."/>
                <person name="Ren S."/>
                <person name="Chen Z."/>
                <person name="Han Z."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Liver cancer</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF GLU-41; ASP-77; 77-ASP-ASP-78; GLY-115; SER-148; TYR-149; HIS-182; ASP-314 AND THR-317</scope>
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        <scope>CATALYTIC ACTIVITY</scope>
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        <scope>TISSUE SPECIFICITY</scope>
        <scope>INVOLVEMENT IN CONDSIAS</scope>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 19-363</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF GLU-41; ASP-77; SER-148; TYR-149; ASN-151; HIS-182; ASP-314 AND THR-317</scope>
    </reference>
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        <citation type="journal article" date="2011" name="Nature" volume="477" first="616" last="620">
            <title>The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase.</title>
            <authorList>
                <person name="Slade D."/>
                <person name="Dunstan M.S."/>
                <person name="Barkauskaite E."/>
                <person name="Weston R."/>
                <person name="Lafite P."/>
                <person name="Dixon N."/>
                <person name="Ahel M."/>
                <person name="Leys D."/>
                <person name="Ahel I."/>
            </authorList>
            <dbReference type="PubMed" id="21892188"/>
            <dbReference type="DOI" id="10.1038/nature10404"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 19-363</scope>
        <scope>SUBSTRATE-BINDING SITE</scope>
        <scope>METAL-BINDING SITES</scope>
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            <title>An HPF1/PARP1-based chemical biology strategy for exploring ADP-ribosylation.</title>
            <authorList>
                <person name="Bonfiglio J.J."/>
                <person name="Leidecker O."/>
                <person name="Dauben H."/>
                <person name="Longarini E.J."/>
                <person name="Colby T."/>
                <person name="San Segundo-Acosta P."/>
                <person name="Perez K.A."/>
                <person name="Matic I."/>
            </authorList>
            <dbReference type="PubMed" id="33186521"/>
            <dbReference type="DOI" id="10.1016/j.cell.2020.09.055"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
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            <title>The regulatory landscape of the human HPF1- and ARH3-dependent ADP-ribosylome.</title>
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                <person name="Hendriks I.A."/>
                <person name="Buch-Larsen S.C."/>
                <person name="Prokhorova E."/>
                <person name="Elsborg J.D."/>
                <person name="Rebak A.K.L.F.S."/>
                <person name="Zhu K."/>
                <person name="Ahel D."/>
                <person name="Lukas C."/>
                <person name="Ahel I."/>
                <person name="Nielsen M.L."/>
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            <dbReference type="PubMed" id="34625544"/>
            <dbReference type="DOI" id="10.1038/s41467-021-26172-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
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                <person name="Fontana P."/>
                <person name="Buch-Larsen S.C."/>
                <person name="Suyari O."/>
                <person name="Smith R."/>
                <person name="Suskiewicz M.J."/>
                <person name="Schuetzenhofer K."/>
                <person name="Ariza A."/>
                <person name="Rack J.G.M."/>
                <person name="Nielsen M.L."/>
                <person name="Ahel I."/>
            </authorList>
            <dbReference type="PubMed" id="37268618"/>
            <dbReference type="DOI" id="10.1038/s41467-023-38793-y"/>
        </citation>
        <scope>CATALYTIC ACTIVITY</scope>
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        <citation type="journal article" date="2006" name="Acta Crystallogr. F" volume="62" first="224" last="227">
            <title>Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of human ARH3, the first eukaryotic protein-ADP-ribosylhydrolase.</title>
            <authorList>
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                <person name="Koch-Nolte F."/>
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                <person name="Weiss M.S."/>
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            </authorList>
            <dbReference type="PubMed" id="16511307"/>
            <dbReference type="DOI" id="10.1107/s1744309106003435"/>
        </citation>
        <scope>PRELIMINARY X-RAY CRYSTALLOGRAPHY (1.13 ANGSTROMS) OF 18-363 IN COMPLEX WITH ADP</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference evidence="32" key="29">
        <citation type="journal article" date="2007" name="Acta Crystallogr. D" volume="63" first="366" last="380">
            <title>On the routine use of soft X-rays in macromolecular crystallography. Part IV. Efficient determination of anomalous substructures in biomacromolecules using longer X-ray wavelengths.</title>
            <authorList>
                <person name="Mueller-Dieckmann C."/>
                <person name="Panjikar S."/>
                <person name="Schmidt A."/>
                <person name="Mueller S."/>
                <person name="Kuper J."/>
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                <person name="Wilmanns M."/>
                <person name="Singh R.K."/>
                <person name="Tucker P.A."/>
                <person name="Weiss M.S."/>
            </authorList>
            <dbReference type="PubMed" id="17327674"/>
            <dbReference type="DOI" id="10.1107/s0907444906055624"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 18-363 IN COMPLEX WITH MAGNESIUM</scope>
        <scope>COFACTOR</scope>
    </reference>
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        <citation type="journal article" date="2018" name="J. Biol. Chem." volume="293" first="14470" last="14480">
            <title>Structure-function analyses reveal the mechanism of the ARH3-dependent hydrolysis of ADP-ribosylation.</title>
            <authorList>
                <person name="Wang M."/>
                <person name="Yuan Z."/>
                <person name="Xie R."/>
                <person name="Ma Y."/>
                <person name="Liu X."/>
                <person name="Yu X."/>
            </authorList>
            <dbReference type="PubMed" id="30045870"/>
            <dbReference type="DOI" id="10.1074/jbc.ra118.004284"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 19-363 IN COMPLEX WITH MAGNESIUM AND ADP-RIBOSE</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF GLU-41; ASP-77; SER-148; TYR-149; HIS-182; ASP-314 AND THR-317</scope>
    </reference>
    <reference evidence="34 35" key="31">
        <citation type="journal article" date="2018" name="J. Biol. Chem." volume="293" first="12350" last="12359">
            <title>Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition.</title>
            <authorList>
                <person name="Pourfarjam Y."/>
                <person name="Ventura J."/>
                <person name="Kurinov I."/>
                <person name="Cho A."/>
                <person name="Moss J."/>
                <person name="Kim I.K."/>
            </authorList>
            <dbReference type="PubMed" id="29907568"/>
            <dbReference type="DOI" id="10.1074/jbc.ra118.003586"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND ADP-RIBOSE</scope>
        <scope>FUNCTION</scope>
        <scope>SUBSTRATE SPECIFICITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF ASP-314</scope>
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        <citation type="journal article" date="2021" name="J. Biol. Chem." volume="296" first="100692" last="100692">
            <title>Structural and biochemical analysis of human ADP-ribosyl-acceptor hydrolase 3 reveals the basis of metal selectivity and different roles for the two magnesium ions.</title>
            <authorList>
                <person name="Pourfarjam Y."/>
                <person name="Ma Z."/>
                <person name="Kurinov I."/>
                <person name="Moss J."/>
                <person name="Kim I.K."/>
            </authorList>
            <dbReference type="PubMed" id="33894202"/>
            <dbReference type="DOI" id="10.1016/j.jbc.2021.100692"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH MAGNESIUM AND ADP-RIBOSE</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>MUTAGENESIS OF ASP-77; ASP-78; ASP-314 AND ASP-316</scope>
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        <citation type="journal article" date="2021" name="Nat. Commun." volume="12" first="4581" last="4581">
            <title>Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal.</title>
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                <person name="Rack J.G.M."/>
                <person name="Liu Q."/>
                <person name="Zorzini V."/>
                <person name="Voorneveld J."/>
                <person name="Ariza A."/>
                <person name="Honarmand Ebrahimi K."/>
                <person name="Reber J.M."/>
                <person name="Krassnig S.C."/>
                <person name="Ahel D."/>
                <person name="van der Marel G.A."/>
                <person name="Mangerich A."/>
                <person name="McCullagh J.S.O."/>
                <person name="Filippov D.V."/>
                <person name="Ahel I."/>
            </authorList>
            <dbReference type="PubMed" id="34321462"/>
            <dbReference type="DOI" id="10.1038/s41467-021-24723-3"/>
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        <scope>X-RAY CRYSTALLOGRAPHY (1.31 ANGSTROMS) OF 19-363 OF VARIANT ALA-41 IN COMPLEX WITH ADP-RIBOSE; HISTONE 2B AND NAD</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>MUTAGENESIS OF ASP-34; GLU-41; THR-76; ASP-77; ASP-78; GLY-115; PHE-143; SER-148; TYR-149; GLY-150; SER-185; LEU-186; ASN-269; GLY-270 AND ILE-271</scope>
    </reference>
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        <citation type="journal article" date="2018" name="Am. J. Hum. Genet." volume="103" first="431" last="439">
            <title>Biallelic mutations in ADPRHL2, encoding ADP-ribosylhydrolase 3, lead to a degenerative pediatric stress-induced epileptic ataxia syndrome.</title>
            <authorList>
                <person name="Ghosh S.G."/>
                <person name="Becker K."/>
                <person name="Huang H."/>
                <person name="Dixon-Salazar T."/>
                <person name="Chai G."/>
                <person name="Salpietro V."/>
                <person name="Al-Gazali L."/>
                <person name="Waisfisz Q."/>
                <person name="Wang H."/>
                <person name="Vaux K.K."/>
                <person name="Stanley V."/>
                <person name="Manole A."/>
                <person name="Akpulat U."/>
                <person name="Weiss M.M."/>
                <person name="Efthymiou S."/>
                <person name="Hanna M.G."/>
                <person name="Minetti C."/>
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            </authorList>
            <dbReference type="PubMed" id="30100084"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2018.07.010"/>
        </citation>
        <scope>INVOLVEMENT IN CONDSIAS</scope>
        <scope>VARIANTS CONDSIAS ASN-34; PRO-79; 106-GLN--SER-363 DEL; LEU-177 AND 334-GLN--SER-363 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANTS CONDSIAS PRO-79; 106-GLN--SER-363 DEL AND 334-GLN--SER-363 DEL</scope>
    </reference>
    <reference key="35">
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            <title>Bi-allelic ADPRHL2 mutations cause neurodegeneration with developmental delay, ataxia, and axonal neuropathy.</title>
            <authorList>
                <person name="Danhauser K."/>
                <person name="Alhaddad B."/>
                <person name="Makowski C."/>
                <person name="Piekutowska-Abramczuk D."/>
                <person name="Syrbe S."/>
                <person name="Gomez-Ospina N."/>
                <person name="Manning M.A."/>
                <person name="Kostera-Pruszczyk A."/>
                <person name="Krahn-Peper C."/>
                <person name="Berutti R."/>
                <person name="Kovacs-Nagy R."/>
                <person name="Gusic M."/>
                <person name="Graf E."/>
                <person name="Laugwitz L."/>
                <person name="Roeblitz M."/>
                <person name="Wroblewski A."/>
                <person name="Hartmann H."/>
                <person name="Das A.M."/>
                <person name="Bueltmann E."/>
                <person name="Fang F."/>
                <person name="Xu M."/>
                <person name="Schatz U.A."/>
                <person name="Karall D."/>
                <person name="Zellner H."/>
                <person name="Haberlandt E."/>
                <person name="Feichtinger R.G."/>
                <person name="Mayr J.A."/>
                <person name="Meitinger T."/>
                <person name="Prokisch H."/>
                <person name="Strom T.M."/>
                <person name="Ploski R."/>
                <person name="Hoffmann G.F."/>
                <person name="Pronicki M."/>
                <person name="Bonnen P.E."/>
                <person name="Morlot S."/>
                <person name="Haack T.B."/>
            </authorList>
            <dbReference type="PubMed" id="30401461"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2018.10.005"/>
        </citation>
        <scope>INVOLVEMENT IN CONDSIAS</scope>
        <scope>VARIANTS CONDSIAS 248-LYS-ILE-249 DELINS ASN; GLY-335 AND 346-TYR--SER-363 DEL</scope>
        <scope>FUNCTION</scope>
        <scope>CHARACTERIZATION OF VARIANTS CONDSIAS 248-LYS-ILE-249 DELINS ASN AND GLY-335</scope>
    </reference>
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            <title>Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response.</title>
            <authorList>
                <person name="Beijer D."/>
                <person name="Agnew T."/>
                <person name="Rack J.G.M."/>
                <person name="Prokhorova E."/>
                <person name="Deconinck T."/>
                <person name="Ceulemans B."/>
                <person name="Peric S."/>
                <person name="Milic Rasic V."/>
                <person name="De Jonghe P."/>
                <person name="Ahel I."/>
                <person name="Baets J."/>
            </authorList>
            <dbReference type="PubMed" id="34479984"/>
            <dbReference type="DOI" id="10.26508/lsa.202101057"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS CONDSIAS PHE-26 AND GLY-335</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF ASP-77 AND ASP-78</scope>
    </reference>
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            <title>Unrestrained poly-ADP-ribosylation provides insights into chromatin regulation and human disease.</title>
            <authorList>
                <person name="Prokhorova E."/>
                <person name="Agnew T."/>
                <person name="Wondisford A.R."/>
                <person name="Tellier M."/>
                <person name="Kaminski N."/>
                <person name="Beijer D."/>
                <person name="Holder J."/>
                <person name="Groslambert J."/>
                <person name="Suskiewicz M.J."/>
                <person name="Zhu K."/>
                <person name="Reber J.M."/>
                <person name="Krassnig S.C."/>
                <person name="Palazzo L."/>
                <person name="Murphy S."/>
                <person name="Nielsen M.L."/>
                <person name="Mangerich A."/>
                <person name="Ahel D."/>
                <person name="Baets J."/>
                <person name="O'Sullivan R.J."/>
                <person name="Ahel I."/>
            </authorList>
            <dbReference type="PubMed" id="34019811"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2021.04.028"/>
        </citation>
        <scope>VARIANT CONDSIAS PHE-26</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF ASP-77 AND ASP-78</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 7 9 10 11 12 13 14 16 17 19 20 21 22 23 24 25">ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1 4 9">
            <text>[(1''-&gt;2')-ADP-alpha-D-ribose](n) + H2O = [(1''-&gt;2')-ADP-alpha-D-ribose](n-1) + ADP-D-ribose</text>
            <dbReference type="Rhea" id="RHEA:52216"/>
            <dbReference type="Rhea" id="RHEA-COMP:16922"/>
            <dbReference type="Rhea" id="RHEA-COMP:16923"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:142512"/>
            <dbReference type="EC" id="3.2.1.143"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1 4 9">
            <dbReference type="Rhea" id="RHEA:52217"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 7">
            <text>1''-O-acetyl-ADP-alpha-D-ribose + H2O = ADP-D-ribose + acetate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:58112"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30089"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:142511"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="4 7">
            <dbReference type="Rhea" id="RHEA:58113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10 11 19 25 26">
            <text>O-(ADP-D-ribosyl)-L-seryl-[protein] + H2O = ADP-D-ribose + L-seryl-[protein]</text>
            <dbReference type="Rhea" id="RHEA:58256"/>
            <dbReference type="Rhea" id="RHEA-COMP:9863"/>
            <dbReference type="Rhea" id="RHEA-COMP:15091"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:29999"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:142556"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10 11 19 25 26">
            <dbReference type="Rhea" id="RHEA:58257"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="18 23">
            <text>alpha-NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+)</text>
            <dbReference type="Rhea" id="RHEA:68792"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17154"/>
            <dbReference type="ChEBI" id="CHEBI:57967"/>
            <dbReference type="ChEBI" id="CHEBI:77017"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1 4 5 13 14 21">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="1 5 13 14 21">Binds 2 magnesium ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="13 14 23">The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage (PubMed:29907568, PubMed:34321462). The glutamate flap (Glu-41) blocks substrate entrance to Mg(2+) in the unliganded closed state (PubMed:29907568, PubMed:30045870, PubMed:34321462). In presence of substrate, Glu-41 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose (PubMed:29907568, PubMed:30045870, PubMed:34321462).</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 3">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-718580">
            <id>Q9NX46</id>
        </interactant>
        <interactant intactId="EBI-12859340">
            <id>Q9NQX1-2</id>
            <label>PRDM5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-718580">
            <id>Q9NX46</id>
        </interactant>
        <interactant intactId="EBI-1105254">
            <id>O95271</id>
            <label>TNKS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6 24">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1 24">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="14">Chromosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6 24 30">Mitochondrion matrix</location>
        </subcellularLocation>
        <text evidence="14">Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="1 17">Ubiquitous (PubMed:16278211). Expressed in skin fibroblasts (PubMed:30830864).</text>
    </comment>
    <comment type="disease" evidence="15 16 17 22 24">
        <disease id="DI-05374">
            <name>Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures</name>
            <acronym>CONDSIAS</acronym>
            <description>An autosomal recessive neurodegenerative disorder characterized by pediatric onset of progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections.</description>
            <dbReference type="MIM" id="618170"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="29">Belongs to the ADP-ribosylglycohydrolase family.</text>
    </comment>
    <comment type="sequence caution" evidence="29">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAK14922" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="3.5.1.-" evidence="4 7"/>
    <dbReference type="EC" id="3.2.1.143" evidence="1 4 9"/>
    <dbReference type="EC" id="3.2.2.-" evidence="10 11 25"/>
    <dbReference type="EMBL" id="AJ313333">
        <property type="protein sequence ID" value="CAC85940.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ427295">
        <property type="protein sequence ID" value="CAD20316.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF212236">
        <property type="protein sequence ID" value="AAK14922.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000453">
        <property type="protein sequence ID" value="BAA91174.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR457237">
        <property type="protein sequence ID" value="CAG33518.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK223037">
        <property type="protein sequence ID" value="BAD96757.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL138787">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014169">
        <property type="protein sequence ID" value="AAH14169.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS402.1"/>
    <dbReference type="RefSeq" id="NP_060295.1">
        <property type="nucleotide sequence ID" value="NM_017825.3"/>
    </dbReference>
    <dbReference type="PDB" id="2FOZ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A=19-363"/>
    </dbReference>
    <dbReference type="PDB" id="2FP0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.05 A"/>
        <property type="chains" value="A/B=19-363"/>
    </dbReference>
    <dbReference type="PDB" id="2G4K">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.82 A"/>
        <property type="chains" value="A=18-363"/>
    </dbReference>
    <dbReference type="PDB" id="5ZQY">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.58 A"/>
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    </dbReference>
    <dbReference type="PDB" id="6D36">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.70 A"/>
        <property type="chains" value="A/B/C/D=1-363"/>
    </dbReference>
    <dbReference type="PDB" id="6D3A">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A/B/C/D=1-363"/>
    </dbReference>
    <dbReference type="PDB" id="7AKR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.95 A"/>
        <property type="chains" value="AAA/BBB/CCC/DDD=19-363"/>
    </dbReference>
    <dbReference type="PDB" id="7AKS">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.86 A"/>
        <property type="chains" value="AAA/CCC/EEE/GGG=19-363"/>
    </dbReference>
    <dbReference type="PDB" id="7ARW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.31 A"/>
        <property type="chains" value="A/B=19-363"/>
    </dbReference>
    <dbReference type="PDB" id="7L9F">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.75 A"/>
        <property type="chains" value="A/B/C/D=1-363"/>
    </dbReference>
    <dbReference type="PDB" id="7L9H">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.85 A"/>
        <property type="chains" value="A/B/C/D=1-363"/>
    </dbReference>
    <dbReference type="PDB" id="7L9I">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.80 A"/>
        <property type="chains" value="A/B/C/D=1-363"/>
    </dbReference>
    <dbReference type="PDBsum" id="2FOZ"/>
    <dbReference type="PDBsum" id="2FP0"/>
    <dbReference type="PDBsum" id="2G4K"/>
    <dbReference type="PDBsum" id="5ZQY"/>
    <dbReference type="PDBsum" id="6D36"/>
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    <dbReference type="AlphaFoldDB" id="Q9NX46"/>
    <dbReference type="SMR" id="Q9NX46"/>
    <dbReference type="BioGRID" id="120276">
        <property type="interactions" value="41"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9NX46">
        <property type="interactions" value="3240"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9NX46">
        <property type="interactions" value="28"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000362273"/>
    <dbReference type="BindingDB" id="Q9NX46"/>
    <dbReference type="ChEMBL" id="CHEMBL4295963"/>
    <dbReference type="GlyGen" id="Q9NX46">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9NX46"/>
    <dbReference type="MetOSite" id="Q9NX46"/>
    <dbReference type="PhosphoSitePlus" id="Q9NX46"/>
    <dbReference type="BioMuta" id="ADPRHL2"/>
    <dbReference type="DMDM" id="74753038"/>
    <dbReference type="jPOST" id="Q9NX46"/>
    <dbReference type="MassIVE" id="Q9NX46"/>
    <dbReference type="PaxDb" id="9606-ENSP00000362273"/>
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    <dbReference type="ProteomicsDB" id="83037"/>
    <dbReference type="Pumba" id="Q9NX46"/>
    <dbReference type="TopDownProteomics" id="Q9NX46"/>
    <dbReference type="Antibodypedia" id="17409">
        <property type="antibodies" value="113 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="54936"/>
    <dbReference type="Ensembl" id="ENST00000373178.5">
        <property type="protein sequence ID" value="ENSP00000362273.4"/>
        <property type="gene ID" value="ENSG00000116863.12"/>
    </dbReference>
    <dbReference type="GeneID" id="54936"/>
    <dbReference type="KEGG" id="hsa:54936"/>
    <dbReference type="MANE-Select" id="ENST00000373178.5">
        <property type="protein sequence ID" value="ENSP00000362273.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_017825.3"/>
        <property type="RefSeq protein sequence ID" value="NP_060295.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001bzt.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21304"/>
    <dbReference type="CTD" id="54936"/>
    <dbReference type="DisGeNET" id="54936"/>
    <dbReference type="GeneCards" id="ADPRS"/>
    <dbReference type="HGNC" id="HGNC:21304">
        <property type="gene designation" value="ADPRS"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000116863">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ADPRS"/>
    <dbReference type="MIM" id="610624">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="618170">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000116863"/>
    <dbReference type="Orphanet" id="694922">
        <property type="disease" value="Childhood-onset stress-induced neurodegenerative ataxia-seizure syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000116863"/>
    <dbReference type="eggNOG" id="ENOG502QUER">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000015369"/>
    <dbReference type="HOGENOM" id="CLU_024566_6_0_1"/>
    <dbReference type="InParanoid" id="Q9NX46"/>
    <dbReference type="OMA" id="HMEHVEA"/>
    <dbReference type="OrthoDB" id="410104at2759"/>
    <dbReference type="PAN-GO" id="Q9NX46">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9NX46"/>
    <dbReference type="BRENDA" id="3.2.1.143">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9NX46"/>
    <dbReference type="Reactome" id="R-HSA-110362">
        <property type="pathway name" value="POLB-Dependent Long Patch Base Excision Repair"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9NX46"/>
    <dbReference type="Agora" id="ENSG00000116863"/>
    <dbReference type="BioGRID-ORCS" id="54936">
        <property type="hits" value="69 hits in 1157 CRISPR screens"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9NX46"/>
    <dbReference type="GeneWiki" id="ADPRHL2"/>
    <dbReference type="GenomeRNAi" id="54936"/>
    <dbReference type="Pharos" id="Q9NX46">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9NX46"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9NX46">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000116863">
        <property type="expression patterns" value="Expressed in oviduct epithelium and 187 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0016604">
        <property type="term" value="C:nuclear body"/>
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        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
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        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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    <dbReference type="GO" id="GO:0140292">
        <property type="term" value="F:ADP-ribosylserine hydrolase activity"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004553">
        <property type="term" value="F:hydrolase activity, hydrolyzing O-glycosyl compounds"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000287">
        <property type="term" value="F:magnesium ion binding"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0061463">
        <property type="term" value="F:O-acetyl-ADP-ribose deacetylase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004649">
        <property type="term" value="F:poly(ADP-ribose) glycohydrolase activity"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006287">
        <property type="term" value="P:base-excision repair, gap-filling"/>
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        <property type="project" value="Reactome"/>
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        <property type="term" value="P:cellular response to superoxide"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060546">
        <property type="term" value="P:negative regulation of necroptotic process"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140290">
        <property type="term" value="P:peptidyl-serine ADP-deribosylation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="DisProt" id="DP03961"/>
    <dbReference type="FunFam" id="1.10.4080.10:FF:000001">
        <property type="entry name" value="ADP-ribose glycohydrolase ARH3"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="ADP-ribosylation/Crystallin J1"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR050792">
        <property type="entry name" value="ADP-ribosylglycohydrolase"/>
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    <dbReference type="InterPro" id="IPR005502">
        <property type="entry name" value="Ribosyl_crysJ1"/>
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    <dbReference type="InterPro" id="IPR036705">
        <property type="entry name" value="Ribosyl_crysJ1_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR16222">
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        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR16222:SF24">
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        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF03747">
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        <property type="match status" value="1"/>
    </dbReference>
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        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0158">Chromosome</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0227">DNA damage</keyword>
    <keyword id="KW-0234">DNA repair</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0460">Magnesium</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0523">Neurodegeneration</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000277613" description="ADP-ribosylhydrolase ARH3">
        <location>
            <begin position="1"/>
            <end position="363"/>
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    </feature>
    <feature type="binding site" evidence="8 13 14 33 34 35">
        <location>
            <position position="41"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 33 34 35 41">
        <location>
            <position position="76"/>
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        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 23 33 34 35 36 37 38 41">
        <location>
            <position position="77"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="13 14 33 34 35">
        <location>
            <position position="77"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 23 33 34 35 36 37 38 41">
        <location>
            <position position="78"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="23 38">
        <location>
            <position position="78"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="13 14 33 34 35">
        <location>
            <begin position="146"/>
            <end position="152"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="13 14 33 34 35">
        <location>
            <position position="182"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="13 34 35">
        <location>
            <position position="235"/>
        </location>
        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="13 34 35">
        <location>
            <position position="271"/>
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        <ligand>
            <name>substrate</name>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 23 33 34 35 36 37 38 40">
        <location>
            <position position="314"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 23 33 34 35 36 37 38 41">
        <location>
            <position position="316"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 23 33 34 35 36 37 38 40">
        <location>
            <position position="316"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 13 14 21 33 34 35 40">
        <location>
            <position position="317"/>
        </location>
        <ligand>
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="site" description="Glutamate flap" evidence="13 14">
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="42">
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085654" description="In CONDSIAS; uncertain significance; reduced protein abundance; increased levels of ADP-ribose; May result in protein misfolding or aggregation." evidence="22 24">
        <original>C</original>
        <variation>F</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081264" description="In CONDSIAS; uncertain significance; dbSNP:rs1557732234." evidence="15">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081265" description="In CONDSIAS; severely reduced protein levels in patient fibroblasts; decreased stability and reduced Tm; reduced alpha-helix content and altered secondary structure detected by circular dichroism spectroscopy; dbSNP:rs1557733311." evidence="15">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="79"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081266" description="In CONDSIAS; no detectable protein in patient fibroblasts." evidence="15">
        <location>
            <begin position="106"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081267" description="In CONDSIAS; uncertain significance; dbSNP:rs200626873." evidence="15">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030579" description="In dbSNP:rs2236387." evidence="27">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="209"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081268" description="In CONDSIAS; no detectable protein levels in patient fibroblasts." evidence="16">
        <original>KI</original>
        <variation>N</variation>
        <location>
            <begin position="248"/>
            <end position="249"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081269" description="In CONDSIAS; no detectable protein in patient fibroblasts." evidence="15">
        <location>
            <begin position="334"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081270" description="In CONDSIAS; uncertain significance; results in accumulation of poly(ADP-ribose) in the nucleus of patient cells after exposure to H(2)O(2); reduced protein abundance in fibroblasts; localization to the cytoplasm in fibroblasts; no effect on hydrolase activity in vitro; may result in reduced protein stability; dbSNP:rs201735454." evidence="16 24">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="335"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_081271" description="In CONDSIAS; uncertain significance." evidence="16">
        <location>
            <begin position="346"/>
            <end position="363"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces hydrolase activity." evidence="23">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significant loss of activity. Does not affect recruitment to DNA lesion regions following DNA damage. Strongly reduced ability to hydrolyze proteins ADP-ribosylated on serine." evidence="3 11 14 23">
        <original>E</original>
        <variation>A</variation>
        <variation>Q</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes hydrolase activity." evidence="23">
        <original>T</original>
        <variation>R</variation>
        <location>
            <position position="76"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them." evidence="11">
        <original>DD</original>
        <variation>AA</variation>
        <location>
            <begin position="77"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity." evidence="1 4 10">
        <original>DD</original>
        <variation>NN</variation>
        <location>
            <begin position="77"/>
            <end position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity. Abolishes Mg(2+) binding. Retains ability to bind ADP-ribose. Does not affect recruitment to DNA lesion regions following DNA damage. Strongly reduced ability to hydrolyze proteins ADP-ribosylated on serine." evidence="3 10 11 14 18 20 21 22 23 24">
        <original>D</original>
        <variation>N</variation>
        <variation>A</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes hydrolase activity." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity." evidence="10 18 20 22 23 24">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="78"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolished ability to bind and hydrolyze proteins ADP-ribosylated on serine. No effect on hydrolase activity." evidence="11 23">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="115"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes hydrolase activity." evidence="23">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine." evidence="3 11 14 23">
        <original>S</original>
        <variation>A</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significant loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine." evidence="3 11 14">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>Y</original>
        <variation>L</variation>
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces hydrolase activity." evidence="23">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="150"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Partial loss of activity." evidence="3">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity. Abolished recruitment to DNA lesion regions following DNA damage. Abolished ability to hydrolyze proteins ADP-ribosylated on serine." evidence="3 11 14">
        <original>H</original>
        <variation>Q</variation>
        <variation>A</variation>
        <location>
            <position position="182"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="186"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slight reduction in activity toward poly(ADP-ribose). Does not affect ability to degrade O-acetyl-ADP-D-ribose." evidence="1 4">
        <original>EE</original>
        <variation>QQ</variation>
        <location>
            <begin position="238"/>
            <end position="239"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Slight reduction in activity toward poly(ADP-ribose). Does not affect ability to degrade O-acetyl-ADP-D-ribose." evidence="1 4">
        <original>EE</original>
        <variation>QQ</variation>
        <location>
            <begin position="261"/>
            <end position="262"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>N</original>
        <variation>A</variation>
        <location>
            <position position="269"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>G</original>
        <variation>C</variation>
        <location>
            <position position="270"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on hydrolase activity." evidence="23">
        <original>I</original>
        <variation>A</variation>
        <location>
            <position position="271"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity. Abolishes Mg(2+) and ADP-ribose binding. Does not affect recruitment to DNA lesion regions following DNA damage. Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them." evidence="3 11 13 14 21">
        <original>D</original>
        <variation>A</variation>
        <variation>E</variation>
        <location>
            <position position="314"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significant loss of activity." evidence="3">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="314"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes hydrolase activity." evidence="21">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Complete loss of activity. Does not affect recruitment to DNA lesion regions following DNA damage. Retains ability to bind proteins ADP-ribosylated on serine but is unable to hydrolyze them." evidence="3 11 14">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="317"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Partial loss of activity." evidence="3">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="317"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; CAG33518." evidence="29" ref="4">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="109"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="19"/>
            <end position="42"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="48"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="54"/>
            <end position="58"/>
        </location>
    </feature>
    <feature type="strand" evidence="45">
        <location>
            <begin position="62"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="77"/>
            <end position="92"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="97"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="turn" evidence="44">
        <location>
            <begin position="113"/>
            <end position="115"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="120"/>
            <end position="127"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="137"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="152"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="158"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="167"/>
            <end position="179"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="185"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="208"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="226"/>
            <end position="234"/>
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    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="241"/>
            <end position="253"/>
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    </feature>
    <feature type="strand" evidence="43">
        <location>
            <begin position="255"/>
            <end position="257"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="260"/>
            <end position="267"/>
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    </feature>
    <feature type="strand" evidence="46">
        <location>
            <begin position="270"/>
            <end position="272"/>
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    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="273"/>
            <end position="275"/>
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    </feature>
    <feature type="helix" evidence="46">
        <location>
            <begin position="277"/>
            <end position="286"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="300"/>
            <end position="310"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="315"/>
            <end position="330"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="332"/>
            <end position="334"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="337"/>
            <end position="340"/>
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    <feature type="helix" evidence="46">
        <location>
            <begin position="346"/>
            <end position="360"/>
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    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="16278211"/>
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    <evidence type="ECO:0000269" key="2">
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            <dbReference type="PubMed" id="16511307"/>
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    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="17015823"/>
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    <evidence type="ECO:0000269" key="4">
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            <dbReference type="PubMed" id="17075046"/>
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    <evidence type="ECO:0000269" key="5">
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            <dbReference type="PubMed" id="17327674"/>
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    <evidence type="ECO:0000269" key="6">
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            <dbReference type="PubMed" id="17991898"/>
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    <evidence type="ECO:0000269" key="7">
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            <dbReference type="PubMed" id="21498885"/>
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    <evidence type="ECO:0000269" key="8">
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            <dbReference type="PubMed" id="21892188"/>
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    <evidence type="ECO:0000269" key="9">
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            <dbReference type="PubMed" id="22433848"/>
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    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="28650317"/>
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    <evidence type="ECO:0000269" key="11">
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            <dbReference type="PubMed" id="29234005"/>
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    <evidence type="ECO:0000269" key="12">
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            <dbReference type="PubMed" id="29480802"/>
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    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="29907568"/>
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    <evidence type="ECO:0000269" key="14">
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            <dbReference type="PubMed" id="30045870"/>
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    <evidence type="ECO:0000269" key="15">
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            <dbReference type="PubMed" id="30100084"/>
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    <evidence type="ECO:0000269" key="16">
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    <evidence type="ECO:0000269" key="17">
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            <dbReference type="PubMed" id="30830864"/>
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    <evidence type="ECO:0000269" key="18">
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            <dbReference type="PubMed" id="31599159"/>
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            <dbReference type="PubMed" id="33186521"/>
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    <evidence type="ECO:0000269" key="25">
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    <evidence type="ECO:0000269" key="27">
        <source ref="5"/>
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    <evidence type="ECO:0000303" key="28">
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    <evidence type="ECO:0000305" key="29"/>
    <evidence type="ECO:0000305" key="30">
        <source>
            <dbReference type="PubMed" id="22433848"/>
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    <evidence type="ECO:0000312" key="31">
        <source>
            <dbReference type="HGNC" id="HGNC:21304"/>
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    <evidence type="ECO:0007744" key="32">
        <source>
            <dbReference type="PDB" id="2G4K"/>
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    <evidence type="ECO:0007744" key="33">
        <source>
            <dbReference type="PDB" id="5ZQY"/>
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    <evidence type="ECO:0007744" key="34">
        <source>
            <dbReference type="PDB" id="6D36"/>
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    <evidence type="ECO:0007744" key="35">
        <source>
            <dbReference type="PDB" id="6D3A"/>
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    <evidence type="ECO:0007744" key="36">
        <source>
            <dbReference type="PDB" id="7AKR"/>
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    <evidence type="ECO:0007744" key="37">
        <source>
            <dbReference type="PDB" id="7AKS"/>
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    <evidence type="ECO:0007744" key="38">
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            <dbReference type="PDB" id="7L9H"/>
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    <evidence type="ECO:0007829" key="43">
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    <evidence type="ECO:0007829" key="45">
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    </evidence>
    <evidence type="ECO:0007829" key="46">
        <source>
            <dbReference type="PDB" id="7ARW"/>
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    <sequence length="363" mass="38947" checksum="5FD99F59F27CD29F" modified="2000-10-01" version="1">MAAAAMAAAAGGGAGAARSLSRFRGCLAGALLGDCVGSFYEAHDTVDLTSVLRHVQSLEPDPGTPGSERTEALYYTDDTAMARALVQSLLAKEAFDEVDMAHRFAQEYKKDPDRGYGAGVVTVFKKLLNPKCRDVFEPARAQFNGKGSYGNGGAMRVAGISLAYSSVQDVQKFARLSAQLTHASSLGYNGAILQALAVHLALQGESSSEHFLKQLLGHMEDLEGDAQSVLDARELGMEERPYSSRLKKIGELLDQASVTREEVVSELGNGIAAFESVPTAIYCFLRCMEPDPEIPSAFNSLQRTLIYSISLGGDTDTIATMAGAIAGAYYGMDQVPESWQQSCEGYEETDILAQSLHRVFQKS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-04-01" modified="2026-01-28" version="258" xmlns="https://uniprot.org/uniprot">
    <accession>P07550</accession>
    <accession>B0LPE4</accession>
    <accession>B2R7X2</accession>
    <accession>O14823</accession>
    <accession>O14824</accession>
    <accession>O14825</accession>
    <accession>O14826</accession>
    <accession>Q4JG18</accession>
    <accession>Q53GA6</accession>
    <accession>Q6GMT4</accession>
    <accession>Q6P4D8</accession>
    <accession>Q8NEQ9</accession>
    <accession>Q96EC3</accession>
    <accession>Q9UCZ0</accession>
    <accession>Q9UCZ1</accession>
    <accession>Q9UCZ2</accession>
    <accession>Q9UCZ3</accession>
    <accession>Q9UH95</accession>
    <accession>Q9UHA1</accession>
    <accession>Q9UMZ5</accession>
    <name>ADRB2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="44">Beta-2 adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Beta-2 adrenoreceptor</fullName>
            <shortName>Beta-2 adrenoceptor</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="46" type="primary">ADRB2</name>
        <name type="synonym">ADRB2R</name>
        <name type="synonym">B2AR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1987" name="FEBS Lett." volume="211" first="200" last="206">
            <title>Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors.</title>
            <authorList>
                <person name="Chung F.-Z."/>
                <person name="Lentes K.-U."/>
                <person name="Gocayne J.D."/>
                <person name="Fitzgerald M.G."/>
                <person name="Robinson D.A."/>
                <person name="Kerlavage A.R."/>
                <person name="Fraser C.M."/>
                <person name="Venter J.C."/>
            </authorList>
            <dbReference type="PubMed" id="3026848"/>
            <dbReference type="DOI" id="10.1016/0014-5793(87)81436-9"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT GLN-27</scope>
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            <tissue>Brain</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>VARIANTS GLN-27; LEU-159; PHE-159 AND ARG-375</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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        <scope>VARIANT GLN-27</scope>
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        <scope>VARIANTS ARG-16 AND GLN-27</scope>
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            <title>Norepinephrine- and epinephrine-induced distinct beta2-adrenoceptor signaling is dictated by GRK2 phosphorylation in cardiomyocytes.</title>
            <authorList>
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            <dbReference type="PubMed" id="18056263"/>
            <dbReference type="DOI" id="10.1074/jbc.m705747200"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-355 AND SER-356</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="12142540"/>
            <dbReference type="DOI" id="10.1126/science.1073308"/>
        </citation>
        <scope>INTERACTION WITH GPRASP1</scope>
    </reference>
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                <person name="Ballif B.A."/>
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            </authorList>
            <dbReference type="PubMed" id="17525332"/>
            <dbReference type="DOI" id="10.1126/science.1140321"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Embryonic kidney</tissue>
        </source>
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                <person name="Shenoy S.K."/>
            </authorList>
            <dbReference type="PubMed" id="19424180"/>
            <dbReference type="DOI" id="10.1038/emboj.2009.128"/>
        </citation>
        <scope>UBIQUITINATION</scope>
        <scope>DEUBIQUITINATION BY USP20 AND USP33</scope>
        <scope>INTERACTION WITH USP20 AND USP33</scope>
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            <authorList>
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            <dbReference type="PubMed" id="19584355"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000444"/>
        </citation>
        <scope>INTERACTION WITH EGLN3 AND VHL</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
        <scope>UBIQUITINATION</scope>
        <scope>HYDROXYLATION AT PRO-382 AND PRO-395</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
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            <authorList>
                <person name="Nabhan J.F."/>
                <person name="Pan H."/>
                <person name="Lu Q."/>
            </authorList>
            <dbReference type="PubMed" id="20559325"/>
            <dbReference type="DOI" id="10.1038/embor.2010.80"/>
        </citation>
        <scope>UBIQUITINATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH ARRDC3</scope>
    </reference>
    <reference key="30">
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            <title>SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane.</title>
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                <person name="von Zastrow M."/>
            </authorList>
            <dbReference type="PubMed" id="20733053"/>
            <dbReference type="DOI" id="10.1083/jcb.201004060"/>
        </citation>
        <scope>INTERACTION WITH SNX27</scope>
    </reference>
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            <title>SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors.</title>
            <authorList>
                <person name="Temkin P."/>
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            </authorList>
            <dbReference type="PubMed" id="21602791"/>
            <dbReference type="DOI" id="10.1038/ncb2252"/>
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        <scope>INTERACTION WITH SNX27</scope>
    </reference>
    <reference key="32">
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            <title>MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound beta(2)-adrenergic receptors.</title>
            <authorList>
                <person name="Han S.O."/>
                <person name="Xiao K."/>
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            </authorList>
            <dbReference type="PubMed" id="23166351"/>
            <dbReference type="DOI" id="10.1083/jcb.201208192"/>
        </citation>
        <scope>INTERACTION WITH MARCHF2; NEDD4; USP20 AND USP33</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>UBIQUITINATION</scope>
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            <authorList>
                <person name="Qi S."/>
                <person name="O'Hayre M."/>
                <person name="Gutkind J.S."/>
                <person name="Hurley J.H."/>
            </authorList>
            <dbReference type="PubMed" id="25220262"/>
            <dbReference type="DOI" id="10.1002/pro.2549"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH ARRDC3</scope>
    </reference>
    <reference key="34">
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            <title>CNIH4 interacts with newly synthesized GPCR and controls their export from the endoplasmic reticulum.</title>
            <authorList>
                <person name="Sauvageau E."/>
                <person name="Rochdi M.D."/>
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                <person name="Bouvier M."/>
            </authorList>
            <dbReference type="PubMed" id="24405750"/>
            <dbReference type="DOI" id="10.1111/tra.12148"/>
        </citation>
        <scope>INTERACTION WITH CNIH4</scope>
    </reference>
    <reference key="35">
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            <authorList>
                <person name="Adachi N."/>
                <person name="Hess D.T."/>
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            </authorList>
            <dbReference type="PubMed" id="27481942"/>
            <dbReference type="DOI" id="10.1074/jbc.m116.725762"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>PALMITOYLATION AT CYS-265 AND CYS-341</scope>
        <scope>MUTAGENESIS OF CYS-265 AND CYS-341</scope>
    </reference>
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                <person name="Xu X."/>
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            </authorList>
            <dbReference type="PubMed" id="33093660"/>
            <dbReference type="DOI" id="10.1038/s41422-020-00424-2"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF TYR-174 AND ASP-300</scope>
    </reference>
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            <authorList>
                <person name="Rasmussen S.G.F."/>
                <person name="Choi H.-J."/>
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                <person name="Kobilka T.S."/>
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                <person name="Sanishvili R."/>
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                <person name="Kobilka B.K."/>
            </authorList>
            <dbReference type="PubMed" id="17952055"/>
            <dbReference type="DOI" id="10.1038/nature06325"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL</scope>
        <scope>TOPOLOGY</scope>
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            <authorList>
                <person name="Cherezov V."/>
                <person name="Rosenbaum D.M."/>
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                <person name="Rasmussen S.G.F."/>
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                <person name="Kobilka T.S."/>
                <person name="Choi H.-J."/>
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                <person name="Kobilka B.K."/>
                <person name="Stevens R.C."/>
            </authorList>
            <dbReference type="PubMed" id="17962520"/>
            <dbReference type="DOI" id="10.1126/science.1150577"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-365 IN COMPLEX WITH CARAZOLOL AND CHOLESTEROL</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>TOPOLOGY</scope>
        <scope>PALMITOYLATION AT CYS-341</scope>
    </reference>
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            <authorList>
                <person name="Hanson M.A."/>
                <person name="Cherezov V."/>
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                <person name="Roth C.B."/>
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                <person name="Velasquez J."/>
                <person name="Kuhn P."/>
                <person name="Stevens R.C."/>
            </authorList>
            <dbReference type="PubMed" id="18547522"/>
            <dbReference type="DOI" id="10.1016/j.str.2008.05.001"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-365 IN COMPLEX WITH TIMOLOL AND CHOLESTEROL</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>TOPOLOGY</scope>
        <scope>PALMITOYLATION AT CYS-341</scope>
    </reference>
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            <authorList>
                <person name="Ring A.M."/>
                <person name="Manglik A."/>
                <person name="Kruse A.C."/>
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                <person name="Weis W.I."/>
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                <person name="Kobilka B.K."/>
            </authorList>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) OF 29-348 IN COMPLEX WITH (R)-ADRENALINE AND G PROTEINS</scope>
        <scope>DISULFIDE BONDS</scope>
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            <authorList>
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                <person name="Innis M."/>
                <person name="Ligget S.B."/>
            </authorList>
            <dbReference type="PubMed" id="7915137"/>
            <dbReference type="DOI" id="10.1021/bi00198a006"/>
        </citation>
        <scope>VARIANTS ARG-16 AND GLN-27</scope>
        <scope>CHARACTERIZATION</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
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                <person name="Turki J."/>
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                <person name="Green S.A."/>
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            </authorList>
            <dbReference type="PubMed" id="7706471"/>
            <dbReference type="DOI" id="10.1172/jci117838"/>
        </citation>
        <scope>VARIANT ARG-16</scope>
        <scope>POLYMORPHISM</scope>
    </reference>
    <comment type="function">
        <text evidence="1 26 31 34 38">G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways (PubMed:2831218, PubMed:7915137). ADRB2 binds epinephrine (Epi) with an approximately 30-fold greater affinity than norepinephrine (NE) (PubMed:2831218, PubMed:33093660, PubMed:7915137). In the heart, Epi- and NE-activated ADRB2 induces rapid and slow cardiomyocyte contraction rate, respectively (By similarity). Both NE and Epi promote coupling to G(s)/PKA pathway to regulate myocyte contraction rate (By similarity). Epi also promotes ADRB2 coupling to G(i) proteins to exert cardioprotective effects especially in the conditions of hypoxia and oxidative stress through the G(i)/PI3K/Akt signaling pathway (By similarity). ADRB2-G(s) signaling delivers proapoptotic signals in cardiomyocytes although G(i)-mediated survival effect appears to predominate (By similarity). ADRB2 also transduces signals independently of PKA to regulate cellular pH by modulating Na(+)/H(+) exchanger SLC9A3 function (PubMed:9560162).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 8 10 11 13 14 15 16 17 18 19 21 22 33 37 38 39">Binds NHERF1 and GPRASP1 (PubMed:9560162). Interacts with ARRB1 and ARRB2. Interacts with SRC (PubMed:9924018). Interacts with USP20 and USP33 (PubMed:19424180, PubMed:23166351). Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with CNIH4 (PubMed:24405750). Interacts with ARRDC3 (PubMed:20559325, PubMed:25220262). Interacts with NEDD4 (PubMed:23166351). Interacts with MARCHF2 (PubMed:23166351).</text>
    </comment>
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        <interactant intactId="EBI-2903663">
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        <experiments>5</experiments>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
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            <id>O14745</id>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-17159452">
            <id>Q9NR21-5</id>
            <label>PARP11</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-749039">
            <id>Q8WVD3</id>
            <label>RNF138</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-751555">
            <id>Q9H0X6</id>
            <label>RNF208</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-632715">
            <id>Q13573</id>
            <label>SNW1</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-491169">
            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P07550</id>
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            <id>Q5T0J7-2</id>
            <label>TEX35</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P07550</id>
        </interactant>
        <interactant intactId="EBI-25830583">
            <id>Q8N0U2</id>
            <label>TMEM61</label>
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        <organismsDiffer>false</organismsDiffer>
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    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="15 16 19 22 26 34">Cell membrane</location>
            <topology evidence="15 20">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="24">Golgi apparatus</location>
        </subcellularLocation>
        <text evidence="15 16 24">Colocalizes with VHL at the cell membrane (PubMed:19584355). Activated receptors are internalized into endosomes prior to their degradation in lysosomes (PubMed:20559325). Activated receptors are also detected within the Golgi apparatus (PubMed:27481942).</text>
    </comment>
    <comment type="PTM">
        <text evidence="6 11 13 23 24">Palmitoylated (PubMed:11146000, PubMed:17962520, PubMed:18547522, PubMed:2540197, PubMed:27481942). Mainly palmitoylated at Cys-341 (PubMed:17962520, PubMed:18547522, PubMed:2540197). Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation (PubMed:11146000). Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi (PubMed:27481942). Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor (PubMed:27481942). Could be depalmitoylated by LYPLA1 at the plasma membrane (PubMed:27481942).</text>
    </comment>
    <comment type="PTM">
        <text evidence="1 6">Phosphorylated by PKA and BARK/GRK2 upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK/GRK2 (PubMed:11146000). Distinct temporal phosphorylation on Ser-355 and Ser-356 by BARK/GRK2 plays a critical role for dictating receptor cellular events and signaling properties induced by Epi or NE in cardiomyocytes (By similarity).</text>
    </comment>
    <comment type="PTM">
        <text evidence="36">Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14 16 19">Polyubiquitinated (PubMed:23166351). Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation (PubMed:19424180, PubMed:20559325, PubMed:23166351). Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent.</text>
    </comment>
    <comment type="PTM">
        <text evidence="14 15">Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.</text>
    </comment>
    <comment type="polymorphism">
        <text>The Gly-16 allele is overrepresented in individuals affected by nocturnal asthma as compared to controls, and appears to be an important genetic factor in the expression of this asthmatic phenotype.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.</text>
    </comment>
    <comment type="sequence caution" evidence="45">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD96745" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
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        <location>
            <position position="312"/>
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        <ligand>
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    <feature type="binding site" evidence="20 53">
        <location>
            <position position="316"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:71406"/>
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    <feature type="binding site" evidence="13 50">
        <location>
            <position position="316"/>
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        <ligand>
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            <dbReference type="ChEBI" id="CHEBI:188157"/>
            <note>inverse agonist</note>
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            <position position="141"/>
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        <location>
            <position position="246"/>
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            <position position="261"/>
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    <feature type="modified residue" description="Phosphoserine; by PKA" evidence="2">
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            <position position="355"/>
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            <position position="6"/>
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            <begin position="184"/>
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            <position position="16"/>
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            <position position="350"/>
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    <feature type="mutagenesis site" description="Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization." evidence="36">
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            <position position="354"/>
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    <feature type="mutagenesis site" description="Does not affect insulin-induced tyrosine phosphorylation or insulin-induced receptor supersensitization." evidence="36">
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            <position position="413"/>
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    <feature type="sequence conflict" description="In Ref. 9; BAG35969." evidence="45" ref="9">
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            <position position="71"/>
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    <feature type="sequence conflict" description="In Ref. 10; BAD96745." evidence="45" ref="10">
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            <position position="261"/>
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    <feature type="sequence conflict" description="In Ref. 14; AAH12481." evidence="45" ref="14">
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            <position position="402"/>
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    <feature type="helix" evidence="57">
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<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="230" xmlns="https://uniprot.org/uniprot">
    <accession>P55263</accession>
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        </alternativeName>
        <alternativeName>
            <fullName evidence="20">N6,N6-dimethyladenosine kinase</fullName>
            <ecNumber evidence="9">2.7.1.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="20">N6-isopentenyladenosine kinase</fullName>
            <ecNumber evidence="9">2.7.1.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName evidence="20">N6-methyladenosine kinase</fullName>
            <ecNumber evidence="9">2.7.1.-</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16 23" type="primary">ADK</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="15">
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            <title>Adenosine kinase and ADAL coordinate detoxification of modified adenosines to safeguard metabolism.</title>
            <authorList>
                <person name="Ogawa A."/>
                <person name="Watanabe S."/>
                <person name="Ozerova I."/>
                <person name="Tsai A.Y."/>
                <person name="Kuchitsu Y."/>
                <person name="Chong H.B."/>
                <person name="Kawakami T."/>
                <person name="Fuse J."/>
                <person name="Han W."/>
                <person name="Kudo R."/>
                <person name="Naito T."/>
                <person name="Sato K."/>
                <person name="Nakazawa T."/>
                <person name="Saheki Y."/>
                <person name="Hirayama A."/>
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            </authorList>
            <dbReference type="PubMed" id="40840445"/>
            <dbReference type="DOI" id="10.1016/j.cell.2025.07.041"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF LEU-33; ASP-35; LEU-57; ALA-153; LEU-155; PHE-187; PHE-218; ASN-313 AND ASP-317</scope>
        <scope>CHARACTERIZATION OF VARIANTS HMAKD GLU-30; ALA-235; GLU-318; SER-319 AND ARG-341</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="1998" name="Biochemistry" volume="37" first="15607" last="15620">
            <title>Structure of human adenosine kinase at 1.5-A resolution.</title>
            <authorList>
                <person name="Mathews I.I."/>
                <person name="Erion M.D."/>
                <person name="Ealick S.E."/>
            </authorList>
            <dbReference type="PubMed" id="9843365"/>
            <dbReference type="DOI" id="10.1021/bi9815445"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF ISOFORM 2 IN COMPLEX WITH MAGNESIUM AND ADENOSINE</scope>
        <scope>ACTIVE SITE</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference evidence="25 26" key="17">
        <citation type="journal article" date="2006" name="J. Med. Chem." volume="49" first="6726" last="6731">
            <title>Crystal structures of human adenosine kinase inhibitor complexes reveal two distinct binding modes.</title>
            <authorList>
                <person name="Muchmore S.W."/>
                <person name="Smith R.A."/>
                <person name="Stewart A.O."/>
                <person name="Cowart M.D."/>
                <person name="Gomtsyan A."/>
                <person name="Matulenko M.A."/>
                <person name="Yu H."/>
                <person name="Severin J.M."/>
                <person name="Bhagwat S.S."/>
                <person name="Lee C.H."/>
                <person name="Kowaluk E.A."/>
                <person name="Jarvis M.F."/>
                <person name="Jakob C.L."/>
            </authorList>
            <dbReference type="PubMed" id="17154503"/>
            <dbReference type="DOI" id="10.1021/jm060189a"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 20-362</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2011" name="Am. J. Hum. Genet." volume="89" first="507" last="515">
            <title>Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function.</title>
            <authorList>
                <person name="Bjursell M.K."/>
                <person name="Blom H.J."/>
                <person name="Cayuela J.A."/>
                <person name="Engvall M.L."/>
                <person name="Lesko N."/>
                <person name="Balasubramaniam S."/>
                <person name="Brandberg G."/>
                <person name="Halldin M."/>
                <person name="Falkenberg M."/>
                <person name="Jakobs C."/>
                <person name="Smith D."/>
                <person name="Struys E."/>
                <person name="von Dobeln U."/>
                <person name="Gustafsson C.M."/>
                <person name="Lundeberg J."/>
                <person name="Wedell A."/>
            </authorList>
            <dbReference type="PubMed" id="21963049"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2011.09.004"/>
        </citation>
        <scope>VARIANTS HMAKD GLU-30; ALA-235 AND GLU-318</scope>
        <scope>CHARACTERIZATION OF VARIANTS HMAKD GLU-30; ALA-235 AND GLU-318</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2016" name="Adv. Rare Dis." volume="3" first="0" last="0">
            <title>Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report.</title>
            <authorList>
                <person name="Shakiba M."/>
                <person name="Mahjoub F."/>
                <person name="Fazilaty H."/>
                <person name="Rezagholizadeh F."/>
                <person name="Shakiba A."/>
                <person name="Ziadlou M."/>
                <person name="Gahl W.A."/>
                <person name="Behnam B."/>
            </authorList>
            <dbReference type="PubMed" id="27500280"/>
            <dbReference type="DOI" id="10.12715/ard.2014.3.2"/>
        </citation>
        <scope>VARIANT HMAKD 177-GLU--HIS-362 DEL</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2016" name="J. Inherit. Metab. Dis." volume="39" first="273" last="283">
            <title>Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options.</title>
            <authorList>
                <person name="Staufner C."/>
                <person name="Lindner M."/>
                <person name="Dionisi-Vici C."/>
                <person name="Freisinger P."/>
                <person name="Dobbelaere D."/>
                <person name="Douillard C."/>
                <person name="Makhseed N."/>
                <person name="Straub B.K."/>
                <person name="Kahrizi K."/>
                <person name="Ballhausen D."/>
                <person name="la Marca G."/>
                <person name="Koelker S."/>
                <person name="Haas D."/>
                <person name="Hoffmann G.F."/>
                <person name="Gruenert S.C."/>
                <person name="Blom H.J."/>
            </authorList>
            <dbReference type="PubMed" id="26642971"/>
            <dbReference type="DOI" id="10.1007/s10545-015-9904-y"/>
        </citation>
        <scope>VARIANTS HMAKD 84-GLN--HIS-362 DEL; SER-319; 326-GLN--HIS-362 DEL AND ARG-341</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2025" name="J. Pediatr. Hematol. Oncol." volume="47" first="e96" last="e98">
            <title>Rare etiology of isolated macrocytosis: adenosine kinase deficiency with a novel mutation.</title>
            <authorList>
                <person name="Oez A."/>
                <person name="Oezdemir A.M."/>
                <person name="Ceylaner S."/>
                <person name="Aydin S."/>
            </authorList>
            <dbReference type="PubMed" id="39899686"/>
            <dbReference type="DOI" id="10.1097/mph.0000000000002993"/>
        </citation>
        <scope>VARIANT HMAKD THR-172</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2021" name="Mol. Genet. Metab." volume="132" first="38" last="43">
            <title>Adenosine kinase deficiency: Three new cases and diagnostic value of hypermethioninemia.</title>
            <authorList>
                <person name="Becker P.H."/>
                <person name="Demir Z."/>
                <person name="Mozer Glassberg Y."/>
                <person name="Sevin C."/>
                <person name="Habes D."/>
                <person name="Imbard A."/>
                <person name="Mussini C."/>
                <person name="Rozenfeld Bar Lev M."/>
                <person name="Davit-Spraul A."/>
                <person name="Benoist J.F."/>
                <person name="Therond P."/>
                <person name="Slama A."/>
                <person name="Jacquemin E."/>
                <person name="Gonzales E."/>
                <person name="Gaignard P."/>
            </authorList>
            <dbReference type="PubMed" id="33309011"/>
            <dbReference type="DOI" id="10.1016/j.ymgme.2020.11.007"/>
        </citation>
        <scope>VARIANTS HMAKD 173-TRP--HIS-362 DEL AND 277-ARG--HIS-362 DEL</scope>
    </reference>
    <comment type="function">
        <text evidence="4 9 10 11 12">Adenosine kinase that mediates the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner: catalyzes phosphorylation of both unmodified and modified adenosines (PubMed:21963049, PubMed:40840445, PubMed:6246102, PubMed:8577746, PubMed:9070863). Plays a key role in the detoxification of modified adenosines containing N(6)-methylated adenine (m6A) post-transcriptional modification (PubMed:40840445). Modified nucleosides are derived from the degradation of RNAs (mRNAs, rRNAs and tRNAs) and possess intrinsic cytotoxicity and must be cleared to prevent metabolic dysfunction (PubMed:40840445). Catalyzes the phosphorylation of the free cytosolic methylated adenosine nucleotides N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A) into adenosine monophosphate (AMP) intermediates that are further detoxified by MAPDA/ADAL (PubMed:40840445).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 9 10 11 12">
            <text>adenosine + ATP = AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:20824"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:456215"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.1.20"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="21">
            <dbReference type="Rhea" id="RHEA:20825"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>N(6)-methyladenosine + ATP = N(6)-methyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86211"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86212"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>N(6),N(6)-dimethyladenosine + ATP = N(6),N(6)-dimethyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86215"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28284"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:235457"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86216"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="9">
            <text>N(6)-(dimethylallyl)adenosine + ATP = N(6)-(dimethylallyl)adenosine 5'-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86219"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:57526"/>
            <dbReference type="ChEBI" id="CHEBI:62881"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86220"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9">
            <text>N(6)-methyladenosine + ATP = N(6)-methyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86211"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86212"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9">
            <text>N(6),N(6)-dimethyladenosine + ATP = N(6),N(6)-dimethyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86215"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28284"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:235457"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86216"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 1</molecule>
        <reaction evidence="9">
            <text>N(6)-(dimethylallyl)adenosine + ATP = N(6)-(dimethylallyl)adenosine 5'-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86219"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:57526"/>
            <dbReference type="ChEBI" id="CHEBI:62881"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86220"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>N(6)-methyladenosine + ATP = N(6)-methyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86211"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:21891"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:144842"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86212"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>N(6),N(6)-dimethyladenosine + ATP = N(6),N(6)-dimethyl-AMP + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86215"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:28284"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:235457"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86216"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <molecule>Isoform 2</molecule>
        <reaction evidence="9">
            <text>N(6)-(dimethylallyl)adenosine + ATP = N(6)-(dimethylallyl)adenosine 5'-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:86219"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:57526"/>
            <dbReference type="ChEBI" id="CHEBI:62881"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="9">
            <dbReference type="Rhea" id="RHEA:86220"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="10 12">
            <name>Mg(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:18420"/>
        </cofactor>
        <text evidence="12">Binds 3 Mg(2+) ions per subunit.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="2 12">Activity is inhibited by 5-iodotubercidin and 5'-amino-5'-deoxyadenosine (PubMed:17154503, PubMed:9070863). Also inhibited by 5-(4-(Dimethylamino)phenyl)-6-(6-morpholin- 4-ylpyridin-3-ylethynyl)pyrimidin-4-ylamine, a alkynylpyrimidine class small-molecule (PubMed:17154503).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="10">0.4 uM for adenosine</KM>
            <KM evidence="9">10 uM for adenosine</KM>
            <KM evidence="9">15 uM for N(6)-methyladenosine (m6A)</KM>
            <KM evidence="9">6.1 uM for N(6),N(6)-dimethyladenosine (m6,6A)</KM>
            <KM evidence="9">10 uM for N(6)-isopentenyladenosine (i6A)</KM>
            <text>kcat is 0.19 sec(-1) with adenosine as substrate. kcat is 0.28 sec(-1) with N(6)-methyladenosine (m6A) as substrate. kcat is 0.27 sec(-1) with N(6),N(6)-dimethyladenosine as substrate. kcat is 0.18 sec(-1) with N(6)-isopentenyladenosine (i6A) as substrate.</text>
        </kinetics>
        <phDependence>
            <text evidence="10">Optimum pH is 6.5.</text>
        </phDependence>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 1</molecule>
        <kinetics>
            <KM evidence="11">41 nM for adenosine</KM>
            <KM evidence="12">0.13 uM for ATP</KM>
        </kinetics>
    </comment>
    <comment type="biophysicochemical properties">
        <molecule>Isoform 2</molecule>
        <kinetics>
            <KM evidence="12">0.12 uM for ATP</KM>
        </kinetics>
    </comment>
    <comment type="pathway">
        <text evidence="22">Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenosine: step 1/1.</text>
    </comment>
    <comment type="subunit">
        <text evidence="13">Monomer.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="21">Cytoplasm</location>
            <location evidence="21">Cytosol</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="3">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="3">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P55263-1</id>
            <name>1</name>
            <name>AK-L</name>
            <name evidence="19">Long</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P55263-2</id>
            <name>2</name>
            <name>AK-S</name>
            <name evidence="19">Short</name>
            <sequence type="described" ref="VSP_046713"/>
        </isoform>
        <isoform>
            <id>P55263-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_043526"/>
        </isoform>
        <isoform>
            <id>P55263-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_004668"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="12">Widely expressed. Highest level in placenta, liver, muscle and kidney.</text>
    </comment>
    <comment type="disease" evidence="4 5 6 7 8 9">
        <disease id="DI-03295">
            <name>Hypermethioninemia due to adenosine kinase deficiency</name>
            <acronym>HMAKD</acronym>
            <description>A metabolic disorder characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine. Homocysteine levels are typically normal.</description>
            <dbReference type="MIM" id="614300"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="20">Belongs to the carbohydrate kinase PfkB family.</text>
    </comment>
    <comment type="sequence caution" evidence="20">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAB01689" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="2.7.1.20" evidence="4 10 11 12"/>
    <dbReference type="EC" id="2.7.1.-" evidence="9"/>
    <dbReference type="EMBL" id="U50196">
        <property type="protein sequence ID" value="AAA97893.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U33936">
        <property type="protein sequence ID" value="AAB01689.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U90338">
        <property type="protein sequence ID" value="AAB50234.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U90339">
        <property type="protein sequence ID" value="AAB50235.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290633">
        <property type="protein sequence ID" value="BAF83322.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301590">
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        <location>
            <position position="1"/>
        </location>
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            <begin position="2"/>
            <end position="362"/>
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            <begin position="8"/>
            <end position="16"/>
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        <location>
            <position position="31"/>
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        <ligand>
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            <position position="35"/>
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        <ligand>
            <name>adenosine</name>
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        <location>
            <position position="49"/>
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        <ligand>
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        </ligand>
    </feature>
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            <position position="81"/>
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        <ligand>
            <name>adenosine</name>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
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    </feature>
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            <position position="85"/>
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        <ligand>
            <name>adenosine</name>
            <dbReference type="ChEBI" id="CHEBI:16335"/>
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    </feature>
    <feature type="binding site" evidence="13 24">
        <location>
            <position position="147"/>
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        <ligand>
            <name>Mg(2+)</name>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="13 24">
        <location>
            <position position="148"/>
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        <ligand>
            <name>Mg(2+)</name>
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        </ligand>
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    <feature type="binding site" evidence="13 24">
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            <position position="317"/>
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        <ligand>
            <name>adenosine</name>
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    <feature type="modified residue" description="N-acetylalanine" evidence="27 28">
        <location>
            <position position="2"/>
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    <feature type="modified residue" description="Phosphotyrosine" evidence="1">
        <location>
            <position position="77"/>
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    </feature>
    <feature type="splice variant" id="VSP_004668" description="In isoform 4." evidence="14">
        <original>MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKPNDQILAEDKHKEL</original>
        <variation>MTSVRENILFGMGNPLLDISAVVDKDFLDK</variation>
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            <begin position="1"/>
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    <feature type="splice variant" id="VSP_046713" description="In isoform 2." evidence="14 15 18 19">
        <original>MAAAEEEPKPKKLKVEAPQAL</original>
        <variation>MTSV</variation>
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            <begin position="1"/>
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            <begin position="186"/>
            <end position="242"/>
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    </feature>
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        <original>G</original>
        <variation>E</variation>
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            <position position="30"/>
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    <feature type="sequence variant" id="VAR_091016" description="In HMAKD." evidence="5">
        <location>
            <begin position="84"/>
            <end position="362"/>
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    </feature>
    <feature type="sequence variant" id="VAR_091017" description="In HMAKD; uncertain significance." evidence="8">
        <original>N</original>
        <variation>T</variation>
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            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_091018" description="In HMAKD." evidence="7">
        <location>
            <begin position="173"/>
            <end position="362"/>
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            <begin position="177"/>
            <end position="362"/>
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            <position position="235"/>
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    <feature type="sequence variant" id="VAR_091020" description="In HMAKD." evidence="7">
        <location>
            <begin position="277"/>
            <end position="362"/>
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    </feature>
    <feature type="sequence variant" id="VAR_066642" description="In HMAKD; abolished ability to mediate phosphorylation of unmodified and modified adenosines; dbSNP:rs397514452." evidence="4 9">
        <original>A</original>
        <variation>E</variation>
        <location>
            <position position="318"/>
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    </feature>
    <feature type="sequence variant" id="VAR_091021" description="In HMAKD; abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="5 9">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="319"/>
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    </feature>
    <feature type="sequence variant" id="VAR_091022" description="In HMAKD." evidence="5">
        <location>
            <begin position="326"/>
            <end position="362"/>
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    <feature type="sequence variant" id="VAR_091023" description="In HMAKD; decreased ability to mediate phosphorylation of unmodified and modified adenosines." evidence="5 9">
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            <position position="341"/>
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    <feature type="mutagenesis site" description="Abolishes nuclear localization." evidence="3">
        <original>KK</original>
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        <variation>AD</variation>
        <location>
            <begin position="11"/>
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    <feature type="mutagenesis site" description="Abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="9">
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            <position position="33"/>
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    <feature type="mutagenesis site" description="Abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="9">
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            <position position="35"/>
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    <feature type="mutagenesis site" description="Abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="9">
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            <position position="57"/>
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    <feature type="mutagenesis site" description="Increased ability to phosphorylate N(6)-methyladenosine (m6A), N(6),N(6)-dimethyladenosine (m6,6A), N(6)-isopentenyladenosine (i6A) and adenosine." evidence="9">
        <original>A</original>
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        <location>
            <position position="153"/>
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    <feature type="mutagenesis site" description="Decreased ability to phosphorylate N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A), but not N(6)-methyladenosine (m6A) or adenosine." evidence="9">
        <original>L</original>
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            <position position="155"/>
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    <feature type="mutagenesis site" description="Abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="9">
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            <position position="187"/>
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            <position position="218"/>
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    <feature type="mutagenesis site" description="Decreased ability to phosphorylate N(6),N(6)-dimethyladenosine (m6,6A) and N(6)-isopentenyladenosine (i6A)." evidence="9">
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            <position position="313"/>
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    <feature type="mutagenesis site" description="Abolished ability to mediate phosphorylation of unmodified and modified adenosines." evidence="9">
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        <location>
            <position position="317"/>
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    <feature type="sequence conflict" description="In Ref. 1; AA sequence." evidence="20" ref="1">
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        <variation>A</variation>
        <location>
            <position position="98"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAB01689." evidence="20" ref="2">
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        <location>
            <position position="133"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAB01689." evidence="20" ref="2">
        <original>K</original>
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        <location>
            <position position="171"/>
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    <feature type="sequence conflict" description="In Ref. 1; AAA97893." evidence="20" ref="1">
        <original>T</original>
        <variation>H</variation>
        <location>
            <position position="190"/>
        </location>
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    <feature type="sequence conflict" description="In Ref. 7; AAH03568." evidence="20" ref="7">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="219"/>
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    <feature type="sequence conflict" description="In Ref. 1; AA sequence." evidence="20" ref="1">
        <original>S</original>
        <variation>V</variation>
        <location>
            <position position="273"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AA sequence." evidence="20" ref="1">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="289"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAB01689." evidence="20" ref="2">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="307"/>
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    <feature type="strand" evidence="29">
        <location>
            <begin position="26"/>
            <end position="29"/>
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    </feature>
    <feature type="strand" evidence="29">
        <location>
            <begin position="33"/>
            <end position="39"/>
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    <feature type="helix" evidence="29">
        <location>
            <begin position="42"/>
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    <feature type="strand" evidence="29">
        <location>
            <begin position="52"/>
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    <feature type="helix" evidence="29">
        <location>
            <begin position="60"/>
            <end position="62"/>
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    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="63"/>
            <end position="72"/>
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    <feature type="strand" evidence="29">
        <location>
            <begin position="76"/>
            <end position="80"/>
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    <feature type="helix" evidence="29">
        <location>
            <begin position="82"/>
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    </feature>
    <feature type="strand" evidence="30">
        <location>
            <begin position="96"/>
            <end position="99"/>
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    <feature type="strand" evidence="29">
        <location>
            <begin position="101"/>
            <end position="110"/>
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    <feature type="helix" evidence="29">
        <location>
            <begin position="111"/>
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    <feature type="strand" evidence="29">
        <location>
            <begin position="126"/>
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    <feature type="strand" evidence="29">
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            <begin position="139"/>
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    <sequence length="362" mass="40545" checksum="48AA4925865BFE70" modified="2000-05-30" version="2">MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKPNDQILAEDKHKELFDELVKKFKVEYHAGGSTQNSIKVAQWMIQQPHKAATFFGCIGIDKFGEILKRKAAEAHVDAHYYEQNEQPTGTCAACITGDNRSLIANLAAANCYKKEKHLDLEKNWMLVEKARVCYIAGFFLTVSPESVLKVAHHASENNRIFTLNLSAPFISQFYKESLMKVMPYVDILFGNETEAATFAREQGFETKDIKEIAKKTQALPKMNSKRQRIVIFTQGRDDTIMATESEVTAFAVLDQDQKEIIDTNGAGDAFVGGFLSQLVSDKPLTECIRAGHYAASIIIRRTGCTFPEKPDFH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-10" modified="2026-01-28" version="158" xmlns="https://uniprot.org/uniprot">
    <accession>Q9GZN8</accession>
    <accession>A8K4J0</accession>
    <accession>D3DVX8</accession>
    <accession>Q5JX81</accession>
    <accession>Q9NWX3</accession>
    <name>ADSSP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="4">Adipose-secreted signaling protein</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ADISSP</name>
        <name evidence="4" type="synonym">C20orf27</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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        <text evidence="1">Adipocyte-secreted protein (adipokine) that acts as a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis at least in part through activation of protein kinase A (PKA).</text>
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        <property type="expression patterns" value="Expressed in nucleus accumbens and 185 other cell types or tissues"/>
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    <dbReference type="ExpressionAtlas" id="Q9GZN8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005615">
        <property type="term" value="C:extracellular space"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008157">
        <property type="term" value="F:protein phosphatase 1 binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990845">
        <property type="term" value="P:adaptive thermogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042593">
        <property type="term" value="P:glucose homeostasis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:1901224">
        <property type="term" value="P:positive regulation of non-canonical NF-kappaB signal transduction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010739">
        <property type="term" value="P:positive regulation of protein kinase A signaling"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030511">
        <property type="term" value="P:positive regulation of transforming growth factor beta receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026794">
        <property type="entry name" value="ADISSP"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13287">
        <property type="entry name" value="ADIPOSE-SECRETED SIGNALING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13287:SF2">
        <property type="entry name" value="ADIPOSE-SECRETED SIGNALING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF15006">
        <property type="entry name" value="DUF4517"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <feature type="initiator methionine" description="Removed" evidence="5">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000079419" description="Adipose-secreted signaling protein">
        <location>
            <begin position="2"/>
            <end position="174"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="5">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="1">
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_040293" description="In isoform 2." evidence="2">
        <original>K</original>
        <variation>KGKCLPGVVGLAQALPVGPGRRAIAA</variation>
        <location>
            <position position="6"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAA91252." evidence="3" ref="1">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="14"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9D1K7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="2">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:15873"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="5">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="174" mass="19291" checksum="DD114F2C1A7D8B97" modified="2007-01-23" version="3">MAAANKGNKPRVRSIRFAAGHDAEGSHSHVHFDEKLHDSVVMVTQESDSSFLVKVGFLKILHRYEITFTLPPVHRLSKDVREAPVPSLHLKLLSVVPVPEGYSVKCEYSAHKEGVLKEEILLACEGGTGTCVRVTVQARVMDRHHGTPMLLDGVKCVGAELEYDSEHSDWHGFD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1991-08-01" modified="2026-01-28" version="226" xmlns="https://uniprot.org/uniprot">
    <accession>P22570</accession>
    <accession>B4DDI7</accession>
    <accession>B4DHX5</accession>
    <accession>B4DQQ4</accession>
    <accession>B4DX24</accession>
    <accession>B7Z7G2</accession>
    <accession>E7EQC1</accession>
    <accession>Q13716</accession>
    <accession>Q4PJI0</accession>
    <accession>Q9BU12</accession>
    <name>ADRO_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>NADPH:adrenodoxin oxidoreductase, mitochondrial</fullName>
            <shortName>AR</shortName>
            <shortName evidence="14">Adrenodoxin reductase</shortName>
            <ecNumber evidence="1">1.18.1.6</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Ferredoxin--NADP(+) reductase</fullName>
            <shortName>Ferredoxin reductase</shortName>
            <ecNumber evidence="11">1.18.1.-</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">FDXR</name>
        <name type="synonym">ADXR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen--&gt;q25 are expressed in steroidogenic tissues.</title>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS SHORT AND LONG)</scope>
        <scope>VARIANT GLN-123</scope>
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    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS LEU-7; GLN-123; VAL-213; LEU-248; TRP-251; CYS-301; MET-345; SER-352 AND ALA-472</scope>
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        <scope>VARIANT GLN-123</scope>
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            <tissue>Caudate nucleus</tissue>
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            <dbReference type="DOI" id="10.1038/s41929-023-01087-z"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2017" name="Am. J. Hum. Genet." volume="101" first="630" last="637">
            <title>FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases.</title>
            <authorList>
                <person name="Paul A."/>
                <person name="Drecourt A."/>
                <person name="Petit F."/>
                <person name="Deguine D.D."/>
                <person name="Vasnier C."/>
                <person name="Oufadem M."/>
                <person name="Masson C."/>
                <person name="Bonnet C."/>
                <person name="Masmoudi S."/>
                <person name="Mosnier I."/>
                <person name="Mahieu L."/>
                <person name="Bouccara D."/>
                <person name="Kaplan J."/>
                <person name="Challe G."/>
                <person name="Domange C."/>
                <person name="Mochel F."/>
                <person name="Sterkers O."/>
                <person name="Gerber S."/>
                <person name="Nitschke P."/>
                <person name="Bole-Feysot C."/>
                <person name="Jonard L."/>
                <person name="Gherbi S."/>
                <person name="Mercati O."/>
                <person name="Ben Aissa I."/>
                <person name="Lyonnet S."/>
                <person name="Roetig A."/>
                <person name="Delahodde A."/>
                <person name="Marlin S."/>
            </authorList>
            <dbReference type="PubMed" id="28965846"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2017.09.007"/>
        </citation>
        <scope>INVOLVEMENT IN ANOA</scope>
        <scope>VARIANTS ANOA VAL-215; TRP-242; CYS-306; SER-327 AND 419-GLN--HIS-491 DEL</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2017" name="Hum. Mol. Genet." volume="26" first="4937" last="4950">
            <title>Biallelic mutations in the ferredoxin reductase gene cause novel mitochondriopathy with optic atrophy.</title>
            <authorList>
                <person name="Peng Y."/>
                <person name="Shinde D.N."/>
                <person name="Valencia C.A."/>
                <person name="Mo J.S."/>
                <person name="Rosenfeld J."/>
                <person name="Truitt Cho M."/>
                <person name="Chamberlin A."/>
                <person name="Li Z."/>
                <person name="Liu J."/>
                <person name="Gui B."/>
                <person name="Brockhage R."/>
                <person name="Basinger A."/>
                <person name="Alvarez-Leon B."/>
                <person name="Heydemann P."/>
                <person name="Magoulas P.L."/>
                <person name="Lewis A.M."/>
                <person name="Scaglia F."/>
                <person name="Gril S."/>
                <person name="Chong S.C."/>
                <person name="Bower M."/>
                <person name="Monaghan K.G."/>
                <person name="Willaert R."/>
                <person name="Plona M.R."/>
                <person name="Dineen R."/>
                <person name="Milan F."/>
                <person name="Hoganson G."/>
                <person name="Powis Z."/>
                <person name="Helbig K.L."/>
                <person name="Keller-Ramey J."/>
                <person name="Harris B."/>
                <person name="Anderson L.C."/>
                <person name="Green T."/>
                <person name="Sukoff Rizzo S.J."/>
                <person name="Kaylor J."/>
                <person name="Chen J."/>
                <person name="Guan M.X."/>
                <person name="Sellars E."/>
                <person name="Sparagana S.P."/>
                <person name="Gibson J.B."/>
                <person name="Reinholdt L.G."/>
                <person name="Tang S."/>
                <person name="Huang T."/>
            </authorList>
            <dbReference type="PubMed" id="29040572"/>
            <dbReference type="DOI" id="10.1093/hmg/ddx377"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>VARIANTS MMDS9B LEU-51; LEU-74; PHE-143; MET-158; ALA-205; PHE-207; 274-LYS--HIS-491 DEL; TYR-353; ASN-368; TRP-386; SER-437 AND CYS-437</scope>
        <scope>CHARACTERIZATION OF VARIANT MMDS9B TRP-386</scope>
        <scope>INVOLVEMENT IN MMDS9B</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2018" name="Hum. Mol. Genet." volume="27" first="2224" last="2224">
            <authorList>
                <person name="Peng Y."/>
                <person name="Shinde D.N."/>
                <person name="Alexander Valencia C."/>
                <person name="Mo J.S."/>
                <person name="Rosenfeld J."/>
                <person name="Cho M.T."/>
                <person name="Chamberlin A."/>
                <person name="Li Z."/>
                <person name="Liu J."/>
                <person name="Gui B."/>
            </authorList>
            <dbReference type="PubMed" id="29554255"/>
            <dbReference type="DOI" id="10.1093/hmg/ddy072"/>
        </citation>
        <scope>ERRATUM OF PUBMED:29040572</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2018" name="J. Hum. Genet." volume="63" first="1211" last="1222">
            <title>Biallelic mutations in FDXR cause neurodegeneration associated with inflammation.</title>
            <authorList>
                <person name="Slone J."/>
                <person name="Peng Y."/>
                <person name="Chamberlin A."/>
                <person name="Harris B."/>
                <person name="Kaylor J."/>
                <person name="McDonald M.T."/>
                <person name="Lemmon M."/>
                <person name="El-Dairi M.A."/>
                <person name="Tchapyjnikov D."/>
                <person name="Gonzalez-Krellwitz L.A."/>
                <person name="Sellars E.A."/>
                <person name="McConkie-Rosell A."/>
                <person name="Reinholdt L.G."/>
                <person name="Huang T."/>
            </authorList>
            <dbReference type="PubMed" id="30250212"/>
            <dbReference type="DOI" id="10.1038/s10038-018-0515-y"/>
        </citation>
        <scope>VARIANTS MMDS9B TRP-155 AND HIS-193</scope>
        <scope>INVOLVEMENT IN MMDS9B</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2021" name="Hum. Mutat." volume="42" first="310" last="319">
            <title>Expanding the clinical and genetic spectrum of FDXR deficiency by functional validation of variants of uncertain significance.</title>
            <authorList>
                <person name="Stenton S.L."/>
                <person name="Piekutowska-Abramczuk D."/>
                <person name="Kulterer L."/>
                <person name="Kopajtich R."/>
                <person name="Claeys K.G."/>
                <person name="Ciara E."/>
                <person name="Eisen J."/>
                <person name="Ploski R."/>
                <person name="Pronicka E."/>
                <person name="Malczyk K."/>
                <person name="Wagner M."/>
                <person name="Wortmann S.B."/>
                <person name="Prokisch H."/>
            </authorList>
            <dbReference type="PubMed" id="33348459"/>
            <dbReference type="DOI" id="10.1002/humu.24160"/>
        </citation>
        <scope>VARIANTS MMDS9B TRP-12; SER-109; ALA-111; 189-LEU--ALA-192 DEL; VAL-211; LEU-228; TYR-353; TRP-386 AND GLN-448</scope>
        <scope>INVOLVEMENT IN MMDS9B</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2023" name="Exp. Eye Res." volume="234" first="109600" last="109600">
            <title>FDXR-associated disease in a Chinese cohort: Unraveling expanded ocular phenotypes and genetic spectrum.</title>
            <authorList>
                <person name="Wei X."/>
                <person name="Li H."/>
                <person name="Zhu T."/>
                <person name="Yao F."/>
                <person name="Sui R."/>
            </authorList>
            <dbReference type="PubMed" id="37481223"/>
            <dbReference type="DOI" id="10.1016/j.exer.2023.109600"/>
        </citation>
        <scope>VARIANTS MMDS9B VAL-128; MET-158; CYS-193; CYS-306 AND LEU-314</scope>
        <scope>INVOLVEMENT IN MMDS9B</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2023" name="Neurol. Sci." volume="44" first="3037" last="3043">
            <title>FDXR-associated disease: a challenging differential diagnosis with inflammatory peripheral neuropathy.</title>
            <authorList>
                <person name="Masnada S."/>
                <person name="Previtali R."/>
                <person name="Erba P."/>
                <person name="Beretta E."/>
                <person name="Camporesi A."/>
                <person name="Chiapparini L."/>
                <person name="Doneda C."/>
                <person name="Iascone M."/>
                <person name="Sartorio M.U.A."/>
                <person name="Spaccini L."/>
                <person name="Veggiotti P."/>
                <person name="Osio M."/>
                <person name="Tonduti D."/>
                <person name="Moroni I."/>
            </authorList>
            <dbReference type="PubMed" id="37046037"/>
            <dbReference type="DOI" id="10.1007/s10072-023-06790-0"/>
        </citation>
        <scope>VARIANT MMDS9B TRP-155</scope>
        <scope>INVOLVEMENT IN MMDS9B</scope>
    </reference>
    <comment type="function">
        <text evidence="1 11">Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver (By similarity). Also acts as a ferredoxin--NADP(+) reductase essential for coenzyme Q biosynthesis: together with FDX2, transfers the electrons required for the hydroxylation reaction performed by COQ6 (PubMed:38425362).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>2 reduced [adrenodoxin] + NADP(+) + H(+) = 2 oxidized [adrenodoxin] + NADPH</text>
            <dbReference type="Rhea" id="RHEA:42312"/>
            <dbReference type="Rhea" id="RHEA-COMP:9998"/>
            <dbReference type="Rhea" id="RHEA-COMP:9999"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33737"/>
            <dbReference type="ChEBI" id="CHEBI:33738"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
            <dbReference type="EC" id="1.18.1.6"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="11">
            <text>2 reduced [2Fe-2S]-[ferredoxin] + NADP(+) + H(+) = 2 oxidized [2Fe-2S]-[ferredoxin] + NADPH</text>
            <dbReference type="Rhea" id="RHEA:20125"/>
            <dbReference type="Rhea" id="RHEA-COMP:10000"/>
            <dbReference type="Rhea" id="RHEA-COMP:10001"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:33737"/>
            <dbReference type="ChEBI" id="CHEBI:33738"/>
            <dbReference type="ChEBI" id="CHEBI:57783"/>
            <dbReference type="ChEBI" id="CHEBI:58349"/>
        </reaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="1">
            <name>FAD</name>
            <dbReference type="ChEBI" id="CHEBI:57692"/>
        </cofactor>
    </comment>
    <comment type="pathway">
        <text evidence="1">Steroid metabolism; cholesterol metabolism.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer. Interacts directly with FDX1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Mitochondrion inner membrane</location>
            <topology evidence="15">Peripheral membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P22570-1</id>
            <name>Short</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P22570-2</id>
            <name>Long</name>
            <sequence type="described" ref="VSP_003416"/>
        </isoform>
        <isoform>
            <id>P22570-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_045135"/>
        </isoform>
        <isoform>
            <id>P22570-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046669"/>
        </isoform>
        <isoform>
            <id>P22570-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_046673"/>
        </isoform>
        <isoform>
            <id>P22570-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_046671 VSP_046672"/>
        </isoform>
        <isoform>
            <id>P22570-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_046670"/>
        </isoform>
    </comment>
    <comment type="disease" evidence="5">
        <disease id="DI-05116">
            <name>Auditory neuropathy and optic atrophy</name>
            <acronym>ANOA</acronym>
            <description>An autosomal recessive disease characterized by hearing loss, visual impairment and optic atrophy, with onset in the first or second decades of life. Optic atrophy is caused by degeneration of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts.</description>
            <dbReference type="MIM" id="617717"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 9 10">
        <disease id="DI-06923">
            <name>Multiple mitochondrial dysfunctions syndrome 9B</name>
            <acronym>MMDS9B</acronym>
            <description>An autosomal recessive disorder characterized by optic and/or auditory neuropathy with onset in the first two decades of life, in some cases associated with developmental delay or regression, global hypotonia, pyramidal, cerebellar signs, and seizures.</description>
            <dbReference type="MIM" id="620887"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform Long</molecule>
        <text evidence="15">Represents 10-20% of all adrenodoxin reductase mRNAs and seems to be inactive.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the ferredoxin--NADP reductase type 1 family.</text>
    </comment>
    <dbReference type="EC" id="1.18.1.6" evidence="1"/>
    <dbReference type="EC" id="1.18.1.-" evidence="11"/>
    <dbReference type="EMBL" id="J03826">
        <property type="protein sequence ID" value="AAB59498.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03826">
        <property type="protein sequence ID" value="AAB59497.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M58509">
        <property type="protein sequence ID" value="AAA51668.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M58508">
        <property type="protein sequence ID" value="AAA51668.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M58509">
        <property type="protein sequence ID" value="AAA51669.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M58508">
        <property type="protein sequence ID" value="AAA51669.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ085780">
        <property type="protein sequence ID" value="AAY68215.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK293208">
        <property type="protein sequence ID" value="BAG56748.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK295307">
        <property type="protein sequence ID" value="BAG58287.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK298908">
        <property type="protein sequence ID" value="BAG61016.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301779">
        <property type="protein sequence ID" value="BAG63236.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301977">
        <property type="protein sequence ID" value="BAH13598.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC068874">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002960">
        <property type="protein sequence ID" value="AAH02960.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11707.1">
        <molecule id="P22570-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58591.1">
        <molecule id="P22570-4"/>
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    <dbReference type="CCDS" id="CCDS58592.1">
        <molecule id="P22570-5"/>
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    <dbReference type="CCDS" id="CCDS58593.1">
        <molecule id="P22570-1"/>
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    <dbReference type="CCDS" id="CCDS58594.1">
        <molecule id="P22570-6"/>
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    <dbReference type="CCDS" id="CCDS58595.1">
        <molecule id="P22570-3"/>
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    <dbReference type="CCDS" id="CCDS58596.1">
        <molecule id="P22570-7"/>
    </dbReference>
    <dbReference type="PIR" id="A40487">
        <property type="entry name" value="A40487"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001244941.2">
        <property type="nucleotide sequence ID" value="NM_001258012.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001244942.2">
        <property type="nucleotide sequence ID" value="NM_001258013.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001244943.2">
        <property type="nucleotide sequence ID" value="NM_001258014.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001244944.1">
        <molecule id="P22570-6"/>
        <property type="nucleotide sequence ID" value="NM_001258015.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001244945.2">
        <property type="nucleotide sequence ID" value="NM_001258016.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004101.3">
        <property type="nucleotide sequence ID" value="NM_004110.5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_077728.3">
        <property type="nucleotide sequence ID" value="NM_024417.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P22570"/>
    <dbReference type="SMR" id="P22570"/>
    <dbReference type="BioGRID" id="108523">
        <property type="interactions" value="78"/>
    </dbReference>
    <dbReference type="FunCoup" id="P22570">
        <property type="interactions" value="2031"/>
    </dbReference>
    <dbReference type="IntAct" id="P22570">
        <property type="interactions" value="38"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000416515"/>
    <dbReference type="DrugBank" id="DB03147">
        <property type="generic name" value="Flavin adenine dinucleotide"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB03461">
        <property type="generic name" value="Nicotinamide adenine dinucleotide phosphate"/>
    </dbReference>
    <dbReference type="GlyGen" id="P22570">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P22570"/>
    <dbReference type="PhosphoSitePlus" id="P22570"/>
    <dbReference type="SwissPalm" id="P22570"/>
    <dbReference type="BioMuta" id="FDXR"/>
    <dbReference type="DMDM" id="85681283"/>
    <dbReference type="REPRODUCTION-2DPAGE" id="IPI00026958"/>
    <dbReference type="jPOST" id="P22570"/>
    <dbReference type="MassIVE" id="P22570"/>
    <dbReference type="PaxDb" id="9606-ENSP00000416515"/>
    <dbReference type="PeptideAtlas" id="P22570"/>
    <dbReference type="ProteomicsDB" id="17542"/>
    <dbReference type="ProteomicsDB" id="4256"/>
    <dbReference type="ProteomicsDB" id="4894"/>
    <dbReference type="ProteomicsDB" id="54003">
        <molecule id="P22570-1"/>
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    <dbReference type="ProteomicsDB" id="54004">
        <molecule id="P22570-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="6867"/>
    <dbReference type="Pumba" id="P22570"/>
    <dbReference type="Antibodypedia" id="3261">
        <property type="antibodies" value="281 antibodies from 29 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2232"/>
    <dbReference type="Ensembl" id="ENST00000420580.6">
        <molecule id="P22570-6"/>
        <property type="protein sequence ID" value="ENSP00000414172.2"/>
        <property type="gene ID" value="ENSG00000161513.13"/>
    </dbReference>
    <dbReference type="GeneID" id="2232"/>
    <dbReference type="KEGG" id="hsa:2232"/>
    <dbReference type="UCSC" id="uc002jlx.4">
        <molecule id="P22570-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:3642"/>
    <dbReference type="ClinPGx" id="PA28086"/>
    <dbReference type="CTD" id="2232"/>
    <dbReference type="DisGeNET" id="2232"/>
    <dbReference type="GeneCards" id="FDXR"/>
    <dbReference type="HGNC" id="HGNC:3642">
        <property type="gene designation" value="FDXR"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000161513">
        <property type="expression patterns" value="Tissue enriched (adrenal)"/>
    </dbReference>
    <dbReference type="MalaCards" id="FDXR"/>
    <dbReference type="MIM" id="103270">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="617717">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="620887">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000161513"/>
    <dbReference type="Orphanet" id="542585">
        <property type="disease" value="Auditory neuropathy-optic atrophy syndrome"/>
    </dbReference>
    <dbReference type="Orphanet" id="543470">
        <property type="disease" value="Optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000161513"/>
    <dbReference type="eggNOG" id="KOG1800">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000013574"/>
    <dbReference type="HOGENOM" id="CLU_024722_3_1_1"/>
    <dbReference type="InParanoid" id="P22570"/>
    <dbReference type="OrthoDB" id="333024at2759"/>
    <dbReference type="PAN-GO" id="P22570">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P22570"/>
    <dbReference type="BioCyc" id="MetaCyc:HS08587-MONOMER"/>
    <dbReference type="PathwayCommons" id="P22570"/>
    <dbReference type="Reactome" id="R-HSA-196108">
        <property type="pathway name" value="Pregnenolone biosynthesis"/>
    </dbReference>
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            <position position="317"/>
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            <begin position="1"/>
            <end position="59"/>
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        <location>
            <begin position="27"/>
            <end position="34"/>
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            <position position="59"/>
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            <end position="131"/>
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            <end position="98"/>
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            <position position="74"/>
        </location>
    </feature>
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            <position position="109"/>
        </location>
    </feature>
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            <position position="111"/>
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            <position position="123"/>
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    </feature>
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        <location>
            <position position="128"/>
        </location>
    </feature>
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        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089888" description="In MMDS9B; uncertain significance." evidence="7 9">
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        <location>
            <position position="155"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089889" description="In MMDS9B; uncertain significance." evidence="6 10">
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        <location>
            <position position="158"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089890" description="In MMDS9B; uncertain significance." evidence="8">
        <location>
            <begin position="189"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089891" description="In MMDS9B; uncertain significance." evidence="10">
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        <variation>C</variation>
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089892" description="In MMDS9B; uncertain significance." evidence="7">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="193"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089893" description="In MMDS9B; uncertain significance." evidence="6">
        <original>T</original>
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        <location>
            <position position="205"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089894" description="In MMDS9B; uncertain significance." evidence="6">
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        <location>
            <position position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089895" description="In MMDS9B; uncertain significance." evidence="8">
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        <location>
            <position position="211"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025193" description="In dbSNP:rs35692345." evidence="12">
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        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080376" description="In ANOA." evidence="5">
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        <variation>V</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089896" description="In MMDS9B; uncertain significance." evidence="8">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080377" description="In ANOA." evidence="5">
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        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025194" description="In dbSNP:rs35072974." evidence="12">
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        <location>
            <position position="248"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025195" description="In dbSNP:rs34038065." evidence="12">
        <original>R</original>
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        <location>
            <position position="251"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089897" description="In MMDS9B; likely pathogenic." evidence="6">
        <location>
            <begin position="274"/>
            <end position="491"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025196" description="In dbSNP:rs34118765." evidence="12">
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        <location>
            <position position="301"/>
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    </feature>
    <feature type="sequence variant" id="VAR_080378" description="In ANOA and MMDS9B." evidence="5 10">
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        <location>
            <position position="306"/>
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    </feature>
    <feature type="sequence variant" id="VAR_089898" description="In MMDS9B; uncertain significance." evidence="10">
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        <location>
            <position position="314"/>
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    </feature>
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            <position position="327"/>
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            <position position="345"/>
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            <position position="352"/>
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            <position position="386"/>
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        <location>
            <begin position="419"/>
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        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089902" description="In MMDS9B; uncertain significance." evidence="6">
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        <location>
            <position position="437"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089903" description="In MMDS9B; uncertain significance." evidence="6">
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        <location>
            <position position="437"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089904" description="In MMDS9B; uncertain significance." evidence="8">
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        <location>
            <position position="448"/>
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    </feature>
    <feature type="sequence variant" id="VAR_025199" description="In dbSNP:rs35769464." evidence="12">
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        <location>
            <position position="472"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAG56748." evidence="15" ref="4">
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        <variation>G</variation>
        <location>
            <position position="223"/>
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    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P08165"/>
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    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P48360"/>
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            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="2845396"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="28965846"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="29040572"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="30250212"/>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="33348459"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
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            <dbReference type="PubMed" id="37046037"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="37481223"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="38425362"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source ref="3"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="2845396"/>
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    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:3642"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="491" mass="53837" checksum="15D07E714F592C9D" modified="2006-01-24" version="3" precursor="true">MASRCWRWWGWSAWPRTRLPPAGSTPSFCHHFSTQEKTPQICVVGSGPAGFYTAQHLLKHPQAHVDIYEKQPVPFGLVRFGVAPDHPEVKNVINTFTQTAHSGRCAFWGNVEVGRDVTVPELREAYHAVVLSYGAEDHRALEIPGEELPGVCSARAFVGWYNGLPENQELEPDLSCDTAVILGQGNVALDVARILLTPPEHLERTDITKAALGVLRQSRVKTVWLVGRRGPLQVAFTIKELREMIQLPGARPILDPVDFLGLQDKIKEVPRPRKRLTELLLRTATEKPGPAEAARQASASRAWGLRFFRSPQQVLPSPDGRRAAGVRLAVTRLEGVDEATRAVPTGDMEDLPCGLVLSSIGYKSRPVDPSVPFDSKLGVIPNVEGRVMDVPGLYCSGWVKRGPTGVIATTMTDSFLTGQMLLQDLKAGLLPSGPRPGYAAIQALLSSRGVRPVSFSDWEKLDAEEVARGQGTGKPREKLVDPQEMLRLLGH</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1997-11-01" modified="2026-01-28" version="209" xmlns="https://uniprot.org/uniprot">
    <accession>Q16186</accession>
    <accession>A0PKB1</accession>
    <accession>Q96FJ7</accession>
    <accession>Q9H1P2</accession>
    <name>ADRM1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Proteasomal ubiquitin receptor ADRM1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>110 kDa cell membrane glycoprotein</fullName>
            <shortName>Gp110</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Adhesion-regulating molecule 1</fullName>
            <shortName>ARM-1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Proteasome regulatory particle non-ATPase 13</fullName>
            <shortName>hRpn13</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Rpn13 homolog</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADRM1</name>
        <name type="synonym">GP110</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-127 AND SER-140</scope>
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            <title>Acute unfolding of a single protein immediately stimulates recruitment of ubiquitin protein ligase E3C (UBE3C) to 26S proteasomes.</title>
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                <person name="Gottlieb C.D."/>
                <person name="Thompson A.C.S."/>
                <person name="Ordureau A."/>
                <person name="Harper J.W."/>
                <person name="Kopito R.R."/>
            </authorList>
            <dbReference type="PubMed" id="31375563"/>
            <dbReference type="DOI" id="10.1074/jbc.ra119.009654"/>
        </citation>
        <scope>UBIQUITINATION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2010" name="Mol. Cell" volume="38" first="404" last="415">
            <title>Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2.</title>
            <authorList>
                <person name="Chen X."/>
                <person name="Lee B.H."/>
                <person name="Finley D."/>
                <person name="Walters K.J."/>
            </authorList>
            <dbReference type="PubMed" id="20471946"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2010.04.019"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 1-407</scope>
        <scope>INTERACTION WITH PSMD1</scope>
        <scope>REGION</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2014" name="Protein Cell" volume="5" first="616" last="630">
            <title>Mechanism of the Rpn13-induced activation of Uch37.</title>
            <authorList>
                <person name="Jiao L."/>
                <person name="Ouyang S."/>
                <person name="Shaw N."/>
                <person name="Song G."/>
                <person name="Feng Y."/>
                <person name="Niu F."/>
                <person name="Qiu W."/>
                <person name="Zhu H."/>
                <person name="Hung L.W."/>
                <person name="Zuo X."/>
                <person name="Eleonora Shtykova V."/>
                <person name="Zhu P."/>
                <person name="Dong Y.H."/>
                <person name="Xu R."/>
                <person name="Liu Z.J."/>
            </authorList>
            <dbReference type="PubMed" id="24752541"/>
            <dbReference type="DOI" id="10.1007/s13238-014-0046-z"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 270-407</scope>
        <scope>INTERACTION WITH UCHL5</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2015" name="Mol. Cell" volume="57" first="887" last="900">
            <title>Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.</title>
            <authorList>
                <person name="Sahtoe D.D."/>
                <person name="van Dijk W.J."/>
                <person name="El Oualid F."/>
                <person name="Ekkebus R."/>
                <person name="Ovaa H."/>
                <person name="Sixma T.K."/>
            </authorList>
            <dbReference type="PubMed" id="25702870"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2014.12.039"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 266-388</scope>
        <scope>INTERACTION WITH UCHL5</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2015" name="Mol. Cell" volume="57" first="901" last="911">
            <title>Structural basis for the activation and inhibition of the UCH37 deubiquitylase.</title>
            <authorList>
                <person name="VanderLinden R.T."/>
                <person name="Hemmis C.W."/>
                <person name="Schmitt B."/>
                <person name="Ndoja A."/>
                <person name="Whitby F.G."/>
                <person name="Robinson H."/>
                <person name="Cohen R.E."/>
                <person name="Yao T."/>
                <person name="Hill C.P."/>
            </authorList>
            <dbReference type="PubMed" id="25702872"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2015.01.016"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 285-386</scope>
        <scope>INTERACTION WITH UCHL5</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2016" name="Structure" volume="24" first="1257" last="1270">
            <title>Structures of Rpn1 T1:Rad23 and hRpn13:hPLIC2 reveal distinct binding mechanisms between substrate receptors and shuttle factors of the proteasome.</title>
            <authorList>
                <person name="Chen X."/>
                <person name="Randles L."/>
                <person name="Shi K."/>
                <person name="Tarasov S.G."/>
                <person name="Aihara H."/>
                <person name="Walters K.J."/>
            </authorList>
            <dbReference type="PubMed" id="27396824"/>
            <dbReference type="DOI" id="10.1016/j.str.2016.05.018"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 1-150</scope>
        <scope>INTERACTION WITH UBIQUITIN AND UBQLN2</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 7 8 9 11 13 14">Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins (PubMed:16815440, PubMed:16906146, PubMed:16990800, PubMed:17139257, PubMed:18497817, PubMed:24752541, PubMed:25702870, PubMed:25702872). This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required (PubMed:16815440, PubMed:16906146, PubMed:16990800, PubMed:17139257, PubMed:18497817, PubMed:24752541, PubMed:25702870, PubMed:25702872). Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:16815440, PubMed:16906146, PubMed:16990800, PubMed:17139257, PubMed:18497817, PubMed:24752541, PubMed:25702870, PubMed:25702872). Within the complex, functions as a proteasomal ubiquitin receptor (PubMed:18497817). Engages and activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation (PubMed:16906146, PubMed:16990800, PubMed:17139257, PubMed:24752541). UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex (PubMed:16906146, PubMed:16990800, PubMed:17139257, PubMed:24752541).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6 7 8 9 10 11 14 15">Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (PubMed:16990800). Interacts with the proteasomal scaffolding protein PSMD1 (PubMed:16815440, PubMed:16906146, PubMed:16990800, PubMed:20471946). Interacts with deubiquitinase UCHL5; this interaction activates the auto-inhibited UCHL5 by deoligomerizing it (PubMed:17139257, PubMed:24752541, PubMed:25702870, PubMed:25702872). Interacts with UBQLN2 and ubiquitin (PubMed:27396824).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-357874">
            <id>Q99460</id>
            <label>PSMD1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-357648">
            <id>Q13200</id>
            <label>PSMD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-359318">
            <id>P55036</id>
            <label>PSMD4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-954531">
            <id>P54727</id>
            <label>RAD23B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-3390054">
            <id>P0CG48</id>
            <label>UBC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-741480">
            <id>Q9UMX0</id>
            <label>UBQLN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-947187">
            <id>Q9UHD9</id>
            <label>UBQLN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-1051183">
            <id>Q9Y5K5</id>
            <label>UCHL5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>24</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-11749875">
            <id>Q9Y5K5-3</id>
            <label>UCHL5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-6174">
            <id>P48510</id>
            <label>DSK2</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-954387">
            <id>Q16186</id>
        </interactant>
        <interactant intactId="EBI-772796">
            <id>O35593</id>
            <label>Psmd14</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="domain">
        <text evidence="9">The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with PSMD1 and ubiquitin. Preferential binding to the proximal subunit of 'Lys-48'-linked diubiquitin allows UCHL5 access to the distal subunit.</text>
    </comment>
    <comment type="PTM">
        <text evidence="12 16">Ubiquitinated by UBE3C in response to proteotoxic stress.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the ADRM1 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="17">Although initially described as a cell membrane glycoprotein, ADRM1 is intracellular and non-glycosylated, and has probably no direct role in cell adhesion.</text>
    </comment>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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            <begin position="353"/>
            <end position="358"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="363"/>
            <end position="371"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="374"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="386"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="395"/>
            <end position="397"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9JMB5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01264"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01265"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="16815440"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="16906146"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
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    </evidence>
    <evidence type="ECO:0000269" key="10">
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    <evidence type="ECO:0000269" key="11">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="25702872"/>
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    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="27396824"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="31375563"/>
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    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="16964243"/>
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    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="19413330"/>
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    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="2KQZ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="2KR0"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="2MKZ"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="4UEM"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="29">
        <source>
            <dbReference type="PDB" id="4WLR"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="30">
        <source>
            <dbReference type="PDB" id="5V1Y"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="31">
        <source>
            <dbReference type="PDB" id="6OI4"/>
        </source>
    </evidence>
    <sequence length="407" mass="42153" checksum="2D38811DCA231864" modified="2002-01-23" version="2">MTTSGALFPSLVPGSRGASNKYLVEFRAGKMSLKGTTVTPDKRKGLVYIQQTDDSLIHFCWKDRTSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSKRLFFWMQEPKTDQDEEHCRKVNEYLNNPPMPGALGASGSSGHELSALGGEGGLQSLLGNMSHSQLMQLIGPAGLGGLGGLGALTGPGLASLLGSSGPPGSSSSSSSRSQSAAVTPSSTTSSTRATPAPSAPAAASATSPSPAPSSGNGASTAASPTQPIQLSDLQSILATMNVPAGPAGGQQVDLASVLTPEIMAPILANADVQERLLPYLPSGESLPQTADEIQNTLTSPQFQQALGMFSAALASGQLGPLMCQFGLPAEAVEAANKGDVEAFAKAMQNNAKPEQKEGDTKDKKDEEEDMSLD</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-08-21" modified="2026-01-28" version="183" xmlns="https://uniprot.org/uniprot">
    <accession>Q9H0C2</accession>
    <name>ADT4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">ADP/ATP translocase 4</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="12">ADP,ATP carrier protein 4</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="5">Adenine nucleotide translocator 4</fullName>
            <shortName evidence="5">ANT 4</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="14">Solute carrier family 25 member 31</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">Sperm flagellar energy carrier protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">SLC25A31</name>
        <name evidence="12" type="synonym">AAC4</name>
        <name evidence="5" type="synonym">ANT4</name>
        <name evidence="13" type="synonym">SFEC</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2005" name="FEBS Lett." volume="579" first="633" last="637">
            <title>A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution.</title>
            <authorList>
                <person name="Dolce V."/>
                <person name="Scarcia P."/>
                <person name="Iacopetta D."/>
                <person name="Palmieri F."/>
            </authorList>
            <dbReference type="PubMed" id="15670820"/>
            <dbReference type="DOI" id="10.1016/j.febslet.2004.12.034"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>TRANSPORT ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2007" name="Dev. Biol." volume="302" first="463" last="476">
            <title>Compartmentalization of a unique ADP/ATP carrier protein SFEC (sperm flagellar energy carrier, AAC4) with glycolytic enzymes in the fibrous sheath of the human sperm flagellar principal piece.</title>
            <authorList>
                <person name="Kim Y.-H."/>
                <person name="Haidl G."/>
                <person name="Schaefer M."/>
                <person name="Egner U."/>
                <person name="Mandal A."/>
                <person name="Herr J.C."/>
            </authorList>
            <dbReference type="PubMed" id="17137571"/>
            <dbReference type="DOI" id="10.1016/j.ydbio.2006.10.004"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2001" name="Genome Res." volume="11" first="422" last="435">
            <title>Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.</title>
            <authorList>
                <person name="Wiemann S."/>
                <person name="Weil B."/>
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                <person name="Ansorge W."/>
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                <person name="Bauersachs S."/>
                <person name="Blum H."/>
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                <person name="Duesterhoeft A."/>
                <person name="Beyer A."/>
                <person name="Koehrer K."/>
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                <person name="Ottenwaelder B."/>
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            </authorList>
            <dbReference type="PubMed" id="11230166"/>
            <dbReference type="DOI" id="10.1101/gr.gr1547r"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2005" name="Nature" volume="434" first="724" last="731">
            <title>Generation and annotation of the DNA sequences of human chromosomes 2 and 4.</title>
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                <person name="Schmutz J."/>
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                <person name="Mardis E.R."/>
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                <person name="Ovcharenko I."/>
                <person name="Furey T.S."/>
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                <person name="Eichler E.E."/>
                <person name="Bork P."/>
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                <person name="Wilson R.K."/>
            </authorList>
            <dbReference type="PubMed" id="15815621"/>
            <dbReference type="DOI" id="10.1038/nature03466"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
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                <person name="Miller J.R."/>
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                <person name="Turner R."/>
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                <person name="Shue B.C."/>
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                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="29658" last="29666">
            <title>Evolutionarily conserved mammalian adenine nucleotide translocase 4 is essential for spermatogenesis.</title>
            <authorList>
                <person name="Brower J.V."/>
                <person name="Rodic N."/>
                <person name="Seki T."/>
                <person name="Jorgensen M."/>
                <person name="Fliess N."/>
                <person name="Yachnis A.T."/>
                <person name="McCarrey J.R."/>
                <person name="Oh S.P."/>
                <person name="Terada N."/>
            </authorList>
            <dbReference type="PubMed" id="17681941"/>
            <dbReference type="DOI" id="10.1074/jbc.m704386200"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2016" name="Sci. Rep." volume="6" first="33516" last="33516">
            <title>TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.</title>
            <authorList>
                <person name="Marginedas-Freixa I."/>
                <person name="Hattab C."/>
                <person name="Bouyer G."/>
                <person name="Halle F."/>
                <person name="Chene A."/>
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                <person name="Cueff A."/>
                <person name="Schmitt M."/>
                <person name="Gamain B."/>
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            </authorList>
            <dbReference type="PubMed" id="27641616"/>
            <dbReference type="DOI" id="10.1038/srep33516"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Proc. Natl. Acad. Sci. U.S.A." volume="112" first="4062" last="4067">
            <title>Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in insulin-producing adenomas.</title>
            <authorList>
                <person name="Cromer M.K."/>
                <person name="Choi M."/>
                <person name="Nelson-Williams C."/>
                <person name="Fonseca A.L."/>
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                <person name="Korah R.M."/>
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                <person name="Mane S."/>
                <person name="Kenney B."/>
                <person name="Malchoff C.D."/>
                <person name="Stalberg P."/>
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                <person name="Westin G."/>
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                <person name="Bjoerklund P."/>
                <person name="Lifton R.P."/>
            </authorList>
            <dbReference type="PubMed" id="25787250"/>
            <dbReference type="DOI" id="10.1073/pnas.1503696112"/>
        </citation>
        <scope>VARIANT GLU-303</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 7 8">ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity) (PubMed:15670820). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). Specifically required during spermatogenesis, probably to mediate ADP:ATP exchange in spermatocytes (PubMed:17137571). Large ATP supplies from mitochondria may be critical for normal progression of spermatogenesis during early stages of meiotic prophase I, including DNA double-strand break repair and chromosomal synapsis (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A31/ANT4 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Among nucleotides, may also exchange ADP for dATP and dADP (PubMed:15670820). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (By similarity). It is however unclear if SLC25A31/ANT4 constitutes a pore-forming component of mPTP or regulates it (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>ADP(in) + ATP(out) = ADP(out) + ATP(in)</text>
            <dbReference type="Rhea" id="RHEA:34999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:35000"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="15">
            <dbReference type="Rhea" id="RHEA:35001"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>dATP(out) + ADP(in) = dATP(in) + ADP(out)</text>
            <dbReference type="Rhea" id="RHEA:73699"/>
            <dbReference type="ChEBI" id="CHEBI:61404"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:73700"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="15">
            <dbReference type="Rhea" id="RHEA:73701"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>dADP(in) + ADP(out) = dADP(out) + ADP(in)</text>
            <dbReference type="Rhea" id="RHEA:72855"/>
            <dbReference type="ChEBI" id="CHEBI:57667"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="15">
            <dbReference type="Rhea" id="RHEA:72856"/>
        </physiologicalReaction>
        <physiologicalReaction direction="right-to-left" evidence="15">
            <dbReference type="Rhea" id="RHEA:72857"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>H(+)(in) = H(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34979"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 4">The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="7">72 uM for ADP</KM>
            <KM evidence="7">120 uM for ATP</KM>
            <Vmax evidence="7">1.3 mmol/min/g enzyme for ATP:ADP exchange</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6149672">
            <id>Q9H0C2</id>
        </interactant>
        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6149672">
            <id>Q9H0C2</id>
        </interactant>
        <interactant intactId="EBI-16439278">
            <id>Q6FHY5</id>
            <label>MEOX2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Mitochondrion inner membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="11">Membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="8">Cell projection</location>
            <location evidence="8">Cilium</location>
            <location evidence="8">Flagellum membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="8 11">In sperm flagellum this protein is located in the fibrous sheath, a non-mitochondrial region (PubMed:17137571). May localize to non-mitochondrial membranes (PubMed:27641616).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="7 8 9 11">Expressed in brain, liver, sperm and testis (PubMed:15670820, PubMed:17137571). In testis, expressed at higher level in spermatocytes, while it is expressed at lower level in spermatogonial cells (PubMed:17681941). Expressed in erythrocytes (at protein level) (PubMed:27641616).</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.</text>
    </comment>
    <comment type="similarity">
        <text evidence="14">Belongs to the mitochondrial carrier (TC 2.A.29) family.</text>
    </comment>
    <dbReference type="EMBL" id="AJ863129">
        <property type="protein sequence ID" value="CAI05952.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY550240">
        <property type="protein sequence ID" value="AAT42263.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL136857">
        <property type="protein sequence ID" value="CAB66791.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC093591">
        <property type="protein sequence ID" value="AAY40974.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471056">
        <property type="protein sequence ID" value="EAX05199.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022032">
        <property type="protein sequence ID" value="AAH22032.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3733.1"/>
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        <property type="nucleotide sequence ID" value="NM_001318467.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_112581.1">
        <property type="nucleotide sequence ID" value="NM_031291.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q9H0C2"/>
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        <property type="interactions" value="67"/>
    </dbReference>
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        <property type="interactions" value="503"/>
    </dbReference>
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        <property type="interactions" value="38"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000281154"/>
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        <property type="family name" value="the mitochondrial carrier (mc) family"/>
    </dbReference>
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        <property type="antibodies" value="154 antibodies from 24 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="83447"/>
    <dbReference type="Ensembl" id="ENST00000281154.6">
        <property type="protein sequence ID" value="ENSP00000281154.4"/>
        <property type="gene ID" value="ENSG00000151475.6"/>
    </dbReference>
    <dbReference type="GeneID" id="83447"/>
    <dbReference type="KEGG" id="hsa:83447"/>
    <dbReference type="MANE-Select" id="ENST00000281154.6">
        <property type="protein sequence ID" value="ENSP00000281154.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_031291.4"/>
        <property type="RefSeq protein sequence ID" value="NP_112581.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003ifl.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25319"/>
    <dbReference type="ClinPGx" id="PA142670904"/>
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        <property type="gene designation" value="SLC25A31"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000151475">
        <property type="expression patterns" value="Tissue enriched (testis)"/>
    </dbReference>
    <dbReference type="MIM" id="610796">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000151475"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160648"/>
    <dbReference type="HOGENOM" id="CLU_015166_12_0_1"/>
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    <dbReference type="OrthoDB" id="270584at2759"/>
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        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9H0C2"/>
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    <dbReference type="Agora" id="ENSG00000151475"/>
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        <property type="hits" value="21 hits in 1147 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SLC25A31">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="SLC25A31"/>
    <dbReference type="GenomeRNAi" id="83447"/>
    <dbReference type="Pharos" id="Q9H0C2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9H0C2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9H0C2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000151475">
        <property type="expression patterns" value="Expressed in adult organism and 18 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
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        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005757">
        <property type="term" value="C:mitochondrial permeability transition pore complex"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="LIFEdb"/>
    </dbReference>
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        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005471">
        <property type="term" value="F:ATP:ADP antiporter activity"/>
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        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
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        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007141">
        <property type="term" value="P:male meiosis I"/>
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    </dbReference>
    <dbReference type="GO" id="GO:0140021">
        <property type="term" value="P:mitochondrial ADP transmembrane transport"/>
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        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990544">
        <property type="term" value="P:mitochondrial ATP transmembrane transport"/>
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        <property type="project" value="InterPro"/>
    </dbReference>
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        <property type="term" value="P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0046902">
        <property type="term" value="P:regulation of mitochondrial membrane permeability"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007283">
        <property type="term" value="P:spermatogenesis"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
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        <property type="entry name" value="Putative ADP/ATP translocase 2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="Mitochondrial carrier domain"/>
        <property type="match status" value="1"/>
    </dbReference>
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        <property type="entry name" value="ADT_euk_type"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002067">
        <property type="entry name" value="MCP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023395">
        <property type="entry name" value="MCP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018108">
        <property type="entry name" value="MCP_transmembrane"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45635">
        <property type="entry name" value="ADP,ATP CARRIER PROTEIN 1-RELATED-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45635:SF40">
        <property type="entry name" value="ADP_ATP TRANSLOCASE 4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00153">
        <property type="entry name" value="Mito_carr"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00927">
        <property type="entry name" value="ADPTRNSLCASE"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00926">
        <property type="entry name" value="MITOCARRIER"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF103506">
        <property type="entry name" value="Mitochondrial carrier"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50920">
        <property type="entry name" value="SOLCAR"/>
        <property type="match status" value="3"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0050">Antiport</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0969">Cilium</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0282">Flagellum</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0999">Mitochondrion inner membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000297624" description="ADP/ATP translocase 4">
        <location>
            <begin position="1"/>
            <end position="315"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="14">
        <location>
            <begin position="1"/>
            <end position="19"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="2">
        <location>
            <begin position="20"/>
            <end position="49"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="14">
        <location>
            <begin position="50"/>
            <end position="86"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="2">
        <location>
            <begin position="87"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="14">
        <location>
            <begin position="112"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="2">
        <location>
            <begin position="122"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="14">
        <location>
            <begin position="143"/>
            <end position="190"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="2">
        <location>
            <begin position="191"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="14">
        <location>
            <begin position="212"/>
            <end position="222"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="2">
        <location>
            <begin position="223"/>
            <end position="243"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="14">
        <location>
            <begin position="244"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="2">
        <location>
            <begin position="284"/>
            <end position="301"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="14">
        <location>
            <begin position="302"/>
            <end position="315"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 1">
        <location>
            <begin position="18"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 2">
        <location>
            <begin position="123"/>
            <end position="213"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 3">
        <location>
            <begin position="220"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for transport activity" evidence="3">
        <location>
            <begin position="247"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nucleotide carrier signature motif" evidence="2">
        <location>
            <begin position="247"/>
            <end position="252"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="92"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="104"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="247"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="sequence variant" id="VAR_074177" evidence="10">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="303"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="G2QNH0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P02722"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P12235"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P48962"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="Q3V132"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6"/>
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        <source>
            <dbReference type="PubMed" id="15670820"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="17137571"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="17681941"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="25787250"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="27641616"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="15670820"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="17137571"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000305" key="15">
        <source>
            <dbReference type="PubMed" id="15670820"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:25319"/>
        </source>
    </evidence>
    <sequence length="315" mass="35022" checksum="9ACE26062CCC9675" modified="2001-03-01" version="1">MHREPAKKKAEKRLFDASSFGKDLLAGGVAAAVSKTAVAPIERVKLLLQVQASSKQISPEARYKGMVDCLVRIPREQGFFSFWRGNLANVIRYFPTQALNFAFKDKYKQLFMSGVNKEKQFWRWFLANLASGGAAGATSLCVVYPLDFARTRLGVDIGKGPEERQFKGLGDCIMKIAKSDGIAGLYQGFGVSVQGIIVYRASYFGAYDTVKGLLPKPKKTPFLVSFFIAQVVTTCSGILSYPFDTVRRRMMMQSGEAKRQYKGTLDCFVKIYQHEGISSFFRGAFSNVLRGTGGALVLVLYDKIKEFFHIDIGGR</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1987-08-13" modified="2026-01-28" version="252" xmlns="https://uniprot.org/uniprot">
    <accession>P05141</accession>
    <accession>B2RCV1</accession>
    <accession>O43350</accession>
    <name>ADT2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="23">ADP/ATP translocase 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="21">ADP,ATP carrier protein 2</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="20">ADP,ATP carrier protein, fibroblast isoform</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="22">Adenine nucleotide translocator 2</fullName>
            <shortName>ANT 2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="23">Solute carrier family 25 member 5</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>ADP/ATP translocase 2, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="24" type="primary">SLC25A5</name>
        <name evidence="4" type="synonym">AAC2</name>
        <name evidence="22" type="synonym">ANT2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ARG-111</scope>
        <source>
            <tissue>Placenta</tissue>
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    </reference>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT ARG-111</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANT ARG-111</scope>
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                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT THR-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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        <scope>PROTEIN SEQUENCE OF 2-23; 32-43; 50-60; 64-92; 81-92; 97-106; 112-138; 172-199; 207-235; 245-259 AND 281-295</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT THR-2</scope>
        <scope>METHYLATION AT LYS-52</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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            <dbReference type="PubMed" id="2829183"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 46-297</scope>
        <source>
            <tissue>Liver</tissue>
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            <dbReference type="PubMed" id="16120388"/>
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        <scope>INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION)</scope>
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            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="19130895"/>
            <dbReference type="DOI" id="10.1016/j.biocel.2008.12.002"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH AK4</scope>
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            <dbReference type="PubMed" id="19608861"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-105 AND LYS-163</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="20797633"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2010.07.029"/>
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        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN MMXD COMPLEX</scope>
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            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <reference key="17">
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            <dbReference type="PubMed" id="21908771"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.012658"/>
        </citation>
        <scope>MALONYLATION AT LYS-23; LYS-92; LYS-96 AND LYS-147</scope>
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    <reference key="18">
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            </authorList>
            <dbReference type="PubMed" id="22223895"/>
            <dbReference type="DOI" id="10.1074/mcp.m111.015131"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
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            <title>Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.</title>
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            <dbReference type="DOI" id="10.1074/mcp.o113.027870"/>
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        <scope>METHYLATION [LARGE SCALE ANALYSIS] AT LYS-52 AND LYS-147</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Colon carcinoma</tissue>
        </source>
    </reference>
    <reference key="21">
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            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
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            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.</title>
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                <person name="Marginedas-Freixa I."/>
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            <dbReference type="PubMed" id="27641616"/>
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        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
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                <person name="Malecki J."/>
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            <dbReference type="PubMed" id="31213526"/>
            <dbReference type="DOI" id="10.1074/jbc.ra119.009045"/>
        </citation>
        <scope>METHYLATION AT LYS-52</scope>
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    <reference key="24">
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            <title>Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis.</title>
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                <person name="Namba T."/>
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                <person name="Pinson A."/>
                <person name="Xing L."/>
                <person name="Kalebic N."/>
                <person name="Wilsch-Braeuninger M."/>
                <person name="Long K.R."/>
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                <person name="Lauer J."/>
                <person name="Bogdanova A."/>
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                <person name="Wimberger P."/>
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            <dbReference type="PubMed" id="31883789"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2019.11.027"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ARHGAP11B</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 10 16">ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31883789). It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (PubMed:20797633).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>ADP(in) + ATP(out) = ADP(out) + ATP(in)</text>
            <dbReference type="Rhea" id="RHEA:34999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>H(+)(in) = H(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34979"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 4">The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 4 9 10 16">Monomer (By similarity). Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2 (PubMed:20797633). Interacts with AK4 (PubMed:19130895). Interacts with ARHGAP11B, thereby inhibiting the mitochondrial permeability transition pore (mPTP) (PubMed:31883789). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="8">(Microbial infection) Interacts with HIV-1 Vpr.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355133">
            <id>P05141</id>
        </interactant>
        <interactant intactId="EBI-21505425">
            <id>Q7Z695</id>
            <label>ADCK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355133">
            <id>P05141</id>
        </interactant>
        <interactant intactId="EBI-5323863">
            <id>Q5S007</id>
            <label>LRRK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355133">
            <id>P05141</id>
        </interactant>
        <interactant intactId="EBI-2606540">
            <id>Q9Y6E7</id>
            <label>SIRT4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-355133">
            <id>P05141</id>
        </interactant>
        <interactant intactId="EBI-713484">
            <id>Q8N357</id>
            <label>SLC35F6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Mitochondrion inner membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="13">Membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="13">May localize to non-mitochondrial membranes.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="13">Expressed in erythrocytes (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.</text>
    </comment>
    <comment type="PTM">
        <text evidence="15">Trimethylated by ANTKMT at Lys-52.</text>
    </comment>
    <comment type="similarity">
        <text evidence="23">Belongs to the mitochondrial carrier (TC 2.A.29) family.</text>
    </comment>
    <dbReference type="EMBL" id="M57424">
        <property type="protein sequence ID" value="AAA51737.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J02683">
        <property type="protein sequence ID" value="AAA35579.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L78810">
        <property type="protein sequence ID" value="AAB39266.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK315292">
        <property type="protein sequence ID" value="BAG37698.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC004000">
        <property type="protein sequence ID" value="AAB96347.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC056160">
        <property type="protein sequence ID" value="AAH56160.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03591">
        <property type="protein sequence ID" value="AAA36749.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14578.1"/>
    <dbReference type="PIR" id="A29132">
        <property type="entry name" value="A29132"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001143.2">
        <property type="nucleotide sequence ID" value="NM_001152.5"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P05141"/>
    <dbReference type="SMR" id="P05141"/>
    <dbReference type="BioGRID" id="106789">
        <property type="interactions" value="459"/>
    </dbReference>
    <dbReference type="CORUM" id="P05141"/>
    <dbReference type="DIP" id="DIP-33873N"/>
    <dbReference type="FunCoup" id="P05141">
        <property type="interactions" value="2949"/>
    </dbReference>
    <dbReference type="IntAct" id="P05141">
        <property type="interactions" value="235"/>
    </dbReference>
    <dbReference type="MINT" id="P05141"/>
    <dbReference type="STRING" id="9606.ENSP00000360671"/>
    <dbReference type="ChEMBL" id="CHEMBL3709670"/>
    <dbReference type="DrugBank" id="DB00720">
        <property type="generic name" value="Clodronic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01077">
        <property type="generic name" value="Etidronic acid"/>
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    <dbReference type="DrugCentral" id="P05141"/>
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    <keyword id="KW-0050">Antiport</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0159">Chromosome partition</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0472">Membrane</keyword>
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            <end position="298"/>
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            <end position="298"/>
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            <end position="37"/>
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            <end position="74"/>
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            <end position="130"/>
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            <end position="178"/>
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            <end position="199"/>
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            <end position="210"/>
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            <end position="231"/>
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            <end position="273"/>
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            <end position="291"/>
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            <end position="297"/>
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            <begin position="235"/>
            <end position="240"/>
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            <begin position="235"/>
            <end position="240"/>
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            <position position="80"/>
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        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
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            <position position="92"/>
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        <ligand>
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            <position position="235"/>
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        <ligand>
            <name>ADP</name>
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            <position position="2"/>
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            <position position="7"/>
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            <position position="23"/>
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            <position position="52"/>
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    </feature>
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            <position position="52"/>
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    </feature>
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            <position position="52"/>
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            <position position="96"/>
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        </location>
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        </location>
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            <position position="147"/>
        </location>
    </feature>
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            <position position="147"/>
        </location>
    </feature>
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        </location>
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            <position position="147"/>
        </location>
    </feature>
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            <position position="163"/>
        </location>
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        <location>
            <position position="166"/>
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    </feature>
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            <position position="268"/>
        </location>
    </feature>
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            <position position="268"/>
        </location>
    </feature>
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        <variation>R</variation>
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            <position position="111"/>
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    <feature type="sequence conflict" description="In Ref. 2; AAA35579." evidence="23" ref="2">
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        <location>
            <position position="6"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAG37698." evidence="23" ref="4">
        <original>K</original>
        <variation>M</variation>
        <location>
            <position position="43"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAA35579." evidence="23" ref="2">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 9; AAA36749." evidence="23" ref="9">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="G2QNH0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P02722"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P12235"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P51881"/>
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    </evidence>
    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="Q09073"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6"/>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16120388"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="19130895"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="20797633"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="2168878"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="21908771"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="27641616"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="3031073"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="31213526"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="31883789"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="8918809"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source ref="7"/>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="2168878"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="3031073"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source>
            <dbReference type="PubMed" id="8918809"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="23"/>
    <evidence type="ECO:0000312" key="24">
        <source>
            <dbReference type="HGNC" id="HGNC:10991"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="28">
        <source>
            <dbReference type="PubMed" id="24129315"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="29">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <sequence length="298" mass="32852" checksum="DC53D083E7217AFE" modified="2011-01-11" version="7">MTDAAVSFAKDFLAGGVAAAISKTAVAPIERVKLLLQVQHASKQITADKQYKGIIDCVVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDKRTQFWLYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKAGAEREFRGLGDCLVKIYKSDGIKGLYQGFNVSVQGIIIYRAAYFGIYDTAKGMLPDPKNTHIVISWMIAQTVTAVAGLTSYPFDTVRRRMMMQSGRKGTDIMYTGTLDCWRKIARDEGGKAFFKGAWSNVLRGMGGAFVLVLYDEIKKYT</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-06-10" modified="2026-01-28" version="172" xmlns="https://uniprot.org/uniprot">
    <accession>Q6ZN18</accession>
    <accession>Q59FS5</accession>
    <accession>Q6ZN62</accession>
    <accession>Q96BG3</accession>
    <name>AEBP2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Zinc finger protein AEBP2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adipocyte enhancer-binding protein 2</fullName>
            <shortName>AE-binding protein 2</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AEBP2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Ohmori Y."/>
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                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3)</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
            <tissue>Uterus</tissue>
        </source>
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            <authorList>
                <person name="Mural R.J."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Eye</tissue>
            <tissue>Uterus</tissue>
        </source>
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            <authorList>
                <person name="Totoki Y."/>
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                <person name="Ohara O."/>
                <person name="Nagase T."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 61-517 (ISOFORM 1)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2002" name="Science" volume="298" first="1039" last="1043">
            <title>Role of histone H3 lysine 27 methylation in Polycomb-group silencing.</title>
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                <person name="Cao R."/>
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                <person name="Wang H."/>
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                <person name="Erdjument-Bromage H."/>
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            </authorList>
            <dbReference type="PubMed" id="12351676"/>
            <dbReference type="DOI" id="10.1126/science.1076997"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <scope>INTERACTION WITH EED; EZH2; RBBP4; RBBP7 AND SUZ12</scope>
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    <reference key="6">
        <citation type="journal article" date="2004" name="Mol. Cell" volume="15" first="57" last="67">
            <title>SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex.</title>
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            </authorList>
            <dbReference type="PubMed" id="15225548"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2004.06.020"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SELF-ASSOCIATION</scope>
        <scope>INTERACTION WITH EED; EZH2; RBBP4 AND SUZ12</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2006" name="Cell" volume="127" first="635" last="648">
            <title>Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.</title>
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            <dbReference type="PubMed" id="17081983"/>
            <dbReference type="DOI" id="10.1016/j.cell.2006.09.026"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-24</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.</title>
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                <person name="Ballif B.A."/>
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                <person name="McDonald E.R. III"/>
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            <dbReference type="PubMed" id="17525332"/>
            <dbReference type="DOI" id="10.1126/science.1140321"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Embryonic kidney</tissue>
        </source>
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            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; SER-210 AND SER-211</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
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            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
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            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
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        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
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            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
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        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
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            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-24 AND SER-390</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
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                <person name="Rigbolt K.T."/>
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            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206 AND SER-390</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-206</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference evidence="9" key="16">
        <citation type="journal article" date="2020" name="Mol. Cell" volume="77" first="1265" last="1278.e7">
            <title>A Dimeric Structural Scaffold for PRC2-PCL Targeting to CpG Island Chromatin.</title>
            <authorList>
                <person name="Chen S."/>
                <person name="Jiao L."/>
                <person name="Liu X."/>
                <person name="Yang X."/>
                <person name="Liu X."/>
            </authorList>
            <dbReference type="PubMed" id="31959557"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2019.12.019"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>ASSOCIATION WITH THE PRC2 COMPLEX</scope>
    </reference>
    <reference evidence="10" key="17">
        <citation type="journal article" date="2018" name="Mol. Cell" volume="69" first="840" last="852.e5">
            <title>Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding.</title>
            <authorList>
                <person name="Chen S."/>
                <person name="Jiao L."/>
                <person name="Shubbar M."/>
                <person name="Yang X."/>
                <person name="Liu X."/>
            </authorList>
            <dbReference type="PubMed" id="29499137"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2018.01.039"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 407-503 IN COMPLEX WITH SUZ12; RBBP4 AND JARID2</scope>
        <scope>FUNCTION</scope>
        <scope>ASSOCIATION WITH THE PRC2 COMPLEX</scope>
        <scope>INTERACTION WITH SUZ12</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6">Acts as an accessory subunit for the core Polycomb repressive complex 2 (PRC2), which mediates histone H3K27 (H3K27me3) trimethylation on chromatin leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:29499137, PubMed:31959557). Plays a role in nucleosome localization of the PRC2 complex (PubMed:29499137).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4 5 6">Self-associates (PubMed:15225548). Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:12351676, PubMed:15225548, PubMed:29499137, PubMed:31959557). Found in a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (PubMed:29499137). Within the PRC2 complex, interacts directly with SUZ12; competes with PHF19 for SUZ12 binding (PubMed:12351676, PubMed:29499137). Interacts with EED, EZH2, and RBBP4 (PubMed:12351676, PubMed:15225548). May also interact with RBBP7 (PubMed:12351676).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-2549423">
            <id>Q6NT76</id>
            <label>HMBOX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>6</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-740738">
            <id>O95751</id>
            <label>LDOC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-724076">
            <id>Q99750</id>
            <label>MDFI</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-79165">
            <id>Q9NRD5</id>
            <label>PICK1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-947459">
            <id>Q9H2G4</id>
            <label>TSPYL2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10255023">
            <id>Q6ZN18-2</id>
        </interactant>
        <interactant intactId="EBI-347633">
            <id>Q9H9D4</id>
            <label>ZNF408</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Nucleus</location>
        </subcellularLocation>
        <text evidence="5">Localizes to chromatin as part of the PRC2 complex.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6ZN18-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6ZN18-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_034359"/>
        </isoform>
        <isoform>
            <id>Q6ZN18-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_034357 VSP_034358"/>
        </isoform>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the AEBP2/jing C2H2-type zinc-finger family.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH15624" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH22220" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="BAD18513" version="1"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="EAW96400" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AK131361">
        <property type="protein sequence ID" value="BAD18513.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK131410">
        <property type="protein sequence ID" value="BAD18557.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471094">
        <property type="protein sequence ID" value="EAW96400.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC015624">
        <property type="protein sequence ID" value="AAH15624.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022220">
        <property type="protein sequence ID" value="AAH22220.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB209384">
        <property type="protein sequence ID" value="BAD92621.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44841.1">
        <molecule id="Q6ZN18-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44842.1">
        <molecule id="Q6ZN18-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS58215.1">
        <molecule id="Q6ZN18-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001107648.1">
        <molecule id="Q6ZN18-1"/>
        <property type="nucleotide sequence ID" value="NM_001114176.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001253972.1">
        <molecule id="Q6ZN18-3"/>
        <property type="nucleotide sequence ID" value="NM_001267043.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_694939.2">
        <molecule id="Q6ZN18-2"/>
        <property type="nucleotide sequence ID" value="NM_153207.5"/>
    </dbReference>
    <dbReference type="PDB" id="5WAI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.90 A"/>
        <property type="chains" value="C/G=407-503"/>
    </dbReference>
    <dbReference type="PDB" id="5Y0U">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=258-357"/>
    </dbReference>
    <dbReference type="PDB" id="5Y1U">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.14 A"/>
        <property type="chains" value="C/D=379-390"/>
    </dbReference>
    <dbReference type="PDB" id="6C23">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="P=209-503"/>
    </dbReference>
    <dbReference type="PDB" id="6C24">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="P=209-503"/>
    </dbReference>
    <dbReference type="PDB" id="6WKR">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="P=209-503"/>
    </dbReference>
    <dbReference type="PDB" id="7KSO">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.90 A"/>
        <property type="chains" value="E=209-503"/>
    </dbReference>
    <dbReference type="PDB" id="8EQV">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.64 A"/>
        <property type="chains" value="C=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="8FYH">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="F/L=1-517"/>
    </dbReference>
    <dbReference type="PDB" id="8T9G">
        <property type="method" value="EM"/>
        <property type="resolution" value="6.20 A"/>
        <property type="chains" value="M/Y=223-517"/>
    </dbReference>
    <dbReference type="PDB" id="8TAS">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.10 A"/>
        <property type="chains" value="Y=224-517"/>
    </dbReference>
    <dbReference type="PDB" id="8TB9">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.00 A"/>
        <property type="chains" value="Y=223-517"/>
    </dbReference>
    <dbReference type="PDB" id="8VMI">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="P=223-517"/>
    </dbReference>
    <dbReference type="PDB" id="8VML">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="P=223-517"/>
    </dbReference>
    <dbReference type="PDB" id="8VNV">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="P=225-503"/>
    </dbReference>
    <dbReference type="PDB" id="8VNZ">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.50 A"/>
        <property type="chains" value="P=223-517"/>
    </dbReference>
    <dbReference type="PDB" id="9C8U">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.10 A"/>
        <property type="chains" value="F=210-503"/>
    </dbReference>
    <dbReference type="PDB" id="9DCH">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.40 A"/>
        <property type="chains" value="F/M=210-503"/>
    </dbReference>
    <dbReference type="PDBsum" id="5WAI"/>
    <dbReference type="PDBsum" id="5Y0U"/>
    <dbReference type="PDBsum" id="5Y1U"/>
    <dbReference type="PDBsum" id="6C23"/>
    <dbReference type="PDBsum" id="6C24"/>
    <dbReference type="PDBsum" id="6WKR"/>
    <dbReference type="PDBsum" id="7KSO"/>
    <dbReference type="PDBsum" id="8EQV"/>
    <dbReference type="PDBsum" id="8FYH"/>
    <dbReference type="PDBsum" id="8T9G"/>
    <dbReference type="PDBsum" id="8TAS"/>
    <dbReference type="PDBsum" id="8TB9"/>
    <dbReference type="PDBsum" id="8VMI"/>
    <dbReference type="PDBsum" id="8VML"/>
    <dbReference type="PDBsum" id="8VNV"/>
    <dbReference type="PDBsum" id="8VNZ"/>
    <dbReference type="PDBsum" id="9C8U"/>
    <dbReference type="PDBsum" id="9DCH"/>
    <dbReference type="AlphaFoldDB" id="Q6ZN18"/>
    <dbReference type="EMDB" id="EMD-21707"/>
    <dbReference type="EMDB" id="EMD-23021"/>
    <dbReference type="EMDB" id="EMD-23022"/>
    <dbReference type="EMDB" id="EMD-23103"/>
    <dbReference type="EMDB" id="EMD-28547"/>
    <dbReference type="EMDB" id="EMD-29578"/>
    <dbReference type="EMDB" id="EMD-29647"/>
    <dbReference type="EMDB" id="EMD-29656"/>
    <dbReference type="EMDB" id="EMD-41110"/>
    <dbReference type="EMDB" id="EMD-41141"/>
    <dbReference type="EMDB" id="EMD-41146"/>
    <dbReference type="EMDB" id="EMD-43357"/>
    <dbReference type="EMDB" id="EMD-43359"/>
    <dbReference type="EMDB" id="EMD-43361"/>
    <dbReference type="EMDB" id="EMD-43362"/>
    <dbReference type="EMDB" id="EMD-46722"/>
    <dbReference type="EMDB" id="EMD-46726"/>
    <dbReference type="EMDB" id="EMD-46751"/>
    <dbReference type="EMDB" id="EMD-7334"/>
    <dbReference type="EMDB" id="EMD-7335"/>
    <dbReference type="SMR" id="Q6ZN18"/>
    <dbReference type="BioGRID" id="125736">
        <property type="interactions" value="49"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2209">
        <property type="entry name" value="Polycomb repressive complex 2.2, EZH2-RBBP4 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2212">
        <property type="entry name" value="Polycomb repressive complex 2.2, EZH1-RBBP7 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2213">
        <property type="entry name" value="Polycomb repressive complex 2.2, EZH2-RBBP7 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-2330">
        <property type="entry name" value="Polycomb repressive complex 2.2, EZH1-RBBP4 variant"/>
    </dbReference>
    <dbReference type="CORUM" id="Q6ZN18"/>
    <dbReference type="DIP" id="DIP-58581N"/>
    <dbReference type="FunCoup" id="Q6ZN18">
        <property type="interactions" value="2047"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6ZN18">
        <property type="interactions" value="33"/>
    </dbReference>
    <dbReference type="MINT" id="Q6ZN18"/>
    <dbReference type="STRING" id="9606.ENSP00000381840"/>
    <dbReference type="BindingDB" id="Q6ZN18"/>
    <dbReference type="ChEMBL" id="CHEMBL3137287"/>
    <dbReference type="GlyGen" id="Q6ZN18">
        <property type="glycosylation" value="2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6ZN18"/>
    <dbReference type="PhosphoSitePlus" id="Q6ZN18"/>
    <dbReference type="BioMuta" id="AEBP2"/>
    <dbReference type="DMDM" id="190358163"/>
    <dbReference type="jPOST" id="Q6ZN18"/>
    <dbReference type="MassIVE" id="Q6ZN18"/>
    <dbReference type="PaxDb" id="9606-ENSP00000381840"/>
    <dbReference type="PeptideAtlas" id="Q6ZN18"/>
    <dbReference type="ProteomicsDB" id="67961">
        <molecule id="Q6ZN18-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="67962">
        <molecule id="Q6ZN18-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="67963">
        <molecule id="Q6ZN18-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q6ZN18"/>
    <dbReference type="Antibodypedia" id="23931">
        <property type="antibodies" value="226 antibodies from 26 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="121536"/>
    <dbReference type="Ensembl" id="ENST00000266508.14">
        <molecule id="Q6ZN18-2"/>
        <property type="protein sequence ID" value="ENSP00000266508.9"/>
        <property type="gene ID" value="ENSG00000139154.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000360995.8">
        <molecule id="Q6ZN18-3"/>
        <property type="protein sequence ID" value="ENSP00000354267.4"/>
        <property type="gene ID" value="ENSG00000139154.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000398864.7">
        <molecule id="Q6ZN18-1"/>
        <property type="protein sequence ID" value="ENSP00000381840.3"/>
        <property type="gene ID" value="ENSG00000139154.16"/>
    </dbReference>
    <dbReference type="GeneID" id="121536"/>
    <dbReference type="KEGG" id="hsa:121536"/>
    <dbReference type="MANE-Select" id="ENST00000266508.14">
        <molecule id="Q6ZN18-2"/>
        <property type="protein sequence ID" value="ENSP00000266508.9"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_153207.5"/>
        <property type="RefSeq protein sequence ID" value="NP_694939.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001ree.3">
        <molecule id="Q6ZN18-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24051"/>
    <dbReference type="ClinPGx" id="PA134875401"/>
    <dbReference type="CTD" id="121536"/>
    <dbReference type="DisGeNET" id="121536"/>
    <dbReference type="GeneCards" id="AEBP2"/>
    <dbReference type="HGNC" id="HGNC:24051">
        <property type="gene designation" value="AEBP2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000139154">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="617934">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000139154"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000139154"/>
    <dbReference type="eggNOG" id="KOG1721">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00510000048519"/>
    <dbReference type="HOGENOM" id="CLU_029789_1_0_1"/>
    <dbReference type="InParanoid" id="Q6ZN18"/>
    <dbReference type="OMA" id="FAENICL"/>
    <dbReference type="OrthoDB" id="9984614at2759"/>
    <dbReference type="PAN-GO" id="Q6ZN18">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6ZN18"/>
    <dbReference type="PathwayCommons" id="Q6ZN18"/>
    <dbReference type="Reactome" id="R-HSA-212300">
        <property type="pathway name" value="PRC2 methylates histones and DNA"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-3214841">
        <property type="pathway name" value="PKMTs methylate histone lysines"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q6ZN18"/>
    <dbReference type="SIGNOR" id="Q6ZN18"/>
    <dbReference type="Agora" id="ENSG00000139154"/>
    <dbReference type="BioGRID-ORCS" id="121536">
        <property type="hits" value="28 hits in 1168 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="F701F3BC">
        <property type="entry name" value="PcG body"/>
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    <dbReference type="ChiTaRS" id="AEBP2">
        <property type="organism name" value="human"/>
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    <dbReference type="GenomeRNAi" id="121536"/>
    <dbReference type="Pharos" id="Q6ZN18">
        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:Q6ZN18"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
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    <dbReference type="RNAct" id="Q6ZN18">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000139154">
        <property type="expression patterns" value="Expressed in calcaneal tendon and 188 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6ZN18">
        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="C:chromatin"/>
        <property type="evidence" value="ECO:0000247"/>
        <property type="project" value="NTNU_SB"/>
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    <dbReference type="GO" id="GO:0035098">
        <property type="term" value="C:ESC/E(Z) complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="F:transcription coregulator activity"/>
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        <property type="project" value="Ensembl"/>
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        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0006325">
        <property type="term" value="P:chromatin organization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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        <property type="term" value="P:negative regulation of transcription by RNA polymerase II"/>
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        <property type="term" value="P:regulation of transcription by RNA polymerase II"/>
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        <property type="entry name" value="Znf_C2H2_sf"/>
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        <property type="entry name" value="Znf_C2H2_type"/>
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        <property type="entry name" value="SH3_AEBP2_C"/>
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        <property type="entry name" value="ZnF_C2H2"/>
        <property type="match status" value="3"/>
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        <property type="entry name" value="beta-beta-alpha zinc fingers"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="ZINC_FINGER_C2H2_2"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0156">Chromatin regulator</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0678">Repressor</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="initiator methionine" description="Removed" evidence="13 15 17">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000341590" description="Zinc finger protein AEBP2">
        <location>
            <begin position="2"/>
            <end position="517"/>
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    </feature>
    <feature type="zinc finger region" description="C2H2-type 1" evidence="1">
        <location>
            <begin position="261"/>
            <end position="286"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 2; degenerate" evidence="1">
        <location>
            <begin position="300"/>
            <end position="322"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2H2-type 3" evidence="1">
        <location>
            <begin position="328"/>
            <end position="352"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="1"/>
            <end position="229"/>
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    </feature>
    <feature type="region of interest" description="Interaction with RBBP4">
        <location>
            <begin position="209"/>
            <end position="294"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="352"/>
            <end position="394"/>
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    </feature>
    <feature type="region of interest" description="Interaction with SUZ12" evidence="5">
        <location>
            <begin position="407"/>
            <end position="478"/>
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    </feature>
    <feature type="region of interest" description="Important for nucleosome binding activity of the PRC2 complex" evidence="5">
        <location>
            <begin position="495"/>
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    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="2">
        <location>
            <begin position="36"/>
            <end position="51"/>
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    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="2">
        <location>
            <begin position="61"/>
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    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="2">
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            <begin position="94"/>
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    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="2">
        <location>
            <begin position="122"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="152"/>
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    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="2">
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            <begin position="166"/>
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    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="2">
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            <begin position="185"/>
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            <begin position="352"/>
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    <feature type="compositionally biased region" description="Basic residues" evidence="2">
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            <begin position="377"/>
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    <feature type="modified residue" description="N-acetylalanine" evidence="13 15 17">
        <location>
            <position position="2"/>
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            <position position="18"/>
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            <position position="24"/>
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            <position position="141"/>
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            <position position="206"/>
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            <position position="210"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="12">
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            <position position="211"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="15 16">
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            <position position="390"/>
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        <location>
            <begin position="1"/>
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    <feature type="splice variant" id="VSP_034358" description="In isoform 3." evidence="7">
        <original>SRMDSED</original>
        <variation>MYTRRYS</variation>
        <location>
            <begin position="217"/>
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    <feature type="splice variant" id="VSP_034359" description="In isoform 2." evidence="8">
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            <begin position="504"/>
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    <feature type="helix" evidence="21">
        <location>
            <begin position="288"/>
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    <feature type="strand" evidence="21">
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            <begin position="292"/>
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            <begin position="312"/>
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    <feature type="strand" evidence="20">
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        <location>
            <begin position="342"/>
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        <location>
            <begin position="415"/>
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    <feature type="turn" evidence="19">
        <location>
            <begin position="421"/>
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    <feature type="strand" evidence="19">
        <location>
            <begin position="427"/>
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    <feature type="strand" evidence="19">
        <location>
            <begin position="455"/>
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    <feature type="strand" evidence="19">
        <location>
            <begin position="460"/>
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    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="464"/>
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    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="471"/>
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        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="477"/>
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    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="482"/>
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    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="486"/>
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    </feature>
    <feature type="helix" evidence="21">
        <location>
            <begin position="490"/>
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    <feature type="strand" evidence="19">
        <location>
            <begin position="496"/>
            <end position="499"/>
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    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00042"/>
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    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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        <source>
            <dbReference type="PubMed" id="12351676"/>
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        <source>
            <dbReference type="PubMed" id="15225548"/>
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            <dbReference type="PubMed" id="14702039"/>
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            <dbReference type="PubMed" id="17081983"/>
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            <dbReference type="PubMed" id="18669648"/>
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    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="19413330"/>
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        <source>
            <dbReference type="PubMed" id="19690332"/>
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    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="20068231"/>
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        <source>
            <dbReference type="PubMed" id="21406692"/>
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        <source>
            <dbReference type="PubMed" id="22814378"/>
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    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="5WAI"/>
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    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="5Y0U"/>
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        <source>
            <dbReference type="PDB" id="6WKR"/>
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    <sequence length="517" mass="54467" checksum="6C59888ACEE4F9AF" modified="2008-06-10" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-05-10" modified="2026-01-28" version="152" xmlns="https://uniprot.org/uniprot">
    <accession>Q96IZ2</accession>
    <accession>B2R7T9</accession>
    <accession>B4DV39</accession>
    <accession>Q5THW1</accession>
    <name>ADTRP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Androgen-dependent TFPI-regulating protein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="5">Fatty acid esters of hydroxy fatty acids hydrolase ADTRP</fullName>
            <shortName evidence="5">FAHFA hydrolase ADTRP</shortName>
            <ecNumber evidence="3">3.1.-.-</ecNumber>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADTRP</name>
        <name type="synonym">C6orf105</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
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                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
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                <person name="Itoh T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Colon</tissue>
            <tissue>Small intestine</tissue>
        </source>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="14574404"/>
            <dbReference type="DOI" id="10.1038/nature02055"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
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            <authorList>
                <person name="Mural R.J."/>
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                <person name="Walenz B."/>
                <person name="Shatkay H."/>
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                <person name="Miller J.R."/>
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                <person name="Fasulo D."/>
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                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
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                <person name="Reinert K."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Bone marrow</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="Blood" volume="118" first="4463" last="4471">
            <title>Novel protein ADTRP regulates TFPI expression and function in human endothelial cells in normal conditions and in response to androgen.</title>
            <authorList>
                <person name="Lupu C."/>
                <person name="Zhu H."/>
                <person name="Popescu N.I."/>
                <person name="Wren J.D."/>
                <person name="Lupu F."/>
            </authorList>
            <dbReference type="PubMed" id="21868574"/>
            <dbReference type="DOI" id="10.1182/blood-2011-05-355370"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2016" name="Nat. Chem. Biol." volume="12" first="367" last="372">
            <title>AIG1 and ADTRP are atypical integral membrane hydrolases that degrade bioactive FAHFAs.</title>
            <authorList>
                <person name="Parsons W.H."/>
                <person name="Kolar M.J."/>
                <person name="Kamat S.S."/>
                <person name="Cognetta A.B. III"/>
                <person name="Hulce J.J."/>
                <person name="Saez E."/>
                <person name="Kahn B.B."/>
                <person name="Saghatelian A."/>
                <person name="Cravatt B.F."/>
            </authorList>
            <dbReference type="PubMed" id="27018888"/>
            <dbReference type="DOI" id="10.1038/nchembio.2051"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TOPOLOGY MODEL</scope>
        <scope>SITE</scope>
        <scope>MUTAGENESIS OF THR-47 AND HIS-131</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3">Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids (PubMed:27018888). Show a preference for FAHFAs with branching distal from the carboxylate head group of the lipids (PubMed:27018888). Regulates the expression and the cell-associated anticoagulant activity of the inhibitor TFPI in endothelial cells (in vitro) (PubMed:21868574).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>9-hexadecanoyloxy-octadecanoate + H2O = 9-hydroxy-octadecanoate + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52052"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:83670"/>
            <dbReference type="ChEBI" id="CHEBI:136286"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52053"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>12-hexadecanoyloxy-octadecanoate + H2O = 12-hydroxyoctadecanoate + hexadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52056"/>
            <dbReference type="ChEBI" id="CHEBI:7896"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:83677"/>
            <dbReference type="ChEBI" id="CHEBI:84201"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52057"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>9-(9Z-hexadecenoyloxy)-octadecanoate + H2O = (9Z)-hexadecenoate + 9-hydroxy-octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52068"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:136286"/>
            <dbReference type="ChEBI" id="CHEBI:136309"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52069"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>12-(9Z-hexadecenoyloxy)-octadecanoate + H2O = 12-hydroxyoctadecanoate + (9Z)-hexadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52072"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:84201"/>
            <dbReference type="ChEBI" id="CHEBI:136312"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52073"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>13-(9Z-hexadecenoyloxy)-octadecanoate + H2O = 13-hydroxy-octadecanoate + (9Z)-hexadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52076"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:32372"/>
            <dbReference type="ChEBI" id="CHEBI:136304"/>
            <dbReference type="ChEBI" id="CHEBI:136315"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52077"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>9-octadecanoyloxy-octadecanoate + H2O = 9-hydroxy-octadecanoate + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52096"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:136286"/>
            <dbReference type="ChEBI" id="CHEBI:136373"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52097"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>12-octadecanoyloxy-octadecanoate + H2O = 12-hydroxyoctadecanoate + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52080"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:84201"/>
            <dbReference type="ChEBI" id="CHEBI:136330"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52081"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>13-octadecanoyloxy-octadecanoate + H2O = 13-hydroxy-octadecanoate + octadecanoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52084"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:25629"/>
            <dbReference type="ChEBI" id="CHEBI:136304"/>
            <dbReference type="ChEBI" id="CHEBI:136335"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52085"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>9-(9Z-octadecenoyloxy)-octadecanoate + H2O = 9-hydroxy-octadecanoate + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52048"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:136282"/>
            <dbReference type="ChEBI" id="CHEBI:136286"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52049"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>12-(9Z-octadecenoyloxy)-octadecanoate + H2O = 12-hydroxyoctadecanoate + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52060"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:84201"/>
            <dbReference type="ChEBI" id="CHEBI:136302"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52061"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>13-(9Z-octadecenoyloxy)-octadecanoate + H2O = 13-hydroxy-octadecanoate + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52064"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:136303"/>
            <dbReference type="ChEBI" id="CHEBI:136304"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52065"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>5-(9Z-octadecenoyloxy)-octadecanoate + H2O = 5-hydroxy-octadecanoate + (9Z)-octadecenoate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:52100"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30823"/>
            <dbReference type="ChEBI" id="CHEBI:136370"/>
            <dbReference type="ChEBI" id="CHEBI:136389"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:52101"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="3">Inhibited by N-hydroxyhydantoin carbamate JJH260 and beta-lactone KC01.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3921528">
            <id>Q96IZ2</id>
        </interactant>
        <interactant intactId="EBI-2807956">
            <id>Q96FZ5</id>
            <label>CMTM7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3921528">
            <id>Q96IZ2</id>
        </interactant>
        <interactant intactId="EBI-11603430">
            <id>Q6PL24</id>
            <label>TMED8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 3">Cell membrane</location>
            <topology evidence="1">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="2">Colocalized with TFPI and CAV1 in lipid rafts.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96IZ2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96IZ2-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041965"/>
        </isoform>
        <isoform>
            <id>Q96IZ2-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_042868"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2">Expressed in cultured endothelial cells and in placenta.</text>
    </comment>
    <comment type="induction">
        <text evidence="2">By androgens.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the AIG1 family.</text>
    </comment>
    <dbReference type="EC" id="3.1.-.-" evidence="3"/>
    <dbReference type="EMBL" id="AK313114">
        <property type="protein sequence ID" value="BAG35936.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK300919">
        <property type="protein sequence ID" value="BAG62551.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL022724">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471087">
        <property type="protein sequence ID" value="EAW55304.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471087">
        <property type="protein sequence ID" value="EAW55306.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007011">
        <property type="protein sequence ID" value="AAH07011.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4521.1">
        <molecule id="Q96IZ2-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS47374.1">
        <molecule id="Q96IZ2-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001137420.1">
        <molecule id="Q96IZ2-2"/>
        <property type="nucleotide sequence ID" value="NM_001143948.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_116133.1">
        <molecule id="Q96IZ2-1"/>
        <property type="nucleotide sequence ID" value="NM_032744.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011513258.1">
        <molecule id="Q96IZ2-3"/>
        <property type="nucleotide sequence ID" value="XM_011514956.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212560.1">
        <molecule id="Q96IZ2-3"/>
        <property type="nucleotide sequence ID" value="XM_054356585.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212561.1">
        <molecule id="Q96IZ2-3"/>
        <property type="nucleotide sequence ID" value="XM_054356586.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212562.1">
        <molecule id="Q96IZ2-3"/>
        <property type="nucleotide sequence ID" value="XM_054356587.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212563.1">
        <molecule id="Q96IZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054356588.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212564.1">
        <molecule id="Q96IZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054356589.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212565.1">
        <molecule id="Q96IZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054356590.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054212566.1">
        <molecule id="Q96IZ2-1"/>
        <property type="nucleotide sequence ID" value="XM_054356591.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96IZ2"/>
    <dbReference type="BioGRID" id="124285">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96IZ2">
        <property type="interactions" value="22"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96IZ2">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="MINT" id="Q96IZ2"/>
    <dbReference type="STRING" id="9606.ENSP00000229583"/>
    <dbReference type="BindingDB" id="Q96IZ2"/>
    <dbReference type="SwissLipids" id="SLP:000001683"/>
    <dbReference type="iPTMnet" id="Q96IZ2"/>
    <dbReference type="PhosphoSitePlus" id="Q96IZ2"/>
    <dbReference type="BioMuta" id="ADTRP"/>
    <dbReference type="DMDM" id="83286865"/>
    <dbReference type="PaxDb" id="9606-ENSP00000229583"/>
    <dbReference type="PeptideAtlas" id="Q96IZ2"/>
    <dbReference type="ProteomicsDB" id="76871">
        <molecule id="Q96IZ2-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76872">
        <molecule id="Q96IZ2-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="76873">
        <molecule id="Q96IZ2-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="63585">
        <property type="antibodies" value="3 antibodies from 3 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84830"/>
    <dbReference type="Ensembl" id="ENST00000229583.9">
        <molecule id="Q96IZ2-2"/>
        <property type="protein sequence ID" value="ENSP00000229583.5"/>
        <property type="gene ID" value="ENSG00000111863.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000414691.8">
        <molecule id="Q96IZ2-1"/>
        <property type="protein sequence ID" value="ENSP00000404416.2"/>
        <property type="gene ID" value="ENSG00000111863.14"/>
    </dbReference>
    <dbReference type="GeneID" id="84830"/>
    <dbReference type="KEGG" id="hsa:84830"/>
    <dbReference type="MANE-Select" id="ENST00000414691.8">
        <property type="protein sequence ID" value="ENSP00000404416.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032744.4"/>
        <property type="RefSeq protein sequence ID" value="NP_116133.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003nab.4">
        <molecule id="Q96IZ2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:21214"/>
    <dbReference type="ClinPGx" id="PA134981312"/>
    <dbReference type="CTD" id="84830"/>
    <dbReference type="DisGeNET" id="84830"/>
    <dbReference type="GeneCards" id="ADTRP"/>
    <dbReference type="HGNC" id="HGNC:21214">
        <property type="gene designation" value="ADTRP"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000111863">
        <property type="expression patterns" value="Tissue enhanced (choroid plexus, intestine, parathyroid gland)"/>
    </dbReference>
    <dbReference type="MIM" id="614348">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000111863"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000111863"/>
    <dbReference type="eggNOG" id="KOG3989">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158284"/>
    <dbReference type="HOGENOM" id="CLU_073346_2_0_1"/>
    <dbReference type="InParanoid" id="Q96IZ2"/>
    <dbReference type="OMA" id="AFFPPWI"/>
    <dbReference type="OrthoDB" id="1898221at2759"/>
    <dbReference type="PAN-GO" id="Q96IZ2">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96IZ2"/>
    <dbReference type="PathwayCommons" id="Q96IZ2"/>
    <dbReference type="SignaLink" id="Q96IZ2"/>
    <dbReference type="Agora" id="ENSG00000111863"/>
    <dbReference type="BioGRID-ORCS" id="84830">
        <property type="hits" value="9 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ADTRP">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84830"/>
    <dbReference type="Pharos" id="Q96IZ2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96IZ2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96IZ2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000111863">
        <property type="expression patterns" value="Expressed in sperm and 155 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96IZ2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005901">
        <property type="term" value="C:caveola"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009986">
        <property type="term" value="C:cell surface"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0012505">
        <property type="term" value="C:endomembrane system"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016787">
        <property type="term" value="F:hydrolase activity"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002042">
        <property type="term" value="P:cell migration involved in sprouting angiogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140052">
        <property type="term" value="P:cellular response to oxidised low-density lipoprotein particle stimulus"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071383">
        <property type="term" value="P:cellular response to steroid hormone stimulus"/>
        <property type="evidence" value="ECO:0000270"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042758">
        <property type="term" value="P:long-chain fatty acid catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030195">
        <property type="term" value="P:negative regulation of blood coagulation"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003332">
        <property type="term" value="P:negative regulation of extracellular matrix constituent secretion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:1903038">
        <property type="term" value="P:negative regulation of leukocyte cell-cell adhesion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002686">
        <property type="term" value="P:negative regulation of leukocyte migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:2000402">
        <property type="term" value="P:negative regulation of lymphocyte migration"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0050709">
        <property type="term" value="P:negative regulation of protein secretion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010628">
        <property type="term" value="P:positive regulation of gene expression"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051897">
        <property type="term" value="P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR006838">
        <property type="entry name" value="ADTRP_AIG1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10989:SF17">
        <property type="entry name" value="ANDROGEN-DEPENDENT TFPI-REGULATING PROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10989">
        <property type="entry name" value="ANDROGEN-INDUCED PROTEIN 1-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04750">
        <property type="entry name" value="Far-17a_AIG1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1003">Cell membrane</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000190100" description="Androgen-dependent TFPI-regulating protein">
        <location>
            <begin position="1"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="7">
        <location>
            <begin position="1"/>
            <end position="3"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="4"/>
            <end position="24"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="7">
        <location>
            <begin position="25"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="47"/>
            <end position="67"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="7">
        <location>
            <begin position="68"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="86"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="7">
        <location>
            <begin position="107"/>
            <end position="119"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="120"/>
            <end position="140"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="7">
        <location>
            <begin position="141"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="155"/>
            <end position="175"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="7">
        <location>
            <begin position="176"/>
            <end position="189"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="1">
        <location>
            <begin position="190"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="7">
        <location>
            <begin position="211"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="site" description="Important for catalytic activity" evidence="3">
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="site" description="Important for catalytic activity" evidence="3">
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_041965" description="In isoform 2." evidence="4">
        <original>L</original>
        <variation>LKNRTAGFDIYQPGSFRQL</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_042868" description="In isoform 3." evidence="6">
        <original>GDMRQPRKKRK</original>
        <variation>VSVQILQRWRLESVGICFQWPDWKSPAKHQLVKNIR</variation>
        <location>
            <begin position="220"/>
            <end position="230"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_024365" description="In dbSNP:rs2076185.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of hydrolase activity." evidence="3">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Loss of hydrolase activity." evidence="3">
        <original>H</original>
        <variation>A</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="21868574"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="27018888"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="27018888"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <evidence type="ECO:0000305" key="7">
        <source>
            <dbReference type="PubMed" id="27018888"/>
        </source>
    </evidence>
    <sequence length="230" mass="26842" checksum="49B964B41C381360" modified="2001-12-01" version="1">MTKTSTCIYHFLVLSWYTFLNYYISQEGKDEVKPKILANGARWKYMTLLNLLLQTIFYGVTCLDDVLKRTKGGKDIKFLTAFRDLLFTTLAFPVSTFVFLAFWILFLYNRDLIYPKVLDTVIPVWLNHAMHTFIFPITLAEVVLRPHSYPSKKTGLTLLAAASIAYISRILWLYFETGTWVYPVFAKLSLLGLAAFFSLSYVFIASIYLLGEKLNHWKWGDMRQPRKKRK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-05-15" modified="2026-01-28" version="146" xmlns="https://uniprot.org/uniprot">
    <accession>Q6UXC1</accession>
    <accession>A2A3D4</accession>
    <accession>B0QZ81</accession>
    <accession>Q5T5S2</accession>
    <accession>Q8NCX7</accession>
    <name>AEGP_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Apical endosomal glycoprotein</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>MAM domain-containing protein 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">MAMDC4</name>
        <name type="synonym">AEGP</name>
        <name type="ORF">UNQ3001/PRO9742</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference evidence="14 15" key="1">
        <citation type="journal article" date="2003" name="Genome Res." volume="13" first="2265" last="2270">
            <title>The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.</title>
            <authorList>
                <person name="Clark H.F."/>
                <person name="Gurney A.L."/>
                <person name="Abaya E."/>
                <person name="Baker K."/>
                <person name="Baldwin D.T."/>
                <person name="Brush J."/>
                <person name="Chen J."/>
                <person name="Chow B."/>
                <person name="Chui C."/>
                <person name="Crowley C."/>
                <person name="Currell B."/>
                <person name="Deuel B."/>
                <person name="Dowd P."/>
                <person name="Eaton D."/>
                <person name="Foster J.S."/>
                <person name="Grimaldi C."/>
                <person name="Gu Q."/>
                <person name="Hass P.E."/>
                <person name="Heldens S."/>
                <person name="Huang A."/>
                <person name="Kim H.S."/>
                <person name="Klimowski L."/>
                <person name="Jin Y."/>
                <person name="Johnson S."/>
                <person name="Lee J."/>
                <person name="Lewis L."/>
                <person name="Liao D."/>
                <person name="Mark M.R."/>
                <person name="Robbie E."/>
                <person name="Sanchez C."/>
                <person name="Schoenfeld J."/>
                <person name="Seshagiri S."/>
                <person name="Simmons L."/>
                <person name="Singh J."/>
                <person name="Smith V."/>
                <person name="Stinson J."/>
                <person name="Vagts A."/>
                <person name="Vandlen R.L."/>
                <person name="Watanabe C."/>
                <person name="Wieand D."/>
                <person name="Woods K."/>
                <person name="Xie M.-H."/>
                <person name="Yansura D.G."/>
                <person name="Yi S."/>
                <person name="Yu G."/>
                <person name="Yuan J."/>
                <person name="Zhang M."/>
                <person name="Zhang Z."/>
                <person name="Goddard A.D."/>
                <person name="Wood W.I."/>
                <person name="Godowski P.J."/>
                <person name="Gray A.M."/>
            </authorList>
            <dbReference type="PubMed" id="12975309"/>
            <dbReference type="DOI" id="10.1101/gr.1293003"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>VARIANT GLY-987</scope>
    </reference>
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            <dbReference type="PubMed" id="15164053"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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            <authorList>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 725-1216 (ISOFORM 3)</scope>
        <scope>VARIANT GLY-987</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
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            <dbReference type="PubMed" id="16959974"/>
            <dbReference type="DOI" id="10.1126/science.1133427"/>
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        <scope>VARIANTS [LARGE SCALE ANALYSIS] THR-244 AND TRP-1174</scope>
    </reference>
    <comment type="function">
        <text evidence="3">Probably involved in the sorting and selective transport of receptors and ligands across polarized epithelia.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Membrane</location>
            <topology evidence="1">Single-pass type I membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6UXC1-1</id>
            <name evidence="9">1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6UXC1-2</id>
            <name evidence="8">2</name>
            <sequence type="described" ref="VSP_052395"/>
        </isoform>
        <isoform>
            <id>Q6UXC1-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_026431 VSP_026432"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>Gene prediction based on similarity to rat ortholog.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="14">May be due to intron retention.</text>
    </comment>
    <dbReference type="EMBL" id="AY358419">
        <property type="protein sequence ID" value="AAQ88785.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL355987">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471090">
        <property type="protein sequence ID" value="EAW88294.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL834531">
        <property type="protein sequence ID" value="CAD39187.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7010.1">
        <molecule id="Q6UXC1-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_996803.2">
        <molecule id="Q6UXC1-2"/>
        <property type="nucleotide sequence ID" value="NM_206920.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q6UXC1"/>
    <dbReference type="SMR" id="Q6UXC1"/>
    <dbReference type="BioGRID" id="127643">
        <property type="interactions" value="157"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q6UXC1">
        <property type="interactions" value="295"/>
    </dbReference>
    <dbReference type="IntAct" id="Q6UXC1">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000319388"/>
    <dbReference type="GlyCosmos" id="Q6UXC1">
        <property type="glycosylation" value="6 sites, No reported glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q6UXC1">
        <property type="glycosylation" value="9 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q6UXC1"/>
    <dbReference type="PhosphoSitePlus" id="Q6UXC1"/>
    <dbReference type="BioMuta" id="MAMDC4"/>
    <dbReference type="DMDM" id="147742916"/>
    <dbReference type="MassIVE" id="Q6UXC1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000319388"/>
    <dbReference type="PeptideAtlas" id="Q6UXC1"/>
    <dbReference type="ProteomicsDB" id="67588">
        <molecule id="Q6UXC1-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="67589">
        <molecule id="Q6UXC1-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="67590">
        <molecule id="Q6UXC1-3"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="64043">
        <property type="antibodies" value="9 antibodies from 7 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="158056"/>
    <dbReference type="Ensembl" id="ENST00000317446.7">
        <molecule id="Q6UXC1-2"/>
        <property type="protein sequence ID" value="ENSP00000319388.2"/>
        <property type="gene ID" value="ENSG00000177943.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000445819.5">
        <molecule id="Q6UXC1-1"/>
        <property type="protein sequence ID" value="ENSP00000411339.1"/>
        <property type="gene ID" value="ENSG00000177943.15"/>
    </dbReference>
    <dbReference type="GeneID" id="158056"/>
    <dbReference type="KEGG" id="hsa:158056"/>
    <dbReference type="MANE-Select" id="ENST00000317446.7">
        <molecule id="Q6UXC1-2"/>
        <property type="protein sequence ID" value="ENSP00000319388.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_206920.3"/>
        <property type="RefSeq protein sequence ID" value="NP_996803.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004cjs.4">
        <molecule id="Q6UXC1-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24083"/>
    <dbReference type="ClinPGx" id="PA142671487"/>
    <dbReference type="CTD" id="158056"/>
    <dbReference type="DisGeNET" id="158056"/>
    <dbReference type="GeneCards" id="MAMDC4"/>
    <dbReference type="HGNC" id="HGNC:24083">
        <property type="gene designation" value="MAMDC4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000177943">
        <property type="expression patterns" value="Tissue enhanced (brain, liver)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000177943"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000177943"/>
    <dbReference type="eggNOG" id="KOG1095">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162046"/>
    <dbReference type="HOGENOM" id="CLU_008233_0_0_1"/>
    <dbReference type="InParanoid" id="Q6UXC1"/>
    <dbReference type="OMA" id="DLCGWYQ"/>
    <dbReference type="OrthoDB" id="8847287at2759"/>
    <dbReference type="PAN-GO" id="Q6UXC1">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6UXC1"/>
    <dbReference type="PathwayCommons" id="Q6UXC1"/>
    <dbReference type="SignaLink" id="Q6UXC1"/>
    <dbReference type="Agora" id="ENSG00000177943"/>
    <dbReference type="BioGRID-ORCS" id="158056">
        <property type="hits" value="19 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="158056"/>
    <dbReference type="Pharos" id="Q6UXC1">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6UXC1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 9"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6UXC1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000177943">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 105 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6UXC1">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007399">
        <property type="term" value="P:nervous system development"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0015031">
        <property type="term" value="P:protein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd00112">
        <property type="entry name" value="LDLa"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="CDD" id="cd06263">
        <property type="entry name" value="MAM"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.120.200">
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="Gene3D" id="4.10.400.10">
        <property type="entry name" value="Low-density Lipoprotein Receptor"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013320">
        <property type="entry name" value="ConA-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036055">
        <property type="entry name" value="LDL_receptor-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023415">
        <property type="entry name" value="LDLR_class-A_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002172">
        <property type="entry name" value="LDrepeatLR_classA_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000998">
        <property type="entry name" value="MAM_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051560">
        <property type="entry name" value="MAM_domain-containing"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23282:SF129">
        <property type="entry name" value="APICAL ENDOSOMAL GLYCOPROTEIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23282">
        <property type="entry name" value="APICAL ENDOSOMAL GLYCOPROTEIN PRECURSOR"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00057">
        <property type="entry name" value="Ldl_recept_a"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00629">
        <property type="entry name" value="MAM"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00261">
        <property type="entry name" value="LDLRECEPTOR"/>
    </dbReference>
    <dbReference type="SMART" id="SM00192">
        <property type="entry name" value="LDLa"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="SMART" id="SM00137">
        <property type="entry name" value="MAM"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF49899">
        <property type="entry name" value="Concanavalin A-like lectins/glucanases"/>
        <property type="match status" value="6"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57424">
        <property type="entry name" value="LDL receptor-like module"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS01209">
        <property type="entry name" value="LDLRA_1"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50068">
        <property type="entry name" value="LDLRA_2"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50060">
        <property type="entry name" value="MAM_2"/>
        <property type="match status" value="6"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-1015">Disulfide bond</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="signal peptide" evidence="4">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000286578" description="Apical endosomal glycoprotein">
        <location>
            <begin position="23"/>
            <end position="1216"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="4">
        <location>
            <begin position="23"/>
            <end position="1151"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="4">
        <location>
            <begin position="1152"/>
            <end position="1172"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="4">
        <location>
            <begin position="1173"/>
            <end position="1216"/>
        </location>
    </feature>
    <feature type="domain" description="LDL-receptor class A 1; truncated" evidence="5">
        <location>
            <begin position="26"/>
            <end position="53"/>
        </location>
    </feature>
    <feature type="domain" description="MAM 1" evidence="6">
        <location>
            <begin position="64"/>
            <end position="222"/>
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    </feature>
    <feature type="domain" description="LDL-receptor class A 2" evidence="5">
        <location>
            <begin position="228"/>
            <end position="266"/>
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    </feature>
    <feature type="domain" description="MAM 2" evidence="6">
        <location>
            <begin position="269"/>
            <end position="425"/>
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    </feature>
    <feature type="domain" description="LDL-receptor class A 3" evidence="5">
        <location>
            <begin position="456"/>
            <end position="491"/>
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    <feature type="domain" description="MAM 3" evidence="6">
        <location>
            <begin position="491"/>
            <end position="644"/>
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        <location>
            <begin position="654"/>
            <end position="809"/>
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    </feature>
    <feature type="domain" description="MAM 5" evidence="6">
        <location>
            <begin position="811"/>
            <end position="969"/>
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    <feature type="domain" description="MAM 6" evidence="6">
        <location>
            <begin position="971"/>
            <end position="1138"/>
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    <feature type="region of interest" description="Disordered" evidence="7">
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            <begin position="280"/>
            <end position="307"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="7">
        <location>
            <begin position="429"/>
            <end position="455"/>
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    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="7">
        <location>
            <begin position="434"/>
            <end position="449"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="203"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="281"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="339"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="636"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="4">
        <location>
            <position position="835"/>
        </location>
    </feature>
    <feature type="disulfide bond" evidence="2 5">
        <location>
            <begin position="229"/>
            <end position="241"/>
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    <feature type="disulfide bond" evidence="2 5">
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            <begin position="236"/>
            <end position="254"/>
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    </feature>
    <feature type="disulfide bond" evidence="2 5">
        <location>
            <begin position="248"/>
            <end position="265"/>
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    </feature>
    <feature type="disulfide bond" evidence="2 5">
        <location>
            <begin position="457"/>
            <end position="468"/>
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    <feature type="disulfide bond" evidence="2 5">
        <location>
            <begin position="464"/>
            <end position="481"/>
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    </feature>
    <feature type="disulfide bond" evidence="2 5">
        <location>
            <begin position="475"/>
            <end position="490"/>
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    </feature>
    <feature type="splice variant" id="VSP_052395" description="In isoform 2." evidence="12">
        <location>
            <begin position="573"/>
            <end position="651"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026431" description="In isoform 3." evidence="13">
        <original>VFEAVAAGVAHSYVALDDL</original>
        <variation>SAGWGAPPPPPPPRAAWTR</variation>
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            <begin position="942"/>
            <end position="960"/>
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    </feature>
    <feature type="splice variant" id="VSP_026432" description="In isoform 3." evidence="13">
        <location>
            <begin position="961"/>
            <end position="1216"/>
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    <feature type="sequence variant" id="VAR_035778" description="In a breast cancer sample; somatic mutation; dbSNP:rs755530502." evidence="10">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032128" description="In dbSNP:rs2275156." evidence="8 11">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="987"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_035779" description="In a breast cancer sample; somatic mutation; dbSNP:rs138623341." evidence="10">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="1174"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P01130"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q63191"/>
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    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00124"/>
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    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00128"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="7">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12975309"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="15164053"/>
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    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="11">
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            <dbReference type="PubMed" id="17974005"/>
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    <evidence type="ECO:0000303" key="12">
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            <dbReference type="PubMed" id="12975309"/>
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    <evidence type="ECO:0000303" key="13">
        <source>
            <dbReference type="PubMed" id="17974005"/>
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    </evidence>
    <evidence type="ECO:0000305" key="14"/>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="EMBL" id="AAQ88785.1"/>
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    </evidence>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:24083"/>
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    </evidence>
    <sequence length="1216" mass="131499" checksum="6E2957EDE7AD2465" modified="2007-05-15" version="2" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1990-01-01" modified="2026-01-28" version="232" xmlns="https://uniprot.org/uniprot">
    <accession>P13945</accession>
    <accession>Q4JFT4</accession>
    <name>ADRB3_HUMAN</name>
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        <recommendedName>
            <fullName evidence="16">Beta-3 adrenergic receptor</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Beta-3 adrenoreceptor</fullName>
            <shortName evidence="2">Beta-3 adrenoceptor</shortName>
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        <name evidence="19" type="primary">ADRB3</name>
        <name type="synonym">ADRB3R</name>
        <name type="synonym">B3AR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1989" name="Science" volume="245" first="1118" last="1121">
            <title>Molecular characterization of the human beta 3-adrenergic receptor.</title>
            <authorList>
                <person name="Emorine L.J."/>
                <person name="Marullo S."/>
                <person name="Briend-Sutren M.-M."/>
                <person name="Patey G."/>
                <person name="Tate K."/>
                <person name="Delavier-Klutchko C."/>
                <person name="Strosberg A.D."/>
            </authorList>
            <dbReference type="PubMed" id="2570461"/>
            <dbReference type="DOI" id="10.1126/science.2570461"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1993" name="Eur. J. Biochem." volume="213" first="1117" last="1124">
            <title>The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes.</title>
            <authorList>
                <person name="van Spronsen A."/>
                <person name="Nahmias C."/>
                <person name="Krief S."/>
                <person name="Briend-Sutren M.-M."/>
                <person name="Strosberg A.D."/>
                <person name="Emorine L.J."/>
            </authorList>
            <dbReference type="PubMed" id="8389293"/>
            <dbReference type="DOI" id="10.1111/j.1432-1033.1993.tb17861.x"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1993" name="FEBS Lett." volume="324" first="127" last="130">
            <title>Molecular cloning of a human beta 3-adrenergic receptor cDNA.</title>
            <authorList>
                <person name="Lelias J.M."/>
                <person name="Kaghad M."/>
                <person name="Rodriguez M."/>
                <person name="Chalon P."/>
                <person name="Bonnin J."/>
                <person name="Dupre I."/>
                <person name="Delpech B."/>
                <person name="Bensaid M."/>
                <person name="Lefur G."/>
                <person name="Ferrara P."/>
                <person name="Caput D."/>
            </authorList>
            <dbReference type="PubMed" id="8389717"/>
            <dbReference type="DOI" id="10.1016/0014-5793(93)81377-c"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2003-11" db="EMBL/GenBank/DDBJ databases">
            <title>cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).</title>
            <authorList>
                <person name="Kopatz S.A."/>
                <person name="Aronstam R.S."/>
                <person name="Sharma S.V."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-06" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="SeattleSNPs variation discovery resource"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>VARIANTS ARG-64 AND CYS-353</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="1992" name="Mol. Pharmacol." volume="42" first="964" last="970">
            <title>Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block.</title>
            <authorList>
                <person name="Granneman J.G."/>
                <person name="Lahners K.N."/>
                <person name="Rao D.D."/>
            </authorList>
            <dbReference type="PubMed" id="1336117"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 392-408</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="1998" name="J. Clin. Invest." volume="102" first="1377" last="1384">
            <title>The negative inotropic effect of beta3-adrenoceptor stimulation is mediated by activation of a nitric oxide synthase pathway in human ventricle.</title>
            <authorList>
                <person name="Gauthier C."/>
                <person name="Leblais V."/>
                <person name="Kobzik L."/>
                <person name="Trochu J.N."/>
                <person name="Khandoudi N."/>
                <person name="Bril A."/>
                <person name="Balligand J.L."/>
                <person name="Le Marec H."/>
            </authorList>
            <dbReference type="PubMed" id="9769330"/>
            <dbReference type="DOI" id="10.1172/jci2191"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="1999" name="Br. J. Pharmacol." volume="126" first="819" last="825">
            <title>Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle.</title>
            <authorList>
                <person name="Igawa Y."/>
                <person name="Yamazaki Y."/>
                <person name="Takeda H."/>
                <person name="Hayakawa K."/>
                <person name="Akahane M."/>
                <person name="Ajisawa Y."/>
                <person name="Yoneyama T."/>
                <person name="Nishizawa O."/>
                <person name="Andersson K.E."/>
            </authorList>
            <dbReference type="PubMed" id="10188996"/>
            <dbReference type="DOI" id="10.1038/sj.bjp.0702358"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="1999" name="J. Biol. Chem." volume="274" first="12017" last="12022">
            <title>The beta3-adrenergic receptor activates mitogen-activated protein kinase in adipocytes through a Gi-dependent mechanism.</title>
            <authorList>
                <person name="Soeder K.J."/>
                <person name="Snedden S.K."/>
                <person name="Cao W."/>
                <person name="Della Rocca G.J."/>
                <person name="Daniel K.W."/>
                <person name="Luttrell L.M."/>
                <person name="Collins S."/>
            </authorList>
            <dbReference type="PubMed" id="10207024"/>
            <dbReference type="DOI" id="10.1074/jbc.274.17.12017"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="Cell Metab." volume="14" first="671" last="683">
            <title>The arrestin domain-containing 3 protein regulates body mass and energy expenditure.</title>
            <authorList>
                <person name="Patwari P."/>
                <person name="Emilsson V."/>
                <person name="Schadt E.E."/>
                <person name="Chutkow W.A."/>
                <person name="Lee S."/>
                <person name="Marsili A."/>
                <person name="Zhang Y."/>
                <person name="Dobrin R."/>
                <person name="Cohen D.E."/>
                <person name="Larsen P.R."/>
                <person name="Zavacki A.M."/>
                <person name="Fong L.G."/>
                <person name="Young S.G."/>
                <person name="Lee R.T."/>
            </authorList>
            <dbReference type="PubMed" id="21982743"/>
            <dbReference type="DOI" id="10.1016/j.cmet.2011.08.011"/>
        </citation>
        <scope>INTERACTION WITH ARRDC3</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="1995" name="N. Engl. J. Med." volume="333" first="352" last="354">
            <title>Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity.</title>
            <authorList>
                <person name="Clement K."/>
                <person name="Vaisse C."/>
                <person name="Manning B.S.J."/>
                <person name="Basdevant A."/>
                <person name="Guy-Grand B."/>
                <person name="Ruiz J."/>
                <person name="Silver K.D."/>
                <person name="Shuldiner A.R."/>
                <person name="Froguel P."/>
                <person name="Strosberg A.D."/>
            </authorList>
            <dbReference type="PubMed" id="7609752"/>
            <dbReference type="DOI" id="10.1056/nejm199508103330605"/>
        </citation>
        <scope>VARIANT ARG-64</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="1996" name="Diabetologia" volume="39" first="349" last="352">
            <title>Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.</title>
            <authorList>
                <person name="Fujisawa T."/>
                <person name="Ikegami H."/>
                <person name="Yamato E."/>
                <person name="Takekawa K."/>
                <person name="Nakagawa Y."/>
                <person name="Hamada Y."/>
                <person name="Oga T."/>
                <person name="Ueda H."/>
                <person name="Shintani M."/>
                <person name="Fukuda M."/>
                <person name="Ogihara T."/>
            </authorList>
            <dbReference type="PubMed" id="8721782"/>
            <dbReference type="DOI" id="10.1007/bf00418352"/>
        </citation>
        <scope>VARIANT ARG-64</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="1996" name="Endocrinology" volume="137" first="2638" last="2641">
            <title>Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant.</title>
            <authorList>
                <person name="Candelore M.R."/>
                <person name="Deng L."/>
                <person name="Tota L.M."/>
                <person name="Kelly L.J."/>
                <person name="Cascieri M.A."/>
                <person name="Strader C.D."/>
            </authorList>
            <dbReference type="PubMed" id="8641219"/>
            <dbReference type="DOI" id="10.1210/endo.137.6.8641219"/>
        </citation>
        <scope>VARIANT ARG-64</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1999" name="Nat. Genet." volume="22" first="239" last="247">
            <title>Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.</title>
            <authorList>
                <person name="Halushka M.K."/>
                <person name="Fan J.-B."/>
                <person name="Bentley K."/>
                <person name="Hsie L."/>
                <person name="Shen N."/>
                <person name="Weder A."/>
                <person name="Cooper R."/>
                <person name="Lipshutz R."/>
                <person name="Chakravarti A."/>
            </authorList>
            <dbReference type="PubMed" id="10391210"/>
            <dbReference type="DOI" id="10.1038/10297"/>
        </citation>
        <scope>VARIANTS ARG-64 AND MET-265</scope>
    </reference>
    <comment type="function">
        <text evidence="3 6 7 10 12 14">G protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, leading to either activation or inhibition of adenylate cyclase and cAMP-dependent pathway, respectively (PubMed:10188996, PubMed:2570461, PubMed:8641219). The rank order of potency for physiological agonists is norepinephrine &gt; epinephrine (PubMed:10188996, PubMed:2570461, PubMed:8641219). Involved in the regulation of thermogenesis and lipolysis in brown and white adipose tissue, after coupling to G(s) proteins and stimulation of the cAMP-PKA axis (By similarity). Also activates lipolytic process by coupling to G(i) proteins and consequent initiation of the ERK1/2 MAP kinase cascade (PubMed:10207024). Participates in relaxation of the blood vessels and the urinary bladder (PubMed:10188996). Also mediates negative inotropic effects in cardiomyocytes through activation of an NO synthase pathway and subsequent increase in cGMP levels, possibly involving G(i/o) protein-mediated coupling (PubMed:9769330).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">Interacts with ARRDC3.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Cell membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed mainly in adipose tissues.</text>
    </comment>
    <comment type="polymorphism">
        <text evidence="13 18">The variant Arg-64 seems to be associated with weight gain (obesity) and is also associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM).</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.</text>
    </comment>
    <dbReference type="EMBL" id="M29932">
        <property type="protein sequence ID" value="AAA35550.1"/>
        <property type="status" value="ALT_TERM"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X72861">
        <property type="protein sequence ID" value="CAA51383.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X70811">
        <property type="protein sequence ID" value="CAA50141.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X70812">
        <property type="protein sequence ID" value="CAA50142.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X70812">
        <property type="protein sequence ID" value="CAA50143.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY487247">
        <property type="protein sequence ID" value="AAR37414.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="DQ104441">
        <property type="protein sequence ID" value="AAY88743.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC075017">
        <property type="protein sequence ID" value="AAH75017.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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            <taxon>Eukaryota</taxon>
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            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
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            <taxon>Haplorrhini</taxon>
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    <reference key="1">
        <citation type="journal article" date="1987" name="Proc. Natl. Acad. Sci. U.S.A." volume="84" first="7580" last="7584">
            <title>cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes.</title>
            <authorList>
                <person name="Neckelmann N."/>
                <person name="Li K."/>
                <person name="Wade R.P."/>
                <person name="Shuster R."/>
                <person name="Wallace D.C."/>
            </authorList>
            <dbReference type="PubMed" id="2823266"/>
            <dbReference type="DOI" id="10.1073/pnas.84.21.7580"/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1989" name="J. Mol. Biol." volume="206" first="261" last="280">
            <title>DNA sequences of two expressed nuclear genes for human mitochondrial ADP/ATP translocase.</title>
            <authorList>
                <person name="Cozens A.L."/>
                <person name="Runswick M.J."/>
                <person name="Walker J.E."/>
            </authorList>
            <dbReference type="PubMed" id="2541251"/>
            <dbReference type="DOI" id="10.1016/0022-2836(89)90477-4"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1989" name="J. Biol. Chem." volume="264" first="13998" last="14004">
            <title>A human muscle adenine nucleotide translocator gene has four exons, is located on chromosome 4, and is differentially expressed.</title>
            <authorList>
                <person name="Li K."/>
                <person name="Warner C.K."/>
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                <person name="Shimizu N."/>
                <person name="Wallace D.C."/>
            </authorList>
            <dbReference type="PubMed" id="2547778"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)71632-3"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2011" name="Nucleic Acids Res." volume="39" first="44" last="58">
            <title>Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing.</title>
            <authorList>
                <person name="Wang W."/>
                <person name="Shen P."/>
                <person name="Thiyagarajan S."/>
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                <person name="Scharfe C."/>
            </authorList>
            <dbReference type="PubMed" id="20843780"/>
            <dbReference type="DOI" id="10.1093/nar/gkq750"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Shatkay H."/>
                <person name="Dew I."/>
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                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
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                <person name="Turner R."/>
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                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
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            <tissue>Eye</tissue>
            <tissue>Mammary gland</tissue>
            <tissue>PNS</tissue>
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    </reference>
    <reference key="7">
        <citation type="journal article" date="1988" name="Proc. Natl. Acad. Sci. U.S.A." volume="85" first="377" last="381">
            <title>Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver.</title>
            <authorList>
                <person name="Houldsworth J."/>
                <person name="Attardi G."/>
            </authorList>
            <dbReference type="PubMed" id="2829183"/>
            <dbReference type="DOI" id="10.1073/pnas.85.2.377"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 1-37</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="submission" date="2004-10" db="UniProtKB">
            <authorList>
                <person name="Bienvenut W.V."/>
            </authorList>
        </citation>
        <scope>PROTEIN SEQUENCE OF 2-31; 34-43; 64-92; 141-147; 189-199 AND 273-296</scope>
        <scope>CLEAVAGE OF INITIATOR METHIONINE</scope>
        <scope>ACETYLATION AT GLY-2</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
        <source>
            <tissue>B-cell lymphoma</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2004" name="Mitochondrion" volume="4" first="223" last="233">
            <title>Mitochondrial membrane permeabilization by HIV-1 Vpr.</title>
            <authorList>
                <person name="Deniaud A."/>
                <person name="Brenner C."/>
                <person name="Kroemer G."/>
            </authorList>
            <dbReference type="PubMed" id="16120388"/>
            <dbReference type="DOI" id="10.1016/j.mito.2004.06.012"/>
        </citation>
        <scope>INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION)</scope>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2011" name="Hum. Mol. Genet." volume="20" first="2964" last="2974">
            <title>adPEO mutations in ANT1 impair ADP-ATP translocation in muscle mitochondria.</title>
            <authorList>
                <person name="Kawamata H."/>
                <person name="Tiranti V."/>
                <person name="Magrane J."/>
                <person name="Chinopoulos C."/>
                <person name="Manfredi G."/>
            </authorList>
            <dbReference type="PubMed" id="21586654"/>
            <dbReference type="DOI" id="10.1093/hmg/ddr200"/>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>CHARACTERIZATION OF VARIANTS PEOA2 PRO-114 AND MET-289</scope>
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    <reference key="13">
        <citation type="journal article" date="2012" name="J. Med. Genet." volume="49" first="146" last="150">
            <title>Complete loss of expression of the ANT1 gene causing cardiomyopathy and myopathy.</title>
            <authorList>
                <person name="Echaniz-Laguna A."/>
                <person name="Chassagne M."/>
                <person name="Ceresuela J."/>
                <person name="Rouvet I."/>
                <person name="Padet S."/>
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                <person name="Nataf S."/>
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                <person name="Bozon D."/>
                <person name="Mousson de Camaret B."/>
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            <dbReference type="PubMed" id="22187496"/>
            <dbReference type="DOI" id="10.1136/jmedgenet-2011-100504"/>
        </citation>
        <scope>INVOLVEMENT IN MTDPS12B</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2013" name="Mol. Membr. Biol." volume="30" first="160" last="168">
            <title>The substrate specificity of the human ADP/ATP carrier AAC1.</title>
            <authorList>
                <person name="Mifsud J."/>
                <person name="Ravaud S."/>
                <person name="Krammer E.M."/>
                <person name="Chipot C."/>
                <person name="Kunji E.R."/>
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            </authorList>
            <dbReference type="PubMed" id="23173940"/>
            <dbReference type="DOI" id="10.3109/09687688.2012.745175"/>
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        <scope>FUNCTION</scope>
        <scope>TRANSPORTER ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="15">
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            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
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                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2016" name="Am. J. Hum. Genet." volume="99" first="860" last="876">
            <title>Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset mitochondrial disease and loss of mitochondrial DNA copy number.</title>
            <authorList>
                <person name="Thompson K."/>
                <person name="Majd H."/>
                <person name="Dallabona C."/>
                <person name="Reinson K."/>
                <person name="King M.S."/>
                <person name="Alston C.L."/>
                <person name="He L."/>
                <person name="Lodi T."/>
                <person name="Jones S.A."/>
                <person name="Fattal-Valevski A."/>
                <person name="Fraenkel N.D."/>
                <person name="Saada A."/>
                <person name="Haham A."/>
                <person name="Isohanni P."/>
                <person name="Vara R."/>
                <person name="Barbosa I.A."/>
                <person name="Simpson M.A."/>
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                <person name="Puusepp S."/>
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                <person name="Rodenburg R.J."/>
                <person name="Suomalainen A."/>
                <person name="Ounap K."/>
                <person name="Elpeleg O."/>
                <person name="Ferrero I."/>
                <person name="McFarland R."/>
                <person name="Kunji E.R."/>
                <person name="Taylor R.W."/>
            </authorList>
            <dbReference type="PubMed" id="27693233"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2016.08.014"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INVOLVEMENT IN MTDPS12A</scope>
        <scope>VARIANTS MTDPS12A HIS-80 AND GLY-235</scope>
        <scope>CHARACTERIZATION OF VARIANTS MTDPS12A HIS-80 AND GLY-235</scope>
        <scope>CHARACTERIZATION OF VARIANTS PEOA2 ASP-90; PRO-98; GLY-104 AND PRO-114</scope>
        <scope>CHARACTERIZATION OF VARIANTS MTDPS12B ASP-123 AND PRO-236</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2016" name="Sci. Rep." volume="6" first="33516" last="33516">
            <title>TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.</title>
            <authorList>
                <person name="Marginedas-Freixa I."/>
                <person name="Hattab C."/>
                <person name="Bouyer G."/>
                <person name="Halle F."/>
                <person name="Chene A."/>
                <person name="Lefevre S.D."/>
                <person name="Cambot M."/>
                <person name="Cueff A."/>
                <person name="Schmitt M."/>
                <person name="Gamain B."/>
                <person name="Lacapere J.J."/>
                <person name="Egee S."/>
                <person name="Bihel F."/>
                <person name="Le Van Kim C."/>
                <person name="Ostuni M.A."/>
            </authorList>
            <dbReference type="PubMed" id="27641616"/>
            <dbReference type="DOI" id="10.1038/srep33516"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2020" name="Neuron" volume="105" first="867" last="881">
            <title>Human-specific ARHGAP11B acts in mitochondria to expand neocortical progenitors by glutaminolysis.</title>
            <authorList>
                <person name="Namba T."/>
                <person name="Doczi J."/>
                <person name="Pinson A."/>
                <person name="Xing L."/>
                <person name="Kalebic N."/>
                <person name="Wilsch-Braeuninger M."/>
                <person name="Long K.R."/>
                <person name="Vaid S."/>
                <person name="Lauer J."/>
                <person name="Bogdanova A."/>
                <person name="Borgonovo B."/>
                <person name="Shevchenko A."/>
                <person name="Keller P."/>
                <person name="Drechsel D."/>
                <person name="Kurzchalia T."/>
                <person name="Wimberger P."/>
                <person name="Chinopoulos C."/>
                <person name="Huttner W.B."/>
            </authorList>
            <dbReference type="PubMed" id="31883789"/>
            <dbReference type="DOI" id="10.1016/j.neuron.2019.11.027"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ARHGAP11B</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2023" name="EMBO Rep." volume="24" first="e57127" last="e57127">
            <title>Human mitochondrial ADP/ATP carrier SLC25A4 operates with a ping-pong kinetic mechanism.</title>
            <authorList>
                <person name="Cimadamore-Werthein C."/>
                <person name="Jaiquel Baron S."/>
                <person name="King M.S."/>
                <person name="Springett R."/>
                <person name="Kunji E.R."/>
            </authorList>
            <dbReference type="PubMed" id="37278158"/>
            <dbReference type="DOI" id="10.15252/embr.202357127"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2000" name="Science" volume="289" first="782" last="785">
            <title>Role of adenine nucleotide translocator 1 in mtDNA maintenance.</title>
            <authorList>
                <person name="Kaukonen J."/>
                <person name="Juselius J.K."/>
                <person name="Tiranti V."/>
                <person name="Kyttala A."/>
                <person name="Zeviani M."/>
                <person name="Comi G.P."/>
                <person name="Keranen J."/>
                <person name="Peltonen L."/>
                <person name="Suomalainen A."/>
            </authorList>
            <dbReference type="PubMed" id="10926541"/>
            <dbReference type="DOI" id="10.1126/science.289.5480.782"/>
        </citation>
        <scope>VARIANTS PEOA2 PRO-114 AND MET-289</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2001" name="Neurology" volume="57" first="2295" last="2298">
            <title>A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.</title>
            <authorList>
                <person name="Napoli L."/>
                <person name="Bordoni A."/>
                <person name="Zeviani M."/>
                <person name="Hadjigeorgiou G.M."/>
                <person name="Sciacco M."/>
                <person name="Tiranti V."/>
                <person name="Terentiou A."/>
                <person name="Moggio M."/>
                <person name="Papadimitriou A."/>
                <person name="Scarlato G."/>
                <person name="Comi G.P."/>
            </authorList>
            <dbReference type="PubMed" id="11756613"/>
            <dbReference type="DOI" id="10.1212/wnl.57.12.2295"/>
        </citation>
        <scope>VARIANT PEOA2 PRO-98</scope>
    </reference>
    <reference key="22">
        <citation type="journal article" date="2002" name="Ann. Neurol." volume="51" first="645" last="648">
            <title>A novel D104G mutation in the adenine nucleotide translocator 1 gene in autosomal dominant progressive external ophthalmoplegia patients with mitochondrial DNA with multiple deletions.</title>
            <authorList>
                <person name="Komaki H."/>
                <person name="Fukazawa T."/>
                <person name="Houzen H."/>
                <person name="Yoshida K."/>
                <person name="Nonaka I."/>
                <person name="Goto Y."/>
            </authorList>
            <dbReference type="PubMed" id="12112115"/>
            <dbReference type="DOI" id="10.1002/ana.10172"/>
        </citation>
        <scope>VARIANT PEOA2 GLY-104</scope>
    </reference>
    <reference key="23">
        <citation type="journal article" date="2003" name="Neurology" volume="60" first="1354" last="1356">
            <title>Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).</title>
            <authorList>
                <person name="Agostino A."/>
                <person name="Valletta L."/>
                <person name="Chinnery P.F."/>
                <person name="Ferrari G."/>
                <person name="Carrara F."/>
                <person name="Taylor R.W."/>
                <person name="Schaefer A.M."/>
                <person name="Turnbull D.M."/>
                <person name="Tiranti V."/>
                <person name="Zeviani M."/>
            </authorList>
            <dbReference type="PubMed" id="12707443"/>
            <dbReference type="DOI" id="10.1212/01.wnl.0000056088.09408.3c"/>
        </citation>
        <scope>VARIANT PEOA2 MET-289</scope>
    </reference>
    <reference key="24">
        <citation type="journal article" date="2005" name="Hum. Mol. Genet." volume="14" first="3079" last="3088">
            <title>Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy.</title>
            <authorList>
                <person name="Palmieri L."/>
                <person name="Alberio S."/>
                <person name="Pisano I."/>
                <person name="Lodi T."/>
                <person name="Meznaric-Petrusa M."/>
                <person name="Zidar J."/>
                <person name="Santoro A."/>
                <person name="Scarcia P."/>
                <person name="Fontanesi F."/>
                <person name="Lamantea E."/>
                <person name="Ferrero I."/>
                <person name="Zeviani M."/>
            </authorList>
            <dbReference type="PubMed" id="16155110"/>
            <dbReference type="DOI" id="10.1093/hmg/ddi341"/>
        </citation>
        <scope>VARIANT MTDPS12B ASP-123</scope>
    </reference>
    <reference key="25">
        <citation type="journal article" date="2005" name="Neuromuscul. Disord." volume="15" first="311" last="315">
            <title>A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia.</title>
            <authorList>
                <person name="Deschauer M."/>
                <person name="Hudson G."/>
                <person name="Mueller T."/>
                <person name="Taylor R.W."/>
                <person name="Chinnery P.F."/>
                <person name="Zierz S."/>
            </authorList>
            <dbReference type="PubMed" id="15792871"/>
            <dbReference type="DOI" id="10.1016/j.nmd.2004.12.004"/>
        </citation>
        <scope>VARIANT PEOA2 ASP-90</scope>
    </reference>
    <reference key="26">
        <citation type="journal article" date="2008" name="J. Neurol." volume="255" first="1384" last="1391">
            <title>Novel Twinkle (PEO1) gene mutations in Mendelian progressive external ophthalmoplegia.</title>
            <authorList>
                <person name="Virgilio R."/>
                <person name="Ronchi D."/>
                <person name="Hadjigeorgiou G.M."/>
                <person name="Bordoni A."/>
                <person name="Saladino F."/>
                <person name="Moggio M."/>
                <person name="Adobbati L."/>
                <person name="Kafetsouli D."/>
                <person name="Tsironi E."/>
                <person name="Previtali S."/>
                <person name="Papadimitriou A."/>
                <person name="Bresolin N."/>
                <person name="Comi G.P."/>
            </authorList>
            <dbReference type="PubMed" id="18575922"/>
            <dbReference type="DOI" id="10.1007/s00415-008-0926-3"/>
        </citation>
        <scope>VARIANTS PEOA2 PRO-98 AND PRO-114</scope>
    </reference>
    <reference key="27">
        <citation type="journal article" date="2015" name="JIMD Rep." volume="22" first="39" last="45">
            <title>Two novel mutations in the SLC25A4 gene in a patient with mitochondrial myopathy.</title>
            <authorList>
                <person name="Koerver-Keularts I.M."/>
                <person name="de Visser M."/>
                <person name="Bakker H.D."/>
                <person name="Wanders R.J."/>
                <person name="Vansenne F."/>
                <person name="Scholte H.R."/>
                <person name="Dorland L."/>
                <person name="Nicolaes G.A."/>
                <person name="Spaapen L.M."/>
                <person name="Smeets H.J."/>
                <person name="Hendrickx A.T."/>
                <person name="van den Bosch B.J."/>
            </authorList>
            <dbReference type="PubMed" id="25732997"/>
            <dbReference type="DOI" id="10.1007/8904_2015_409"/>
        </citation>
        <scope>VARIANT MTDPS12B PRO-236</scope>
    </reference>
    <reference key="28">
        <citation type="journal article" date="2018" name="Neurol. Genet." volume="4" first="e256" last="e256">
            <title>Expanding the phenotype of de novo SLC25A4-linked mitochondrial disease to include mild myopathy.</title>
            <authorList>
                <person name="King M.S."/>
                <person name="Thompson K."/>
                <person name="Hopton S."/>
                <person name="He L."/>
                <person name="Kunji E.R.S."/>
                <person name="Taylor R.W."/>
                <person name="Ortiz-Gonzalez X.R."/>
            </authorList>
            <dbReference type="PubMed" id="30046662"/>
            <dbReference type="DOI" id="10.1212/nxg.0000000000000256"/>
        </citation>
        <scope>VARIANT GLN-33</scope>
        <scope>CHARACTERIZATION OF VARIANT GLN-33</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 3 14 16 19 21 22">ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:21586654, PubMed:27693233, PubMed:23173940, PubMed:30046662). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). Substrate exchange across the membrane occurs consecutively with one substrate being transported first, then dissociating from the substrate binding site before the second substrate binds for transport in the opposite direction (PubMed:37278158). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31883789). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31883789). It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14 16">
            <text>ADP(in) + ATP(out) = ADP(out) + ATP(in)</text>
            <dbReference type="Rhea" id="RHEA:34999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="3">
            <text>H(+)(in) = H(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34979"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 3 14">The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) PubMed:23173940. The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (PubMed:21586654, PubMed:23173940). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).</text>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="16">23.7 uM for ATP</KM>
            <Vmax evidence="16">14.6 nmol/min/mg enzyme for ATP uptake</Vmax>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 3 21">Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (By similarity). Interacts with ARL2BP (By similarity). Interacts with ARHGAP11B, thereby inhibiting the mitochondrial permeability transition pore (mPTP) (PubMed:31883789). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="11">(Microbial infection) Interacts with HIV-1 Vpr.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359074">
            <id>P12235</id>
        </interactant>
        <interactant intactId="EBI-5323863">
            <id>Q5S007</id>
            <label>LRRK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359074">
            <id>P12235</id>
        </interactant>
        <interactant intactId="EBI-16085263">
            <id>P22736-1</id>
            <label>NR4A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-359074">
            <id>P12235</id>
        </interactant>
        <interactant intactId="EBI-356254">
            <id>P12236</id>
            <label>SLC25A6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="14">Mitochondrion inner membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="18">Membrane</location>
            <topology evidence="5">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="3 18">The complex formed with ARL2BP, ARL2 and SLC25A4/ANT1 is expressed in mitochondria (By similarity). May localize to non-mitochondrial membranes (PubMed:27641616).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="18">Expressed in erythrocytes (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.</text>
    </comment>
    <comment type="PTM">
        <text evidence="3">Under cell death induction, transglutaminated by TGM2. Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers.</text>
    </comment>
    <comment type="disease" evidence="6 7 8 9 10 13 14 19">
        <disease id="DI-00944">
            <name>Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2</name>
            <acronym>PEOA2</acronym>
            <description>A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.</description>
            <dbReference type="MIM" id="609283"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="12 15 17 19">
        <disease id="DI-03934">
            <name>Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type</name>
            <acronym>MTDPS12B</acronym>
            <description>An autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria.</description>
            <dbReference type="MIM" id="615418"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="19">
        <disease id="DI-04880">
            <name>Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type</name>
            <acronym>MTDPS12A</acronym>
            <description>An autosomal dominant mitochondrial disorder characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies.</description>
            <dbReference type="MIM" id="617184"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="27">Belongs to the mitochondrial carrier (TC 2.A.29) family.</text>
    </comment>
    <dbReference type="EMBL" id="J02966">
        <property type="protein sequence ID" value="AAA61223.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J04982">
        <property type="protein sequence ID" value="AAA51736.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206346">
        <property type="protein sequence ID" value="ADP92294.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206347">
        <property type="protein sequence ID" value="ADP92295.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206348">
        <property type="protein sequence ID" value="ADP92296.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206349">
        <property type="protein sequence ID" value="ADP92297.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206350">
        <property type="protein sequence ID" value="ADP92298.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206351">
        <property type="protein sequence ID" value="ADP92299.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206352">
        <property type="protein sequence ID" value="ADP92300.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206353">
        <property type="protein sequence ID" value="ADP92301.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206354">
        <property type="protein sequence ID" value="ADP92302.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206355">
        <property type="protein sequence ID" value="ADP92303.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206356">
        <property type="protein sequence ID" value="ADP92304.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206357">
        <property type="protein sequence ID" value="ADP92305.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206358">
        <property type="protein sequence ID" value="ADP92306.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206359">
        <property type="protein sequence ID" value="ADP92307.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206360">
        <property type="protein sequence ID" value="ADP92308.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206361">
        <property type="protein sequence ID" value="ADP92309.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="HQ206362">
        <property type="protein sequence ID" value="ADP92310.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    </feature>
    <feature type="repeat" description="Solcar 1">
        <location>
            <begin position="6"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 2">
        <location>
            <begin position="111"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 3">
        <location>
            <begin position="212"/>
            <end position="297"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for transport activity" evidence="19">
        <location>
            <begin position="235"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nucleotide carrier signature motif" evidence="2">
        <location>
            <begin position="235"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="80"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="92"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="235"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylglycine" evidence="23">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="4">
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6,N6,N6-trimethyllysine" evidence="4">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="147"/>
        </location>
    </feature>
    <feature type="modified residue" description="S-nitrosocysteine" evidence="4">
        <location>
            <position position="160"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="3">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_090742" description="Found in a patient with mild childhood-onset myopathy without evidence of other clinical features such as cardiomyopathy, encephalopathy or ophthalmoplegia; likely pathogenic; abolishes ADP transport." evidence="20">
        <original>K</original>
        <variation>Q</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078071" description="In MTDPS12A; decreased function in ADP transport; dbSNP:rs886041081." evidence="19">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038814" description="In PEOA2; decreased function in ADP transport." evidence="10 19">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022459" description="In PEOA2; decreased function in ADP transport; dbSNP:rs104893876." evidence="7 13 19">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022460" description="In PEOA2; decreased function in ADP transport; dbSNP:rs28999114." evidence="8 19">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012111" description="In PEOA2; decreased function in ADP transport; inverted direction of ADP:ATP transport, with ATP entering the mitochondrial matrix; dbSNP:rs104893873." evidence="6 13 14 19">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_038815" description="In MTDPS12B; loss of function in ADP transport; dbSNP:rs121912683." evidence="12 19">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="123"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078072" description="In MTDPS12A; severely decreased function in ADP transport; dbSNP:rs886041082." evidence="19">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_078073" description="In MTDPS12B; loss of function in ADP transport; dbSNP:rs770816416." evidence="17 19">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012112" description="In PEOA2; inverted direction of ADP:ATP transport, with ATP entering the mitochondrial matrix; dbSNP:rs104893874." evidence="6 9 14">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA61223." evidence="27" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="16"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA61223." evidence="27" ref="1">
        <original>KGA</original>
        <variation>RR</variation>
        <location>
            <begin position="147"/>
            <end position="149"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA61223." evidence="27" ref="1">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="G2QNH0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P02722"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P48962"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="Q05962"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5"/>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="10926541"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="11756613"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="12112115"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12707443"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="15792871"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="16120388"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="16155110"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="18575922"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="21586654"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="22187496"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="23173940"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="25732997"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="18">
        <source>
            <dbReference type="PubMed" id="27641616"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="19">
        <source>
            <dbReference type="PubMed" id="27693233"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="20">
        <source>
            <dbReference type="PubMed" id="30046662"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="21">
        <source>
            <dbReference type="PubMed" id="31883789"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="22">
        <source>
            <dbReference type="PubMed" id="37278158"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="23">
        <source ref="8"/>
    </evidence>
    <evidence type="ECO:0000303" key="24">
        <source>
            <dbReference type="PubMed" id="2541251"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="25">
        <source>
            <dbReference type="PubMed" id="25732997"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="26">
        <source>
            <dbReference type="PubMed" id="2823266"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="27"/>
    <evidence type="ECO:0000312" key="28">
        <source>
            <dbReference type="HGNC" id="HGNC:10990"/>
        </source>
    </evidence>
    <sequence length="298" mass="33064" checksum="59F0DFAEC4E7CFBB" modified="2007-01-23" version="4">MGDHAWSFLKDFLAGGVAAAVSKTAVAPIERVKLLLQVQHASKQISAEKQYKGIIDCVVRIPKEQGFLSFWRGNLANVIRYFPTQALNFAFKDKYKQLFLGGVDRHKQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKGAAQREFHGLGDCIIKIFKSDGLRGLYQGFNVSVQGIIIYRAAYFGVYDTAKGMLPDPKNVHIFVSWMIAQSVTAVAGLVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIAKDEGAKAFFKGAWSNVLRGMGGAFVLVLYDEIKKYV</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-10-11" modified="2026-01-28" version="167" xmlns="https://uniprot.org/uniprot">
    <accession>Q96SZ5</accession>
    <accession>B1AL29</accession>
    <name>AEDO_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>2-aminoethanethiol dioxygenase</fullName>
            <ecNumber evidence="4 5 7">1.13.11.19</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Cysteamine dioxygenase</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">ADO</name>
        <name type="synonym">C10orf22</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="15164054"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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            <authorList>
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                <consortium name="The MGC Project Team"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANTS TRP-25 AND ALA-39</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Testis</tissue>
        </source>
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                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-270</scope>
        <scope>VARIANT ALA-39</scope>
        <source>
            <tissue>Teratocarcinoma</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="25189" last="25198">
            <title>Discovery and characterization of a second mammalian thiol dioxygenase, cysteamine dioxygenase.</title>
            <authorList>
                <person name="Dominy J.E. Jr."/>
                <person name="Simmons C.R."/>
                <person name="Hirschberger L.L."/>
                <person name="Hwang J."/>
                <person name="Coloso R.M."/>
                <person name="Stipanuk M.H."/>
            </authorList>
            <dbReference type="PubMed" id="17581819"/>
            <dbReference type="DOI" id="10.1074/jbc.m703089200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2018" name="Angew. Chem. Int. Ed." volume="57" first="8149" last="8153">
            <title>Cofactor Biogenesis in Cysteamine Dioxygenase: C-F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine.</title>
            <authorList>
                <person name="Wang Y."/>
                <person name="Griffith W.P."/>
                <person name="Li J."/>
                <person name="Koto T."/>
                <person name="Wherritt D.J."/>
                <person name="Fritz E."/>
                <person name="Liu A."/>
            </authorList>
            <dbReference type="PubMed" id="29752763"/>
            <dbReference type="DOI" id="10.1002/anie.201803907"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
        <scope>CROSS-LINK</scope>
        <scope>MUTAGENESIS OF TYR-87; TYR-222 AND TYR-223</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2019" name="Science" volume="365" first="65" last="69">
            <title>Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants.</title>
            <authorList>
                <person name="Masson N."/>
                <person name="Keeley T.P."/>
                <person name="Giuntoli B."/>
                <person name="White M.D."/>
                <person name="Puerta M.L."/>
                <person name="Perata P."/>
                <person name="Hopkinson R.J."/>
                <person name="Flashman E."/>
                <person name="Licausi F."/>
                <person name="Ratcliffe P.J."/>
            </authorList>
            <dbReference type="PubMed" id="31273118"/>
            <dbReference type="DOI" id="10.1126/science.aaw0112"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>BIOPHYSICOCHEMICAL PROPERTIES</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2020" name="J. Biol. Chem." volume="295" first="11789" last="11802">
            <title>Characterization of the nonheme iron center of cysteamine dioxygenase and its interaction with substrates.</title>
            <authorList>
                <person name="Wang Y."/>
                <person name="Davis I."/>
                <person name="Chan Y."/>
                <person name="Naik S.G."/>
                <person name="Griffith W.P."/>
                <person name="Liu A."/>
            </authorList>
            <dbReference type="PubMed" id="32601061"/>
            <dbReference type="DOI" id="10.1074/jbc.ra120.013915"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference evidence="12" key="10">
        <citation type="journal article" date="2021" name="J. Biol. Chem." volume="297" first="101176" last="101176">
            <title>Crystal structure of human cysteamine dioxygenase provides a structural rationale for its function as an oxygen sensor.</title>
            <authorList>
                <person name="Wang Y."/>
                <person name="Shin I."/>
                <person name="Li J."/>
                <person name="Liu A."/>
            </authorList>
            <dbReference type="PubMed" id="34508780"/>
            <dbReference type="DOI" id="10.1016/j.jbc.2021.101176"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF MUTANTS SER-18/SER-239 IN COMPLEX WITH NICKEL</scope>
        <scope>SUBUNIT</scope>
        <scope>COFACTOR</scope>
        <scope>IRON-BINDING SITES</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5 6 7">Plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate (PubMed:17581819, PubMed:29752763, PubMed:31273118, PubMed:32601061). Catalyzes the oxidation of cysteamine (2-aminoethanethiol) to hypotaurine (PubMed:17581819, PubMed:29752763, PubMed:32601061). Catalyzes the oxidation of regulators of G-protein signaling 4 (RGS4) and 5 (RGS5) and interleukin-32 (IL32) (PubMed:31273118, PubMed:32601061).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4 5 7">
            <text>cysteamine + O2 = hypotaurine + H(+)</text>
            <dbReference type="Rhea" id="RHEA:14409"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:57853"/>
            <dbReference type="ChEBI" id="CHEBI:58029"/>
            <dbReference type="EC" id="1.13.11.19"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:14410"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6 7">
            <text>N-terminal L-cysteinyl-[protein] + O2 = N-terminal S-hydroxy-S-oxy-L-cysteinyl-[protein] + H(+)</text>
            <dbReference type="Rhea" id="RHEA:70895"/>
            <dbReference type="Rhea" id="RHEA-COMP:12707"/>
            <dbReference type="Rhea" id="RHEA-COMP:17973"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:15379"/>
            <dbReference type="ChEBI" id="CHEBI:65250"/>
            <dbReference type="ChEBI" id="CHEBI:156254"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="11">
            <dbReference type="Rhea" id="RHEA:70896"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="8">
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
        </cofactor>
    </comment>
    <comment type="biophysicochemical properties">
        <kinetics>
            <KM evidence="5">3.4 mM for cysteamine</KM>
            <KM evidence="6">123 uM for RGS4</KM>
            <KM evidence="6">71.51 uM for RGS5</KM>
            <KM evidence="6">33.6 uM for IL32</KM>
        </kinetics>
    </comment>
    <comment type="subunit">
        <text evidence="8">Monomer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11102284">
            <id>Q96SZ5</id>
        </interactant>
        <interactant intactId="EBI-1051165">
            <id>P40123</id>
            <label>CAP2</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-11102284">
            <id>Q96SZ5</id>
        </interactant>
        <interactant intactId="EBI-11988027">
            <id>Q9NRI5-2</id>
            <label>DISC1</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-11102284">
            <id>Q96SZ5</id>
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        <interactant intactId="EBI-751192">
            <id>Q5HYJ3</id>
            <label>FAM76B</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB55123" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
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    <dbReference type="EC" id="1.13.11.19" evidence="4 5 7"/>
    <dbReference type="EMBL" id="AL133417">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="CH471083">
        <property type="protein sequence ID" value="EAW54235.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC018660">
        <property type="protein sequence ID" value="AAH18660.3"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC028589">
        <property type="protein sequence ID" value="AAH28589.2"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="BC067740">
        <property type="protein sequence ID" value="AAH67740.2"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK027453">
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    <dbReference type="CCDS" id="CCDS7266.2"/>
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    <dbReference type="PDB" id="7REI">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.78 A"/>
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    <dbReference type="PDB" id="8U9J">
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        <property type="gene designation" value="ADO"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0408">Iron</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0560">Oxidoreductase</keyword>
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    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="21"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="140"/>
            <end position="164"/>
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    </feature>
    <feature type="binding site" evidence="8 12">
        <location>
            <position position="112"/>
        </location>
        <ligand>
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 12">
        <location>
            <position position="114"/>
        </location>
        <ligand>
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="8 12">
        <location>
            <position position="193"/>
        </location>
        <ligand>
            <name>Fe cation</name>
            <dbReference type="ChEBI" id="CHEBI:24875"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="cross-link" description="3'-(S-cysteinyl)-tyrosine (Cys-Tyr)" evidence="5">
        <location>
            <begin position="220"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025333" description="In dbSNP:rs2236295." evidence="3">
        <original>G</original>
        <variation>W</variation>
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_025334" description="In dbSNP:rs10995311." evidence="2 3">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_033691" description="In dbSNP:rs569705.">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Moderate reduction in enzyme activity." evidence="5">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="87"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Significant reduction in enzyme activity." evidence="5">
        <original>Y</original>
        <variation>A</variation>
        <variation>F</variation>
        <location>
            <position position="222"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No significant reduction in enzyme activity." evidence="5">
        <original>Y</original>
        <variation>A</variation>
        <location>
            <position position="223"/>
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        <location>
            <begin position="9"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="47"/>
            <end position="60"/>
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    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="63"/>
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    <feature type="strand" evidence="13">
        <location>
            <begin position="84"/>
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    <feature type="strand" evidence="13">
        <location>
            <begin position="97"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="108"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="118"/>
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    <feature type="helix" evidence="13">
        <location>
            <begin position="138"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="153"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="159"/>
            <end position="164"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="166"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="183"/>
            <end position="186"/>
        </location>
    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="192"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="helix" evidence="13">
        <location>
            <begin position="214"/>
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    <feature type="strand" evidence="13">
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            <begin position="222"/>
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    <feature type="strand" evidence="13">
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            <begin position="241"/>
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    </feature>
    <feature type="strand" evidence="13">
        <location>
            <begin position="258"/>
            <end position="260"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="17581819"/>
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            <dbReference type="PubMed" id="29752763"/>
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    </evidence>
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        <source>
            <dbReference type="PubMed" id="31273118"/>
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    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="32601061"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="34508780"/>
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    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="17581819"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="11">
        <source>
            <dbReference type="PubMed" id="31273118"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PDB" id="7REI"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="13">
        <source>
            <dbReference type="PDB" id="7REI"/>
        </source>
    </evidence>
    <sequence length="270" mass="29751" checksum="6B496CCF16E92C9D" modified="2006-02-21" version="2">MPRDNMASLIQRIARQACLTFRGSGGGRGASDRDAASGPEAPMQPGFPENLSKLKSLLTQLRAEDLNIAPRKATLQPLPPNLPPVTYMHIYETDGFSLGVFLLKSGTSIPLHDHPGMHGMLKVLYGTVRISCMDKLDAGGGQRPRALPPEQQFEPPLQPREREAVRPGVLRSRAEYTEASGPCILTPHRDNLHQIDAVEGPAAFLDILAPPYDPDDGRDCHYYRVLEPVRPKEASSSACDLPREVWLLETPQADDFWCEGEPYPGPKVFP</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-03-18" modified="2026-01-28" version="177" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WTP8</accession>
    <accession>C9J571</accession>
    <accession>Q9BSA5</accession>
    <accession>Q9H9X7</accession>
    <name>AEN_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Apoptosis-enhancing nuclease</fullName>
            <ecNumber>3.1.-.-</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Interferon-stimulated 20 kDa exonuclease-like 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AEN</name>
        <name type="synonym">ISG20L1</name>
        <name type="ORF">SBBI58</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2000-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Zhang W."/>
                <person name="Li N."/>
                <person name="Wan T."/>
                <person name="Chen T."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT ASP-140</scope>
    </reference>
    <reference key="2">
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                <person name="Birditt B."/>
                <person name="Bloom S."/>
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                <person name="Burke J."/>
                <person name="Butler J."/>
                <person name="Cook A."/>
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                <person name="DeCaprio D."/>
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                <person name="Dors M."/>
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                <person name="Friedman C."/>
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                <person name="Hensley G."/>
                <person name="Johnson E."/>
                <person name="Jones C."/>
                <person name="Kamat A."/>
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                <person name="Locke D.P."/>
                <person name="Madan A."/>
                <person name="Munson G."/>
                <person name="Jaffe D.B."/>
                <person name="Lui A."/>
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                <person name="Mauceli E."/>
                <person name="Naylor J.W."/>
                <person name="Nesbitt R."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Ratcliffe A."/>
                <person name="Rounsley S."/>
                <person name="She X."/>
                <person name="Sneddon K.M.B."/>
                <person name="Stewart S."/>
                <person name="Sougnez C."/>
                <person name="Stone S.M."/>
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                <person name="Vincent D."/>
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                <person name="Zimmer A.R."/>
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                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16572171"/>
            <dbReference type="DOI" id="10.1038/nature04601"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
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                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT ASP-140</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <scope>VARIANT ASP-140</scope>
        <source>
            <tissue>Colon</tissue>
            <tissue>Muscle</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
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                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
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                <person name="Fujimori K."/>
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                <person name="Ono Y."/>
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                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Nomura Y."/>
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                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-325 (ISOFORM 1)</scope>
        <scope>VARIANT ASP-140</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2005" name="Biochem. Biophys. Res. Commun." volume="337" first="39" last="47">
            <title>Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis.</title>
            <authorList>
                <person name="Lee J.-H."/>
                <person name="Koh Y.A."/>
                <person name="Cho C.-K."/>
                <person name="Lee S.J."/>
                <person name="Lee Y.-S."/>
                <person name="Bae S."/>
            </authorList>
            <dbReference type="PubMed" id="16171785"/>
            <dbReference type="DOI" id="10.1016/j.bbrc.2005.08.264"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INDUCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="Oncogene" volume="27" first="3797" last="3810">
            <title>p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis.</title>
            <authorList>
                <person name="Kawase T."/>
                <person name="Ichikawa H."/>
                <person name="Ohta T."/>
                <person name="Nozaki N."/>
                <person name="Tashiro F."/>
                <person name="Ohki R."/>
                <person name="Taya Y."/>
            </authorList>
            <dbReference type="PubMed" id="18264133"/>
            <dbReference type="DOI" id="10.1038/onc.2008.32"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INDUCTION</scope>
        <scope>NUCLEAR LOCALIZATION SIGNAL</scope>
        <scope>NUCLEOLAR LOCALIZATION SIGNAL</scope>
        <scope>MUTAGENESIS OF ASP-114; GLU-116 AND ASP-258</scope>
    </reference>
    <comment type="function">
        <text evidence="4 5">Exonuclease with activity against single- and double-stranded DNA and RNA. Mediates p53-induced apoptosis. When induced by p53 following DNA damage, digests double-stranded DNA to form single-stranded DNA and amplifies DNA damage signals, leading to enhancement of apoptosis.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10176499">
            <id>C9JG97</id>
            <label>AAMP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-727274">
            <id>Q13685</id>
            <label>AAMP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-489887">
            <id>P50402</id>
            <label>EMD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-371922">
            <id>Q96B26</id>
            <label>EXOSC8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-1104907">
            <id>Q3T906</id>
            <label>GNPTAB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10172004">
            <id>Q8IX15-3</id>
            <label>HOMEZ</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-745305">
            <id>Q13422</id>
            <label>IKZF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-742808">
            <id>Q5VWX1</id>
            <label>KHDRBS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10171697">
            <id>Q6A162</id>
            <label>KRT40</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10172150">
            <id>P60370</id>
            <label>KRTAP10-5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10172290">
            <id>P60409</id>
            <label>KRTAP10-7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10171774">
            <id>P60410</id>
            <label>KRTAP10-8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-741037">
            <id>Q9BRK4</id>
            <label>LZTS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10225084">
            <id>Q86VM6</id>
            <label>MBNL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-10172526">
            <id>Q9UJV3-2</id>
            <label>MID2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-742948">
            <id>Q5JR59</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-1105124">
            <id>Q5VU43</id>
            <label>PDE4DIP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-713786">
            <id>Q8IXK0</id>
            <label>PHC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-741520">
            <id>Q86SE5</id>
            <label>RALYL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-8638511">
            <id>P0DJD3</id>
            <label>RBMY1A1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-8642021">
            <id>Q15415</id>
            <label>RBMY1J</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-1050213">
            <id>Q96KN7</id>
            <label>RPGRIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-2212028">
            <id>Q9Y2D8</id>
            <label>SSX2IP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-717810">
            <id>Q08117</id>
            <label>TLE5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-719493">
            <id>P14373</id>
            <label>TRIM27</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-725997">
            <id>Q8WV44</id>
            <label>TRIM41</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-740718">
            <id>O43298</id>
            <label>ZBTB43</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-742740">
            <id>Q96BR9</id>
            <label>ZBTB8A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-711679">
            <id>Q9NTW7</id>
            <label>ZFP64</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-1210473">
            <id>Q96PQ6</id>
            <label>ZNF317</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-8637627">
            <id>Q8WTP8</id>
        </interactant>
        <interactant intactId="EBI-751409">
            <id>Q8WTR7</id>
            <label>ZNF473</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-727274">
            <id>Q13685</id>
            <label>AAMP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-712814">
            <id>P54257</id>
            <label>HAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-2556193">
            <id>Q63ZY3</id>
            <label>KANK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-741037">
            <id>Q9BRK4</id>
            <label>LZTS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-10246152">
            <id>Q5T7P8-2</id>
            <label>SYT6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12119298">
            <id>Q8WTP8-2</id>
        </interactant>
        <interactant intactId="EBI-347633">
            <id>Q9H9D4</id>
            <label>ZNF408</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
            <location>Nucleolus</location>
        </subcellularLocation>
        <text>Localized predomintly in the nucleolus. Translocates from the nucleolus to the nucleoplasm upon apoptosis induction.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8WTP8-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8WTP8-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_032132"/>
        </isoform>
    </comment>
    <comment type="induction">
        <text evidence="4 5">Up-regulated by p53/TP53 in response to ionizing radiation and DNA-damaging agents such as adriamycin. Phosphorylation of p53/TP53 at 'Ser-15' is required for effective induction.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH14407" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB14091" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EC" id="3.1.-.-"/>
    <dbReference type="EMBL" id="AF327352">
        <property type="protein sequence ID" value="AAL56012.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC013489">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471101">
        <property type="protein sequence ID" value="EAX02009.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC005164">
        <property type="protein sequence ID" value="AAH05164.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014407">
        <property type="protein sequence ID" value="AAH14407.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC020988">
        <property type="protein sequence ID" value="AAH20988.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK022546">
        <property type="protein sequence ID" value="BAB14091.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10344.1">
        <molecule id="Q8WTP8-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_073604.3">
        <molecule id="Q8WTP8-1"/>
        <property type="nucleotide sequence ID" value="NM_022767.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_005255023.1">
        <molecule id="Q8WTP8-1"/>
        <property type="nucleotide sequence ID" value="XM_005254966.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_016877978.1">
        <molecule id="Q8WTP8-1"/>
        <property type="nucleotide sequence ID" value="XM_017022489.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288902.1">
        <molecule id="Q8WTP8-1"/>
        <property type="nucleotide sequence ID" value="XM_047432946.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_047288903.1">
        <molecule id="Q8WTP8-1"/>
        <property type="nucleotide sequence ID" value="XM_047432947.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8WTP8"/>
    <dbReference type="SMR" id="Q8WTP8"/>
    <dbReference type="BioGRID" id="122292">
        <property type="interactions" value="48"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8WTP8">
        <property type="interactions" value="2435"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8WTP8">
        <property type="interactions" value="42"/>
    </dbReference>
    <dbReference type="MINT" id="Q8WTP8"/>
    <dbReference type="STRING" id="9606.ENSP00000331944"/>
    <dbReference type="iPTMnet" id="Q8WTP8"/>
    <dbReference type="PhosphoSitePlus" id="Q8WTP8"/>
    <dbReference type="BioMuta" id="AEN"/>
    <dbReference type="DMDM" id="296434390"/>
    <dbReference type="CPTAC" id="CPTAC-2613"/>
    <dbReference type="jPOST" id="Q8WTP8"/>
    <dbReference type="MassIVE" id="Q8WTP8"/>
    <dbReference type="PaxDb" id="9606-ENSP00000331944"/>
    <dbReference type="PeptideAtlas" id="Q8WTP8"/>
    <dbReference type="ProteomicsDB" id="74578">
        <molecule id="Q8WTP8-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74579">
        <molecule id="Q8WTP8-2"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8WTP8"/>
    <dbReference type="Antibodypedia" id="28501">
        <property type="antibodies" value="79 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="64782"/>
    <dbReference type="Ensembl" id="ENST00000332810.4">
        <molecule id="Q8WTP8-1"/>
        <property type="protein sequence ID" value="ENSP00000331944.3"/>
        <property type="gene ID" value="ENSG00000181026.16"/>
    </dbReference>
    <dbReference type="GeneID" id="64782"/>
    <dbReference type="KEGG" id="hsa:64782"/>
    <dbReference type="MANE-Select" id="ENST00000332810.4">
        <property type="protein sequence ID" value="ENSP00000331944.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_022767.4"/>
        <property type="RefSeq protein sequence ID" value="NP_073604.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002bmt.3">
        <molecule id="Q8WTP8-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25722"/>
    <dbReference type="ClinPGx" id="PA162375720"/>
    <dbReference type="CTD" id="64782"/>
    <dbReference type="DisGeNET" id="64782"/>
    <dbReference type="GeneCards" id="AEN"/>
    <dbReference type="HGNC" id="HGNC:25722">
        <property type="gene designation" value="AEN"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000181026">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="610177">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000181026"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000181026"/>
    <dbReference type="eggNOG" id="KOG2249">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161660"/>
    <dbReference type="HOGENOM" id="CLU_022453_0_0_1"/>
    <dbReference type="InParanoid" id="Q8WTP8"/>
    <dbReference type="OMA" id="TDTEQYM"/>
    <dbReference type="OrthoDB" id="16516at2759"/>
    <dbReference type="PAN-GO" id="Q8WTP8">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WTP8"/>
    <dbReference type="PathwayCommons" id="Q8WTP8"/>
    <dbReference type="SignaLink" id="Q8WTP8"/>
    <dbReference type="Agora" id="ENSG00000181026"/>
    <dbReference type="BioGRID-ORCS" id="64782">
        <property type="hits" value="12 hits in 1156 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AEN">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="64782"/>
    <dbReference type="Pharos" id="Q8WTP8">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8WTP8"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WTP8">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000181026">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 139 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WTP8">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031965">
        <property type="term" value="C:nuclear membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005730">
        <property type="term" value="C:nucleolus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004529">
        <property type="term" value="F:DNA exonuclease activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004527">
        <property type="term" value="F:exonuclease activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003676">
        <property type="term" value="F:nucleic acid binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042771">
        <property type="term" value="P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010212">
        <property type="term" value="P:response to ionizing radiation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006396">
        <property type="term" value="P:RNA processing"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.420.10:FF:000007">
        <property type="entry name" value="Interferon-stimulated exonuclease gene 20"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.420.10">
        <property type="entry name" value="Ribonuclease H-like superfamily/Ribonuclease H"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR047021">
        <property type="entry name" value="REXO1/3/4-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013520">
        <property type="entry name" value="Ribonucl_H"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012337">
        <property type="entry name" value="RNaseH-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036397">
        <property type="entry name" value="RNaseH_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12801:SF57">
        <property type="entry name" value="APOPTOSIS-ENHANCING NUCLEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12801">
        <property type="entry name" value="RNA EXONUCLEASE REXO1 / RECO3 FAMILY MEMBER-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00929">
        <property type="entry name" value="RNase_T"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00479">
        <property type="entry name" value="EXOIII"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53098">
        <property type="entry name" value="Ribonuclease H-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-0227">DNA damage</keyword>
    <keyword id="KW-0269">Exonuclease</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0540">Nuclease</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000324088" description="Apoptosis-enhancing nuclease">
        <location>
            <begin position="1"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="domain" description="Exonuclease">
        <location>
            <begin position="110"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="85"/>
            <end position="105"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="281"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nucleolar localization signal">
        <location>
            <begin position="27"/>
            <end position="35"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear localization signal" evidence="5">
        <location>
            <begin position="165"/>
            <end position="188"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="308"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_032132" description="In isoform 2." evidence="8">
        <original>YWPDDLAHGSRGGAREAQDRRN</original>
        <variation>STQYWALKQKSEKQDSGLNSGAFV</variation>
        <location>
            <begin position="304"/>
            <end position="325"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039651" description="In dbSNP:rs3743477.">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039652" description="In dbSNP:rs8026929.">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="88"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_039653" description="In dbSNP:rs8027765." evidence="2 3 6 7">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="140"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes exonuclease activity; when associated with A-116 and A-258." evidence="5">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="114"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes exonuclease activity; when associated with A-114 and A-258." evidence="5">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="116"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes exonuclease activity; when associated with A-114 and A-116." evidence="5">
        <original>D</original>
        <variation>A</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="16171785"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="18264133"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <sequence length="325" mass="36350" checksum="F230BA301CB4FD88" modified="2010-05-18" version="2">MVPREAPESAQCLCPSLTIPNAKDVLRKRHKRRSRQHQRFMARKALLQEQGLLSMPPEPGSSPLPTPFGAATATEAASSGKQCLRAGSGSAPCSRRPAPGKASGPLPSKCVAIDCEMVGTGPRGRVSELARCSIVSYHGNVLYDKYIRPEMPIADYRTRWSGITRQHMRKAVPFQVAQKEILKLLKGKVVVGHALHNDFQALKYVHPRSQTRDTTYVPNFLSEPGLHTRARVSLKDLALQLLHKKIQVGQHGHSSVEDATTAMELYRLVEVQWEQQEARSLWTCPEDREPDSSTDMEQYMEDQYWPDDLAHGSRGGAREAQDRRN</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-07-01" modified="2026-01-28" version="221" xmlns="https://uniprot.org/uniprot">
    <accession>P10109</accession>
    <accession>B0YJ14</accession>
    <accession>Q53YD6</accession>
    <name>ADX_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adrenodoxin, mitochondrial</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Adrenal ferredoxin</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Ferredoxin-1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Hepatoredoxin</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">FDX1</name>
        <name type="synonym">ADX</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1988" name="DNA" volume="7" first="609" last="615">
            <title>Cloning and structure of the human adrenodoxin gene.</title>
            <authorList>
                <person name="Chang C.-Y."/>
                <person name="Wu D.-A."/>
                <person name="Lai C.-C."/>
                <person name="Miller W.L."/>
                <person name="Chung B.-C."/>
            </authorList>
            <dbReference type="PubMed" id="3229285"/>
            <dbReference type="DOI" id="10.1089/dna.1988.7.609"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1988" name="J. Biol. Chem." volume="263" first="3240" last="3244">
            <title>Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells.</title>
            <authorList>
                <person name="Picado-Leonard J."/>
                <person name="Voutilainen R."/>
                <person name="Kao L.-C."/>
                <person name="Chung B.-C."/>
                <person name="Strauss J.F. III"/>
                <person name="Miller W.L."/>
            </authorList>
            <dbReference type="PubMed" id="3343244"/>
            <dbReference type="DOI" id="10.1016/s0021-9258(18)69061-1"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1988" name="Arch. Biochem. Biophys." volume="264" first="383" last="391">
            <title>Molecular cloning and sequence analysis of human placental ferredoxin.</title>
            <authorList>
                <person name="Mittal S."/>
                <person name="Zhu Y.-Z."/>
                <person name="Vickery L.E."/>
            </authorList>
            <dbReference type="PubMed" id="2969697"/>
            <dbReference type="DOI" id="10.1016/0003-9861(88)90303-7"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1990" name="DNA Cell Biol." volume="9" first="205" last="212">
            <title>Structure, sequence, chromosomal location, and evolution of the human ferredoxin gene family.</title>
            <authorList>
                <person name="Chang C.-Y."/>
                <person name="Wu D.-A."/>
                <person name="Mohandas T.K."/>
                <person name="Chung B.-C."/>
            </authorList>
            <dbReference type="PubMed" id="2340092"/>
            <dbReference type="DOI" id="10.1089/dna.1990.9.205"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]</scope>
    </reference>
    <reference key="5">
        <citation type="submission" date="2003-05" db="EMBL/GenBank/DDBJ databases">
            <title>Cloning of human full-length CDSs in BD Creator(TM) system donor vector.</title>
            <authorList>
                <person name="Kalnine N."/>
                <person name="Chen X."/>
                <person name="Rolfs A."/>
                <person name="Halleck A."/>
                <person name="Hines L."/>
                <person name="Eisenstein S."/>
                <person name="Koundinya M."/>
                <person name="Raphael J."/>
                <person name="Moreira D."/>
                <person name="Kelley T."/>
                <person name="LaBaer J."/>
                <person name="Lin Y."/>
                <person name="Phelan M."/>
                <person name="Farmer A."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <reference key="6">
        <citation type="submission" date="2007-02" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <consortium name="NHLBI resequencing and genotyping service (RS&amp;G)"/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Lung</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2003" name="Bioelectrochemistry" volume="59" first="41" last="47">
            <title>Electrochemical behaviour of human adrenodoxin on a pyrolytic graphite electrode.</title>
            <authorList>
                <person name="Johnson D."/>
                <person name="Norman S."/>
                <person name="Tuckey R.C."/>
                <person name="Martin L.L."/>
            </authorList>
            <dbReference type="PubMed" id="12699818"/>
            <dbReference type="DOI" id="10.1016/s1567-5394(02)00188-3"/>
        </citation>
        <scope>CYCLIC VOLTAMMETRY</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2008" name="Proc. Natl. Acad. Sci. U.S.A." volume="105" first="10762" last="10767">
            <title>A quantitative atlas of mitotic phosphorylation.</title>
            <authorList>
                <person name="Dephoure N."/>
                <person name="Zhou C."/>
                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
                <person name="Bakalarski C.E."/>
                <person name="Elledge S.J."/>
                <person name="Gygi S.P."/>
            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="journal article" date="2010" name="Proc. Natl. Acad. Sci. U.S.A." volume="107" first="11775" last="11780">
            <title>Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis.</title>
            <authorList>
                <person name="Sheftel A.D."/>
                <person name="Stehling O."/>
                <person name="Pierik A.J."/>
                <person name="Elsasser H.P."/>
                <person name="Muhlenhoff U."/>
                <person name="Webert H."/>
                <person name="Hobler A."/>
                <person name="Hannemann F."/>
                <person name="Bernhardt R."/>
                <person name="Lill R."/>
            </authorList>
            <dbReference type="PubMed" id="20547883"/>
            <dbReference type="DOI" id="10.1073/pnas.1004250107"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="11">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
            </authorList>
            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="1991" name="Biochemistry" volume="30" first="9078" last="9083">
            <title>1H NMR spectra of vertebrate [2Fe-2S] ferredoxins. Hyperfine resonances suggest different electron delocalization patterns from plant ferredoxins.</title>
            <authorList>
                <person name="Skjeldal L."/>
                <person name="Markley J.L."/>
                <person name="Coghlan V.M."/>
                <person name="Vickery L.E."/>
            </authorList>
            <dbReference type="PubMed" id="1909889"/>
            <dbReference type="DOI" id="10.1021/bi00101a024"/>
        </citation>
        <scope>STRUCTURE BY NMR</scope>
    </reference>
    <reference key="16">
        <citation type="submission" date="2010-11" db="PDB data bank">
            <title>Crystal structure of human ferredoxin-1 (FDX1) in complex with iron-sulfur cluster.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 61-184 IN COMPLEX WITH IRON-SULFUR CLUSTER</scope>
        <scope>COFACTOR</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2011" name="Proc. Natl. Acad. Sci. U.S.A." volume="108" first="10139" last="10143">
            <title>Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.</title>
            <authorList>
                <person name="Strushkevich N."/>
                <person name="MacKenzie F."/>
                <person name="Cherkesova T."/>
                <person name="Grabovec I."/>
                <person name="Usanov S."/>
                <person name="Park H.W."/>
            </authorList>
            <dbReference type="PubMed" id="21636783"/>
            <dbReference type="DOI" id="10.1073/pnas.1019441108"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 62-175 IN COMPLEX WITH IRON-SULFUR CLUSTER AND CYP11A1</scope>
        <scope>FUNCTION</scope>
        <scope>COFACTOR</scope>
        <scope>INTERACTION WITH CYP11A1</scope>
    </reference>
    <comment type="function">
        <text evidence="1 5 6">Essential for the synthesis of various steroid hormones (PubMed:20547883, PubMed:21636783). Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis (PubMed:20547883, PubMed:21636783). Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage (PubMed:20547883, PubMed:21636783). Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons (By similarity).</text>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="6 7">
            <name>[2Fe-2S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:190135"/>
        </cofactor>
        <text evidence="6 7">Binds 1 [2Fe-2S] cluster.</text>
    </comment>
    <comment type="biophysicochemical properties">
        <redoxPotential>
            <text>E(0) is -448 mV.</text>
        </redoxPotential>
    </comment>
    <comment type="subunit">
        <text evidence="6 7">Interacts with CYP11A1.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Mitochondrion matrix</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Highest levels in the adrenal gland (at protein level). Also detected in kidney and testis (at protein level).</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the adrenodoxin/putidaredoxin family.</text>
    </comment>
    <dbReference type="EMBL" id="M23668">
        <property type="protein sequence ID" value="AAA50462.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03548">
        <property type="protein sequence ID" value="AAA96806.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M18003">
        <property type="protein sequence ID" value="AAA76853.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M34788">
        <property type="protein sequence ID" value="AAA35829.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M34786">
        <property type="protein sequence ID" value="AAA35856.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M34784">
        <property type="protein sequence ID" value="AAA35856.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M34785">
        <property type="protein sequence ID" value="AAA35855.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M34783">
        <property type="protein sequence ID" value="AAA35855.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT006681">
        <property type="protein sequence ID" value="AAP35327.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="EF444978">
        <property type="protein sequence ID" value="ACA05992.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC010284">
        <property type="protein sequence ID" value="AAH10284.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017063">
        <property type="protein sequence ID" value="AAH17063.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8344.1"/>
    <dbReference type="PIR" id="A31853">
        <property type="entry name" value="AXHU"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004100.1">
        <property type="nucleotide sequence ID" value="NM_004109.5"/>
    </dbReference>
    <dbReference type="PDB" id="3N9Y">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="C/D=62-175"/>
    </dbReference>
    <dbReference type="PDB" id="3N9Z">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.17 A"/>
        <property type="chains" value="C/D=62-184"/>
    </dbReference>
    <dbReference type="PDB" id="3NA0">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.50 A"/>
        <property type="chains" value="C/D=88-155"/>
    </dbReference>
    <dbReference type="PDB" id="3NA1">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.25 A"/>
        <property type="chains" value="C/D=62-184"/>
    </dbReference>
    <dbReference type="PDB" id="3P1M">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.54 A"/>
        <property type="chains" value="A/B/C/D/E/F/G/H=61-184"/>
    </dbReference>
    <dbReference type="PDB" id="7M8I">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.94 A"/>
        <property type="chains" value="A/B/C=61-184"/>
    </dbReference>
    <dbReference type="PDBsum" id="3N9Y"/>
    <dbReference type="PDBsum" id="3N9Z"/>
    <dbReference type="PDBsum" id="3NA0"/>
    <dbReference type="PDBsum" id="3NA1"/>
    <dbReference type="PDBsum" id="3P1M"/>
    <dbReference type="PDBsum" id="7M8I"/>
    <dbReference type="AlphaFoldDB" id="P10109"/>
    <dbReference type="BMRB" id="P10109"/>
    <dbReference type="SMR" id="P10109"/>
    <dbReference type="BioGRID" id="108521">
        <property type="interactions" value="44"/>
    </dbReference>
    <dbReference type="FunCoup" id="P10109">
        <property type="interactions" value="883"/>
    </dbReference>
    <dbReference type="IntAct" id="P10109">
        <property type="interactions" value="12"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000260270"/>
    <dbReference type="DrugBank" id="DB00648">
        <property type="generic name" value="Mitotane"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P10109"/>
    <dbReference type="iPTMnet" id="P10109"/>
    <dbReference type="PhosphoSitePlus" id="P10109"/>
    <dbReference type="BioMuta" id="FDX1"/>
    <dbReference type="DMDM" id="113471"/>
    <dbReference type="jPOST" id="P10109"/>
    <dbReference type="MassIVE" id="P10109"/>
    <dbReference type="PaxDb" id="9606-ENSP00000260270"/>
    <dbReference type="PeptideAtlas" id="P10109"/>
    <dbReference type="ProteomicsDB" id="52566"/>
    <dbReference type="Pumba" id="P10109"/>
    <dbReference type="TopDownProteomics" id="P10109"/>
    <dbReference type="Antibodypedia" id="32013">
        <property type="antibodies" value="123 antibodies from 25 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2230"/>
    <dbReference type="Ensembl" id="ENST00000260270.3">
        <property type="protein sequence ID" value="ENSP00000260270.2"/>
        <property type="gene ID" value="ENSG00000137714.4"/>
    </dbReference>
    <dbReference type="GeneID" id="2230"/>
    <dbReference type="KEGG" id="hsa:2230"/>
    <dbReference type="MANE-Select" id="ENST00000260270.3">
        <property type="protein sequence ID" value="ENSP00000260270.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_004109.5"/>
        <property type="RefSeq protein sequence ID" value="NP_004100.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001pkx.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:3638"/>
    <dbReference type="ClinPGx" id="PA28082"/>
    <dbReference type="CTD" id="2230"/>
    <dbReference type="DisGeNET" id="2230"/>
    <dbReference type="GeneCards" id="FDX1"/>
    <dbReference type="HGNC" id="HGNC:3638">
        <property type="gene designation" value="FDX1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000137714">
        <property type="expression patterns" value="Tissue enriched (adrenal)"/>
    </dbReference>
    <dbReference type="MIM" id="103260">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000137714"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000137714"/>
    <dbReference type="eggNOG" id="KOG3309">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000156916"/>
    <dbReference type="HOGENOM" id="CLU_082632_2_1_1"/>
    <dbReference type="InParanoid" id="P10109"/>
    <dbReference type="OMA" id="TPMEEDM"/>
    <dbReference type="OrthoDB" id="268593at2759"/>
    <dbReference type="PAN-GO" id="P10109">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P10109"/>
    <dbReference type="PathwayCommons" id="P10109"/>
    <dbReference type="Reactome" id="R-HSA-1362409">
        <property type="pathway name" value="Mitochondrial iron-sulfur cluster biogenesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-196108">
        <property type="pathway name" value="Pregnenolone biosynthesis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-211976">
        <property type="pathway name" value="Endogenous sterols"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-2395516">
        <property type="pathway name" value="Electron transport from NADPH to Ferredoxin"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-5579026">
        <property type="pathway name" value="Defective CYP11A1 causes AICSR"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9857492">
        <property type="pathway name" value="Protein lipoylation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P10109"/>
    <dbReference type="Agora" id="ENSG00000137714"/>
    <dbReference type="BioGRID-ORCS" id="2230">
        <property type="hits" value="176 hits in 1150 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="FDX1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P10109"/>
    <dbReference type="GeneWiki" id="Adrenal_ferredoxin"/>
    <dbReference type="GenomeRNAi" id="2230"/>
    <dbReference type="Pharos" id="P10109">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P10109"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 11"/>
    </dbReference>
    <dbReference type="RNAct" id="P10109">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000137714">
        <property type="expression patterns" value="Expressed in adrenal tissue and 206 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005759">
        <property type="term" value="C:mitochondrial matrix"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051537">
        <property type="term" value="F:2 iron, 2 sulfur cluster binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0009055">
        <property type="term" value="F:electron transfer activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005506">
        <property type="term" value="F:iron ion binding"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071320">
        <property type="term" value="P:cellular response to cAMP"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:1904322">
        <property type="term" value="P:cellular response to forskolin"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008203">
        <property type="term" value="P:cholesterol metabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0022900">
        <property type="term" value="P:electron transport chain"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042446">
        <property type="term" value="P:hormone biosynthetic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140647">
        <property type="term" value="P:P450-containing electron transport chain"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006694">
        <property type="term" value="P:steroid biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd00207">
        <property type="entry name" value="fer2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.10.20.30:FF:000013">
        <property type="entry name" value="Adrenodoxin, mitochondrial"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.10.20.30">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036010">
        <property type="entry name" value="2Fe-2S_ferredoxin-like_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001041">
        <property type="entry name" value="2Fe-2S_ferredoxin-type"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001055">
        <property type="entry name" value="Adrenodoxin-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018298">
        <property type="entry name" value="Adrenodoxin_Fe-S_BS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR012675">
        <property type="entry name" value="Beta-grasp_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23426:SF26">
        <property type="entry name" value="ADRENODOXIN, MITOCHONDRIAL"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23426">
        <property type="entry name" value="FERREDOXIN/ADRENODOXIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00111">
        <property type="entry name" value="Fer2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00355">
        <property type="entry name" value="ADRENODOXIN"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF54292">
        <property type="entry name" value="2Fe-2S ferredoxin-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51085">
        <property type="entry name" value="2FE2S_FER_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00814">
        <property type="entry name" value="ADX"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0001">2Fe-2S</keyword>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0153">Cholesterol metabolism</keyword>
    <keyword id="KW-0249">Electron transport</keyword>
    <keyword id="KW-0408">Iron</keyword>
    <keyword id="KW-0411">Iron-sulfur</keyword>
    <keyword id="KW-0443">Lipid metabolism</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0753">Steroid metabolism</keyword>
    <keyword id="KW-0755">Steroidogenesis</keyword>
    <keyword id="KW-1207">Sterol metabolism</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="transit peptide" description="Mitochondrion">
        <location>
            <begin position="1"/>
            <end position="60"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000000988" description="Adrenodoxin, mitochondrial">
        <location>
            <begin position="61"/>
            <end position="184"/>
        </location>
    </feature>
    <feature type="domain" description="2Fe-2S ferredoxin-type" evidence="3">
        <location>
            <begin position="67"/>
            <end position="171"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="35"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="4">
        <location>
            <begin position="46"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="binding site">
        <location>
            <position position="106"/>
        </location>
        <ligand>
            <name>[2Fe-2S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:190135"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="112"/>
        </location>
        <ligand>
            <name>[2Fe-2S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:190135"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="115"/>
        </location>
        <ligand>
            <name>[2Fe-2S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:190135"/>
        </ligand>
    </feature>
    <feature type="binding site">
        <location>
            <position position="152"/>
        </location>
        <ligand>
            <name>[2Fe-2S] cluster</name>
            <dbReference type="ChEBI" id="CHEBI:190135"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="63"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine; alternate" evidence="2">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine; alternate" evidence="2">
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="2">
        <location>
            <position position="158"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="9">
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="67"/>
            <end position="72"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="78"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="89"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="turn" evidence="10">
        <location>
            <begin position="101"/>
            <end position="106"/>
        </location>
    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="108"/>
            <end position="111"/>
        </location>
    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="116"/>
            <end position="118"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="121"/>
            <end position="124"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="132"/>
            <end position="139"/>
        </location>
    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="141"/>
            <end position="143"/>
        </location>
    </feature>
    <feature type="strand" evidence="10">
        <location>
            <begin position="148"/>
            <end position="150"/>
        </location>
    </feature>
    <feature type="helix" evidence="10">
        <location>
            <begin position="151"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="158"/>
            <end position="160"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="163"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="171"/>
            <end position="174"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P00257"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P46656"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00465"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="20547883"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21636783"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source ref="16"/>
    </evidence>
    <evidence type="ECO:0000305" key="8"/>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="10">
        <source>
            <dbReference type="PDB" id="3N9Y"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="11">
        <source>
            <dbReference type="PDB" id="3P1M"/>
        </source>
    </evidence>
    <sequence length="184" mass="19393" checksum="A234EC601136C85F" modified="1989-07-01" version="1" precursor="true">MAAAGGARLLRAASAVLGGPAGRWLHHAGSRAGSSGLLRNRGPGGSAEASRSLSVSARARSSSEDKITVHFINRDGETLTTKGKVGDSLLDVVVENNLDIDGFGACEGTLACSTCHLIFEDHIYEKLDAITDEENDMLDLAYGLTDRSRLGCQICLTKSMDNMTVRVPETVADARQSIDVGKTS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1989-10-01" modified="2026-01-28" version="253" xmlns="https://uniprot.org/uniprot">
    <accession>P12236</accession>
    <accession>Q96C49</accession>
    <name>ADT3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="19">ADP/ATP translocase 3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="16">ADP,ATP carrier protein 3</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="15">ADP,ATP carrier protein, isoform T2</fullName>
            <shortName evidence="15">ANT 2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="17">Adenine nucleotide translocator 3</fullName>
            <shortName evidence="17">ANT 3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="19">Solute carrier family 25 member 6</fullName>
        </alternativeName>
        <component>
            <recommendedName>
                <fullName>ADP/ATP translocase 3, N-terminally processed</fullName>
            </recommendedName>
        </component>
    </protein>
    <gene>
        <name evidence="20" type="primary">SLC25A6</name>
        <name evidence="16" type="synonym">AAC3</name>
        <name evidence="17" type="synonym">ANT3</name>
        <name evidence="18" type="ORF">CDABP0051</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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    <comment type="function">
        <text evidence="1 5 7">ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:15033708). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A6/ANT3 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:15033708). It is however unclear if SLC25A6/ANT3 constitutes a pore-forming component of mPTP or regulates it (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>ADP(in) + ATP(out) = ADP(out) + ATP(in)</text>
            <dbReference type="Rhea" id="RHEA:34999"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5">
            <text>H(+)(in) = H(+)(out)</text>
            <dbReference type="Rhea" id="RHEA:34979"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
        </reaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="1 5">The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2 4">Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A6/ANT3 (By similarity).</text>
    </comment>
    <comment type="subunit">
        <text evidence="9">(Microbial infection) Interacts with influenza A virus PB1-F2 protein.</text>
    </comment>
    <comment type="subunit">
        <text evidence="8">(Microbial infection) Interacts with HIV-1 Vpr.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-432924">
            <id>P63010</id>
            <label>AP2B1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-948001">
            <id>Q15323</id>
            <label>KRT31</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-5323863">
            <id>Q5S007</id>
            <label>LRRK2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-741037">
            <id>Q9BRK4</id>
            <label>LZTS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-10172526">
            <id>Q9UJV3-2</id>
            <label>MID2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-742948">
            <id>Q5JR59</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-945833">
            <id>Q7Z3S9</id>
            <label>NOTCH2NLA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-359074">
            <id>P12235</id>
            <label>SLC25A4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-750487">
            <id>Q8WW24</id>
            <label>TEKT4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-359224">
            <id>Q13077</id>
            <label>TRAF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-740098">
            <id>P36406</id>
            <label>TRIM23</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-742327">
            <id>Q15654</id>
            <label>TRIP6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-354158">
            <id>P21796</id>
            <label>VDAC1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-356254">
            <id>P12236</id>
        </interactant>
        <interactant intactId="EBI-12579807">
            <id>P0C0U1</id>
            <label>PB1</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Mitochondrion inner membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="10">Membrane</location>
            <topology evidence="6">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="3">The complex formed with ARL2BP, ARL2 and SLC25A6/ANT3 is expressed in mitochondria (By similarity). May localize to non-mitochondrial membranes (By similarity).</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Expressed in erythrocytes (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="2">The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.</text>
    </comment>
    <comment type="PTM">
        <text evidence="11">Trimethylated by ANTKMT at Lys-52.</text>
    </comment>
    <comment type="miscellaneous">
        <text evidence="12">The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes and escapes X-inactivation.</text>
    </comment>
    <comment type="similarity">
        <text evidence="19">Belongs to the mitochondrial carrier (TC 2.A.29) family.</text>
    </comment>
    <dbReference type="EMBL" id="AY007135">
        <property type="protein sequence ID" value="AAG01998.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007295">
        <property type="protein sequence ID" value="AAH07295.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007850">
        <property type="protein sequence ID" value="AAH07850.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008737">
        <property type="protein sequence ID" value="AAH08737.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008935">
        <property type="protein sequence ID" value="AAH08935.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC014775">
        <property type="protein sequence ID" value="AAH14775.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC031912">
        <property type="protein sequence ID" value="AAH31912.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="J03592">
        <property type="protein sequence ID" value="AAA36750.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14114.1"/>
    <dbReference type="PIR" id="S03894">
        <property type="entry name" value="S03894"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001627.2">
        <property type="nucleotide sequence ID" value="NM_001636.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P12236"/>
    <dbReference type="SMR" id="P12236"/>
    <dbReference type="BioGRID" id="106790">
        <property type="interactions" value="478"/>
    </dbReference>
    <dbReference type="FunCoup" id="P12236">
        <property type="interactions" value="3078"/>
    </dbReference>
    <dbReference type="IntAct" id="P12236">
        <property type="interactions" value="305"/>
    </dbReference>
    <dbReference type="MINT" id="P12236"/>
    <dbReference type="STRING" id="9606.ENSP00000370808"/>
    <dbReference type="ChEMBL" id="CHEMBL4105854"/>
    <dbReference type="DrugBank" id="DB00720">
        <property type="generic name" value="Clodronic acid"/>
    </dbReference>
    <dbReference type="DrugBank" id="DB01077">
        <property type="generic name" value="Etidronic acid"/>
    </dbReference>
    <dbReference type="DrugCentral" id="P12236"/>
    <dbReference type="TCDB" id="2.A.29.1.10">
        <property type="family name" value="the mitochondrial carrier (mc) family"/>
    </dbReference>
    <dbReference type="GlyGen" id="P12236">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P12236"/>
    <dbReference type="MetOSite" id="P12236"/>
    <dbReference type="PhosphoSitePlus" id="P12236"/>
    <dbReference type="SwissPalm" id="P12236"/>
    <dbReference type="BioMuta" id="SLC25A6"/>
    <dbReference type="DMDM" id="113463"/>
    <dbReference type="jPOST" id="P12236"/>
    <dbReference type="MassIVE" id="P12236"/>
    <dbReference type="PaxDb" id="9606-ENSP00000370808"/>
    <dbReference type="PeptideAtlas" id="P12236"/>
    <dbReference type="ProteomicsDB" id="52837"/>
    <dbReference type="Pumba" id="P12236"/>
    <dbReference type="TopDownProteomics" id="P12236"/>
    <dbReference type="Antibodypedia" id="23393">
        <property type="antibodies" value="291 antibodies from 30 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="293"/>
    <dbReference type="Ensembl" id="ENST00000381401.11">
        <property type="protein sequence ID" value="ENSP00000370808.5"/>
        <property type="gene ID" value="ENSG00000169100.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000711212.2">
        <property type="protein sequence ID" value="ENSP00000518609.1"/>
        <property type="gene ID" value="ENSG00000292334.2"/>
    </dbReference>
    <dbReference type="GeneID" id="293"/>
    <dbReference type="KEGG" id="hsa:293"/>
    <dbReference type="MANE-Select" id="ENST00000381401.11">
        <property type="protein sequence ID" value="ENSP00000370808.5"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001636.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001627.2"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:10992"/>
    <dbReference type="ClinPGx" id="PA35868"/>
    <dbReference type="CTD" id="293"/>
    <dbReference type="DisGeNET" id="293"/>
    <dbReference type="GeneCards" id="SLC25A6"/>
    <dbReference type="HGNC" id="HGNC:10992">
        <property type="gene designation" value="SLC25A6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000169100">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="300151">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="403000">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000169100"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000169100"/>
    <dbReference type="eggNOG" id="KOG0749">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000162883"/>
    <dbReference type="HOGENOM" id="CLU_015166_12_0_1"/>
    <dbReference type="InParanoid" id="P12236"/>
    <dbReference type="OMA" id="CFARTLK"/>
    <dbReference type="OrthoDB" id="270584at2759"/>
    <dbReference type="PAN-GO" id="P12236">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P12236"/>
    <dbReference type="PathwayCommons" id="P12236"/>
    <dbReference type="Reactome" id="R-HSA-1268020">
        <property type="pathway name" value="Mitochondrial protein import"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-168277">
        <property type="pathway name" value="Influenza Virus Induced Apoptosis"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-180897">
        <property type="pathway name" value="Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-83936">
        <property type="pathway name" value="Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9837999">
        <property type="pathway name" value="Mitochondrial protein degradation"/>
    </dbReference>
    <dbReference type="SignaLink" id="P12236"/>
    <dbReference type="Agora" id="ENSG00000169100"/>
    <dbReference type="BioGRID-ORCS" id="293">
        <property type="hits" value="10 hits in 625 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="232F8A39">
        <property type="entry name" value="P-body"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SLC25A6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="SLC25A6"/>
    <dbReference type="GenomeRNAi" id="293"/>
    <dbReference type="Pharos" id="P12236">
        <property type="development level" value="Tchem"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P12236"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome Y"/>
    </dbReference>
    <dbReference type="RNAct" id="P12236">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000169100">
        <property type="expression patterns" value="Expressed in cartilage tissue and 212 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P12236">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="Reactome"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005744">
        <property type="term" value="C:TIM23 mitochondrial import inner membrane translocase complex"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005471">
        <property type="term" value="F:ATP:ADP antiporter activity"/>
        <property type="evidence" value="ECO:0000303"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006915">
        <property type="term" value="P:apoptotic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0140021">
        <property type="term" value="P:mitochondrial ADP transmembrane transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990544">
        <property type="term" value="P:mitochondrial ATP transmembrane transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:1901029">
        <property type="term" value="P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="FunFam" id="1.50.40.10:FF:000002">
        <property type="entry name" value="Putative ADP/ATP translocase 2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.50.40.10">
        <property type="entry name" value="Mitochondrial carrier domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002113">
        <property type="entry name" value="ADT_euk_type"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002067">
        <property type="entry name" value="MCP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR023395">
        <property type="entry name" value="MCP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR018108">
        <property type="entry name" value="MCP_transmembrane"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45635">
        <property type="entry name" value="ADP,ATP CARRIER PROTEIN 1-RELATED-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45635:SF13">
        <property type="entry name" value="ADP_ATP TRANSLOCASE 3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00153">
        <property type="entry name" value="Mito_carr"/>
        <property type="match status" value="3"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00927">
        <property type="entry name" value="ADPTRNSLCASE"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00926">
        <property type="entry name" value="MITOCARRIER"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF103506">
        <property type="entry name" value="Mitochondrial carrier"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50920">
        <property type="entry name" value="SOLCAR"/>
        <property type="match status" value="3"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0050">Antiport</keyword>
    <keyword id="KW-0053">Apoptosis</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0903">Direct protein sequencing</keyword>
    <keyword id="KW-0945">Host-virus interaction</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0488">Methylation</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0999">Mitochondrion inner membrane</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000425781" description="ADP/ATP translocase 3">
        <location>
            <begin position="1"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="initiator methionine" description="Removed; alternate" evidence="14 21 23 25">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000090584" description="ADP/ATP translocase 3, N-terminally processed">
        <location>
            <begin position="2"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="19">
        <location>
            <begin position="1"/>
            <end position="7"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=1" evidence="2">
        <location>
            <begin position="8"/>
            <end position="37"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="19">
        <location>
            <begin position="38"/>
            <end position="74"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=2" evidence="2">
        <location>
            <begin position="75"/>
            <end position="99"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="19">
        <location>
            <begin position="100"/>
            <end position="109"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=3" evidence="2">
        <location>
            <begin position="110"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="19">
        <location>
            <begin position="131"/>
            <end position="178"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=4" evidence="2">
        <location>
            <begin position="179"/>
            <end position="199"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="19">
        <location>
            <begin position="200"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=5" evidence="2">
        <location>
            <begin position="211"/>
            <end position="231"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="19">
        <location>
            <begin position="232"/>
            <end position="273"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical; Name=6" evidence="2">
        <location>
            <begin position="274"/>
            <end position="291"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="19">
        <location>
            <begin position="292"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 1">
        <location>
            <begin position="6"/>
            <end position="98"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 2">
        <location>
            <begin position="111"/>
            <end position="201"/>
        </location>
    </feature>
    <feature type="repeat" description="Solcar 3">
        <location>
            <begin position="212"/>
            <end position="297"/>
        </location>
    </feature>
    <feature type="region of interest" description="Important for transport activity" evidence="3">
        <location>
            <begin position="235"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nucleotide carrier signature motif" evidence="2">
        <location>
            <begin position="235"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="80"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="92"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="2">
        <location>
            <position position="235"/>
        </location>
        <ligand>
            <name>ADP</name>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="23">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylthreonine; in ADP/ATP translocase 3, N-terminally processed" evidence="14 21 23 25">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6,N6,N6-trimethyllysine" evidence="11 24">
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="22">
        <location>
            <position position="105"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="22">
        <location>
            <position position="268"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_054819" evidence="13">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAA36750." evidence="19" ref="5">
        <original>KHTQ</original>
        <variation>RHA</variation>
        <location>
            <begin position="105"/>
            <end position="108"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="G2QNH0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P02722"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="P12235"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="4">
        <source>
            <dbReference type="UniProtKB" id="P32007"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="5">
        <source>
            <dbReference type="UniProtKB" id="P48962"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="6"/>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="15033708"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="16120388"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="16201016"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="27641616"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="31213526"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="8486369"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source ref="4"/>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="2541251"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source>
            <dbReference type="PubMed" id="31341297"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="17">
        <source>
            <dbReference type="PubMed" id="8486369"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="19"/>
    <evidence type="ECO:0000312" key="20">
        <source>
            <dbReference type="HGNC" id="HGNC:10992"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="22223895"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="24129315"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="25944712"/>
        </source>
    </evidence>
    <sequence length="298" mass="32866" checksum="18534E9F0E49672F" modified="2007-01-23" version="4">MTEQAISFAKDFLAGGIAAAISKTAVAPIERVKLLLQVQHASKQIAADKQYKGIVDCIVRIPKEQGVLSFWRGNLANVIRYFPTQALNFAFKDKYKQIFLGGVDKHTQFWRYFAGNLASGGAAGATSLCFVYPLDFARTRLAADVGKSGTEREFRGLGDCLVKITKSDGIRGLYQGFSVSVQGIIIYRAAYFGVYDTAKGMLPDPKNTHIVVSWMIAQTVTAVAGVVSYPFDTVRRRMMMQSGRKGADIMYTGTVDCWRKIFRDEGGKAFFKGAWSNVLRGMGGAFVLVLYDELKKVI</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="206" xmlns="https://uniprot.org/uniprot">
    <accession>P55197</accession>
    <accession>B1ANA8</accession>
    <accession>Q5JT37</accession>
    <accession>Q5VX90</accession>
    <accession>Q66K63</accession>
    <name>AF10_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="14">Protein AF-10</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ALL1-fused gene from chromosome 10 protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15" type="primary">MLLT10</name>
        <name evidence="11" type="synonym">AF10</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <scope>INTERACTION WITH DOT1L</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4)</scope>
        <source>
            <tissue>Ovary</tissue>
            <tissue>Prostate</tissue>
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        <scope>SELF-ASSOCIATION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DNA-BINDING</scope>
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        <scope>INTERACTION WITH SS18</scope>
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        <scope>INTERACTION WITH YEATS4</scope>
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        <scope>FUNCTION</scope>
        <scope>SELF-ASSOCIATION</scope>
        <scope>INTERACTION WITH FSTL3</scope>
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        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-280</scope>
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        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-208 IN COMPLEX WITH HISTONE H3 PEPTIDE AND ZINC</scope>
        <scope>INTERACTION WITH HISTONE H3</scope>
        <scope>MUTAGENESIS OF ILE-22; VAL-80; ALA-106; LEU-107; ILE-109; PHE-114; MET-120; GLU-179 AND TYR-190</scope>
        <scope>FUNCTION</scope>
        <scope>REGION</scope>
    </reference>
    <reference evidence="18 19" key="18">
        <citation type="submission" date="2018-02" db="PDB data bank">
            <title>Crystal structure of an AF10 fragment.</title>
            <authorList>
                <person name="Zhang H."/>
                <person name="Tempel W."/>
                <person name="Bountra C."/>
                <person name="Arrowsmith C.H."/>
                <person name="Edwards A.M."/>
                <person name="Min J."/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 704-779</scope>
    </reference>
    <comment type="function">
        <text evidence="9 10">Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302).</text>
    </comment>
    <comment type="subunit">
        <text evidence="6 7 8 9 10">Self-associates. Interacts with FSTL3 isoform 2; the interaction enhances MLLT10 in vitro transcriptional activity and self-association. Interacts with YEATS4. Interacts with SS18. Interacts with DOT1L; this interaction also occurs with the KMT2A/MLL1 fusion protein. Interacts with histone H3; interaction is necessary for MLLT10 binding to nucleosomes; interaction is inhibited by histone H3 'Lys-27' methylations (H3K27me1, H3K27me2 and H3K27me3) amd acetylation; interaction stabilizes association of MLLT10 at chromatin; interaction is essential for histone H3 'Lys-79' dimethylation (H3K79me2) (PubMed:26439302).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1104952">
            <id>P55197</id>
        </interactant>
        <interactant intactId="EBI-491549">
            <id>P35222</id>
            <label>CTNNB1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1104952">
            <id>P55197</id>
        </interactant>
        <interactant intactId="EBI-2619253">
            <id>Q8TEK3</id>
            <label>DOT1L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-12018822">
            <id>Q12951-2</id>
            <label>FOXI1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-2798841">
            <id>P35680</id>
            <label>HNF1B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-12197079">
            <id>P84074</id>
            <label>HPCA</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-749635">
            <id>P61601</id>
            <label>NCALD</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-11526590">
            <id>P14859-6</id>
            <label>POU2F1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-12029004">
            <id>P78424</id>
            <label>POU6F2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-740343">
            <id>Q93062-3</id>
            <label>RBPMS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-12853322">
            <id>P55197-2</id>
        </interactant>
        <interactant intactId="EBI-11980193">
            <id>Q14119</id>
            <label>VEZF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P55197-4</id>
            <name>4</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P55197-1</id>
            <name>1</name>
            <sequence type="described" ref="VSP_047517 VSP_047518 VSP_047519"/>
        </isoform>
        <isoform>
            <id>P55197-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_043044 VSP_043045"/>
        </isoform>
        <isoform>
            <id>P55197-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_044552 VSP_044553"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Expressed abundantly in testis.</text>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.</text>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.</text>
    </comment>
    <comment type="sequence caution" evidence="14">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="BC129946"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/4/AF10"/>
    </comment>
    <dbReference type="EMBL" id="U13948">
        <property type="protein sequence ID" value="AAA79972.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY598745">
        <property type="protein sequence ID" value="AAT47519.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL161799">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL358780">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL359697">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL357372">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC080577">
        <property type="protein sequence ID" value="AAH80577.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC094844">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC129946">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55706.1">
        <molecule id="P55197-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55707.1">
        <molecule id="P55197-3"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55708.1">
        <molecule id="P55197-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7135.1">
        <molecule id="P55197-1"/>
    </dbReference>
    <dbReference type="PIR" id="I38759">
        <property type="entry name" value="I38759"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001182555.1">
        <molecule id="P55197-4"/>
        <property type="nucleotide sequence ID" value="NM_001195626.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001182556.1">
        <molecule id="P55197-2"/>
        <property type="nucleotide sequence ID" value="NM_001195627.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001182557.1">
        <molecule id="P55197-3"/>
        <property type="nucleotide sequence ID" value="NM_001195628.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001182559.1">
        <molecule id="P55197-3"/>
        <property type="nucleotide sequence ID" value="NM_001195630.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001311225.1">
        <molecule id="P55197-3"/>
        <property type="nucleotide sequence ID" value="NM_001324296.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004632.1">
        <molecule id="P55197-1"/>
        <property type="nucleotide sequence ID" value="NM_004641.4"/>
    </dbReference>
    <dbReference type="PDB" id="5DAG">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.60 A"/>
        <property type="chains" value="A=1-208"/>
    </dbReference>
    <dbReference type="PDB" id="5DAH">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.61 A"/>
        <property type="chains" value="A/B=1-208"/>
    </dbReference>
    <dbReference type="PDB" id="6CKN">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.49 A"/>
        <property type="chains" value="A/B=704-779"/>
    </dbReference>
    <dbReference type="PDB" id="6CKO">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.00 A"/>
        <property type="chains" value="A/B=704-779"/>
    </dbReference>
    <dbReference type="PDB" id="6JN2">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.60 A"/>
        <property type="chains" value="A=699-782"/>
    </dbReference>
    <dbReference type="PDB" id="7MJU">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=19-208"/>
    </dbReference>
    <dbReference type="PDBsum" id="5DAG"/>
    <dbReference type="PDBsum" id="5DAH"/>
    <dbReference type="PDBsum" id="6CKN"/>
    <dbReference type="PDBsum" id="6CKO"/>
    <dbReference type="PDBsum" id="6JN2"/>
    <dbReference type="PDBsum" id="7MJU"/>
    <dbReference type="AlphaFoldDB" id="P55197"/>
    <dbReference type="SMR" id="P55197"/>
    <dbReference type="BioGRID" id="113723">
        <property type="interactions" value="57"/>
    </dbReference>
    <dbReference type="CORUM" id="P55197"/>
    <dbReference type="DIP" id="DIP-37633N"/>
    <dbReference type="FunCoup" id="P55197">
        <property type="interactions" value="3421"/>
    </dbReference>
    <dbReference type="IntAct" id="P55197">
        <property type="interactions" value="44"/>
    </dbReference>
    <dbReference type="MINT" id="P55197"/>
    <dbReference type="STRING" id="9606.ENSP00000307411"/>
    <dbReference type="GlyCosmos" id="P55197">
        <property type="glycosylation" value="2 sites, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="P55197">
        <property type="glycosylation" value="11 sites, 1 O-linked glycan (9 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P55197"/>
    <dbReference type="PhosphoSitePlus" id="P55197"/>
    <dbReference type="BioMuta" id="MLLT10"/>
    <dbReference type="DMDM" id="527504034"/>
    <dbReference type="jPOST" id="P55197"/>
    <dbReference type="MassIVE" id="P55197"/>
    <dbReference type="PaxDb" id="9606-ENSP00000307411"/>
    <dbReference type="PeptideAtlas" id="P55197"/>
    <dbReference type="ProteomicsDB" id="3249"/>
    <dbReference type="ProteomicsDB" id="56802">
        <molecule id="P55197-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56803">
        <molecule id="P55197-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65583"/>
    <dbReference type="Pumba" id="P55197"/>
    <dbReference type="Antibodypedia" id="1417">
        <property type="antibodies" value="384 antibodies from 33 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="8028"/>
    <dbReference type="Ensembl" id="ENST00000307729.12">
        <molecule id="P55197-4"/>
        <property type="protein sequence ID" value="ENSP00000307411.7"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377059.7">
        <molecule id="P55197-4"/>
        <property type="protein sequence ID" value="ENSP00000366258.4"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377072.8">
        <molecule id="P55197-1"/>
        <property type="protein sequence ID" value="ENSP00000366272.3"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377091.7">
        <molecule id="P55197-2"/>
        <property type="protein sequence ID" value="ENSP00000366295.2"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000377100.8">
        <molecule id="P55197-3"/>
        <property type="protein sequence ID" value="ENSP00000366304.3"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000621220.4">
        <molecule id="P55197-2"/>
        <property type="protein sequence ID" value="ENSP00000484335.1"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000631589.1">
        <molecule id="P55197-4"/>
        <property type="protein sequence ID" value="ENSP00000488569.1"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000652497.1">
        <molecule id="P55197-3"/>
        <property type="protein sequence ID" value="ENSP00000498595.1"/>
        <property type="gene ID" value="ENSG00000078403.18"/>
    </dbReference>
    <dbReference type="GeneID" id="8028"/>
    <dbReference type="KEGG" id="hsa:8028"/>
    <dbReference type="MANE-Select" id="ENST00000307729.12">
        <property type="protein sequence ID" value="ENSP00000307411.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001195626.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001182555.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001iqq.3">
        <molecule id="P55197-4"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16063"/>
    <dbReference type="ClinPGx" id="PA30849"/>
    <dbReference type="CTD" id="8028"/>
    <dbReference type="DisGeNET" id="8028"/>
    <dbReference type="GeneCards" id="MLLT10"/>
    <dbReference type="HGNC" id="HGNC:16063">
        <property type="gene designation" value="MLLT10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000078403">
        <property type="expression patterns" value="Tissue enhanced (testis)"/>
    </dbReference>
    <dbReference type="MalaCards" id="MLLT10"/>
    <dbReference type="MIM" id="602409">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000078403"/>
    <dbReference type="Orphanet" id="99861">
        <property type="disease" value="Precursor T-cell acute lymphoblastic leukemia"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000078403"/>
    <dbReference type="eggNOG" id="KOG0956">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157711"/>
    <dbReference type="HOGENOM" id="CLU_128812_0_0_1"/>
    <dbReference type="InParanoid" id="P55197"/>
    <dbReference type="OMA" id="XTCYICD"/>
    <dbReference type="OrthoDB" id="20839at2759"/>
    <dbReference type="PAN-GO" id="P55197">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P55197"/>
    <dbReference type="PathwayCommons" id="P55197"/>
    <dbReference type="SignaLink" id="P55197"/>
    <dbReference type="SIGNOR" id="P55197"/>
    <dbReference type="Agora" id="ENSG00000078403"/>
    <dbReference type="BioGRID-ORCS" id="8028">
        <property type="hits" value="21 hits in 1171 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="MLLT10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="P55197"/>
    <dbReference type="GeneWiki" id="MLLT10"/>
    <dbReference type="GenomeRNAi" id="8028"/>
    <dbReference type="Pharos" id="P55197">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P55197"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="P55197">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000078403">
        <property type="expression patterns" value="Expressed in buccal mucosa cell and 187 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P55197">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032991">
        <property type="term" value="C:protein-containing complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003682">
        <property type="term" value="F:chromatin binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003677">
        <property type="term" value="F:DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042393">
        <property type="term" value="F:histone binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031491">
        <property type="term" value="F:nucleosome binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045944">
        <property type="term" value="P:positive regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006357">
        <property type="term" value="P:regulation of transcription by RNA polymerase II"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="CDD" id="cd20901">
        <property type="entry name" value="CC_AF10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd15708">
        <property type="entry name" value="ePHD_AF10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd15574">
        <property type="entry name" value="PHD_AF10_AF17"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="DisProt" id="DP02852"/>
    <dbReference type="FunFam" id="3.30.40.10:FF:000042">
        <property type="entry name" value="protein AF-10 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.40.10:FF:000053">
        <property type="entry name" value="protein AF-10 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.40.10">
        <property type="entry name" value="Zinc/RING finger domain, C3HC4 (zinc finger)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049773">
        <property type="entry name" value="AF10-like_CC"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049781">
        <property type="entry name" value="AF10/AF17_PHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049775">
        <property type="entry name" value="AF10_ePHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034732">
        <property type="entry name" value="EPHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050701">
        <property type="entry name" value="Histone_Mod_Regulator"/>
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    <dbReference type="InterPro" id="IPR019786">
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        <property type="match status" value="1"/>
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        <property type="match status" value="2"/>
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    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0656">Proto-oncogene</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
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    <keyword id="KW-0863">Zinc-finger</keyword>
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            <begin position="223"/>
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        <location>
            <begin position="595"/>
            <end position="604"/>
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            <begin position="855"/>
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            <position position="266"/>
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            <position position="627"/>
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            <position position="664"/>
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        <original>RCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQSVPHDRYNKTCYICDEQGRESKAATGACMTCNKHGCRQAFHVTCAQFAGLLCE</original>
        <variation>MVCNSCWLASSENVTPGYIEHHCACASPHPRCLVSNVPPVSGALMHCFWACLTTAAFFGPQSFTTCHMSFLVSRDILFYIYGFMPFISVVIWRFKKERW</variation>
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            <begin position="81"/>
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        <original>RCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVSTMEPIVLQ</original>
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            <begin position="81"/>
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        <original>N</original>
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            <position position="566"/>
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        <original>EQHQAFLYQLMQHHHQQHHQPELQQL</original>
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            <begin position="986"/>
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            <begin position="1012"/>
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        <original>I</original>
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            <begin position="26"/>
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            <begin position="39"/>
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        <location>
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    <feature type="strand" evidence="23">
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    <sequence length="1068" mass="113320" checksum="0C4D9B77F61BFEEE" modified="2013-07-24" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-05-20" modified="2026-01-28" version="181" xmlns="https://uniprot.org/uniprot">
    <accession>Q8IUX7</accession>
    <accession>Q14113</accession>
    <accession>Q59ER7</accession>
    <accession>Q6ZSC7</accession>
    <accession>Q7KZ79</accession>
    <name>AEBP1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Adipocyte enhancer-binding protein 1</fullName>
            <shortName>AE-binding protein 1</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Aortic carboxypeptidase-like protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AEBP1</name>
        <name type="synonym">ACLP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1998" name="J. Biol. Chem." volume="273" first="15654" last="15660">
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        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-528 AND ASN-922</scope>
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        <scope>INVOLVEMENT IN EDSCLL2</scope>
    </reference>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH COLLAGEN</scope>
        <scope>DOMAIN</scope>
        <scope>INVOLVEMENT IN EDSCLL2</scope>
        <scope>VARIANT EDSCLL2 581-CYS--PHE-1158 DEL</scope>
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    <comment type="function">
        <molecule>Isoform 1</molecule>
        <text evidence="9">As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.</text>
    </comment>
    <comment type="function">
        <molecule>Isoform 2</molecule>
        <text evidence="2">May positively regulate MAP-kinase activity in adipocytes, leading to enhanced adipocyte proliferation and reduced adipocyte differentiation. May also positively regulate NF-kappa-B activity in macrophages by promoting the phosphorylation and subsequent degradation of I-kappa-B-alpha (NFKBIA), leading to enhanced macrophage inflammatory responsiveness. Can act as a transcriptional repressor.</text>
    </comment>
    <comment type="subunit">
        <text evidence="2 9">Isoform 1: Interacts with different types of collagen, including collagens I, III, and V (PubMed:29606302). Isoform 2: Interacts with GNG5, NFKBIA, MAPK1, MAPK3 and PTEN. Interaction with MAPK1 may stimulate DNA-binding. May interact with calmodulin. Binds to DNA in vitro.</text>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location evidence="2">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8IUX7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8IUX7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_033467 VSP_033468 VSP_033469"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="10">Expressed in osteoblast and visceral fat.</text>
    </comment>
    <comment type="domain">
        <molecule>Isoform 1</molecule>
        <text evidence="9">The F5/8 type C domain binds to different types of collagen, including collagens I, III, and V.</text>
    </comment>
    <comment type="PTM">
        <text evidence="1">Phosphorylated by MAPK1 in vitro.</text>
    </comment>
    <comment type="disease" evidence="8 9">
        <disease id="DI-05255">
            <name>Ehlers-Danlos syndrome, classic-like, 2</name>
            <acronym>EDSCLL2</acronym>
            <description>A variant form of Ehlers-Danlos syndrome, a connective tissue disorder. EDSCLL2 patients show severe joint and skin laxity, osteoporosis affecting the hips and spine, osteoarthritis, soft redundant skin that can be acrogeria-like, delayed wound healing with abnormal atrophic scarring, and shoulder, hip, knee, and ankle dislocations. Additional variable features include gastrointestinal and genitourinary manifestations (bowel rupture, gut dysmotility, cryptorchidism, and hernias), vascular complications (mitral valve prolapse and aortic root dilation), and skeletal anomalies. EDSCLL2 inheritance is autosomal recessive.</description>
            <dbReference type="MIM" id="618000"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the peptidase M14 family.</text>
    </comment>
    <comment type="caution">
        <text evidence="13">Although related to peptidase M14 family, lacks the active site residues and zinc-binding sites, suggesting that it has no carboxypeptidase activity.</text>
    </comment>
    <comment type="sequence caution" evidence="13">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAD92981" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF053944">
        <property type="protein sequence ID" value="AAC25585.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK127541">
        <property type="protein sequence ID" value="BAC87026.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
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        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="F5_F8_type_C"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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        <property type="entry name" value="CRBOXYPTASEA"/>
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        <property type="match status" value="1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
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    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0248">Ehlers-Danlos syndrome</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
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    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0678">Repressor</keyword>
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    <keyword id="KW-0732">Signal</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
    <feature type="signal peptide" evidence="3">
        <location>
            <begin position="1"/>
            <end position="25"/>
        </location>
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    <feature type="chain" id="PRO_0000333189" description="Adipocyte enhancer-binding protein 1">
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            <begin position="26"/>
            <end position="1158"/>
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            <begin position="383"/>
            <end position="540"/>
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    </feature>
    <feature type="domain" description="Peptidase M14" evidence="5">
        <location>
            <begin position="563"/>
            <end position="904"/>
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    </feature>
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        <location>
            <begin position="41"/>
            <end position="387"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for DNA-binding and interaction with NFKBIA" evidence="1">
        <location>
            <begin position="390"/>
            <end position="555"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with MAPK1 and MAPK3" evidence="1">
        <location>
            <begin position="421"/>
            <end position="624"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with PTEN" evidence="1">
        <location>
            <begin position="555"/>
            <end position="985"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for transcriptional repression" evidence="1">
        <location>
            <begin position="941"/>
            <end position="1158"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with MAPK1 and MAPK3" evidence="1">
        <location>
            <begin position="1006"/>
            <end position="1158"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="6">
        <location>
            <begin position="1108"/>
            <end position="1141"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="6">
        <location>
            <begin position="45"/>
            <end position="55"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="100"/>
            <end position="110"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="6">
        <location>
            <begin position="116"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="182"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="6">
        <location>
            <begin position="193"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="211"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="6">
        <location>
            <begin position="252"/>
            <end position="266"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="267"/>
            <end position="289"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="6">
        <location>
            <begin position="290"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="6">
        <location>
            <begin position="326"/>
            <end position="371"/>
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    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="6">
        <location>
            <begin position="1108"/>
            <end position="1137"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="7">
        <location>
            <position position="528"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="7">
        <location>
            <position position="922"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033467" description="In isoform 2." evidence="12">
        <location>
            <begin position="1"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033468" description="In isoform 2." evidence="12">
        <original>ITQGRDSSIHDDFVTTFFVGFSNDSQTWVMYTNGYEEM</original>
        <variation>MRKWWAPCPGSWLCSHCLGEGWALRGAGSTALRPASPQ</variation>
        <location>
            <begin position="458"/>
            <end position="495"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033469" description="In isoform 2." evidence="12">
        <original>AP</original>
        <variation>ARECGGLAGALSGGGVLGWASRHPAKDNPASLAA</variation>
        <location>
            <begin position="543"/>
            <end position="544"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043118" description="In dbSNP:rs2537188.">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="273"/>
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    </feature>
    <feature type="sequence variant" id="VAR_080664" description="In EDSCLL2." evidence="9">
        <location>
            <begin position="581"/>
            <end position="1158"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_043119" description="In dbSNP:rs11770649.">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="648"/>
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    <feature type="sequence variant" id="VAR_043120" description="In dbSNP:rs4724285.">
        <original>P</original>
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            <position position="1001"/>
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    <feature type="sequence variant" id="VAR_043121" description="In dbSNP:rs13928." evidence="11">
        <original>K</original>
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            <position position="1133"/>
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    </feature>
    <feature type="sequence variant" id="VAR_043122" description="In dbSNP:rs13898.">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="1148"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC25585." evidence="13" ref="1">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="145"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC25585." evidence="13" ref="1">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="218"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC87026." evidence="13" ref="2">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="569"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC87026." evidence="13" ref="2">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="715"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC87026." evidence="13" ref="2">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="884"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAD92981." evidence="13" ref="3">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="1079"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q640N1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00081"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01379"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="6">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="19159218"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="27023906"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="29606302"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="8920928"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <sequence length="1158" mass="130929" checksum="1D7F4A20451646AE" modified="2003-03-01" version="1" precursor="true"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-06-13" modified="2026-01-28" version="191" xmlns="https://uniprot.org/uniprot">
    <accession>Q9UHB7</accession>
    <accession>B2RP19</accession>
    <accession>B7WPD2</accession>
    <accession>Q498B2</accession>
    <accession>Q59FB3</accession>
    <accession>Q6P592</accession>
    <accession>Q8TDR1</accession>
    <accession>Q9P0E4</accession>
    <name>AFF4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>AF4/FMR2 family member 4</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ALL1-fused gene from chromosome 5q31 protein</fullName>
            <shortName>Protein AF-5q31</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Major CDK9 elongation factor-associated protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AFF4</name>
        <name type="synonym">AF5Q31</name>
        <name type="synonym">MCEF</name>
        <name type="ORF">HSPC092</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <title>AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23).</title>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>DEVELOPMENTAL STAGE</scope>
        <source>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>PROTEIN SEQUENCE OF 111-122</scope>
        <scope>IDENTIFICATION IN P-TEFB COMPLEX</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <source>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-363 (ISOFORMS 1/2)</scope>
        <source>
            <tissue>Blood</tissue>
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            <tissue>Skin</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 788-1163 (ISOFORM 2)</scope>
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            <tissue>Cervix carcinoma</tissue>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549; SER-814; SER-1043 AND SER-1055</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387; SER-388; SER-389; SER-392; SER-671; SER-694; SER-703; SER-706; TYR-712; SER-1043; SER-1055; SER-1058 AND SER-1062</scope>
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            <dbReference type="PubMed" id="20471948"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2010.04.013"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE SEC COMPLEX</scope>
    </reference>
    <reference key="18">
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            <title>AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia.</title>
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            <dbReference type="PubMed" id="20159561"/>
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        </citation>
        <scope>FUNCTION</scope>
        <scope>IDENTIFICATION IN THE SEC COMPLEX</scope>
    </reference>
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            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-814; SER-836 AND SER-1043</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <authorList>
                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="21">
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            <authorList>
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            <dbReference type="PubMed" id="22195968"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2011.12.008"/>
        </citation>
        <scope>IDENTIFICATION IN THE SEC COMPLEX</scope>
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            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
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            <dbReference type="PubMed" id="21406692"/>
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        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="23">
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            </authorList>
            <dbReference type="PubMed" id="22483617"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2012.03.007"/>
        </citation>
        <scope>INTERACTION WITH ELL2</scope>
    </reference>
    <reference key="24">
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            <dbReference type="PubMed" id="22895430"/>
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        </citation>
        <scope>REVIEW ON THE SUPER ELONGATION COMPLEX</scope>
    </reference>
    <reference key="25">
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            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-212; SER-487; THR-674; SER-680; SER-703; SER-706; SER-814; SER-836; SER-1043 AND SER-1058</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
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            <authorList>
                <person name="Chou S."/>
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            <dbReference type="PubMed" id="23251033"/>
            <dbReference type="DOI" id="10.1073/pnas.1216971110"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Wang L."/>
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            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487 AND SER-706</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="28">
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            <title>Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.</title>
            <authorList>
                <person name="Izumi K."/>
                <person name="Nakato R."/>
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                <person name="Edmondson A.C."/>
                <person name="Noon S."/>
                <person name="Dulik M.C."/>
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            </authorList>
            <dbReference type="PubMed" id="25730767"/>
            <dbReference type="DOI" id="10.1038/ng.3229"/>
        </citation>
        <scope>INVOLVEMENT IN CHOPS</scope>
        <scope>VARIANTS CHOPS ALA-254; SER-254 AND TRP-258</scope>
    </reference>
    <reference key="29">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-583</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="30">
        <citation type="journal article" date="2018" name="Cell Rep." volume="24" first="2141" last="2154">
            <title>Positive Regulation of Transcription by Human ZMYND8 through Its Association with P-TEFb Complex.</title>
            <authorList>
                <person name="Ghosh K."/>
                <person name="Tang M."/>
                <person name="Kumari N."/>
                <person name="Nandy A."/>
                <person name="Basu S."/>
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            </authorList>
            <dbReference type="PubMed" id="30134174"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2018.07.064"/>
        </citation>
        <scope>INTERACTION WITH CDK9</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="31">
        <citation type="journal article" date="2024" name="Mol. Cell" volume="84" first="4824" last="4842">
            <title>The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release.</title>
            <authorList>
                <person name="Wang Z."/>
                <person name="Song A."/>
                <person name="Tao B."/>
                <person name="Miao M."/>
                <person name="Luo Y.Q."/>
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                <person name="Yin Z."/>
                <person name="Xiao R."/>
                <person name="Zhou X."/>
                <person name="Shang X.Y."/>
                <person name="Hu S."/>
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            </authorList>
            <dbReference type="PubMed" id="39603240"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2024.10.046"/>
        </citation>
        <scope>PHOSPHORYLATION AT SER-549</scope>
        <scope>DEPHOSPHORYLATION AT SER-549</scope>
    </reference>
    <reference key="32">
        <citation type="journal article" date="2011" name="Nature" volume="469" first="539" last="542">
            <title>Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.</title>
            <authorList>
                <person name="Varela I."/>
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            </authorList>
            <dbReference type="PubMed" id="21248752"/>
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        </citation>
        <scope>VARIANT THR-757</scope>
    </reference>
    <comment type="function">
        <text evidence="5 6 10">Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4 5 6 8 9 12">Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3) (PubMed:12065898, PubMed:20159561, PubMed:20471948, PubMed:22195968, PubMed:22483617, PubMed:30134174). Interacts with ELL3; the interaction is direct (By similarity). Interacts with ELL2; the interaction is direct and leads to stabilize ELL2 and prevent ELL2 ubiquitination and degradation (PubMed:22483617).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-432924">
            <id>P63010</id>
            <label>AP2B1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-2479671">
            <id>O60563</id>
            <label>CCNT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-618309">
            <id>Q08379</id>
            <label>GOLGA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-1384215">
            <id>Q03111</id>
            <label>MLLT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>11</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-716132">
            <id>P42568</id>
            <label>MLLT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-742948">
            <id>Q5JR59</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-747107">
            <id>Q8IUQ4</id>
            <label>SIAH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-355744">
            <id>Q12933</id>
            <label>TRAF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
        </interactant>
        <interactant intactId="EBI-6164389">
            <id>P04608</id>
            <label>tat</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10261324">
            <id>Q9UHB7-2</id>
        </interactant>
        <interactant intactId="EBI-432924">
            <id>P63010</id>
            <label>AP2B1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10261324">
            <id>Q9UHB7-2</id>
        </interactant>
        <interactant intactId="EBI-618309">
            <id>Q08379</id>
            <label>GOLGA2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10261324">
            <id>Q9UHB7-2</id>
        </interactant>
        <interactant intactId="EBI-742948">
            <id>Q5JR59</id>
            <label>MTUS2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10261324">
            <id>Q9UHB7-2</id>
        </interactant>
        <interactant intactId="EBI-747107">
            <id>Q8IUQ4</id>
            <label>SIAH1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-10261324">
            <id>Q9UHB7-2</id>
        </interactant>
        <interactant intactId="EBI-355744">
            <id>Q12933</id>
            <label>TRAF2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Chromosome</location>
        </subcellularLocation>
        <text evidence="1">Associates to transcriptionally active chromatin but not at snRNA genes.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9UHB7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9UHB7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_019220 VSP_019221"/>
        </isoform>
        <isoform>
            <id>Q9UHB7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_019218 VSP_019219"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3 4">Ubiquitously expressed. Strongly expressed in heart, placenta, skeletal muscle, pancreas and to a lower extent in brain.</text>
    </comment>
    <comment type="developmental stage">
        <text evidence="3">Expressed in fetal heart, lung, brain and to a lower extent liver.</text>
    </comment>
    <comment type="PTM">
        <text evidence="13">Dephosphorylated at Ser-549 by the PNUTS-PP1 complex, promoting RNA polymerase II transcription pause-release.</text>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a KMT2A/MLL1-AFF4 fusion protein.</text>
    </comment>
    <comment type="disease" evidence="11">
        <disease id="DI-04427">
            <name>CHOPS syndrome</name>
            <acronym>CHOPS</acronym>
            <description>A syndrome characterized by cognitive impairment, coarse facies, heart defects, obesity, pulmonary involvement, short stature, and skeletal dysplasia.</description>
            <dbReference type="MIM" id="616368"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="17">Belongs to the AF4 family.</text>
    </comment>
    <comment type="sequence caution" evidence="17">
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    <feature type="modified residue" description="N6-acetyllysine" evidence="1">
        <location>
            <position position="822"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="24 25">
        <location>
            <position position="836"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20 21 22 24 25">
        <location>
            <position position="1043"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20 21">
        <location>
            <position position="1055"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20 22 23 25">
        <location>
            <position position="1058"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="20">
        <location>
            <position position="1062"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="27">
        <location>
            <position position="583"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_019218" description="In isoform 3." evidence="15">
        <original>ESQ</original>
        <variation>VSK</variation>
        <location>
            <begin position="351"/>
            <end position="353"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_019219" description="In isoform 3." evidence="15">
        <location>
            <begin position="354"/>
            <end position="1163"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_019220" description="In isoform 2." evidence="14 16">
        <original>EKAPSSSSNCPPSAPTLDSSK</original>
        <variation>VKCWGPGAFENHSTCHVTFPG</variation>
        <location>
            <begin position="880"/>
            <end position="900"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_019221" description="In isoform 2." evidence="14 16">
        <location>
            <begin position="901"/>
            <end position="1163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_053003" description="In dbSNP:rs34527550.">
        <original>T</original>
        <variation>P</variation>
        <location>
            <position position="136"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073790" description="In CHOPS; dbSNP:rs786205233." evidence="11">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073791" description="In CHOPS; dbSNP:rs786205679." evidence="11">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_073792" description="In CHOPS; dbSNP:rs786205680." evidence="11">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_064693" description="Found in a clear cell renal carcinoma case; somatic mutation." evidence="7">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="757"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAM00184." evidence="17" ref="2">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAM00184." evidence="17" ref="2">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="359"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAM00184." evidence="17" ref="2">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="383"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAM00184." evidence="17" ref="2">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="445"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 7; AAF28915." evidence="17" ref="7">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="870"/>
        </location>
    </feature>
    <feature type="helix" evidence="28">
        <location>
            <begin position="4"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="47"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="helix" evidence="29">
        <location>
            <begin position="59"/>
            <end position="62"/>
        </location>
    </feature>
    <feature type="turn" evidence="29">
        <location>
            <begin position="63"/>
            <end position="65"/>
        </location>
    </feature>
    <feature type="helix" evidence="30">
        <location>
            <begin position="315"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="915"/>
            <end position="931"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="935"/>
            <end position="958"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="967"/>
            <end position="981"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="993"/>
            <end position="1017"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="1019"/>
            <end position="1032"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="1087"/>
            <end position="1116"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="1117"/>
            <end position="1120"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="1121"/>
            <end position="1131"/>
        </location>
    </feature>
    <feature type="turn" evidence="31">
        <location>
            <begin position="1136"/>
            <end position="1138"/>
        </location>
    </feature>
    <feature type="helix" evidence="31">
        <location>
            <begin position="1141"/>
            <end position="1159"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q9ESC8"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="10588740"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="12065898"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="20159561"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="20471948"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="21248752"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="22195968"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="22483617"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="23251033"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="25730767"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="30134174"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="39603240"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source>
            <dbReference type="PubMed" id="11042152"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="15">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="16">
        <source ref="3"/>
    </evidence>
    <evidence type="ECO:0000305" key="17"/>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="17081983"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="18220336"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="20">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="21">
        <source>
            <dbReference type="PubMed" id="18691976"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="22">
        <source>
            <dbReference type="PubMed" id="19369195"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="23">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="25">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="26">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="27">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="28">
        <source>
            <dbReference type="PDB" id="4IMY"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="29">
        <source>
            <dbReference type="PDB" id="4OR5"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="30">
        <source>
            <dbReference type="PDB" id="5JW9"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="31">
        <source>
            <dbReference type="PDB" id="6KN5"/>
        </source>
    </evidence>
    <sequence length="1163" mass="127459" checksum="474E1906B8832AC1" modified="2000-05-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="237" xmlns="https://uniprot.org/uniprot">
    <accession>P55196</accession>
    <accession>O75087</accession>
    <accession>O75088</accession>
    <accession>O75089</accession>
    <accession>Q59FP0</accession>
    <accession>Q5TIG6</accession>
    <accession>Q5TIG7</accession>
    <accession>Q9NSN7</accession>
    <accession>Q9NU92</accession>
    <name>AFAD_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Afadin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ALL1-fused gene from chromosome 6 protein</fullName>
            <shortName>Protein AF-6</shortName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="16">Afadin adherens junction formation factor</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">AFDN</name>
        <name type="synonym">AF6</name>
        <name type="synonym">MLLT4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation.</title>
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                <person name="Prasad R."/>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH KMT2A</scope>
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    <reference key="2">
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                <person name="Saito S."/>
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            <dbReference type="PubMed" id="9679199"/>
            <dbReference type="DOI" id="10.1093/dnares/5.2.115"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 3)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
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                <person name="King A."/>
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                <person name="Lawlor S."/>
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                <person name="Maslen G.L."/>
                <person name="Matthews L."/>
                <person name="McCann O.T."/>
                <person name="McLaren S.J."/>
                <person name="McLay K."/>
                <person name="McMurray A."/>
                <person name="Moore M.J.F."/>
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                <person name="Niblett D."/>
                <person name="Nickerson T."/>
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                <person name="Oliver K."/>
                <person name="Overton-Larty E.K."/>
                <person name="Parker A."/>
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                <person name="Phillimore B.J.C.T."/>
                <person name="Phillips S."/>
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                <person name="Smith M."/>
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                <person name="Tracey A."/>
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            </authorList>
            <dbReference type="PubMed" id="14574404"/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <authorList>
                <person name="Totoki Y."/>
                <person name="Toyoda A."/>
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                <person name="Ohara O."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 13-1824 (ISOFORM 6)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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                <person name="Mehrle A."/>
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                <person name="Bahr A."/>
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                <person name="Schupp I."/>
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            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 335-1824 (ISOFORM 5)</scope>
        <source>
            <tissue>Amygdala</tissue>
        </source>
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                <person name="Reymond N."/>
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            </authorList>
            <dbReference type="PubMed" id="11024295"/>
            <dbReference type="DOI" id="10.1016/s0378-1119(00)00316-4"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH NECTIN3</scope>
    </reference>
    <reference key="8">
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            <title>Nectin and afadin: novel organizers of intercellular junctions.</title>
            <authorList>
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                <person name="Nakanishi H."/>
            </authorList>
            <dbReference type="PubMed" id="12456712"/>
            <dbReference type="DOI" id="10.1242/jcs.00167"/>
        </citation>
        <scope>REVIEW ON INTERACTION</scope>
    </reference>
    <reference key="9">
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            <title>Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry.</title>
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            <dbReference type="PubMed" id="15144186"/>
            <dbReference type="DOI" id="10.1021/ac035352d"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="10">
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            <title>Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction.</title>
            <authorList>
                <person name="Tang L.-Y."/>
                <person name="Deng N."/>
                <person name="Wang L.-S."/>
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                <person name="Wu D.-Q."/>
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            </authorList>
            <dbReference type="PubMed" id="17693683"/>
            <dbReference type="DOI" id="10.1074/mcp.m700120-mcp200"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Embryonic kidney</tissue>
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            <title>Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.</title>
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                <person name="Cantin G.T."/>
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            <dbReference type="PubMed" id="18220336"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
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    <reference key="12">
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            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
                <person name="Zhou C."/>
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            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-1107; SER-1182; THR-1232; SER-1721; SER-1779 AND SER-1799</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
                <person name="Slijper M."/>
                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
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            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182 AND SER-1721</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
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                <person name="Gnad F."/>
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                <person name="Jensen T.S."/>
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            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1721; SER-1779 AND SER-1799</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
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                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
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                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216; SER-256; SER-424; SER-512; SER-557; SER-562; SER-589; SER-655; SER-1083; SER-1107; SER-1143; SER-1173; SER-1182; SER-1199; THR-1232; SER-1238; SER-1275; SER-1328; THR-1330; SER-1501; SER-1512 AND SER-1721</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246; SER-1182; THR-1211; SER-1696 AND SER-1799</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2018" name="Cell Rep." volume="25" first="2132" last="2147">
            <title>A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote alpha-Toxin Cytotoxicity.</title>
            <authorList>
                <person name="Shah J."/>
                <person name="Rouaud F."/>
                <person name="Guerrera D."/>
                <person name="Vasileva E."/>
                <person name="Popov L.M."/>
                <person name="Kelley W.L."/>
                <person name="Rubinstein E."/>
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                <person name="Amieva M.R."/>
                <person name="Citi S."/>
            </authorList>
            <dbReference type="PubMed" id="30463011"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2018.10.088"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH ADAM10</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="20">
        <citation type="journal article" date="2005" name="J. Biol. Chem." volume="280" first="13841" last="13847">
            <title>Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Xu Y."/>
                <person name="Yang Y."/>
                <person name="Huang A."/>
                <person name="Wu J."/>
                <person name="Shi Y."/>
            </authorList>
            <dbReference type="PubMed" id="15684424"/>
            <dbReference type="DOI" id="10.1074/jbc.m411065200"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 1003-1094 IN COMPLEX WITH NRXN1 AND BCR</scope>
    </reference>
    <reference key="21">
        <citation type="journal article" date="2006" name="Angew. Chem. Int. Ed." volume="45" first="3790" last="3795">
            <title>Discovery of low-molecular-weight ligands for the AF6 PDZ domain.</title>
            <authorList>
                <person name="Joshi M."/>
                <person name="Vargas C."/>
                <person name="Boisguerin P."/>
                <person name="Diehl A."/>
                <person name="Krause G."/>
                <person name="Schmieder P."/>
                <person name="Moelling K."/>
                <person name="Hagen V."/>
                <person name="Schade M."/>
                <person name="Oschkinat H."/>
            </authorList>
            <dbReference type="PubMed" id="16671149"/>
            <dbReference type="DOI" id="10.1002/anie.200503965"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 1001-1095</scope>
    </reference>
    <comment type="function">
        <text evidence="2 3 9 11">Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 9 10 11">Homodimer. Interacts with F-actin, nectin and NECTIN3. Essential for the association of nectin and E-cadherin. Isoform 1/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1 and RIT2 (By similarity). Interacts with NRXN1 and BCR. Interacts with ADAM10; the interaction locks ADAM10 at adherens junctions following ADAM10 recruitment to adherens junctions by TSPAN33 (PubMed:30463011).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-2903122">
            <id>P33151</id>
            <label>CDH5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-351394">
            <id>Q16643</id>
            <label>DBN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-739696">
            <id>P25791</id>
            <label>LMO2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-968728">
            <id>O14807</id>
            <label>MRAS</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-718419">
            <id>Q92692</id>
            <label>NECTIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-6979889">
            <id>Q92692-2</id>
            <label>NECTIN2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-2826725">
            <id>Q9NQS3</id>
            <label>NECTIN3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-621482">
            <id>P12931</id>
            <label>SRC</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-359815">
            <id>P31946</id>
            <label>YWHAB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-359832">
            <id>P61981</id>
            <label>YWHAG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-25475850">
            <id>P0DTC4</id>
            <label>E</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-365875">
            <id>P55196</id>
        </interactant>
        <interactant intactId="EBI-25487741">
            <id>P59637</id>
            <label>E</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="11">Cell junction</location>
            <location evidence="11">Adherens junction</location>
        </subcellularLocation>
        <text evidence="2">Not found at cell-matrix AJs.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P55196-4</id>
            <name>4</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P55196-2</id>
            <name>1</name>
            <name>s-afadin</name>
            <sequence type="described" ref="VSP_038707 VSP_038708 VSP_000217 VSP_000218"/>
        </isoform>
        <isoform>
            <id>P55196-1</id>
            <name>2</name>
            <name>l-afadin</name>
            <sequence type="described" ref="VSP_038707 VSP_038708 VSP_038709 VSP_038711"/>
        </isoform>
        <isoform>
            <id>P55196-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_038707 VSP_038708 VSP_038709 VSP_038710"/>
        </isoform>
        <isoform>
            <id>P55196-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_041197 VSP_041198 VSP_041199"/>
        </isoform>
        <isoform>
            <id>P55196-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_038707 VSP_019257"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text>The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich C-terminal domain interacts with F-actin.</text>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving AFDN is associated with acute leukemias. Translocation t(6;11)(q27;q23) with KMT2A/MLL1. The result is a rogue activator protein.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text evidence="15">May be due to intron retention.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 2</molecule>
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            <dbReference type="PDB" id="7QCR"/>
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    <sequence length="1824" mass="206804" checksum="51486232F183A3BA" modified="2010-02-09" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="190" xmlns="https://uniprot.org/uniprot">
    <accession>P55198</accession>
    <accession>Q59F28</accession>
    <accession>Q96IU3</accession>
    <accession>Q9H5F6</accession>
    <accession>Q9UF49</accession>
    <name>AF17_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Protein AF-17</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>ALL1-fused gene from chromosome 17 protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">MLLT6</name>
        <name type="synonym">AF17</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="Proc. Natl. Acad. Sci. U.S.A." volume="91" first="8107" last="8111">
            <title>Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia.</title>
            <authorList>
                <person name="Prasad R."/>
                <person name="Leshkowitz D."/>
                <person name="Gu Y."/>
                <person name="Alder H."/>
                <person name="Nakamura T."/>
                <person name="Saito H."/>
                <person name="Huebner K."/>
                <person name="Berger R."/>
                <person name="Croce C.M."/>
                <person name="Canaani E."/>
            </authorList>
            <dbReference type="PubMed" id="8058765"/>
            <dbReference type="DOI" id="10.1073/pnas.91.17.8107"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH KMT2A/MLL1</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="1045" last="1049">
            <title>DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.</title>
            <authorList>
                <person name="Zody M.C."/>
                <person name="Garber M."/>
                <person name="Adams D.J."/>
                <person name="Sharpe T."/>
                <person name="Harrow J."/>
                <person name="Lupski J.R."/>
                <person name="Nicholson C."/>
                <person name="Searle S.M."/>
                <person name="Wilming L."/>
                <person name="Young S.K."/>
                <person name="Abouelleil A."/>
                <person name="Allen N.R."/>
                <person name="Bi W."/>
                <person name="Bloom T."/>
                <person name="Borowsky M.L."/>
                <person name="Bugalter B.E."/>
                <person name="Butler J."/>
                <person name="Chang J.L."/>
                <person name="Chen C.-K."/>
                <person name="Cook A."/>
                <person name="Corum B."/>
                <person name="Cuomo C.A."/>
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                <person name="DeCaprio D."/>
                <person name="Dewar K."/>
                <person name="FitzGerald M."/>
                <person name="Gilbert J."/>
                <person name="Gibson R."/>
                <person name="Gnerre S."/>
                <person name="Goldstein S."/>
                <person name="Grafham D.V."/>
                <person name="Grocock R."/>
                <person name="Hafez N."/>
                <person name="Hagopian D.S."/>
                <person name="Hart E."/>
                <person name="Norman C.H."/>
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                <person name="Jaffe D.B."/>
                <person name="Jones M."/>
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                <person name="LaButti K."/>
                <person name="Laird G."/>
                <person name="Lehoczky J."/>
                <person name="Liu X."/>
                <person name="Lokyitsang T."/>
                <person name="Loveland J."/>
                <person name="Lui A."/>
                <person name="Macdonald P."/>
                <person name="Major J.E."/>
                <person name="Matthews L."/>
                <person name="Mauceli E."/>
                <person name="McCarroll S.A."/>
                <person name="Mihalev A.H."/>
                <person name="Mudge J."/>
                <person name="Nguyen C."/>
                <person name="Nicol R."/>
                <person name="O'Leary S.B."/>
                <person name="Osoegawa K."/>
                <person name="Schwartz D.C."/>
                <person name="Shaw-Smith C."/>
                <person name="Stankiewicz P."/>
                <person name="Steward C."/>
                <person name="Swarbreck D."/>
                <person name="Venkataraman V."/>
                <person name="Whittaker C.A."/>
                <person name="Yang X."/>
                <person name="Zimmer A.R."/>
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                <person name="Birren B.W."/>
                <person name="Rogers J."/>
                <person name="Lander E.S."/>
                <person name="Nusbaum C."/>
            </authorList>
            <dbReference type="PubMed" id="16625196"/>
            <dbReference type="DOI" id="10.1038/nature04689"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
        <citation type="submission" date="2005-03" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Totoki Y."/>
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                <person name="Tanaka A."/>
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                <person name="Ohara O."/>
                <person name="Nagase T."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-1093</scope>
        <source>
            <tissue>Spleen</tissue>
        </source>
    </reference>
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                <person name="Watanabe T."/>
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                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
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                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 624-1093</scope>
        <source>
            <tissue>Ileal mucosa</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 624-1093</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="BMC Genomics" volume="8" first="399" last="399">
            <title>The full-ORF clone resource of the German cDNA consortium.</title>
            <authorList>
                <person name="Bechtel S."/>
                <person name="Rosenfelder H."/>
                <person name="Duda A."/>
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                <person name="Ernst U."/>
                <person name="Wellenreuther R."/>
                <person name="Mehrle A."/>
                <person name="Schuster C."/>
                <person name="Bahr A."/>
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                <person name="Schupp I."/>
            </authorList>
            <dbReference type="PubMed" id="17974005"/>
            <dbReference type="DOI" id="10.1186/1471-2164-8-399"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 648-1093</scope>
        <source>
            <tissue>Testis</tissue>
        </source>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2009" name="Sci. Signal." volume="2" first="RA46" last="RA46">
            <title>Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.</title>
            <authorList>
                <person name="Mayya V."/>
                <person name="Lundgren D.H."/>
                <person name="Hwang S.-I."/>
                <person name="Rezaul K."/>
                <person name="Wu L."/>
                <person name="Eng J.K."/>
                <person name="Rodionov V."/>
                <person name="Han D.K."/>
            </authorList>
            <dbReference type="PubMed" id="19690332"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000007"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-451</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Leukemic T-cell</tissue>
        </source>
    </reference>
    <reference key="8">
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            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258; SER-378 AND SER-423</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2015" name="Mol. Cell" volume="60" first="319" last="327">
            <title>The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.</title>
            <authorList>
                <person name="Chen S."/>
                <person name="Yang Z."/>
                <person name="Wilkinson A.W."/>
                <person name="Deshpande A.J."/>
                <person name="Sidoli S."/>
                <person name="Krajewski K."/>
                <person name="Strahl B.D."/>
                <person name="Garcia B.A."/>
                <person name="Armstrong S.A."/>
                <person name="Patel D.J."/>
                <person name="Gozani O."/>
            </authorList>
            <dbReference type="PubMed" id="26439302"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2015.08.019"/>
        </citation>
        <scope>INTERACTION WITH HISTONE H3</scope>
    </reference>
    <comment type="subunit">
        <text evidence="4">Interacts with histone H3; interaction is necessary for MLLT6 binding to nucleosomes; interaction is inhibited by histone H3 'Lys-27' methylations (H3K27me1, H3K27me2 and H3K27me3).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-702390">
            <id>Q9UBB4</id>
            <label>ATXN10</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-740209">
            <id>P53567</id>
            <label>CEBPG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-10192698">
            <id>Q02930-3</id>
            <label>CREB5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-717919">
            <id>Q4V328</id>
            <label>GRIPAP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-14568740">
            <id>B7ZLY0</id>
            <label>PHC2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-714158">
            <id>Q13526</id>
            <label>PIN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-11741437">
            <id>Q08117-2</id>
            <label>TLE5</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-10173939">
            <id>Q9UMX0-2</id>
            <label>UBQLN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-711226">
            <id>Q9NRR5</id>
            <label>UBQLN4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-740216">
            <id>P55198</id>
        </interactant>
        <interactant intactId="EBI-746595">
            <id>Q96E35</id>
            <label>ZMYND19</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving MLLT6 is associated with acute leukemias. Translocation t(11;17)(q23;q21) with KMT2A/MLL1. The result is a rogue activator protein.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH07237" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB15670" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/7/AF17"/>
    </comment>
    <dbReference type="EMBL" id="U07932">
        <property type="protein sequence ID" value="AAA21145.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006449">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB209633">
        <property type="protein sequence ID" value="BAD92870.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027133">
        <property type="protein sequence ID" value="BAB15670.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC007237">
        <property type="protein sequence ID" value="AAH07237.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133659">
        <property type="protein sequence ID" value="CAB63772.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11327.1"/>
    <dbReference type="PIR" id="I38533">
        <property type="entry name" value="I38533"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005928.2">
        <property type="nucleotide sequence ID" value="NM_005937.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P55198"/>
    <dbReference type="SMR" id="P55198"/>
    <dbReference type="BioGRID" id="110448">
        <property type="interactions" value="109"/>
    </dbReference>
    <dbReference type="FunCoup" id="P55198">
        <property type="interactions" value="1691"/>
    </dbReference>
    <dbReference type="IntAct" id="P55198">
        <property type="interactions" value="61"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000479910"/>
    <dbReference type="GlyCosmos" id="P55198">
        <property type="glycosylation" value="18 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="P55198">
        <property type="glycosylation" value="31 sites, 2 O-linked glycans (31 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P55198"/>
    <dbReference type="PhosphoSitePlus" id="P55198"/>
    <dbReference type="BioMuta" id="MLLT6"/>
    <dbReference type="DMDM" id="215273929"/>
    <dbReference type="jPOST" id="P55198"/>
    <dbReference type="MassIVE" id="P55198"/>
    <dbReference type="PaxDb" id="9606-ENSP00000479910"/>
    <dbReference type="PeptideAtlas" id="P55198"/>
    <dbReference type="ProteomicsDB" id="56804"/>
    <dbReference type="Pumba" id="P55198"/>
    <dbReference type="Antibodypedia" id="73458">
        <property type="antibodies" value="121 antibodies from 20 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="4302"/>
    <dbReference type="Ensembl" id="ENST00000618876.2">
        <property type="protein sequence ID" value="ENSP00000477969.1"/>
        <property type="gene ID" value="ENSG00000275851.4"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000621332.5">
        <property type="protein sequence ID" value="ENSP00000479910.1"/>
        <property type="gene ID" value="ENSG00000275023.6"/>
    </dbReference>
    <dbReference type="GeneID" id="4302"/>
    <dbReference type="KEGG" id="hsa:4302"/>
    <dbReference type="MANE-Select" id="ENST00000621332.5">
        <property type="protein sequence ID" value="ENSP00000479910.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_005937.4"/>
        <property type="RefSeq protein sequence ID" value="NP_005928.2"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:7138"/>
    <dbReference type="ClinPGx" id="PA30854"/>
    <dbReference type="CTD" id="4302"/>
    <dbReference type="DisGeNET" id="4302"/>
    <dbReference type="GeneCards" id="MLLT6"/>
    <dbReference type="HGNC" id="HGNC:7138">
        <property type="gene designation" value="MLLT6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000275023">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="600328">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000275023"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000275023"/>
    <dbReference type="eggNOG" id="KOG0956">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000158572"/>
    <dbReference type="InParanoid" id="P55198"/>
    <dbReference type="OMA" id="EKHPAHH"/>
    <dbReference type="OrthoDB" id="20839at2759"/>
    <dbReference type="PAN-GO" id="P55198">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P55198"/>
    <dbReference type="PathwayCommons" id="P55198"/>
    <dbReference type="SignaLink" id="P55198"/>
    <dbReference type="Agora" id="ENSG00000275023"/>
    <dbReference type="BioGRID-ORCS" id="4302">
        <property type="hits" value="31 hits in 1160 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="MLLT6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="4302"/>
    <dbReference type="Pharos" id="P55198">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P55198"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 17"/>
    </dbReference>
    <dbReference type="RNAct" id="P55198">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000275023">
        <property type="expression patterns" value="Expressed in right uterine tube and 101 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P55198">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042393">
        <property type="term" value="F:histone binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031491">
        <property type="term" value="F:nucleosome binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006325">
        <property type="term" value="P:chromatin organization"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035811">
        <property type="term" value="P:negative regulation of urine volume"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010765">
        <property type="term" value="P:positive regulation of sodium ion transport"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045944">
        <property type="term" value="P:positive regulation of transcription by RNA polymerase II"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006355">
        <property type="term" value="P:regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006357">
        <property type="term" value="P:regulation of transcription by RNA polymerase II"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0036359">
        <property type="term" value="P:renal potassium excretion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035812">
        <property type="term" value="P:renal sodium excretion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0070295">
        <property type="term" value="P:renal water absorption"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd15709">
        <property type="entry name" value="ePHD_AF17"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd15574">
        <property type="entry name" value="PHD_AF10_AF17"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.40.10:FF:000042">
        <property type="entry name" value="protein AF-10 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.40.10:FF:000053">
        <property type="entry name" value="protein AF-10 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.40.10">
        <property type="entry name" value="Zinc/RING finger domain, C3HC4 (zinc finger)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR049781">
        <property type="entry name" value="AF10/AF17_PHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR034732">
        <property type="entry name" value="EPHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050701">
        <property type="entry name" value="Histone_Mod_Regulator"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019786">
        <property type="entry name" value="Zinc_finger_PHD-type_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011011">
        <property type="entry name" value="Znf_FYVE_PHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001965">
        <property type="entry name" value="Znf_PHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR019787">
        <property type="entry name" value="Znf_PHD-finger"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR013083">
        <property type="entry name" value="Znf_RING/FYVE/PHD"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13793">
        <property type="entry name" value="PHD FINGER PROTEINS"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13793:SF90">
        <property type="entry name" value="PROTEIN AF-17"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13831">
        <property type="entry name" value="PHD_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF13832">
        <property type="entry name" value="zf-HC5HC2H_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00249">
        <property type="entry name" value="PHD"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57903">
        <property type="entry name" value="FYVE/PHD zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS51805">
        <property type="entry name" value="EPHD"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS01359">
        <property type="entry name" value="ZF_PHD_1"/>
        <property type="match status" value="1"/>
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    <dbReference type="PROSITE" id="PS50016">
        <property type="entry name" value="ZF_PHD_2"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0160">Chromosomal rearrangement</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0656">Proto-oncogene</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000215937" description="Protein AF-17">
        <location>
            <begin position="1"/>
            <end position="1093"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="PHD-type 1" evidence="1">
        <location>
            <begin position="5"/>
            <end position="57"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C2HC pre-PHD-type" evidence="2">
        <location>
            <begin position="62"/>
            <end position="95"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="PHD-type 2" evidence="2">
        <location>
            <begin position="118"/>
            <end position="181"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="185"/>
            <end position="500"/>
        </location>
    </feature>
    <feature type="region of interest" description="Leucine-zipper">
        <location>
            <begin position="729"/>
            <end position="764"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="775"/>
            <end position="871"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1060"/>
            <end position="1093"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="3">
        <location>
            <begin position="191"/>
            <end position="212"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="231"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="3">
        <location>
            <begin position="258"/>
            <end position="268"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="282"/>
            <end position="300"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="301"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="317"/>
            <end position="340"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="345"/>
            <end position="354"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="3">
        <location>
            <begin position="374"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="410"/>
            <end position="425"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="465"/>
            <end position="484"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="787"/>
            <end position="796"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="804"/>
            <end position="813"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="818"/>
            <end position="832"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="839"/>
            <end position="853"/>
        </location>
    </feature>
    <feature type="site" description="KMT2A/MLL1 fusion point (in acute myeloid leukemia patient)">
        <location>
            <position position="551"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="378"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="7">
        <location>
            <position position="423"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="6">
        <location>
            <position position="451"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080170" description="In dbSNP:rs17855918.">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022076" description="In dbSNP:rs2241012.">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA21145." evidence="5" ref="1">
        <original>Q</original>
        <variation>T</variation>
        <location>
            <position position="126"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAD92870." evidence="5" ref="3">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="735"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAB15670." evidence="5" ref="4">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="1065"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00146"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01146"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="26439302"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="7">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="1093" mass="112048" checksum="C55F0801D9A0A5C1" modified="2018-03-28" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="201" xmlns="https://uniprot.org/uniprot">
    <accession>P42568</accession>
    <accession>B1AMQ2</accession>
    <accession>B2R7B3</accession>
    <accession>B7Z755</accession>
    <accession>D3DRJ8</accession>
    <accession>Q8IVB0</accession>
    <name>AF9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="28">Protein AF-9</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="24">ALL1-fused gene from chromosome 9 protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="26">Myeloid/lymphoid or mixed-lineage leukemia translocated to chromosome 3 protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>YEATS domain-containing protein 3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="26 29" type="primary">MLLT3</name>
        <name evidence="24 27" type="synonym">AF9</name>
        <name type="synonym">YEATS3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs.</title>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>CHROMOSOMAL TRANSLOCATION WITH KMT2A</scope>
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
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                <person name="Ishida S."/>
                <person name="Ono Y."/>
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                <person name="Yosida M."/>
                <person name="Hotuta T."/>
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                <person name="Shiohata N."/>
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                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
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                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="22">
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            <title>The same site on the integrase-binding domain of lens epithelium-derived growth factor is a therapeutic target for MLL leukemia and HIV.</title>
            <authorList>
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                <person name="Cierpicki T."/>
            </authorList>
            <dbReference type="PubMed" id="25305204"/>
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        </citation>
        <scope>INTERACTION OF FUSION PROTEIN KMT2A-MLLT3 WITH PSIP1 AND MEN1</scope>
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    <reference key="23">
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            <title>Uncovering global SUMOylation signaling networks in a site-specific manner.</title>
            <authorList>
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            </authorList>
            <dbReference type="PubMed" id="25218447"/>
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        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
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                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="25">
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            <title>MLLT3 governs human haematopoietic stem-cell self-renewal and engraftment.</title>
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                <person name="Calvanese V."/>
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                <person name="Bolan T.J."/>
                <person name="Vavilina A."/>
                <person name="Su T."/>
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                <person name="Wang Y."/>
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                <person name="Mikkola H.K.A."/>
            </authorList>
            <dbReference type="PubMed" id="31776511"/>
            <dbReference type="DOI" id="10.1038/s41586-019-1790-2"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="26">
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            <title>Positive Regulation of Transcription by Human ZMYND8 through Its Association with P-TEFb Complex.</title>
            <authorList>
                <person name="Ghosh K."/>
                <person name="Tang M."/>
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                <person name="Nandy A."/>
                <person name="Basu S."/>
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            </authorList>
            <dbReference type="PubMed" id="30134174"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2018.07.064"/>
        </citation>
        <scope>INTERACTION WITH CDK9</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference evidence="30" key="27">
        <citation type="journal article" date="2013" name="Structure" volume="21" first="176" last="183">
            <title>Leukemia fusion target AF9 is an intrinsically disordered transcriptional regulator that recruits multiple partners via coupled folding and binding.</title>
            <authorList>
                <person name="Leach B.I."/>
                <person name="Kuntimaddi A."/>
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                <person name="Cierpicki T."/>
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            </authorList>
            <dbReference type="PubMed" id="23260655"/>
            <dbReference type="DOI" id="10.1016/j.str.2012.11.011"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 490-568 IN COMPLEX WITH AFF1</scope>
    </reference>
    <reference evidence="33" key="28">
        <citation type="journal article" date="2014" name="Cell" volume="159" first="558" last="571">
            <title>AF9 YEATS domain links histone acetylation to DOT1L-mediated H3K79 methylation.</title>
            <authorList>
                <person name="Li Y."/>
                <person name="Wen H."/>
                <person name="Xi Y."/>
                <person name="Tanaka K."/>
                <person name="Wang H."/>
                <person name="Peng D."/>
                <person name="Ren Y."/>
                <person name="Jin Q."/>
                <person name="Dent S.Y."/>
                <person name="Li W."/>
                <person name="Li H."/>
                <person name="Shi X."/>
            </authorList>
            <dbReference type="PubMed" id="25417107"/>
            <dbReference type="DOI" id="10.1016/j.cell.2014.09.049"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9AC PEPTIDE</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF PHE-28; HIS-56; SER-58; PHE-59; GLY-77; TYR-78; PHE-81 AND ASP-103</scope>
    </reference>
    <reference evidence="34 35" key="29">
        <citation type="journal article" date="2016" name="Mol. Cell" volume="62" first="181" last="193">
            <title>Molecular coupling of histone crotonylation and active transcription by AF9 YEATS domain.</title>
            <authorList>
                <person name="Li Y."/>
                <person name="Sabari B.R."/>
                <person name="Panchenko T."/>
                <person name="Wen H."/>
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                <person name="Wan L."/>
                <person name="Huang H."/>
                <person name="Tang Z."/>
                <person name="Zhao Y."/>
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                <person name="Shi X."/>
                <person name="Allis C.D."/>
                <person name="Li H."/>
            </authorList>
            <dbReference type="PubMed" id="27105114"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2016.03.028"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9CR PEPTIDE</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF PHE-28; HIS-56; SER-58; PHE-59; GLY-77 AND TYR-78</scope>
    </reference>
    <reference evidence="31 32" key="30">
        <citation type="journal article" date="2016" name="Structure" volume="24" first="1606" last="1612">
            <title>Structural insights into histone crotonyl-lysine recognition by the AF9 YEATS domain.</title>
            <authorList>
                <person name="Zhang Q."/>
                <person name="Zeng L."/>
                <person name="Zhao C."/>
                <person name="Ju Y."/>
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            </authorList>
            <dbReference type="PubMed" id="27545619"/>
            <dbReference type="DOI" id="10.1016/j.str.2016.05.023"/>
        </citation>
        <scope>STRUCTURE BY NMR OF 1-138</scope>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF PHE-59 AND TYR-78</scope>
    </reference>
    <reference evidence="36" key="31">
        <citation type="journal article" date="2018" name="Nat. Chem. Biol." volume="14" first="1140" last="1149">
            <title>Structure-guided development of YEATS domain inhibitors by targeting pi-pi-pi stacking.</title>
            <authorList>
                <person name="Li X."/>
                <person name="Li X.M."/>
                <person name="Jiang Y."/>
                <person name="Liu Z."/>
                <person name="Cui Y."/>
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                <person name="Tian G."/>
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                <person name="Shi X."/>
                <person name="Allis C.D."/>
                <person name="Li H."/>
                <person name="Li Y."/>
                <person name="Li X.D."/>
            </authorList>
            <dbReference type="PubMed" id="30374167"/>
            <dbReference type="DOI" id="10.1038/s41589-018-0144-y"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-138 IN COMPLEX WITH INHIBITOR</scope>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
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        <citation type="journal article" date="2018" name="Nat. Commun." volume="9" first="4574" last="4574">
            <title>Structural insights into the pi-pi-pi stacking mechanism and DNA-binding activity of the YEATS domain.</title>
            <authorList>
                <person name="Klein B.J."/>
                <person name="Vann K.R."/>
                <person name="Andrews F.H."/>
                <person name="Wang W.W."/>
                <person name="Zhang J."/>
                <person name="Zhang Y."/>
                <person name="Beloglazkina A.A."/>
                <person name="Mi W."/>
                <person name="Li Y."/>
                <person name="Li H."/>
                <person name="Shi X."/>
                <person name="Kutateladze A.G."/>
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                <person name="Liu W.R."/>
                <person name="Kutateladze T.G."/>
            </authorList>
            <dbReference type="PubMed" id="30385749"/>
            <dbReference type="DOI" id="10.1038/s41467-018-07072-6"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 1-138 IN COMPLEX WITH H3K9CR PEPTIDE</scope>
        <scope>FUNCTION</scope>
        <scope>DOMAIN</scope>
        <scope>MUTAGENESIS OF 61-ARG--LYS-67; 78-TYR-ALA-79 AND TYR-78</scope>
    </reference>
    <reference evidence="39 40" key="33">
        <citation type="journal article" date="2025" name="Nat. Struct. Mol. Biol." volume="32" first="709" last="718">
            <title>A multivalent engagement of ENL with MOZ.</title>
            <authorList>
                <person name="Becht D.C."/>
                <person name="Selvam K."/>
                <person name="Lachance C."/>
                <person name="Cote V."/>
                <person name="Li K."/>
                <person name="Nguyen M.C."/>
                <person name="Pareek A."/>
                <person name="Shi X."/>
                <person name="Wen H."/>
                <person name="Blanco M.A."/>
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                <person name="Kutateladze T.G."/>
            </authorList>
            <dbReference type="PubMed" id="39794553"/>
            <dbReference type="DOI" id="10.1038/s41594-024-01455-8"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-138 IN COMPLEX WITH KAT6A</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH KAT6A</scope>
    </reference>
    <comment type="function">
        <text evidence="8 9 15 16 17 19 20 21 22">Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948, PubMed:25417107, PubMed:27105114, PubMed:27545619). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated (PubMed:25417107, PubMed:27105114, PubMed:27545619, PubMed:30374167, PubMed:30385749). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25417107, PubMed:27105114, PubMed:27545619). Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114). Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3 (PubMed:25417107, PubMed:27105114, PubMed:30385749). In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones (PubMed:27105114, PubMed:27545619). Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me) (PubMed:25417107). Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than conferring, HSC stemness (PubMed:31776511). Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L (PubMed:31776511). May play a role in leukemogenic gene transcription (PubMed:39794553).</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="19">Crotonylated lysine binding is strongly inhibited by the peptide XL-07i, carrying a 2-furancarbonyl side chain and capped with a hydrophobic carboxybenzyl group (PubMed:30374167). XL-07i targets the unique pi-pi-pi stacking interaction at the crotonylation recognition site (PubMed:30374167).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6 8 9 10 12 13 15 18 22">Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3) (PubMed:20159561, PubMed:20471948, PubMed:22195968, PubMed:23260655, PubMed:25417107, PubMed:30134174). Interacts with BCOR (PubMed:10898795). Interacts with CBX8 (PubMed:11313972). Interacts with ALKBH4 (PubMed:23145062). Interacts with acetylated or crotonylated KAT6A/MOZ; the interaction is direct (PubMed:39794553).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-2610180">
            <id>P51825</id>
            <label>AFF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-395282">
            <id>Q9UHB7</id>
            <label>AFF4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-8637516">
            <id>Q9NXW9</id>
            <label>ALKBH4</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-743771">
            <id>Q92624</id>
            <label>APPBP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-16028932">
            <id>Q6W2J9-1</id>
            <label>BCOR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-712912">
            <id>Q9HC52</id>
            <label>CBX8</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-2619253">
            <id>Q8TEK3</id>
            <label>DOT1L</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-8468186">
            <id>Q8IZU1</id>
            <label>FAM9A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-2801965">
            <id>Q5JXC2</id>
            <label>MIIP</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>4</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-12227803">
            <id>Q5SQQ9-2</id>
            <label>VAX1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-716132">
            <id>P42568</id>
        </interactant>
        <interactant intactId="EBI-10172590">
            <id>Q7Z3I7</id>
            <label>ZNF572</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 16">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="15 16">Chromosome</location>
        </subcellularLocation>
        <text evidence="15 16">Colocalizes with acylated histone H3 (PubMed:25417107, PubMed:27105114). Colocalizes with histone H3 crotonylated at 'Lys-18' (H3K18cr) (PubMed:27105114).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P42568-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P42568-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_054924"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="21">Enriched in undifferentiated hematopoietic stem cells in fetal liver, cord blood and bone marrow.</text>
    </comment>
    <comment type="domain">
        <text evidence="15 16 17 19 20">The YEATS domain specifically recognizes and binds acylated histones, with a marked preference for histones that are crotonylated (PubMed:27105114, PubMed:27545619). Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity (PubMed:25417107, PubMed:27105114). Binds crotonylated lysine through a non-canonical pi-pi-pi stacking mechanism (PubMed:30374167, PubMed:30385749). The YEATS domain also binds DNA (PubMed:30385749).</text>
    </comment>
    <comment type="disease">
        <text evidence="4 11 14 23">A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with KMT2A/MLL1. The result is a rogue activator protein. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).</text>
    </comment>
    <comment type="disease">
        <text evidence="7">A chromosomal aberration involving MLLT3 was observed in a patient with neuromotor development delay, cerebellar ataxia and epilepsy. Translocation t(4;9)(q35;p22).</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/5/mllt3"/>
    </comment>
    <dbReference type="EMBL" id="L13744">
        <property type="protein sequence ID" value="AAA58361.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301474">
        <property type="protein sequence ID" value="BAH13491.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK312914">
        <property type="protein sequence ID" value="BAG35760.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL354879">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL512635">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL513498">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL163193">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL627410">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471071">
        <property type="protein sequence ID" value="EAW58631.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471071">
        <property type="protein sequence ID" value="EAW58632.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC036089">
        <property type="protein sequence ID" value="AAH36089.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS6494.1">
        <molecule id="P42568-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS69579.1">
        <molecule id="P42568-2"/>
    </dbReference>
    <dbReference type="PIR" id="I39411">
        <property type="entry name" value="I39411"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001273620.1">
        <molecule id="P42568-2"/>
        <property type="nucleotide sequence ID" value="NM_001286691.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_004520.2">
        <molecule id="P42568-1"/>
        <property type="nucleotide sequence ID" value="NM_004529.4"/>
    </dbReference>
    <dbReference type="PDB" id="2LM0">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=490-568"/>
    </dbReference>
    <dbReference type="PDB" id="2MV7">
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            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Lung</tissue>
            <tissue>Uterus</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3)</scope>
        <source>
            <tissue>Skin</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2011" name="Eur. J. Cell Biol." volume="90" first="376" last="389">
            <title>AFAP1L1 is a novel adaptor protein of the AFAP family that interacts with cortactin and localizes to invadosomes.</title>
            <authorList>
                <person name="Snyder B.N."/>
                <person name="Cho Y."/>
                <person name="Qian Y."/>
                <person name="Coad J.E."/>
                <person name="Flynn D.C."/>
                <person name="Cunnick J.M."/>
            </authorList>
            <dbReference type="PubMed" id="21333378"/>
            <dbReference type="DOI" id="10.1016/j.ejcb.2010.11.016"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH CTTN</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="6">May be involved in podosome and invadosome formation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="6">Interacts with CTTN.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-1053644">
            <id>Q8TED9</id>
        </interactant>
        <interactant intactId="EBI-448202">
            <id>O95257</id>
            <label>GADD45G</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>8</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cell projection</location>
            <location evidence="6">Podosome</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cell projection</location>
            <location evidence="6">Invadopodium</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
            <location evidence="6">Cytoskeleton</location>
            <location evidence="6">Stress fiber</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8TED9-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8TED9-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_026859"/>
        </isoform>
        <isoform>
            <id>Q8TED9-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_026857 VSP_026858"/>
        </isoform>
        <isoform>
            <id>Q8TED9-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_026856"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6">Expressed in breast, colon and brain. In all 3 tissues, expressed in the microvasculature (at protein level). In addition, in the breast, found in the contractile myoepithelial cell layer which surrounds the breast ducts (at protein level). In the colon, expressed in the mucous membrane and colonic crypts and in the smooth muscle cell layer which provide movement of the colon (at protein level). In the cerebellum, localized around the Purkinje neurons and the granule cells of the granular layer, but not inside cell bodies (at protein level). Outside of the cerebellar cortex, expressed in glial cells (at protein level). Highly expressed away from the cell bodies within the dentate nucleus (at protein level).</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB85011" version="1"/>
        </conflict>
        <text>Extended N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AK074185">
        <property type="protein sequence ID" value="BAB85011.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK094067">
        <property type="protein sequence ID" value="BAC04277.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK095980">
        <property type="protein sequence ID" value="BAC04664.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC040723">
        <property type="protein sequence ID" value="AAH40723.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125093">
        <property type="protein sequence ID" value="AAI25094.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC125094">
        <property type="protein sequence ID" value="AAI25095.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS34274.1">
        <molecule id="Q8TED9-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS54932.1">
        <molecule id="Q8TED9-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001139809.1">
        <molecule id="Q8TED9-2"/>
        <property type="nucleotide sequence ID" value="NM_001146337.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309991.1">
        <property type="nucleotide sequence ID" value="NM_001323062.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001309992.1">
        <molecule id="Q8TED9-3"/>
        <property type="nucleotide sequence ID" value="NM_001323063.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_689619.1">
        <molecule id="Q8TED9-1"/>
        <property type="nucleotide sequence ID" value="NM_152406.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TED9"/>
    <dbReference type="SMR" id="Q8TED9"/>
    <dbReference type="BioGRID" id="126390">
        <property type="interactions" value="20"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TED9">
        <property type="interactions" value="631"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TED9">
        <property type="interactions" value="18"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000296721"/>
    <dbReference type="GlyGen" id="Q8TED9">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8TED9"/>
    <dbReference type="PhosphoSitePlus" id="Q8TED9"/>
    <dbReference type="BioMuta" id="AFAP1L1"/>
    <dbReference type="DMDM" id="156630522"/>
    <dbReference type="jPOST" id="Q8TED9"/>
    <dbReference type="MassIVE" id="Q8TED9"/>
    <dbReference type="PaxDb" id="9606-ENSP00000296721"/>
    <dbReference type="PeptideAtlas" id="Q8TED9"/>
    <dbReference type="ProteomicsDB" id="74452">
        <molecule id="Q8TED9-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74453">
        <molecule id="Q8TED9-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74454">
        <molecule id="Q8TED9-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="74455">
        <molecule id="Q8TED9-4"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="2023">
        <property type="antibodies" value="74 antibodies from 21 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="134265"/>
    <dbReference type="Ensembl" id="ENST00000296721.9">
        <molecule id="Q8TED9-1"/>
        <property type="protein sequence ID" value="ENSP00000296721.4"/>
        <property type="gene ID" value="ENSG00000157510.15"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000515000.1">
        <molecule id="Q8TED9-2"/>
        <property type="protein sequence ID" value="ENSP00000424427.1"/>
        <property type="gene ID" value="ENSG00000157510.15"/>
    </dbReference>
    <dbReference type="GeneID" id="134265"/>
    <dbReference type="KEGG" id="hsa:134265"/>
    <dbReference type="MANE-Select" id="ENST00000296721.9">
        <property type="protein sequence ID" value="ENSP00000296721.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_152406.4"/>
        <property type="RefSeq protein sequence ID" value="NP_689619.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003lqh.4">
        <molecule id="Q8TED9-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:26714"/>
    <dbReference type="ClinPGx" id="PA162375772"/>
    <dbReference type="CTD" id="134265"/>
    <dbReference type="DisGeNET" id="134265"/>
    <dbReference type="GeneCards" id="AFAP1L1"/>
    <dbReference type="HGNC" id="HGNC:26714">
        <property type="gene designation" value="AFAP1L1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000157510">
        <property type="expression patterns" value="Tissue enhanced (skeletal)"/>
    </dbReference>
    <dbReference type="MIM" id="614410">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000157510"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000157510"/>
    <dbReference type="eggNOG" id="ENOG502R3HG">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183067"/>
    <dbReference type="HOGENOM" id="CLU_014418_1_0_1"/>
    <dbReference type="InParanoid" id="Q8TED9"/>
    <dbReference type="OMA" id="HSCEVVP"/>
    <dbReference type="OrthoDB" id="9937741at2759"/>
    <dbReference type="PAN-GO" id="Q8TED9">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8TED9"/>
    <dbReference type="PathwayCommons" id="Q8TED9"/>
    <dbReference type="SignaLink" id="Q8TED9"/>
    <dbReference type="Agora" id="ENSG00000157510"/>
    <dbReference type="BioGRID-ORCS" id="134265">
        <property type="hits" value="7 hits in 1142 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFAP1L1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="134265"/>
    <dbReference type="Pharos" id="Q8TED9">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8TED9"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TED9">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000157510">
        <property type="expression patterns" value="Expressed in apex of heart and 134 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042995">
        <property type="term" value="C:cell projection"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002102">
        <property type="term" value="C:podosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001725">
        <property type="term" value="C:stress fiber"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="CDD" id="cd13306">
        <property type="entry name" value="PH1_AFAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd13307">
        <property type="entry name" value="PH2_AFAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000189">
        <property type="entry name" value="Actin filament associated protein 1-like 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.30.29.30:FF:000020">
        <property type="entry name" value="Actin filament-associated protein 1-like 2 isoform 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR030113">
        <property type="entry name" value="AFAP"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14338">
        <property type="entry name" value="ACTIN FILAMENT-ASSOCIATED PROTEIN 1 FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR14338:SF1">
        <property type="entry name" value="ACTIN FILAMENT-ASSOCIATED PROTEIN 1-LIKE 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0965">Cell junction</keyword>
    <keyword id="KW-0966">Cell projection</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <feature type="chain" id="PRO_0000295239" description="Actin filament-associated protein 1-like 1">
        <location>
            <begin position="1"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="domain" description="PH 1" evidence="4">
        <location>
            <begin position="220"/>
            <end position="316"/>
        </location>
    </feature>
    <feature type="domain" description="PH 2" evidence="4">
        <location>
            <begin position="418"/>
            <end position="512"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="82"/>
            <end position="145"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="173"/>
            <end position="211"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="566"/>
            <end position="604"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="705"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="3">
        <location>
            <begin position="611"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="177"/>
            <end position="190"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="587"/>
            <end position="596"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="710"/>
            <end position="729"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="5">
        <location>
            <begin position="759"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="98"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="104"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="153"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="329"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="343"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="2">
        <location>
            <position position="557"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="747"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026856" description="In isoform 4." evidence="7">
        <location>
            <begin position="1"/>
            <end position="385"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026857" description="In isoform 3." evidence="8">
        <original>RLSQEKQTSDSDSVGVGDNCSTLGRRETCDHGKGKKS</original>
        <variation>VYLSPLSLPQARQWPLNTGSTPGELTGWGESQATAKL</variation>
        <location>
            <begin position="341"/>
            <end position="377"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026858" description="In isoform 3." evidence="8">
        <location>
            <begin position="378"/>
            <end position="768"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_026859" description="In isoform 2." evidence="8">
        <location>
            <begin position="719"/>
            <end position="761"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC04664." evidence="9" ref="2">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC04664." evidence="9" ref="2">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="106"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAC04664." evidence="9" ref="2">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="325"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="D4AB98"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q8BZI0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="21333378"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <sequence length="768" mass="86432" checksum="5DC1B952E797110F" modified="2007-07-24" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1995-11-01" modified="2026-01-28" version="192" xmlns="https://uniprot.org/uniprot">
    <accession>P43652</accession>
    <accession>A8K3E1</accession>
    <accession>Q32MR3</accession>
    <accession>Q4W5C5</accession>
    <name>AFAM_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Afamin</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="14">Alpha-albumin</fullName>
            <shortName>Alpha-Alb</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AFM</name>
        <name type="synonym">ALB2</name>
        <name type="synonym">ALBA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1994" name="J. Biol. Chem." volume="269" first="18149" last="18154">
            <title>Afamin is a new member of the albumin, alpha-fetoprotein, and vitamin D-binding protein gene family.</title>
            <authorList>
                <person name="Lichenstein H.S."/>
                <person name="Lyons D.E."/>
                <person name="Wurfel M.M."/>
                <person name="Johnson D.A."/>
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                <person name="Halim A."/>
                <person name="Hesse C."/>
                <person name="Carlsohn E."/>
                <person name="Brinkmalm G."/>
                <person name="Larson G."/>
            </authorList>
            <dbReference type="PubMed" id="19838169"/>
            <dbReference type="DOI" id="10.1038/nmeth.1392"/>
        </citation>
        <scope>GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-109; ASN-383 AND ASN-402</scope>
        <scope>STRUCTURE OF CARBOHYDRATES</scope>
        <source>
            <tissue>Cerebrospinal fluid</tissue>
        </source>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2016" name="Elife" volume="5" first="0" last="0">
            <title>Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin.</title>
            <authorList>
                <person name="Mihara E."/>
                <person name="Hirai H."/>
                <person name="Yamamoto H."/>
                <person name="Tamura-Kawakami K."/>
                <person name="Matano M."/>
                <person name="Kikuchi A."/>
                <person name="Sato T."/>
                <person name="Takagi J."/>
            </authorList>
            <dbReference type="PubMed" id="26902720"/>
            <dbReference type="DOI" id="10.7554/elife.11621"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>SUBUNIT</scope>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2017" name="Structure" volume="25" first="1907" last="1915">
            <title>Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport.</title>
            <authorList>
                <person name="Naschberger A."/>
                <person name="Orry A."/>
                <person name="Lechner S."/>
                <person name="Bowler M.W."/>
                <person name="Nurizzo D."/>
                <person name="Novokmet M."/>
                <person name="Keller M.A."/>
                <person name="Oemer G."/>
                <person name="Seppi D."/>
                <person name="Haslbeck M."/>
                <person name="Pansi K."/>
                <person name="Dieplinger H."/>
                <person name="Rupp B."/>
            </authorList>
            <dbReference type="PubMed" id="29153507"/>
            <dbReference type="DOI" id="10.1016/j.str.2017.10.006"/>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 22-599 IN COMPLEX WITH PALMITOLEIC ACID</scope>
        <scope>GLYCOSYLATION AT ASN-402 AND ASN-488</scope>
        <scope>DISULFIDE BONDS</scope>
        <scope>DOMAIN</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4 7 11 15">Functions as a carrier for hydrophobic molecules in body fluids (Probable). Essential for the solubility and activity of lipidated Wnt family members, including WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B (PubMed:26902720). Binds vitamin E (PubMed:12463752, PubMed:15952736). May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient (PubMed:15952736). May be involved in the transport of vitamin E across the blood-brain barrier (PubMed:19046407).</text>
    </comment>
    <comment type="subunit">
        <text evidence="11">Forms a 1:1 complex with Wnt family members; interacts with WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-20737924">
            <id>P43652</id>
        </interactant>
        <interactant intactId="EBI-3644922">
            <id>P56703</id>
            <label>WNT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-20737924">
            <id>P43652</id>
        </interactant>
        <interactant intactId="EBI-2899665">
            <id>P27467</id>
            <label>Wnt3a</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 4 11 13">Secreted</location>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="2 4 13">High level detected in plasma but also in extravascular fluids such as follicular and cerebrospinal fluids (at protein level).</text>
    </comment>
    <comment type="domain">
        <text evidence="12 15">The second albumin domain forms a deep binding pocket that contains palmitoleic acid (in vitro) (PubMed:29153507). Palmitoleic acid is most likely not the physiological ligand. Instead, this pocket may accomodate the covalently bound lipid moiety of Wnt family members (Probable).</text>
    </comment>
    <comment type="PTM">
        <text evidence="3 4 5 6 8 9 10 12">N-glycosylated; more than 90% of the glycans are sialylated.</text>
    </comment>
    <comment type="similarity">
        <text evidence="1">Belongs to the ALB/AFP/VDB family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAA21612.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U51243">
        <property type="protein sequence ID" value="AAC50720.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="BAF83245.1"/>
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        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAA68197.1"/>
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        <property type="entry name" value="I39424"/>
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        <property type="entry name" value="I39426"/>
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        <property type="nucleotide sequence ID" value="NM_001133.2"/>
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        <property type="interactions" value="13"/>
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        <property type="interactions" value="58"/>
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        <property type="interactions" value="24"/>
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        <property type="generic name" value="Copper"/>
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        <property type="glycosylation" value="21 N-Linked glycans (6 sites)"/>
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        <property type="glycosylation" value="6 sites, 30 glycans"/>
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        <property type="antibodies" value="1 sequenced antibody"/>
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        <property type="antibodies" value="267 antibodies from 32 providers"/>
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        <property type="protein sequence ID" value="ENSP00000226355.3"/>
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        <property type="RefSeq protein sequence ID" value="NP_001124.1"/>
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        <property type="organism name" value="human"/>
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        <property type="gene designation" value="AFM"/>
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        <property type="type" value="gene"/>
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        <property type="taxonomic scope" value="Eukaryota"/>
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        <property type="component" value="Chromosome 4"/>
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        <property type="molecule type" value="protein"/>
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        <property type="entry name" value="Serum_albumin-like"/>
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            <end position="599"/>
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            <end position="599"/>
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            <position position="402"/>
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        <location>
            <position position="488"/>
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        <location>
            <begin position="77"/>
            <end position="86"/>
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        <location>
            <begin position="99"/>
            <end position="114"/>
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    <feature type="disulfide bond" evidence="1 12">
        <location>
            <begin position="113"/>
            <end position="124"/>
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    <feature type="disulfide bond" evidence="1">
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            <begin position="148"/>
            <end position="193"/>
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    <feature type="disulfide bond" evidence="1 12">
        <location>
            <begin position="192"/>
            <end position="201"/>
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    <feature type="disulfide bond" evidence="1 12">
        <location>
            <begin position="224"/>
            <end position="270"/>
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            <end position="277"/>
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        <location>
            <begin position="289"/>
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            <begin position="302"/>
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            <end position="385"/>
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            <begin position="384"/>
            <end position="393"/>
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<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="196" xmlns="https://uniprot.org/uniprot">
    <accession>P51825</accession>
    <accession>B4DTU1</accession>
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            <fullName>AF4/FMR2 family member 1</fullName>
        </recommendedName>
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            <fullName>ALL1-fused gene from chromosome 4 protein</fullName>
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        </alternativeName>
        <alternativeName>
            <fullName>Protein FEL</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Proto-oncogene AF4</fullName>
        </alternativeName>
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        <name type="synonym">MLLT2</name>
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        <name type="scientific">Homo sapiens</name>
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        <dbReference type="NCBI Taxonomy" id="9606"/>
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            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    </organism>
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                <person name="Fujiwara T."/>
                <person name="Ono T."/>
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                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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                <person name="Senba T."/>
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                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; SER-212; THR-220; SER-750 AND THR-755</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; SER-212; SER-588 AND SER-750</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206 AND SER-750</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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            <dbReference type="PubMed" id="20068231"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
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            <dbReference type="PubMed" id="22195968"/>
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        <scope>IDENTIFICATION IN THE SEC COMPLEX</scope>
    </reference>
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            <dbReference type="PubMed" id="22895430"/>
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        <scope>REVIEW ON THE SUPER ELONGATION COMPLEX</scope>
    </reference>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <scope>STRUCTURE BY NMR OF 738-779 IN COMPLEX WITH MLLT3</scope>
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        <scope>VARIANT [LARGE SCALE ANALYSIS] LYS-1204</scope>
    </reference>
    <comment type="subunit">
        <text evidence="4 5">Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2610180">
            <id>P51825</id>
        </interactant>
        <interactant intactId="EBI-716132">
            <id>P42568</id>
            <label>MLLT3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2610180">
            <id>P51825</id>
        </interactant>
        <interactant intactId="EBI-6164389">
            <id>P04608</id>
            <label>tat</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-24213872">
            <id>P51825-3</id>
        </interactant>
        <interactant intactId="EBI-2808808">
            <id>P53367</id>
            <label>ARFIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="8">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P51825-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P51825-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_046095 VSP_046096"/>
        </isoform>
        <isoform>
            <id>P51825-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_046096"/>
        </isoform>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.</text>
    </comment>
    <comment type="similarity">
        <text evidence="8">Belongs to the AF4 family.</text>
    </comment>
    <comment type="sequence caution" evidence="8">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAA36642" version="1"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/3/AF4"/>
    </comment>
    <dbReference type="EMBL" id="L13773">
        <property type="protein sequence ID" value="AAA58360.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="L25050">
        <property type="protein sequence ID" value="AAA36642.1"/>
        <property type="status" value="ALT_FRAME"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK300364">
        <property type="protein sequence ID" value="BAG62103.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AC092658">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC093779">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="AC093827">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3616.1">
        <molecule id="P51825-1"/>
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    <dbReference type="CCDS" id="CCDS54775.1">
        <molecule id="P51825-2"/>
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    <dbReference type="CCDS" id="CCDS93557.1">
        <molecule id="P51825-3"/>
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    <dbReference type="PIR" id="A58198">
        <property type="entry name" value="A58198"/>
    </dbReference>
    <dbReference type="PIR" id="I39410">
        <property type="entry name" value="I39410"/>
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    <dbReference type="RefSeq" id="NP_001160165.1">
        <molecule id="P51825-2"/>
        <property type="nucleotide sequence ID" value="NM_001166693.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001300888.1">
        <molecule id="P51825-3"/>
        <property type="nucleotide sequence ID" value="NM_001313959.2"/>
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    <dbReference type="RefSeq" id="NP_001300889.1">
        <property type="nucleotide sequence ID" value="NM_001313960.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_005926.1">
        <molecule id="P51825-1"/>
        <property type="nucleotide sequence ID" value="NM_005935.4"/>
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    <dbReference type="RefSeq" id="XP_005263064.1">
        <molecule id="P51825-2"/>
        <property type="nucleotide sequence ID" value="XM_005263007.4"/>
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    <dbReference type="RefSeq" id="XP_011530275.1">
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        <property type="nucleotide sequence ID" value="XM_011531973.4"/>
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        <molecule id="P51825-2"/>
        <property type="nucleotide sequence ID" value="XM_054350052.1"/>
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        <molecule id="P51825-2"/>
        <property type="nucleotide sequence ID" value="XM_054350053.1"/>
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        <property type="chains" value="A=738-779"/>
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    <dbReference type="AlphaFoldDB" id="P51825"/>
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        <property type="glycosylation" value="1 site"/>
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    <dbReference type="PaxDb" id="9606-ENSP00000378578"/>
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        <property type="gene ID" value="ENSG00000172493.24"/>
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        <property type="gene ID" value="ENSG00000172493.24"/>
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    <dbReference type="KEGG" id="hsa:4299"/>
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        <property type="protein sequence ID" value="ENSP00000378578.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001166693.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001160165.1"/>
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    <dbReference type="HGNC" id="HGNC:7135">
        <property type="gene designation" value="AFF1"/>
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    <dbReference type="HPA" id="ENSG00000172493">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFF1"/>
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    </dbReference>
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</entry>
<entry dataset="Swiss-Prot" created="2005-06-21" modified="2026-01-28" version="183" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N4X5</accession>
    <accession>A8K6P7</accession>
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        <recommendedName>
            <fullName>Actin filament-associated protein 1-like 2</fullName>
            <shortName>AFAP1-like protein 2</shortName>
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        <name type="primary">AFAP1L2</name>
        <name type="synonym">KIAA1914</name>
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    <organism>
        <name type="scientific">Homo sapiens</name>
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        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
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            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2002-01" db="EMBL/GenBank/DDBJ databases">
            <title>XB130, a novel adaptor protein for Src binding and activation.</title>
            <authorList>
                <person name="Bai X.-H."/>
                <person name="Keshavjee S."/>
                <person name="Liu M."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2001" name="DNA Res." volume="8" first="179" last="187">
            <title>Prediction of the coding sequences of unidentified human genes. XXI. The complete sequences of 60 new cDNA clones from brain which code for large proteins.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="11572484"/>
            <dbReference type="DOI" id="10.1093/dnares/8.4.179"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
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                <person name="Griffiths C."/>
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                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
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                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
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                <person name="Wray P.W."/>
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                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Murakawa K."/>
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                <person name="Tanai H."/>
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                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
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                <person name="Hikiji T."/>
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                <person name="Ikema Y."/>
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                <person name="Kawakami T."/>
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                <person name="Senba T."/>
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                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
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                <person name="Satoh T."/>
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                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
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                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4)</scope>
        <source>
            <tissue>Cerebellum</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Pancreas</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2007" name="J. Biol. Chem." volume="282" first="16401" last="16412">
            <title>XB130, a novel adaptor protein for signal transduction.</title>
            <authorList>
                <person name="Xu J."/>
                <person name="Bai X.-H."/>
                <person name="Lodyga M."/>
                <person name="Han B."/>
                <person name="Xiao H."/>
                <person name="Keshavjee S."/>
                <person name="Hu J."/>
                <person name="Zhang H."/>
                <person name="Yang B.B."/>
                <person name="Liu M."/>
            </authorList>
            <dbReference type="PubMed" id="17412687"/>
            <dbReference type="DOI" id="10.1074/jbc.m701684200"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH SRC</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>MUTAGENESIS OF TYR-4</scope>
        <scope>PHOSPHORYLATION</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2008" name="Cell Commun. Signal." volume="6" first="7" last="7">
            <title>Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells.</title>
            <authorList>
                <person name="Emaduddin M."/>
                <person name="Edelmann M.J."/>
                <person name="Kessler B.M."/>
                <person name="Feller S.M."/>
            </authorList>
            <dbReference type="PubMed" id="18844995"/>
            <dbReference type="DOI" id="10.1186/1478-811x-6-7"/>
        </citation>
        <scope>PHOSPHORYLATION</scope>
        <scope>INTERACTION WITH LCK</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="10">
        <citation type="submission" date="2005-11" db="PDB data bank">
            <title>Solution structure of the C-terminal PH domain of hypothetical protein KIAA1914 from human.</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 354-448</scope>
    </reference>
    <comment type="function">
        <text evidence="5">May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6">Interacts with SRC. Interacts with LCK when tyrosine phosphorylated.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N4X5-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N4X5-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_014255"/>
        </isoform>
        <isoform>
            <id>Q8N4X5-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_014254 VSP_014256"/>
        </isoform>
        <isoform>
            <id>Q8N4X5-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_036211 VSP_014255"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Detected in spleen and thyroid, and at lower levels in kidney, brain, lung and pancreas.</text>
    </comment>
    <comment type="PTM">
        <text evidence="5 6">Tyrosine phosphorylated (by SRC).</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB67807" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF474151">
        <property type="protein sequence ID" value="AAQ05765.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB067501">
        <property type="protein sequence ID" value="BAB67807.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005383">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL133384">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL355302">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027470">
        <property type="protein sequence ID" value="BAB55135.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291712">
        <property type="protein sequence ID" value="BAF84401.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK123108">
        <property type="protein sequence ID" value="BAG53870.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC024314">
        <property type="protein sequence ID" value="AAH24314.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC033212">
        <property type="protein sequence ID" value="AAH33212.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31286.1">
        <molecule id="Q8N4X5-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31287.1">
        <molecule id="Q8N4X5-2"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS91356.1">
        <molecule id="Q8N4X5-4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001001936.1">
        <molecule id="Q8N4X5-1"/>
        <property type="nucleotide sequence ID" value="NM_001001936.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001274753.1">
        <property type="nucleotide sequence ID" value="NM_001287824.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_115939.1">
        <molecule id="Q8N4X5-2"/>
        <property type="nucleotide sequence ID" value="NM_032550.4"/>
    </dbReference>
    <dbReference type="PDB" id="2COF">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=354-447"/>
    </dbReference>
    <dbReference type="PDBsum" id="2COF"/>
    <dbReference type="AlphaFoldDB" id="Q8N4X5"/>
    <dbReference type="BMRB" id="Q8N4X5"/>
    <dbReference type="SMR" id="Q8N4X5"/>
    <dbReference type="BioGRID" id="124161">
        <property type="interactions" value="21"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8N4X5">
        <property type="interactions" value="642"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N4X5">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="MINT" id="Q8N4X5"/>
    <dbReference type="STRING" id="9606.ENSP00000303042"/>
    <dbReference type="GlyCosmos" id="Q8N4X5">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q8N4X5">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8N4X5"/>
    <dbReference type="PhosphoSitePlus" id="Q8N4X5"/>
    <dbReference type="BioMuta" id="AFAP1L2"/>
    <dbReference type="DMDM" id="68052360"/>
    <dbReference type="jPOST" id="Q8N4X5"/>
    <dbReference type="MassIVE" id="Q8N4X5"/>
    <dbReference type="PaxDb" id="9606-ENSP00000303042"/>
    <dbReference type="PeptideAtlas" id="Q8N4X5"/>
    <dbReference type="ProteomicsDB" id="71986">
        <molecule id="Q8N4X5-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71987">
        <molecule id="Q8N4X5-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71988">
        <molecule id="Q8N4X5-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71989">
        <molecule id="Q8N4X5-4"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="31934">
        <property type="antibodies" value="134 antibodies from 34 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84632"/>
    <dbReference type="Ensembl" id="ENST00000304129.9">
        <molecule id="Q8N4X5-1"/>
        <property type="protein sequence ID" value="ENSP00000303042.4"/>
        <property type="gene ID" value="ENSG00000169129.17"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000369271.7">
        <molecule id="Q8N4X5-2"/>
        <property type="protein sequence ID" value="ENSP00000358276.3"/>
        <property type="gene ID" value="ENSG00000169129.17"/>
    </dbReference>
    <dbReference type="GeneID" id="84632"/>
    <dbReference type="KEGG" id="hsa:84632"/>
    <dbReference type="MANE-Select" id="ENST00000304129.9">
        <property type="protein sequence ID" value="ENSP00000303042.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001001936.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001001936.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001lbn.5">
        <molecule id="Q8N4X5-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:25901"/>
    <dbReference type="ClinPGx" id="PA162375773"/>
    <dbReference type="CTD" id="84632"/>
    <dbReference type="DisGeNET" id="84632"/>
    <dbReference type="GeneCards" id="AFAP1L2"/>
    <dbReference type="HGNC" id="HGNC:25901">
        <property type="gene designation" value="AFAP1L2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000169129">
        <property type="expression patterns" value="Tissue enhanced (lymphoid tissue, parathyroid gland, thyroid gland)"/>
    </dbReference>
    <dbReference type="MIM" id="612420">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000169129"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000169129"/>
    <dbReference type="eggNOG" id="ENOG502QQA8">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000183067"/>
    <dbReference type="HOGENOM" id="CLU_014418_0_0_1"/>
    <dbReference type="InParanoid" id="Q8N4X5"/>
    <dbReference type="OMA" id="FPPNCPD"/>
    <dbReference type="OrthoDB" id="8443615at2759"/>
    <dbReference type="PAN-GO" id="Q8N4X5">
        <property type="GO annotations" value="9 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N4X5"/>
    <dbReference type="PathwayCommons" id="Q8N4X5"/>
    <dbReference type="SignaLink" id="Q8N4X5"/>
    <dbReference type="SIGNOR" id="Q8N4X5"/>
    <dbReference type="Agora" id="ENSG00000169129"/>
    <dbReference type="BioGRID-ORCS" id="84632">
        <property type="hits" value="9 hits in 1151 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFAP1L2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q8N4X5"/>
    <dbReference type="GenomeRNAi" id="84632"/>
    <dbReference type="Pharos" id="Q8N4X5">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8N4X5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8N4X5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000169129">
        <property type="expression patterns" value="Expressed in sural nerve and 145 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8N4X5">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005886">
        <property type="term" value="C:plasma membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030296">
        <property type="term" value="F:protein tyrosine kinase activator activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042169">
        <property type="term" value="F:SH2 domain binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0017124">
        <property type="term" value="F:SH3 domain binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006954">
        <property type="term" value="P:inflammatory response"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045893">
        <property type="term" value="P:positive regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0045742">
        <property type="term" value="P:positive regulation of epidermal growth factor receptor signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0032757">
        <property type="term" value="P:positive regulation of interleukin-8 production"/>
        <property type="evidence" value="ECO:0000314"/>
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        <property type="term" value="P:regulation of interleukin-6 production"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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    <dbReference type="GO" id="GO:0007346">
        <property type="term" value="P:regulation of mitotic cell cycle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HGNC-UCL"/>
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        <property type="entry name" value="PH1_AFAP"/>
        <property type="match status" value="1"/>
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        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.30.29.30:FF:000171">
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    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="2"/>
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        <property type="entry name" value="PH-like_dom_sf"/>
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    <dbReference type="InterPro" id="IPR001849">
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    <dbReference type="PANTHER" id="PTHR14338">
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        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR14338:SF4">
        <property type="entry name" value="ACTIN FILAMENT-ASSOCIATED PROTEIN 1-LIKE 2"/>
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    <keyword id="KW-0002">3D-structure</keyword>
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    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
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            <begin position="1"/>
            <end position="818"/>
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            <begin position="175"/>
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            <begin position="353"/>
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            <begin position="66"/>
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            <begin position="513"/>
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            <begin position="765"/>
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            <begin position="652"/>
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        <location>
            <begin position="85"/>
            <end position="94"/>
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        <location>
            <begin position="123"/>
            <end position="139"/>
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    <feature type="modified residue" description="Phosphotyrosine" evidence="1">
        <location>
            <position position="56"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="408"/>
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        <location>
            <position position="413"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="484"/>
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        <location>
            <begin position="1"/>
            <end position="478"/>
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            <position position="135"/>
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            <begin position="766"/>
            <end position="769"/>
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            <begin position="811"/>
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            <position position="522"/>
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            <position position="726"/>
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        <original>Y</original>
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        <location>
            <position position="4"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAF84401." evidence="10" ref="4">
        <original>E</original>
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            <position position="13"/>
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    <feature type="sequence conflict" description="In Ref. 4; BAF84401." evidence="10" ref="4">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAB55135." evidence="10" ref="4">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="567"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAB55135." evidence="10" ref="4">
        <location>
            <position position="596"/>
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    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAB55135." evidence="10" ref="4">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="605"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAQ05765." evidence="10" ref="1">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="608"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; BAF84401." evidence="10" ref="4">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="630"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAQ05765." evidence="10" ref="1">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="758"/>
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    <feature type="strand" evidence="11">
        <location>
            <begin position="359"/>
            <end position="364"/>
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    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="367"/>
            <end position="375"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="380"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="390"/>
            <end position="396"/>
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    </feature>
    <feature type="turn" evidence="11">
        <location>
            <begin position="398"/>
            <end position="400"/>
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    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="402"/>
            <end position="404"/>
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    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="414"/>
            <end position="419"/>
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    </feature>
    <feature type="strand" evidence="11">
        <location>
            <begin position="422"/>
            <end position="428"/>
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    </feature>
    <feature type="helix" evidence="11">
        <location>
            <begin position="432"/>
            <end position="445"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5DTU0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
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        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="17412687"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="18844995"/>
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    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="11572484"/>
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    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007829" key="11">
        <source>
            <dbReference type="PDB" id="2COF"/>
        </source>
    </evidence>
    <sequence length="818" mass="91300" checksum="36040D6D09491DA8" modified="2002-10-01" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-03-06" modified="2026-01-28" version="167" xmlns="https://uniprot.org/uniprot">
    <accession>Q8WV93</accession>
    <accession>Q8N6A3</accession>
    <name>AFG1L_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="5">AFG1-like ATPase</fullName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="3">Lactation elevated protein 1</fullName>
            <ecNumber evidence="4">3.6.-.-</ecNumber>
        </alternativeName>
        <alternativeName>
            <fullName>Protein AFG1 homolog</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="5" type="primary">AFG1L</name>
        <name type="synonym">AFG1</name>
        <name evidence="3" type="synonym">LACE1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Stiburek L."/>
            </authorList>
            <dbReference type="PubMed" id="26759378"/>
            <dbReference type="DOI" id="10.1042/bj20151029"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <scope>MUTAGENESIS OF LYS-142; THR-143 AND GLU-214</scope>
        <scope>INTERACTION WITH YME1L1</scope>
        <scope>COX4I1 AND COX5A</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2016" name="Oncotarget" volume="7" first="47687" last="47698">
            <title>LACE1 interacts with p53 and mediates its mitochondrial translocation and apoptosis.</title>
            <authorList>
                <person name="Cesnekova J."/>
                <person name="Spacilova J."/>
                <person name="Hansikova H."/>
                <person name="Houstek J."/>
                <person name="Zeman J."/>
                <person name="Stiburek L."/>
            </authorList>
            <dbReference type="PubMed" id="27323408"/>
            <dbReference type="DOI" id="10.18632/oncotarget.9959"/>
        </citation>
        <scope>INTERACTION WITH TP53</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <comment type="function">
        <text evidence="1 2">Putative mitochondrial ATPase. Plays a role in mitochondrial morphology and mitochondrial protein metabolism. Promotes degradation of excess nuclear-encoded complex IV subunits (COX4I1, COX5A and COX6A1) and normal activity of complexes III and IV of the respiratory chain (PubMed:26759378, PubMed:27323408). Mediates mitochondrial translocation of TP53 and its transcription-independent apoptosis in response to genotoxic stress (PubMed:27323408).</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 2">Found in several complexes of 140-500 kDa. Interacts with YME1L1 (PubMed:26759378). Interacts with COX4I1 (PubMed:26759378). Interacts with COX5A (PubMed:26759378). Interacts with TP53; mediates mitochondrial translocation of TP53 in response to genotoxic stress such as mitomycin C treatment (PubMed:27323408).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2865743">
            <id>Q8WV93</id>
        </interactant>
        <interactant intactId="EBI-744695">
            <id>Q8N9N5</id>
            <label>BANP</label>
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        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2865743">
            <id>Q8WV93</id>
        </interactant>
        <interactant intactId="EBI-7062247">
            <id>Q9UHD4</id>
            <label>CIDEB</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Mitochondrion membrane</location>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the AFG1 ATPase family.</text>
    </comment>
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        <property type="protein sequence ID" value="AAM74228.1"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
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        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <dbReference type="EMBL" id="BC018445">
        <property type="protein sequence ID" value="AAH18445.2"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="CCDS" id="CCDS5067.1"/>
    <dbReference type="RefSeq" id="NP_001309934.1">
        <property type="nucleotide sequence ID" value="NM_001323005.1"/>
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    <dbReference type="RefSeq" id="NP_660358.2">
        <property type="nucleotide sequence ID" value="NM_145315.4"/>
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    <dbReference type="AlphaFoldDB" id="Q8WV93"/>
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        <property type="interactions" value="14"/>
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        <property type="interactions" value="2999"/>
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        <property type="interactions" value="10"/>
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    <dbReference type="STRING" id="9606.ENSP00000357973"/>
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        <property type="antibodies" value="167 antibodies from 21 providers"/>
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    <dbReference type="DNASU" id="246269"/>
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        <property type="protein sequence ID" value="ENSP00000357973.3"/>
        <property type="gene ID" value="ENSG00000135537.18"/>
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        <property type="protein sequence ID" value="ENSP00000357973.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_145315.5"/>
        <property type="RefSeq protein sequence ID" value="NP_660358.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003psj.4">
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:16411"/>
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    <dbReference type="GeneCards" id="AFG1L"/>
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        <property type="gene designation" value="AFG1L"/>
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    <dbReference type="HPA" id="ENSG00000135537">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="617469">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000135537"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000135537"/>
    <dbReference type="eggNOG" id="KOG2383">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000013227"/>
    <dbReference type="HOGENOM" id="CLU_008681_3_1_1"/>
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    <dbReference type="OMA" id="ARRFINM"/>
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        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8WV93"/>
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    <dbReference type="SignaLink" id="Q8WV93"/>
    <dbReference type="Agora" id="ENSG00000135537"/>
    <dbReference type="BioGRID-ORCS" id="246269">
        <property type="hits" value="17 hits in 1158 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="LACE1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="246269"/>
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        <property type="development level" value="Tbio"/>
    </dbReference>
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    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 6"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8WV93">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000135537">
        <property type="expression patterns" value="Expressed in left testis and 102 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8WV93">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031966">
        <property type="term" value="C:mitochondrial membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0035694">
        <property type="term" value="P:mitochondrial protein catabolic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0141164">
        <property type="term" value="P:mitochondrial protein quality control"/>
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    <dbReference type="GO" id="GO:0007005">
        <property type="term" value="P:mitochondrion organization"/>
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        <property type="entry name" value="Lactation elevated 1 (Predicted)"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
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    <dbReference type="InterPro" id="IPR005654">
        <property type="entry name" value="ATPase_AFG1-like"/>
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    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
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        <property type="entry name" value="ZapE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12169:SF6">
        <property type="entry name" value="AFG1-LIKE ATPASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12169">
        <property type="entry name" value="ATPASE N2B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF03969">
        <property type="entry name" value="AFG1_ATPase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <feature type="chain" id="PRO_0000279521" description="AFG1-like ATPase">
        <location>
            <begin position="1"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="136"/>
            <end position="143"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="209"/>
            <end position="214"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="mutagenesis site" description="Does not affect mitochondrial targeting. Increased amount of unprocessed protein form. Fails to rescue the increased accumulation of complex IV subunits in AFG1L-deficient cell line. Reduces mitochondrial targeting; when associated with V-143." evidence="1">
        <original>K</original>
        <variation>A</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces mitochondrial targeting. Increased amount of unprocessed protein form. Reduces mitochondrial targeting; when associated with A-142." evidence="1">
        <original>T</original>
        <variation>V</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Does not affect subcellular location. Fails to rescue the increased accumulation of complex IV subunits in AFG1L-deficient cell line." evidence="1">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="214"/>
        </location>
    </feature>
    <evidence type="ECO:0000269" key="1">
        <source>
            <dbReference type="PubMed" id="26759378"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="27323408"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="3">
        <source>
            <dbReference type="PubMed" id="12079282"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <evidence type="ECO:0000312" key="5">
        <source>
            <dbReference type="HGNC" id="HGNC:16411"/>
        </source>
    </evidence>
    <sequence length="481" mass="54845" checksum="5B612E3B657DCA12" modified="2004-03-01" version="2">MAASWSLLVTLRPLAQSPLRGRCVGCGAWAAALAPLATAPGKPFWKAYTVQTSESMTPTATSETYLKALAVCHGPLDHYDFLIKAHELKDDEHQRRVIQCLQKLHEDLKGYNIEAEGLFSKLFSRSKPPRGLYVYGDVGTGKTMVMDMFYAYVEMKRKKRVHFHGFMLDVHKRIHRLKQSLPKRKPGFMAKSYDPIAPIAEEISEEACLLCFDEFQVTDIADAMILKQLFENLFKNGVVVVATSNRPPEDLYKNGLQRANFVPFIAVLKEYCNTVQLDSGIDYRKRELPAAGKLYYLTSEADVEAVMDKLFDELAQKQNDLTRPRILKVQGRELRLNKACGTVADCTFEELCERPLGASDYLELSKNFDTIFLRNIPQFTLANRTQGRRFITLIDNFYDLKVRIICSASTPISSLFLHQHHDSELEQSRILMDDLGLSQDSAEGLSMFTGEEEIFAFQRTISRLTEMQTEQYWNEGDRTKK</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>P51816</accession>
    <accession>A2RTY4</accession>
    <accession>B4DXD5</accession>
    <accession>B7WNQ1</accession>
    <accession>B7ZLD6</accession>
    <accession>B7ZLD9</accession>
    <accession>O43786</accession>
    <accession>O60215</accession>
    <accession>P78407</accession>
    <accession>Q13521</accession>
    <accession>Q14323</accession>
    <accession>Q7Z2F7</accession>
    <accession>Q7Z400</accession>
    <accession>Q9UNA5</accession>
    <name>AFF2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="11">AF4/FMR2 family member 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Protein FMR-2</fullName>
            <shortName>FMR2P</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Protein Ox19</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">AFF2</name>
        <name type="synonym">FMR2</name>
        <name type="synonym">OX19</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1996" name="Nat. Genet." volume="13" first="105" last="108">
            <title>Identification of the gene FMR2, associated with FRAXE mental retardation.</title>
            <authorList>
                <person name="Gecz J."/>
                <person name="Gedeon A.K."/>
                <person name="Sutherland G.R."/>
                <person name="Mulley J.C."/>
            </authorList>
            <dbReference type="PubMed" id="8673085"/>
            <dbReference type="DOI" id="10.1038/ng0596-105"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <source>
            <tissue>Fetal brain</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="1996" name="Nat. Genet." volume="13" first="109" last="113">
            <title>Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island.</title>
            <authorList>
                <person name="Gu Y."/>
                <person name="Shen Y."/>
                <person name="Gibbs R.A."/>
                <person name="Nelson D.L."/>
            </authorList>
            <dbReference type="PubMed" id="8673086"/>
            <dbReference type="DOI" id="10.1038/ng0596-109"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1996" name="Hum. Mol. Genet." volume="5" first="275" last="282">
            <title>A candidate gene for mild mental handicap at the FRAXE fragile site.</title>
            <authorList>
                <person name="Chakrabarti L."/>
                <person name="Knight S.J.L."/>
                <person name="Flannery A.V."/>
                <person name="Davies K.E."/>
            </authorList>
            <dbReference type="PubMed" id="8824884"/>
            <dbReference type="DOI" id="10.1093/hmg/5.2.275"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)</scope>
        <source>
            <tissue>Fetal brain</tissue>
        </source>
    </reference>
    <reference key="4">
        <citation type="journal article" date="1997" name="Genomics" volume="44" first="201" last="213">
            <title>Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators.</title>
            <authorList>
                <person name="Gecz J."/>
                <person name="Bielby S."/>
                <person name="Sutherland G.R."/>
                <person name="Mulley J.C."/>
            </authorList>
            <dbReference type="PubMed" id="9299237"/>
            <dbReference type="DOI" id="10.1006/geno.1997.4867"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="1998" name="Hum. Mol. Genet." volume="7" first="441" last="448">
            <title>Expression of the murine homologue of FMR2 in mouse brain and during development.</title>
            <authorList>
                <person name="Chakrabarti L."/>
                <person name="Bristulf J."/>
                <person name="Foss G.S."/>
                <person name="Davies K.E."/>
            </authorList>
            <dbReference type="PubMed" id="9467002"/>
            <dbReference type="DOI" id="10.1093/hmg/7.3.441"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2003" name="Mol. Biol. Evol." volume="20" first="1281" last="1289">
            <title>Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees.</title>
            <authorList>
                <person name="Kitano T."/>
                <person name="Schwarz C."/>
                <person name="Nickel B."/>
                <person name="Paeaebo S."/>
            </authorList>
            <dbReference type="PubMed" id="12777533"/>
            <dbReference type="DOI" id="10.1093/molbev/msg134"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 526-896</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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        <scope>FUNCTION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-430 AND THR-517</scope>
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        <scope>INVOLVEMENT IN XLID109</scope>
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    <comment type="function">
        <text evidence="2">RNA-binding protein. Might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2">Nucleus speckle</location>
        </subcellularLocation>
        <text>When splicing is inhibited, accumulates in enlarged speckles.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P51816-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P51816-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_000211 VSP_000212 VSP_000213"/>
        </isoform>
        <isoform>
            <id>P51816-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_000211 VSP_000212 VSP_000216"/>
        </isoform>
        <isoform>
            <id>P51816-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_000211 VSP_000212 VSP_000213 VSP_000214 VSP_000215"/>
        </isoform>
        <isoform>
            <id>P51816-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_000211 VSP_000213"/>
        </isoform>
        <isoform>
            <id>P51816-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_000212 VSP_000213"/>
        </isoform>
        <isoform>
            <id>P51816-7</id>
            <name>7</name>
            <sequence type="described" ref="VSP_043237 VSP_043238"/>
        </isoform>
        <text>Additional isoforms seem to exist.</text>
    </comment>
    <comment type="tissue specificity">
        <text>Brain (most abundant in hippocampus and amygdala), placenta and lung.</text>
    </comment>
    <comment type="disease" evidence="2 3">
        <disease id="DI-01629">
            <name>Intellectual developmental disorder, X-linked 109</name>
            <acronym>XLID109</acronym>
            <description>A form of mild to moderate intellectual disability associated with learning difficulties, communication deficits, attention problems, hyperactivity, and autistic behavior. It is associated with a fragile site on chromosome Xq28. Intellectual disability is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.</description>
            <dbReference type="MIM" id="309548"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry. It is caused either by silencing of the AFF2 gene as a consequence of a CCG expansion located upstream of this gene or by deletion within the gene. Loss of AFF2 expression is correlated with FRAXE CCG(N) expansion. Normal individuals have 6-35 copies of the repeat, whereas cytogenetically positive, developmentally delayed males have more than 200 copies and show methylation of the associated CPG island.</text>
    </comment>
    <comment type="similarity">
        <text evidence="10">Belongs to the AF4 family.</text>
    </comment>
    <dbReference type="EMBL" id="U48436">
        <property type="protein sequence ID" value="AAC82513.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="L76569">
        <property type="protein sequence ID" value="AAA99416.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X95463">
        <property type="protein sequence ID" value="CAA64730.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012624">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012603">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012604">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012605">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012606">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012607">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012608">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012609">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012610">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012611">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012612">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012613">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012614">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012615">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012616">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012617">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012618">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012619">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012620">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012621">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012622">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF012623">
        <property type="protein sequence ID" value="AAB71534.1"/>
        <property type="status" value="JOINED"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AJ001550">
        <property type="protein sequence ID" value="CAA04822.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB102644">
        <property type="protein sequence ID" value="BAC81113.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101711">
        <property type="protein sequence ID" value="BAC80300.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101712">
        <property type="protein sequence ID" value="BAC80301.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101713">
        <property type="protein sequence ID" value="BAC80302.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101714">
        <property type="protein sequence ID" value="BAC80303.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101715">
        <property type="protein sequence ID" value="BAC80304.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101716">
        <property type="protein sequence ID" value="BAC80305.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101717">
        <property type="protein sequence ID" value="BAC80306.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101718">
        <property type="protein sequence ID" value="BAC80307.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101719">
        <property type="protein sequence ID" value="BAC80308.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101720">
        <property type="protein sequence ID" value="BAC80309.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101721">
        <property type="protein sequence ID" value="BAC80310.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101722">
        <property type="protein sequence ID" value="BAC80311.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101723">
        <property type="protein sequence ID" value="BAC80312.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101724">
        <property type="protein sequence ID" value="BAC80313.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101725">
        <property type="protein sequence ID" value="BAC80314.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101726">
        <property type="protein sequence ID" value="BAC80315.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101727">
        <property type="protein sequence ID" value="BAC80316.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101728">
        <property type="protein sequence ID" value="BAC80317.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101729">
        <property type="protein sequence ID" value="BAC80318.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB101730">
        <property type="protein sequence ID" value="BAC80319.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK301927">
        <property type="protein sequence ID" value="BAG63347.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC002368">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC005731">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC006516">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC015552">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC231841">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471171">
        <property type="protein sequence ID" value="EAW61288.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC132683">
        <property type="protein sequence ID" value="AAI32684.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143740">
        <property type="protein sequence ID" value="AAI43741.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC143744">
        <property type="protein sequence ID" value="AAI43745.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AH008014">
        <property type="protein sequence ID" value="AAD45878.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14684.1">
        <molecule id="P51816-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55521.1">
        <molecule id="P51816-7"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS76040.1">
        <molecule id="P51816-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS78510.1">
        <molecule id="P51816-3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001162593.1">
        <molecule id="P51816-3"/>
        <property type="nucleotide sequence ID" value="NM_001169122.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001162594.1">
        <molecule id="P51816-5"/>
        <property type="nucleotide sequence ID" value="NM_001169123.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001162595.1">
        <molecule id="P51816-6"/>
        <property type="nucleotide sequence ID" value="NM_001169124.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001162596.1">
        <molecule id="P51816-2"/>
        <property type="nucleotide sequence ID" value="NM_001169125.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001164099.1">
        <molecule id="P51816-7"/>
        <property type="nucleotide sequence ID" value="NM_001170628.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_002016.2">
        <molecule id="P51816-1"/>
        <property type="nucleotide sequence ID" value="NM_002025.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P51816"/>
    <dbReference type="SMR" id="P51816"/>
    <dbReference type="BioGRID" id="108620">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="FunCoup" id="P51816">
        <property type="interactions" value="168"/>
    </dbReference>
    <dbReference type="IntAct" id="P51816">
        <property type="interactions" value="8"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000359489"/>
    <dbReference type="GlyGen" id="P51816">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P51816"/>
    <dbReference type="PhosphoSitePlus" id="P51816"/>
    <dbReference type="BioMuta" id="AFF2"/>
    <dbReference type="DMDM" id="116241242"/>
    <dbReference type="MassIVE" id="P51816"/>
    <dbReference type="PaxDb" id="9606-ENSP00000359489"/>
    <dbReference type="PeptideAtlas" id="P51816"/>
    <dbReference type="ProteomicsDB" id="56419">
        <molecule id="P51816-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56420">
        <molecule id="P51816-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56421">
        <molecule id="P51816-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56422">
        <molecule id="P51816-4"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56423">
        <molecule id="P51816-5"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56424">
        <molecule id="P51816-6"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56425">
        <molecule id="P51816-7"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="529">
        <property type="antibodies" value="151 antibodies from 23 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="2334"/>
    <dbReference type="Ensembl" id="ENST00000286437.7">
        <molecule id="P51816-7"/>
        <property type="protein sequence ID" value="ENSP00000286437.5"/>
        <property type="gene ID" value="ENSG00000155966.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000342251.7">
        <molecule id="P51816-3"/>
        <property type="protein sequence ID" value="ENSP00000345459.4"/>
        <property type="gene ID" value="ENSG00000155966.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000370457.9">
        <molecule id="P51816-6"/>
        <property type="protein sequence ID" value="ENSP00000359486.6"/>
        <property type="gene ID" value="ENSG00000155966.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000370458.5">
        <molecule id="P51816-4"/>
        <property type="protein sequence ID" value="ENSP00000359487.1"/>
        <property type="gene ID" value="ENSG00000155966.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000370460.7">
        <molecule id="P51816-1"/>
        <property type="protein sequence ID" value="ENSP00000359489.2"/>
        <property type="gene ID" value="ENSG00000155966.14"/>
    </dbReference>
    <dbReference type="GeneID" id="2334"/>
    <dbReference type="KEGG" id="hsa:2334"/>
    <dbReference type="MANE-Select" id="ENST00000370460.7">
        <property type="protein sequence ID" value="ENSP00000359489.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_002025.4"/>
        <property type="RefSeq protein sequence ID" value="NP_002016.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc004fco.4">
        <molecule id="P51816-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:3776"/>
    <dbReference type="ClinPGx" id="PA28192"/>
    <dbReference type="CTD" id="2334"/>
    <dbReference type="DisGeNET" id="2334"/>
    <dbReference type="GeneCards" id="AFF2"/>
    <dbReference type="HGNC" id="HGNC:3776">
        <property type="gene designation" value="AFF2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000155966">
        <property type="expression patterns" value="Tissue enhanced (bone marrow, epididymis, placenta)"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFF2"/>
    <dbReference type="MIM" id="300806">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="309548">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000155966"/>
    <dbReference type="Orphanet" id="100973">
        <property type="disease" value="FRAXE intellectual disability"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000155966"/>
    <dbReference type="eggNOG" id="ENOG502QUIB">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182974"/>
    <dbReference type="HOGENOM" id="CLU_006484_0_0_1"/>
    <dbReference type="InParanoid" id="P51816"/>
    <dbReference type="OMA" id="SMELPDP"/>
    <dbReference type="OrthoDB" id="6382204at2759"/>
    <dbReference type="PAN-GO" id="P51816">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P51816"/>
    <dbReference type="PathwayCommons" id="P51816"/>
    <dbReference type="SignaLink" id="P51816"/>
    <dbReference type="SIGNOR" id="P51816"/>
    <dbReference type="Agora" id="ENSG00000155966"/>
    <dbReference type="BioGRID-ORCS" id="2334">
        <property type="hits" value="16 hits in 766 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="804901D1">
        <property type="entry name" value="Nuclear speckle"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFF2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AFF2"/>
    <dbReference type="GenomeRNAi" id="2334"/>
    <dbReference type="Pharos" id="P51816">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P51816"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome X"/>
    </dbReference>
    <dbReference type="RNAct" id="P51816">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000155966">
        <property type="expression patterns" value="Expressed in cortical plate and 121 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016607">
        <property type="term" value="C:nuclear speck"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0002151">
        <property type="term" value="F:G-quadruplex RNA binding"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007420">
        <property type="term" value="P:brain development"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007611">
        <property type="term" value="P:learning or memory"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006397">
        <property type="term" value="P:mRNA processing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010629">
        <property type="term" value="P:negative regulation of gene expression"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035063">
        <property type="term" value="P:nuclear speck organization"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010468">
        <property type="term" value="P:regulation of gene expression"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="MGI"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043484">
        <property type="term" value="P:regulation of RNA splicing"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008380">
        <property type="term" value="P:RNA splicing"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="Gene3D" id="6.10.250.2670">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR007797">
        <property type="entry name" value="AF4/FMR2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043640">
        <property type="entry name" value="AF4/FMR2_CHD"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR043639">
        <property type="entry name" value="AF4_int"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10528">
        <property type="entry name" value="AF4/FMR2 FAMILY MEMBER"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR10528:SF18">
        <property type="entry name" value="AF4_FMR2 FAMILY MEMBER 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF05110">
        <property type="entry name" value="AF-4"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18875">
        <property type="entry name" value="AF4_int"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF18876">
        <property type="entry name" value="AFF4_CHD"/>
        <property type="match status" value="1"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
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        <name type="scientific">Homo sapiens</name>
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            <taxon>Eukaryota</taxon>
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            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
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            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
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    <reference key="1">
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            <title>Identification and characterization of AFG3L2, a novel paraplegin-related gene.</title>
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                <person name="Banfi S."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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    <reference key="2">
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Eye</tissue>
        </source>
    </reference>
    <reference key="3">
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            <title>Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia.</title>
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                <person name="Atorino L."/>
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                <person name="Casari G."/>
            </authorList>
            <dbReference type="PubMed" id="14623864"/>
            <dbReference type="DOI" id="10.1083/jcb.200304112"/>
        </citation>
        <scope>INTERACTION WITH SPG7</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2007" name="Mol. Biol. Cell" volume="18" first="3582" last="3590">
            <title>OPA1 processing reconstituted in yeast depends on the subunit composition of the m-AAA protease in mitochondria.</title>
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                <person name="Duvezin-Caubet S."/>
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            <dbReference type="PubMed" id="17615298"/>
            <dbReference type="DOI" id="10.1091/mbc.e07-02-0164"/>
        </citation>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="5">
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            <title>Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia.</title>
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                <person name="Koppen M."/>
                <person name="Metodiev M.D."/>
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            </authorList>
            <dbReference type="PubMed" id="17101804"/>
            <dbReference type="DOI" id="10.1128/mcb.01470-06"/>
        </citation>
        <scope>SUBUNIT</scope>
    </reference>
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                <person name="Augustin S."/>
                <person name="Gerdes F."/>
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                <person name="Langer T."/>
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            </authorList>
            <dbReference type="PubMed" id="19748354"/>
            <dbReference type="DOI" id="10.1016/j.molcel.2009.07.018"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>MUTAGENESIS OF LYS-354 AND GLU-408</scope>
    </reference>
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                <person name="Burkard T.R."/>
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            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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        <citation type="journal article" date="2012" name="EMBO Rep." volume="13" first="378" last="385">
            <title>Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment.</title>
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                <person name="Greene A.W."/>
                <person name="Grenier K."/>
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            </authorList>
            <dbReference type="PubMed" id="22354088"/>
            <dbReference type="DOI" id="10.1038/embor.2012.14"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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                <person name="Musova Z."/>
                <person name="Kaiserova M."/>
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            </authorList>
            <dbReference type="PubMed" id="24272953"/>
            <dbReference type="DOI" id="10.1007/s12311-013-0538-z"/>
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        <scope>INVOLVEMENT IN SCA28</scope>
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    <reference key="10">
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            <dbReference type="PubMed" id="24814845"/>
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        <scope>INVOLVEMENT IN SCA28</scope>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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            <dbReference type="PubMed" id="26504172"/>
            <dbReference type="DOI" id="10.1083/jcb.201504062"/>
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        <scope>FUNCTION</scope>
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        <scope>INTERACTION WITH SPG7</scope>
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                <person name="Tabarki B."/>
            </authorList>
            <dbReference type="PubMed" id="28449981"/>
            <dbReference type="DOI" id="10.1016/j.pediatrneurol.2017.03.019"/>
        </citation>
        <scope>VARIANT THR-572</scope>
    </reference>
    <reference key="40">
        <citation type="journal article" date="2018" name="Hum. Mutat." volume="39" first="2060" last="2071">
            <title>Concurrent AFG3L2 and SPG7 mutations associated with syndromic parkinsonism and optic atrophy with aberrant OPA1 processing and mitochondrial network fragmentation.</title>
            <authorList>
                <person name="Magri S."/>
                <person name="Fracasso V."/>
                <person name="Plumari M."/>
                <person name="Alfei E."/>
                <person name="Ghezzi D."/>
                <person name="Gellera C."/>
                <person name="Rusmini P."/>
                <person name="Poletti A."/>
                <person name="Di Bella D."/>
                <person name="Elia A.E."/>
                <person name="Pantaleoni C."/>
                <person name="Taroni F."/>
            </authorList>
            <dbReference type="PubMed" id="30252181"/>
            <dbReference type="DOI" id="10.1002/humu.23658"/>
        </citation>
        <scope>VARIANT OPA12 CYS-468</scope>
        <scope>CHARACTERIZATION OF VARIANT OPA12 CYS-468</scope>
        <scope>CHARACTERIZATION OF VARIANT SCA28 LYS-691</scope>
        <scope>MUTAGENESIS OF GLU-575</scope>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH SPG7</scope>
    </reference>
    <reference key="41">
        <citation type="journal article" date="2019" name="Cerebellum" volume="18" first="817" last="822">
            <title>Spinocerebellar ataxia type 28-phenotypic and molecular characterization of a family with heterozygous and compound-heterozygous mutations in AFG3L2.</title>
            <authorList>
                <person name="Tunc S."/>
                <person name="Dulovic-Mahlow M."/>
                <person name="Baumann H."/>
                <person name="Baaske M.K."/>
                <person name="Jahn M."/>
                <person name="Junker J."/>
                <person name="Muenchau A."/>
                <person name="Brueggemann N."/>
                <person name="Lohmann K."/>
            </authorList>
            <dbReference type="PubMed" id="31111429"/>
            <dbReference type="DOI" id="10.1007/s12311-019-01036-2"/>
        </citation>
        <scope>VARIANTS SCA28 CYS-616 AND MET-723</scope>
    </reference>
    <reference key="42">
        <citation type="journal article" date="2020" name="Acta Neuropathol. Commun." volume="8" first="93" last="93">
            <title>A novel AFG3L2 mutation close to AAA domain leads to aberrant OMA1 and OPA1 processing in a family with optic atrophy.</title>
            <authorList>
                <person name="Baderna V."/>
                <person name="Schultz J."/>
                <person name="Kearns L.S."/>
                <person name="Fahey M."/>
                <person name="Thompson B.A."/>
                <person name="Ruddle J.B."/>
                <person name="Huq A."/>
                <person name="Maltecca F."/>
            </authorList>
            <dbReference type="PubMed" id="32600459"/>
            <dbReference type="DOI" id="10.1186/s40478-020-00975-w"/>
        </citation>
        <scope>VARIANT OPA12 GLU-337</scope>
        <scope>CHARACTERIZATION OF VARIANT OPA12 GLU-337</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="43">
        <citation type="journal article" date="2020" name="Ann. Neurol." volume="88" first="18" last="32">
            <title>ATPase domain AFG3L2 mutations alter OPA1 processing and cause optic neuropathy.</title>
            <authorList>
                <person name="Caporali L."/>
                <person name="Magri S."/>
                <person name="Legati A."/>
                <person name="Del Dotto V."/>
                <person name="Tagliavini F."/>
                <person name="Balistreri F."/>
                <person name="Nasca A."/>
                <person name="La Morgia C."/>
                <person name="Carbonelli M."/>
                <person name="Valentino M.L."/>
                <person name="Lamantea E."/>
                <person name="Baratta S."/>
                <person name="Schoels L."/>
                <person name="Schuele R."/>
                <person name="Barboni P."/>
                <person name="Cascavilla M.L."/>
                <person name="Maresca A."/>
                <person name="Capristo M."/>
                <person name="Ardissone A."/>
                <person name="Pareyson D."/>
                <person name="Cammarata G."/>
                <person name="Melzi L."/>
                <person name="Zeviani M."/>
                <person name="Peverelli L."/>
                <person name="Lamperti C."/>
                <person name="Marzoli S.B."/>
                <person name="Fang M."/>
                <person name="Synofzik M."/>
                <person name="Ghezzi D."/>
                <person name="Carelli V."/>
                <person name="Taroni F."/>
            </authorList>
            <dbReference type="PubMed" id="32219868"/>
            <dbReference type="DOI" id="10.1002/ana.25723"/>
        </citation>
        <scope>INVOLVEMENT IN OPA12</scope>
        <scope>VARIANTS SPAX5 GLU-306; VAL-462 AND LYS-620</scope>
        <scope>VARIANTS OPA12 PHE-346; SER-377; GLY-407; ILE-430; VAL-462; LYS-465; LEU-514 AND CYS-605</scope>
        <scope>CHARACTERIZATION OF VARIANTS OPA12 GLY-407; VAL-462; LYS-465 AND LEU-514</scope>
        <scope>CHARACTERIZATION OF VARIANT SPAX5 LYS-620</scope>
    </reference>
    <reference key="44">
        <citation type="journal article" date="2020" name="Neurol. Genet." volume="6" first="e428" last="e428">
            <title>Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.</title>
            <authorList>
                <person name="Charif M."/>
                <person name="Chevrollier A."/>
                <person name="Gueguen N."/>
                <person name="Bris C."/>
                <person name="Goudenege D."/>
                <person name="Desquiret-Dumas V."/>
                <person name="Leruez S."/>
                <person name="Colin E."/>
                <person name="Meunier A."/>
                <person name="Vignal C."/>
                <person name="Smirnov V."/>
                <person name="Defoort-Dhellemmes S."/>
                <person name="Drumare Bouvet I."/>
                <person name="Goizet C."/>
                <person name="Votruba M."/>
                <person name="Jurkute N."/>
                <person name="Yu-Wai-Man P."/>
                <person name="Tagliavini F."/>
                <person name="Caporali L."/>
                <person name="La Morgia C."/>
                <person name="Carelli V."/>
                <person name="Procaccio V."/>
                <person name="Zanlonghi X."/>
                <person name="Meunier I."/>
                <person name="Reynier P."/>
                <person name="Bonneau D."/>
                <person name="Amati-Bonneau P."/>
                <person name="Lenaers G."/>
            </authorList>
            <dbReference type="PubMed" id="32548275"/>
            <dbReference type="DOI" id="10.1212/nxg.0000000000000428"/>
        </citation>
        <scope>VARIANTS OPA12 ALA-74; ARG-337; GLU-337; LYS-376; SER-416; LEU-514 AND SER-644</scope>
    </reference>
    <comment type="function">
        <text evidence="6 7 12 19 24 25 30 31 32 33 35 38 39 40 41 42">Catalytic component of the m-AAA protease, a protease that plays a key role in proteostasis of inner mitochondrial membrane proteins, and which is essential for axonal and neuron development (PubMed:19748354, PubMed:28396416, PubMed:29932645, PubMed:30683687, PubMed:31327635, PubMed:37917749, PubMed:38157846). AFG3L2 possesses both ATPase and protease activities: the ATPase activity is required to unfold substrates, threading them into the internal proteolytic cavity for hydrolysis into small peptide fragments (PubMed:19748354, PubMed:31327635). The m-AAA protease carries out quality control in the inner membrane of the mitochondria by mediating degradation of mistranslated or misfolded polypeptides (PubMed:26504172, PubMed:30683687, PubMed:34718584). The m-AAA protease complex also promotes the processing and maturation of mitochondrial proteins, such as MRPL32/bL32m, PINK1 and SP7 (PubMed:22354088, PubMed:29932645, PubMed:30252181). Mediates protein maturation of the mitochondrial ribosomal subunit MRPL32/bL32m by catalyzing the cleavage of the presequence of MRPL32/bL32m prior to assembly into the mitochondrial ribosome (PubMed:29932645). Required for SPG7 maturation into its active mature form after SPG7 cleavage by mitochondrial-processing peptidase (MPP) (PubMed:30252181). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Acts as a regulator of calcium in neurons by mediating degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (PubMed:27642048, PubMed:28396416). Promotes the proteolytic degradation of GHITM upon hyperpolarization of mitochondria: progressive GHITM degradation leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (PubMed:35912435). Also acts as a regulator of mitochondrial glutathione homeostasis by mediating cleavage and degradation of SLC25A39 (PubMed:37917749, PubMed:38157846). SLC25A39 cleavage is prevented when SLC25A39 binds iron-sulfur (PubMed:37917749, PubMed:38157846). Involved in the regulation of OMA1-dependent processing of OPA1 (PubMed:17615298, PubMed:29545505, PubMed:30252181, PubMed:30683687, PubMed:32600459). May act by mediating processing of OMA1 precursor, participating in OMA1 maturation (PubMed:29545505).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="7">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="7">
            <dbReference type="Rhea" id="RHEA:13066"/>
        </physiologicalReaction>
    </comment>
    <comment type="cofactor">
        <cofactor evidence="35">
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
        </cofactor>
        <text evidence="35">Binds 1 zinc ion per subunit.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 4 5 13 17 23 24 25 31 32 35">Homohexamer (PubMed:24055473, PubMed:29932645, PubMed:31327635). Forms heterohexamers with SPG7 (PubMed:14623864, PubMed:17101804, PubMed:26387735, PubMed:28396416, PubMed:30252181). The m-AAA protease is either composed of homohexamers of AFG3L2 or heterohexamers of AFG3L2 and SPG7 (PubMed:17101804, PubMed:28396416). Interacts with MAIP1 (PubMed:27499296, PubMed:27642048). Interacts with DNAJC19 (By similarity). Interacts with PHB2 (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="45 46 47">Mitochondrion inner membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Ubiquitous. Highly expressed in the cerebellar Purkinje cells.</text>
    </comment>
    <comment type="PTM">
        <text evidence="32">Upon import into the mitochondrion, the N-terminal transit peptide is cleaved to generate an intermediate form which undergoes autocatalytic proteolytic processing to generate the proteolytically active mature form.</text>
    </comment>
    <comment type="disease" evidence="8 9 10 14 15 16 18 21 22 27 28 32 34 35">
        <disease id="DI-02675">
            <name>Spinocerebellar ataxia 28</name>
            <acronym>SCA28</acronym>
            <description>Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA28 is an autosomal dominant cerebellar ataxia (ADCA) with a slow progressive course and no evidence of sensory involvement or cognitive impairment.</description>
            <dbReference type="MIM" id="610246"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="11 36">
        <disease id="DI-03374">
            <name>Spastic ataxia 5, autosomal recessive</name>
            <acronym>SPAX5</acronym>
            <description>A neurodegenerative disorder characterized by early onset spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy.</description>
            <dbReference type="MIM" id="614487"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="20 29 32 36 37 38">
        <disease id="DI-05893">
            <name>Optic atrophy 12</name>
            <acronym>OPA12</acronym>
            <description>An autosomal dominant disease characterized by progressive visual loss in association with optic atrophy. Atrophy of the optic disk indicates a deficiency in the number of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. OPA12 patients manifest slowly progressive visual impairment with onset usually in the first decade. Some patients may exhibit additional features including impaired intellectual development, dystonia, movement disorders, or ataxia.</description>
            <dbReference type="MIM" id="618977"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="44">In the N-terminal section; belongs to the AAA ATPase family.</text>
    </comment>
    <comment type="similarity">
        <text evidence="44">In the C-terminal section; belongs to the peptidase M41 family.</text>
    </comment>
    <dbReference type="EC" id="3.4.24.-" evidence="4 7 12 31 35 41 42"/>
    <dbReference type="EC" id="3.6.-.-" evidence="7 35"/>
    <dbReference type="EMBL" id="Y18314">
        <property type="protein sequence ID" value="CAB48398.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC065016">
        <property type="protein sequence ID" value="AAH65016.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS11859.1"/>
    <dbReference type="RefSeq" id="NP_006787.2">
        <property type="nucleotide sequence ID" value="NM_006796.3"/>
    </dbReference>
    <dbReference type="PDB" id="2LNA">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=164-251"/>
    </dbReference>
    <dbReference type="PDB" id="6NYY">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.00 A"/>
        <property type="chains" value="A/B/C/D/E/F=272-797"/>
    </dbReference>
    <dbReference type="PDBsum" id="2LNA"/>
    <dbReference type="PDBsum" id="6NYY"/>
    <dbReference type="AlphaFoldDB" id="Q9Y4W6"/>
    <dbReference type="BMRB" id="Q9Y4W6"/>
    <dbReference type="EMDB" id="EMD-0552"/>
    <dbReference type="SMR" id="Q9Y4W6"/>
    <dbReference type="BioGRID" id="116139">
        <property type="interactions" value="392"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-10318">
        <property type="entry name" value="m-AAA protease complex, AFG3L2 variant"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-10319">
        <property type="entry name" value="m-AAA protease complex, AFG3L2-SPG7 variant"/>
    </dbReference>
    <dbReference type="CORUM" id="Q9Y4W6"/>
    <dbReference type="FunCoup" id="Q9Y4W6">
        <property type="interactions" value="2609"/>
    </dbReference>
    <dbReference type="MINT" id="Q9Y4W6"/>
    <dbReference type="STRING" id="9606.ENSP00000269143"/>
    <dbReference type="BindingDB" id="Q9Y4W6"/>
    <dbReference type="ChEMBL" id="CHEMBL4802020"/>
    <dbReference type="DrugBank" id="DB00171">
        <property type="generic name" value="ATP"/>
    </dbReference>
    <dbReference type="MEROPS" id="M41.007"/>
    <dbReference type="GlyGen" id="Q9Y4W6">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9Y4W6"/>
    <dbReference type="MetOSite" id="Q9Y4W6"/>
    <dbReference type="PhosphoSitePlus" id="Q9Y4W6"/>
    <dbReference type="SwissPalm" id="Q9Y4W6"/>
    <dbReference type="BioMuta" id="AFG3L2"/>
    <dbReference type="DMDM" id="126302516"/>
    <dbReference type="jPOST" id="Q9Y4W6"/>
    <dbReference type="MassIVE" id="Q9Y4W6"/>
    <dbReference type="PaxDb" id="9606-ENSP00000269143"/>
    <dbReference type="PeptideAtlas" id="Q9Y4W6"/>
    <dbReference type="ProteomicsDB" id="86254"/>
    <dbReference type="Pumba" id="Q9Y4W6"/>
    <dbReference type="TopDownProteomics" id="Q9Y4W6"/>
    <dbReference type="Antibodypedia" id="1387">
        <property type="antibodies" value="265 antibodies from 31 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10939"/>
    <dbReference type="Ensembl" id="ENST00000269143.8">
        <property type="protein sequence ID" value="ENSP00000269143.2"/>
        <property type="gene ID" value="ENSG00000141385.13"/>
    </dbReference>
    <dbReference type="GeneID" id="10939"/>
    <dbReference type="KEGG" id="hsa:10939"/>
    <dbReference type="MANE-Select" id="ENST00000269143.8">
        <property type="protein sequence ID" value="ENSP00000269143.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006796.3"/>
        <property type="RefSeq protein sequence ID" value="NP_006787.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002kqz.3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:315"/>
    <dbReference type="ClinPGx" id="PA24612"/>
    <dbReference type="CTD" id="10939"/>
    <dbReference type="DisGeNET" id="10939"/>
    <dbReference type="GeneCards" id="AFG3L2"/>
    <dbReference type="GeneReviews" id="AFG3L2"/>
    <dbReference type="HGNC" id="HGNC:315">
        <property type="gene designation" value="AFG3L2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000141385">
        <property type="expression patterns" value="Tissue enhanced (skeletal)"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFG3L2"/>
    <dbReference type="MIM" id="604581">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="610246">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="614487">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="618977">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000141385"/>
    <dbReference type="Orphanet" id="313772">
        <property type="disease" value="Early-onset spastic ataxia-myoclonic epilepsy-neuropathy syndrome"/>
    </dbReference>
    <dbReference type="Orphanet" id="101109">
        <property type="disease" value="Spinocerebellar ataxia type 28"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000141385"/>
    <dbReference type="eggNOG" id="KOG0731">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159566"/>
    <dbReference type="HOGENOM" id="CLU_000688_23_1_1"/>
    <dbReference type="InParanoid" id="Q9Y4W6"/>
    <dbReference type="OMA" id="ARQKGNF"/>
    <dbReference type="OrthoDB" id="1413014at2759"/>
    <dbReference type="PAN-GO" id="Q9Y4W6">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9Y4W6"/>
    <dbReference type="BRENDA" id="3.4.24.B18">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q9Y4W6"/>
    <dbReference type="Reactome" id="R-HSA-8949664">
        <property type="pathway name" value="Processing of SMDT1"/>
    </dbReference>
    <dbReference type="Reactome" id="R-HSA-9837999">
        <property type="pathway name" value="Mitochondrial protein degradation"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q9Y4W6"/>
    <dbReference type="Agora" id="ENSG00000141385"/>
    <dbReference type="BioGRID-ORCS" id="10939">
        <property type="hits" value="754 hits in 1181 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="91857CE7">
        <property type="entry name" value="Nucleolus"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFG3L2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q9Y4W6"/>
    <dbReference type="GeneWiki" id="AFG3L2"/>
    <dbReference type="GenomeRNAi" id="10939"/>
    <dbReference type="Pharos" id="Q9Y4W6">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9Y4W6"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 18"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9Y4W6">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000141385">
        <property type="expression patterns" value="Expressed in Brodmann (1909) area 23 and 198 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9Y4W6">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005745">
        <property type="term" value="C:m-AAA complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005743">
        <property type="term" value="C:mitochondrial inner membrane"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProt"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0033011">
        <property type="term" value="C:perinuclear theca"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120238">
        <property type="term" value="C:sperm glycocalyx"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0120212">
        <property type="term" value="C:sperm head-tail coupling apparatus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097225">
        <property type="term" value="C:sperm midpiece"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097228">
        <property type="term" value="C:sperm principal piece"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0004176">
        <property type="term" value="F:ATP-dependent peptidase activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0004222">
        <property type="term" value="F:metalloendopeptidase activity"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0008237">
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        <property type="project" value="UniProtKB"/>
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        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="ProtInc"/>
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    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0007409">
        <property type="term" value="P:axonogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0036444">
        <property type="term" value="P:calcium import into the mitochondrion"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0072753">
        <property type="term" value="P:cellular response to glutathione"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042407">
        <property type="term" value="P:cristae formation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0033619">
        <property type="term" value="P:membrane protein proteolysis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051560">
        <property type="term" value="P:mitochondrial calcium ion homeostasis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008053">
        <property type="term" value="P:mitochondrial fusion"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0034982">
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        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0141164">
        <property type="term" value="P:mitochondrial protein quality control"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0055001">
        <property type="term" value="P:muscle cell development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042552">
        <property type="term" value="P:myelination"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0021675">
        <property type="term" value="P:nerve development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="GO" id="GO:0007528">
        <property type="term" value="P:neuromuscular junction development"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016540">
        <property type="term" value="P:protein autoprocessing"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0030163">
        <property type="term" value="P:protein catabolic process"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051604">
        <property type="term" value="P:protein maturation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0016485">
        <property type="term" value="P:protein processing"/>
        <property type="evidence" value="ECO:0000250"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0006508">
        <property type="term" value="P:proteolysis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0110097">
        <property type="term" value="P:regulation of calcium import into the mitochondrion"/>
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        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0040014">
        <property type="term" value="P:regulation of multicellular organism growth"/>
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        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0060013">
        <property type="term" value="P:righting reflex"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="CDD" id="cd19501">
        <property type="entry name" value="RecA-like_FtsH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.8.60:FF:000019">
        <property type="entry name" value="AFG3-like AAA ATPase 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.20.58.760:FF:000003">
        <property type="entry name" value="AFG3-like AAA ATPase 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.1690.20:FF:000001">
        <property type="entry name" value="AFG3-like AAA ATPase 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000001">
        <property type="entry name" value="ATP-dependent zinc metalloprotease FtsH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.60">
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="3.40.1690.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.20.58.760">
        <property type="entry name" value="Peptidase M41"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="HAMAP" id="MF_01458">
        <property type="entry name" value="FtsH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041569">
        <property type="entry name" value="AAA_lid_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050928">
        <property type="entry name" value="ATP-dep_Zn_Metalloprotease"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003959">
        <property type="entry name" value="ATPase_AAA_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003960">
        <property type="entry name" value="ATPase_AAA_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR005936">
        <property type="entry name" value="FtsH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011546">
        <property type="entry name" value="Pept_M41_FtsH_extracell"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000642">
        <property type="entry name" value="Peptidase_M41"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037219">
        <property type="entry name" value="Peptidase_M41-like"/>
    </dbReference>
    <dbReference type="NCBIfam" id="TIGR01241">
        <property type="entry name" value="FtsH_fam"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43655:SF9">
        <property type="entry name" value="AFG3-LIKE PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR43655">
        <property type="entry name" value="ATP-DEPENDENT PROTEASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00004">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17862">
        <property type="entry name" value="AAA_lid_3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF06480">
        <property type="entry name" value="FtsH_ext"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01434">
        <property type="entry name" value="Peptidase_M41"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF140990">
        <property type="entry name" value="FtsH protease domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00674">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0482">Metalloprotease</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0999">Mitochondrion inner membrane</keyword>
    <keyword id="KW-0523">Neurodegeneration</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0645">Protease</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0950">Spinocerebellar ataxia</keyword>
    <keyword id="KW-0809">Transit peptide</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <feature type="transit peptide" description="Mitochondrion" evidence="1">
        <location>
            <begin position="1"/>
            <end position="38"/>
        </location>
    </feature>
    <feature type="propeptide" id="PRO_0000442311" description="Removed in mature form" evidence="1">
        <location>
            <begin position="39"/>
            <end position="66"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000442312" description="Mitochondrial inner membrane m-AAA protease component AFG3L2">
        <location>
            <begin position="67"/>
            <end position="797"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="47">
        <location>
            <begin position="39"/>
            <end position="142"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="143"/>
            <end position="163"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial intermembrane" evidence="47">
        <location>
            <begin position="164"/>
            <end position="250"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="251"/>
            <end position="271"/>
        </location>
    </feature>
    <feature type="topological domain" description="Mitochondrial matrix" evidence="47">
        <location>
            <begin position="272"/>
            <end position="797"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="76"/>
            <end position="126"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="759"/>
            <end position="797"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="85"/>
            <end position="100"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Gly residues" evidence="3">
        <location>
            <begin position="108"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="775"/>
            <end position="797"/>
        </location>
    </feature>
    <feature type="active site" evidence="47">
        <location>
            <position position="575"/>
        </location>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="310"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="311"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="352"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="353"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="354"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="355"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="356"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="47 50">
        <location>
            <position position="490"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 50">
        <location>
            <position position="574"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 50">
        <location>
            <position position="578"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="binding site" evidence="35 50">
        <location>
            <position position="649"/>
        </location>
        <ligand>
            <name>Zn(2+)</name>
            <dbReference type="ChEBI" id="CHEBI:29105"/>
            <note>catalytic</note>
        </ligand>
    </feature>
    <feature type="modified residue" description="N6-succinyllysine" evidence="1">
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084603" description="In OPA12; uncertain significance." evidence="37">
        <original>E</original>
        <variation>A</variation>
        <location>
            <position position="74"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089087" description="In SCA28; uncertain significance; dbSNP:rs1373473541." evidence="18">
        <original>V</original>
        <variation>I</variation>
        <location>
            <position position="191"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084604" description="In SPAX5; uncertain significance; dbSNP:rs1908569446." evidence="36">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="306"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084605" description="In OPA12; loss-of-function variant resulting in aberrant OPA1 processing and mitochondrial fragmentation; dbSNP:rs1908566777." evidence="37 38">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084606" description="In OPA12." evidence="37">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="337"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084607" description="In OPA12; uncertain significance; dbSNP:rs755893615." evidence="36">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="346"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084608" description="In OPA12; uncertain significance." evidence="37">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="376"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084609" description="In OPA12; uncertain significance; dbSNP:rs1908507433." evidence="36">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="377"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084610" description="In OPA12; uncertain significance; decreased proteolytic function; dbSNP:rs1908371616." evidence="36">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="407"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084611" description="In OPA12; uncertain significance." evidence="37">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="416"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084612" description="In OPA12; uncertain significance; dbSNP:rs1908369114." evidence="36">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="430"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_063544" description="In SCA28; abolished ability to degrade substrate proteins; dbSNP:rs151344512." evidence="8 35">
        <original>N</original>
        <variation>T</variation>
        <location>
            <position position="432"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084613" description="In OPA12 and SPAX5; decreased proteolytic function; dbSNP:rs912546325." evidence="36">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="462"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084614" description="In OPA12; decreased proteolytic function; dbSNP:rs1908309088." evidence="36">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="465"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084615" description="In OPA12; decreased proteolytic function resulting in impaired autocatalytic processing and impaired proteolytic maturation of SPG7; does not affect the interaction with SPG7; dbSNP:rs1020764190." evidence="20 29 32">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="468"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084616" description="In OPA12; decreased proteolytic function; dbSNP:rs1908300748." evidence="36 37">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="514"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_089088" description="Found in patients from a consanguineous family with progressive microcephaly, early onset seizures, spasticity and basal ganglia involvement; uncertain significance; decreased ATPase and ability to degrade substrate proteins; dbSNP:rs562861748." evidence="26 35">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="572"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084617" description="In OPA12; uncertain significance; dbSNP:rs773240455." evidence="36">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="605"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_067330" description="In SPAX5 and SCA28; hypomorphic mutation; impaired oligomerization with itself and SPG7; increased ATPase and proteolytic activities; dbSNP:rs387906889." evidence="11 34 35">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="616"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084618" description="In SPAX5; impaired function shown in a yeast complementation assay; dbSNP:rs1907907851." evidence="36">
        <original>Q</original>
        <variation>K</variation>
        <location>
            <position position="620"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080736" description="In SCA28; uncertain significance; dbSNP:rs756912142." evidence="28">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="621"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_084619" description="In OPA12; uncertain significance; dbSNP:rs1226952405." evidence="37">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="644"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_064402" description="In SCA28; dbSNP:rs151344513." evidence="10">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="654"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_064403" description="In SCA28; abolished ability to degrade substrate proteins; dbSNP:rs151344515." evidence="10 35">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="666"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_064404" description="In SCA28; dbSNP:rs151344515." evidence="10">
        <original>M</original>
        <variation>T</variation>
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    <feature type="mutagenesis site" description="Abolished protease activity. Loss of autocatalytic processing. Impaired proteolytic maturation of SPG7." evidence="31 32 35">
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    <feature type="mutagenesis site" description="Impaired ability to degrade substrates without affecting the ATPase activity." evidence="35">
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    <feature type="sequence conflict" description="In Ref. 1; CAB48398." evidence="44" ref="1">
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    <feature type="sequence conflict" description="In Ref. 1; CAB48398." evidence="44" ref="1">
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    <reference key="1">
        <citation type="journal article" date="2004" name="J. Biol. Chem." volume="279" first="54793" last="54801">
            <title>Conversion of mechanical force into biochemical signaling.</title>
            <authorList>
                <person name="Han B."/>
                <person name="Bai X.H."/>
                <person name="Lodyga M."/>
                <person name="Xu J."/>
                <person name="Yang B.B."/>
                <person name="Keshavjee S."/>
                <person name="Post M."/>
                <person name="Liu M."/>
            </authorList>
            <dbReference type="PubMed" id="15485829"/>
            <dbReference type="DOI" id="10.1074/jbc.m406880200"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH SRC</scope>
        <scope>PHOSPHORYLATION BY SRC</scope>
        <scope>MUTAGENESIS OF PRO-71; PRO-77; TYR-93; TYR-94; TYR-125; TYR-451 AND TYR-453</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
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    <comment type="function">
        <text evidence="1 7">Can cross-link actin filaments into both network and bundle structures (By similarity). May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton. Seems to play a role in the development and progression of prostate adenocarcinoma by regulating cell-matrix adhesions and migration in the cancer cells.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Monomer and homomultimer. Interacts via its C-terminus with F-actin; probably involving AFAP1 multimers (By similarity). Interacts with activated SRC SH3-SH2 domains. Interacts via its PH 1 domain with PRKCA, PRKCB and PRKCI (By similarity).</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
            <location evidence="7">Cytoskeleton</location>
            <location evidence="7">Stress fiber</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N556-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N556-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_044838"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 10">Low expression in normal breast epithelial cell line MCF-10A and in tumorigenic breast cancer cell lines MCF-7, T-47D and ZR-75-1. Highly expressed in the invasive breast cancer cell lines MDA-MB-231 and MDA-MB-435. Overexpressed in prostate carcinoma.</text>
    </comment>
    <comment type="PTM">
        <text evidence="7">Phosphorylated on tyrosine residues by SRC.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Knockdown in MDA-MB-231 cells resulted in loss of actin stress fibers, decreased adhesion and spreading on fibronectin.</text>
    </comment>
    <dbReference type="EMBL" id="AF188700">
        <property type="protein sequence ID" value="AAG17055.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK290807">
        <property type="protein sequence ID" value="BAF83496.1"/>
        <property type="molecule type" value="mRNA"/>
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    <dbReference type="EMBL" id="AK297631">
        <property type="protein sequence ID" value="BAG60004.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC004169">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
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    <keyword id="KW-0025">Alternative splicing</keyword>
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    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
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            <begin position="1"/>
            <end position="730"/>
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            <end position="249"/>
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            <begin position="512"/>
            <end position="537"/>
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            <end position="637"/>
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            <begin position="557"/>
            <end position="648"/>
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            <begin position="71"/>
            <end position="74"/>
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            <end position="97"/>
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    </feature>
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            <begin position="451"/>
            <end position="456"/>
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    <feature type="compositionally biased region" description="Pro residues" evidence="5">
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            <begin position="60"/>
            <end position="85"/>
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            <begin position="268"/>
            <end position="283"/>
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        <location>
            <position position="1"/>
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        <location>
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        <location>
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            <position position="510"/>
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        <location>
            <position position="403"/>
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    </feature>
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        <location>
            <position position="518"/>
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        <variation>A</variation>
        <location>
            <position position="71"/>
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    </feature>
    <feature type="mutagenesis site" description="No effect on tyrosine phosphorylation." evidence="7">
        <original>P</original>
        <variation>A</variation>
        <location>
            <position position="77"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-94; F-125; F-451 and F-453." evidence="7">
        <original>Y</original>
        <variation>F</variation>
        <location>
            <position position="93"/>
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    </feature>
    <feature type="mutagenesis site" description="Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-125; F-451 and F-453." evidence="7">
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            <position position="125"/>
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    <feature type="mutagenesis site" description="Reduces phosphorylation and phosphorylation of SRC at Y-416; when associated with F-93; F-94; F-125 and F-451." evidence="7">
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            <position position="453"/>
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            <position position="238"/>
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    <feature type="sequence conflict" description="In Ref. 2; BAF83496." evidence="13" ref="2">
        <original>T</original>
        <variation>A</variation>
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            <position position="465"/>
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    <feature type="sequence conflict" description="In Ref. 2; BAG60004." evidence="13" ref="2">
        <original>A</original>
        <variation>V</variation>
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            <position position="561"/>
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    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q80YS6"/>
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    </evidence>
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        <source>
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    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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            <dbReference type="PubMed" id="15485829"/>
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            <dbReference type="PubMed" id="15489334"/>
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            <dbReference type="PubMed" id="17520695"/>
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    <evidence type="ECO:0000269" key="10">
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            <dbReference type="PubMed" id="17885682"/>
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    <evidence type="ECO:0000303" key="12">
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    <evidence type="ECO:0000305" key="13"/>
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        <source>
            <dbReference type="PubMed" id="18669648"/>
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        <source>
            <dbReference type="PubMed" id="20068231"/>
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    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="21406692"/>
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        <source>
            <dbReference type="PubMed" id="22814378"/>
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    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="23186163"/>
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    </evidence>
    <evidence type="ECO:0007744" key="19">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="730" mass="80725" checksum="4E916BB4F82F5547" modified="2008-02-05" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2000-05-30" modified="2026-01-28" version="169" xmlns="https://uniprot.org/uniprot">
    <accession>Q13015</accession>
    <name>AF1Q_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Protein AF1q</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">MLLT11</name>
        <name type="synonym">AF1Q</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <dbReference type="PubMed" id="16710414"/>
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                <consortium name="The MGC Project Team"/>
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            <dbReference type="PubMed" id="15489334"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Bone marrow</tissue>
            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
        </source>
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    <reference key="6">
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            <dbReference type="PubMed" id="21269460"/>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>MUTAGENESIS OF 24-LEU--LEU-32</scope>
        <scope>UBIQUITINATION</scope>
        <scope>NUCLEAR EXPORT SIGNAL</scope>
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            <dbReference type="PubMed" id="24880125"/>
            <dbReference type="DOI" id="10.1016/j.yexcr.2014.05.013"/>
        </citation>
        <scope>INTERACTION WITH HSPA8 AND LAMP2</scope>
    </reference>
    <reference key="9">
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            <title>AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.</title>
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            <dbReference type="PubMed" id="26079538"/>
            <dbReference type="DOI" id="10.18632/oncotarget.4136"/>
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        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH TCF7</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <comment type="function">
        <text evidence="2 4">Cofactor for the transcription factor TCF7 (PubMed:26079538). Involved in regulation of lymphoid development by driving multipotent hematopoietic progenitor cells towards a T cell fate (PubMed:21715312).</text>
    </comment>
    <comment type="subunit">
        <text evidence="3 4">Interacts with HSPA8 and LAMP2 isoform A; the interaction may target MLLT11 for degradation via chaperone-mediated autophagy (PubMed:24880125). Interacts with TCF7 (PubMed:26079538).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6269719">
            <id>Q13015</id>
        </interactant>
        <interactant intactId="EBI-458391">
            <id>P04271</id>
            <label>S100B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6269719">
            <id>Q13015</id>
        </interactant>
        <interactant intactId="EBI-2119465">
            <id>P36402</id>
            <label>TCF7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-6269719">
            <id>Q13015</id>
        </interactant>
        <interactant intactId="EBI-6289575">
            <id>Q7L0X0</id>
            <label>TRIL</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="2 4">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2 4">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Cytoplasm</location>
            <location evidence="2">Cytoskeleton</location>
            <location evidence="2">Microtubule organizing center</location>
            <location evidence="2">Centrosome</location>
        </subcellularLocation>
        <text evidence="2">Continuous nuclear export is followed by degradation.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="4 5">Expressed in myoepithelial cells of normal breast tissue (at protein level) (PubMed:26079538). Highly expressed in thymus (PubMed:7833468). Expressed in colon, small intestine, prostate and ovary. Not detected in peripheral blood lymphocytes and spleen (PubMed:7833468).</text>
    </comment>
    <comment type="PTM">
        <text evidence="2">Ubiquitinated, leading to degradation.</text>
    </comment>
    <comment type="disease">
        <text>A chromosomal aberration involving MLLT11 is found in acute leukemias. Translocation t(1;11)(q21;q23) with KMT2A/MLL1.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the MLLT11 family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/12/AF1q"/>
    </comment>
    <dbReference type="EMBL" id="U16954">
        <property type="protein sequence ID" value="AAA70088.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BT006799">
        <property type="protein sequence ID" value="AAP35445.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CR456879">
        <property type="protein sequence ID" value="CAG33160.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL590133">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC006471">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC008445">
        <property type="protein sequence ID" value="AAH08445.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009624">
        <property type="protein sequence ID" value="AAH09624.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC019253">
        <property type="protein sequence ID" value="AAH19253.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC021703">
        <property type="protein sequence ID" value="AAH21703.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC022448">
        <property type="protein sequence ID" value="AAH22448.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS982.1"/>
    <dbReference type="PIR" id="I38889">
        <property type="entry name" value="I38889"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006809.1">
        <property type="nucleotide sequence ID" value="NM_006818.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q13015"/>
    <dbReference type="SMR" id="Q13015"/>
    <dbReference type="BioGRID" id="116161">
        <property type="interactions" value="69"/>
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    <dbReference type="FunCoup" id="Q13015">
        <property type="interactions" value="911"/>
    </dbReference>
    <dbReference type="IntAct" id="Q13015">
        <property type="interactions" value="32"/>
    </dbReference>
    <dbReference type="MINT" id="Q13015"/>
    <dbReference type="STRING" id="9606.ENSP00000357917"/>
    <dbReference type="GlyGen" id="Q13015">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q13015"/>
    <dbReference type="MetOSite" id="Q13015"/>
    <dbReference type="PhosphoSitePlus" id="Q13015"/>
    <dbReference type="BioMuta" id="MLLT11"/>
    <dbReference type="jPOST" id="Q13015"/>
    <dbReference type="MassIVE" id="Q13015"/>
    <dbReference type="PaxDb" id="9606-ENSP00000357917"/>
    <dbReference type="PeptideAtlas" id="Q13015"/>
    <dbReference type="ProteomicsDB" id="59101"/>
    <dbReference type="Pumba" id="Q13015"/>
    <dbReference type="TopDownProteomics" id="Q13015"/>
    <dbReference type="Antibodypedia" id="34047">
        <property type="antibodies" value="116 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="10962"/>
    <dbReference type="Ensembl" id="ENST00000368921.5">
        <property type="protein sequence ID" value="ENSP00000357917.3"/>
        <property type="gene ID" value="ENSG00000213190.5"/>
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    <dbReference type="GeneID" id="10962"/>
    <dbReference type="KEGG" id="hsa:10962"/>
    <dbReference type="MANE-Select" id="ENST00000368921.5">
        <property type="protein sequence ID" value="ENSP00000357917.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006818.4"/>
        <property type="RefSeq protein sequence ID" value="NP_006809.1"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16997"/>
    <dbReference type="ClinPGx" id="PA142671347"/>
    <dbReference type="CTD" id="10962"/>
    <dbReference type="DisGeNET" id="10962"/>
    <dbReference type="GeneCards" id="MLLT11"/>
    <dbReference type="HGNC" id="HGNC:16997">
        <property type="gene designation" value="MLLT11"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000213190">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="MalaCards" id="MLLT11"/>
    <dbReference type="MIM" id="604684">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000213190"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000213190"/>
    <dbReference type="eggNOG" id="ENOG502S7MB">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000009895"/>
    <dbReference type="HOGENOM" id="CLU_2440320_0_0_1"/>
    <dbReference type="InParanoid" id="Q13015"/>
    <dbReference type="OMA" id="RISPVDF"/>
    <dbReference type="OrthoDB" id="9991950at2759"/>
    <dbReference type="PAN-GO" id="Q13015">
        <property type="GO annotations" value="5 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q13015"/>
    <dbReference type="PathwayCommons" id="Q13015"/>
    <dbReference type="SignaLink" id="Q13015"/>
    <dbReference type="SIGNOR" id="Q13015"/>
    <dbReference type="Agora" id="ENSG00000213190"/>
    <dbReference type="BioGRID-ORCS" id="10962">
        <property type="hits" value="12 hits in 1153 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="MLLT11">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="10962"/>
    <dbReference type="Pharos" id="Q13015">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q13015"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 1"/>
    </dbReference>
    <dbReference type="RNAct" id="Q13015">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000213190">
        <property type="expression patterns" value="Expressed in pons and 199 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q13015">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005813">
        <property type="term" value="C:centrosome"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005739">
        <property type="term" value="C:mitochondrion"/>
        <property type="evidence" value="ECO:0006056"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097191">
        <property type="term" value="P:extrinsic apoptotic signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097193">
        <property type="term" value="P:intrinsic apoptotic signaling pathway"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043065">
        <property type="term" value="P:positive regulation of apoptotic process"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045893">
        <property type="term" value="P:positive regulation of DNA-templated transcription"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051901">
        <property type="term" value="P:positive regulation of mitochondrial depolarization"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0090200">
        <property type="term" value="P:positive regulation of release of cytochrome c from mitochondria"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026778">
        <property type="entry name" value="MLLT11_fam"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR033461">
        <property type="entry name" value="WRNPLPNID"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15404">
        <property type="entry name" value="PROTEIN AF1Q"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR15404:SF2">
        <property type="entry name" value="PROTEIN AF1Q"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF15017">
        <property type="entry name" value="WRNPLPNID"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0160">Chromosomal rearrangement</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-0656">Proto-oncogene</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000064471" description="Protein AF1q">
        <location>
            <begin position="1"/>
            <end position="90"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="Nuclear export signal" evidence="2">
        <location>
            <begin position="24"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="1">
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Constitutive nuclear sequestration." evidence="2">
        <original>LSELEGLGL</original>
        <variation>ASEAEGAGA</variation>
        <location>
            <begin position="24"/>
            <end position="32"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P97783"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="21715312"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="24880125"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="26079538"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="7833468"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="90" mass="10061" checksum="B37C6F7303C9EBF8" modified="1996-11-01" version="1">MRDPVSSQYSSFLFWRMPIPELDLSELEGLGLSDTATYKVKDSSVGKMIGQATAADQEKNPEGDGLLEYSTFNFWRAPIASIHSFELDLL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="178" xmlns="https://uniprot.org/uniprot">
    <accession>P51826</accession>
    <accession>B7ZM46</accession>
    <accession>B9EGL9</accession>
    <accession>D3DVI6</accession>
    <accession>Q53RD6</accession>
    <accession>Q53S47</accession>
    <accession>Q53SI6</accession>
    <accession>Q53TB9</accession>
    <accession>Q59F27</accession>
    <accession>Q8IWJ5</accession>
    <name>AFF3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>AF4/FMR2 family member 3</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Lymphoid nuclear protein related to AF4</fullName>
            <shortName>Protein LAF-4</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="6 8" type="primary">AFF3</name>
        <name type="synonym">LAF4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Chung W.K."/>
                <person name="Reymond A."/>
            </authorList>
            <dbReference type="PubMed" id="33961779"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2021.04.001"/>
        </citation>
        <scope>VARIANTS KINS ALA-231; LEU-231; SER-233; THR-233; VAL-233 AND GLY-235</scope>
        <scope>INVOLVEMENT IN KINS</scope>
    </reference>
    <comment type="function">
        <text>Putative transcription activator that may function in lymphoid development and oncogenesis. Binds, in vitro, to double-stranded DNA.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>P51826-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>P51826-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_041120"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text>Preferentially expressed in lymphoid tissues, highest levels being found in the thymus.</text>
    </comment>
    <comment type="disease" evidence="3 4">
        <disease id="DI-06095">
            <name>KINSSHIP syndrome</name>
            <acronym>KINS</acronym>
            <description>An autosomal dominant disease characterized by developmental delay, impaired intellectual development, seizures, short stature, mesomelic dysplasia, dysmorphic facial features, horseshoe or hypoplastic kidney, and failure to thrive.</description>
            <dbReference type="MIM" id="619297"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7">Belongs to the AF4 family.</text>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/315/LAF4"/>
    </comment>
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        <property type="protein sequence ID" value="AAA98763.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC092667">
        <property type="protein sequence ID" value="AAY24278.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010736">
        <property type="protein sequence ID" value="AAY14792.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC073118">
        <property type="protein sequence ID" value="AAY24187.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC018690">
        <property type="protein sequence ID" value="AAY24315.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01854.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01855.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01856.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01857.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01858.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471127">
        <property type="protein sequence ID" value="EAX01859.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC036895">
        <property type="protein sequence ID" value="AAH36895.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC136579">
        <property type="protein sequence ID" value="AAI36580.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC144266">
        <property type="protein sequence ID" value="AAI44267.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAD92871.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="P51826-1"/>
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        <property type="nucleotide sequence ID" value="NM_001025108.2"/>
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        <molecule id="P51826-1"/>
        <property type="nucleotide sequence ID" value="NM_001386135.1"/>
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        <molecule id="P51826-1"/>
        <property type="nucleotide sequence ID" value="NM_002285.3"/>
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        <molecule id="P51826-1"/>
        <property type="nucleotide sequence ID" value="XM_005263943.5"/>
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    <dbReference type="RefSeq" id="XP_011509476.1">
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        <property type="nucleotide sequence ID" value="XM_011511174.4"/>
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        <property type="nucleotide sequence ID" value="XM_047444280.1"/>
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    <dbReference type="RefSeq" id="XP_047300237.1">
        <molecule id="P51826-2"/>
        <property type="nucleotide sequence ID" value="XM_047444281.1"/>
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        <molecule id="P51826-1"/>
        <property type="nucleotide sequence ID" value="XM_047444283.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054197967.1">
        <molecule id="P51826-2"/>
        <property type="nucleotide sequence ID" value="XM_054341992.1"/>
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    <dbReference type="RefSeq" id="XP_054197968.1">
        <molecule id="P51826-2"/>
        <property type="nucleotide sequence ID" value="XM_054341993.1"/>
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        <property type="nucleotide sequence ID" value="XM_054341994.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054197970.1">
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        <property type="nucleotide sequence ID" value="XM_054341995.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054197972.1">
        <molecule id="P51826-1"/>
        <property type="nucleotide sequence ID" value="XM_054341997.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="P51826"/>
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        <property type="interactions" value="15"/>
    </dbReference>
    <dbReference type="FunCoup" id="P51826">
        <property type="interactions" value="1941"/>
    </dbReference>
    <dbReference type="IntAct" id="P51826">
        <property type="interactions" value="7"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000386834"/>
    <dbReference type="GlyGen" id="P51826">
        <property type="glycosylation" value="6 sites, 1 O-linked glycan (5 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="P51826"/>
    <dbReference type="PhosphoSitePlus" id="P51826"/>
    <dbReference type="BioMuta" id="AFF3"/>
    <dbReference type="DMDM" id="126302515"/>
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    <dbReference type="MassIVE" id="P51826"/>
    <dbReference type="PaxDb" id="9606-ENSP00000386834"/>
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        <molecule id="P51826-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="56429">
        <molecule id="P51826-2"/>
    </dbReference>
    <dbReference type="Antibodypedia" id="32831">
        <property type="antibodies" value="57 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3899"/>
    <dbReference type="Ensembl" id="ENST00000317233.8">
        <molecule id="P51826-1"/>
        <property type="protein sequence ID" value="ENSP00000317421.4"/>
        <property type="gene ID" value="ENSG00000144218.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409236.6">
        <molecule id="P51826-1"/>
        <property type="protein sequence ID" value="ENSP00000387207.1"/>
        <property type="gene ID" value="ENSG00000144218.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000409579.5">
        <molecule id="P51826-2"/>
        <property type="protein sequence ID" value="ENSP00000386834.1"/>
        <property type="gene ID" value="ENSG00000144218.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000672756.2">
        <molecule id="P51826-1"/>
        <property type="protein sequence ID" value="ENSP00000500419.1"/>
        <property type="gene ID" value="ENSG00000144218.21"/>
    </dbReference>
    <dbReference type="GeneID" id="3899"/>
    <dbReference type="KEGG" id="hsa:3899"/>
    <dbReference type="MANE-Select" id="ENST00000672756.2">
        <property type="protein sequence ID" value="ENSP00000500419.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001386135.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001373064.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc002tag.4">
        <molecule id="P51826-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:6473"/>
    <dbReference type="ClinPGx" id="PA30264"/>
    <dbReference type="CTD" id="3899"/>
    <dbReference type="DisGeNET" id="3899"/>
    <dbReference type="GeneCards" id="AFF3"/>
    <dbReference type="HGNC" id="HGNC:6473">
        <property type="gene designation" value="AFF3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000144218">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFF3"/>
    <dbReference type="MIM" id="601464">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="619297">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000144218"/>
    <dbReference type="Orphanet" id="632603">
        <property type="disease" value="Mesomelic dysplasia-digital anomalies-intellectual disability syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000144218"/>
    <dbReference type="eggNOG" id="ENOG502QU9C">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00950000182974"/>
    <dbReference type="HOGENOM" id="CLU_006484_1_1_1"/>
    <dbReference type="InParanoid" id="P51826"/>
    <dbReference type="OMA" id="NSHRDCK"/>
    <dbReference type="OrthoDB" id="6382204at2759"/>
    <dbReference type="PAN-GO" id="P51826">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="P51826"/>
    <dbReference type="PathwayCommons" id="P51826"/>
    <dbReference type="SignaLink" id="P51826"/>
    <dbReference type="SIGNOR" id="P51826"/>
    <dbReference type="Agora" id="ENSG00000144218"/>
    <dbReference type="BioGRID-ORCS" id="3899">
        <property type="hits" value="20 hits in 1148 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFF3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AFF3"/>
    <dbReference type="GenomeRNAi" id="3899"/>
    <dbReference type="Pharos" id="P51826">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:P51826"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
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        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000144218">
        <property type="expression patterns" value="Expressed in cortical plate and 172 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="P51826">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016604">
        <property type="term" value="C:nuclear body"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032783">
        <property type="term" value="C:super elongation complex"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003700">
        <property type="term" value="F:DNA-binding transcription factor activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003690">
        <property type="term" value="F:double-stranded DNA binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0035116">
        <property type="term" value="P:embryonic hindlimb morphogenesis"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="BHF-UCL"/>
    </dbReference>
    <dbReference type="GO" id="GO:0010468">
        <property type="term" value="P:regulation of gene expression"/>
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        <property type="project" value="GO_Central"/>
    </dbReference>
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        <property type="entry name" value="AF4/FMR2_CHD"/>
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        <property type="entry name" value="AF4_int"/>
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        <property type="match status" value="2"/>
    </dbReference>
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        <property type="entry name" value="AF4_int"/>
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    <keyword id="KW-0010">Activator</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0242">Dwarfism</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0804">Transcription</keyword>
    <keyword id="KW-0805">Transcription regulation</keyword>
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        <location>
            <begin position="1"/>
            <end position="1226"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="1">
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            <begin position="24"/>
            <end position="65"/>
        </location>
    </feature>
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            <begin position="783"/>
            <end position="856"/>
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    <feature type="region of interest" description="Disordered" evidence="1">
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            <begin position="879"/>
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    <feature type="region of interest" description="Disordered" evidence="1">
        <location>
            <begin position="1100"/>
            <end position="1138"/>
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    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="1">
        <location>
            <begin position="24"/>
            <end position="37"/>
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        <location>
            <begin position="42"/>
            <end position="52"/>
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    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="1">
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            <begin position="123"/>
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        <location>
            <begin position="251"/>
            <end position="261"/>
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    <feature type="compositionally biased region" description="Polar residues" evidence="1">
        <location>
            <begin position="334"/>
            <end position="344"/>
        </location>
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        <location>
            <begin position="381"/>
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    <feature type="modified residue" description="Phosphoserine" evidence="9">
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            <position position="231"/>
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        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="231"/>
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    </feature>
    <feature type="sequence variant" id="VAR_085677" description="In KINS." evidence="4">
        <original>A</original>
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            <position position="233"/>
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    </feature>
    <feature type="sequence variant" id="VAR_085678" description="In KINS." evidence="3 4">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085679" description="In KINS." evidence="4">
        <original>A</original>
        <variation>V</variation>
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            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_085680" description="In KINS." evidence="4">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030805" description="In dbSNP:rs4851223.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="358"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_030806" description="In dbSNP:rs1047265.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="494"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_080758" description="Found in a consanguineous family with intellectual disability; uncertain significance." evidence="2">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1215"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA98763." evidence="7" ref="1">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="87"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA98763." evidence="7" ref="1">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="421"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA98763." evidence="7" ref="1">
        <original>T</original>
        <variation>YL</variation>
        <location>
            <position position="1030"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA98763." evidence="7" ref="1">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="1120"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAA98763." evidence="7" ref="1">
        <original>SPA</original>
        <variation>FPG</variation>
        <location>
            <begin position="1125"/>
            <end position="1127"/>
        </location>
    </feature>
    <evidence type="ECO:0000256" key="1">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="2">
        <source>
            <dbReference type="PubMed" id="28397838"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="31388108"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="33961779"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="5">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="6">
        <source>
            <dbReference type="PubMed" id="28397838"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="7"/>
    <evidence type="ECO:0000312" key="8">
        <source>
            <dbReference type="HGNC" id="HGNC:6473"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="9">
        <source>
            <dbReference type="PubMed" id="19369195"/>
        </source>
    </evidence>
    <sequence length="1226" mass="133503" checksum="BD2D90358609E156" modified="2018-09-12" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-04-29" modified="2026-01-28" version="187" xmlns="https://uniprot.org/uniprot">
    <accession>Q8NB90</accession>
    <accession>C9JT97</accession>
    <accession>Q86XW1</accession>
    <accession>Q8NI20</accession>
    <accession>Q8TDL7</accession>
    <name>AFG2A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">ATPase family gene 2 protein homolog A</fullName>
            <ecNumber evidence="1">3.6.4.10</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="16">AFG2 AAA ATPase homolog A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="15">Ribosome biogenesis protein SPATA5</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">Spermatogenesis-associated factor protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="15">Spermatogenesis-associated protein 5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="16" type="primary">AFG2A</name>
        <name evidence="13" type="synonym">SPAF</name>
        <name evidence="12" type="synonym">SPATA5</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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            <authorList>
                <person name="Tanaka A.J."/>
                <person name="Cho M.T."/>
                <person name="Millan F."/>
                <person name="Juusola J."/>
                <person name="Retterer K."/>
                <person name="Joshi C."/>
                <person name="Niyazov D."/>
                <person name="Garnica A."/>
                <person name="Gratz E."/>
                <person name="Deardorff M."/>
                <person name="Wilkins A."/>
                <person name="Ortiz-Gonzalez X."/>
                <person name="Mathews K."/>
                <person name="Panzer K."/>
                <person name="Brilstra E."/>
                <person name="van Gassen K.L."/>
                <person name="Volker-Touw C.M."/>
                <person name="van Binsbergen E."/>
                <person name="Sobreira N."/>
                <person name="Hamosh A."/>
                <person name="McKnight D."/>
                <person name="Monaghan K.G."/>
                <person name="Chung W.K."/>
            </authorList>
            <dbReference type="PubMed" id="26299366"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2015.07.014"/>
        </citation>
        <scope>INVOLVEMENT IN NEDHSB</scope>
        <scope>VARIANTS NEDHSB GLN-84; ILE-90; THR-100; THR-330 DEL; LEU-448; LEU-488; GLN-529; CYS-626; GLY-628; GLN-784 AND VAL-844</scope>
    </reference>
    <reference key="12">
        <citation type="journal article" date="2016" name="Clin. Genet." volume="90" first="437" last="444">
            <title>Characterization of SPATA5-related encephalopathy in early childhood.</title>
            <authorList>
                <person name="Kurata H."/>
                <person name="Terashima H."/>
                <person name="Nakashima M."/>
                <person name="Okazaki T."/>
                <person name="Matsumura W."/>
                <person name="Ohno K."/>
                <person name="Saito Y."/>
                <person name="Maegaki Y."/>
                <person name="Kubota M."/>
                <person name="Nanba E."/>
                <person name="Saitsu H."/>
                <person name="Matsumoto N."/>
                <person name="Kato M."/>
            </authorList>
            <dbReference type="PubMed" id="27246907"/>
            <dbReference type="DOI" id="10.1111/cge.12813"/>
        </citation>
        <scope>INVOLVEMENT IN NEDHSB</scope>
    </reference>
    <reference key="13">
        <citation type="journal article" date="2017" name="Nat. Struct. Mol. Biol." volume="24" first="325" last="336">
            <title>Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.</title>
            <authorList>
                <person name="Hendriks I.A."/>
                <person name="Lyon D."/>
                <person name="Young C."/>
                <person name="Jensen L.J."/>
                <person name="Vertegaal A.C."/>
                <person name="Nielsen M.L."/>
            </authorList>
            <dbReference type="PubMed" id="28112733"/>
            <dbReference type="DOI" id="10.1038/nsmb.3366"/>
        </citation>
        <scope>SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-859</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="14">
        <citation type="journal article" date="2022" name="Cell Rep." volume="38" first="110597" last="110597">
            <title>Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly.</title>
            <authorList>
                <person name="Ni C."/>
                <person name="Schmitz D.A."/>
                <person name="Lee J."/>
                <person name="Pawlowski K."/>
                <person name="Wu J."/>
                <person name="Buszczak M."/>
            </authorList>
            <dbReference type="PubMed" id="35354024"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2022.110597"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH AIRIM</scope>
        <scope>INTERACTION WITH PRE-60S RIBOSOMAL PARTICLES</scope>
        <scope>VARIANTS NEDHSB THR-330 DEL AND GLY-628</scope>
        <scope>CHARACTERIZATION OF VARIANTS NEDHSB THR-330 DEL AND GLY-628</scope>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2024" name="Cell" volume="0" first="0" last="0">
            <title>The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.</title>
            <authorList>
                <person name="Krishnamoorthy V."/>
                <person name="Foglizzo M."/>
                <person name="Dilley R.L."/>
                <person name="Wu A."/>
                <person name="Datta A."/>
                <person name="Dutta P."/>
                <person name="Campbell L.J."/>
                <person name="Degtjarik O."/>
                <person name="Musgrove L.J."/>
                <person name="Calabrese A.N."/>
                <person name="Zeqiraj E."/>
                <person name="Greenberg R.A."/>
            </authorList>
            <dbReference type="PubMed" id="38554706"/>
            <dbReference type="DOI" id="10.1016/j.cell.2024.03.002"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>MUTAGENESIS OF GLY-185 AND PHE-323</scope>
        <scope>CHARACTERIZATION OF VARIANTS NEDHSB THR-100; THR-330 DEL; GLN-529; CYS-626 AND GLN-784</scope>
        <scope>CATALYTIC ACTIVITY</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2017" name="Adv. Exp. Med. Biol." volume="980" first="59" last="66">
            <title>Isolated hearing impairment caused by SPATA5 mutations in a family with variable phenotypic expression.</title>
            <authorList>
                <person name="Szczaluba K."/>
                <person name="Szymanska K."/>
                <person name="Kosinska J."/>
                <person name="Pollak A."/>
                <person name="Murcia V."/>
                <person name="Kedra A."/>
                <person name="Stawinski P."/>
                <person name="Rydzanicz M."/>
                <person name="Demkow U."/>
                <person name="Ploski R."/>
            </authorList>
            <dbReference type="PubMed" id="28293831"/>
            <dbReference type="DOI" id="10.1007/5584_2016_206"/>
        </citation>
        <scope>VARIANT NEDHSB THR-330 DEL</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2021" name="Int. J. Mol. Sci." volume="22" first="0" last="0">
            <title>Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS.</title>
            <authorList>
                <person name="Braun F."/>
                <person name="Hentschel A."/>
                <person name="Sickmann A."/>
                <person name="Marteau T."/>
                <person name="Hertel S."/>
                <person name="Foerster F."/>
                <person name="Prokisch H."/>
                <person name="Wagner M."/>
                <person name="Wortmann S."/>
                <person name="Della Marina A."/>
                <person name="Koelbel H."/>
                <person name="Roos A."/>
                <person name="Schara-Schmidt U."/>
            </authorList>
            <dbReference type="PubMed" id="34360601"/>
            <dbReference type="DOI" id="10.3390/ijms22157835"/>
        </citation>
        <scope>VARIANTS NEDHSB 132-GLN--LEU-893 DEL AND THR-330 DEL</scope>
    </reference>
    <comment type="function">
        <text evidence="2 9 10">ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024, PubMed:38554706). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (By similarity).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="10">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="3.6.4.10"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="10">
            <dbReference type="Rhea" id="RHEA:13066"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="10">AFG2A alone display limited ATPase activity and is not regulated by RNA or DNA binding. In the context of 55LCC heterohexameric ATPase complex, the ATPase activity increases and is stimulated by DNA binding and inhibited in presence of RNA.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10">Part of the 55LCC heterohexameric ATPase complex composed at least of AIRIM, AFG2A, AFG2B and CINP (PubMed:35354024, PubMed:38554706). Associates with pre-60S ribosomal particles (PubMed:35354024).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-3184062">
            <id>Q8NB90</id>
        </interactant>
        <interactant intactId="EBI-7950854">
            <id>Q9BVQ7</id>
            <label>AFG2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>14</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="2">Mitochondrion</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cytoplasm</location>
            <location evidence="4">Cytoskeleton</location>
            <location evidence="4">Spindle</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8NB90-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8NB90-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_033048 VSP_033049"/>
        </isoform>
        <isoform>
            <id>Q8NB90-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_033046 VSP_033047"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="1">The first ATP-binding region binds ATP with low affinity whereas the second ATP-binding region binds ATP with high affinity.</text>
    </comment>
    <comment type="disease" evidence="5 6 7 8 9 10">
        <disease id="DI-04554">
            <name>Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities</name>
            <acronym>NEDHSB</acronym>
            <description>An autosomal recessive disorder characterized by intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss.</description>
            <dbReference type="MIM" id="616577"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="15">Belongs to the AAA ATPase family. AFG2 subfamily.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.10" evidence="1"/>
    <dbReference type="EMBL" id="AF361489">
        <property type="protein sequence ID" value="AAM00262.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF479656">
        <property type="protein sequence ID" value="AAM43608.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK091384">
        <property type="protein sequence ID" value="BAC03651.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC021205">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC026402">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC097492">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC109357">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC048217">
        <property type="protein sequence ID" value="AAH48217.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS3730.1">
        <molecule id="Q8NB90-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001304728.1">
        <property type="nucleotide sequence ID" value="NM_001317799.1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_660208.2">
        <molecule id="Q8NB90-1"/>
        <property type="nucleotide sequence ID" value="NM_145207.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_011529981.1">
        <molecule id="Q8NB90-2"/>
        <property type="nucleotide sequence ID" value="XM_011531679.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="XP_054205056.1">
        <molecule id="Q8NB90-2"/>
        <property type="nucleotide sequence ID" value="XM_054349081.1"/>
    </dbReference>
    <dbReference type="PDB" id="8RHN">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.50 A"/>
        <property type="chains" value="E/F/G/H/K/L/M/N=1-893"/>
    </dbReference>
    <dbReference type="PDB" id="9LGO">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.51 A"/>
        <property type="chains" value="A/B/D/E=1-886"/>
    </dbReference>
    <dbReference type="PDBsum" id="8RHN"/>
    <dbReference type="PDBsum" id="9LGO"/>
    <dbReference type="AlphaFoldDB" id="Q8NB90"/>
    <dbReference type="EMDB" id="EMD-15778"/>
    <dbReference type="EMDB" id="EMD-15846"/>
    <dbReference type="EMDB" id="EMD-15847"/>
    <dbReference type="EMDB" id="EMD-19177"/>
    <dbReference type="EMDB" id="EMD-63069"/>
    <dbReference type="SMR" id="Q8NB90"/>
    <dbReference type="BioGRID" id="127927">
        <property type="interactions" value="130"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-9182">
        <property type="entry name" value="SPATA5-SPATA5L1 ATPase complex"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8NB90">
        <property type="interactions" value="1409"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8NB90">
        <property type="interactions" value="1097"/>
    </dbReference>
    <dbReference type="MINT" id="Q8NB90"/>
    <dbReference type="STRING" id="9606.ENSP00000274008"/>
    <dbReference type="ChEMBL" id="CHEMBL2311230"/>
    <dbReference type="GlyGen" id="Q8NB90">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8NB90"/>
    <dbReference type="MetOSite" id="Q8NB90"/>
    <dbReference type="PhosphoSitePlus" id="Q8NB90"/>
    <dbReference type="BioMuta" id="SPATA5"/>
    <dbReference type="DMDM" id="308153554"/>
    <dbReference type="jPOST" id="Q8NB90"/>
    <dbReference type="MassIVE" id="Q8NB90"/>
    <dbReference type="PaxDb" id="9606-ENSP00000274008"/>
    <dbReference type="PeptideAtlas" id="Q8NB90"/>
    <dbReference type="ProteomicsDB" id="72749">
        <molecule id="Q8NB90-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="72750">
        <molecule id="Q8NB90-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="72751">
        <molecule id="Q8NB90-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8NB90"/>
    <dbReference type="Antibodypedia" id="26869">
        <property type="antibodies" value="50 antibodies from 19 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="166378"/>
    <dbReference type="Ensembl" id="ENST00000274008.5">
        <molecule id="Q8NB90-1"/>
        <property type="protein sequence ID" value="ENSP00000274008.3"/>
        <property type="gene ID" value="ENSG00000145375.10"/>
    </dbReference>
    <dbReference type="GeneID" id="166378"/>
    <dbReference type="KEGG" id="hsa:166378"/>
    <dbReference type="MANE-Select" id="ENST00000274008.5">
        <property type="protein sequence ID" value="ENSP00000274008.3"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_145207.3"/>
        <property type="RefSeq protein sequence ID" value="NP_660208.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003iez.5">
        <molecule id="Q8NB90-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:18119"/>
    <dbReference type="ClinPGx" id="PA38294"/>
    <dbReference type="CTD" id="166378"/>
    <dbReference type="DisGeNET" id="166378"/>
    <dbReference type="GeneCards" id="AFG2A"/>
    <dbReference type="HGNC" id="HGNC:18119">
        <property type="gene designation" value="AFG2A"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000145375">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFG2A"/>
    <dbReference type="MIM" id="613940">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="616577">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000145375"/>
    <dbReference type="Orphanet" id="457351">
        <property type="disease" value="Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000145375"/>
    <dbReference type="eggNOG" id="KOG0730">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000157323"/>
    <dbReference type="HOGENOM" id="CLU_000688_10_0_1"/>
    <dbReference type="InParanoid" id="Q8NB90"/>
    <dbReference type="OrthoDB" id="27435at2759"/>
    <dbReference type="PAN-GO" id="Q8NB90">
        <property type="GO annotations" value="2 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8NB90"/>
    <dbReference type="PathwayCommons" id="Q8NB90"/>
    <dbReference type="SignaLink" id="Q8NB90"/>
    <dbReference type="Agora" id="ENSG00000145375"/>
    <dbReference type="BioGRID-ORCS" id="166378">
        <property type="hits" value="696 hits in 1170 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SPATA5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="SPATA5"/>
    <dbReference type="GenomeRNAi" id="166378"/>
    <dbReference type="Pharos" id="Q8NB90">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8NB90"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 4"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8NB90">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000145375">
        <property type="expression patterns" value="Expressed in tendon of biceps brachii and 149 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8NB90">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="FlyBase"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005819">
        <property type="term" value="C:spindle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990275">
        <property type="term" value="F:preribosome binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007420">
        <property type="term" value="P:brain development"/>
        <property type="evidence" value="ECO:0000315"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030154">
        <property type="term" value="P:cell differentiation"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042273">
        <property type="term" value="P:ribosomal large subunit biogenesis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007283">
        <property type="term" value="P:spermatogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd19503">
        <property type="entry name" value="RecA-like_CDC48_NLV2_r1-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd19511">
        <property type="entry name" value="RecA-like_CDC48_r2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000567">
        <property type="entry name" value="ATPase, AAA family protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.8.60:FF:000068">
        <property type="entry name" value="spermatogenesis-associated protein 5 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.8.60:FF:000069">
        <property type="entry name" value="spermatogenesis-associated protein 5 isoform X1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.40.40.20:FF:000015">
        <property type="entry name" value="spermatogenesis-associated protein 5 isoform X2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:000012">
        <property type="entry name" value="Transitional endoplasmic reticulum ATPase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.60">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.40.40.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050168">
        <property type="entry name" value="AAA_ATPase_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041569">
        <property type="entry name" value="AAA_lid_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR009010">
        <property type="entry name" value="Asp_de-COase-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003959">
        <property type="entry name" value="ATPase_AAA_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003960">
        <property type="entry name" value="ATPase_AAA_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23077">
        <property type="entry name" value="AAA-FAMILY ATPASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23077:SF27">
        <property type="entry name" value="ATPASE FAMILY GENE 2 PROTEIN HOMOLOG A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00004">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17862">
        <property type="entry name" value="AAA_lid_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50692">
        <property type="entry name" value="ADC-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00674">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0143">Chaperone</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0225">Disease variant</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-1017">Isopeptide bond</keyword>
    <keyword id="KW-0496">Mitochondrion</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0690">Ribosome biogenesis</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <keyword id="KW-0832">Ubl conjugation</keyword>
    <feature type="chain" id="PRO_0000330583" description="ATPase family gene 2 protein homolog A">
        <location>
            <begin position="1"/>
            <end position="893"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with AFG2B and CINP" evidence="10">
        <location>
            <begin position="1"/>
            <end position="237"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="1"/>
            <end position="26"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="1"/>
            <end position="10"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="11"/>
            <end position="25"/>
        </location>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="394"/>
            <end position="401"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="668"/>
            <end position="675"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="17">
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="274"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="cross-link" description="Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)" evidence="18">
        <location>
            <position position="859"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033046" description="In isoform 3." evidence="11">
        <original>GPE</original>
        <variation>VGC</variation>
        <location>
            <begin position="694"/>
            <end position="696"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033047" description="In isoform 3." evidence="11">
        <location>
            <begin position="697"/>
            <end position="893"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033048" description="In isoform 2." evidence="14">
        <original>ALMRPGRIDR</original>
        <variation>VPPSQTFLLL</variation>
        <location>
            <begin position="781"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033049" description="In isoform 2." evidence="14">
        <location>
            <begin position="791"/>
            <end position="893"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042703" description="In dbSNP:rs35430470.">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="27"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075775" description="In NEDHSB; dbSNP:rs745858366." evidence="5">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075776" description="In NEDHSB; dbSNP:rs796051893." evidence="5">
        <original>S</original>
        <variation>I</variation>
        <location>
            <position position="90"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075777" description="In NEDHSB; decreased protein stability; no effect on interaction with AFG2B and CINP; affects cell viability; dbSNP:rs796051895." evidence="5 10">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086543" description="In NEDHSB." evidence="8">
        <location>
            <begin position="132"/>
            <end position="893"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075778" description="In NEDHSB; impaired maturation of pre-60S ribosome; decreased protein stability; decreases interaction with AFG2B and CINP; affects cell viability." evidence="5 7 8 9 10">
        <location>
            <position position="330"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075779" description="In NEDHSB; dbSNP:rs766034355." evidence="5">
        <original>S</original>
        <variation>L</variation>
        <location>
            <position position="448"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075780" description="In NEDHSB." evidence="5">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="488"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075781" description="In NEDHSB; decreased protein stability; no effect on interaction with AFG2B and CINP; affects cell viability; dbSNP:rs567175477." evidence="5 10">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="529"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075782" description="In NEDHSB; decreased protein stability; no effect on interaction with AFG2B and CINP; affects cell viability; dbSNP:rs1553969639." evidence="5 10">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="626"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075783" description="In NEDHSB; impaired maturation of pre-60S ribosome; dbSNP:rs768528444." evidence="5 9">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="628"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042704" description="In dbSNP:rs35133326.">
        <original>S</original>
        <variation>Y</variation>
        <location>
            <position position="673"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075784" description="In NEDHSB; decreased protein stability; no effect on interaction with AFG2B and CINP; affects cell viability; dbSNP:rs796051894." evidence="5 10">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="784"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_075785" description="In NEDHSB; dbSNP:rs796051892." evidence="5">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="844"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="No effect on protein stability. No effect on interaction with AFG2B." evidence="10">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="185"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Reduces protein stability." evidence="10">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH48217." evidence="15" ref="5">
        <location>
            <position position="55"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00262." evidence="15" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00262." evidence="15" ref="1">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="210"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAC03651." evidence="15" ref="3">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="568"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00262." evidence="15" ref="1">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="603"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAC03651." evidence="15" ref="3">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="614"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAM43608." evidence="15" ref="2">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="695"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00262." evidence="15" ref="1">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="851"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAM00262." evidence="15" ref="1">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="891"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="P32794"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3UMC0"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="18445686"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="26299366"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="27246907"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="28293831"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="34360601"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="35354024"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="38554706"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="26299366"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="13">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000303" key="14">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="15"/>
    <evidence type="ECO:0000312" key="16">
        <source>
            <dbReference type="HGNC" id="HGNC:18119"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="28112733"/>
        </source>
    </evidence>
    <sequence length="893" mass="97904" checksum="60214147CBB31F4A" modified="2010-10-05" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-11-08" modified="2026-01-28" version="163" xmlns="https://uniprot.org/uniprot">
    <accession>Q5BKT4</accession>
    <accession>Q6NS98</accession>
    <accession>Q96DU0</accession>
    <accession>Q96SM6</accession>
    <name>AG10A_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="1">Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase A</fullName>
            <ecNumber evidence="1">2.4.1.256</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-1,2-glucosyltransferase ALG10-A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-2-glucosyltransferase ALG10-A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="4">Asparagine-linked glycosylation protein 10 homolog A</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="4" type="primary">ALG10</name>
        <name evidence="4" type="synonym">ALG10A</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2002" name="Mol. Biol. Evol." volume="19" first="1451" last="1463">
            <title>Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate.</title>
            <authorList>
                <person name="Oriol R."/>
                <person name="Martinez-Duncker I."/>
                <person name="Chantret I."/>
                <person name="Mollicone R."/>
                <person name="Codogno P."/>
            </authorList>
            <dbReference type="PubMed" id="12200473"/>
            <dbReference type="DOI" id="10.1093/oxfordjournals.molbev.a004208"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Embryo</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Nat. Genet." volume="36" first="40" last="45">
            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
            <authorList>
                <person name="Ota T."/>
                <person name="Suzuki Y."/>
                <person name="Nishikawa T."/>
                <person name="Otsuki T."/>
                <person name="Sugiyama T."/>
                <person name="Irie R."/>
                <person name="Wakamatsu A."/>
                <person name="Hayashi K."/>
                <person name="Sato H."/>
                <person name="Nagai K."/>
                <person name="Kimura K."/>
                <person name="Makita H."/>
                <person name="Sekine M."/>
                <person name="Obayashi M."/>
                <person name="Nishi T."/>
                <person name="Shibahara T."/>
                <person name="Tanaka T."/>
                <person name="Ishii S."/>
                <person name="Yamamoto J."/>
                <person name="Saito K."/>
                <person name="Kawai Y."/>
                <person name="Isono Y."/>
                <person name="Nakamura Y."/>
                <person name="Nagahari K."/>
                <person name="Murakami K."/>
                <person name="Yasuda T."/>
                <person name="Iwayanagi T."/>
                <person name="Wagatsuma M."/>
                <person name="Shiratori A."/>
                <person name="Sudo H."/>
                <person name="Hosoiri T."/>
                <person name="Kaku Y."/>
                <person name="Kodaira H."/>
                <person name="Kondo H."/>
                <person name="Sugawara M."/>
                <person name="Takahashi M."/>
                <person name="Kanda K."/>
                <person name="Yokoi T."/>
                <person name="Furuya T."/>
                <person name="Kikkawa E."/>
                <person name="Omura Y."/>
                <person name="Abe K."/>
                <person name="Kamihara K."/>
                <person name="Katsuta N."/>
                <person name="Sato K."/>
                <person name="Tanikawa M."/>
                <person name="Yamazaki M."/>
                <person name="Ninomiya K."/>
                <person name="Ishibashi T."/>
                <person name="Yamashita H."/>
                <person name="Murakawa K."/>
                <person name="Fujimori K."/>
                <person name="Tanai H."/>
                <person name="Kimata M."/>
                <person name="Watanabe M."/>
                <person name="Hiraoka S."/>
                <person name="Chiba Y."/>
                <person name="Ishida S."/>
                <person name="Ono Y."/>
                <person name="Takiguchi S."/>
                <person name="Watanabe S."/>
                <person name="Yosida M."/>
                <person name="Hotuta T."/>
                <person name="Kusano J."/>
                <person name="Kanehori K."/>
                <person name="Takahashi-Fujii A."/>
                <person name="Hara H."/>
                <person name="Tanase T.-O."/>
                <person name="Nomura Y."/>
                <person name="Togiya S."/>
                <person name="Komai F."/>
                <person name="Hara R."/>
                <person name="Takeuchi K."/>
                <person name="Arita M."/>
                <person name="Imose N."/>
                <person name="Musashino K."/>
                <person name="Yuuki H."/>
                <person name="Oshima A."/>
                <person name="Sasaki N."/>
                <person name="Aotsuka S."/>
                <person name="Yoshikawa Y."/>
                <person name="Matsunawa H."/>
                <person name="Ichihara T."/>
                <person name="Shiohata N."/>
                <person name="Sano S."/>
                <person name="Moriya S."/>
                <person name="Momiyama H."/>
                <person name="Satoh N."/>
                <person name="Takami S."/>
                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
                <person name="Takemoto M."/>
                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 149-473</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. In the lumen of the endoplasmic reticulum, adds the third and last glucose residue from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide intermediate Glc(2)Man(9)GlcNAc(2)-PP-Dol to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>an alpha-D-Glc-(1-&gt;3)-alpha-D-Glc-(1-&gt;3)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl beta-D-glucosyl phosphate = a alpha-D-Glc-(1-&gt;2)-alpha-D-Glc-(1-&gt;3)-alpha-D-Glc-(1-&gt;3)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:29543"/>
            <dbReference type="Rhea" id="RHEA-COMP:19498"/>
            <dbReference type="Rhea" id="RHEA-COMP:19502"/>
            <dbReference type="Rhea" id="RHEA-COMP:19512"/>
            <dbReference type="Rhea" id="RHEA-COMP:19522"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57525"/>
            <dbReference type="ChEBI" id="CHEBI:57683"/>
            <dbReference type="ChEBI" id="CHEBI:132522"/>
            <dbReference type="ChEBI" id="CHEBI:132523"/>
            <dbReference type="EC" id="2.4.1.256"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:29544"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="1">Protein modification; protein glycosylation.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-7797864">
            <id>P11912</id>
            <label>CD79A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-781551">
            <id>Q9Y282</id>
            <label>ERGIC3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-11956479">
            <id>P23142-4</id>
            <label>FBLN1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-2868124">
            <id>Q9BSE4</id>
            <label>HERPUD2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-749270">
            <id>Q8N6R1</id>
            <label>SERP2</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-13064220">
            <id>Q5BKT4</id>
        </interactant>
        <interactant intactId="EBI-18037857">
            <id>Q3SXP7</id>
            <label>SHISAL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="1">Endoplasmic reticulum membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the ALG10 glucosyltransferase family.</text>
    </comment>
    <comment type="sequence caution" evidence="3">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB55272" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EC" id="2.4.1.256" evidence="1"/>
    <dbReference type="EMBL" id="AJ312278">
        <property type="protein sequence ID" value="CAC41349.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC070347">
        <property type="protein sequence ID" value="AAH70347.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC090948">
        <property type="protein sequence ID" value="AAH90948.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK027657">
        <property type="protein sequence ID" value="BAB55272.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS41769.1"/>
    <dbReference type="RefSeq" id="NP_116223.3">
        <property type="nucleotide sequence ID" value="NM_032834.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5BKT4"/>
    <dbReference type="BioGRID" id="124356">
        <property type="interactions" value="55"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5BKT4">
        <property type="interactions" value="2741"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5BKT4">
        <property type="interactions" value="42"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000266483"/>
    <dbReference type="CAZy" id="GT59">
        <property type="family name" value="Glycosyltransferase Family 59"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5BKT4">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5BKT4"/>
    <dbReference type="PhosphoSitePlus" id="Q5BKT4"/>
    <dbReference type="SwissPalm" id="Q5BKT4"/>
    <dbReference type="BioMuta" id="ALG10"/>
    <dbReference type="DMDM" id="74736030"/>
    <dbReference type="jPOST" id="Q5BKT4"/>
    <dbReference type="MassIVE" id="Q5BKT4"/>
    <dbReference type="PaxDb" id="9606-ENSP00000266483"/>
    <dbReference type="PeptideAtlas" id="Q5BKT4"/>
    <dbReference type="ProteomicsDB" id="62698"/>
    <dbReference type="Pumba" id="Q5BKT4"/>
    <dbReference type="Antibodypedia" id="55444">
        <property type="antibodies" value="84 antibodies from 17 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="84920"/>
    <dbReference type="Ensembl" id="ENST00000266483.7">
        <property type="protein sequence ID" value="ENSP00000266483.2"/>
        <property type="gene ID" value="ENSG00000139133.7"/>
    </dbReference>
    <dbReference type="GeneID" id="84920"/>
    <dbReference type="KEGG" id="hsa:84920"/>
    <dbReference type="MANE-Select" id="ENST00000266483.7">
        <property type="protein sequence ID" value="ENSP00000266483.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_032834.4"/>
        <property type="RefSeq protein sequence ID" value="NP_116223.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001rlm.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23162"/>
    <dbReference type="ClinPGx" id="PA134732019"/>
    <dbReference type="CTD" id="84920"/>
    <dbReference type="DisGeNET" id="84920"/>
    <dbReference type="GeneCards" id="ALG10"/>
    <dbReference type="HGNC" id="HGNC:23162">
        <property type="gene designation" value="ALG10"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000139133">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ALG10"/>
    <dbReference type="MIM" id="618355">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000139133"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000139133"/>
    <dbReference type="eggNOG" id="KOG2642">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012906"/>
    <dbReference type="HOGENOM" id="CLU_017053_1_0_1"/>
    <dbReference type="InParanoid" id="Q5BKT4"/>
    <dbReference type="OMA" id="VWDSKIT"/>
    <dbReference type="OrthoDB" id="4769at2759"/>
    <dbReference type="PAN-GO" id="Q5BKT4">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5BKT4"/>
    <dbReference type="BRENDA" id="2.4.1.256">
        <property type="organism ID" value="2681"/>
    </dbReference>
    <dbReference type="PathwayCommons" id="Q5BKT4"/>
    <dbReference type="Reactome" id="R-HSA-446193">
        <property type="pathway name" value="Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q5BKT4"/>
    <dbReference type="UniPathway" id="UPA00378"/>
    <dbReference type="Agora" id="ENSG00000139133"/>
    <dbReference type="BioGRID-ORCS" id="84920">
        <property type="hits" value="54 hits in 1059 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ALG10">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="84920"/>
    <dbReference type="Pharos" id="Q5BKT4">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5BKT4"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5BKT4">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000139133">
        <property type="expression patterns" value="Expressed in primordial germ cell in gonad and 109 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5BKT4">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005789">
        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0106073">
        <property type="term" value="F:dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006488">
        <property type="term" value="P:dolichol-linked oligosaccharide biosynthetic process"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0006487">
        <property type="term" value="P:protein N-linked glycosylation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR016900">
        <property type="entry name" value="Alg10"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12989">
        <property type="entry name" value="ALPHA-1,2-GLUCOSYLTRANSFERASE ALG10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR12989:SF11">
        <property type="entry name" value="DOL-P-GLC:GLC(2)MAN(9)GLCNAC(2)-PP-DOL ALPHA-1,2-GLUCOSYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF04922">
        <property type="entry name" value="DIE2_ALG10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PIRSF" id="PIRSF028810">
        <property type="entry name" value="Alpha1_2_glucosyltferase_Alg10"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000215447" description="Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase A">
        <location>
            <begin position="1"/>
            <end position="473"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="1"/>
            <end position="6"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="7"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="28"/>
            <end position="64"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="65"/>
            <end position="85"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="86"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="98"/>
            <end position="118"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="119"/>
            <end position="130"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="131"/>
            <end position="151"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="152"/>
            <end position="172"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="173"/>
            <end position="175"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="176"/>
            <end position="196"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="197"/>
            <end position="249"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="250"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="271"/>
            <end position="283"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="284"/>
            <end position="304"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="305"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="324"/>
            <end position="344"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="345"/>
            <end position="367"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="368"/>
            <end position="388"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="389"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="393"/>
            <end position="413"/>
        </location>
    </feature>
    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="414"/>
            <end position="436"/>
        </location>
    </feature>
    <feature type="transmembrane region" description="Helical" evidence="2">
        <location>
            <begin position="437"/>
            <end position="457"/>
        </location>
    </feature>
    <feature type="topological domain" description="Cytoplasmic" evidence="2">
        <location>
            <begin position="458"/>
            <end position="473"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAH70347." evidence="3" ref="2">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="184"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; CAC41349." evidence="3" ref="1">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAB55272." evidence="3" ref="3">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="384"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="Q5I7T1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000305" key="3"/>
    <evidence type="ECO:0000312" key="4">
        <source>
            <dbReference type="HGNC" id="HGNC:23162"/>
        </source>
    </evidence>
    <sequence length="473" mass="55606" checksum="1860D4E61ACBC2A0" modified="2005-04-12" version="1">MAQLEGYYFSAALSCTFLVSCLLFSAFSRALREPYMDEIFHLPQAQRYCEGHFSLSQWDPMITTLPGLYLVSIGVIKPAIWIFGWSEHVVCSIGMLRFVNLLFSVGNFYLLYLLFCKVQPRNKAASSIQRVLSTLTLAVFPTLYFFNFLYYTEAGSMFFTLFAYLMCLYGNHKTSAFLGFCGFMFRQTNIIWAVFCAGNVIAQKLTEAWKTELQKKEDRLPPIKGPFAEFRKILQFLLAYSMSFKNLSMLLLLTWPYILLGFLFCAFVVVNGGIVIGDRSSHEACLHFPQLFYFFSFTLFFSFPHLLSPSKIKTFLSLVWKRRILFFVVTLVSVFLVWKFTYAHKYLLADNRHYTFYVWKRVFQRYETVKYLLVPAYIFAGWSIADSLKSKSIFWNLMFFICLFTVIVPQKLLEFRYFILPYVIYRLNIPLPPTSRLICELSCYAVVNFITFFIFLNKTFQWPNSQDIQRFMW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-03-29" modified="2026-01-28" version="159" xmlns="https://uniprot.org/uniprot">
    <accession>Q6ULP2</accession>
    <accession>D6W5E9</accession>
    <accession>Q6ZM66</accession>
    <accession>Q86VW3</accession>
    <accession>Q8TCF3</accession>
    <accession>Q9H7E3</accession>
    <accession>Q9HAB9</accession>
    <accession>Q9NXS4</accession>
    <name>AFTIN_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Aftiphilin</fullName>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">AFTPH</name>
        <name type="synonym">AFTH</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] OF 724-936 (ISOFORM 4)</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>IDENTIFICATION IN THE AFTIPHILIN-P200-GAMMA-SYNERGIN COMPLEX</scope>
        <scope>INTERACTION WITH HEATR5B; SYNRG; AP1G1; CLTCL1 AND GGA1</scope>
        <scope>SUBCELLULAR LOCATION</scope>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-617</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
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    <comment type="function">
        <text evidence="6">Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025).</text>
    </comment>
    <comment type="subunit">
        <text evidence="5 6">Self-associates (PubMed:15758025). Interacts with GGA1 (via GAE domain) (PubMed:14665628, PubMed:15758025). Interacts with GGA3 (via GAE domain), AP1G1 (via GAE domain) and AP1G2 (via GAE domain) (PubMed:14665628). Component of the aftiphilin/p200/gamma-synergin complex, at least composed of AFTPH/aftiphilin, HEATR5B/p200a and SYNRG/gamma-synergin, which plays a role in the AP1G1/AP-1-mediated protein trafficking from early to recycling endosomes (PubMed:15758025). Within the complex interacts with HEATR5B/p200a and SYNRG/gamma-synergin; the interactions are direct (PubMed:15758025). Interacts with AP1G1/AP-1; the interaction is required to recruit AFTPH/aftiphilin to the perinuclear region of the cell (PubMed:15758025). Interacts with CLTCL1/Clathrin (PubMed:15758025).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2848714">
            <id>Q6ULP2</id>
        </interactant>
        <interactant intactId="EBI-7240490">
            <id>Q9UMZ2</id>
            <label>SYNRG</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5 6">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasm</location>
            <location evidence="6">Perinuclear region</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="6">Cytoplasmic vesicle</location>
            <location evidence="6">Clathrin-coated vesicle</location>
        </subcellularLocation>
        <text evidence="5 6">Co-localizes with AP1G1/AP-1 in the cytoplasm (PubMed:14665628, PubMed:15758025). Recruited to the perinuclear region by AP1G1/AP-1 (PubMed:15758025).</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q6ULP2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q6ULP2-6</id>
            <name>2</name>
            <sequence type="described" ref="VSP_059492 VSP_059495"/>
        </isoform>
        <isoform>
            <id>Q6ULP2-7</id>
            <name>3</name>
            <sequence type="described" ref="VSP_059493 VSP_059494"/>
        </isoform>
        <isoform>
            <id>Q6ULP2-8</id>
            <name>4</name>
            <sequence type="described" ref="VSP_059492"/>
        </isoform>
        <isoform>
            <id>Q6ULP2-9</id>
            <name>5</name>
            <sequence type="described" ref="VSP_059495"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text evidence="1">The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself (By similarity).</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 3</molecule>
        <text evidence="10">May be due to intron retention.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="AAH22247" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="frameshift">
            <sequence resource="EMBL-CDS" id="AAH22247" version="1"/>
        </conflict>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB13930" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="10">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB14949" version="1"/>
        </conflict>
        <text>Truncated N-terminus.</text>
    </comment>
    <dbReference type="EMBL" id="AY367088">
        <property type="protein sequence ID" value="AAR14726.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK000087">
        <property type="protein sequence ID" value="BAA90936.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK021899">
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        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="BAB14949.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="CAE46209.1"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="EAW99938.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="EAW99941.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
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        <property type="protein sequence ID" value="AAH22247.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
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        <property type="protein sequence ID" value="AAH47529.1"/>
        <property type="molecule type" value="mRNA"/>
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        <molecule id="Q6ULP2-6"/>
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        <molecule id="Q6ULP2-1"/>
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        <molecule id="Q6ULP2-8"/>
        <property type="nucleotide sequence ID" value="NM_001002243.3"/>
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    <dbReference type="RefSeq" id="NP_001362900.1">
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        <property type="nucleotide sequence ID" value="NM_001375971.1"/>
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    <dbReference type="RefSeq" id="NP_060127.3">
        <molecule id="Q6ULP2-6"/>
        <property type="nucleotide sequence ID" value="NM_017657.4"/>
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        <property type="nucleotide sequence ID" value="NM_203437.3"/>
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        <property type="glycosylation" value="2 sites, 1 glycan"/>
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        <property type="glycosylation" value="2 sites, 1 O-linked glycan (2 sites)"/>
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        <molecule id="Q6ULP2-1"/>
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        <property type="antibodies" value="105 antibodies from 21 providers"/>
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    <dbReference type="DNASU" id="54812"/>
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        <property type="protein sequence ID" value="ENSP00000238856.4"/>
        <property type="gene ID" value="ENSG00000119844.18"/>
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        <property type="protein sequence ID" value="ENSP00000387071.1"/>
        <property type="gene ID" value="ENSG00000119844.18"/>
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    <dbReference type="Ensembl" id="ENST00000695864.1">
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        <property type="protein sequence ID" value="ENSP00000512229.1"/>
        <property type="gene ID" value="ENSG00000119844.18"/>
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    <dbReference type="GeneID" id="54812"/>
    <dbReference type="KEGG" id="hsa:54812"/>
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        <property type="protein sequence ID" value="ENSP00000387071.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_203437.4"/>
        <property type="RefSeq protein sequence ID" value="NP_982261.2"/>
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    <dbReference type="UCSC" id="uc002scz.4">
        <molecule id="Q6ULP2-1"/>
        <property type="organism name" value="human"/>
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    <dbReference type="AGR" id="HGNC:25951"/>
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        <property type="gene designation" value="AFTPH"/>
    </dbReference>
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        <property type="expression patterns" value="Low tissue specificity"/>
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    <dbReference type="MIM" id="619628">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000119844"/>
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    <dbReference type="eggNOG" id="ENOG502QPXF">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="GeneTree" id="ENSGT00940000154186"/>
    <dbReference type="HOGENOM" id="CLU_017041_0_0_1"/>
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    <dbReference type="OrthoDB" id="5917212at2759"/>
    <dbReference type="PAN-GO" id="Q6ULP2">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q6ULP2"/>
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    <dbReference type="SignaLink" id="Q6ULP2"/>
    <dbReference type="Agora" id="ENSG00000119844"/>
    <dbReference type="BioGRID-ORCS" id="54812">
        <property type="hits" value="14 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AFTPH">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AFTPH"/>
    <dbReference type="GenomeRNAi" id="54812"/>
    <dbReference type="Pharos" id="Q6ULP2">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q6ULP2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 2"/>
    </dbReference>
    <dbReference type="RNAct" id="Q6ULP2">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000119844">
        <property type="expression patterns" value="Expressed in renal medulla and 209 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q6ULP2">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030121">
        <property type="term" value="C:AP-1 adaptor complex"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005794">
        <property type="term" value="C:Golgi apparatus"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0005654">
        <property type="term" value="C:nucleoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="HPA"/>
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    <dbReference type="GO" id="GO:0048471">
        <property type="term" value="C:perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-SubCell"/>
    </dbReference>
    <dbReference type="GO" id="GO:0032588">
        <property type="term" value="C:trans-Golgi network membrane"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0030276">
        <property type="term" value="F:clathrin binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0015031">
        <property type="term" value="P:protein transport"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="InterPro" id="IPR046359">
        <property type="entry name" value="Aftin-like"/>
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        <property type="entry name" value="Clathrin-bd"/>
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        <property type="entry name" value="AFTIPHILIN"/>
        <property type="match status" value="1"/>
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    <dbReference type="PANTHER" id="PTHR16156">
        <property type="entry name" value="AFTIPHILIN A-RELATED"/>
        <property type="match status" value="1"/>
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    <dbReference type="Pfam" id="PF15045">
        <property type="entry name" value="Clathrin_bdg"/>
        <property type="match status" value="1"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-0653">Protein transport</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <feature type="chain" id="PRO_0000064488" description="Aftiphilin">
        <location>
            <begin position="1"/>
            <end position="936"/>
        </location>
    </feature>
    <feature type="region of interest" description="Interaction with AP1G1, AP1G2, GGA1 and GGA3" evidence="5">
        <location>
            <begin position="1"/>
            <end position="523"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1"/>
            <end position="36"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="197"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="374"/>
            <end position="409"/>
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    </feature>
    <feature type="region of interest" description="Interaction with AP1G1" evidence="6">
        <location>
            <begin position="386"/>
            <end position="610"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="589"/>
            <end position="637"/>
        </location>
    </feature>
    <feature type="region of interest" description="Clathrin-binding" evidence="3">
        <location>
            <begin position="825"/>
            <end position="829"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="WXXF motif 1">
        <location>
            <begin position="28"/>
            <end position="31"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="WXXF motif 2">
        <location>
            <begin position="432"/>
            <end position="435"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="WXXF motif 3 (partial)">
        <location>
            <begin position="436"/>
            <end position="438"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="WXXF motif 4">
        <location>
            <begin position="478"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="short sequence motif" description="CLTCL1/Clathrin-binding" evidence="6">
        <location>
            <begin position="716"/>
            <end position="718"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="4">
        <location>
            <begin position="19"/>
            <end position="29"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="374"/>
            <end position="389"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="595"/>
            <end position="610"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="4">
        <location>
            <begin position="617"/>
            <end position="628"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13 14">
        <location>
            <position position="151"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="395"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="15">
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="11 12 14">
        <location>
            <position position="617"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_059492" description="In isoform 2 and isoform 4." evidence="7 8">
        <location>
            <begin position="819"/>
            <end position="846"/>
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    </feature>
    <feature type="splice variant" id="VSP_059493" description="In isoform 3." evidence="9">
        <original>AS</original>
        <variation>GT</variation>
        <location>
            <begin position="819"/>
            <end position="820"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_059494" description="In isoform 3." evidence="9">
        <location>
            <begin position="821"/>
            <end position="936"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_059495" description="In isoform 2 and isoform 5." evidence="7 8">
        <original>T</original>
        <variation>TS</variation>
        <location>
            <position position="887"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_056728" description="In dbSNP:rs35986567.">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="233"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_056729" description="In dbSNP:rs3770740.">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_056730" description="In dbSNP:rs3770739.">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="550"/>
        </location>
    </feature>
    <feature type="mutagenesis site" description="Abolishes the interaction with CLTCL1/Clathrin." evidence="6">
        <original>YQW</original>
        <variation>SQS</variation>
        <location>
            <begin position="716"/>
            <end position="718"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB14949." evidence="10" ref="2">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="705"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BAB13930." evidence="10" ref="2">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="734"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAR14726." evidence="10" ref="1">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="850"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH22247." evidence="10" ref="5">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="894"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 5; AAH47529." evidence="10" ref="5">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="904"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
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        <source>
            <dbReference type="UniProtKB" id="Q80WT5"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14665628"/>
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    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15758025"/>
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    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source>
            <dbReference type="PubMed" id="17974005"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="10"/>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="16964243"/>
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    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <sequence length="936" mass="102113" checksum="7F84B4D6890BCDF7" modified="2018-03-28" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2005-11-08" modified="2026-01-28" version="151" xmlns="https://uniprot.org/uniprot">
    <accession>Q5I7T1</accession>
    <accession>B2RPF4</accession>
    <name>AG10B_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="10">Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase B</fullName>
            <ecNumber evidence="6">2.4.1.256</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-1,2-glucosyltransferase ALG10-A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-2-glucosyltransferase ALG10-B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="11">Asparagine-linked glycosylation protein 10 homolog B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="8">Potassium channel regulator 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="11" type="primary">ALG10B</name>
        <name evidence="8" type="synonym">KCR1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2003" name="FASEB J." volume="17" first="2263" last="2265">
            <title>The IKr drug response is modulated by KCR1 in transfected cardiac and noncardiac cell lines.</title>
            <authorList>
                <person name="Kupershmidt S."/>
                <person name="Yang I.C.-H."/>
                <person name="Hayashi K."/>
                <person name="Wei J."/>
                <person name="Chanthaphaychith S."/>
                <person name="Petersen C.I."/>
                <person name="Johns D.C."/>
                <person name="George A.L. Jr."/>
                <person name="Roden D.M."/>
                <person name="Balser J.R."/>
            </authorList>
            <dbReference type="PubMed" id="14525949"/>
            <dbReference type="DOI" id="10.1096/fj.02-1057fje"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>VARIANT GLY-84</scope>
    </reference>
    <reference key="2">
        <citation type="submission" date="2004-12" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="George A.L. Jr."/>
            </authorList>
        </citation>
        <scope>SEQUENCE REVISION</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="346" last="351">
            <title>The finished DNA sequence of human chromosome 12.</title>
            <authorList>
                <person name="Scherer S.E."/>
                <person name="Muzny D.M."/>
                <person name="Buhay C.J."/>
                <person name="Chen R."/>
                <person name="Cree A."/>
                <person name="Ding Y."/>
                <person name="Dugan-Rocha S."/>
                <person name="Gill R."/>
                <person name="Gunaratne P."/>
                <person name="Harris R.A."/>
                <person name="Hawes A.C."/>
                <person name="Hernandez J."/>
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                <person name="Hume J."/>
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                <person name="David R."/>
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                <person name="Eaves K.A."/>
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                <person name="Emery-Cohen A.J."/>
                <person name="Escotto M."/>
                <person name="Flagg N."/>
                <person name="Forbes L.D."/>
                <person name="Gabisi A.M."/>
                <person name="Garza M."/>
                <person name="Hamilton C."/>
                <person name="Henderson N."/>
                <person name="Hernandez O."/>
                <person name="Hines S."/>
                <person name="Hogues M.E."/>
                <person name="Huang M."/>
                <person name="Idlebird D.G."/>
                <person name="Johnson R."/>
                <person name="Jolivet A."/>
                <person name="Jones S."/>
                <person name="Kagan R."/>
                <person name="King L.M."/>
                <person name="Leal B."/>
                <person name="Lebow H."/>
                <person name="Lee S."/>
                <person name="LeVan J.M."/>
                <person name="Lewis L.C."/>
                <person name="London P."/>
                <person name="Lorensuhewa L.M."/>
                <person name="Loulseged H."/>
                <person name="Lovett D.A."/>
                <person name="Lucier A."/>
                <person name="Lucier R.L."/>
                <person name="Ma J."/>
                <person name="Madu R.C."/>
                <person name="Mapua P."/>
                <person name="Martindale A.D."/>
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                <person name="Mendez S."/>
                <person name="Mercado C."/>
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                <person name="Miner Z.L."/>
                <person name="Minja E."/>
                <person name="Mitchell T."/>
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                <person name="Munidasa M."/>
                <person name="Ngo R.N."/>
                <person name="Nguyen N.B."/>
                <person name="Nickerson E."/>
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                <person name="Nwokenkwo S."/>
                <person name="Obregon M."/>
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                <person name="Pu L.-L."/>
                <person name="Puazo M."/>
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                <person name="Rabata D."/>
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                <person name="Sonaike T."/>
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                <person name="Svetz L.A."/>
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                <person name="Trejos Z.Y."/>
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                <person name="Ukegbu O.N."/>
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            </authorList>
            <dbReference type="PubMed" id="16541075"/>
            <dbReference type="DOI" id="10.1038/nature04569"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="4">
        <citation type="submission" date="2005-07" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
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            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT GLY-84</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT GLY-84</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2004" name="Proc. Natl. Acad. Sci. U.S.A." volume="101" first="11773" last="11778">
            <title>In vivo identification of genes that modify ether-a-go-go-related gene activity in Caenorhabditis elegans may also affect human cardiac arrhythmia.</title>
            <authorList>
                <person name="Petersen C.I."/>
                <person name="McFarland T.R."/>
                <person name="Stepanovic S.Z."/>
                <person name="Yang P."/>
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            </authorList>
            <dbReference type="PubMed" id="15280551"/>
            <dbReference type="DOI" id="10.1073/pnas.0306005101"/>
        </citation>
        <scope>VARIANT VAL-446</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2011" name="J. Mol. Cell. Cardiol." volume="50" first="50" last="57">
            <title>A KCR1 variant implicated in susceptibility to the long QT syndrome.</title>
            <authorList>
                <person name="Hayashi K."/>
                <person name="Fujino N."/>
                <person name="Ino H."/>
                <person name="Uchiyama K."/>
                <person name="Sakata K."/>
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                <person name="Sakamoto Y."/>
                <person name="Tsubokawa T."/>
                <person name="Hodatsu A."/>
                <person name="Yasuda T."/>
                <person name="Kanaya H."/>
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                <person name="Higashida H."/>
                <person name="Yamagishi M."/>
            </authorList>
            <dbReference type="PubMed" id="20950623"/>
            <dbReference type="DOI" id="10.1016/j.yjmcc.2010.10.007"/>
        </citation>
        <scope>VARIANT ASP-33</scope>
        <scope>CHARACTERIZATION OF VARIANT ASP-33</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>PATHWAY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <comment type="function">
        <text evidence="6">Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation. The assembly of dolichol-linked oligosaccharides begins on the cytosolic side of the endoplasmic reticulum membrane and finishes in its lumen. The sequential addition of sugars to dolichol pyrophosphate produces dolichol-linked oligosaccharides containing fourteen sugars, including two GlcNAcs, nine mannoses and three glucoses. Once assembled, the oligosaccharide is transferred from the lipid to nascent proteins by oligosaccharyltransferases. In the lumen of the endoplasmic reticulum, adds the third and last glucose residue from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide intermediate Glc(2)Man(9)GlcNAc(2)-PP-Dol to produce Glc(3)Man(9)GlcNAc(2)-PP-Dol.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="6">
            <text>an alpha-D-Glc-(1-&gt;3)-alpha-D-Glc-(1-&gt;3)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl beta-D-glucosyl phosphate = a alpha-D-Glc-(1-&gt;2)-alpha-D-Glc-(1-&gt;3)-alpha-D-Glc-(1-&gt;3)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;3)-[alpha-D-Man-(1-&gt;2)-alpha-D-Man-(1-&gt;6)]-alpha-D-Man-(1-&gt;6)]-beta-D-Man-(1-&gt;4)-beta-D-GlcNAc-(1-&gt;4)-alpha-D-GlcNAc-diphospho-di-trans,poly-cis-dolichol + a di-trans,poly-cis-dolichyl phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:29543"/>
            <dbReference type="Rhea" id="RHEA-COMP:19498"/>
            <dbReference type="Rhea" id="RHEA-COMP:19502"/>
            <dbReference type="Rhea" id="RHEA-COMP:19512"/>
            <dbReference type="Rhea" id="RHEA-COMP:19522"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:57525"/>
            <dbReference type="ChEBI" id="CHEBI:57683"/>
            <dbReference type="ChEBI" id="CHEBI:132522"/>
            <dbReference type="ChEBI" id="CHEBI:132523"/>
            <dbReference type="EC" id="2.4.1.256"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="6">
            <dbReference type="Rhea" id="RHEA:29544"/>
        </physiologicalReaction>
    </comment>
    <comment type="pathway">
        <text evidence="6">Protein modification; protein glycosylation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1">Interacts with KCNH1; may regulate KCNH1, possibly by regulating its N-glycosylation. Interacts with KCNH2; may reduce KCNH2 sensitivity to classic proarrhythmic drug blockade, possibly by regulating its N-glycosylation.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18075734">
            <id>Q5I7T1</id>
        </interactant>
        <interactant intactId="EBI-7797864">
            <id>P11912</id>
            <label>CD79A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-18075734">
            <id>Q5I7T1</id>
        </interactant>
        <interactant intactId="EBI-18037857">
            <id>Q3SXP7</id>
            <label>SHISAL1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="6">Endoplasmic reticulum membrane</location>
            <topology evidence="2">Multi-pass membrane protein</topology>
        </subcellularLocation>
        <text evidence="1">Also detected at the plasma membrane.</text>
    </comment>
    <comment type="tissue specificity">
        <text evidence="3">Highly expressed in heart, placenta, liver, kidney and pancreas. Weakly expressed in lung, skeletal muscle and brain.</text>
    </comment>
    <comment type="similarity">
        <text evidence="9">Belongs to the ALG10 glucosyltransferase family.</text>
    </comment>
    <dbReference type="EC" id="2.4.1.256" evidence="6"/>
    <dbReference type="EMBL" id="AY845858">
        <property type="protein sequence ID" value="AAW31756.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC117372">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471111">
        <property type="protein sequence ID" value="EAW57795.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137413">
        <property type="protein sequence ID" value="AAI37414.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC137414">
        <property type="protein sequence ID" value="AAI37415.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS31772.1"/>
    <dbReference type="RefSeq" id="NP_001013642.2">
        <property type="nucleotide sequence ID" value="NM_001013620.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5I7T1"/>
    <dbReference type="BioGRID" id="126840">
        <property type="interactions" value="49"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5I7T1">
        <property type="interactions" value="2237"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5I7T1">
        <property type="interactions" value="13"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000310120"/>
    <dbReference type="GlyGen" id="Q5I7T1">
        <property type="glycosylation" value="1 site, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5I7T1"/>
    <dbReference type="PhosphoSitePlus" id="Q5I7T1"/>
    <dbReference type="SwissPalm" id="Q5I7T1"/>
    <dbReference type="BioMuta" id="ALG10B"/>
    <dbReference type="DMDM" id="296434391"/>
    <dbReference type="jPOST" id="Q5I7T1"/>
    <dbReference type="MassIVE" id="Q5I7T1"/>
    <dbReference type="PaxDb" id="9606-ENSP00000310120"/>
    <dbReference type="PeptideAtlas" id="Q5I7T1"/>
    <dbReference type="ProteomicsDB" id="62974"/>
    <dbReference type="Pumba" id="Q5I7T1"/>
    <dbReference type="Antibodypedia" id="55463">
        <property type="antibodies" value="74 antibodies from 13 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="144245"/>
    <dbReference type="Ensembl" id="ENST00000308742.9">
        <property type="protein sequence ID" value="ENSP00000310120.4"/>
        <property type="gene ID" value="ENSG00000175548.9"/>
    </dbReference>
    <dbReference type="GeneID" id="144245"/>
    <dbReference type="KEGG" id="hsa:144245"/>
    <dbReference type="MANE-Select" id="ENST00000308742.9">
        <property type="protein sequence ID" value="ENSP00000310120.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001013620.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001013642.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001rln.5">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:31088"/>
    <dbReference type="ClinPGx" id="PA134936082"/>
    <dbReference type="CTD" id="144245"/>
    <dbReference type="DisGeNET" id="144245"/>
    <dbReference type="GeneCards" id="ALG10B"/>
    <dbReference type="HGNC" id="HGNC:31088">
        <property type="gene designation" value="ALG10B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000175548">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="ALG10B"/>
    <dbReference type="MIM" id="603313">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000175548"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000175548"/>
    <dbReference type="eggNOG" id="KOG2642">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00390000012906"/>
    <dbReference type="HOGENOM" id="CLU_017053_1_0_1"/>
    <dbReference type="InParanoid" id="Q5I7T1"/>
    <dbReference type="OMA" id="FPINWNT"/>
    <dbReference type="OrthoDB" id="4769at2759"/>
    <dbReference type="PAN-GO" id="Q5I7T1">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5I7T1"/>
    <dbReference type="PathwayCommons" id="Q5I7T1"/>
    <dbReference type="Reactome" id="R-HSA-446193">
        <property type="pathway name" value="Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q5I7T1"/>
    <dbReference type="UniPathway" id="UPA00378"/>
    <dbReference type="Agora" id="ENSG00000175548"/>
    <dbReference type="BioGRID-ORCS" id="144245">
        <property type="hits" value="116 hits in 1082 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="ALG10B">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="144245"/>
    <dbReference type="Pharos" id="Q5I7T1">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5I7T1"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 12"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5I7T1">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000175548">
        <property type="expression patterns" value="Expressed in calcaneal tendon and 159 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q5I7T1">
        <property type="expression patterns" value="baseline and differential"/>
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        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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        <property type="term" value="C:endoplasmic reticulum membrane"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="UniProtKB"/>
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        <property type="term" value="C:lumenal side of endoplasmic reticulum membrane"/>
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        <property type="term" value="F:dolichyl pyrophosphate Glc2Man9GlcNAc2 alpha-1,2-glucosyltransferase activity"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:dolichol-linked oligosaccharide biosynthetic process"/>
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        <property type="project" value="UniProtKB"/>
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        <property type="term" value="P:protein N-linked glycosylation"/>
        <property type="evidence" value="ECO:0000316"/>
        <property type="project" value="UniProtKB"/>
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        <property type="entry name" value="Alg10"/>
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        <property type="entry name" value="ALPHA-1,2-GLUCOSYLTRANSFERASE ALG10"/>
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    <dbReference type="PANTHER" id="PTHR12989:SF12">
        <property type="entry name" value="DOL-P-GLC:GLC(2)MAN(9)GLCNAC(2)-PP-DOL ALPHA-1,2-GLUCOSYLTRANSFERASE-RELATED"/>
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        <property type="entry name" value="DIE2_ALG10"/>
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    <dbReference type="PIRSF" id="PIRSF028810">
        <property type="entry name" value="Alpha1_2_glucosyltferase_Alg10"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0256">Endoplasmic reticulum</keyword>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-0472">Membrane</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <keyword id="KW-0812">Transmembrane</keyword>
    <keyword id="KW-1133">Transmembrane helix</keyword>
    <feature type="chain" id="PRO_0000215448" description="Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase B">
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            <begin position="1"/>
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    <feature type="transmembrane region" description="Helical" evidence="2">
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            <begin position="7"/>
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            <begin position="176"/>
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            <begin position="366"/>
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        <location>
            <begin position="393"/>
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    <feature type="topological domain" description="Extracellular" evidence="2">
        <location>
            <begin position="414"/>
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            <begin position="437"/>
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        <location>
            <begin position="458"/>
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    <feature type="sequence variant" id="VAR_089086" description="Found in a patient with ventricular fibrillation and QT prolongation; uncertain significance; dbSNP:rs188043534." evidence="6">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="33"/>
        </location>
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    <feature type="sequence variant" id="VAR_048217" description="In dbSNP:rs6582584." evidence="3 5 7">
        <original>A</original>
        <variation>G</variation>
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            <position position="84"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_061002" description="In dbSNP:rs57963306.">
        <original>S</original>
        <variation>N</variation>
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            <position position="383"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_023753" description="In dbSNP:rs61730283." evidence="4">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="446"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="O88788"/>
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    </evidence>
    <evidence type="ECO:0000255" key="2"/>
    <evidence type="ECO:0000269" key="3">
        <source>
            <dbReference type="PubMed" id="14525949"/>
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            <dbReference type="PubMed" id="15280551"/>
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            <dbReference type="PubMed" id="15489334"/>
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            <dbReference type="PubMed" id="20950623"/>
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        <source ref="4"/>
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    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14525949"/>
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    <evidence type="ECO:0000305" key="10">
        <source>
            <dbReference type="PubMed" id="14525949"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="11">
        <source>
            <dbReference type="HGNC" id="HGNC:31088"/>
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    </evidence>
    <sequence length="473" mass="55448" checksum="47D0CF7B6C84B8EC" modified="2010-05-18" version="2">MAQLEGYCFSAALSCTFLVSCLLFSAFSRALREPYMDEIFHLPQAQRYCEGHFSLSQWDPMITTLPGLYLVSVGVVKPAIWIFAWSEHVVCSIGMLRFVNLLFSVGNFYLLYLLFHKVQPRNKAASSIQRVLSTLTLAVFPTLYFFNFLYYTEAGSMFFTLFAYLMCLYGNHKTSAFLGFCGFMFRQTNIIWAVFCAGNVIAQKLTEAWKTELQKKEDRLPPIKGPFAEFRKILQFLLAYSMSFKNLSMLFCLTWPYILLGFLFCAFVVVNGGIVIGDRSSHEACLHFPQLFYFFSFTLFFSFPHLLSPSKIKTFLSLVWKHGILFLVVTLVSVFLVWKFTYAHKYLLADNRHYTFYVWKRVFQRYAILKYLLVPAYIFAGWSIADSLKSKPIFWNLMFFICLFIVIVPQKLLEFRYFILPYVIYRLNITLPPTSRLVCELSCYAIVNFITFYIFLNKTFQWPNSQDIQRFMW</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-04-29" modified="2026-01-28" version="184" xmlns="https://uniprot.org/uniprot">
    <accession>Q9BVQ7</accession>
    <accession>C9JHR5</accession>
    <accession>Q9H8W7</accession>
    <accession>Q9HA41</accession>
    <name>AFG2B_HUMAN</name>
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        <recommendedName>
            <fullName>ATPase family gene 2 protein homolog B</fullName>
            <ecNumber evidence="2">3.6.4.10</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>AFG2 AAA ATPase homolog B</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="13">Ribosome biogenesis protein SPATA5L1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Spermatogenesis-associated protein 5-like protein 1</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15" type="primary">AFG2B</name>
        <name evidence="12" type="synonym">SPATA5L1</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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            <title>Complete sequencing and characterization of 21,243 full-length human cDNAs.</title>
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                <person name="Moriya S."/>
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                <person name="Terashima Y."/>
                <person name="Suzuki O."/>
                <person name="Nakagawa S."/>
                <person name="Senoh A."/>
                <person name="Mizoguchi H."/>
                <person name="Goto Y."/>
                <person name="Shimizu F."/>
                <person name="Wakebe H."/>
                <person name="Hishigaki H."/>
                <person name="Watanabe T."/>
                <person name="Sugiyama A."/>
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                <person name="Kawakami B."/>
                <person name="Yamazaki M."/>
                <person name="Watanabe K."/>
                <person name="Kumagai A."/>
                <person name="Itakura S."/>
                <person name="Fukuzumi Y."/>
                <person name="Fujimori Y."/>
                <person name="Komiyama M."/>
                <person name="Tashiro H."/>
                <person name="Tanigami A."/>
                <person name="Fujiwara T."/>
                <person name="Ono T."/>
                <person name="Yamada K."/>
                <person name="Fujii Y."/>
                <person name="Ozaki K."/>
                <person name="Hirao M."/>
                <person name="Ohmori Y."/>
                <person name="Kawabata A."/>
                <person name="Hikiji T."/>
                <person name="Kobatake N."/>
                <person name="Inagaki H."/>
                <person name="Ikema Y."/>
                <person name="Okamoto S."/>
                <person name="Okitani R."/>
                <person name="Kawakami T."/>
                <person name="Noguchi S."/>
                <person name="Itoh T."/>
                <person name="Shigeta K."/>
                <person name="Senba T."/>
                <person name="Matsumura K."/>
                <person name="Nakajima Y."/>
                <person name="Mizuno T."/>
                <person name="Morinaga M."/>
                <person name="Sasaki M."/>
                <person name="Togashi T."/>
                <person name="Oyama M."/>
                <person name="Hata H."/>
                <person name="Watanabe M."/>
                <person name="Komatsu T."/>
                <person name="Mizushima-Sugano J."/>
                <person name="Satoh T."/>
                <person name="Shirai Y."/>
                <person name="Takahashi Y."/>
                <person name="Nakagawa K."/>
                <person name="Okumura K."/>
                <person name="Nagase T."/>
                <person name="Nomura N."/>
                <person name="Kikuchi H."/>
                <person name="Masuho Y."/>
                <person name="Yamashita R."/>
                <person name="Nakai K."/>
                <person name="Yada T."/>
                <person name="Nakamura Y."/>
                <person name="Ohara O."/>
                <person name="Isogai T."/>
                <person name="Sugano S."/>
            </authorList>
            <dbReference type="PubMed" id="14702039"/>
            <dbReference type="DOI" id="10.1038/ng1285"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3)</scope>
        <scope>VARIANT GLN-252</scope>
        <source>
            <tissue>Mammary gland</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2006" name="Nature" volume="440" first="671" last="675">
            <title>Analysis of the DNA sequence and duplication history of human chromosome 15.</title>
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                <person name="Garber M."/>
                <person name="Sharpe T."/>
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                <person name="Rowen L."/>
                <person name="O'Neill K."/>
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                <person name="Dors M."/>
                <person name="Eichler E.E."/>
                <person name="Engels R."/>
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                <person name="Nesbitt R."/>
                <person name="Nicol R."/>
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                <person name="Ratcliffe A."/>
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                <person name="Stewart S."/>
                <person name="Sougnez C."/>
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            </authorList>
            <dbReference type="PubMed" id="16572171"/>
            <dbReference type="DOI" id="10.1038/nature04601"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="3">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
        <scope>VARIANT GLN-252</scope>
        <source>
            <tissue>Cervix</tissue>
        </source>
    </reference>
    <reference key="4">
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            <title>EML3 is a nuclear microtubule-binding protein required for the correct alignment of chromosomes in metaphase.</title>
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                <person name="Tegha-Dunghu J."/>
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                <person name="Krause R."/>
                <person name="Erfle H."/>
                <person name="Walter T."/>
                <person name="Held M."/>
                <person name="Rogers P."/>
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                <person name="Ruppert T."/>
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                <person name="Gruss O.J."/>
            </authorList>
            <dbReference type="PubMed" id="18445686"/>
            <dbReference type="DOI" id="10.1242/jcs.019174"/>
        </citation>
        <scope>SUBCELLULAR LOCATION</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="6">
        <citation type="journal article" date="2012" name="Proc. Natl. Acad. Sci. U.S.A." volume="109" first="12449" last="12454">
            <title>N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.</title>
            <authorList>
                <person name="Van Damme P."/>
                <person name="Lasa M."/>
                <person name="Polevoda B."/>
                <person name="Gazquez C."/>
                <person name="Elosegui-Artola A."/>
                <person name="Kim D.S."/>
                <person name="De Juan-Pardo E."/>
                <person name="Demeyer K."/>
                <person name="Hole K."/>
                <person name="Larrea E."/>
                <person name="Timmerman E."/>
                <person name="Prieto J."/>
                <person name="Arnesen T."/>
                <person name="Sherman F."/>
                <person name="Gevaert K."/>
                <person name="Aldabe R."/>
            </authorList>
            <dbReference type="PubMed" id="22814378"/>
            <dbReference type="DOI" id="10.1073/pnas.1210303109"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2021" name="Am. J. Hum. Genet." volume="108" first="2006" last="2016">
            <title>Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.</title>
            <authorList>
                <person name="Richard E.M."/>
                <person name="Bakhtiari S."/>
                <person name="Marsh A.P.L."/>
                <person name="Kaiyrzhanov R."/>
                <person name="Wagner M."/>
                <person name="Shetty S."/>
                <person name="Pagnozzi A."/>
                <person name="Nordlie S.M."/>
                <person name="Guida B.S."/>
                <person name="Cornejo P."/>
                <person name="Magee H."/>
                <person name="Liu J."/>
                <person name="Norton B.Y."/>
                <person name="Webster R.I."/>
                <person name="Worgan L."/>
                <person name="Hakonarson H."/>
                <person name="Li J."/>
                <person name="Guo Y."/>
                <person name="Jain M."/>
                <person name="Blesson A."/>
                <person name="Rodan L.H."/>
                <person name="Abbott M.A."/>
                <person name="Comi A."/>
                <person name="Cohen J.S."/>
                <person name="Alhaddad B."/>
                <person name="Meitinger T."/>
                <person name="Lenz D."/>
                <person name="Ziegler A."/>
                <person name="Kotzaeridou U."/>
                <person name="Brunet T."/>
                <person name="Chassevent A."/>
                <person name="Smith-Hicks C."/>
                <person name="Ekstein J."/>
                <person name="Weiden T."/>
                <person name="Hahn A."/>
                <person name="Zharkinbekova N."/>
                <person name="Turnpenny P."/>
                <person name="Tucci A."/>
                <person name="Yelton M."/>
                <person name="Horvath R."/>
                <person name="Gungor S."/>
                <person name="Hiz S."/>
                <person name="Oktay Y."/>
                <person name="Lochmuller H."/>
                <person name="Zollino M."/>
                <person name="Morleo M."/>
                <person name="Marangi G."/>
                <person name="Nigro V."/>
                <person name="Torella A."/>
                <person name="Pinelli M."/>
                <person name="Amenta S."/>
                <person name="Husain R.A."/>
                <person name="Grossmann B."/>
                <person name="Rapp M."/>
                <person name="Steen C."/>
                <person name="Marquardt I."/>
                <person name="Grimmel M."/>
                <person name="Grasshoff U."/>
                <person name="Korenke G.C."/>
                <person name="Owczarek-Lipska M."/>
                <person name="Neidhardt J."/>
                <person name="Radio F.C."/>
                <person name="Mancini C."/>
                <person name="Claps Sepulveda D.J."/>
                <person name="McWalter K."/>
                <person name="Begtrup A."/>
                <person name="Crunk A."/>
                <person name="Guillen Sacoto M.J."/>
                <person name="Person R."/>
                <person name="Schnur R.E."/>
                <person name="Mancardi M.M."/>
                <person name="Kreuder F."/>
                <person name="Striano P."/>
                <person name="Zara F."/>
                <person name="Chung W.K."/>
                <person name="Marks W.A."/>
                <person name="van Eyk C.L."/>
                <person name="Webber D.L."/>
                <person name="Corbett M.A."/>
                <person name="Harper K."/>
                <person name="Berry J.G."/>
                <person name="MacLennan A.H."/>
                <person name="Gecz J."/>
                <person name="Tartaglia M."/>
                <person name="Salpietro V."/>
                <person name="Christodoulou J."/>
                <person name="Kaslin J."/>
                <person name="Padilla-Lopez S."/>
                <person name="Bilguvar K."/>
                <person name="Munchau A."/>
                <person name="Ahmed Z.M."/>
                <person name="Hufnagel R.B."/>
                <person name="Fahey M.C."/>
                <person name="Maroofian R."/>
                <person name="Houlden H."/>
                <person name="Sticht H."/>
                <person name="Mane S.M."/>
                <person name="Rad A."/>
                <person name="Vona B."/>
                <person name="Jin S.C."/>
                <person name="Haack T.B."/>
                <person name="Makowski C."/>
                <person name="Hirsch Y."/>
                <person name="Riazuddin S."/>
                <person name="Kruer M.C."/>
            </authorList>
            <dbReference type="PubMed" id="34626583"/>
            <dbReference type="DOI" id="10.1016/j.ajhg.2021.08.003"/>
        </citation>
        <scope>INVOLVEMENT IN DFNB119</scope>
        <scope>INVOLVEMENT IN NEDHLS</scope>
        <scope>VARIANTS DFNB119 VAL-176 AND MET-466</scope>
        <scope>VARIANTS NEDHLS ALA-26; GLY-29; PRO-41; TRP-64; TYR-66; LEU-71; HIS-172; GLU-245; SER-360; GLU-364; ILE-400; PRO-438; ASP-519; SER-561; 609-SER--ILE-753 DEL; 640-ARG--ILE-753 DEL; LYS-658; ARG-669 AND VAL-689</scope>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
    <reference key="8">
        <citation type="journal article" date="2022" name="Cell Rep." volume="38" first="110597" last="110597">
            <title>Labeling of heterochronic ribosomes reveals C1ORF109 and SPATA5 control a late step in human ribosome assembly.</title>
            <authorList>
                <person name="Ni C."/>
                <person name="Schmitz D.A."/>
                <person name="Lee J."/>
                <person name="Pawlowski K."/>
                <person name="Wu J."/>
                <person name="Buszczak M."/>
            </authorList>
            <dbReference type="PubMed" id="35354024"/>
            <dbReference type="DOI" id="10.1016/j.celrep.2022.110597"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>INTERACTION WITH AIRIM</scope>
        <scope>INTERACTION WITH PRE-60S RIBOSOMAL PARTICLES</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2024" name="Cell" volume="0" first="0" last="0">
            <title>The SPATA5-SPATA5L1 ATPase complex directs replisome proteostasis to ensure genome integrity.</title>
            <authorList>
                <person name="Krishnamoorthy V."/>
                <person name="Foglizzo M."/>
                <person name="Dilley R.L."/>
                <person name="Wu A."/>
                <person name="Datta A."/>
                <person name="Dutta P."/>
                <person name="Campbell L.J."/>
                <person name="Degtjarik O."/>
                <person name="Musgrove L.J."/>
                <person name="Calabrese A.N."/>
                <person name="Zeqiraj E."/>
                <person name="Greenberg R.A."/>
            </authorList>
            <dbReference type="PubMed" id="38554706"/>
            <dbReference type="DOI" id="10.1016/j.cell.2024.03.002"/>
        </citation>
        <scope>FUNCTION</scope>
        <scope>SUBUNIT</scope>
        <scope>CHARACTERIZATION OF VARIANT DFNB119 MET-466</scope>
        <scope>CHARACTERIZATION OF VARIANTS NEDHLS PRO-41; TRP-64; TYR-66; GLU-245 AND VAL-689</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <comment type="function">
        <text evidence="9 10">ATP-dependent chaperone part of the 55LCC heterohexameric ATPase complex which is chromatin-associated and promotes replisome proteostasis to maintain replication fork progression and genome stability. Required for replication fork progression, sister chromatid cohesion, and chromosome stability. The ATPase activity is specifically enhanced by replication fork DNA and is coupled to cysteine protease-dependent cleavage of replisome substrates in response to replication fork damage. Uses ATPase activity to process replisome substrates in S-phase, facilitating their proteolytic turnover from chromatin to ensure DNA replication and mitotic fidelity (PubMed:38554706). Plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="14">
            <text>ATP + H2O = ADP + phosphate + H(+)</text>
            <dbReference type="Rhea" id="RHEA:13065"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:43474"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="3.6.4.10"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="14">
            <dbReference type="Rhea" id="RHEA:13066"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="10">In the context of 55LCC heterohexameric ATPase complex, the ATPase activity is stimulated by DNA binding and inhibited in presence of RNA.</text>
    </comment>
    <comment type="subunit">
        <text evidence="9 10">Part of the 55LCC heterohexameric ATPase complex composed at least of AIRIM, AFG2A, AFG2B and CINP (PubMed:35354024, PubMed:38554706). Associates with pre-60S ribosomal particles (PubMed:35354024).</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7950854">
            <id>Q9BVQ7</id>
        </interactant>
        <interactant intactId="EBI-3184062">
            <id>Q8NB90</id>
            <label>AFG2A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>14</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7950854">
            <id>Q9BVQ7</id>
        </interactant>
        <interactant intactId="EBI-7950854">
            <id>Q9BVQ7</id>
            <label>AFG2B</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
            <location evidence="7">Cytoskeleton</location>
            <location evidence="7">Spindle</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="1">Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q9BVQ7-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q9BVQ7-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_033052 VSP_033053"/>
        </isoform>
        <isoform>
            <id>Q9BVQ7-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_033050 VSP_033051"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="8">Expressed in both neurons and glia during embryonic and adult stages of brain development.</text>
    </comment>
    <comment type="disease" evidence="8 10">
        <disease id="DI-06271">
            <name>Deafness, autosomal recessive, 119</name>
            <acronym>DFNB119</acronym>
            <description>A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.</description>
            <dbReference type="MIM" id="619615"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="disease" evidence="8 10">
        <disease id="DI-06272">
            <name>Neurodevelopmental disorder with hearing loss and spasticity</name>
            <acronym>NEDHLS</acronym>
            <description>An autosomal recessive neurodevelopmental disorder characterized by hearing loss, global developmental delay, impaired intellectual development, hypotonia, spastic-dystonic cerebral palsy, focal or generalized epilepsy, and microcephaly.</description>
            <dbReference type="MIM" id="619616"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="similarity">
        <text evidence="13">Belongs to the AAA ATPase family. AFG2 subfamily.</text>
    </comment>
    <dbReference type="EC" id="3.6.4.10" evidence="2"/>
    <dbReference type="EMBL" id="AK022348">
        <property type="protein sequence ID" value="BAB14017.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK023232">
        <property type="protein sequence ID" value="BAB14482.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK291457">
        <property type="protein sequence ID" value="BAF84146.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025580">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC090527">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC000981">
        <property type="protein sequence ID" value="AAH00981.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS10123.1">
        <molecule id="Q9BVQ7-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS81877.1">
        <molecule id="Q9BVQ7-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001310569.1">
        <molecule id="Q9BVQ7-2"/>
        <property type="nucleotide sequence ID" value="NM_001323640.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_076968.2">
        <molecule id="Q9BVQ7-1"/>
        <property type="nucleotide sequence ID" value="NM_024063.3"/>
    </dbReference>
    <dbReference type="PDB" id="8RHN">
        <property type="method" value="EM"/>
        <property type="resolution" value="4.50 A"/>
        <property type="chains" value="I/J/O/P=1-753"/>
    </dbReference>
    <dbReference type="PDB" id="9LGO">
        <property type="method" value="EM"/>
        <property type="resolution" value="3.51 A"/>
        <property type="chains" value="C/F=1-749"/>
    </dbReference>
    <dbReference type="PDBsum" id="8RHN"/>
    <dbReference type="PDBsum" id="9LGO"/>
    <dbReference type="AlphaFoldDB" id="Q9BVQ7"/>
    <dbReference type="EMDB" id="EMD-19177"/>
    <dbReference type="EMDB" id="EMD-63069"/>
    <dbReference type="SMR" id="Q9BVQ7"/>
    <dbReference type="BioGRID" id="122496">
        <property type="interactions" value="130"/>
    </dbReference>
    <dbReference type="ComplexPortal" id="CPX-9182">
        <property type="entry name" value="SPATA5-SPATA5L1 ATPase complex"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q9BVQ7">
        <property type="interactions" value="856"/>
    </dbReference>
    <dbReference type="IntAct" id="Q9BVQ7">
        <property type="interactions" value="1306"/>
    </dbReference>
    <dbReference type="MINT" id="Q9BVQ7"/>
    <dbReference type="STRING" id="9606.ENSP00000305494"/>
    <dbReference type="GlyGen" id="Q9BVQ7">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q9BVQ7"/>
    <dbReference type="PhosphoSitePlus" id="Q9BVQ7"/>
    <dbReference type="SwissPalm" id="Q9BVQ7"/>
    <dbReference type="BioMuta" id="SPATA5L1"/>
    <dbReference type="DMDM" id="292495038"/>
    <dbReference type="jPOST" id="Q9BVQ7"/>
    <dbReference type="MassIVE" id="Q9BVQ7"/>
    <dbReference type="PaxDb" id="9606-ENSP00000305494"/>
    <dbReference type="PeptideAtlas" id="Q9BVQ7"/>
    <dbReference type="ProteomicsDB" id="79225">
        <molecule id="Q9BVQ7-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="79226">
        <molecule id="Q9BVQ7-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="79227">
        <molecule id="Q9BVQ7-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q9BVQ7"/>
    <dbReference type="Antibodypedia" id="24428">
        <property type="antibodies" value="110 antibodies from 22 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="79029"/>
    <dbReference type="Ensembl" id="ENST00000305560.11">
        <molecule id="Q9BVQ7-1"/>
        <property type="protein sequence ID" value="ENSP00000305494.6"/>
        <property type="gene ID" value="ENSG00000171763.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000531970.5">
        <molecule id="Q9BVQ7-2"/>
        <property type="protein sequence ID" value="ENSP00000436823.1"/>
        <property type="gene ID" value="ENSG00000171763.21"/>
    </dbReference>
    <dbReference type="GeneID" id="79029"/>
    <dbReference type="KEGG" id="hsa:79029"/>
    <dbReference type="MANE-Select" id="ENST00000305560.11">
        <property type="protein sequence ID" value="ENSP00000305494.6"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_024063.3"/>
        <property type="RefSeq protein sequence ID" value="NP_076968.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001zve.4">
        <molecule id="Q9BVQ7-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:28762"/>
    <dbReference type="ClinPGx" id="PA134923477"/>
    <dbReference type="CTD" id="79029"/>
    <dbReference type="DisGeNET" id="79029"/>
    <dbReference type="GeneCards" id="AFG2B"/>
    <dbReference type="HGNC" id="HGNC:28762">
        <property type="gene designation" value="AFG2B"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000171763">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AFG2B"/>
    <dbReference type="MIM" id="619578">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="MIM" id="619615">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="MIM" id="619616">
        <property type="type" value="phenotype"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000171763"/>
    <dbReference type="Orphanet" id="90636">
        <property type="disease" value="Rare autosomal recessive non-syndromic sensorineural deafness type DFNB"/>
    </dbReference>
    <dbReference type="Orphanet" id="659975">
        <property type="disease" value="Sensorineural hearing loss-spastic quadriplegia-intellectual disability syndrome"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000171763"/>
    <dbReference type="eggNOG" id="KOG0730">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000160700"/>
    <dbReference type="HOGENOM" id="CLU_000688_12_2_1"/>
    <dbReference type="InParanoid" id="Q9BVQ7"/>
    <dbReference type="OMA" id="DRHIYVA"/>
    <dbReference type="OrthoDB" id="27435at2759"/>
    <dbReference type="PAN-GO" id="Q9BVQ7">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q9BVQ7"/>
    <dbReference type="PathwayCommons" id="Q9BVQ7"/>
    <dbReference type="SignaLink" id="Q9BVQ7"/>
    <dbReference type="Agora" id="ENSG00000171763"/>
    <dbReference type="BioGRID-ORCS" id="79029">
        <property type="hits" value="707 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="SPATA5L1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="79029"/>
    <dbReference type="Pharos" id="Q9BVQ7">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q9BVQ7"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 15"/>
    </dbReference>
    <dbReference type="RNAct" id="Q9BVQ7">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000171763">
        <property type="expression patterns" value="Expressed in lower esophagus mucosa and 185 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q9BVQ7">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005829">
        <property type="term" value="C:cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005819">
        <property type="term" value="C:spindle"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034098">
        <property type="term" value="C:VCP-NPL4-UFD1 AAA ATPase complex"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005524">
        <property type="term" value="F:ATP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0016887">
        <property type="term" value="F:ATP hydrolysis activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031593">
        <property type="term" value="F:polyubiquitin modification-dependent protein binding"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:1990275">
        <property type="term" value="F:preribosome binding"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0097352">
        <property type="term" value="P:autophagosome maturation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0051228">
        <property type="term" value="P:mitotic spindle disassembly"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043161">
        <property type="term" value="P:proteasome-mediated ubiquitin-dependent protein catabolic process"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0030970">
        <property type="term" value="P:retrograde protein transport, ER to cytosol"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042273">
        <property type="term" value="P:ribosomal large subunit biogenesis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd19511">
        <property type="entry name" value="RecA-like_CDC48_r2-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.8.60:FF:000075">
        <property type="entry name" value="Spermatogenesis-associated protein 5-like protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:001081">
        <property type="entry name" value="Spermatogenesis-associated protein 5-like protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.8.60:FF:000038">
        <property type="entry name" value="spermatogenesis-associated protein 5-like protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.40.50.300:FF:001161">
        <property type="entry name" value="spermatogenesis-associated protein 5-like protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.8.60">
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003593">
        <property type="entry name" value="AAA+_ATPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR050168">
        <property type="entry name" value="AAA_ATPase_domain"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041569">
        <property type="entry name" value="AAA_lid_3"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003959">
        <property type="entry name" value="ATPase_AAA_core"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR003960">
        <property type="entry name" value="ATPase_AAA_CS"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23077">
        <property type="entry name" value="AAA-FAMILY ATPASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23077:SF194">
        <property type="entry name" value="ATPASE FAMILY GENE 2 PROTEIN HOMOLOG B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00004">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17862">
        <property type="entry name" value="AAA_lid_3"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00382">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS00674">
        <property type="entry name" value="AAA"/>
        <property type="match status" value="2"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0067">ATP-binding</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0206">Cytoskeleton</keyword>
    <keyword id="KW-0209">Deafness</keyword>
    <keyword id="KW-0887">Epilepsy</keyword>
    <keyword id="KW-0378">Hydrolase</keyword>
    <keyword id="KW-0991">Intellectual disability</keyword>
    <keyword id="KW-1010">Non-syndromic deafness</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0690">Ribosome biogenesis</keyword>
    <feature type="chain" id="PRO_0000330586" description="ATPase family gene 2 protein homolog B">
        <location>
            <begin position="1"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="region of interest" description="Required for interaction with AFG2A and CINP" evidence="10">
        <location>
            <begin position="1"/>
            <end position="189"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="171"/>
            <end position="203"/>
        </location>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="241"/>
            <end position="248"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>1</label>
        </ligand>
    </feature>
    <feature type="binding site" evidence="3">
        <location>
            <begin position="505"/>
            <end position="512"/>
        </location>
        <ligand>
            <name>ATP</name>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <label>2</label>
        </ligand>
    </feature>
    <feature type="modified residue" description="N-acetylmethionine" evidence="16">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033050" description="In isoform 3." evidence="11">
        <original>VIGTPTLKQRKEILQVITSKMPISSHVD</original>
        <variation>NGLGGFAHCRWNLGRFWRHLAAPEAFAS</variation>
        <location>
            <begin position="365"/>
            <end position="392"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033051" description="In isoform 3." evidence="11">
        <location>
            <begin position="393"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033052" description="In isoform 2." evidence="11">
        <original>EFQEVFNR</original>
        <variation>GKYKELKK</variation>
        <location>
            <begin position="613"/>
            <end position="620"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_033053" description="In isoform 2." evidence="11">
        <location>
            <begin position="621"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086544" description="In NEDHLS." evidence="8">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="26"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086545" description="In NEDHLS; dbSNP:rs2140692680." evidence="8">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="29"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086546" description="In NEDHLS; reduces interaction with AFG2A and CINP; reduces cell viability." evidence="8 10">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="41"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086547" description="In NEDHLS; strongly reduces interaction with AFG2A and CINP; reduces cell viability; dbSNP:rs1212383243." evidence="8 10">
        <original>R</original>
        <variation>W</variation>
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086548" description="In NEDHLS; reduces interaction with AFG2A and CINP; reduces cell viability; dbSNP:rs1220970567." evidence="8 10">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086549" description="In NEDHLS; dbSNP:rs776678464." evidence="8">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048111" description="In dbSNP:rs1153850.">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="119"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086550" description="In NEDHLS; dbSNP:rs765620529." evidence="8">
        <original>P</original>
        <variation>H</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086551" description="In DFNB119; dbSNP:rs145451123." evidence="8">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="176"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086552" description="In NEDHLS; no effect on interaction with AFG2A and CINP; strongly reduces cell viability; dbSNP:rs1230836596." evidence="8 10">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="245"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_059085" description="In dbSNP:rs7182723." evidence="5 6">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="252"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086553" description="In NEDHLS." evidence="8">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="360"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086554" description="In NEDHLS; dbSNP:rs1890180619." evidence="8">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="364"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086555" description="In NEDHLS; dbSNP:rs1372719653." evidence="8">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="400"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086556" description="In NEDHLS; dbSNP:rs1480279583." evidence="8">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="438"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086557" description="In DFNB119; no effect on interaction with AFG2A and CINP; reduces cell viability; dbSNP:rs34675173." evidence="8 10">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="466"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086558" description="In NEDHLS; dbSNP:rs757503048." evidence="8">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="519"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086559" description="In NEDHLS; dbSNP:rs2140721648." evidence="8">
        <original>L</original>
        <variation>S</variation>
        <location>
            <position position="561"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_048112" description="In dbSNP:rs16943025.">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="592"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086560" description="In NEDHLS." evidence="8">
        <location>
            <begin position="609"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086561" description="In NEDHLS." evidence="8">
        <location>
            <begin position="640"/>
            <end position="753"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086562" description="In NEDHLS; dbSNP:rs1890623871." evidence="8">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="658"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086563" description="In NEDHLS; dbSNP:rs1890625577." evidence="8">
        <original>M</original>
        <variation>R</variation>
        <location>
            <position position="669"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_086564" description="In NEDHLS; no effect on interaction with AFG2A and CINP; reduces cell viability; dbSNP:rs777812455." evidence="8 10">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="689"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; BAB14017." evidence="13" ref="1">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="257"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1">
        <source>
            <dbReference type="UniProtKB" id="D4A2B7"/>
        </source>
    </evidence>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="P32794"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3"/>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="18445686"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="34626583"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="35354024"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="38554706"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="12">
        <source>
            <dbReference type="PubMed" id="34626583"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="13"/>
    <evidence type="ECO:0000305" key="14">
        <source>
            <dbReference type="PubMed" id="38554706"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="15">
        <source>
            <dbReference type="HGNC" id="HGNC:28762"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="22814378"/>
        </source>
    </evidence>
    <sequence length="753" mass="80710" checksum="E92A4483681017ED" modified="2010-03-23" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2010-05-18" modified="2026-01-28" version="86" xmlns="https://uniprot.org/uniprot">
    <accession>C9J202</accession>
    <name>AG1L2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative glycosyltransferase ALG1L2</fullName>
            <ecNumber>2.4.1.-</ecNumber>
        </recommendedName>
    </protein>
    <gene>
        <name type="primary">ALG1L2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
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                <person name="Weinstock G."/>
                <person name="Gibbs R.A."/>
            </authorList>
            <dbReference type="PubMed" id="16641997"/>
            <dbReference type="DOI" id="10.1038/nature04728"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="1">Putative glycosyltransferase.</text>
    </comment>
    <comment type="similarity">
        <text evidence="3">Belongs to the glycosyltransferase group 1 family.</text>
    </comment>
    <dbReference type="EC" id="2.4.1.-"/>
    <dbReference type="EMBL" id="AC083906">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001129624.1">
        <property type="nucleotide sequence ID" value="NM_001136152.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="C9J202"/>
    <dbReference type="SMR" id="C9J202"/>
    <dbReference type="BioGRID" id="570052">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000479850"/>
    <dbReference type="iPTMnet" id="C9J202"/>
    <dbReference type="PhosphoSitePlus" id="C9J202"/>
    <dbReference type="BioMuta" id="ALG1L2"/>
    <dbReference type="jPOST" id="C9J202"/>
    <dbReference type="MassIVE" id="C9J202"/>
    <dbReference type="PaxDb" id="9606-ENSP00000479850"/>
    <dbReference type="PeptideAtlas" id="C9J202"/>
    <dbReference type="ProteomicsDB" id="8145"/>
    <dbReference type="Antibodypedia" id="77419">
        <property type="antibodies" value="2 antibodies from 2 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="644974"/>
    <dbReference type="Ensembl" id="ENST00000425059.1">
        <property type="protein sequence ID" value="ENSP00000479850.1"/>
        <property type="gene ID" value="ENSG00000251287.9"/>
    </dbReference>
    <dbReference type="GeneID" id="644974"/>
    <dbReference type="KEGG" id="hsa:644974"/>
    <dbReference type="MANE-Select" id="ENST00000425059.1">
        <property type="protein sequence ID" value="ENSP00000479850.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001136152.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001129624.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc011bld.2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:37258"/>
    <dbReference type="ClinPGx" id="PA165696819"/>
    <dbReference type="CTD" id="644974"/>
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    <dbReference type="GeneCards" id="ALG1L2"/>
    <dbReference type="HGNC" id="HGNC:37258">
        <property type="gene designation" value="ALG1L2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000251287">
        <property type="expression patterns" value="Tissue enhanced (retina)"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000251287"/>
    <dbReference type="eggNOG" id="KOG2941">
        <property type="taxonomic scope" value="Eukaryota"/>
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    <dbReference type="HOGENOM" id="CLU_012079_2_1_1"/>
    <dbReference type="InParanoid" id="C9J202"/>
    <dbReference type="OMA" id="FKEAPLD"/>
    <dbReference type="OrthoDB" id="614844at2759"/>
    <dbReference type="PAN-GO" id="C9J202">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="C9J202"/>
    <dbReference type="Agora" id="ENSG00000251287"/>
    <dbReference type="BioGRID-ORCS" id="644974">
        <property type="hits" value="11 hits in 156 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="644974"/>
    <dbReference type="Pharos" id="C9J202">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:C9J202"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 3"/>
    </dbReference>
    <dbReference type="RNAct" id="C9J202">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000251287">
        <property type="expression patterns" value="Expressed in male germ line stem cell (sensu Vertebrata) in testis and 97 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005783">
        <property type="term" value="C:endoplasmic reticulum"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0000030">
        <property type="term" value="F:mannosyltransferase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.2000">
        <property type="entry name" value="Glycogen Phosphorylase B"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR026051">
        <property type="entry name" value="ALG1-like"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001296">
        <property type="entry name" value="Glyco_trans_1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13036">
        <property type="entry name" value="BETA1,4 MANNOSYLTRANSFERASE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR13036:SF2">
        <property type="entry name" value="GLYCOSYLTRANSFERASE ALG1L2-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00534">
        <property type="entry name" value="Glycos_transf_1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF53756">
        <property type="entry name" value="UDP-Glycosyltransferase/glycogen phosphorylase"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0328">Glycosyltransferase</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0808">Transferase</keyword>
    <feature type="chain" id="PRO_0000393966" description="Putative glycosyltransferase ALG1L2">
        <location>
            <begin position="1"/>
            <end position="215"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="2">
        <location>
            <begin position="40"/>
            <end position="66"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="2">
        <location>
            <begin position="43"/>
            <end position="62"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000256" key="2">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="3"/>
    <sequence length="215" mass="24154" checksum="FE270225343D6A1C" modified="2009-11-03" version="1">MGATAGWAVTVYDKPASFFKEAPLDLQHRLFMKLGSTHSPFRARSEPEDPDTERSAFTERDSGSGLVTRLHERPALLVSSTSWTEFEQLTLDGQNLPSLVCVITGKGPLREYYSRLIHQKHFQHIQVCIPWLEGRGLPPLLGSVDLDVCLDTSSSGLDLPMKVVDMFRCCLPACAVNFKCLHELVKHEENRLVFEDSEELAAQLQYFADAFLKLS</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1999-07-15" modified="2026-01-28" version="229" xmlns="https://uniprot.org/uniprot">
    <accession>Q99490</accession>
    <accession>A8K9F7</accession>
    <accession>F8VVT9</accession>
    <accession>O00578</accession>
    <accession>Q548E0</accession>
    <accession>Q8IWU3</accession>
    <name>AGAP2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2</fullName>
            <shortName>AGAP-2</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-gamma-1</fullName>
            <shortName>Cnt-g1</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>GTP-binding and GTPase-activating protein 2</fullName>
            <shortName>GGAP2</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Phosphatidylinositol 3-kinase enhancer</fullName>
            <shortName>PIKE</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP2</name>
        <name type="synonym">CENTG1</name>
        <name type="synonym">KIAA0167</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <scope>ALTERNATIVE SPLICING (ISOFORM 2)</scope>
        <scope>VARIANT VAL-1124</scope>
    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)</scope>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>FUNCTION</scope>
        <source>
            <tissue>Heart</tissue>
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    </reference>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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    <comment type="function">
        <text evidence="9 10 11 12">GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.</text>
    </comment>
    <comment type="activity regulation">
        <text>GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation.</text>
    </comment>
    <comment type="subunit">
        <text evidence="1 10 11 12">Isoform 1 interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2 (By similarity). Isoform 2 interacts with activated AKT1 in the presence of guanine nucleotides, and with the AP-1 complex.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2361824">
            <id>Q99490</id>
        </interactant>
        <interactant intactId="EBI-475899">
            <id>P06213</id>
            <label>INSR</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7737644">
            <id>Q99490-2</id>
        </interactant>
        <interactant intactId="EBI-749537">
            <id>P42229</id>
            <label>STAT5A</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7737644">
            <id>Q99490-2</id>
        </interactant>
        <interactant intactId="EBI-7737664">
            <id>Q08501</id>
            <label>Prlr</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-7737644">
            <id>Q99490-2</id>
        </interactant>
        <interactant intactId="EBI-617434">
            <id>P42230</id>
            <label>Stat5a</label>
        </interactant>
        <organismsDiffer>true</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 1</molecule>
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location>Nucleus</location>
        </subcellularLocation>
    </comment>
    <comment type="subcellular location">
        <molecule>Isoform 2</molecule>
        <subcellularLocation>
            <location>Cytoplasm</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q99490-1</id>
            <name>1</name>
            <name>PIKE-L</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q99490-2</id>
            <name>2</name>
            <name>PIKE-A</name>
            <sequence type="described" ref="VSP_018531 VSP_018532 VSP_018533"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="9 10 11 12 13">Isoform 1 is brain-specific. Isoform 2 is ubiquitously expressed, with highest levels in brain and heart.</text>
    </comment>
    <comment type="domain">
        <text>G domain binds GTP and has GTPase activity.</text>
    </comment>
    <comment type="domain">
        <text>Arf-GAP domain interacts with G domain and may regulate its GTPase activity.</text>
    </comment>
    <comment type="domain">
        <text>Although both PH domains of isoforms 1 and 2 bind phospholipids, they differently regulate subcellular location. PH domain of isoform 1 directs the protein to the nucleus, but PH domain of isoform 2 directs it to the cytosol. PH domain of isoform 2 is required for binding to AP-1.</text>
    </comment>
    <comment type="PTM">
        <text evidence="15">Isoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN, preventing its apoptotic cleavage.</text>
    </comment>
    <comment type="similarity">
        <text evidence="7 23">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <comment type="sequence caution" evidence="23">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA11484" version="2"/>
        </conflict>
    </comment>
    <comment type="online information" name="Atlas of Genetics and Cytogenetics in Oncology and Haematology">
        <link uri="https://atlasgeneticsoncology.org/gene/44037/CENTG1"/>
    </comment>
    <dbReference type="EMBL" id="U81031">
        <property type="protein sequence ID" value="AAC39522.2"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF384128">
        <property type="protein sequence ID" value="AAO39848.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY128689">
        <property type="protein sequence ID" value="AAM97540.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D79989">
        <property type="protein sequence ID" value="BAA11484.2"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF413077">
        <property type="protein sequence ID" value="AAL04171.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK292672">
        <property type="protein sequence ID" value="BAF85361.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC025165">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471054">
        <property type="protein sequence ID" value="EAW97049.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC028020">
        <property type="protein sequence ID" value="AAH28020.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44932.1">
        <molecule id="Q99490-1"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS8951.1">
        <molecule id="Q99490-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001116244.1">
        <molecule id="Q99490-1"/>
        <property type="nucleotide sequence ID" value="NM_001122772.3"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_055585.1">
        <molecule id="Q99490-2"/>
        <property type="nucleotide sequence ID" value="NM_014770.4"/>
    </dbReference>
    <dbReference type="PDB" id="2BMJ">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="2.10 A"/>
        <property type="chains" value="A=402-577"/>
    </dbReference>
    <dbReference type="PDB" id="2IWR">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.50 A"/>
        <property type="chains" value="A=402-577"/>
    </dbReference>
    <dbReference type="PDB" id="2RLO">
        <property type="method" value="NMR"/>
        <property type="chains" value="A=674-914"/>
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    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="8">
        <location>
            <begin position="775"/>
            <end position="790"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="8">
        <location>
            <begin position="1154"/>
            <end position="1172"/>
        </location>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="413"/>
            <end position="420"/>
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        <ligand>
            <name>GTP</name>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
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    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="457"/>
            <end position="461"/>
        </location>
        <ligand>
            <name>GTP</name>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
        </ligand>
    </feature>
    <feature type="binding site" evidence="4">
        <location>
            <begin position="515"/>
            <end position="518"/>
        </location>
        <ligand>
            <name>GTP</name>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="149"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="24">
        <location>
            <position position="638"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="750"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="752"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="808"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="927"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="2">
        <location>
            <position position="985"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="3">
        <location>
            <position position="1178"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018531" description="In isoform 2." evidence="18 19 20 21 22">
        <location>
            <begin position="1"/>
            <end position="336"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018532" description="In isoform 2." evidence="18 19 20 21 22">
        <original>ASTRDRKMLKFISGIFTKSTGGPPGSGPLPGPPSLSSGSGSRELLGAELRASPK</original>
        <variation>MHAQRQFVVAAVRAEVRRHEVAKQALNRLRKLAERVDDPELQDSIQASLDSIRE</variation>
        <location>
            <begin position="337"/>
            <end position="390"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018533" description="In isoform 2." evidence="18 19 20 21 22">
        <location>
            <begin position="853"/>
            <end position="872"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036183" description="In a breast cancer sample; somatic mutation." evidence="16">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="339"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026438" description="In a glioblastoma cell line." evidence="14">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="455"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_022046" description="In dbSNP:rs2301553.">
        <original>G</original>
        <variation>S</variation>
        <location>
            <position position="507"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026439" description="In a sarcoma cell line." evidence="14">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="518"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026440" description="In a neuroblastoma cell line." evidence="14">
        <original>T</original>
        <variation>I</variation>
        <location>
            <position position="568"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026441" description="In a glioblastoma cell line." evidence="14">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="651"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026442" description="In a glioblastoma cell line." evidence="14">
        <original>E</original>
        <variation>V</variation>
        <location>
            <position position="767"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_036184" description="In a breast cancer sample; somatic mutation." evidence="16">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="816"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026443" description="In a glioblastoma cell line." evidence="14">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="939"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026444" description="In a sarcoma cell line." evidence="14">
        <original>V</original>
        <variation>M</variation>
        <location>
            <position position="947"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_026445" description="In a glioblastoma cell line." evidence="14">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="1022"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_055532" description="In dbSNP:rs238521." evidence="17">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="1124"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="39"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>TG</original>
        <variation>PR</variation>
        <location>
            <begin position="49"/>
            <end position="50"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="85"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="117"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="159"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4; AAM97540." evidence="23" ref="4">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC39522." evidence="23" ref="1">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="1137"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAC39522." evidence="23" ref="1">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="1147"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="406"/>
            <end position="412"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="415"/>
            <end position="417"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="419"/>
            <end position="428"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="438"/>
            <end position="448"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="451"/>
            <end position="459"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="461"/>
            <end position="463"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="466"/>
            <end position="471"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="473"/>
            <end position="480"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="484"/>
            <end position="501"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="503"/>
            <end position="505"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="509"/>
            <end position="515"/>
        </location>
    </feature>
    <feature type="strand" evidence="25">
        <location>
            <begin position="521"/>
            <end position="523"/>
        </location>
    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="529"/>
            <end position="539"/>
        </location>
    </feature>
    <feature type="strand" evidence="26">
        <location>
            <begin position="540"/>
            <end position="548"/>
        </location>
    </feature>
    <feature type="turn" evidence="26">
        <location>
            <begin position="549"/>
            <end position="552"/>
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    </feature>
    <feature type="helix" evidence="26">
        <location>
            <begin position="555"/>
            <end position="574"/>
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    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="677"/>
            <end position="686"/>
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    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="695"/>
            <end position="703"/>
        </location>
    </feature>
    <feature type="turn" evidence="27">
        <location>
            <begin position="704"/>
            <end position="706"/>
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    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="707"/>
            <end position="713"/>
        </location>
    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="714"/>
            <end position="719"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="724"/>
            <end position="730"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="732"/>
            <end position="734"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="878"/>
            <end position="881"/>
        </location>
    </feature>
    <feature type="strand" evidence="27">
        <location>
            <begin position="887"/>
            <end position="894"/>
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    </feature>
    <feature type="helix" evidence="27">
        <location>
            <begin position="895"/>
            <end position="913"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="15">
        <location sequence="Q99490-2">
            <position position="682"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphotyrosine" evidence="15">
        <location sequence="Q99490-2">
            <position position="774"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000250" key="2">
        <source>
            <dbReference type="UniProtKB" id="Q3UHD9"/>
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    </evidence>
    <evidence type="ECO:0000250" key="3">
        <source>
            <dbReference type="UniProtKB" id="Q8CGU4"/>
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    </evidence>
    <evidence type="ECO:0000255" key="4"/>
    <evidence type="ECO:0000255" key="5">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
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    </evidence>
    <evidence type="ECO:0000255" key="6">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
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    </evidence>
    <evidence type="ECO:0000255" key="7">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01402"/>
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    </evidence>
    <evidence type="ECO:0000256" key="8">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
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    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="12640130"/>
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    <evidence type="ECO:0000269" key="10">
        <source>
            <dbReference type="PubMed" id="14761976"/>
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    <evidence type="ECO:0000269" key="11">
        <source>
            <dbReference type="PubMed" id="15118108"/>
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    </evidence>
    <evidence type="ECO:0000269" key="12">
        <source>
            <dbReference type="PubMed" id="16079295"/>
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    </evidence>
    <evidence type="ECO:0000269" key="13">
        <source>
            <dbReference type="PubMed" id="16150119"/>
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    </evidence>
    <evidence type="ECO:0000269" key="14">
        <source>
            <dbReference type="PubMed" id="16263930"/>
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    </evidence>
    <evidence type="ECO:0000269" key="15">
        <source>
            <dbReference type="PubMed" id="16841086"/>
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    </evidence>
    <evidence type="ECO:0000269" key="16">
        <source>
            <dbReference type="PubMed" id="16959974"/>
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    </evidence>
    <evidence type="ECO:0000269" key="17">
        <source>
            <dbReference type="PubMed" id="9192850"/>
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    </evidence>
    <evidence type="ECO:0000303" key="18">
        <source>
            <dbReference type="PubMed" id="12640130"/>
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    </evidence>
    <evidence type="ECO:0000303" key="19">
        <source>
            <dbReference type="PubMed" id="14702039"/>
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    </evidence>
    <evidence type="ECO:0000303" key="20">
        <source>
            <dbReference type="PubMed" id="15489334"/>
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    <evidence type="ECO:0000303" key="21">
        <source>
            <dbReference type="PubMed" id="8724849"/>
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    </evidence>
    <evidence type="ECO:0000303" key="22">
        <source ref="5"/>
    </evidence>
    <evidence type="ECO:0000305" key="23"/>
    <evidence type="ECO:0007744" key="24">
        <source>
            <dbReference type="PubMed" id="19690332"/>
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    <evidence type="ECO:0007829" key="25">
        <source>
            <dbReference type="PDB" id="2BMJ"/>
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    <evidence type="ECO:0007829" key="26">
        <source>
            <dbReference type="PDB" id="2IWR"/>
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    <evidence type="ECO:0007829" key="27">
        <source>
            <dbReference type="PDB" id="2RLO"/>
        </source>
    </evidence>
    <sequence length="1192" mass="124591" checksum="AA90AC711E50A975" modified="2025-06-18" version="3"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-04-08" modified="2026-01-28" version="157" xmlns="https://uniprot.org/uniprot">
    <accession>Q8TF27</accession>
    <accession>B9EIP7</accession>
    <accession>D3DWE4</accession>
    <name>AGA11_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 11</fullName>
            <shortName>AGAP-11</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-gamma-like protein KIAA1975</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP11</name>
        <name type="synonym">KIAA1975</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2001" name="DNA Res." volume="8" first="319" last="327">
            <title>Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.</title>
            <authorList>
                <person name="Nagase T."/>
                <person name="Kikuno R."/>
                <person name="Ohara O."/>
            </authorList>
            <dbReference type="PubMed" id="11853319"/>
            <dbReference type="DOI" id="10.1093/dnares/8.6.319"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <reference key="2">
        <citation type="submission" date="2005-09" db="EMBL/GenBank/DDBJ databases">
            <authorList>
                <person name="Mural R.J."/>
                <person name="Istrail S."/>
                <person name="Sutton G.G."/>
                <person name="Florea L."/>
                <person name="Halpern A.L."/>
                <person name="Mobarry C.M."/>
                <person name="Lippert R."/>
                <person name="Walenz B."/>
                <person name="Shatkay H."/>
                <person name="Dew I."/>
                <person name="Miller J.R."/>
                <person name="Flanigan M.J."/>
                <person name="Edwards N.J."/>
                <person name="Bolanos R."/>
                <person name="Fasulo D."/>
                <person name="Halldorsson B.V."/>
                <person name="Hannenhalli S."/>
                <person name="Turner R."/>
                <person name="Yooseph S."/>
                <person name="Lu F."/>
                <person name="Nusskern D.R."/>
                <person name="Shue B.C."/>
                <person name="Zheng X.H."/>
                <person name="Zhong F."/>
                <person name="Delcher A.L."/>
                <person name="Huson D.H."/>
                <person name="Kravitz S.A."/>
                <person name="Mouchard L."/>
                <person name="Reinert K."/>
                <person name="Remington K.A."/>
                <person name="Clark A.G."/>
                <person name="Waterman M.S."/>
                <person name="Eichler E.E."/>
                <person name="Adams M.D."/>
                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
                <person name="Venter J.C."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
        <scope>VARIANT VAL-82</scope>
    </reference>
    <reference key="3">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
        <scope>VARIANT VAL-82</scope>
        <source>
            <tissue>Lung</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="6">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="similarity">
        <text evidence="6">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <comment type="sequence caution" evidence="6">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAB85561" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AL136982">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB075855">
        <property type="protein sequence ID" value="BAB85561.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471142">
        <property type="protein sequence ID" value="EAW80308.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471142">
        <property type="protein sequence ID" value="EAW80307.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471142">
        <property type="protein sequence ID" value="EAW80310.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471142">
        <property type="protein sequence ID" value="EAW80311.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC140762">
        <property type="protein sequence ID" value="AAI40763.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8TF27"/>
    <dbReference type="SMR" id="Q8TF27"/>
    <dbReference type="BioGRID" id="125637">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q8TF27">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8TF27">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="Q8TF27"/>
    <dbReference type="iPTMnet" id="Q8TF27"/>
    <dbReference type="PhosphoSitePlus" id="Q8TF27"/>
    <dbReference type="BioMuta" id="HGNC:29421"/>
    <dbReference type="DMDM" id="182641995"/>
    <dbReference type="jPOST" id="Q8TF27"/>
    <dbReference type="MassIVE" id="Q8TF27"/>
    <dbReference type="PeptideAtlas" id="Q8TF27"/>
    <dbReference type="ProteomicsDB" id="74544"/>
    <dbReference type="DNASU" id="119385"/>
    <dbReference type="AGR" id="HGNC:29421"/>
    <dbReference type="ClinPGx" id="PA164715011"/>
    <dbReference type="GeneCards" id="AGAP11"/>
    <dbReference type="HGNC" id="HGNC:29421">
        <property type="gene designation" value="AGAP11"/>
    </dbReference>
    <dbReference type="MIM" id="621159">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q8TF27"/>
    <dbReference type="PAN-GO" id="Q8TF27">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8TF27"/>
    <dbReference type="PathwayCommons" id="Q8TF27"/>
    <dbReference type="SignaLink" id="Q8TF27"/>
    <dbReference type="BioGRID-ORCS" id="119385">
        <property type="hits" value="13 hits in 242 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGAP11">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="119385"/>
    <dbReference type="Pharos" id="Q8TF27">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8TF27"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8TF27">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08853">
        <property type="entry name" value="ArfGap_AGAP2"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
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        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
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        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF8">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 11"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000328758" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 11">
        <location>
            <begin position="1"/>
            <end position="550"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="121"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="328"/>
            <end position="448"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="487"/>
            <end position="516"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="520"/>
            <end position="549"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="343"/>
            <end position="366"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="232"/>
            <end position="270"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="3">
        <location>
            <begin position="245"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_042518" description="In dbSNP:rs2641563." evidence="4 5">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="82"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="6"/>
    <sequence length="550" mass="60549" checksum="A3A6A204B3ACC967" modified="2008-04-08" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2003-01-27" modified="2026-01-28" version="204" xmlns="https://uniprot.org/uniprot">
    <accession>Q96P47</accession>
    <accession>B3KNZ8</accession>
    <accession>E9PAL8</accession>
    <accession>Q59EN0</accession>
    <accession>Q96RK3</accession>
    <name>AGAP3_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3</fullName>
            <shortName>AGAP-3</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>CRAM-associated GTPase</fullName>
            <shortName>CRAG</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>Centaurin-gamma-3</fullName>
            <shortName>Cnt-g3</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>MR1-interacting protein</fullName>
            <shortName>MRIP-1</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP3</name>
        <name type="synonym">CENTG3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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    <reference key="2">
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5)</scope>
        <source>
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    </reference>
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                <person name="Chinwalla A.T."/>
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            </authorList>
            <dbReference type="PubMed" id="12853948"/>
            <dbReference type="DOI" id="10.1038/nature01782"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="5">
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            <authorList>
                <person name="Mural R.J."/>
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                <person name="Hunkapiller M.W."/>
                <person name="Myers E.W."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
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                <person name="Ohara O."/>
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        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 45-855 (ISOFORM 3)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
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            <title>AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase.</title>
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                <person name="Meurer S."/>
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            </authorList>
            <dbReference type="PubMed" id="15381706"/>
            <dbReference type="DOI" id="10.1074/jbc.m410565200"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
    </reference>
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            <title>A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein.</title>
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                <person name="Qin Q."/>
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            </authorList>
            <dbReference type="PubMed" id="16461359"/>
            <dbReference type="DOI" id="10.1083/jcb.200505079"/>
        </citation>
        <scope>TISSUE SPECIFICITY</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>INTERACTION WITH PML</scope>
        <scope>ACTIVITY REGULATION</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="9">
        <citation type="journal article" date="2006" name="Nat. Biotechnol." volume="24" first="1285" last="1292">
            <title>A probability-based approach for high-throughput protein phosphorylation analysis and site localization.</title>
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                <person name="Beausoleil S.A."/>
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            <dbReference type="PubMed" id="16964243"/>
            <dbReference type="DOI" id="10.1038/nbt1240"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="10">
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            <title>A quantitative atlas of mitotic phosphorylation.</title>
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                <person name="Dephoure N."/>
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                <person name="Villen J."/>
                <person name="Beausoleil S.A."/>
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            </authorList>
            <dbReference type="PubMed" id="18669648"/>
            <dbReference type="DOI" id="10.1073/pnas.0805139105"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-324 AND THR-326</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
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            <title>Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.</title>
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                <person name="Gauci S."/>
                <person name="Helbig A.O."/>
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                <person name="Krijgsveld J."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="19413330"/>
            <dbReference type="DOI" id="10.1021/ac9004309"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
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            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
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                <person name="Zhou H."/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-324; SER-443 AND SER-538</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
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    </reference>
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            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
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                <person name="Bian Y."/>
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            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
        </source>
    </reference>
    <reference key="14">
        <citation type="submission" date="2009-08" db="PDB data bank">
            <title>Crystal structure of the Ras-like domain of CENTG3.</title>
            <authorList>
                <consortium name="Structural genomics consortium (SGC)"/>
            </authorList>
        </citation>
        <scope>X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 90-255</scope>
    </reference>
    <comment type="function">
        <text evidence="7 11">GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway.</text>
    </comment>
    <comment type="activity regulation">
        <text evidence="7">GTPase activity is stimulated by oxidative stress.</text>
    </comment>
    <comment type="subunit">
        <text evidence="7">Interacts with PML. Interacts with expanded polyglutamine proteins.</text>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="7">Cytoplasm</location>
        </subcellularLocation>
        <text>In cells upon oxidative stress or in brains of Machado-Joseph disease patients, translocates to PML nuclear bodies.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q96P47-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q96P47-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_018534 VSP_018535"/>
        </isoform>
        <isoform>
            <id>Q96P47-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_018536 VSP_018537"/>
        </isoform>
        <isoform>
            <id>Q96P47-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_040373"/>
        </isoform>
        <isoform>
            <id>Q96P47-5</id>
            <name>5</name>
            <sequence type="described" ref="VSP_054890 VSP_054891"/>
        </isoform>
        <isoform>
            <id>Q96P47-6</id>
            <name>6</name>
            <sequence type="described" ref="VSP_040373 VSP_018536 VSP_018537"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="6 7">Widely expressed.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4 11">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <dbReference type="EMBL" id="AF359283">
        <property type="protein sequence ID" value="AAK48932.2"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF413079">
        <property type="protein sequence ID" value="AAL04173.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK055393">
        <property type="protein sequence ID" value="BAG51510.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC010973">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471173">
        <property type="protein sequence ID" value="EAW54026.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="CH471173">
        <property type="protein sequence ID" value="EAW54028.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AB209781">
        <property type="protein sequence ID" value="BAD93018.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS43681.1">
        <molecule id="Q96P47-4"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS55185.1">
        <molecule id="Q96P47-6"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS64802.1">
        <molecule id="Q96P47-5"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001036000.1">
        <molecule id="Q96P47-6"/>
        <property type="nucleotide sequence ID" value="NM_001042535.4"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001268229.1">
        <molecule id="Q96P47-5"/>
        <property type="nucleotide sequence ID" value="NM_001281300.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_114152.3">
        <molecule id="Q96P47-4"/>
        <property type="nucleotide sequence ID" value="NM_031946.6"/>
    </dbReference>
    <dbReference type="PDB" id="3IHW">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="1.92 A"/>
        <property type="chains" value="A=90-255"/>
    </dbReference>
    <dbReference type="PDBsum" id="3IHW"/>
    <dbReference type="AlphaFoldDB" id="Q96P47"/>
    <dbReference type="SMR" id="Q96P47"/>
    <dbReference type="BioGRID" id="125551">
        <property type="interactions" value="103"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96P47">
        <property type="interactions" value="1336"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96P47">
        <property type="interactions" value="61"/>
    </dbReference>
    <dbReference type="MINT" id="Q96P47"/>
    <dbReference type="STRING" id="9606.ENSP00000380413"/>
    <dbReference type="GlyGen" id="Q96P47">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96P47"/>
    <dbReference type="PhosphoSitePlus" id="Q96P47"/>
    <dbReference type="BioMuta" id="AGAP3"/>
    <dbReference type="DMDM" id="97535922"/>
    <dbReference type="jPOST" id="Q96P47"/>
    <dbReference type="MassIVE" id="Q96P47"/>
    <dbReference type="PaxDb" id="9606-ENSP00000380413"/>
    <dbReference type="PeptideAtlas" id="Q96P47"/>
    <dbReference type="ProteomicsDB" id="19042"/>
    <dbReference type="ProteomicsDB" id="3514"/>
    <dbReference type="ProteomicsDB" id="77618">
        <molecule id="Q96P47-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77619">
        <molecule id="Q96P47-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77620">
        <molecule id="Q96P47-3"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="77621">
        <molecule id="Q96P47-4"/>
    </dbReference>
    <dbReference type="Pumba" id="Q96P47"/>
    <dbReference type="Antibodypedia" id="1445">
        <property type="antibodies" value="147 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="116988"/>
    <dbReference type="Ensembl" id="ENST00000397238.7">
        <molecule id="Q96P47-4"/>
        <property type="protein sequence ID" value="ENSP00000380413.2"/>
        <property type="gene ID" value="ENSG00000133612.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000463381.5">
        <molecule id="Q96P47-5"/>
        <property type="protein sequence ID" value="ENSP00000418016.1"/>
        <property type="gene ID" value="ENSG00000133612.21"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000473312.5">
        <molecule id="Q96P47-6"/>
        <property type="protein sequence ID" value="ENSP00000418921.1"/>
        <property type="gene ID" value="ENSG00000133612.21"/>
    </dbReference>
    <dbReference type="GeneID" id="116988"/>
    <dbReference type="KEGG" id="hsa:116988"/>
    <dbReference type="MANE-Select" id="ENST00000397238.7">
        <molecule id="Q96P47-4"/>
        <property type="protein sequence ID" value="ENSP00000380413.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_031946.7"/>
        <property type="RefSeq protein sequence ID" value="NP_114152.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003wje.3">
        <molecule id="Q96P47-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:16923"/>
    <dbReference type="ClinPGx" id="PA26413"/>
    <dbReference type="CTD" id="116988"/>
    <dbReference type="DisGeNET" id="116988"/>
    <dbReference type="GeneCards" id="AGAP3"/>
    <dbReference type="HGNC" id="HGNC:16923">
        <property type="gene designation" value="AGAP3"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000133612">
        <property type="expression patterns" value="Tissue enhanced (brain)"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000133612"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000133612"/>
    <dbReference type="eggNOG" id="KOG0705">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000159586"/>
    <dbReference type="HOGENOM" id="CLU_007326_4_0_1"/>
    <dbReference type="InParanoid" id="Q96P47"/>
    <dbReference type="OMA" id="KHRWKKS"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="Q96P47">
        <property type="GO annotations" value="4 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96P47"/>
    <dbReference type="PathwayCommons" id="Q96P47"/>
    <dbReference type="SignaLink" id="Q96P47"/>
    <dbReference type="Agora" id="ENSG00000133612"/>
    <dbReference type="BioGRID-ORCS" id="116988">
        <property type="hits" value="13 hits in 1154 CRISPR screens"/>
    </dbReference>
    <dbReference type="CD-CODE" id="FB4E32DD">
        <property type="entry name" value="Presynaptic clusters and postsynaptic densities"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGAP3">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="EvolutionaryTrace" id="Q96P47"/>
    <dbReference type="GeneWiki" id="CENTG3"/>
    <dbReference type="GenomeRNAi" id="116988"/>
    <dbReference type="Pharos" id="Q96P47">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96P47"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96P47">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000133612">
        <property type="expression patterns" value="Expressed in right hemisphere of cerebellum and 180 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96P47">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0071944">
        <property type="term" value="C:cell periphery"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0098978">
        <property type="term" value="C:glutamatergic synapse"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005634">
        <property type="term" value="C:nucleus"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0014069">
        <property type="term" value="C:postsynaptic density"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005525">
        <property type="term" value="F:GTP binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0031593">
        <property type="term" value="F:polyubiquitin modification-dependent protein binding"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0034614">
        <property type="term" value="P:cellular response to reactive oxygen species"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0043161">
        <property type="term" value="P:proteasome-mediated ubiquitin-dependent protein catabolic process"/>
        <property type="evidence" value="ECO:0000266"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0099072">
        <property type="term" value="P:regulation of postsynaptic membrane neurotransmitter receptor levels"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="Ensembl"/>
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    <dbReference type="CDD" id="cd08855">
        <property type="entry name" value="ArfGap_AGAP3"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd04103">
        <property type="entry name" value="Centaurin_gamma"/>
        <property type="match status" value="1"/>
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    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="2.30.29.30:FF:000077">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
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    <dbReference type="FunFam" id="3.40.50.300:FF:000178">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
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    <dbReference type="FunFam" id="2.30.29.30:FF:000199">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3"/>
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    <dbReference type="Gene3D" id="1.25.40.20">
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    <dbReference type="Gene3D" id="1.10.220.150">
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        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
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        <property type="entry name" value="Ras"/>
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    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
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        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
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        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
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        <property type="entry name" value="PH domain-like"/>
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        <property type="entry name" value="ANK_REP_REGION"/>
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        <property type="entry name" value="PH_DOMAIN"/>
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    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0342">GTP-binding</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0547">Nucleotide-binding</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000074220" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3">
        <location>
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            <begin position="87"/>
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            <begin position="367"/>
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    <feature type="domain" description="Arf-GAP" evidence="3">
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            <begin position="626"/>
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    <feature type="repeat" description="ANK 1">
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            <begin position="748"/>
            <end position="777"/>
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            <begin position="785"/>
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            <begin position="818"/>
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            <begin position="1"/>
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    </feature>
    <feature type="region of interest" description="Small GTPase-like">
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            <begin position="84"/>
            <end position="375"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
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            <begin position="428"/>
            <end position="568"/>
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    </feature>
    <feature type="region of interest" description="Disordered" evidence="5">
        <location>
            <begin position="853"/>
            <end position="875"/>
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    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="5">
        <location>
            <begin position="10"/>
            <end position="23"/>
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    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="5">
        <location>
            <begin position="495"/>
            <end position="512"/>
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    </feature>
    <feature type="compositionally biased region" description="Basic residues" evidence="5">
        <location>
            <begin position="541"/>
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    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="98"/>
            <end position="105"/>
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        <ligand>
            <name>GTP</name>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
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            <begin position="142"/>
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        </location>
        <ligand>
            <name>GTP</name>
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        </ligand>
    </feature>
    <feature type="binding site" evidence="1">
        <location>
            <begin position="198"/>
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        </location>
        <ligand>
            <name>GTP</name>
            <dbReference type="ChEBI" id="CHEBI:37565"/>
        </ligand>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="12 13">
        <location>
            <position position="324"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="12">
        <location>
            <position position="326"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13">
        <location>
            <position position="443"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13">
        <location>
            <position position="538"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054890" description="In isoform 5." evidence="8">
        <location>
            <begin position="1"/>
            <end position="192"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018534" description="In isoform 2." evidence="9">
        <original>MNFQ</original>
        <variation>MFGGAGPG</variation>
        <location>
            <begin position="1"/>
            <end position="4"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018535" description="In isoform 2." evidence="9">
        <original>QSPQQQQ</original>
        <variation>GPSQ</variation>
        <location>
            <begin position="9"/>
            <end position="15"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_040373" description="In isoform 4 and isoform 6." evidence="11">
        <original>Q</original>
        <variation>QSLAAPGGGGAAAQQLVCGGQFGGAGPGAGGGGGPSQ</variation>
        <location>
            <position position="15"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018536" description="In isoform 3 and isoform 6." evidence="10">
        <original>SRKGADLDREKKAAECKVDS</original>
        <variation>ICATVSNFSSTKRPFQLLPN</variation>
        <location>
            <begin position="341"/>
            <end position="360"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_018537" description="In isoform 3 and isoform 6." evidence="10">
        <location>
            <begin position="361"/>
            <end position="875"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_054891" description="In isoform 5." evidence="8">
        <location>
            <begin position="463"/>
            <end position="565"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="91"/>
            <end position="97"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="104"/>
            <end position="113"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="125"/>
            <end position="133"/>
        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="136"/>
            <end position="144"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="146"/>
            <end position="148"/>
        </location>
    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="151"/>
            <end position="156"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="158"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="169"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="188"/>
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        </location>
    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="193"/>
            <end position="198"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="212"/>
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            <begin position="222"/>
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    </feature>
    <feature type="strand" evidence="14">
        <location>
            <begin position="226"/>
            <end position="231"/>
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    </feature>
    <feature type="turn" evidence="14">
        <location>
            <begin position="232"/>
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    </feature>
    <feature type="helix" evidence="14">
        <location>
            <begin position="238"/>
            <end position="252"/>
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    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="4">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU01402"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="5">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15381706"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="16461359"/>
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    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="9">
        <source ref="2"/>
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    <evidence type="ECO:0000303" key="10">
        <source ref="6"/>
    </evidence>
    <evidence type="ECO:0000305" key="11"/>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="14">
        <source>
            <dbReference type="PDB" id="3IHW"/>
        </source>
    </evidence>
    <sequence length="875" mass="95044" checksum="3F0D04EE00F42E1E" modified="2006-05-16" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="166" xmlns="https://uniprot.org/uniprot">
    <accession>Q96P64</accession>
    <name>AGAP4_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="7">Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4</fullName>
            <shortName>AGAP-4</shortName>
        </recommendedName>
        <alternativeName>
            <fullName evidence="7">Centaurin-gamma-like family member 1</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="7">Centaurin-gamma-like family member 5</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="7" type="primary">AGAP4</name>
        <name evidence="7" type="synonym">AGAP8</name>
        <name evidence="7" type="synonym">CTGLF1</name>
        <name evidence="7" type="synonym">CTGLF5</name>
        <name evidence="6" type="synonym">MRIP2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="submission" date="2001-08" db="EMBL/GenBank/DDBJ databases">
            <title>Molecular cloning of MRIP2, a novel gene located on human chromosome 10.</title>
            <authorList>
                <person name="Gong L."/>
                <person name="Wu K."/>
            </authorList>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <scope>VARIANT GLU-661</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
                <person name="Swarbreck D."/>
                <person name="Ashurst J.L."/>
                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D.C."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Cahill P."/>
                <person name="Camire D."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="5">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <dbReference type="EMBL" id="AF411132">
        <property type="protein sequence ID" value="AAL10290.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC012044">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS7215.1"/>
    <dbReference type="RefSeq" id="NP_001263272.2">
        <property type="nucleotide sequence ID" value="NM_001276343.2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_597703.2">
        <property type="nucleotide sequence ID" value="NM_133446.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q96P64"/>
    <dbReference type="SMR" id="Q96P64"/>
    <dbReference type="BioGRID" id="125632">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q96P64">
        <property type="interactions" value="253"/>
    </dbReference>
    <dbReference type="IntAct" id="Q96P64">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="Q96P64"/>
    <dbReference type="STRING" id="9606.ENSP00000392513"/>
    <dbReference type="GlyGen" id="Q96P64">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q96P64"/>
    <dbReference type="PhosphoSitePlus" id="Q96P64"/>
    <dbReference type="BioMuta" id="AGAP4"/>
    <dbReference type="DMDM" id="296434392"/>
    <dbReference type="jPOST" id="Q96P64"/>
    <dbReference type="MassIVE" id="Q96P64"/>
    <dbReference type="PaxDb" id="9606-ENSP00000392513"/>
    <dbReference type="PeptideAtlas" id="Q96P64"/>
    <dbReference type="ProteomicsDB" id="77638"/>
    <dbReference type="Antibodypedia" id="58589">
        <property type="antibodies" value="80 antibodies from 16 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="119016"/>
    <dbReference type="Ensembl" id="ENST00000448048.7">
        <property type="protein sequence ID" value="ENSP00000392513.2"/>
        <property type="gene ID" value="ENSG00000188234.16"/>
    </dbReference>
    <dbReference type="GeneID" id="119016"/>
    <dbReference type="KEGG" id="hsa:119016"/>
    <dbReference type="UCSC" id="uc057szm.1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23459"/>
    <dbReference type="ClinPGx" id="PA164715122"/>
    <dbReference type="CTD" id="119016"/>
    <dbReference type="GeneCards" id="AGAP4"/>
    <dbReference type="HGNC" id="HGNC:23459">
        <property type="gene designation" value="AGAP4"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000188234">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621155">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000188234"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000188234"/>
    <dbReference type="eggNOG" id="KOG0705">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163475"/>
    <dbReference type="HOGENOM" id="CLU_007326_4_0_1"/>
    <dbReference type="InParanoid" id="Q96P64"/>
    <dbReference type="OMA" id="SKFWLMS"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="Q96P64">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q96P64"/>
    <dbReference type="PathwayCommons" id="Q96P64"/>
    <dbReference type="SignaLink" id="Q96P64"/>
    <dbReference type="Agora" id="ENSG00000188234"/>
    <dbReference type="BioGRID-ORCS" id="119016">
        <property type="hits" value="42 hits in 689 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGAP4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="119016"/>
    <dbReference type="Pharos" id="Q96P64">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q96P64"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q96P64">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000188234">
        <property type="expression patterns" value="Expressed in cerebellar hemisphere and 99 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q96P64">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08853">
        <property type="entry name" value="ArfGap_AGAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000027">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF7">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000284673" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4">
        <location>
            <begin position="1"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="259"/>
            <end position="420"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="441"/>
            <end position="561"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="600"/>
            <end position="629"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="633"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="456"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="185"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="231"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="359"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="519"/>
            <end position="540"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="188"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="203"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="235"/>
            <end position="250"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="519"/>
            <end position="530"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="531"/>
            <end position="540"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_031804" description="In dbSNP:rs1169771928." evidence="4">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="661"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAL10290." evidence="5" ref="1">
        <original>T</original>
        <variation>S</variation>
        <location>
            <position position="334"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source ref="1"/>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0000312" key="6">
        <source>
            <dbReference type="EMBL" id="AAL10290.1"/>
        </source>
    </evidence>
    <evidence type="ECO:0000312" key="7">
        <source>
            <dbReference type="HGNC" id="HGNC:23459"/>
        </source>
    </evidence>
    <sequence length="663" mass="73070" checksum="49F11692C58577E2" modified="2010-05-18" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2008-09-02" modified="2026-01-28" version="133" xmlns="https://uniprot.org/uniprot">
    <accession>A6NIR3</accession>
    <accession>A8MSN5</accession>
    <name>AGAP5_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 5</fullName>
            <shortName>AGAP-5</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-gamma-like family member 2</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP5</name>
        <name type="synonym">CTGLF2</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
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                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
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                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
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                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
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                <person name="Brown J.Y."/>
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                <person name="Burrill W."/>
                <person name="Burton J."/>
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                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <dbReference type="EMBL" id="AC073389">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AC022400">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC127746">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44439.1"/>
    <dbReference type="RefSeq" id="NP_001137472.1">
        <property type="nucleotide sequence ID" value="NM_001144000.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="A6NIR3"/>
    <dbReference type="SMR" id="A6NIR3"/>
    <dbReference type="BioGRID" id="609497">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="A6NIR3">
        <property type="interactions" value="261"/>
    </dbReference>
    <dbReference type="IntAct" id="A6NIR3">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="MINT" id="A6NIR3"/>
    <dbReference type="STRING" id="9606.ENSP00000363207"/>
    <dbReference type="GlyGen" id="A6NIR3">
        <property type="glycosylation" value="2 sites, 1 O-linked glycan (1 site)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="A6NIR3"/>
    <dbReference type="PhosphoSitePlus" id="A6NIR3"/>
    <dbReference type="BioMuta" id="AGAP5"/>
    <dbReference type="jPOST" id="A6NIR3"/>
    <dbReference type="MassIVE" id="A6NIR3"/>
    <dbReference type="PaxDb" id="9606-ENSP00000363207"/>
    <dbReference type="PeptideAtlas" id="A6NIR3"/>
    <dbReference type="ProteomicsDB" id="1279"/>
    <dbReference type="Antibodypedia" id="68077">
        <property type="antibodies" value="41 antibodies from 5 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="729092"/>
    <dbReference type="Ensembl" id="ENST00000374094.9">
        <property type="protein sequence ID" value="ENSP00000363207.4"/>
        <property type="gene ID" value="ENSG00000172650.15"/>
    </dbReference>
    <dbReference type="GeneID" id="729092"/>
    <dbReference type="KEGG" id="hsa:729092"/>
    <dbReference type="MANE-Select" id="ENST00000374094.9">
        <property type="protein sequence ID" value="ENSP00000363207.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001144000.4"/>
        <property type="RefSeq protein sequence ID" value="NP_001137472.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc009xri.4">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23467"/>
    <dbReference type="ClinPGx" id="PA164715123"/>
    <dbReference type="CTD" id="729092"/>
    <dbReference type="DisGeNET" id="729092"/>
    <dbReference type="GeneCards" id="AGAP5"/>
    <dbReference type="HGNC" id="HGNC:23467">
        <property type="gene designation" value="AGAP5"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000172650">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621156">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000172650"/>
    <dbReference type="eggNOG" id="KOG0705">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163475"/>
    <dbReference type="InParanoid" id="A6NIR3"/>
    <dbReference type="OMA" id="PNISHRD"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="A6NIR3">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="A6NIR3"/>
    <dbReference type="PathwayCommons" id="A6NIR3"/>
    <dbReference type="SignaLink" id="A6NIR3"/>
    <dbReference type="Agora" id="ENSG00000172650"/>
    <dbReference type="BioGRID-ORCS" id="729092">
        <property type="hits" value="317 hits in 1046 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="729092"/>
    <dbReference type="Pharos" id="A6NIR3">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:A6NIR3"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="A6NIR3">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000172650">
        <property type="expression patterns" value="Expressed in body of pancreas and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="A6NIR3">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08853">
        <property type="entry name" value="ArfGap_AGAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000027">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF7">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000349205" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 5">
        <location>
            <begin position="1"/>
            <end position="686"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="282"/>
            <end position="443"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="464"/>
            <end position="584"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="623"/>
            <end position="652"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="656"/>
            <end position="685"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type; degenerate" evidence="2">
        <location>
            <begin position="479"/>
            <end position="502"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="205"/>
            <end position="242"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="256"/>
            <end position="278"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="382"/>
            <end position="404"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="211"/>
            <end position="225"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="226"/>
            <end position="241"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="258"/>
            <end position="273"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC127746." evidence="4" ref="2">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="8"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC127746." evidence="4" ref="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC127746." evidence="4" ref="2">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="482"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="686" mass="75492" checksum="C51D1E96C6179B24" modified="2011-01-11" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="160" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VW22</accession>
    <name>AGAP6_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6</fullName>
            <shortName>AGAP-6</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-gamma-like family member 3</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP6</name>
        <name type="synonym">CTGLF3</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
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                <person name="Brown J.Y."/>
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                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
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                <person name="Nickerson T."/>
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                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
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                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
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                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
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                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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    <reference key="2">
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            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
    </reference>
    <comment type="function">
        <text evidence="5">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5VW22-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5VW22-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_040815"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10.</text>
    </comment>
    <comment type="miscellaneous">
        <molecule>Isoform 1</molecule>
        <text>Prediction based on family homologs sequence.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="frameshift">
            <sequence resource="EMBL" id="BC131545"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AL442003">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC131545">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS44397.1">
        <molecule id="Q5VW22-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001071133.2">
        <molecule id="Q5VW22-2"/>
        <property type="nucleotide sequence ID" value="NM_001077665.3"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VW22"/>
    <dbReference type="SMR" id="Q5VW22"/>
    <dbReference type="BioGRID" id="135969">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5VW22">
        <property type="interactions" value="249"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000500374"/>
    <dbReference type="GlyGen" id="Q5VW22">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VW22"/>
    <dbReference type="PhosphoSitePlus" id="Q5VW22"/>
    <dbReference type="BioMuta" id="AGAP6"/>
    <dbReference type="DMDM" id="74756919"/>
    <dbReference type="jPOST" id="Q5VW22"/>
    <dbReference type="MassIVE" id="Q5VW22"/>
    <dbReference type="PaxDb" id="9606-ENSP00000400972"/>
    <dbReference type="PeptideAtlas" id="Q5VW22"/>
    <dbReference type="ProteomicsDB" id="65507">
        <molecule id="Q5VW22-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="65508">
        <molecule id="Q5VW22-2"/>
    </dbReference>
    <dbReference type="DNASU" id="414189"/>
    <dbReference type="Ensembl" id="ENST00000374056.10">
        <molecule id="Q5VW22-1"/>
        <property type="protein sequence ID" value="ENSP00000363168.6"/>
        <property type="gene ID" value="ENSG00000204149.16"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000412531.7">
        <molecule id="Q5VW22-2"/>
        <property type="protein sequence ID" value="ENSP00000500374.1"/>
        <property type="gene ID" value="ENSG00000204149.16"/>
    </dbReference>
    <dbReference type="GeneID" id="414189"/>
    <dbReference type="KEGG" id="hsa:414189"/>
    <dbReference type="MANE-Select" id="ENST00000412531.7">
        <molecule id="Q5VW22-2"/>
        <property type="protein sequence ID" value="ENSP00000500374.1"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001077665.3"/>
        <property type="RefSeq protein sequence ID" value="NP_001071133.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc001jix.5">
        <molecule id="Q5VW22-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23466"/>
    <dbReference type="CTD" id="414189"/>
    <dbReference type="GeneCards" id="AGAP6"/>
    <dbReference type="HGNC" id="HGNC:23466">
        <property type="gene designation" value="AGAP6"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000204149">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621157">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000204149"/>
    <dbReference type="eggNOG" id="KOG0705">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000163475"/>
    <dbReference type="InParanoid" id="Q5VW22"/>
    <dbReference type="OMA" id="ANAVWEY"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="Q5VW22">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VW22"/>
    <dbReference type="PathwayCommons" id="Q5VW22"/>
    <dbReference type="SignaLink" id="Q5VW22"/>
    <dbReference type="Agora" id="ENSG00000204149"/>
    <dbReference type="BioGRID-ORCS" id="414189">
        <property type="hits" value="487 hits in 1056 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGAP6">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="414189"/>
    <dbReference type="Pharos" id="Q5VW22">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VW22"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VW22">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000204149">
        <property type="expression patterns" value="Expressed in pituitary gland and 92 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000027">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF7">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at transcript level"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000284674" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6">
        <location>
            <begin position="1"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="259"/>
            <end position="420"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="441"/>
            <end position="561"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="600"/>
            <end position="629"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="633"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="456"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="185"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="231"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="359"/>
            <end position="381"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="188"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="203"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="235"/>
            <end position="250"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_040815" description="In isoform 2." evidence="4">
        <original>P</original>
        <variation>PEALEFNLSANPESSTIFQRNSQT</variation>
        <location>
            <position position="73"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC131545." evidence="5" ref="2">
        <original>R</original>
        <variation>G</variation>
        <location>
            <position position="37"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC131545." evidence="5" ref="2">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="70"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="663" mass="73127" checksum="D37B8B139F967113" modified="2004-12-07" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="153" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VUJ5</accession>
    <accession>A6NGH4</accession>
    <name>AGAP7_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Putative Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 7</fullName>
            <shortName>AGAP-7</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 7 pseudogene</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Centaurin-gamma-like family member 4</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP7P</name>
        <name type="synonym">AGAP7</name>
        <name type="synonym">CTGLF4</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
                <person name="Swarbreck D."/>
                <person name="Ashurst J.L."/>
                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D.C."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Cahill P."/>
                <person name="Camire D."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <comment type="function">
        <text evidence="4">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10.</text>
    </comment>
    <comment type="similarity">
        <text evidence="4">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <comment type="caution">
        <text evidence="4">Could be the product of a pseudogene.</text>
    </comment>
    <dbReference type="EMBL" id="AL589822">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VUJ5"/>
    <dbReference type="SMR" id="Q5VUJ5"/>
    <dbReference type="BioGRID" id="575652">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5VUJ5">
        <property type="interactions" value="6"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5VUJ5">
        <property type="interactions" value="3"/>
    </dbReference>
    <dbReference type="MINT" id="Q5VUJ5"/>
    <dbReference type="GlyGen" id="Q5VUJ5">
        <property type="glycosylation" value="1 site"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VUJ5"/>
    <dbReference type="PhosphoSitePlus" id="Q5VUJ5"/>
    <dbReference type="BioMuta" id="HGNC:23465"/>
    <dbReference type="DMDM" id="74756856"/>
    <dbReference type="jPOST" id="Q5VUJ5"/>
    <dbReference type="MassIVE" id="Q5VUJ5"/>
    <dbReference type="PeptideAtlas" id="Q5VUJ5"/>
    <dbReference type="AGR" id="HGNC:23465"/>
    <dbReference type="GeneCards" id="AGAP7P"/>
    <dbReference type="HGNC" id="HGNC:23465">
        <property type="gene designation" value="AGAP7P"/>
    </dbReference>
    <dbReference type="InParanoid" id="Q5VUJ5"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="Q5VUJ5">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VUJ5"/>
    <dbReference type="PathwayCommons" id="Q5VUJ5"/>
    <dbReference type="SignaLink" id="Q5VUJ5"/>
    <dbReference type="Pharos" id="Q5VUJ5">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VUJ5"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Unplaced"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VUJ5">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08836">
        <property type="entry name" value="ArfGap_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.25.40.20:FF:000027">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR002110">
        <property type="entry name" value="Ankyrin_rpt"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF7">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF12796">
        <property type="entry name" value="Ank_2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00169">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00248">
        <property type="entry name" value="ANK"/>
        <property type="match status" value="2"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF48403">
        <property type="entry name" value="Ankyrin repeat"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50088">
        <property type="entry name" value="ANK_REPEAT"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="uncertain"/>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000284675" description="Putative Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 7">
        <location>
            <begin position="1"/>
            <end position="663"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="259"/>
            <end position="420"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="441"/>
            <end position="561"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 1">
        <location>
            <begin position="600"/>
            <end position="629"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK 2">
        <location>
            <begin position="633"/>
            <end position="662"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="456"/>
            <end position="479"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="182"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="231"/>
            <end position="255"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Low complexity" evidence="3">
        <location>
            <begin position="188"/>
            <end position="202"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="203"/>
            <end position="216"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="235"/>
            <end position="250"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="4"/>
    <sequence length="663" mass="73211" checksum="036912A99532FAE0" modified="2004-12-07" version="1"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-03-15" modified="2026-01-28" version="183" xmlns="https://uniprot.org/uniprot">
    <accession>Q8N302</accession>
    <accession>O00581</accession>
    <accession>Q53YS3</accession>
    <accession>Q9BU84</accession>
    <accession>Q9NW66</accession>
    <name>AGGF1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Angiogenic factor with G patch and FHA domains 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>Angiogenic factor VG5Q</fullName>
            <shortName>hVG5Q</shortName>
        </alternativeName>
        <alternativeName>
            <fullName>G patch domain-containing protein 7</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Vasculogenesis gene on 5q protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGGF1</name>
        <name type="synonym">GPATC7</name>
        <name type="synonym">GPATCH7</name>
        <name type="synonym">VG5Q</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-664</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="7">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-11 AND SER-344</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="5">Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion.</text>
    </comment>
    <comment type="subunit">
        <text evidence="5">Interacts with the secreted angiogenic factor TNFSF12.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
            <label>AGGF1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-465781">
            <id>Q9UL45</id>
            <label>BLOC1S6</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-1237044">
            <id>O43143</id>
            <label>DHX15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-740282">
            <id>Q9NVF7</id>
            <label>FBXO28</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-10268010">
            <id>Q8N8X9</id>
            <label>MAB21L3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>5</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-747899">
            <id>Q8N302</id>
        </interactant>
        <interactant intactId="EBI-348259">
            <id>Q96EZ8</id>
            <label>MCRS1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-25837549">
            <id>P28329-3</id>
            <label>CHAT</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-348399">
            <id>P22607</id>
            <label>FGFR3</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-351506">
            <id>P06396</id>
            <label>GSN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-748974">
            <id>Q96CV9</id>
            <label>OPTN</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-716404">
            <id>P16284</id>
            <label>PECAM1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-2559665">
            <id>Q5JTV8</id>
            <label>TOR1AIP1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-353844">
            <id>P08670</id>
            <label>VIM</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-25838028">
            <id>Q8N302-2</id>
        </interactant>
        <interactant intactId="EBI-25900580">
            <id>Q9Y649</id>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="5">Cytoplasm</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="5">Secreted</location>
        </subcellularLocation>
        <text>Cytoplasmic in microvascular endothelial cells. Upon angiogenesis, when endothelial cell tube formation is initiated, it is secreted.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q8N302-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q8N302-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_009631 VSP_009632"/>
        </isoform>
        <isoform>
            <id>Q8N302-3</id>
            <name>3</name>
            <sequence type="described" ref="VSP_009633 VSP_009634"/>
        </isoform>
    </comment>
    <comment type="tissue specificity">
        <text evidence="5">Widely expressed. Expressed in endothelial cells, vascular smooth muscle cells and osteoblasts. Expressed in umbilical vein endothelial cells and microvascular endothelial cells.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous termination">
            <sequence resource="EMBL-CDS" id="AAH29382" version="2"/>
        </conflict>
        <text>Truncated C-terminus.</text>
    </comment>
    <comment type="sequence caution" evidence="9">
        <conflict type="erroneous initiation">
            <sequence resource="EMBL-CDS" id="BAA91519" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AY500994">
        <property type="protein sequence ID" value="AAR97615.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AY500996">
        <property type="protein sequence ID" value="AAR97617.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U84971">
        <property type="protein sequence ID" value="AAB60856.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002828">
        <property type="protein sequence ID" value="AAH02828.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC029382">
        <property type="protein sequence ID" value="AAH29382.2"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AK001145">
        <property type="protein sequence ID" value="BAA91519.1"/>
        <property type="status" value="ALT_INIT"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS4035.1">
        <molecule id="Q8N302-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_060516.2">
        <molecule id="Q8N302-1"/>
        <property type="nucleotide sequence ID" value="NM_018046.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q8N302"/>
    <dbReference type="SMR" id="Q8N302"/>
    <dbReference type="BioGRID" id="120419">
        <property type="interactions" value="62"/>
    </dbReference>
    <dbReference type="CORUM" id="Q8N302"/>
    <dbReference type="FunCoup" id="Q8N302">
        <property type="interactions" value="1454"/>
    </dbReference>
    <dbReference type="IntAct" id="Q8N302">
        <property type="interactions" value="689"/>
    </dbReference>
    <dbReference type="MINT" id="Q8N302"/>
    <dbReference type="STRING" id="9606.ENSP00000316109"/>
    <dbReference type="GlyGen" id="Q8N302">
        <property type="glycosylation" value="2 sites"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q8N302"/>
    <dbReference type="PhosphoSitePlus" id="Q8N302"/>
    <dbReference type="BioMuta" id="AGGF1"/>
    <dbReference type="DMDM" id="45477317"/>
    <dbReference type="jPOST" id="Q8N302"/>
    <dbReference type="MassIVE" id="Q8N302"/>
    <dbReference type="PaxDb" id="9606-ENSP00000316109"/>
    <dbReference type="PeptideAtlas" id="Q8N302"/>
    <dbReference type="ProteomicsDB" id="71746">
        <molecule id="Q8N302-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71747">
        <molecule id="Q8N302-2"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="71748">
        <molecule id="Q8N302-3"/>
    </dbReference>
    <dbReference type="Pumba" id="Q8N302"/>
    <dbReference type="Antibodypedia" id="12482">
        <property type="antibodies" value="265 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="55109"/>
    <dbReference type="Ensembl" id="ENST00000312916.12">
        <molecule id="Q8N302-1"/>
        <property type="protein sequence ID" value="ENSP00000316109.7"/>
        <property type="gene ID" value="ENSG00000164252.14"/>
    </dbReference>
    <dbReference type="Ensembl" id="ENST00000506806.1">
        <molecule id="Q8N302-3"/>
        <property type="protein sequence ID" value="ENSP00000424733.1"/>
        <property type="gene ID" value="ENSG00000164252.14"/>
    </dbReference>
    <dbReference type="GeneID" id="55109"/>
    <dbReference type="KEGG" id="hsa:55109"/>
    <dbReference type="MANE-Select" id="ENST00000312916.12">
        <property type="protein sequence ID" value="ENSP00000316109.7"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_018046.5"/>
        <property type="RefSeq protein sequence ID" value="NP_060516.2"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003kes.4">
        <molecule id="Q8N302-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:24684"/>
    <dbReference type="ClinPGx" id="PA134951291"/>
    <dbReference type="CTD" id="55109"/>
    <dbReference type="DisGeNET" id="55109"/>
    <dbReference type="GeneCards" id="AGGF1"/>
    <dbReference type="HGNC" id="HGNC:24684">
        <property type="gene designation" value="AGGF1"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000164252">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MalaCards" id="AGGF1"/>
    <dbReference type="MIM" id="608464">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000164252"/>
    <dbReference type="Orphanet" id="90308">
        <property type="disease" value="Capillary-lymphatic-venous malformation with segmental distribution"/>
    </dbReference>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000164252"/>
    <dbReference type="eggNOG" id="KOG0154">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00730000111121"/>
    <dbReference type="HOGENOM" id="CLU_023817_1_0_1"/>
    <dbReference type="InParanoid" id="Q8N302"/>
    <dbReference type="OMA" id="QLHKTHA"/>
    <dbReference type="OrthoDB" id="2538319at2759"/>
    <dbReference type="PAN-GO" id="Q8N302">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q8N302"/>
    <dbReference type="PathwayCommons" id="Q8N302"/>
    <dbReference type="Reactome" id="R-HSA-6802952">
        <property type="pathway name" value="Signaling by BRAF and RAF1 fusions"/>
    </dbReference>
    <dbReference type="SignaLink" id="Q8N302"/>
    <dbReference type="SIGNOR" id="Q8N302"/>
    <dbReference type="Agora" id="ENSG00000164252"/>
    <dbReference type="BioGRID-ORCS" id="55109">
        <property type="hits" value="13 hits in 1152 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGGF1">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="AGGF1"/>
    <dbReference type="GenomeRNAi" id="55109"/>
    <dbReference type="Pharos" id="Q8N302">
        <property type="development level" value="Tbio"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q8N302"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 5"/>
    </dbReference>
    <dbReference type="RNAct" id="Q8N302">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000164252">
        <property type="expression patterns" value="Expressed in choroid plexus epithelium and 200 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="Q8N302">
        <property type="expression patterns" value="baseline and differential"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005576">
        <property type="term" value="C:extracellular region"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0048471">
        <property type="term" value="C:perinuclear region of cytoplasm"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0042802">
        <property type="term" value="F:identical protein binding"/>
        <property type="evidence" value="ECO:0000353"/>
        <property type="project" value="IntAct"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003676">
        <property type="term" value="F:nucleic acid binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001525">
        <property type="term" value="P:angiogenesis"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="GO" id="GO:0007155">
        <property type="term" value="P:cell adhesion"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0045766">
        <property type="term" value="P:positive regulation of angiogenesis"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001938">
        <property type="term" value="P:positive regulation of endothelial cell proliferation"/>
        <property type="evidence" value="ECO:0000314"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="GO" id="GO:0001570">
        <property type="term" value="P:vasculogenesis"/>
        <property type="evidence" value="ECO:0000304"/>
        <property type="project" value="UniProtKB"/>
    </dbReference>
    <dbReference type="CDD" id="cd22686">
        <property type="entry name" value="FHA_AGGF1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd16164">
        <property type="entry name" value="OCRE_VG5Q"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="2.60.200.20:FF:000016">
        <property type="entry name" value="Angiogenic factor with G patch and FHA domains 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.60.200.20">
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR053027">
        <property type="entry name" value="AGGF1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR035624">
        <property type="entry name" value="AGGF1_OCRE"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000253">
        <property type="entry name" value="FHA_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR000467">
        <property type="entry name" value="G_patch_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR041591">
        <property type="entry name" value="OCRE"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR008984">
        <property type="entry name" value="SMAD_FHA_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23106">
        <property type="entry name" value="ANGIOGENIC FACTOR WITH G PATCH AND FHA DOMAINS 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR23106:SF24">
        <property type="entry name" value="ANGIOGENIC FACTOR WITH G PATCH AND FHA DOMAINS 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF00498">
        <property type="entry name" value="FHA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01585">
        <property type="entry name" value="G-patch"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF17780">
        <property type="entry name" value="OCRE"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00240">
        <property type="entry name" value="FHA"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00443">
        <property type="entry name" value="G_patch"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF49879">
        <property type="entry name" value="SMAD/FHA domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50006">
        <property type="entry name" value="FHA_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50174">
        <property type="entry name" value="G_PATCH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0037">Angiogenesis</keyword>
    <keyword id="KW-0175">Coiled coil</keyword>
    <keyword id="KW-0963">Cytoplasm</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0964">Secreted</keyword>
    <feature type="initiator methionine" description="Removed" evidence="10">
        <location>
            <position position="1"/>
        </location>
    </feature>
    <feature type="chain" id="PRO_0000064495" description="Angiogenic factor with G patch and FHA domains 1">
        <location>
            <begin position="2"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="domain" description="FHA" evidence="2">
        <location>
            <begin position="434"/>
            <end position="487"/>
        </location>
    </feature>
    <feature type="domain" description="G-patch" evidence="3">
        <location>
            <begin position="619"/>
            <end position="665"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="1"/>
            <end position="22"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="259"/>
            <end position="307"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="322"/>
            <end position="384"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="586"/>
            <end position="617"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="4">
        <location>
            <begin position="655"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="coiled-coil region" evidence="1">
        <location>
            <begin position="18"/>
            <end position="88"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Pro residues" evidence="4">
        <location>
            <begin position="1"/>
            <end position="18"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="279"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="4">
        <location>
            <begin position="335"/>
            <end position="355"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Acidic residues" evidence="4">
        <location>
            <begin position="364"/>
            <end position="383"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="586"/>
            <end position="609"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="4">
        <location>
            <begin position="680"/>
            <end position="690"/>
        </location>
    </feature>
    <feature type="modified residue" description="N-acetylalanine" evidence="10">
        <location>
            <position position="2"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="7"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="11"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="12">
        <location>
            <position position="344"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="11">
        <location>
            <position position="664"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009631" description="In isoform 2." evidence="7">
        <original>EELSKILQRGRNEDNKKSDVEVQTENHAPWSISDYFYQ</original>
        <variation>RGPPQPRAPSSPGEAFEARDSLGRGPWQGLRTTVEYLK</variation>
        <location>
            <begin position="72"/>
            <end position="109"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009632" description="In isoform 2." evidence="7">
        <location>
            <begin position="110"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009633" description="In isoform 3." evidence="8">
        <original>EPAS</original>
        <variation>VIKC</variation>
        <location>
            <begin position="173"/>
            <end position="176"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_009634" description="In isoform 3." evidence="8">
        <location>
            <begin position="177"/>
            <end position="714"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017901" description="Displays a stronger angiogenic activity; dbSNP:rs34203073." evidence="5">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="133"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037446" description="In dbSNP:rs9715897.">
        <original>T</original>
        <variation>A</variation>
        <location>
            <position position="180"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_037447" description="In dbSNP:rs17856835." evidence="6">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="471"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_017902" description="In dbSNP:rs34400049." evidence="5">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="698"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 4." evidence="9" ref="4">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="370"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00086"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="3">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00092"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="4">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14961121"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="7">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="8">
        <source ref="2"/>
    </evidence>
    <evidence type="ECO:0000305" key="9"/>
    <evidence type="ECO:0007744" key="10">
        <source>
            <dbReference type="PubMed" id="19413330"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="11">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="12">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <sequence length="714" mass="80977" checksum="3CC88FBDA9853EF1" modified="2004-03-15" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2007-04-17" modified="2026-01-28" version="155" xmlns="https://uniprot.org/uniprot">
    <accession>Q5VTM2</accession>
    <accession>D3YTF3</accession>
    <name>AGAP9_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9</fullName>
            <shortName>AGAP-9</shortName>
        </recommendedName>
        <alternativeName>
            <fullName>Centaurin-gamma-like family member 6</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGAP9</name>
        <name type="synonym">CTGLF6</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="2004" name="Nature" volume="429" first="375" last="381">
            <title>The DNA sequence and comparative analysis of human chromosome 10.</title>
            <authorList>
                <person name="Deloukas P."/>
                <person name="Earthrowl M.E."/>
                <person name="Grafham D.V."/>
                <person name="Rubenfield M."/>
                <person name="French L."/>
                <person name="Steward C.A."/>
                <person name="Sims S.K."/>
                <person name="Jones M.C."/>
                <person name="Searle S."/>
                <person name="Scott C."/>
                <person name="Howe K."/>
                <person name="Hunt S.E."/>
                <person name="Andrews T.D."/>
                <person name="Gilbert J.G.R."/>
                <person name="Swarbreck D."/>
                <person name="Ashurst J.L."/>
                <person name="Taylor A."/>
                <person name="Battles J."/>
                <person name="Bird C.P."/>
                <person name="Ainscough R."/>
                <person name="Almeida J.P."/>
                <person name="Ashwell R.I.S."/>
                <person name="Ambrose K.D."/>
                <person name="Babbage A.K."/>
                <person name="Bagguley C.L."/>
                <person name="Bailey J."/>
                <person name="Banerjee R."/>
                <person name="Bates K."/>
                <person name="Beasley H."/>
                <person name="Bray-Allen S."/>
                <person name="Brown A.J."/>
                <person name="Brown J.Y."/>
                <person name="Burford D.C."/>
                <person name="Burrill W."/>
                <person name="Burton J."/>
                <person name="Cahill P."/>
                <person name="Camire D."/>
                <person name="Carter N.P."/>
                <person name="Chapman J.C."/>
                <person name="Clark S.Y."/>
                <person name="Clarke G."/>
                <person name="Clee C.M."/>
                <person name="Clegg S."/>
                <person name="Corby N."/>
                <person name="Coulson A."/>
                <person name="Dhami P."/>
                <person name="Dutta I."/>
                <person name="Dunn M."/>
                <person name="Faulkner L."/>
                <person name="Frankish A."/>
                <person name="Frankland J.A."/>
                <person name="Garner P."/>
                <person name="Garnett J."/>
                <person name="Gribble S."/>
                <person name="Griffiths C."/>
                <person name="Grocock R."/>
                <person name="Gustafson E."/>
                <person name="Hammond S."/>
                <person name="Harley J.L."/>
                <person name="Hart E."/>
                <person name="Heath P.D."/>
                <person name="Ho T.P."/>
                <person name="Hopkins B."/>
                <person name="Horne J."/>
                <person name="Howden P.J."/>
                <person name="Huckle E."/>
                <person name="Hynds C."/>
                <person name="Johnson C."/>
                <person name="Johnson D."/>
                <person name="Kana A."/>
                <person name="Kay M."/>
                <person name="Kimberley A.M."/>
                <person name="Kershaw J.K."/>
                <person name="Kokkinaki M."/>
                <person name="Laird G.K."/>
                <person name="Lawlor S."/>
                <person name="Lee H.M."/>
                <person name="Leongamornlert D.A."/>
                <person name="Laird G."/>
                <person name="Lloyd C."/>
                <person name="Lloyd D.M."/>
                <person name="Loveland J."/>
                <person name="Lovell J."/>
                <person name="McLaren S."/>
                <person name="McLay K.E."/>
                <person name="McMurray A."/>
                <person name="Mashreghi-Mohammadi M."/>
                <person name="Matthews L."/>
                <person name="Milne S."/>
                <person name="Nickerson T."/>
                <person name="Nguyen M."/>
                <person name="Overton-Larty E."/>
                <person name="Palmer S.A."/>
                <person name="Pearce A.V."/>
                <person name="Peck A.I."/>
                <person name="Pelan S."/>
                <person name="Phillimore B."/>
                <person name="Porter K."/>
                <person name="Rice C.M."/>
                <person name="Rogosin A."/>
                <person name="Ross M.T."/>
                <person name="Sarafidou T."/>
                <person name="Sehra H.K."/>
                <person name="Shownkeen R."/>
                <person name="Skuce C.D."/>
                <person name="Smith M."/>
                <person name="Standring L."/>
                <person name="Sycamore N."/>
                <person name="Tester J."/>
                <person name="Thorpe A."/>
                <person name="Torcasso W."/>
                <person name="Tracey A."/>
                <person name="Tromans A."/>
                <person name="Tsolas J."/>
                <person name="Wall M."/>
                <person name="Walsh J."/>
                <person name="Wang H."/>
                <person name="Weinstock K."/>
                <person name="West A.P."/>
                <person name="Willey D.L."/>
                <person name="Whitehead S.L."/>
                <person name="Wilming L."/>
                <person name="Wray P.W."/>
                <person name="Young L."/>
                <person name="Chen Y."/>
                <person name="Lovering R.C."/>
                <person name="Moschonas N.K."/>
                <person name="Siebert R."/>
                <person name="Fechtel K."/>
                <person name="Bentley D."/>
                <person name="Durbin R.M."/>
                <person name="Hubbard T."/>
                <person name="Doucette-Stamm L."/>
                <person name="Beck S."/>
                <person name="Smith D.R."/>
                <person name="Rogers J."/>
            </authorList>
            <dbReference type="PubMed" id="15164054"/>
            <dbReference type="DOI" id="10.1038/nature02462"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)</scope>
        <source>
            <tissue>Brain</tissue>
        </source>
    </reference>
    <comment type="function">
        <text evidence="5">Putative GTPase-activating protein.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>Q5VTM2-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>Q5VTM2-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_044549 VSP_044550 VSP_044551"/>
        </isoform>
    </comment>
    <comment type="miscellaneous">
        <text>Encoded by one of the numerous copies of centaurin gamma-like genes clustered in the q11 region of chromosome 10.</text>
    </comment>
    <comment type="similarity">
        <text evidence="5">Belongs to the centaurin gamma-like family.</text>
    </comment>
    <dbReference type="EMBL" id="AL591684">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC171845">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS73125.1">
        <molecule id="Q5VTM2-2"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_001177739.1">
        <molecule id="Q5VTM2-2"/>
        <property type="nucleotide sequence ID" value="NM_001190810.1"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="Q5VTM2"/>
    <dbReference type="SMR" id="Q5VTM2"/>
    <dbReference type="BioGRID" id="568033">
        <property type="interactions" value="2"/>
    </dbReference>
    <dbReference type="FunCoup" id="Q5VTM2">
        <property type="interactions" value="249"/>
    </dbReference>
    <dbReference type="IntAct" id="Q5VTM2">
        <property type="interactions" value="1"/>
    </dbReference>
    <dbReference type="GlyCosmos" id="Q5VTM2">
        <property type="glycosylation" value="1 site, 1 glycan"/>
    </dbReference>
    <dbReference type="GlyGen" id="Q5VTM2">
        <property type="glycosylation" value="3 sites, 1 O-linked glycan (2 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="Q5VTM2"/>
    <dbReference type="PhosphoSitePlus" id="Q5VTM2"/>
    <dbReference type="BioMuta" id="AGAP9"/>
    <dbReference type="DMDM" id="145558891"/>
    <dbReference type="jPOST" id="Q5VTM2"/>
    <dbReference type="MassIVE" id="Q5VTM2"/>
    <dbReference type="PeptideAtlas" id="Q5VTM2"/>
    <dbReference type="Antibodypedia" id="67499">
        <property type="antibodies" value="52 antibodies from 9 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="642517"/>
    <dbReference type="Ensembl" id="ENST00000452145.6">
        <molecule id="Q5VTM2-2"/>
        <property type="protein sequence ID" value="ENSP00000392206.2"/>
        <property type="gene ID" value="ENSG00000204172.12"/>
    </dbReference>
    <dbReference type="GeneID" id="642517"/>
    <dbReference type="KEGG" id="hsa:642517"/>
    <dbReference type="MANE-Select" id="ENST00000452145.6">
        <molecule id="Q5VTM2-2"/>
        <property type="protein sequence ID" value="ENSP00000392206.2"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_001190810.1"/>
        <property type="RefSeq protein sequence ID" value="NP_001177739.1"/>
    </dbReference>
    <dbReference type="UCSC" id="uc057tbu.1">
        <molecule id="Q5VTM2-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:23463"/>
    <dbReference type="CTD" id="642517"/>
    <dbReference type="GeneCards" id="AGAP9"/>
    <dbReference type="HGNC" id="HGNC:23463">
        <property type="gene designation" value="AGAP9"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000204172">
        <property type="expression patterns" value="Low tissue specificity"/>
    </dbReference>
    <dbReference type="MIM" id="621158">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000204172"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000204172"/>
    <dbReference type="GeneTree" id="ENSGT00940000163475"/>
    <dbReference type="HOGENOM" id="CLU_392755_0_0_1"/>
    <dbReference type="InParanoid" id="Q5VTM2"/>
    <dbReference type="OMA" id="KEWWIRS"/>
    <dbReference type="OrthoDB" id="6136903at2759"/>
    <dbReference type="PAN-GO" id="Q5VTM2">
        <property type="GO annotations" value="3 GO annotations based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="Q5VTM2"/>
    <dbReference type="PathwayCommons" id="Q5VTM2"/>
    <dbReference type="SignaLink" id="Q5VTM2"/>
    <dbReference type="Agora" id="ENSG00000204172"/>
    <dbReference type="BioGRID-ORCS" id="642517">
        <property type="hits" value="36 hits in 681 CRISPR screens"/>
    </dbReference>
    <dbReference type="GenomeRNAi" id="642517"/>
    <dbReference type="Pharos" id="Q5VTM2">
        <property type="development level" value="Tdark"/>
    </dbReference>
    <dbReference type="PRO" id="PR:Q5VTM2"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 10"/>
    </dbReference>
    <dbReference type="RNAct" id="Q5VTM2">
        <property type="molecule type" value="protein"/>
    </dbReference>
    <dbReference type="Bgee" id="ENSG00000204172">
        <property type="expression patterns" value="Expressed in right uterine tube and 95 other cell types or tissues"/>
    </dbReference>
    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0003924">
        <property type="term" value="F:GTPase activity"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
    </dbReference>
    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
    </dbReference>
    <dbReference type="CDD" id="cd08853">
        <property type="entry name" value="ArfGap_AGAP2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="CDD" id="cd01250">
        <property type="entry name" value="PH_AGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000001">
        <property type="entry name" value="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.25.40.20">
        <property type="entry name" value="Ankyrin repeat-containing domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.40.50.300">
        <property type="entry name" value="P-loop containing nucleotide triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="2.30.29.30">
        <property type="entry name" value="Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR036770">
        <property type="entry name" value="Ankyrin_rpt-contain_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR051282">
        <property type="entry name" value="Arf-GAP_GTPase_ANK_PH"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR027417">
        <property type="entry name" value="P-loop_NTPase"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR011993">
        <property type="entry name" value="PH-like_dom_sf"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001849">
        <property type="entry name" value="PH_domain"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819:SF7">
        <property type="entry name" value="ARF-GAP WITH GTPASE, ANK REPEAT AND PH DOMAIN-CONTAINING PROTEIN 4-RELATED"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR45819">
        <property type="entry name" value="CENTAURIN-GAMMA-1A"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SMART" id="SM00233">
        <property type="entry name" value="PH"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF52540">
        <property type="entry name" value="P-loop containing nucleoside triphosphate hydrolases"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF50729">
        <property type="entry name" value="PH domain-like"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50297">
        <property type="entry name" value="ANK_REP_REGION"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50003">
        <property type="entry name" value="PH_DOMAIN"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="inferred from homology"/>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0040">ANK repeat</keyword>
    <keyword id="KW-0343">GTPase activation</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000284677" description="Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 9">
        <location>
            <begin position="1"/>
            <end position="703"/>
        </location>
    </feature>
    <feature type="domain" description="PH" evidence="1">
        <location>
            <begin position="327"/>
            <end position="488"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="509"/>
            <end position="629"/>
        </location>
    </feature>
    <feature type="repeat" description="ANK">
        <location>
            <begin position="631"/>
            <end position="700"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="524"/>
            <end position="547"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="249"/>
            <end position="287"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="299"/>
            <end position="323"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="427"/>
            <end position="449"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="271"/>
            <end position="286"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Basic and acidic residues" evidence="3">
        <location>
            <begin position="303"/>
            <end position="318"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044549" description="In isoform 2." evidence="4">
        <original>MFEDVFSDSGNTGNFDRGKKRRLTIIECGCDINMMIDLAKVADLVLMLIDASFGFEMEMFEFLNICQAHGFPKILGVLTHLDSFKHNKQLKKTKKRLKHRFWTEVYQDKVGLTHELVQSLISTYSTIDAKMASSRVTLLSNSKPLGSEAIDNQG</original>
        <variation>MGNILTCRVHPS</variation>
        <location>
            <begin position="1"/>
            <end position="154"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044550" description="In isoform 2." evidence="4">
        <original>E</original>
        <variation>EALEFNLSANPEASTIFQRNSQTDALEFNSSANPEASTIFQRNSQTD</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_044551" description="In isoform 2." evidence="4">
        <original>CDLGDTSSYHTK</original>
        <variation>VSTERFSQQYSSCSTIFLDDSTAIQHYLTMTIISVTLEIPHHITQRDADRSLSIPDEQLHSFA</variation>
        <location>
            <begin position="229"/>
            <end position="240"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC171845." evidence="5" ref="2">
        <original>K</original>
        <variation>E</variation>
        <location>
            <position position="495"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; BC171845." evidence="5" ref="2">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="508"/>
        </location>
    </feature>
    <evidence type="ECO:0000255" key="1">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00145"/>
        </source>
    </evidence>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <sequence length="703" mass="77972" checksum="28D84F589E15A0EB" modified="2007-04-17" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="1988-01-01" modified="2026-01-28" version="251" xmlns="https://uniprot.org/uniprot">
    <accession>P06280</accession>
    <accession>Q6LER7</accession>
    <name>AGAL_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="49">Alpha-galactosidase A</fullName>
            <ecNumber evidence="24 26">3.2.1.22</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName>Alpha-D-galactosidase A</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Alpha-D-galactoside galactohydrolase</fullName>
        </alternativeName>
        <alternativeName>
            <fullName evidence="49">Galactosylgalactosylglucosylceramidase GLA</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Melibiase</fullName>
        </alternativeName>
        <innName>Agalsidase</innName>
    </protein>
    <gene>
        <name evidence="52" type="primary">GLA</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA]</scope>
        <source>
            <tissue>Fibroblast</tissue>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
        <source>
            <tissue>Lymphoblast</tissue>
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            <dbReference type="PubMed" id="7626884"/>
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        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA]</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]</scope>
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                <person name="Guffon N."/>
                <person name="Froissart R."/>
                <person name="Chevalier-Porst F."/>
                <person name="Maire I."/>
            </authorList>
            <dbReference type="PubMed" id="9452111"/>
            <dbReference type="DOI" id="10.1002/humu.1380110190"/>
        </citation>
        <scope>VARIANTS FD SER-40; SER-215; ASP-224; TYR-313 AND TRP-THR-SER-247 INS</scope>
    </reference>
    <reference key="41">
        <citation type="journal article" date="1999" name="Biochem. Biophys. Res. Commun." volume="257" first="708" last="713">
            <title>Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches.</title>
            <authorList>
                <person name="Germain D.P."/>
                <person name="Poenaru L."/>
            </authorList>
            <dbReference type="PubMed" id="10208848"/>
            <dbReference type="DOI" id="10.1006/bbrc.1999.0310"/>
        </citation>
        <scope>VARIANTS FD TRP-202; GLY-223; ASP-224; GLN-301 AND LYS-327</scope>
    </reference>
    <reference key="42">
        <citation type="journal article" date="1999" name="Clin. Chim. Acta" volume="280" first="81" last="89">
            <title>The multiple cases of Fabry disease in a Russian family caused by an E341K amino acid substitution in the alpha-galactosidase A.</title>
            <authorList>
                <person name="Beyer E.M."/>
                <person name="Karpova E.A."/>
                <person name="Udalova O.V."/>
                <person name="Ploos van Amstel J.K."/>
                <person name="van Diggelen O.P."/>
                <person name="Tsvetkova I.V."/>
            </authorList>
            <dbReference type="PubMed" id="10090526"/>
            <dbReference type="DOI" id="10.1016/s0009-8981(98)00133-8"/>
        </citation>
        <scope>VARIANT FD LYS-341</scope>
    </reference>
    <reference key="43">
        <citation type="journal article" date="2000" name="Biochim. Biophys. Acta" volume="1501" first="227" last="235">
            <title>Characterization of two alpha-galactosidase mutants (Q279E and R301Q) found in an atypical variant of Fabry disease.</title>
            <authorList>
                <person name="Kase R."/>
                <person name="Bierfreund U."/>
                <person name="Klein A."/>
                <person name="Kolter T."/>
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            </authorList>
            <dbReference type="PubMed" id="10838196"/>
            <dbReference type="DOI" id="10.1016/s0925-4439(00)00024-7"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS FD GLU-279 AND GLN-301</scope>
        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>ACTIVITY REGULATION</scope>
    </reference>
    <reference key="44">
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            <title>Twenty novel mutations in the alpha-galactosidase A gene causing Fabry disease.</title>
            <authorList>
                <person name="Topaloglu A.K."/>
                <person name="Ashley G.A."/>
                <person name="Tong B."/>
                <person name="Shabbeer J."/>
                <person name="Astrin K.H."/>
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                <person name="Desnick R.J."/>
            </authorList>
            <dbReference type="PubMed" id="10666480"/>
            <dbReference type="DOI" id="10.1007/bf03401993"/>
        </citation>
        <scope>VARIANTS FD VAL-42; CYS-112; ARG-142; ARG-148; VAL-165; ASP-183; SER-215; CYS-235; LEU-236; HIS-244; LEU-259; ILE-267; PHE-289; GLU-321; GLU-358 DEL AND TYR-378</scope>
    </reference>
    <reference key="45">
        <citation type="journal article" date="2000" name="Clin. Genet." volume="58" first="228" last="233">
            <title>Identification of four novel mutations in five unrelated Korean families with Fabry disease.</title>
            <authorList>
                <person name="Lee J.-K."/>
                <person name="Kim G.-H."/>
                <person name="Kim J.-S."/>
                <person name="Kim K.-K."/>
                <person name="Lee M.-C."/>
                <person name="Yoo H.-W."/>
            </authorList>
            <dbReference type="PubMed" id="11076046"/>
            <dbReference type="DOI" id="10.1034/j.1399-0004.2000.580311.x"/>
        </citation>
        <scope>VARIANT FD ASN-266</scope>
    </reference>
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            <title>Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes.</title>
            <authorList>
                <person name="Ashton-Prolla P."/>
                <person name="Tong B."/>
                <person name="Shabbeer J."/>
                <person name="Astrin K.H."/>
                <person name="Eng C.M."/>
                <person name="Desnick R.J."/>
            </authorList>
            <dbReference type="PubMed" id="10916280"/>
        </citation>
        <scope>VARIANTS FD LEU-40; SER-95; CYS-112; HIS-112; ASN-148; ARG-172; VAL-187; SER-224; ARG-226; GLN-227; THR-230; HIS-266; GLN-301 AND TYR-320</scope>
    </reference>
    <reference key="47">
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            <title>Identification of a novel de novo mutation (G373D) in the alpha-galactosidase A gene (GLA) in a patient affected with Fabry disease.</title>
            <authorList>
                <person name="Germain D.P."/>
                <person name="Salard D."/>
                <person name="Fellmann F."/>
                <person name="Azibi K."/>
                <person name="Caillaud C."/>
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                <person name="Poenaru L."/>
            </authorList>
            <dbReference type="PubMed" id="11295840"/>
            <dbReference type="DOI" id="10.1002/humu.41"/>
        </citation>
        <scope>VARIANT FD ASP-373</scope>
    </reference>
    <reference key="48">
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            <title>Fabry disease: 20 novel GLA mutations in 35 families.</title>
            <authorList>
                <person name="Blaydon D."/>
                <person name="Hill J.A."/>
                <person name="Winchester B.G."/>
            </authorList>
            <dbReference type="PubMed" id="11668641"/>
            <dbReference type="DOI" id="10.1002/humu.1219"/>
        </citation>
        <scope>VARIANTS FD TYR-46; GLY-47; PRO-49; SER-94; SER-95; CYS-112; SER-113; THR-143; SER-215; ARG-258; ARG-259; ILE-267; HIS-279; HIS-280; HIS-298; TYR-313; HIS-363; ASP-377; ALA-409 AND THR-409</scope>
    </reference>
    <reference key="49">
        <citation type="journal article" date="2002" name="Medicine (Baltimore)" volume="81" first="122" last="138">
            <title>Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course.</title>
            <authorList>
                <person name="Branton M.H."/>
                <person name="Schiffmann R."/>
                <person name="Sabnis S.G."/>
                <person name="Murray G.J."/>
                <person name="Quirk J.M."/>
                <person name="Altarescu G."/>
                <person name="Goldfarb L."/>
                <person name="Brady R.O."/>
                <person name="Balow J.E."/>
                <person name="Austin H.A. III"/>
                <person name="Kopp J.B."/>
            </authorList>
            <dbReference type="PubMed" id="11889412"/>
            <dbReference type="DOI" id="10.1097/00005792-200203000-00003"/>
        </citation>
        <scope>VARIANT FD PRO-143</scope>
    </reference>
    <reference key="50">
        <citation type="journal article" date="2003" name="Clin. Genet." volume="63" first="205" last="209">
            <title>Two novel mutations in the alpha-galactosidase A gene in Chinese patients with Fabry disease.</title>
            <authorList>
                <person name="Yang C.-C."/>
                <person name="Lai L.-W."/>
                <person name="Whitehair O."/>
                <person name="Hwu W.-L."/>
                <person name="Chiang S.-C."/>
                <person name="Lien Y.-H.H."/>
            </authorList>
            <dbReference type="PubMed" id="12694230"/>
            <dbReference type="DOI" id="10.1034/j.1399-0004.2003.00050.x"/>
        </citation>
        <scope>VARIANT FD ALA-410</scope>
    </reference>
    <reference key="51">
        <citation type="journal article" date="2003" name="Clin. Genet." volume="63" first="476" last="482">
            <title>Analysis of splice-site mutations of the alpha-galactosidase A gene in Fabry disease.</title>
            <authorList>
                <person name="Lai L.-W."/>
                <person name="Whitehair O."/>
                <person name="Wu M.-J."/>
                <person name="O'Meara M."/>
                <person name="Lien Y.-H.H."/>
            </authorList>
            <dbReference type="PubMed" id="12786754"/>
            <dbReference type="DOI" id="10.1034/j.1399-0004.2003.00077.x"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANT FD THR-65</scope>
    </reference>
    <reference key="52">
        <citation type="journal article" date="2004" name="Eur. J. Hum. Genet." volume="12" first="678" last="681">
            <title>Remarkable variability in renal disease in a large Slovenian family with Fabry disease.</title>
            <authorList>
                <person name="Verovnik F."/>
                <person name="Benko D."/>
                <person name="Vujkovac B."/>
                <person name="Linthorst G.E."/>
            </authorList>
            <dbReference type="PubMed" id="15162124"/>
            <dbReference type="DOI" id="10.1038/sj.ejhg.5201184"/>
        </citation>
        <scope>VARIANT FD SER-272</scope>
    </reference>
    <reference key="53">
        <citation type="journal article" date="2005" name="Hum. Mutat." volume="25" first="299" last="305">
            <title>Detection of alpha-galactosidase a mutations causing Fabry disease by denaturing high performance liquid chromatography.</title>
            <authorList>
                <person name="Shabbeer J."/>
                <person name="Robinson M."/>
                <person name="Desnick R.J."/>
            </authorList>
            <dbReference type="PubMed" id="15712228"/>
            <dbReference type="DOI" id="10.1002/humu.20144"/>
        </citation>
        <scope>VARIANTS FD VAL-31; LEU-42; ARG-43; ASN-93; CYS-112; HIS-112; SER-112; SER-134; VAL-135; ASP-171; PHE-201; SER-215; GLU-234; ASP-261; TYR-264; VAL-264; GLY-276; PRO-285; PHE-300; ALA-328; VAL-328; LYS-338; ALA-358; GLU-358 DEL; ARG-404 DEL AND SER-414</scope>
    </reference>
    <reference key="54">
        <citation type="journal article" date="2006" name="Arch. Neurol." volume="63" first="453" last="457">
            <title>Later-onset Fabry disease: an adult variant presenting with the cramp-fasciculation syndrome.</title>
            <authorList>
                <person name="Nance C.S."/>
                <person name="Klein C.J."/>
                <person name="Banikazemi M."/>
                <person name="Dikman S.H."/>
                <person name="Phelps R.G."/>
                <person name="McArthur J.C."/>
                <person name="Rodriguez M."/>
                <person name="Desnick R.J."/>
            </authorList>
            <dbReference type="PubMed" id="16533976"/>
            <dbReference type="DOI" id="10.1001/archneur.63.3.453"/>
        </citation>
        <scope>VARIANT FD THR-143</scope>
    </reference>
    <reference key="55">
        <citation type="journal article" date="2009" name="Hum. Mutat." volume="30" first="1397" last="1405">
            <title>Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G&gt;A (IVS4+919G&gt;A).</title>
            <authorList>
                <person name="Hwu W.L."/>
                <person name="Chien Y.H."/>
                <person name="Lee N.C."/>
                <person name="Chiang S.C."/>
                <person name="Dobrovolny R."/>
                <person name="Huang A.C."/>
                <person name="Yeh H.Y."/>
                <person name="Chao M.C."/>
                <person name="Lin S.J."/>
                <person name="Kitagawa T."/>
                <person name="Desnick R.J."/>
                <person name="Hsu L.W."/>
            </authorList>
            <dbReference type="PubMed" id="19621417"/>
            <dbReference type="DOI" id="10.1002/humu.21074"/>
        </citation>
        <scope>VARIANTS FD 12-CYS--LEU-14 DEL; PRO-46; GLN-66; ASN-93; VAL-120; THR-219; GLN-356 AND CYS-360</scope>
        <scope>CHARACTERIZATION OF VARIANTS FD 12-CYS--LEU-14 DEL; PRO-46; GLN-66; ASN-93; VAL-120; THR-219; GLN-356 AND CYS-360</scope>
    </reference>
    <reference key="56">
        <citation type="journal article" date="2016" name="Hum. Mutat." volume="37" first="43" last="51">
            <title>Functional and clinical consequences of novel alpha-galactosidase A mutations in Fabry disease.</title>
            <authorList>
                <person name="Lukas J."/>
                <person name="Scalia S."/>
                <person name="Eichler S."/>
                <person name="Pockrandt A.M."/>
                <person name="Dehn N."/>
                <person name="Cozma C."/>
                <person name="Giese A.K."/>
                <person name="Rolfs A."/>
            </authorList>
            <dbReference type="PubMed" id="26415523"/>
            <dbReference type="DOI" id="10.1002/humu.22910"/>
        </citation>
        <scope>CHARACTERIZATION OF VARIANTS FD ASP-20; PRO-20; PRO-21; GLY-33; GLU-35; TRP-36; SER-40; THR-42; PRO-45; ASP-48; TYR-56; LEU-60; PHE-64; ASP-80; HIS-86; ASN-91; THR-91; SER-94; TYR-94; ILE-113; THR-121; LEU-164; GLY-164; GLN-167; PHE-180; VAL-187; SER-196; THR-198; TYR-202; ARG-204; ARG-213; LEU-214; MET-219; PRO-227; SER-228; VAL-242; PHE-243; PRO-247; LYS-249; THR-253; ALA-254; ARG-259; ARG-262; GLY-269; GLY-276; VAL-309; ASN-315; ALA-316; SER-317; TYR-320; ARG-323; ARG-327; LEU-327; ARG-328; ARG-330; PRO-342; GLY-352; PRO-356; LYS-358; SER-360; ALA-375; SER-392; SER-399 AND ARG-404 DEL</scope>
        <scope>CHARACTERIZATION OF VARIANTS PRO-3; VAL-3; GLY-71; THR-154; VAL-289 AND ASN-313</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
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            <title>A novel mutation of alpha-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family.</title>
            <authorList>
                <person name="Ge W."/>
                <person name="Wei B."/>
                <person name="Zhu H."/>
                <person name="Miao Z."/>
                <person name="Zhang W."/>
                <person name="Leng C."/>
                <person name="Li J."/>
                <person name="Zhang D."/>
                <person name="Sun M."/>
                <person name="Xu X."/>
            </authorList>
            <dbReference type="PubMed" id="27211852"/>
            <dbReference type="DOI" id="10.1080/00207454.2016.1191483"/>
        </citation>
        <scope>VARIANT FD ARG-47</scope>
        <scope>CHARACTERIZATION OF VARIANTS FD ARG-47 AND GLY-47</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>FUNCTION</scope>
    </reference>
    <reference key="58">
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            <title>Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant.</title>
            <authorList>
                <person name="Lenders M."/>
                <person name="Weidemann F."/>
                <person name="Kurschat C."/>
                <person name="Canaan-Kuehl S."/>
                <person name="Duning T."/>
                <person name="Stypmann J."/>
                <person name="Schmitz B."/>
                <person name="Reiermann S."/>
                <person name="Kraemer J."/>
                <person name="Blaschke D."/>
                <person name="Wanner C."/>
                <person name="Brand S.M."/>
                <person name="Brand E."/>
            </authorList>
            <dbReference type="PubMed" id="27142856"/>
            <dbReference type="DOI" id="10.1186/s13023-016-0441-z"/>
        </citation>
        <scope>VARIANT FD THR-143</scope>
    </reference>
    <comment type="function">
        <text evidence="5 37">Catalyzes the hydrolysis of glycosphingolipids and participates in their degradation in the lysosome.</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="24 26">
            <text>Hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-D-galactosides, including galactose oligosaccharides, galactomannans and galactolipids.</text>
            <dbReference type="EC" id="3.2.1.22"/>
        </reaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 37">
            <text>a globoside Gb3Cer (d18:1(4E)) + H2O = a beta-D-Gal-(1-&gt;4)-beta-D-Glc-(1&lt;-&gt;1)-Cer(d18:1(4E)) + D-galactose</text>
            <dbReference type="Rhea" id="RHEA:21112"/>
            <dbReference type="ChEBI" id="CHEBI:4139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:17950"/>
            <dbReference type="ChEBI" id="CHEBI:18313"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="50 51">
            <dbReference type="Rhea" id="RHEA:21113"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="5 37">
            <text>a globoside Gb3Cer + H2O = a beta-D-galactosyl-(1-&gt;4)-beta-D-glucosyl-(1&lt;-&gt;1)-ceramide + D-galactose</text>
            <dbReference type="Rhea" id="RHEA:48020"/>
            <dbReference type="ChEBI" id="CHEBI:4139"/>
            <dbReference type="ChEBI" id="CHEBI:15377"/>
            <dbReference type="ChEBI" id="CHEBI:79208"/>
            <dbReference type="ChEBI" id="CHEBI:88154"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="50 51">
            <dbReference type="Rhea" id="RHEA:48021"/>
        </physiologicalReaction>
    </comment>
    <comment type="activity regulation">
        <text evidence="5 37">Galactosylgalactosylglucosylceramidase activity is stimulated by saposin B and ammonium chloride.</text>
    </comment>
    <comment type="subunit">
        <text evidence="14">Homodimer.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2513305">
            <id>P06280</id>
        </interactant>
        <interactant intactId="EBI-1048799">
            <id>Q2TAA5</id>
            <label>ALG11</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>2</experiments>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-2513305">
            <id>P06280</id>
        </interactant>
        <interactant intactId="EBI-1057058">
            <id>Q99523</id>
            <label>SORT1</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location>Lysosome</location>
        </subcellularLocation>
    </comment>
    <comment type="RNA editing">
        <location>
            <position position="396" evidence="27"/>
        </location>
        <text>Partially edited.</text>
    </comment>
    <comment type="disease" evidence="2 3 4 5 6 7 8 9 10 11 12 13 15 16 17 18 20 21 22 23 24 25 26 28 29 30 31 32 33 34 35 36 38 39 40 41 42 43 44 45 46 47 48">
        <disease id="DI-01544">
            <name>Fabry disease</name>
            <acronym>FD</acronym>
            <description>Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.</description>
            <dbReference type="MIM" id="301500"/>
        </disease>
        <text>The disease is caused by variants affecting the gene represented in this entry.</text>
    </comment>
    <comment type="pharmaceutical">
        <text>Available under the names Replagal (from Shire) and Fabrazyme (from Genzyme). Used as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease. The differences between Replagal (also known as agalsidase alpha) and Fabrazyme (also known as agalsidase beta) lies in the glycosylation patterns. Agalsidase beta is produced in the hamster CHO cell line while agalsidase alpha is produced in human cell lines.</text>
    </comment>
    <comment type="similarity">
        <text evidence="49">Belongs to the glycosyl hydrolase 27 family.</text>
    </comment>
    <dbReference type="EC" id="3.2.1.22" evidence="24 26"/>
    <dbReference type="EMBL" id="X05790">
        <property type="protein sequence ID" value="CAA29232.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X14448">
        <property type="protein sequence ID" value="CAA32617.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="U78027">
        <property type="protein sequence ID" value="AAB64203.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AL035422">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC002689">
        <property type="protein sequence ID" value="AAH02689.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M13571">
        <property type="protein sequence ID" value="AAA51676.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="D00039">
        <property type="protein sequence ID" value="BAA34059.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M18242">
        <property type="protein sequence ID" value="AAA52514.1"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="EMBL" id="X16889">
        <property type="status" value="NOT_ANNOTATED_CDS"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="M20317">
        <property type="protein sequence ID" value="AAA52559.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS14484.1"/>
    <dbReference type="PIR" id="S04081">
        <property type="entry name" value="GBHUA"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_000160.1">
        <property type="nucleotide sequence ID" value="NM_000169.3"/>
    </dbReference>
    <dbReference type="PDB" id="1R46">
        <property type="method" value="X-ray"/>
        <property type="resolution" value="3.25 A"/>
        <property type="chains" value="A/B=32-429"/>
    </dbReference>
    <dbReference type="PDB" id="1R47">
        <property type="method" value="X-ray"/>
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            <position position="139"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="14">
        <location>
            <position position="192"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="N-linked (GlcNAc...) asparagine" evidence="14 19">
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="52"/>
            <end position="94"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="56"/>
            <end position="63"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="142"/>
            <end position="172"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="202"/>
            <end position="223"/>
        </location>
    </feature>
    <feature type="disulfide bond">
        <location>
            <begin position="378"/>
            <end position="382"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077365" description="Does not affect enzyme activity; dbSNP:rs150547672." evidence="24">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077366" description="Does not affect enzyme activity; dbSNP:rs869312133." evidence="24">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="3"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062550" description="In FD; has 4% of wild-type activity." evidence="20">
        <location>
            <begin position="12"/>
            <end position="14"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077367" description="In FD; loss of enzyme activity; dbSNP:rs869312134." evidence="24">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012362" description="In FD; atypical; loss of enzyme activity; dbSNP:rs104894847." evidence="24 31 44">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="20"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077368" description="In FD; loss of enzyme activity; dbSNP:rs869312135." evidence="24">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="21"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012363" description="In FD; dbSNP:rs869312448." evidence="16 43">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="31"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000431" description="In FD; dbSNP:rs1569306168." evidence="32">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="32"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077369" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312136." evidence="24">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="33"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000432" description="In FD; dbSNP:rs104894835." evidence="28 32 35">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="34"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077370" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312137." evidence="24">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="35"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000433" description="In FD." evidence="34">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="35"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077371" description="In FD; loss of enzyme activity; dbSNP:rs869312138." evidence="24">
        <original>L</original>
        <variation>W</variation>
        <location>
            <position position="36"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012364" description="In FD; dbSNP:rs398123199." evidence="6">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000434" description="In FD; loss of enzyme activity; dbSNP:rs104894831." evidence="21 24 44 47">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="40"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062551" description="In FD; dbSNP:rs797044613." evidence="16">
        <original>M</original>
        <variation>L</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077372" description="In FD; loss of enzyme activity; dbSNP:rs398123201." evidence="24">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012365" description="In FD; dbSNP:rs797044613." evidence="4 41">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="42"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062552" description="In FD; dbSNP:rs886044906." evidence="16">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="43"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012366" description="In FD." evidence="43">
        <original>LH</original>
        <variation>RS</variation>
        <location>
            <begin position="45"/>
            <end position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077373" description="In FD; loss of enzyme activity." evidence="24">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="45"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062553" description="In FD; has 36% of wild-type activity." evidence="20">
        <original>H</original>
        <variation>P</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012367" description="In FD; dbSNP:rs398123203." evidence="43">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012368" description="In FD; dbSNP:rs1928582757." evidence="9">
        <original>H</original>
        <variation>Y</variation>
        <location>
            <position position="46"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012369" description="In FD; decreased alpha-galactosidase activity." evidence="9 26">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_076478" description="In FD; decreased alpha-galactosidase activity." evidence="26">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="47"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077374" description="In FD; loss of enzyme activity; dbSNP:rs869312254." evidence="24">
        <original>E</original>
        <variation>D</variation>
        <location>
            <position position="48"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000435" description="In FD." evidence="34">
        <original>R</original>
        <variation>L</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012370" description="In FD; dbSNP:rs398123205." evidence="9">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012371" description="In FD." evidence="41">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="49"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000436" description="In FD; dbSNP:rs1057521047." evidence="38 42">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000437" description="In FD; dbSNP:rs869312256." evidence="29">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="52"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000438" description="In FD; dbSNP:rs869312258." evidence="29">
        <original>C</original>
        <variation>F</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000439" description="In FD; dbSNP:rs104894836." evidence="28">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012372" description="In FD; loss of enzyme activity; dbSNP:rs869312258." evidence="24 41">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="56"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000440" description="In FD." evidence="29">
        <original>E</original>
        <variation>K</variation>
        <location>
            <position position="59"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077375" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312262." evidence="24">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="60"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077376" description="In FD; loss of enzyme activity; dbSNP:rs869312139." evidence="24">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="64"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032290" description="In FD; does not affect enzyme function; dbSNP:rs104894848." evidence="12 48">
        <original>S</original>
        <variation>T</variation>
        <location>
            <position position="65"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000441" description="In FD; has 52% of wild-type activity; dbSNP:rs104894833." evidence="13 20 30 44">
        <original>E</original>
        <variation>Q</variation>
        <location>
            <position position="66"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077377" description="Does not affect enzyme activity; dbSNP:rs781927744." evidence="24">
        <original>E</original>
        <variation>G</variation>
        <location>
            <position position="71"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000442" description="In FD; atypical." evidence="44 46">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="72"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077378" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs781838005." evidence="24">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="80"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000443" description="In FD; dbSNP:rs1569304898." evidence="32">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="85"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012373" description="In FD." evidence="43">
        <original>Y</original>
        <variation>C</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077379" description="In FD; loss of enzyme activity; dbSNP:rs869312140." evidence="24">
        <original>Y</original>
        <variation>H</variation>
        <location>
            <position position="86"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012374" description="In FD." evidence="43">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000444" description="In FD; dbSNP:rs1569304886." evidence="29">
        <original>L</original>
        <variation>R</variation>
        <location>
            <position position="89"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077380" description="In FD; loss of enzyme activity; dbSNP:rs869312141." evidence="24">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012375" description="In FD; mild; loss of enzyme activity; dbSNP:rs869312141." evidence="24 43">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="91"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012376" description="In FD; dbSNP:rs886041315." evidence="41">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012377" description="In FD; dbSNP:rs886041315." evidence="43">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="92"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012378" description="In FD." evidence="41">
        <original>D</original>
        <variation>G</variation>
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062554" description="In FD; has no enzyme activity; dbSNP:rs869312270." evidence="16 20">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="93"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012379" description="In FD; loss of enzyme activity; dbSNP:rs2147480697." evidence="9 24">
        <original>C</original>
        <variation>S</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012380" description="In FD; loss of enzyme activity; dbSNP:rs113173389." evidence="24 43">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="94"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012381" description="In FD." evidence="6 9">
        <original>W</original>
        <variation>S</variation>
        <location>
            <position position="95"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012382" description="In FD; dbSNP:rs1569304867." evidence="43">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="97"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000445" description="In FD; dbSNP:rs869312273." evidence="29">
        <original>R</original>
        <variation>K</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012383" description="In FD." evidence="43">
        <original>R</original>
        <variation>T</variation>
        <location>
            <position position="100"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000446" description="In FD.">
        <location>
            <begin position="112"/>
            <end position="117"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000447" description="In FD; dbSNP:rs104894834." evidence="4 6 9 13 16 30 44">
        <original>R</original>
        <variation>C</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000448" description="In FD; mild; dbSNP:rs372966991." evidence="6 16 29">
        <original>R</original>
        <variation>H</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062555" description="In FD; dbSNP:rs104894834." evidence="16">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="112"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077381" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312142." evidence="24">
        <original>F</original>
        <variation>I</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012384" description="In FD; mild; dbSNP:rs869312142." evidence="43">
        <original>F</original>
        <variation>L</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012385" description="In FD; dbSNP:rs2147480502." evidence="9">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="113"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000449" description="In FD.">
        <original>LA</original>
        <variation>PT</variation>
        <location>
            <begin position="120"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062556" description="In FD; has 42% of wild-type activity." evidence="20">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="120"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077382" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs782197638." evidence="24">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="121"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000450" description="In FD." evidence="38">
        <original>G</original>
        <variation>E</variation>
        <location>
            <position position="128"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000451" description="In FD; dbSNP:rs869312298." evidence="29">
        <original>L</original>
        <variation>P</variation>
        <location>
            <position position="131"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012386" description="In FD; dbSNP:rs2147477791." evidence="16 43">
        <original>Y</original>
        <variation>S</variation>
        <location>
            <position position="134"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062557" description="In FD; dbSNP:rs1569304221." evidence="16">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="135"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012387" description="In FD; dbSNP:rs1928326524." evidence="43">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="138"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012388" description="In FD; dbSNP:rs886044845." evidence="4">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000452" description="In FD." evidence="33 44">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="142"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000453" description="In FD; dbSNP:rs104894845." evidence="10 29">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012389" description="In FD; uncertain significance; dbSNP:rs104894845." evidence="9 17 25 43">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="143"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000454" description="In FD; dbSNP:rs782085638." evidence="29">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="144"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000455" description="In FD; mild; dbSNP:rs104894837." evidence="29">
        <original>P</original>
        <variation>S</variation>
        <location>
            <position position="146"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012390" description="In FD; dbSNP:rs1555985829." evidence="6">
        <original>S</original>
        <variation>N</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012391" description="In FD; dbSNP:rs1569304190." evidence="4 43">
        <original>S</original>
        <variation>R</variation>
        <location>
            <position position="148"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077383" description="Does not affect enzyme activity; dbSNP:rs869312143." evidence="24">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="154"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000456" description="In FD; dbSNP:rs28935195." evidence="32">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000457" description="In FD; dbSNP:rs869312307." evidence="30 33 44">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="156"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012392" description="In FD; dbSNP:rs869312311." evidence="42">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000458" description="In FD; dbSNP:rs28935196." evidence="28">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="162"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012393" description="In FD." evidence="43">
        <original>G</original>
        <variation>V</variation>
        <location>
            <position position="163"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077384" description="In FD; loss of enzyme activity." evidence="24">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077385" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312144." evidence="24">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="164"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000459" description="In FD." evidence="4 34">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="165"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000460" description="In FD." evidence="30 33 44">
        <original>L</original>
        <variation>V</variation>
        <location>
            <position position="166"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077386" description="In FD; loss of enzyme activity." evidence="24">
        <original>L</original>
        <variation>Q</variation>
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012394" description="In FD." evidence="43">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="170"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062558" description="In FD." evidence="16">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="171"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012395" description="In FD." evidence="6">
        <original>C</original>
        <variation>R</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000461" description="In FD; dbSNP:rs869312318." evidence="29">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="172"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077387" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312145." evidence="24">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="180"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012396" description="In FD; dbSNP:rs398123212." evidence="4">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="183"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077388" description="In FD; loss of enzyme activity; dbSNP:rs869312146." evidence="24">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012397" description="In FD; decreased enzyme activity; dbSNP:rs869312340." evidence="6 24">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="187"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077389" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312147." evidence="24">
        <original>R</original>
        <variation>S</variation>
        <location>
            <position position="196"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077390" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs727503950." evidence="24">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="198"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062559" description="In FD." evidence="16">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="201"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000462" description="In FD; dbSNP:rs104894838." evidence="3">
        <original>C</original>
        <variation>W</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012398" description="In FD; loss of enzyme activity; dbSNP:rs869312344." evidence="24 43">
        <original>C</original>
        <variation>Y</variation>
        <location>
            <position position="202"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077391" description="In FD; loss of enzyme activity; dbSNP:rs869312148." evidence="24">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="204"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012399" description="In FD." evidence="43">
        <location>
            <begin position="205"/>
            <end position="207"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000463" description="In FD; dbSNP:rs397515870." evidence="38 41">
        <original>P</original>
        <variation>T</variation>
        <location>
            <position position="205"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077392" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312149." evidence="24">
        <original>K</original>
        <variation>R</variation>
        <location>
            <position position="213"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077393" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312150." evidence="24">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="214"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000464" description="In FD; mild; dbSNP:rs28935197." evidence="4 9 16 35 47">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="215"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012400" description="In FD; dbSNP:rs1928199003." evidence="43">
        <original>Y</original>
        <variation>D</variation>
        <location>
            <position position="216"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077394" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312151." evidence="24">
        <original>I</original>
        <variation>M</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000465" description="In FD." evidence="29">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062560" description="In FD; has 46% of wild-type activity; dbSNP:rs2147473404." evidence="20">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="219"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012401" description="In FD; dbSNP:rs869312381." evidence="3">
        <original>C</original>
        <variation>G</variation>
        <location>
            <position position="223"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000466" description="In FD; dbSNP:rs1555985175." evidence="3 47">
        <original>N</original>
        <variation>D</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012402" description="In FD; dbSNP:rs869312383." evidence="6">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="224"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012403" description="In FD; dbSNP:rs1928196393." evidence="6">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="226"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077395" description="In FD; loss of enzyme activity; dbSNP:rs104894840." evidence="24">
        <original>R</original>
        <variation>P</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000467" description="In FD; dbSNP:rs104894840." evidence="6 28">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="227"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077396" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312152." evidence="24">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="228"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012404" description="In FD; dbSNP:rs1928195468." evidence="6">
        <original>A</original>
        <variation>T</variation>
        <location>
            <position position="230"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000468" description="In FD." evidence="40">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="231"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062561" description="In FD." evidence="16">
        <original>D</original>
        <variation>E</variation>
        <location>
            <position position="234"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012405" description="In FD; dbSNP:rs797044746." evidence="4">
        <original>S</original>
        <variation>C</variation>
        <location>
            <position position="235"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012406" description="In FD; dbSNP:rs869312386." evidence="41">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012407" description="In FD." evidence="4">
        <original>W</original>
        <variation>L</variation>
        <location>
            <position position="236"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012408" description="In FD." evidence="44">
        <original>I</original>
        <variation>N</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077397" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs397515873." evidence="24">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="242"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077398" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs397515874." evidence="24">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="243"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012409" description="In FD; dbSNP:rs727503948." evidence="4">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000469" description="In FD; dbSNP:rs727503948." evidence="29">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="244"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077399" description="In FD; loss of enzyme activity; dbSNP:rs869312393." evidence="24">
        <original>S</original>
        <variation>P</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000470" description="In FD.">
        <original>S</original>
        <variation>SWTS</variation>
        <location>
            <position position="247"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077400" description="In FD; uncertain significance; decreased enzyme activity." evidence="24">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="249"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077401" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs727505292." evidence="24">
        <original>I</original>
        <variation>T</variation>
        <location>
            <position position="253"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077402" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312153." evidence="24">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="254"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012410" description="In FD." evidence="9">
        <original>G</original>
        <variation>R</variation>
        <location>
            <position position="258"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012411" description="In FD; dbSNP:rs869312399." evidence="4">
        <original>P</original>
        <variation>L</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012412" description="In FD; decreased enzyme activity; dbSNP:rs869312399." evidence="9 24">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="259"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012413" description="In FD." evidence="30 44">
        <original>G</original>
        <variation>A</variation>
        <location>
            <position position="260"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012414" description="In FD; dbSNP:rs869312401." evidence="16 44">
        <original>G</original>
        <variation>D</variation>
        <location>
            <position position="261"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077403" description="In FD; loss of enzyme activity; dbSNP:rs869312154." evidence="24">
        <original>W</original>
        <variation>R</variation>
        <location>
            <position position="262"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012415" description="In FD; dbSNP:rs869312404." evidence="43">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="263"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000471" description="In FD; dbSNP:rs28935486." evidence="16 28">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062562" description="In FD; dbSNP:rs190347120." evidence="16">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="264"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012416" description="In FD." evidence="42">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="265"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032291" description="In FD." evidence="6">
        <original>D</original>
        <variation>H</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012418" description="In FD; dbSNP:rs869312407." evidence="7">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000472" description="In FD; dbSNP:rs28935487." evidence="28">
        <original>D</original>
        <variation>V</variation>
        <location>
            <position position="266"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012419" description="In FD; dbSNP:rs730880451." evidence="4 9">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="267"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000473" description="In FD; dbSNP:rs28935488." evidence="35">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="269"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077404" description="In FD; loss of enzyme activity; dbSNP:rs28935488." evidence="24">
        <original>V</original>
        <variation>G</variation>
        <location>
            <position position="269"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000474" description="In FD." evidence="29">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_032292" description="In FD; dbSNP:rs28935495." evidence="15">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062563" description="In FD; loss of enzyme activity; dbSNP:rs869312432." evidence="16 24">
        <original>S</original>
        <variation>G</variation>
        <location>
            <position position="276"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000475" description="In FD; mild; does not significantly affect the enzyme activity but the mutant protein levels are decreased presumably in the ER of the cells; dbSNP:rs28935485." evidence="5 13 30 44">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012420" description="In FD." evidence="9">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="279"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012421" description="In FD." evidence="9">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="280"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000476" description="In FD; dbSNP:rs1928171557." evidence="38">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="284"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062564" description="In FD." evidence="16">
        <original>A</original>
        <variation>P</variation>
        <location>
            <position position="285"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012422" description="In FD; dbSNP:rs104894839." evidence="43">
        <original>W</original>
        <variation>C</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012423" description="In FD." evidence="41">
        <original>W</original>
        <variation>G</variation>
        <location>
            <position position="287"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000477" description="In FD; dbSNP:rs869312437." evidence="29">
        <original>A</original>
        <variation>D</variation>
        <location>
            <position position="288"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012424" description="In FD; dbSNP:rs140329381." evidence="4">
        <original>I</original>
        <variation>F</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077405" description="Decreased enzyme activity; dbSNP:rs140329381." evidence="24">
        <original>I</original>
        <variation>V</variation>
        <location>
            <position position="289"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012425" description="In FD; atypical; dbSNP:rs104894846." evidence="30 31 44">
        <original>M</original>
        <variation>I</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000478" description="In FD; mild; dbSNP:rs104894830." evidence="18">
        <original>M</original>
        <variation>V</variation>
        <location>
            <position position="296"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000479" description="In FD; dbSNP:rs28935489." evidence="28">
        <original>S</original>
        <variation>F</variation>
        <location>
            <position position="297"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012426" description="In FD." evidence="9 41">
        <original>N</original>
        <variation>H</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000480" description="In FD; dbSNP:rs869312444." evidence="38">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012427" description="In FD; dbSNP:rs1569302985." evidence="43">
        <original>N</original>
        <variation>S</variation>
        <location>
            <position position="298"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_062565" description="In FD; dbSNP:rs2147472132." evidence="16">
        <original>L</original>
        <variation>F</variation>
        <location>
            <position position="300"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000481" description="In FD; mild; does not significantly affect the enzyme activity but the mutant protein levels are decreased presumably in the ER of the cells; dbSNP:rs104894828." evidence="3 5 6 13 22 30 32 36 44">
        <original>R</original>
        <variation>Q</variation>
        <location>
            <position position="301"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077406" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312155." evidence="24">
        <original>A</original>
        <variation>V</variation>
        <location>
            <position position="309"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077407" description="Does not affect enzyme activity; dbSNP:rs28935490." evidence="24">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000482" description="In FD; dbSNP:rs28935490." evidence="9 28 47">
        <original>D</original>
        <variation>Y</variation>
        <location>
            <position position="313"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077408" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312156." evidence="24">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="315"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012429" description="In FD." evidence="42">
        <location>
            <begin position="316"/>
            <end position="322"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077409" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312157." evidence="24">
        <original>V</original>
        <variation>A</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000483" description="In FD." evidence="34">
        <original>V</original>
        <variation>E</variation>
        <location>
            <position position="316"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077410" description="In FD; loss of enzyme activity; dbSNP:rs869312158." evidence="24">
        <original>I</original>
        <variation>S</variation>
        <location>
            <position position="317"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012430" description="In FD." evidence="30 44">
        <original>N</original>
        <variation>K</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012431" description="In FD; loss of enzyme activity." evidence="6 24">
        <original>N</original>
        <variation>Y</variation>
        <location>
            <position position="320"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_012432" description="In FD; dbSNP:rs730880439." evidence="4">
        <original>Q</original>
        <variation>E</variation>
        <location>
            <position position="321"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_077411" description="In FD; uncertain significance; decreased enzyme activity; dbSNP:rs869312159." evidence="24">
        <original>P</original>
        <variation>R</variation>
        <location>
            <position position="323"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_000484" description="In FD; dbSNP:rs28935491." evidence="3 35">
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        </source>
    </evidence>
    <evidence type="ECO:0007829" key="56">
        <source>
            <dbReference type="PDB" id="6IBT"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="57">
        <source>
            <dbReference type="PDB" id="8K7F"/>
        </source>
    </evidence>
    <sequence length="429" mass="48767" checksum="613F8BF21B107D7B" modified="1988-08-01" version="1" precursor="true">MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="1996-10-01" modified="2026-01-28" version="214" xmlns="https://uniprot.org/uniprot">
    <accession>P52594</accession>
    <accession>B3KUL1</accession>
    <accession>E9PHX7</accession>
    <accession>Q15277</accession>
    <accession>Q4VAS0</accession>
    <accession>Q4VAS1</accession>
    <accession>Q4VAS3</accession>
    <accession>Q53QT8</accession>
    <accession>Q53R11</accession>
    <name>AGFG1_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP domain and FG repeat-containing protein 1</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>HIV-1 Rev-binding protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Nucleoporin-like protein RIP</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Rev-interacting protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Rev/Rex activation domain-binding protein</fullName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGFG1</name>
        <name type="synonym">HRB</name>
        <name type="synonym">RAB</name>
        <name type="synonym">RIP</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <citation type="journal article" date="2010" name="Sci. Signal." volume="3" first="RA3" last="RA3">
            <title>Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.</title>
            <authorList>
                <person name="Olsen J.V."/>
                <person name="Vermeulen M."/>
                <person name="Santamaria A."/>
                <person name="Kumar C."/>
                <person name="Miller M.L."/>
                <person name="Jensen L.J."/>
                <person name="Gnad F."/>
                <person name="Cox J."/>
                <person name="Jensen T.S."/>
                <person name="Nigg E.A."/>
                <person name="Brunak S."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="20068231"/>
            <dbReference type="DOI" id="10.1126/scisignal.2000475"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
        </source>
    </reference>
    <reference key="15">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="16">
        <citation type="journal article" date="2011" name="Sci. Signal." volume="4" first="RS3" last="RS3">
            <title>System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.</title>
            <authorList>
                <person name="Rigbolt K.T."/>
                <person name="Prokhorova T.A."/>
                <person name="Akimov V."/>
                <person name="Henningsen J."/>
                <person name="Johansen P.T."/>
                <person name="Kratchmarova I."/>
                <person name="Kassem M."/>
                <person name="Mann M."/>
                <person name="Olsen J.V."/>
                <person name="Blagoev B."/>
            </authorList>
            <dbReference type="PubMed" id="21406692"/>
            <dbReference type="DOI" id="10.1126/scisignal.2001570"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="17">
        <citation type="journal article" date="2012" name="Nat. Cell Biol." volume="14" first="488" last="501">
            <title>Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning.</title>
            <authorList>
                <person name="Umasankar P.K."/>
                <person name="Sanker S."/>
                <person name="Thieman J.R."/>
                <person name="Chakraborty S."/>
                <person name="Wendland B."/>
                <person name="Tsang M."/>
                <person name="Traub L.M."/>
            </authorList>
            <dbReference type="PubMed" id="22484487"/>
            <dbReference type="DOI" id="10.1038/ncb2473"/>
        </citation>
        <scope>INTERACTION WITH FCHO1</scope>
    </reference>
    <reference key="18">
        <citation type="journal article" date="2013" name="J. Proteome Res." volume="12" first="260" last="271">
            <title>Toward a comprehensive characterization of a human cancer cell phosphoproteome.</title>
            <authorList>
                <person name="Zhou H."/>
                <person name="Di Palma S."/>
                <person name="Preisinger C."/>
                <person name="Peng M."/>
                <person name="Polat A.N."/>
                <person name="Heck A.J."/>
                <person name="Mohammed S."/>
            </authorList>
            <dbReference type="PubMed" id="23186163"/>
            <dbReference type="DOI" id="10.1021/pr300630k"/>
        </citation>
        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-167; THR-177; SER-181 AND SER-362</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Cervix carcinoma</tissue>
            <tissue>Erythroleukemia</tissue>
        </source>
    </reference>
    <reference key="19">
        <citation type="journal article" date="2014" name="J. Proteomics" volume="96" first="253" last="262">
            <title>An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.</title>
            <authorList>
                <person name="Bian Y."/>
                <person name="Song C."/>
                <person name="Cheng K."/>
                <person name="Dong M."/>
                <person name="Wang F."/>
                <person name="Huang J."/>
                <person name="Sun D."/>
                <person name="Wang L."/>
                <person name="Ye M."/>
                <person name="Zou H."/>
            </authorList>
            <dbReference type="PubMed" id="24275569"/>
            <dbReference type="DOI" id="10.1016/j.jprot.2013.11.014"/>
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        <scope>PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
        <source>
            <tissue>Liver</tissue>
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    </reference>
    <reference key="20">
        <citation type="journal article" date="2015" name="Proteomics" volume="15" first="2519" last="2524">
            <title>N-terminome analysis of the human mitochondrial proteome.</title>
            <authorList>
                <person name="Vaca Jacome A.S."/>
                <person name="Rabilloud T."/>
                <person name="Schaeffer-Reiss C."/>
                <person name="Rompais M."/>
                <person name="Ayoub D."/>
                <person name="Lane L."/>
                <person name="Bairoch A."/>
                <person name="Van Dorsselaer A."/>
                <person name="Carapito C."/>
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            <dbReference type="PubMed" id="25944712"/>
            <dbReference type="DOI" id="10.1002/pmic.201400617"/>
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        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="21">
        <citation type="submission" date="2006-12" db="PDB data bank">
            <title>Solution structure of the ARFGAP domain of human RIP.</title>
            <authorList>
                <consortium name="RIKEN structural genomics initiative (RSGI)"/>
            </authorList>
        </citation>
        <scope>STRUCTURE BY NMR OF 14-134</scope>
    </reference>
    <comment type="function">
        <text evidence="1 4 5 6">Required for vesicle docking or fusion during acrosome biogenesis (By similarity). May play a role in RNA trafficking or localization. In case of infection by HIV-1, acts as a cofactor for viral Rev and promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm. This step is essential for HIV-1 replication.</text>
    </comment>
    <comment type="subunit">
        <text evidence="4 7 8 9">Interacts with EPS15R and EPS15. Interacts with FCHO1.</text>
    </comment>
    <comment type="interaction">
        <interactant intactId="EBI-996560">
            <id>P52594</id>
        </interactant>
        <interactant intactId="EBI-396684">
            <id>P42566</id>
            <label>EPS15</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>3</experiments>
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    <comment type="interaction">
        <interactant intactId="EBI-996560">
            <id>P52594</id>
        </interactant>
        <interactant intactId="EBI-10269689">
            <id>Q9P242</id>
            <label>NYAP2</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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            <id>P52594</id>
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            <id>P56282</id>
            <label>POLE2</label>
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        <organismsDiffer>false</organismsDiffer>
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    <comment type="interaction">
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        </interactant>
        <interactant intactId="EBI-1052205">
            <id>P51809</id>
            <label>VAMP7</label>
        </interactant>
        <organismsDiffer>false</organismsDiffer>
        <experiments>7</experiments>
    </comment>
    <comment type="subcellular location">
        <subcellularLocation>
            <location evidence="4 8">Nucleus</location>
        </subcellularLocation>
        <subcellularLocation>
            <location evidence="4">Cytoplasmic vesicle</location>
        </subcellularLocation>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
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            <id>P52594-1</id>
            <name>1</name>
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            <sequence type="described" ref="VSP_017600"/>
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            <sequence type="described" ref="VSP_017601"/>
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            <id>P52594-4</id>
            <name>4</name>
            <sequence type="described" ref="VSP_046186 VSP_017601"/>
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    <comment type="tissue specificity">
        <text evidence="8">Ubiquitously expressed.</text>
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    <comment type="domain">
        <text>Contains FG repeats. The FG repeat region is required for acting as a cofactor of HIV-1 Rev.</text>
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        <text evidence="1">O-glycosylated.</text>
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        <conflict type="miscellaneous discrepancy">
            <sequence resource="EMBL-CDS" id="BAG53473" version="1"/>
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        <text>Aberrant splicing within exon 1.</text>
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        <property type="match status" value="1"/>
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    <dbReference type="FunFam" id="1.10.220.150:FF:000005">
        <property type="entry name" value="Arf-GAP domain and FG repeat-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="3.30.450.50:FF:000005">
        <property type="entry name" value="arf-GAP domain and FG repeat-containing protein 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Gene3D" id="3.30.450.50">
        <property type="entry name" value="Longin domain"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052248">
        <property type="entry name" value="Arf-GAP_FG-repeat_protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46134:SF1">
        <property type="entry name" value="ARF-GAP DOMAIN AND FG REPEAT-CONTAINING PROTEIN 1"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46134">
        <property type="entry name" value="DRONGO, ISOFORM F"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
        <property type="match status" value="1"/>
    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0002">3D-structure</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0968">Cytoplasmic vesicle</keyword>
    <keyword id="KW-0217">Developmental protein</keyword>
    <keyword id="KW-0221">Differentiation</keyword>
    <keyword id="KW-0238">DNA-binding</keyword>
    <keyword id="KW-0325">Glycoprotein</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-0509">mRNA transport</keyword>
    <keyword id="KW-0539">Nucleus</keyword>
    <keyword id="KW-0597">Phosphoprotein</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0744">Spermatogenesis</keyword>
    <keyword id="KW-0813">Transport</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000204904" description="Arf-GAP domain and FG repeat-containing protein 1">
        <location>
            <begin position="1"/>
            <end position="562"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="11"/>
            <end position="135"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="29"/>
            <end position="52"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="145"/>
            <end position="193"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="176"/>
            <end position="191"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="167"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphothreonine" evidence="13 14 17">
        <location>
            <position position="177"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="13 15 16 17 18">
        <location>
            <position position="181"/>
        </location>
    </feature>
    <feature type="modified residue" description="Phosphoserine" evidence="17">
        <location>
            <position position="362"/>
        </location>
    </feature>
    <feature type="glycosylation site" description="O-linked (GlcNAc) serine" evidence="1">
        <location>
            <position position="367"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_017600" description="In isoform 2." evidence="11">
        <location>
            <begin position="232"/>
            <end position="271"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_046186" description="In isoform 4." evidence="10">
        <original>G</original>
        <variation>AFRMLSSSCSFGEFTSAFPLQATHS</variation>
        <location>
            <position position="272"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_017601" description="In isoform 3 and isoform 4." evidence="10 11">
        <location>
            <begin position="513"/>
            <end position="514"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA61667." evidence="12" ref="2">
        <original>H</original>
        <variation>R</variation>
        <location>
            <position position="25"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; CAA61667." evidence="12" ref="2">
        <original>A</original>
        <variation>R</variation>
        <location>
            <position position="429"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; BAG53473." evidence="12" ref="3">
        <original>F</original>
        <variation>S</variation>
        <location>
            <position position="542"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="4"/>
            <end position="21"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="24"/>
            <end position="27"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="30"/>
            <end position="32"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="39"/>
            <end position="41"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="42"/>
            <end position="45"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="46"/>
            <end position="48"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="50"/>
            <end position="56"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="59"/>
            <end position="61"/>
        </location>
    </feature>
    <feature type="strand" evidence="19">
        <location>
            <begin position="65"/>
            <end position="67"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="68"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="75"/>
            <end position="83"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="85"/>
            <end position="93"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="94"/>
            <end position="96"/>
        </location>
    </feature>
    <feature type="turn" evidence="19">
        <location>
            <begin position="99"/>
            <end position="101"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="110"/>
            <end position="121"/>
        </location>
    </feature>
    <feature type="helix" evidence="19">
        <location>
            <begin position="130"/>
            <end position="134"/>
        </location>
    </feature>
    <feature type="strand" evidence="20">
        <location>
            <begin position="157"/>
            <end position="159"/>
        </location>
    </feature>
    <feature type="helix" evidence="20">
        <location>
            <begin position="160"/>
            <end position="164"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="4">
        <source>
            <dbReference type="PubMed" id="10613896"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="5">
        <source>
            <dbReference type="PubMed" id="14701878"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="6">
        <source>
            <dbReference type="PubMed" id="15749819"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="7">
        <source>
            <dbReference type="PubMed" id="22484487"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="8">
        <source>
            <dbReference type="PubMed" id="7634337"/>
        </source>
    </evidence>
    <evidence type="ECO:0000269" key="9">
        <source>
            <dbReference type="PubMed" id="7637788"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="10">
        <source>
            <dbReference type="PubMed" id="14702039"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="11">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="12"/>
    <evidence type="ECO:0007744" key="13">
        <source>
            <dbReference type="PubMed" id="18669648"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="14">
        <source>
            <dbReference type="PubMed" id="19690332"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="15">
        <source>
            <dbReference type="PubMed" id="20068231"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="16">
        <source>
            <dbReference type="PubMed" id="21406692"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="17">
        <source>
            <dbReference type="PubMed" id="23186163"/>
        </source>
    </evidence>
    <evidence type="ECO:0007744" key="18">
        <source>
            <dbReference type="PubMed" id="24275569"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="19">
        <source>
            <dbReference type="PDB" id="2OLM"/>
        </source>
    </evidence>
    <evidence type="ECO:0007829" key="20">
        <source>
            <dbReference type="PDB" id="2VX8"/>
        </source>
    </evidence>
    <sequence length="562" mass="58260" checksum="9A2242217F53B4D9" modified="2002-11-28" version="2"> </sequence>
</entry>
<entry dataset="Swiss-Prot" created="2004-06-21" modified="2026-01-28" version="172" xmlns="https://uniprot.org/uniprot">
    <accession>O95081</accession>
    <accession>O75429</accession>
    <accession>Q96AB9</accession>
    <accession>Q96GL4</accession>
    <name>AGFG2_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName>Arf-GAP domain and FG repeat-containing protein 2</fullName>
        </recommendedName>
        <alternativeName>
            <fullName>HIV-1 Rev-binding protein-like protein</fullName>
        </alternativeName>
        <alternativeName>
            <fullName>Rev/Rex activation domain-binding protein related</fullName>
            <shortName>RAB-R</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name type="primary">AGFG2</name>
        <name type="synonym">HRBL</name>
        <name type="synonym">RABR</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
    <reference key="1">
        <citation type="journal article" date="1997" name="Genes Dev." volume="11" first="2239" last="2249">
            <title>Binding specificity and in vivo targets of the EH domain, a novel protein-protein interaction module.</title>
            <authorList>
                <person name="Salcini A.E."/>
                <person name="Confalonieri S."/>
                <person name="Doria M."/>
                <person name="Santolini E."/>
                <person name="Tassi E."/>
                <person name="Minenkova O."/>
                <person name="Cesareni G."/>
                <person name="Pelicci P.G."/>
                <person name="Di Fiore P.P."/>
            </authorList>
            <dbReference type="PubMed" id="9303539"/>
            <dbReference type="DOI" id="10.1101/gad.11.17.2239"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
    </reference>
    <reference key="2">
        <citation type="journal article" date="2004" name="Genome Res." volume="14" first="2121" last="2127">
            <title>The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).</title>
            <authorList>
                <consortium name="The MGC Project Team"/>
            </authorList>
            <dbReference type="PubMed" id="15489334"/>
            <dbReference type="DOI" id="10.1101/gr.2596504"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
        <source>
            <tissue>Brain</tissue>
            <tissue>Placenta</tissue>
        </source>
    </reference>
    <reference key="3">
        <citation type="journal article" date="1998" name="Genome Res." volume="8" first="1060" last="1073">
            <title>Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes.</title>
            <authorList>
                <person name="Gloeckner G."/>
                <person name="Scherer S."/>
                <person name="Schattevoy R."/>
                <person name="Boright A.P."/>
                <person name="Weber J."/>
                <person name="Tsui L.-C."/>
                <person name="Rosenthal A."/>
            </authorList>
            <dbReference type="PubMed" id="9799793"/>
            <dbReference type="DOI" id="10.1101/gr.8.10.1060"/>
        </citation>
        <scope>NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 75-481</scope>
    </reference>
    <reference key="4">
        <citation type="journal article" date="2009" name="Science" volume="325" first="834" last="840">
            <title>Lysine acetylation targets protein complexes and co-regulates major cellular functions.</title>
            <authorList>
                <person name="Choudhary C."/>
                <person name="Kumar C."/>
                <person name="Gnad F."/>
                <person name="Nielsen M.L."/>
                <person name="Rehman M."/>
                <person name="Walther T.C."/>
                <person name="Olsen J.V."/>
                <person name="Mann M."/>
            </authorList>
            <dbReference type="PubMed" id="19608861"/>
            <dbReference type="DOI" id="10.1126/science.1175371"/>
        </citation>
        <scope>ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173</scope>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <reference key="5">
        <citation type="journal article" date="2011" name="BMC Syst. Biol." volume="5" first="17" last="17">
            <title>Initial characterization of the human central proteome.</title>
            <authorList>
                <person name="Burkard T.R."/>
                <person name="Planyavsky M."/>
                <person name="Kaupe I."/>
                <person name="Breitwieser F.P."/>
                <person name="Buerckstuemmer T."/>
                <person name="Bennett K.L."/>
                <person name="Superti-Furga G."/>
                <person name="Colinge J."/>
            </authorList>
            <dbReference type="PubMed" id="21269460"/>
            <dbReference type="DOI" id="10.1186/1752-0509-5-17"/>
        </citation>
        <scope>IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]</scope>
    </reference>
    <comment type="subunit">
        <text evidence="1">Interacts with EPS15R.</text>
    </comment>
    <comment type="alternative products">
        <event type="alternative splicing"/>
        <isoform>
            <id>O95081-1</id>
            <name>1</name>
            <sequence type="displayed"/>
        </isoform>
        <isoform>
            <id>O95081-2</id>
            <name>2</name>
            <sequence type="described" ref="VSP_010667 VSP_010668"/>
        </isoform>
    </comment>
    <comment type="domain">
        <text>Contains FG repeats and 4 N-P-F repeats.</text>
    </comment>
    <comment type="sequence caution" evidence="5">
        <conflict type="erroneous gene model prediction">
            <sequence resource="EMBL-CDS" id="AAC78803" version="1"/>
        </conflict>
    </comment>
    <dbReference type="EMBL" id="AF015042">
        <property type="protein sequence ID" value="AAD01550.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC009393">
        <property type="protein sequence ID" value="AAH09393.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="BC017329">
        <property type="protein sequence ID" value="AAH17329.1"/>
        <property type="molecule type" value="mRNA"/>
    </dbReference>
    <dbReference type="EMBL" id="AF053356">
        <property type="protein sequence ID" value="AAC78803.1"/>
        <property type="status" value="ALT_SEQ"/>
        <property type="molecule type" value="Genomic_DNA"/>
    </dbReference>
    <dbReference type="CCDS" id="CCDS5697.1">
        <molecule id="O95081-1"/>
    </dbReference>
    <dbReference type="RefSeq" id="NP_006067.3">
        <molecule id="O95081-1"/>
        <property type="nucleotide sequence ID" value="NM_006076.4"/>
    </dbReference>
    <dbReference type="AlphaFoldDB" id="O95081"/>
    <dbReference type="SMR" id="O95081"/>
    <dbReference type="BioGRID" id="109504">
        <property type="interactions" value="28"/>
    </dbReference>
    <dbReference type="ELM" id="O95081"/>
    <dbReference type="FunCoup" id="O95081">
        <property type="interactions" value="247"/>
    </dbReference>
    <dbReference type="IntAct" id="O95081">
        <property type="interactions" value="5"/>
    </dbReference>
    <dbReference type="STRING" id="9606.ENSP00000300176"/>
    <dbReference type="GlyCosmos" id="O95081">
        <property type="glycosylation" value="11 sites, 2 glycans"/>
    </dbReference>
    <dbReference type="GlyGen" id="O95081">
        <property type="glycosylation" value="16 sites, 2 O-linked glycans (14 sites)"/>
    </dbReference>
    <dbReference type="iPTMnet" id="O95081"/>
    <dbReference type="PhosphoSitePlus" id="O95081"/>
    <dbReference type="BioMuta" id="AGFG2"/>
    <dbReference type="jPOST" id="O95081"/>
    <dbReference type="MassIVE" id="O95081"/>
    <dbReference type="PaxDb" id="9606-ENSP00000300176"/>
    <dbReference type="PeptideAtlas" id="O95081"/>
    <dbReference type="ProteomicsDB" id="50647">
        <molecule id="O95081-1"/>
    </dbReference>
    <dbReference type="ProteomicsDB" id="50648">
        <molecule id="O95081-2"/>
    </dbReference>
    <dbReference type="Pumba" id="O95081"/>
    <dbReference type="Antibodypedia" id="16493">
        <property type="antibodies" value="147 antibodies from 27 providers"/>
    </dbReference>
    <dbReference type="DNASU" id="3268"/>
    <dbReference type="Ensembl" id="ENST00000300176.9">
        <molecule id="O95081-1"/>
        <property type="protein sequence ID" value="ENSP00000300176.4"/>
        <property type="gene ID" value="ENSG00000106351.14"/>
    </dbReference>
    <dbReference type="GeneID" id="3268"/>
    <dbReference type="KEGG" id="hsa:3268"/>
    <dbReference type="MANE-Select" id="ENST00000300176.9">
        <property type="protein sequence ID" value="ENSP00000300176.4"/>
        <property type="RefSeq nucleotide sequence ID" value="NM_006076.5"/>
        <property type="RefSeq protein sequence ID" value="NP_006067.3"/>
    </dbReference>
    <dbReference type="UCSC" id="uc003uvf.4">
        <molecule id="O95081-1"/>
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="AGR" id="HGNC:5177"/>
    <dbReference type="ClinPGx" id="PA29451"/>
    <dbReference type="CTD" id="3268"/>
    <dbReference type="DisGeNET" id="3268"/>
    <dbReference type="GeneCards" id="AGFG2"/>
    <dbReference type="HGNC" id="HGNC:5177">
        <property type="gene designation" value="AGFG2"/>
    </dbReference>
    <dbReference type="HPA" id="ENSG00000106351">
        <property type="expression patterns" value="Tissue enriched (salivary)"/>
    </dbReference>
    <dbReference type="MIM" id="604019">
        <property type="type" value="gene"/>
    </dbReference>
    <dbReference type="OpenTargets" id="ENSG00000106351"/>
    <dbReference type="VEuPathDB" id="HostDB:ENSG00000106351"/>
    <dbReference type="eggNOG" id="KOG0702">
        <property type="taxonomic scope" value="Eukaryota"/>
    </dbReference>
    <dbReference type="GeneTree" id="ENSGT00940000161071"/>
    <dbReference type="HOGENOM" id="CLU_027801_0_0_1"/>
    <dbReference type="InParanoid" id="O95081"/>
    <dbReference type="OMA" id="DVFGDIW"/>
    <dbReference type="OrthoDB" id="6036at2759"/>
    <dbReference type="PAN-GO" id="O95081">
        <property type="GO annotations" value="1 GO annotation based on evolutionary models"/>
    </dbReference>
    <dbReference type="PhylomeDB" id="O95081"/>
    <dbReference type="PathwayCommons" id="O95081"/>
    <dbReference type="SignaLink" id="O95081"/>
    <dbReference type="Agora" id="ENSG00000106351"/>
    <dbReference type="BioGRID-ORCS" id="3268">
        <property type="hits" value="12 hits in 1155 CRISPR screens"/>
    </dbReference>
    <dbReference type="ChiTaRS" id="AGFG2">
        <property type="organism name" value="human"/>
    </dbReference>
    <dbReference type="GeneWiki" id="HRBL"/>
    <dbReference type="GenomeRNAi" id="3268"/>
    <dbReference type="Pharos" id="O95081">
        <property type="development level" value="Tbio"/>
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    <dbReference type="PRO" id="PR:O95081"/>
    <dbReference type="Proteomes" id="UP000005640">
        <property type="component" value="Chromosome 7"/>
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    <dbReference type="RNAct" id="O95081">
        <property type="molecule type" value="protein"/>
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    <dbReference type="Bgee" id="ENSG00000106351">
        <property type="expression patterns" value="Expressed in parotid gland and 140 other cell types or tissues"/>
    </dbReference>
    <dbReference type="ExpressionAtlas" id="O95081">
        <property type="expression patterns" value="baseline and differential"/>
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    <dbReference type="GO" id="GO:0005737">
        <property type="term" value="C:cytoplasm"/>
        <property type="evidence" value="ECO:0000318"/>
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    <dbReference type="GO" id="GO:0031410">
        <property type="term" value="C:cytoplasmic vesicle"/>
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    <dbReference type="GO" id="GO:0016020">
        <property type="term" value="C:membrane"/>
        <property type="evidence" value="ECO:0007005"/>
        <property type="project" value="UniProtKB"/>
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    <dbReference type="GO" id="GO:0005096">
        <property type="term" value="F:GTPase activator activity"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="InterPro"/>
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    <dbReference type="GO" id="GO:0008270">
        <property type="term" value="F:zinc ion binding"/>
        <property type="evidence" value="ECO:0007669"/>
        <property type="project" value="UniProtKB-KW"/>
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    <dbReference type="GO" id="GO:0001675">
        <property type="term" value="P:acrosome assembly"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0045109">
        <property type="term" value="P:intermediate filament organization"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="GO" id="GO:0007289">
        <property type="term" value="P:spermatid nucleus differentiation"/>
        <property type="evidence" value="ECO:0000318"/>
        <property type="project" value="GO_Central"/>
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    <dbReference type="CDD" id="cd17903">
        <property type="entry name" value="ArfGap_AGFG2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="FunFam" id="1.10.220.150:FF:000005">
        <property type="entry name" value="Arf-GAP domain and FG repeat-containing protein 1"/>
        <property type="match status" value="1"/>
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    <dbReference type="Gene3D" id="1.10.220.150">
        <property type="entry name" value="Arf GTPase activating protein"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR052248">
        <property type="entry name" value="Arf-GAP_FG-repeat_protein"/>
    </dbReference>
    <dbReference type="InterPro" id="IPR037278">
        <property type="entry name" value="ARFGAP/RecO"/>
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    <dbReference type="InterPro" id="IPR001164">
        <property type="entry name" value="ArfGAP_dom"/>
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    <dbReference type="InterPro" id="IPR038508">
        <property type="entry name" value="ArfGAP_dom_sf"/>
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    <dbReference type="PANTHER" id="PTHR46134:SF4">
        <property type="entry name" value="ARF-GAP DOMAIN AND FG REPEAT-CONTAINING PROTEIN 2"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PANTHER" id="PTHR46134">
        <property type="entry name" value="DRONGO, ISOFORM F"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="Pfam" id="PF01412">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PRINTS" id="PR00405">
        <property type="entry name" value="REVINTRACTNG"/>
    </dbReference>
    <dbReference type="SMART" id="SM00105">
        <property type="entry name" value="ArfGap"/>
        <property type="match status" value="1"/>
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    <dbReference type="SUPFAM" id="SSF57863">
        <property type="entry name" value="ArfGap/RecO-like zinc finger"/>
        <property type="match status" value="1"/>
    </dbReference>
    <dbReference type="PROSITE" id="PS50115">
        <property type="entry name" value="ARFGAP"/>
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    </dbReference>
    <proteinExistence type="evidence at protein level"/>
    <keyword id="KW-0007">Acetylation</keyword>
    <keyword id="KW-0025">Alternative splicing</keyword>
    <keyword id="KW-0479">Metal-binding</keyword>
    <keyword id="KW-1267">Proteomics identification</keyword>
    <keyword id="KW-1185">Reference proteome</keyword>
    <keyword id="KW-0677">Repeat</keyword>
    <keyword id="KW-0862">Zinc</keyword>
    <keyword id="KW-0863">Zinc-finger</keyword>
    <feature type="chain" id="PRO_0000204828" description="Arf-GAP domain and FG repeat-containing protein 2">
        <location>
            <begin position="1"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="domain" description="Arf-GAP" evidence="2">
        <location>
            <begin position="27"/>
            <end position="153"/>
        </location>
    </feature>
    <feature type="zinc finger region" description="C4-type" evidence="2">
        <location>
            <begin position="47"/>
            <end position="70"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="150"/>
            <end position="220"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="271"/>
            <end position="309"/>
        </location>
    </feature>
    <feature type="region of interest" description="Disordered" evidence="3">
        <location>
            <begin position="431"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="157"/>
            <end position="166"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="188"/>
            <end position="210"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="283"/>
            <end position="298"/>
        </location>
    </feature>
    <feature type="compositionally biased region" description="Polar residues" evidence="3">
        <location>
            <begin position="454"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="modified residue" description="N6-acetyllysine" evidence="6">
        <location>
            <position position="173"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010667" description="In isoform 2." evidence="4">
        <original>YVPPDQVKGPT</original>
        <variation>PDTFPRRLCQL</variation>
        <location>
            <begin position="145"/>
            <end position="155"/>
        </location>
    </feature>
    <feature type="splice variant" id="VSP_010668" description="In isoform 2." evidence="4">
        <location>
            <begin position="157"/>
            <end position="481"/>
        </location>
    </feature>
    <feature type="sequence variant" id="VAR_050566" description="In dbSNP:rs34731997.">
        <original>T</original>
        <variation>N</variation>
        <location>
            <position position="365"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD01550." evidence="5" ref="1">
        <original>V</original>
        <variation>L</variation>
        <location>
            <position position="96"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 1; AAD01550." evidence="5" ref="1">
        <original>D</original>
        <variation>N</variation>
        <location>
            <position position="124"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 3; AAC78803." evidence="5" ref="3">
        <original>Q</original>
        <variation>H</variation>
        <location>
            <position position="206"/>
        </location>
    </feature>
    <feature type="sequence conflict" description="In Ref. 2; AAH17329." evidence="5" ref="2">
        <original>M</original>
        <variation>T</variation>
        <location>
            <position position="349"/>
        </location>
    </feature>
    <evidence type="ECO:0000250" key="1"/>
    <evidence type="ECO:0000255" key="2">
        <source>
            <dbReference type="PROSITE-ProRule" id="PRU00288"/>
        </source>
    </evidence>
    <evidence type="ECO:0000256" key="3">
        <source>
            <dbReference type="SAM" id="MobiDB-lite"/>
        </source>
    </evidence>
    <evidence type="ECO:0000303" key="4">
        <source>
            <dbReference type="PubMed" id="15489334"/>
        </source>
    </evidence>
    <evidence type="ECO:0000305" key="5"/>
    <evidence type="ECO:0007744" key="6">
        <source>
            <dbReference type="PubMed" id="19608861"/>
        </source>
    </evidence>
    <sequence length="481" mass="48963" checksum="A89202A0F0924FE2" modified="2004-06-21" version="2">MVMAAKKGPGPGGGVSGGKAEAEAASEVWCRRVRELGGCSQAGNRHCFECAQRGVTYVDITVGSFVCTTCSGLLRGLNPPHRVKSISMTTFTEPEVVFLQSRGNEVCRKIWLGLFDARTSLVPDSRDPQKVKEFLQEKYEKKRWYVPPDQVKGPTYTKGSASTPVQGSIPEGKPLRTLLGDPAPSLSVAASTSSQPVSQSHARTSQARSTQPPPHSSVKKASTDLLADIGGDPFAAPQMAPAFAAFPAFGGQTPSQGGFANFDAFSSGPSSSVFGSLPPAGQASFQAQPTPAGSSQGTPFGATPLAPASQPNSLADVGSFLGPGVPAAGVPSSLFGMAGQVPPLQSVTMGGGGGSSTGLAFGAFTNPFTAPAAQSPLPSTNPFQPNGLAPGPGFGMSSAGPGFPQAVPPTGAFASSFPAPLFPPQTPLVQQQNGSSFGDLGSAKLGQRPLSQPAGISTNPFMTGPSSSPFASKPPTTNPFL</sequence>
</entry>
<entry dataset="Swiss-Prot" created="2006-10-17" modified="2026-01-28" version="167" xmlns="https://uniprot.org/uniprot">
    <accession>Q53H12</accession>
    <accession>Q75KN1</accession>
    <accession>Q96GC3</accession>
    <accession>Q9NP48</accession>
    <name>AGK_HUMAN</name>
    <protein>
        <recommendedName>
            <fullName evidence="15">Acylglycerol kinase, mitochondrial</fullName>
            <shortName evidence="15">hAGK</shortName>
            <ecNumber evidence="4">2.7.1.107</ecNumber>
            <ecNumber evidence="1">2.7.1.138</ecNumber>
            <ecNumber evidence="4">2.7.1.94</ecNumber>
        </recommendedName>
        <alternativeName>
            <fullName evidence="16">Multiple substrate lipid kinase</fullName>
            <shortName evidence="16">HsMuLK</shortName>
            <shortName evidence="16">MuLK</shortName>
            <shortName evidence="16">Multi-substrate lipid kinase</shortName>
        </alternativeName>
    </protein>
    <gene>
        <name evidence="15 19" type="primary">AGK</name>
        <name evidence="16" type="synonym">MULK</name>
    </gene>
    <organism>
        <name type="scientific">Homo sapiens</name>
        <name type="common">Human</name>
        <dbReference type="NCBI Taxonomy" id="9606"/>
        <lineage>
            <taxon>Eukaryota</taxon>
            <taxon>Metazoa</taxon>
            <taxon>Chordata</taxon>
            <taxon>Craniata</taxon>
            <taxon>Vertebrata</taxon>
            <taxon>Euteleostomi</taxon>
            <taxon>Mammalia</taxon>
            <taxon>Eutheria</taxon>
            <taxon>Euarchontoglires</taxon>
            <taxon>Primates</taxon>
            <taxon>Haplorrhini</taxon>
            <taxon>Catarrhini</taxon>
            <taxon>Hominidae</taxon>
            <taxon>Homo</taxon>
        </lineage>
    </organism>
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        <scope>NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)</scope>
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            <dbReference type="PubMed" id="14702039"/>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)</scope>
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        <scope>NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)</scope>
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        <scope>FUNCTION</scope>
        <scope>CATALYTIC ACTIVITY</scope>
        <scope>COFACTOR</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>TISSUE SPECIFICITY</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>IDENTIFICATION IN THE TIM22 COMPLEX</scope>
        <scope>MUTAGENESIS OF GLY-126</scope>
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        <scope>FUNCTION</scope>
        <scope>SUBCELLULAR LOCATION</scope>
        <scope>IDENTIFICATION IN THE TIM22 COMPLEX</scope>
        <scope>INVOLVEMENT IN MTDPS10</scope>
        <scope>MUTAGENESIS OF GLY-126</scope>
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            <dbReference type="PubMed" id="37009826"/>
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        <scope>INTERACTION WITH SMIM26</scope>
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        <scope>VARIANT MTDPS10 327-LYS--GLN-422 DEL</scope>
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        <scope>VARIANTS MTDPS10 137-ARG--GLN-422 DEL AND 291-GLN--GLN-422 DEL</scope>
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    <comment type="function">
        <text evidence="1 4 11 12">Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15939762). Does not phosphorylate sphingosine (PubMed:15939762). Phosphorylates ceramide (By similarity). Phosphorylates 1,2-dioleoylglycerol more rapidly than 2,3-dioleoylglycerol (By similarity). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (PubMed:28712724, PubMed:28712726). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (PubMed:28712724, PubMed:28712726). In the TIM22 complex, required for the import of a subset of metabolite carriers into mitochondria, such as ANT1/SLC25A4 and SLC25A24, while it is not required for the import of TIMM23 (PubMed:28712724). Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth (PubMed:15939762).</text>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a monoacylglycerol + ATP = a monoacyl-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:19293"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17408"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:77589"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.1.94"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:19294"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:10272"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17815"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:58608"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.1.107"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:10273"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="1">
            <text>an N-acylsphing-4-enine + ATP = an N-acylsphing-4-enine 1-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:17929"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:52639"/>
            <dbReference type="ChEBI" id="CHEBI:57674"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
            <dbReference type="EC" id="2.7.1.138"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="1">
            <dbReference type="Rhea" id="RHEA:17930"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:41079"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:74544"/>
            <dbReference type="ChEBI" id="CHEBI:75757"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:41080"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:40327"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:52333"/>
            <dbReference type="ChEBI" id="CHEBI:74546"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:40328"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 1-acyl-sn-glycerol + ATP = a 1-acyl-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:33747"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:57970"/>
            <dbReference type="ChEBI" id="CHEBI:64683"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:33748"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>1-hexadecanoyl-sn-glycerol + ATP = 1-hexadecanoyl-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43308"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:57518"/>
            <dbReference type="ChEBI" id="CHEBI:75542"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:43309"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>a 2-acylglycerol + ATP = a 2-acyl-sn-glycerol 3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:39847"/>
            <dbReference type="ChEBI" id="CHEBI:15378"/>
            <dbReference type="ChEBI" id="CHEBI:17389"/>
            <dbReference type="ChEBI" id="CHEBI:30616"/>
            <dbReference type="ChEBI" id="CHEBI:64982"/>
            <dbReference type="ChEBI" id="CHEBI:456216"/>
        </reaction>
        <physiologicalReaction direction="left-to-right" evidence="18">
            <dbReference type="Rhea" id="RHEA:39848"/>
        </physiologicalReaction>
    </comment>
    <comment type="catalytic activity">
        <reaction evidence="4">
            <text>2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + ATP = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+)</text>
            <dbReference type="Rhea" id="RHEA:43316"/>
            <dbRefer